Anda di halaman 1dari 625


Gill, Emma and Abigail

Alison, Jonathan and Sophie
and to
Pat, Ethan and Molly
Content Strategist: Jeremy Bowes
Content Development Specialist: Sheila Black
Project Manager: Luca Prez
Designer: Christian Bilbow
Illustration Manager: Jennifer Rose
and Intensive
Care AZ
An Encyclopaedia of Principles
and Practice

Steve M Yentis BSc MBBS MD MA FRCA

Consultant Anaesthetist, Chelsea and Westminster Hospital;
Honorary Reader, Imperial College London, UK


Consultant Anaesthetist, The National Hospital for Neurology and Neurosurgery;
Honorary Senior Lecturer, The Institute of Neurology, London, UK


Specialty Registrar, Imperial School of Anaesthesia, London, UK

Original contributions by Gary B Smith BM FRCA FRCP

2013 Elsevier Ltd. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
Publishers permissions policies and our arrangements with organizations such as the Copyright Clearance
Center and the Copyright Licensing Agency, can be found at our website:

This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).

First edition 1993

Second edition 2000
Third edition 2004
Fourth edition 2009
Fifth edition 2013

ISBN 978-0-7020-4420-5

1 British Library Cataloguing in Publication Data

A catalogue record for this book is available from the British Library

2 Library of Congress Cataloging in Publication Data

A catalog record for this book is available from the Library of Congress

Knowledge and best practice in this field are constantly changing. As new research and experience broaden
our understanding, changes in research methods, professional practices, or medical treatment may become
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using
any information, methods, compounds, or experiments described herein. In using such information or methods
they should be mindful of their own safety and the safety of others, including parties for whom they have a
professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most
current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be
administered, to verify the recommended dose or formula, the method and duration of administration, and
contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of
their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient,
and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any
liability for any injury and/or damage to persons or property as a matter of products liability, negligence or
otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the
material herein.

Working together to grow publishers
policy is to use
libraries in developing countries paper manufactured
from sustainable forests | |

Printed in China

In the 20 years since the publication of the first edition of activities performed by our anaesthetic, intensive care,
of our textbook, we have been delighted to find that nursing and other colleagues, and also reflects the ever-
the AZ has been adopted by both trainees and estab- changing field in which we work.
lished practitioners alike. Whilst our original idea was to
produce a readily accessible source of information for The publication of a textbook requires the support of
those sitting the Royal College of Anaesthetists Fellow- a multitude of people. We are indebted to our colleagues,
ship examinations, it is now obvious that the book both junior and senior, who have gently criticised previ-
appeals to a far wider readership. We hope that the AZ ous editions; their suggestions have been invaluable and
will continue to be useful to all staff who help us care have directly resulted in changes found in each new
for patients on a daily basis, as well as to anaesthetists edition over the years. We also thank the staff of Elsevier
and intensivists of all grades. and their predecessors for their support during the life
of this project. Finally, this is the first edition of the AZ
As with previous new editions, each entry has been on which two of the original authors, SMY and NPH,
reviewed and, where appropriate, revised, and new ones have worked without the third, Gary Smith, though his
inserted. For the first time, we have compiled a struc- contributions exist throughout the book in both the
tured checklist of entries, at the back of the book, that format and content of entries from previous editions. We
we hope will be useful to those planning their revision shall both miss Garys expertise, input and good humour,
for exams. but are delighted to welcome James Ip to the team.

The difference between the list of entries in the first

edition and those in the current one continues to increase, SMY
with a huge expansion of new entries and revision of NPH
existing ones. This change acknowledges the enormous JKI
breadth of information needed to satisfy the vast range

Explanatory notes

Arrangement of text Recommended International

Entries are arranged alphabetically, with some related Non-proprietary Names (rINNs)
subjects grouped together to make coverage of one Following work undertaken by the World Health Organ-
subject easier. For example, entries relating to tracheal ization, recent European law requires the replacement
intubation may be found under I as in Intubation, awake; of existing national drug nomenclature with rINNs. For
Intubation, blind nasal, etc. most drugs, rINNS are identical to the British Approved
Name (BAN). The Medicines Control Agency (UK) has
Cross-referencing proposed a two-stage process for the introduction of
Bold type indicates a cross-reference. An abbreviation rINNs. For substances where the change is substantial,
highlighted in bold type refers to an entry in its fully both names will appear on manufacturers labels and
spelled form. For example, ARDS may occur . . . refers leaflets for a number of years, with the rINN preceding
to the entry Acute respiratory distress syndrome. Further the BAN on the drug label. For drugs where the change
instructions appear in italics. presents little hazard, the change will be immediate.
For some drugs which do not appear in either of the
above two categories, the British (or USP) name may
Reference to a suitable article is provided at the foot of
still be used.
the entry where appropriate.
There are over 200 affected drugs, many of them no
Proper names
longer available. Affected drugs that are mentioned in
Where possible, a short biographical note is provided
this book (though not all of them have their own entries)
at the foot of the entry when a person is mentioned.
are listed below though please note that, in common
Dates of birth and death are given, or the date of descrip-
with the British Pharmacopoeia, the terms adrenaline
tion if these dates are unknown. No dates are given
and noradrenaline will be used throughout the text in
for contemporary names. Where more than one epony-
preference to epinephrine and norepinephrine respec-
mous entry occurs, e.g. Haldane apparatus and
tively, because of their status as natural hormones.
Haldane effect, details are given under the first entry.
Thus (with the exception of adrenaline and noradrena-
The term anaesthetist is used in the English sense,
line), the format for affected drugs is rINN (BAN), e.g.
i.e. a medical practitioner who practises anaesthesia;
Tetracaine hydrochloride (Amethocaine). Non-BAN,
the terms anesthesiologist and anaesthesiologist are
non-rINN names are also provided for certain other
not used.
drugs (for example, Isoproterenol, see Isoprenaline) to
Drugs help direct non-UK readers or those unfamiliar with UK
Individual drugs have entries where they have especial terminology.
relevance to, or may by given by, the anaesthetist or
intensivist. Where many different drugs exist within the Examination revision checklist
same group, for example -adrenergic receptor antago- At the back of the book is a checklist based on entries
nists, those which may be given intravenously have their of particular relevance to examination candidates, that
own entry, whilst the others are described under the have been classified and listed alphabetically in order to
group description. The reader is referred back to entries support systematic study of examination topics accord-
describing drug groups and classes where appropriate. ing to the subject area.

continued over page

Explanatory notes


Adrenaline Epinephrine
Amethocaine Tetracaine
Amoxycillin Amoxicillin
Amphetamine Amfetamine
Amylobarbitone Amobarbital
Beclomethasone Beclometasone
Benzhexol Trihexyphenidyl
Benztropine Benzatropine
Busulphan Busulfan
Cephazolin Cefazolin
Cephradine Cefradine
Cephramandole Ceframandole
Chlormethiazole Clomethiazole
Chlorpheniramine Chlorphenamine
Corticotrophin Corticotropin
Cyclosporin Ciclosporin
Dicyclomine Dicycloverine
Dothiepin Dosulepin
Ethamsylate Etamsylate
Ethacrynic acid Etacrynic acid
Frusemide Furosemide
Indomethacin Indometacin
Lignocaine Lidocaine
Methohexitone Methohexital
Methylene blue Methylthioninium chloride
Noradrenaline Norepinephrine
Oxpentifylline Pentoxifylline
Phenobarbitone Phenobarbital
Sodium cromoglycate Sodium cromoglicate
Sulphadiazine Sulfadiazine
Sulphasalazine Sulfasalazine
Tetracosactrin Tetracosactide
Thiopentone Thiopental
Tribavarin Ribavarin
Trimeprazine Alimemazine



ACE inhibitors angiotensin converting enzyme GFR glomerular filtration rate

inhibitors GIT gastrointestinal tract
ACTH adrenocorticotrophic hormone GTN glyceryl trinitrate
ADP adenosine diphosphate HCO3 bicarbonate
AF atrial fibrillation HDU high dependency unit
AIDS acquired immune deficiency syndrome HIV human immunodeficiency virus
cAMP cyclic adenosine monophosphate HLA human leucocyte antigen
APACHE acute physiology and chronic health 5-HT 5-hydroxytryptamine
ICP intracranial pressure
ARDS acute respiratory distress syndrome
ICU intensive care unit
ASA American Society of Anesthesiologists
IgA, IgG, etc., immunoglobulin A, G, etc.
ASD atrial septal defect
im intramuscular
ATP adenosine triphosphate
IMV intermittent mandatory ventilation
AV atrioventricular
IPPV intermittent positive pressure ventilation
bd twice daily
iv intravenous
BP blood pressure
IVRA intravenous regional anaesthesia
CMRO2 cerebral metabolic rate for oxygen
JVP jugular venous pressure
CNS central nervous system
LMA laryngeal mask airway
CO2 carbon dioxide
MAC minimal alveolar concentration
COPD chronic obstructive pulmonary disease
MAP mean arterial pressure
CPAP continuous positive airway pressure
MH malignant hyperthermia
CPR cardiopulmonary resuscitation
MI myocardial infarction
CSE combined spinalextradural
MODS multiple organ dysfunction syndrome
CSF cerebrospinal fluid
MRI magnetic resonance imaging
CT computed tomography
mw molecular weight
CVA cerebrovascular accident
NAD(P) nicotinamide adenine dinucleotide
CVP central venous pressure (phosphate)
CVS cardiovascular system NHS National Health Service
CXR chest X-ray NICE National Institute for Health and Clinical
DIC disseminated intravascular coagulation Excellence
DNA deoxyribonucleic acid NMDA N-methyl-D-aspartate
2,3-DPG 2,3-diphosphoglycerate N2O nitrous oxide
DVT deep vein thrombosis NSAID non-steroidal anti-inflammatory drug
ECF extracellular fluid O2 oxygen
ECG electrocardiography od once daily
EDTA ethylenediaminetetraacetate ODA/P operating department assistant/practitioner
EEG electroencephalography PCO2 partial pressure of carbon dioxide
EMG electromyography PE pulmonary embolus
ENT ear, nose and throat PEEP positive end-expiratory pressure
FEV1 forced expiratory volume in 1 s PO2 partial pressure of oxygen
FIO2 fractional inspired concentration of oxygen PONV postoperative nausea and vomiting
FRC functional residual capacity pr per rectum
FVC forced vital capacity qds four times daily
G gauge RNA ribonucleic acid
GABA -aminobutyric acid RS respiratory system


sc subcutaneous TIVA total intravenous anaesthesia

SIRS systemic inflammatory response syndrome TPN total parenteral nutrition
SLE systemic lupus erythematosus TURP transurethral resection of prostate
SVP saturated vapour pressure UK United Kingdom
SVR systemic vascular resistance US(A) United States (of America)
SVT supraventricular tachycardia VF ventricular fibrillation
TB tuberculosis V / Q ventilation/perfusion
tds three times daily VSD ventricular septal defect
TENS transcutaneous electrical nerve stimulation VT ventricular tachycardia

A severity characterisation of trauma (ASCOT). impair ventilation and be associated with reduced
Trauma scale derived from the Glasgow coma scale, sys- venous return, cardiac output, renal blood flow and urine
tolic BP, revised trauma score, abbreviated injury scale output. Increased CVP may lead to raised ICP. Diag-
and age. A logistic regression equation provides a prob- nosed by clinical features and intra-abdominal pressure
ability of mortality. Excludes patients with very poor or measurement (performed via a bladder catheter or
very good prognoses. Has been claimed to be superior nasogastric tube, in combination with a water column
to the trauma revised injury severity score system, manometer).
although is more complex. Management includes laparotomy silastic material
Champion HR, Copes WS, Sacco WJ, etal (1996). J to cover the abdominal contents. Paracentesis may be
Trauma; 40: 428 effective if raised intra-abdominal pressure is due to
accumulation of fluid, e.g. ascites. Full resuscitation must
AadO2, see Alveolararterial oxygen difference be performed before decompression as rapid release of
pressure may result in sudden washout of inflammatory
ABA, see American Board of Anesthesiology mediators from ischaemic tissues, causing acidosis and
hypotension. Mortality of the syndrome is 2570%.
Abbott, Edward Gilbert, see Morton, William Malbrain ML, Cheatham ML, Kirkpatrick A etal (2006).
Intensive Care Med; 32: 172232, and Cheatham ML,
Abbreviated injury scale (AIS). Trauma scale first Malbrain ML, Kirkpatrick A (2007). Intensive Care
described in 1971 and updated many times since. Com- Med; 33: 95162
prises a classification of injuries with each given a six- See also, Compartment syndromes
digit code (the last indicating severity, with 1 = minor
and 6 = fatal). The codes are linked to International Abdominal field block. Technique using 100200ml
Classification of Diseases codes, thus aiding standardisa- local anaesthetic agent, involving infiltration of the skin,
tion of records. The anatomical profile is a refinement subcutaneous tissues, abdominal muscles and fascia. Pro-
in which the locations of injuries are divided into four vides analgesia of the abdominal wall and anterior peri-
categories; the AIS scores are added and the square toneum, but not of the viscera. Now rarely used. Rectus
root taken to minimise the contribution of less severe sheath block, transversus abdominis plane block, iliac
injuries. crest block and inguinal hernia field block are more
Copes WS, Lawnick M, Champion HR, Sacco WJ (1988). specific blocks.
J Trauma; 28: 7886
Abdominal sepsis, see Intra-abdominal sepsis
Abciximab. Monoclonal antibody used as an antiplate-
let drug and adjunct to aspirin and heparin in high-risk Abdominal trauma. May be blunt (e.g. road traffic acci-
patients undergoing percutaneous coronary interven- dents) or penetrating (e.g. stabbing, bullet wounds).
tion. Consists of Fab fragments of immunoglobulin Often carries a high morbidity and mortality because
directed against the glycoprotein IIb/IIIa receptor on injuries may go undetected. Massive intra-abdominal
the platelet surface. Inhibits platelet aggregation and blood loss or abdominal compartment syndrome may
thrombus formation; effects last 2448h after infusion. follow. The abdomen can be divided into three areas:
Careful consideration of risks and benefits should intrathoracic: protected by the bony thoracic cage.
precede use since risk of bleeding is increased. Licensed Contains the spleen, liver, stomach and diaphragm.
for single use only. Injury may be associated with rib fractures. The dia-
Dosage: initial loading of 250g/kg over 1min iv, phragm may also be injured by blows to the lower
followed by iv infusion of 125ng/kg/min (max 10g/ abdomen (which impart pressure waves to the dia-
min) 1060min (up to 24h in unstable angina) before phragm) or by penetrating injuries of the chest.
angioplasty with 125g/kg/min (up to 10g/min for true abdomen: contains the small and large bowel,
12h afterwards). bladder and, in the female, uterus, fallopian tubes
Side effects: bleeding, hypotension, nausea, bradycar- and ovaries.
dia. Thrombocytopenia occurs rarely. retroperitoneal: contains the kidneys, ureters, pan-
creas and duodenum. May result in massive blood
Abdominal compartment syndrome. Combination of loss from retroperitoneal venous injury.
increased intra-abdominal pressure and organ dysfunc- Management:
tion (e.g. following abdominal trauma or extensive basic resuscitation as for trauma generally.
surgery) resulting from haemorrhage or expansion of initial assessment: examination of the anterior
the third space fluid compartment. May also follow liver abdominal wall, both flanks, back, buttocks,
transplantation, sepsis, burns and acute pancreatitis. perineum (and in men, the urethral meatus) for
Intra-abdominal pressures above 2025 cmH2O may bruises, lacerations, entry and exit wounds. Signs

2 ABO blood groups

may be masked by unconsciousness, spinal cord reduction in incidence of events from a% to b%, it
injury or the effects of alcohol or drugs. Abdominal equals (a b)%.
swelling usually indicates intra-abdominal haemor- See also, Meta-analysis; Odds ratio; Relative risk
rhage; abdominal guarding or rigidity usually indi- reduction
cates visceral injury. Absence of bowel sounds may
indicate intraperitoneal haemorrhage or peritoneal Abuse of anaesthetic agents. May occur because of
soiling with bowel contents. Colonic or rectal inju- easy access to potent drugs by operating theatre or ICU
ries may cause blood pr. A high index of suspicion staff. Opioid analgesic drugs are the most commonly
is required for retroperitoneal injuries since exami- abused agents, but others include benzodiazepines and
nation is difficult. inhalational anaesthetic agents. Abuse may be suggested
imaging: abdominal X-ray may reveal free gas by behavioural or mood changes, or excessive and inap-
under the diaphragm (erect or semi-erect; may propriate requests for opioids. Main considerations
also be visible on CXR) or laterally (lateral decu include the safety of patients, counselling and psychiatric
bitus X-ray); other investigations include pelvic therapy for the abuser and legal aspects of drug abuse.
X-ray and urological radiology if indicated (e.g. iv May be associated with alcoholism.
urogram), CT and MRI scanning and ultrasound. Bryson EO, Silverstein JH (2008). Anesthesiology; 109:
peritoneal lavage is indicated in blunt abdominal 90517
trauma associated with: See also, Misuse of Drugs Act; Sick doctor scheme; Sub-
- altered pain response (head injury, spinal cord stance abuse
injury, drugs, etc.).
- unexplained hypovolaemia following multiple Acarbose. Inhibitor of intestinal alpha glucosidases and
trauma. pancreatic amylase; used in the treatment of diabetes
- equivocal diagnostic findings. mellitus, usually in combination with a biguanide or sul-
insertion of a nasogastric tube and urinary catheter phonylurea. Delays digestion and absorption of starch
(provided no urethral injury; a suprapubic catheter and sucrose and has a small blood glucose-lowering
may be necessary). effect.
indications for laparotomy include penetrating inju- See also, Meglitinides; Thiazolidinediones
ries, obvious intra-abdominal haemorrhage, signs of
bowel perforation or a positive peritoneal lavage. Accessory nerve block. Performed for spasm of trape-
See also, Pelvic trauma zius and sternomastoid muscles (there is no sensory
component to the nerve). 510ml local anaesthetic
ABO blood groups. Discovered in 1900 by Landsteiner agent is injected 2cm below the mastoid process into the
in Vienna. Antigens may be present on red blood cells, sternomastoid muscle, through which the nerve runs.
with antibodies in the plasma (Table 1). The antibodies,
mostly type-M immunoglobulins, develop within the first Accident, major, see Incident, major
few months of life, presumably in response to naturally
occurring antigens of similar structure to the blood anti- ACD, Acidcitratedextrose solution, see Blood storage
gens. Infusion of blood containing an ABO antigen into
ACD-CPR, Active compression decompression CPR,
a patient who already has the corresponding antibody
see Cardiac massage; Cardiopulmonary resuscitation
may lead to an adverse reaction; hence the description
of group O individuals as universal donors, and of group ACE, Angiotensin converting enzyme, see Renin/
AB individuals as universal recipients. angiotensin system
[Karl Landsteiner (18681943), Austrian-born US
pathologist] ACE anaesthetic mixture. Mixture of alcohol, chloro-
See also, Blood compatibility testing; Blood groups; form and diethyl ether, in a ratio of 1:2:3 parts, sug-
Blood transfusion gested in 1860 as an alternative to chloroform alone.
Popular into the 1900s as a means of reducing total dose
ABPI, see Ankle Brachial Pressure Index and side effects of any one of the three drugs.
Abruption, see Antepartum haemorrhage ACE inhibitors, see Angiotensin converting enzyme
Absolute risk reduction. Indicator of treatment effect
in clinical trials, representing the decrease in risk of a Acetaminophen, see Paracetamol
given treatment compared with a control treatment, i.e.
the inverse of the number needed to treat. For a Acetazolamide. Carbonic anhydrase inhibitor. Reduces
renal bicarbonate formation and hydrogen ion excretion
at the proximal convoluted tubule, thereby inducing a
metabolic acidosis. A weak diuretic, but rarely used as
Table 1 Antigens and antibodies in ABO blood groups such. Also used to treat glaucoma, metabolic alkalosis,
altitude sickness and childhood epilepsy. Useful in the
Group Incidence in UK (%) Red cell antigen Plasma antibody treatment of severe hyperphosphataemia as it promotes
urinary excretion of phosphate. May be used to lower
A 42 A Anti-B ICP (e.g. in benign intracranial hypertension) by reduc-
B 8 B Anti-A ing CSF production. Has been used to alkalinise the
AB 3 A and B None urine in tumour lysis syndrome or to enhance excretion
O 47 None Anti-A and anti-B in drug intoxications, e.g. with salicylates.
Dosage: 0.250.5g orally/iv od/bd.
Acetylcholinesterase 3

CH3 O (a)

CH3 N+ CH2 CH2 O C CH3 Nicotinic

Somatic muscle

CH3 Nicotinic Muscarinic

Fig. 1 Structure of acetylcholine
Nicotinic Adrenergic
Most nerves

Acetylcholine (ACh). Neurotransmitter, the acetyl

To sweat Nicotinic Muscarinic
ester of choline (Fig. 1). Synthesised from acetylcoen- Sympathetic
zyme A and choline in nerve ending cytoplasm; the reac-
tion is catalysed by choline acetyltransferase. Choline is To adrenal Nicotinic
actively transported into the nerve and acetylcoenzyme medulla
A is formed in mitochondria. ACh is stored in vesicles.
ACh is the transmitter at: (b)
autonomic ganglia.
parasympathetic postganglionic nerve endings.
sympathetic postganglionic nerve endings at sweat
glands and some muscle blood vessels.
the neuromuscular junction. 10 nm
many parts of the CNS, where it has a prominent
role in learning.
Actions may be broadly divided into either muscarinic
or nicotinic, depending on the acetylcholine receptors
involved. ACh is hydrolysed to choline and acetate by
acetylcholinesterase on the postsynaptic membrane. Lipids
Other esterases also exist, e.g. plasma cholinesterase.
See also, Acetylcholine receptors; Neuromuscular trans-
mission; Parasympathetic nervous system; Sympathetic Cytoskeleton
nervous system; Synaptic transmission
Fig. 2 (a) Types of acetylcholine receptors. (b) Structure of nicotinic
Acetylcholine receptors. Transmembrane receptors
acetylcholine receptor
activated by acetylcholine (ACh). Classified according
to their relative sensitivity to nicotine or muscarine
(Fig. 2a).
Nicotinic receptors: ligand-gated ion channels present
at numerous sites within the nervous system; notable M3: Gq-coupled; smooth muscle (increased tone,
examples include the neuromuscular junction (NMJ) e.g. bronchiolar, intestinal), exocrine glands (stimu-
and autonomic ganglia. Each receptor consists of five latory), brain (stimulatory at vomiting centre).
glycosylated protein subunits that project into the M4/5: brain and adrenal medulla.
synaptic cleft. The adult receptor consists of 2 , , Muscarinic receptor agonists include bethanechol,
and units. The subunit is replaced by a subunit carbachol and pilocarpine (in the eye); antagonists
in the neonate. The subunits span the postsynaptic include hyoscine, atropine and ipratropium bromide.
membrane, forming a cylinder around a central ion The activation threshold of muscarinic receptors is lower
channel (Fig. 2b). The two subunits of each receptor than that of nicotinic receptors. Injection of ACh or poi-
carry the binding sites for ACh. Occupation of these soning with anticholinesterases thus causes parasympa-
sites opens the ion channel, allowing cations (mainly thetic stimulation and sweating at lower doses, before
sodium, potassium and calcium) to flow into the cell having effects at autonomic ganglia and the NMJ at
down their concentration gradients; this produces an higher doses.
excitatory postsynaptic potential. If these summate See also, Neuromuscular transmission; Parasympathetic
and exceed the threshold potential, an action poten- nervous system; Sympathetic nervous system; Synaptic
tial is generated. Non-depolarising neuromuscular transmission
blocking drugs are reversible competitive antagonists
of these receptors at the NMJ. Acetylcholinesterase. Enzyme present at the synaptic
Muscarinic receptors: G protein-coupled receptors, membranes of cholinergic synapses and neuromuscular
largely coupled to either adenylate cyclase or phos- junctions. Also found in red blood cells and the placenta.
pholipase C, via Gi and Gq proteins respectively. Metabolises acetylcholine (ACh) to acetate and choline,
Mediate postganglionic neurotransmission via para- thus terminating its action. The N(CH3)3+ moeity of ACh
sympathetic neurones, as well as sympathetic out- binds to the anionic site of the enzyme, and the acetate
flow to sweat glands (Fig. 2a). Classified according to end of ACh forms an intermediate bond at the esteratic
structural subtype, distribution and function: site. Choline is liberated, and the intermediate substrate/
M1: Gq-coupled; stomach (stimulates acid secre- enzyme complex is then hydrolysed to release acetate
tion) and brain (memory formation). (Fig. 3).
M2: Gi-coupled; heart; decreases heart rate, con- See also, Acetylcholinesterase inhibitors; Neuromuscular
tractility and atrioventricular nodal conduction. transmission; Synaptic transmission
4 Acetylcholinesterase inhibitors

Centrally acting acetylcholinesterase inhibitors (e.g.

Acetylcholine donepezil, rivastigmine, galantamine) are used for symp-
O tomatic treatment of Alzheimers dementia. Of anaes-
+ thetic relevance because of their side effects (including
(CH3)3 N CH2 CH2 O C CH3 nausea, vomiting, fatigue, muscle cramps, increased
H creatine kinase, convulsions, bradycardia, confusion),
enhancement of the actions of suxamethonium, and pos-
sible antagonism of non-depolarising neuromuscular
Anionic site Esteratic site blocking drugs.
[Alois Alzheimer (18641915), German neurologist and
Choline O Acetylated See also, Neuromuscular transmission; Organophospho-
+ enzyme rus poisoning
(CH3)3 N CH2 CH2 OH C CH3
O N-Acetylcysteine. Derivative of the naturally occurring
amino acid, L-cysteine. A free radical scavenger, licensed
as an antidote to paracetamol poisoning. Acts by restor-
ing depleted hepatic stores of glutathione and providing
O an alternative substrate for a toxic metabolite of
Acetate paracetamol. Also used as an ocular lubricant and to
C CH3 prevent nephropathy due to radiological contrast media
in patients with reduced renal function.
H Has been investigated for the treatment of fulminant
O hepatic failure, MODS, acute lung injury and neuropsy-
chiatric complications of carbon monoxide poisoning,
as well as a possible role in protection against myo
cardial reperfusion injury. Also used as a mucolytic
Fig. 3 Action of acetylcholinesterase
because of its ability to split disulphide bonds in mucus
Acetylcholinesterase inhibitors. Substances that paracetamol poisoning: 150mg/kg (to a maximum
increase acetylcholine (ACh) concentrations by inhibit- of 12g) in 200ml 5% dextrose iv over 1h, followed
ing acetylcholinesterase (AChE). Used clinically for by 50mg/kg in 500ml dextrose over 4h, then
their action at the neuromuscular junction in myasthenia 100mg/kg in 1 litre dextrose over 16h.
gravis and in the reversal of non-depolarising neuro to reduce viscosity of airway secretions: 200mg 8
muscular blockade. Concurrent administration of an hourly, orally. May be delivered by nebuliser.
antimuscarinic agent, e.g. atropine or glycopyrronium, Side effects: rashes, anaphylaxis. Has been associated
reduces unwanted effects of increased ACh concentra- with bronchospasm in asthmatics.
tions at muscarinic receptors. Effects at ganglia are
minimal at normal doses. Central effects may occur if the
drug readily crosses the bloodbrain barrier, e.g. physo- Achalasia. Disorder of oesophageal motility caused by
stigmine (used to treat the central anticholinergic idiopathic degeneration of nerve cells in the myenteric
syndrome). plexus or vagal nuclei. Results in dysphagia and oesoph-
Have also been used to treat tachyarrhythmias. ageal dilatation. A similar condition may result from
Classified according to mechanism of action: American trypanosomal infection (Chagas disease).
reversible competitive inhibitors: competitive inhi-
Aspiration pneumonitis or repeated chest infections
bition at the anionic site of AChE prevents binding may occur. Treated by mechanical distension of the
of ACh, e.g. edrophonium, tetrahydroaminocrine. lower oesophagus or by surgery. Hellers cardiomyot-
oxydiaphoretic (or acid-transferring) inhibitors:
omy (longitudinal myotomy leaving the mucosa intact)
act as an alternative substrate for AChE, producing may be undertaken via abdominal or thoracic approaches.
a more stable carbamylated enzyme complex. Sub- Preoperative respiratory assessment is essential. Patients
sequent hydrolysis of the complex and thus reacti- are at high risk of aspirating oesophageal contents, and
vation of the enzyme is slow. Examples: rapid sequence induction is indicated.
- neostigmine, physostigmine (few hours). [Carlos Chagas (18791934), Brazilian physician; Ernst
- pyridostigmine (several hours). Heller (18771964), German surgeon]
- distigmine (up to a day). See also, Aspiration of gastric contents; Induction, rapid
organophosphorus compounds: act by irreversibly
phosphorylating the esteratic site of AChE; inhibi-
tion can last for weeks until new enzyme is synthe- Achondroplasia. Skeletal disorder, inherited as an auto-
sised. Examples include: ecothiopate (used for the somal dominant gene, although most cases arise by spon-
treatment of glaucoma); parathion (an insecticide); taneous mutation. Results in dwarfism, with a normal
sarin nerve gas (a chemical weapon). size trunk and shortened limbs. Flat face, bulging skull
Acetylcholinesterase inhibitors augment depolarising vault and spinal deformity may make tracheal intubation
neuromuscular blockade and may cause depolarising difficult, and the larynx may be smaller than normal.
blockade in overdose. They may also cause bradycardia, Obstructive sleep apnoea may occur. Foramen magnum
hypotension, agitation, miosis, increased GIT activity, and spinal canal stenoses may be present, the former
sweating and salivation. resulting in cord compression on neck extension, the
Acidosis, metabolic 5

latter making neuraxial blockade difficult and reducing - filtered HCO3 and excreted H+ form carbonic
volume requirements for epidural anaesthesia. acid.
- carbonic acid is converted to CO2 and water by
Aciclovir. Antiviral drug; an analogue of nucleoside carbonic anhydrase on the cell membrane.
2-deoxyguanosine. Inhibits viral DNA polymerase; - CO2 and water diffuse into the cell and reform
active against herpes viruses and used in the treatment carbonic acid (catalysed again by carbonic
of encephalitis, varicella zoster (chickenpox/shingles) anhydrase).
and postherpetic neuralgia, and for prophylaxis and - carbonic acid dissociates into HCO3 and H+.
treatment of herpes infections in immunocompromised - HCO3 passes into the blood; H+ is exchanged for
patients. Treatment should start at onset of infection; the Na+, etc.
by forming dihydrogen phosphate from monohy-
drug does not eradicate the virus but may markedly
attenuate the clinical infection. drogen phosphate in the distal tubule (HPO4 +H+
Dosage: H2PO4). The H+ is supplied from carbonic acid,
as topical cream, 5 times daily.
leaving HCO3, which passes into the blood.
by combination of ammonia, passing out of the cells,
200800mg orally, 25 times daily in adults.
10mg/kg iv tds, infused over 1h.
with H+, supplied as above. Resultant ammonium
Side effects: rashes, GIT disturbances, hepatic and ions cannot pass back into the cells and are excreted.
renal impairment, blood dyscrasias, headache, dizzi- In acidbase disorders, the primary change determines
ness, severe local inflammation after iv use, confusion, whether a disturbance is respiratory or metabolic. The
convulsions, coma. direction of change in H+ concentration determines aci-
dosis or alkalosis. Renal and respiratory compensation
act to restore normal pH, not reverse the primary change.
Acid. Species that acts as a proton (H+) donor when in For example, in the HendersonHasselbalch equation:
solution (BrnstedLowry definition).
[Johannes N Brnsted (18791947), Danish chemist; [HCO3 ]
pH = pKa + log
Thomas M Lowry (18741936), English chemist] [CO2 ]
See also, Acidbase balance; Acidosis adjustment of the HCO3/CO2 concentration ratio
restores pH towards its normal value, e.g.:
Acidaemia. Arterial pH < 7.35 or hydrogen ion concen- primary change: increased CO2; leads to decreased
tration > 45nmol/l. pH (respiratory acidosis).
See also, Acidbase balance; Acidosis compensation: HCO3 retention by kidneys;
increased ammonium secretion, etc.
Acidbase balance. Maintenance of stable pH in body An alternative approach, suggested by Stewart in 1983,
fluids is necessary for normal enzyme activity, ion distri- focuses on the strong ion difference to explain the
bution and protein structure. Blood pH is normally underlying processes rather than the above traditional
maintained at 7.357.45 (hydrogen ion [H+] concentra- approach, which concentrates more on interpretation of
tion 3545nmol/l); intracellular pH changes with extra- measurements. It is based on the degree of dissociation
cellular pH. During normal metabolism of neutral of ions in solution, in particular the effects of strong ions
substances, organic acids are produced that generate and weak acids, and the role of bicarbonate as a marker
hydrogen ions. of acidbase imbalance rather than a cause.
Maintenance of pH depends on: [Peter Stewart (19211993), Canadian physiologist]
buffers in tissues and blood, which minimise changes See also, Acid; Base; Blood gas interpretation; Breathing,
in H+ concentration. control of; Davenport diagram; Siggaard-Andersen
regulation by kidneys and lungs; the kidneys excrete nomogram
about 6080mmol and the lungs about 15000
20000mmol H+ per day. Acidcitratedextrose solution, see Blood storage
Because of the relationship between CO2, carbonic acid,
bicarbonate (HCO3) and H+, and the ability to excrete Acidosis. A process in which arterial pH < 7.35 (or
CO2 rapidly from the lungs, respiratory function is hydrogen ion > 45mmol/l), or would be < 7.35 if there
important in acidbase balance: were no compensatory mechanisms of acidbase balance.
See also, Acidosis, metabolic; Acidosis, respiratory
H 2O + CO2 H 2CO3 HCO3 + H +
Thus hyper- and hypoventilation cause alkalosis and aci- Acidosis, metabolic. Acidosis due to metabolic causes,
dosis respectively. Similarly, hyper- or hypoventilation resulting in an inappropriately low pH for the measured
may compensate for non-respiratory acidosis or alkalo- arterial PCO2.
sis respectively, by returning pH towards normal. Caused by:
Sources of H+ excreted via the kidneys include lactic increased acid production:
acid from blood cells, muscle and brain, sulphuric acid - ketone bodies, e.g. in diabetes mellitus.
from metabolism of sulphur-containing proteins, and - lactate, e.g. in shock, exercise.
acetoacetic acid from fatty acid metabolism. acid ingestion: e.g. salicylate poisoning.
The kidney can compensate for acidbase distur- +
failure to excrete hydrogen ions (H ):
bances in three ways: - renal failure.

by regulating the reabsorption of filtered HCO3 - distal renal tubular acidosis.
at the proximal convoluted tubule (normally - carbonic anhydrase inhibitors.
8090%): excessive loss of bicarbonate:
- filtered Na+ is exchanged for H+ across the tubule - diarrhoea.
cell membrane. - gastrointestinal fistulae.
6 Acidosis, respiratory

- proximal renal tubular acidosis. Acromegaly. Disease caused by excessive growth

- ureteroenterostomy. hormone secretion after puberty; usually caused by a
May be differentiated by the presence or absence of pituitary adenoma but ectopic secretion may also occur.
an anion gap: Incidence is 68 per million per year.
anion gap metabolic acidosis occurs in renal failure, Features:
lactic acidosis, ketoacidosis, rhabdomyolysis and enlarged jaw, tongue and larynx; widespread
following ingestion of certain toxins (e.g. salicylates, increase in soft tissue mass; enlarged feet and hands.
methanol, ethylene glycol). Nerve entrapment may occur, e.g. carpal tunnel
non-anion gap (hyperchloraemic) metabolic acido- syndrome.
sis is caused by the administration of chloride- respiratory obstruction, including sleep apnoea.
containing solutions (e.g. saline) in large volumes, tendency towards diabetes mellitus, hypertension
amino acid solutions, diarrhoea, pancreatic fistulae, and cardiac failure (may be due to cardiomyopa-
ileal loop procedures, after rapid correction of a thy). Thyroid and adrenal impairment may occur.
chronically compensated respiratory alkalosis or Apart from the above diseases, acromegaly may present
renal tubular acidosis. difficulties with tracheal intubation and maintenance of
Primary change: increased H+/decreased the airway.
bicarbonate. Treatment is primarily pituitary surgery with or
Compensation: without subsequent radiotherapy. Some patients respond
hyperventilation: plasma bicarbonate falls by about to bromocriptine or somatostatin analogues.
1.3mmol/l for every 1 kPa acute decrease in arterial Nemergut EC, Dumont AS, Barry UT, Laws ER (2007).
PCO2, which usually does not fall below 1.31.9 kPa Anesth Analg; 101: 117081
increased renal H secretion. ACS, see Acute coronary syndromes
hyperventilation (Kussmaul breathing). ACT, Activated clotting time, see Coagulation studies
confusion, weakness, coma.
cardiac depression.
Activated protein C, see Protein C
Acta Anaesthesiologica Scandinavica. Official journal of
Treatment: the Scandinavian Society of Anaesthesiology and Inten-
of underlying cause.
sive Care Medicine, first published in 1957.
bicarbonate therapy is reserved for treatment of
severe acidaemia (e.g. pH under 7.1) because of ACTH, see Adrenocorticotrophic hormone
problems associated with its use. If bicarbonate is
required, a formula for iv infusion is: Actin. One of the protein components of muscle (mw
base excess body weight (kg) 43000). In muscle, arranged into a double strand of thin
mmol filaments (F-actin) with globular beads (G-actin), to
which myosin binds, along their length. Present in all
Half this amount is given initially. cells as microfilaments.
other agents under investigation include sodium See also, Muscle contraction
dichloroacetate, Carbicarb (sodium bicarbonate and
carbonate in equimolar concentrations) and THAM Action potential. Sequential changes in membrane
(2-amino-2-hydroxymethyl-1,3-propanediol). potential that result in the propagation of electrical
Morris CG, Low J (2008). Anaesthesia; 63: 294301 and impulses in excitable cells. Neuronal, myocardial and
396411 cardiac nodal action potentials have distinct character-
See also, Acidaemia; Acidbase balance istics, determined by their underlying ionic fluxes (Fig. 4).
Neuronal action potential (Fig. 4a):
A: depolarisation of the membrane by 15 mV
Acidosis, respiratory. Acidosis due to increased arterial (threshold level).
PCO2. Caused by alveolar hypoventilation. B: rapid depolarisation to +40 mV.
Primary change: increased arterial PCO2.
C: repolarisation, rapid at first then slow.
D: hyperpolarisation.
initial rise in plasma bicarbonate due to increased
E: return to the resting membrane potential.
carbonic acid formation and dissociation. Slow initial depolarisation causes opening of voltage-
increased acid secretion/bicarbonate retention by
gated sodium channels (VGSCs) and influx of Na+ into
the kidneys. In acute hypercapnia, bicarbonate con- the cell, which causes further rapid depolarisation. Na+
centration increases by about 0.7mmol/l per 1 kPa conductance then falls as the VGSCs enter an inactivated
rise in arterial PCO2. In chronic hypercapnia it state. K+ efflux via voltage-gated potassium channels
increases by 2.6mmol/l per 1 kPa. occurs more slowly and helps bring about repolarisation.
Effects: those of hypercapnia.
Normal ion distribution (and hence the resting mem-
Treatment: of underlying cause.
brane potential) is restored by the action of the sodium/
See also, Acidaemia; Acidbase balance potassium pump. The action potential is followed by a
refractory period.
Myocardial action potential (Fig. 4b):
ACLS, see Advanced Cardiac Life Support +
phase 0: fast depolarisation and Na influx via
Acquired immune deficiency syndrome (AIDS), see phase 1: onset of repolarisation due to sodium
Human immunodeficiency viral infection channel closure.
Acupuncture 7

phase 0: depolarisation caused by opening of L-type

VGCCs and Ca2+ influx.
phase 3: repolarisation caused by K efflux.
+40 Notably, there is no contribution by Na+ flux to the
action potential in pacemaker cells.
Cardiac excitability is modulated by autonomic inputs
0 and antiarrythmic drugs via their effects on Na+, K+ and
Ca2+ conductance.

B See also, Nernst equation; Nerve conduction

55 Activated charcoal, see Charcoal, activated

70 D
Activated clotting time, see Coagulation studies

Activated protein C, see Protein C

0 1 2 3
Time (ms) Activation energy. Energy required to initiate a chemi-
cal reaction. For ignition of explosive mixtures of anaes-
(b) thetic agents the energy may be provided by sparks, e.g.
from electrical equipment or build-up of static electric-
+20 1 ity. Combustion of cyclopropane requires less activation
energy than that of diethyl ether. Activation energy is
0 less for mixtures with O2 than with air, and least for
stoichiometric mixtures of reactants.
See also, Explosions and fires

0 Active compression/decompression cardiopulmo-

nary resuscitation, see Cardiac massage; Cardiopulmo-
nary resuscitation

4 Active transport. Energy-requiring transport of parti-

cles across cell membranes. Protein pumps within the
membranes utilise energy which is usually supplied by
0 100 200 ATP metabolism, in order to move ions and molecules,
Time (ms) often against concentration gradients. A typical example
is the sodium/potassium pump.
+30 Acupuncture. Use of fine needles (usually 3033 G) to
produce healing and pain relief. Originated in China
thousands of years ago, and closely linked with the phi-
losophy and practice of traditional Chinese medicine.
0 Thus abnormalities in the flow of Qi (Chi: the life energy
that circulates around the body along meridians, nour-
ishing the internal organs) result in imbalance between

0 3
Yin and Yang, the two polar opposites present in all
30 aspects of the universe. Internal abnormalities may be
diagnosed by pulse diagnosis (palpation of the radial
arteries at different positions and depths). The appropri-
4 4 ate organ is then treated by acupuncture at specific
60 points on the skin, often along the meridian named after,
and related to, that organ. Yin and Yang, and flow of Qi,
0 100 200 are thus restored.
Time (ms) Modern Western acupuncture involves needle inser-
tion at sites chosen for more scientific reasons; e.g.
Fig. 4 (a) Nerve action potential (solid) showing changes in sodium around an affected area, at trigger points found nearby,
(dotted) and potassium (dashed) conductance. (b) Cardiac action or more proximally but within the appropriate derma-
potential (see text). (c) Sinoatrial nodal action potential tome. These may be combined with distant or local tra-
ditional points, although conclusive evidence for the
phase 2: plateau due to Ca2+ influx via voltage-gated existence of acupuncture points and meridians has never
calcium channels (VGCCs). been shown. The needles may be left inserted and stimu-
phase 3: repolarisation and K efflux. lated manually, electrically or thermally to increase
phase 4: resting membrane potential. intensity of stimulation. Pressure at acupuncture points
The long plateau of phase 2 prolongs the refractory (acupressure) may produce similar but less intense
period, preventing tetanisation. stimulation.
Cardiac nodal action potential (Fig. 4c): Possible mechanisms:
phase 4: slow spontaneous depolarisation (pace- local reflex pathways at spinal level.
maker potential) caused by a fall in K+ efflux and closure of the gate in the gate control theory of
slow Ca2+ influx via T-type VGCCs. pain.
8 Acute coronary syndromes

central release of endorphins/enkephalins, and pos- ECG pattern). Bundle branch block may be evident.
sibly involvement of other neurotransmitters. NSTEACS may coexist with a normal ECG or:
modulation of the memory of pain. S-T segment depression; S-T segment elevation
Still used widely in China. Increasingly used in the West insufficient to meet reperfusion therapy criteria (see
for chronic pain, musculoskeletal disorders, headache below); T wave flattening or inversion; or biphasic
and migraine, and other disorders in which modern T waves.
Western medicine has had little success. Claims that acu- cardiac biomarkers:
puncture may be employed alone to provide analgesia - cardiac enzymes: largely replaced by troponins.
for surgery are now viewed with scepticism, although it - cardiac troponins:
has been used to provide analgesia and reduce PONV, - regulatory proteins involved in cardiac and
e.g. 5min stimulation at the point P6 (pericardium 6: skeletal muscle contraction.
12 inches [2.55cm] proximal to the distal wrist - composed of three subunits: C, T and I; plasma
crease, between flexor carpi radialis and palmaris longus levels of the latter two are both specific and
tendons). sensitive markers for myocardial damage.
Wang SM, Kain ZN, White P (2008). Anesth Analg; 106: - levels may not rise until 68h after onset of
60210 and 61121 symptoms; samples are therefore routinely
taken at 12h in order to establish a negative
Acute coronary syndromes (ACS). Group of clinical result.
conditions characterised by acute myocardial ischaemia; - levels peak at around 24h, correlating with the
usually caused by acute thrombus formation within a extent of infarction, and may remain elevated
coronary artery upon the exposed surface of a ruptured for 710 days.
or eroded atheromatous plaque. May also occur due - may be elevated in myocardial damage due to
to coronary artery spasm, arteritis or sudden severe other causes, e.g. myocarditis, contusion and
hypo- or hypertension. also other non-cardiac critical illness (e.g. sepsis,
Classification: renal failure, PE), probably reflecting myocar-
S-T segment elevation myocardial infarction dial injury but in most cases not related to coro-
(STEMI): ACS with ST segment elevation on nary artery disease. Likely benefit of NSTEMI
12-lead ECG. Suggestive of total coronary artery treatment in these cases should be assessed on
occlusion. Consistently associated with elevated an individual patient basis.
plasma biomarkers of myocardial damage. Immedi- echocardiography: may be used to assess regional
ate reperfusion therapy (see below) significantly and global ventricular function; regional wall
improves outcomes. ACS with new-onset left bundle motion abnormalities and loss of thickness suggest
branch block (LBBB) or evidence of posterior acute infarction. Also useful in diagnosing compli-
infarction is included in this category for treatment cations of MI (e.g. ventricular aneurysm, mitral
purposes. regurgitation, mural thrombus).
non S-T segment elevation acute coronary syn- Immediate management of suspected ACS:
dromes (NSTEACS): suggestive of sub-total arte- O2 via facemask (if evidence of hypoxia, pulmonary
rial occlusion. Immediate reperfusion therapy is not oedema or ongoing ischaemia), cardiac monitoring,
indicated, although early (within 24h) percutane- 12-lead ECG, iv access.
ous transluminal coronary angioplasty (PTCA) may aspirin 300mg orally.
be considered in high-risk patients. Further subdi- analgesia (e.g. iv morphine in 2mg increments).
vided into: sublingual GTN.
- non S-T segment elevation myocardial infarction associated pulmonary oedema and arrhythmias
(NSTEMI); normal or non-specific changes on should be treated in the usual way.
ECG, with elevated cardiac biomarkers. consideration for immediate reperfusion therapy if:
- unstable angina: ACS without elevated cardiac - presentation < 12h after symptom onset, unre-
biomarkers. lieved by GTN.
Clinical features: - S-T segment elevation > 0.1 mV in two or
pain as for myocardial ischaemia. more contiguous chest leads or two adjacent
arrhythmias; cardiac arrest may occur. limb leads.
anxiety, sweating, pallor, dyspnoea. - new-onset LBBB.
hypertension or hypotension. - posterior infarction (dominant R wave and S-T
cardiac failure and cardiogenic shock. depression in V1V2 chest leads).
Severe infarction is usually associated with more Reperfusion strategies include:
severe symptoms and signs than unstable angina, pharmacological thrombolytic therapy: agents
although painless/silent infarction is also common. include streptokinase, alteplase, tenecteplase
Differential diagnosis: pain and ECG changes may and reteplase. Survival benefit is reduced with
occur with lesions of: increasing delay, and is negligible from 12 h after
heart/great vessels, e.g. aortic dissection, onset of symptoms. Administration of thrombolysis
pericarditis. within 1 h of the patient calling for professional
lung, e.g. PE, chest infection. help is a national audit standard. Contraindications
oesophagus, e.g. spasm, inflammation, rupture. include active bleeding, recent trauma (including
abdominal organs, e.g. peptic ulcer disease, pancre- surgery and CPR), previous haemorrhagic stroke
atitis, cholecystitis. or recent CVA, uncontrolled hypertension and
Investigations: pregnancy.
12-lead ECG (see Myocardial infarction for charac- primary PTCA.
teristic features of STEMI and their localisation by emergency coronary artery bypass surgery.
Acute kidney injury 9

Thrombolysis is generally only preferred if primary Acute kidney injury (AKI). Previously referred to as
PTCA is unavailable or there would be delay of > 90min acute renal failure, describing a rapid deterioration
in delivering it and the presentation is within 3h of (within 48h) from baseline renal function; classified
symptom onset. Primary PTCA is particularly superior according to severity by the RIFLE criteria. An indepen-
if: there is cardiogenic shock; there are contraindications dent risk factor for in-hospital morbidity and mortality
to thrombolysis; or the patient is at high risk of death and a major cause of death in ICU, especially as part of
(e.g. age > 75, previous MI, extensive anterior infarct). MODS. May develop with or without pre-existing renal
Emergency surgery is generally reserved for those impairment. May follow any severe acute illness, dehy-
known to have disease uncorrectable by PTCA or in dration, trauma or major surgery (especially involving
whom primary PTCA fails. the heart and great vessels), hepatic failure, obstetric
Patients not meeting criteria for immediate reperfu- emergencies, and any condition involving sustained
sion (i.e. those with NSTEACS) are managed either hypotension.
invasively (PTCA within 24h plus abciximab iv) or con- May be classified as:
servatively (pharmacological management only). High- prerenal: caused by renal hypoperfusion, e.g. shock,
risk patients are most likely to benefit from invasive hypovolaemia, cardiac failure, renal artery stenosis.
therapy. renal: caused by renal disease:
Pharmacological adjuncts include: - glomerular, e.g.:
clopidogrel and low-molecular weight heparin (e.g. - glomerulonephritis.
enoxaparin): should be given to all patients (in - diabetes mellitus.
the absence of contraindications) with definite or - amyloid.
strongly suspected ACS, in addition to aspirin. Pra- - tubulointerstitial, e.g.:
sugrel and ticagrelor are newer alternatives to clopi- - acute tubular necrosis (ATN): accounts for
dogrel for certain patients. 75% of hospital AKI. Caused by renal hypoper-
GTN sublingually or by iv infusion if pain persists. fusion or ischaemia and/or chemical toxicity,
glycoprotein IIB/IIIa inhibitors (e.g. abciximab and trauma or sepsis. Nephrotoxins include analge-
tirofiban): beneficial in patients undergoing PTCA, sics (e.g. chronic aspirin and paracetamol
those at high risk of death, or both. therapy), NSAIDs, aminoglycosides, immuno-
-adrenergic receptor antagonists: reduce the rate suppressive drugs, radiological contrast media
of reinfarction and VF and should be commenced and heavy metals. Usually (but not always)
within 24h if there are no contraindications, e.g. associated with oliguria (caused by tubular cell
heart block, pulmonary oedema, hypotension. necrosis, tubular obstruction and cortical arte-
Those unable to receive -blockers should receive riolar vasoconstriction).
one of the non-dihydropyridine calcium channel - acute cortical necrosis: typically associated
blocking drugs (e.g. verapamil). with placental abruption, pre-eclampsia and
ACE inhibitors: improve long-term survival after septic abortion, but also with factors causing
MI and should be commenced within 24h, assum- ATN. Confirmed by renal biopsy. Usually
ing no contraindications. irreversible.
magnesium and potassium supplementation to - tubulointerstitial nephritis/pyelonephritis.
maintain normal levels reduces the indidence of - polycystic renal disease.
arrhythmias. Prophylactic administration of antiar- - tubular obstruction, e.g. in myeloma,
rhythmic drugs is no longer recommended. myoglobinuria.
Kumar A, Cannon CP (2009). Mayo Clin Proc; 84: 917 - vascular, e.g. hypertension, connective tissue
38, 102136 disease.
postrenal: caused by obstruction in the urinary tract,
Acute cortical necrosis, see Renal failure e.g. bladder tumour, prostatic hypertrophy.
Distinction between renal and pre- or postrenal
Acute crisis resource management, see Crisis resource failure is important since diagnosis guides treatment,
management and early intervention can prevent irreversible
Acute demyelinating encephalomyelopathy, see Features:
Demyelinating diseases oliguria/anuria.
uraemia and accumulation of other substances
Acute life-threatening events recognition and (e.g. drugs): nausea, vomiting, malaise, increased
treatment (ALERT). Multiprofessional course aimed bleeding and susceptibility to infection, decreased
at reducing the incidence of potentially avoidable cardiac healing.
arrests and admissions to ICU. Targeted especially at reduced sodium and water excretion and oedema,
junior doctors and ward nurses. Sharing principles hypertension, hyperkalaemia, acidosis.
of many life-support training programmes (e.g. ALS, The following may aid diagnosis:
ATLS, APLS, CCrISP), its development embraces both analysis of urine: e.g. tubular casts may be seen in
clinical governance and multiprofessional education. ATN, myoglobinuria may be present.
Uses a structured and prioritised system of patient plasma and urine indices (Table 2).
assessment and management to recognise and treat seri- flushing of the urinary catheter using aseptic
ously ill patients or those at risk of deterioration. technique.
Smith GB, Osgood VM, Crane S (2002). Resuscitation; assessment of cardiac and volume status to exclude
52: 2816 hypovolaemia.
See also, Early warning scores; Medical emergency team; a fluid challenge of, e.g. 200300ml: increased urine
Outreach team output may occur in incipient prerenal failure.
10 Acute lung injury

pulmonary wedge pressure 18mmHg or absence

Table 2 Investigations used to differentiate between prerenal
of clinical evidence of left atrial hypertension.
oliguria and acute kidney injury
arterial hypoxaemia resistant to oxygen therapy

Investigation Prerenal oliguria Renal failure alone (PaO2/FIO2 < 39.9 kPa [300mmHg] for defini-
tion of ALI; < 26.6 kPa [200mmHg] for definition
Specific gravity >1.020 <1.010 of ARDS), regardless of the level of ventilatory
Urine osmolality (mosmol/kg) >500 <350 support.
Urine sodium (mmol/l) <20 >40 Other features:
Urine/plasma osmolality ratio >2 <1.1 reduced respiratory compliance, lung volumes and
Urine/plasma urea ratio >20 <10 increased work of breathing.
Urine/plasma creatinine ratio >40 <20 V/Q mismatch with increased shunt.
Fractional sodium excretion (%) <1 >1 pulmonary vascular resistance may be raised.
Renal failure index <1 >1 in uncomplicated ALI, plasma oncotic pressure is

Fractional sodium excretion =

urine/plasma sodium ratio
100% normal.
urea/plasma creatinine ratio MODS may occur and is a common cause of death.
Pathophysiology: ALI results from damage to either
urine sodium
and renal failure index = the lung epithelium or endothelium. Two pathways of
urine/plasma creatinine ratio
injury exist:
direct insult to lung, e.g. aspiration, smoke
indirect result of an acute systemic inflammatory
diuretic administration, e.g. furosemide or mannitol: response involving both humoral (activation
increased urine output may occur in incipient ATN of complement, coagulation and kinin systems;
but there is no evidence of a prophylactic or thera- release of mediators including cytokines, oxidants,
peutic effect; however reduction in renal O2 demand nitric oxide) and cellular (neutrophils, macro-
(furosemide) and scavenging of free radicals (man- phages and lymphocytes) components. Pulmonary
nitol) have been suggested as being theoretically infiltration by neutrophils leads to interstitial fibro-
beneficial. sis, possibly as a result of damage caused by free
renal ultrasound or biopsy. radicals. Examples include sepsis, pancreatitis and
Management: fat embolism.
directed at the primary cause with optimisation of Histopathological findings can be divided into three
renal blood flow. phases: exudative (oedema and haemorrhage), pro
monitoring of weight, cardiovascular status, includ- liferative (organisation and repair) and fibrotic.
ing JVP/CVP/pulmonary capillary wedge pressure Management involves prompt treatment of the
as appropriate, urea and electrolytes, and acidbase underlying cause and supportive therapy:
status. Accurate recording of fluid balance is vital. general support: nutrition, DVT prophylaxis, pre-
fluid restriction if appropriate, e.g. previous hours vention of infection.
urine output + 30ml/h whilst oliguric. O2 therapy, accepting SpO2 > 90%. CPAP is often
H2 receptor antagonists are commonly adminis- helpful as it improves FRC.
tered to reduce GIT haemorrhage. ventilatory support: IPPV may be necessary if
treatment of hyperkalaemia. CPAP is ineffective. Lung protection strategies
monitoring of drug levels, as clearance may be improve survival in ARDS and consist of using low
reduced considerably. tidal volumes/inspiratory pressures (e.g. 46ml/kg
various dialysis therapies. and PPlateau < 30 cmH2O) with moderate PEEP, tol-
adequate nutrition. erating a degree of respiratory acidosis (permissive
Bellomo R, Kellum JA, Ronco C (2012). Lancet; 380: hypercapnia). High-pressure recruitment manoeu-
75666 vres and high PEEP are often beneficial in
life-threatening hypoxaemia, but increase the risk
Acute lung injury (ALI). Syndrome of pulmonary of barotrauma and impaired cardiac output.
inflammation and increased pulmonary capillary perme- Additional ventilatory strategies include inverse
ability associated with a variety of clinical, radiological ratio ventilation (at I:E ratios of up to 4:1), airway
and physiological abnormalities that cannot be explained pressure release ventilation and high-frequency
by, but may coexist with, left atrial or pulmonary capil- ventilation. Extracorporeal membrane oxygenation
lary hypertension. Associated with sepsis, major trauma, has been used with varying success. Extracorporeal
aspiration pneumonitis, blood transfusion, pancreatitis, CO2 removal may be useful in life-threatening
cardiopulmonary bypass and fat embolism. Onset is hypercapnia.
usually within 23 days of the precipitating illness or prone ventilation improves oxygenation in some
injury, although direct lung insults usually have a shorter patients, although overall mortality is not signifi-
latency. Acute respiratory distress syndrome (ARDS) is cantly improved.
now regarded to be the most severe form of ALI, with diuresis and fluid restriction are often instituted to
a mortality of 4060%. The definitions of ALI and reduce lung water, although avoidance of initial
ARDS are increasingly being challenged and diagnostic fluid overload is thought to be more important.
criteria vary, but the most commonly used are those inhaled vasodilator drugs (e.g. prostacyclin, nitric
defined by the 1994 American-European Consensus oxide) have been used to decrease pulmonary vas-
Committee: cular resistance in aerated areas of lung, thereby
acute onset. reducing V /Q mismatch and improving oxygenation,
bilateral diffuse infiltrates seen on the CXR. but with no demonstrable improved survival.
Adenosine monophosphate, cyclic 11

corticosteroid therapy is controversial. There potassium conductance and reduced calcium conduc-
appears to be no benefit to their prophylactic tance). Also an inhibitory CNS neurotransmitter.
administration, or in high-dose, short-term therapy The drug of choice for treatment of SVT (including
at the onset of ALI/ARDS. However, corticoste- that associated with WolffParkinsonWhite syndrome),
roids may have a role in refractory ARDS. and diagnosis of other tachyarrhythmias by slowing
free radical scavengers, antiprostaglandins and anti- atrioventricular conduction. Its short half-life (810s)
proteases have been investigated. and lack of negative inotropism make it an attractive
Diaz JV, Brower R, Calfee CS, Matthay MA (2010). Crit alternative to verapamil. Not included in the Vaughan
Care Med; 38: 164450 Williams classification of antiarrhythmic drugs.
Has also been used as a directly acting vasodilator
Acute-phase response. A reaction of the haemopoietic drug in hypotensive anaesthesia. Increases cardiac
and hepatic systems to inflammation or tissue injury, output, with stable heart rate. Its effects are rapidly
assumed to be of benefit to the host. There is a rise in reversible on stopping the infusion.
the number/activity of certain cells (neutrophils, plate- Dosage:
lets) and plasma proteins (e.g. fibrinogen, complement, SVT: 6mg by rapid iv injection into a central or
C-reactive protein, plasminogen, haptoglobin) involved large peripheral vein; if unsuccessful after 12min,
in host defence, whilst there is a reduction in proteins may be followed by up to two further boluses of
with transport and binding functions (e.g. albumin, hae- 12mg.
moglobin, transferrin). Initiated by actions of cytokine hypotensive anaesthesia: 50300g/kg/min. ATP
mediators such as interleukins (IL-1, IL-1, IL-6 and has also been used.
IL-11), tumour necrosis factors ( and ) and leukaemia Side effects are usually mild and include flushing,
inhibitory factor. dyspnoea and nausea. Bronchoconstriction may occur
Serum levels of acute-phase proteins (e.g. C-reactive in asthmatics. Bradycardia is resistant to atropine.
protein) can be helpful in diagnosis, monitoring and Adenosines action is prolonged in dipyridamole
prognosis of certain diseases. The rise in fibrinogen levels therapy (because uptake of adenosine is inhibited)
causes an elevation in ESR. The fall in albumin is due to and reduced by theophylline and other xanthines
redistribution and decreased hepatic synthesis. (because of competitive antagonism). Transplanted
hearts are particularly sensitive to adenosines effects.
Acute physiology, age, chronic health evaluation, see [EM Vaughan Williams, English pharmacologist]
APACHE III scoring system
Adenosine monophosphate, cyclic (cAMP). Cyclic
Acute physiology and chronic health evaluation, see adenosine 3,5-monophosphate, formed from ATP by the
APACHE/APACHE II scoring systems enzyme adenylate cyclase. Activation of surface receptors
may cause a guanine nucleotide regulatory protein (G
Acute physiology score (APS). Physiological compo- protein) to interact with adenylate cyclase with resultant
nent of severity of illness scoring systems, such as changes in intracellular cAMP levels (Fig. 5). Many sub-
APACHE II/III and Simplified APS. Weighted values stances act on surface receptors in this way, including
(e.g. 04 in APACHE II) are assigned to each of a range catecholamines, vasopressin, ACTH, histamine, gluca-
of physiological variables (e.g. temperature, mean arte- gon, parathyroid hormone and calcitonin.
rial blood pressure, serum creatinine) on the basis of its Some substances inhibit adenylate cyclase via an
derangement from an established normal range, as inhibitory regulatory protein, e.g. noradrenaline at 2-
measured either upon ICU admission or within 24h of adrenergic receptors (Fig. 5).
entry. The sum of all assigned weighted values for the cAMP is termed a second messenger as it causes
physiological variables that comprise a given scoring phosphorylation of proteins, particularly enzymes, by
system constitutes the acute physiological score. The activating protein kinases. Phosphorylation changes
higher the acute physiology score, the sicker the patient. enzyme and thus cellular activity. cAMP is inactivated
See also, Mortality/survival prediction on intensive care
unit; Simplified acute physiology score
-Receptor 2-Receptor
Acute respiratory distress syndrome (ARDS), see
Acute lung injury
Cell membrane
Acute tubular necrosis, see Renal failure
Gs Gi
Acyclovir, see Aciclovir cyclase
Addiction, see Alcoholism; Substance abuse
Addisons disease, see Adrenocortical insufficiency
ADEM, Acute demyelinating encephalomyelopathy, see Protein kinase of enzymes +
Demyelinating diseases other proteins

Adenosine. Nucleoside, of importance in energy homeo- Gs, stimulatory guanine nucleotide regulatory protein
stasis at the cellular level. Reduces O2 consumption, Gi, inhibitory guanine nucleotide regulatory protein
increases coronary blood flow, causes vasodilatation and
slows atrioventricular conduction (possibly via increased Fig. 5 cAMP involvement in transmembrane signalling
12 Adenosine triphosphate and diphosphate

by phosphodiesterase to 5-AMP. Phosphodiesterase Ideally the opening pressure should be as low as possible
inhibitors, e.g. aminophylline and enoximone, increase to reduce resistance to expiration, but not so low as to
cAMP levels. allow the reservoir bag to empty through it. Most contain
a thin disc held against its seating by a spring, as in the
Adenosine triphosphate and diphosphate (ATP and original Heidbrink valve. Adjusting the tension in the
ADP). ATP is the most important high-energy phos- spring, usually by screwing the valve top, alters the pres-
phate compound. When hydrolysed to form ADP, it sure at which the valve opens. The valve must be vertical
releases energy that may be utilised in many cellular in order to function correctly.
processes, e.g. active transport, muscle contraction. Its Modern valves, even when screwed fully down, will
phosphate bonds are formed using energy from catabo- open at high pressures (60 cmH2O). Most are now
lism; aerobic respiration generates 38 moles of ATP per encased in a hood for scavenging of waste gases.
mole of glucose, while anaerobic respiration (i.e. simple [Jay A Heidbrink (18751957), US anaesthetist]
glycolysis) yields 2 moles of ATP. See also, Anaesthetic breathing systems; Non-rebreathing
Other high-energy phosphate compounds include valves
phosphocreatine (in muscle), ADP itself, and other
nucleotides. ADP, see Adenosine triphosphate and diphosphate
See also, Cytochrome oxidase system; Metabolism; Tri-
carboxylic acid cycle Adrenal gland. Situated on the upper pole of the kidney,
each gland is composed of an outer cortex and an inner
Adenylate cyclase, see Adenosine monophosphate, medulla. The cortex consists of the outer zona glomeru-
cyclic losa (secreting aldosterone), the middle zona fasciculata
(secreting glucocorticoids) and inner zona reticularis
ADH, Antidiuretic hormone, see Vasopressin (secreting sex hormones). Hypersecretion may result
in hyperaldosteronism, Cushings syndrome and
Adhesion molecules. Molecules normally sited on virilisation/feminisation respectively. Hyposecretion
cell surfaces, involved in embryogenesis, cell growth and causes adrenocortical insufficiency.
differentiation, and wound repair. Also mediate endo- The adrenal medulla is thought to be derived from a
thelial cell/leucocyte adhesion, transendothelial migra- sympathetic ganglion in which the postganglionic neu-
tion and cytotoxic T-cell-induced lysis. Four major rones have lost their axons, and secrete catecholamines
families exist: integrins, cadherins, selectins (named after into the bloodstream. Hypersecretion results in phaeo-
the tissues in which they were discovered: L-selectin chromocytoma. See also, Sympathetic nervous system
[leucocytes], E-selectin [endothelial cells], P-selectin
[platelets]) and members of the immunoglobulin Adrenaline (Epinephrine). Catecholamine, acting as a
superfamily. hormone and neurotransmitter in the sympathetic
In general, contact between an adhesion receptor and nervous system and brainstem pathways. Synthesised
the extracellular milieu results in the transmission of and released from the adrenal gland medulla and
information allowing the cell to interact with its environ- central adrenergic neurones (for structure, synthesis and
ment. Defective interactions involving adhesion mole- metabolism, see Catecholamines). Called epinephrine in
cules are implicated in disease (e.g. certain skin diseases, the USA because the name adrenaline, used in other
metastasis of cancer cells). Many pathogens use adhe- countries, was too similar to the US-registered trade
sion receptors to penetrate tissue cells. Overexpression name Adrenalin that referred to a specific product
of intravascular adhesion molecules or receptors has (both adrenaline (Latin) and epinephrine (Greek)
been implicated in rheumatoid arthritis and rejection of referring to the location of the adrenal gland on the
transplanted organs. Control of vascular integrity and kidney).
defence against invasive pathogens require regulation of Stimulates both - and -adrenergic receptors; dis-
adhesive interactions among blood cells and between plays predominantly -effects at low doses, - at higher
blood cells and the vessel walls. Circulating leucocytes doses. Low-dose infusion may lower BP by causing vaso-
bind to the selectins of activated endothelial cells, dilatation in muscle via 2-receptors, despite increased
become activated by chemoattractants and migrate cardiac output via 1-receptors. Higher doses cause 1-
through intracellular gaps to the site of inflammation. mediated vasoconstriction and increased systolic BP,
Thus adhesion molecules play a part in the inflammatory although diastolic pressure may still decrease.
response in sepsis. Clinical uses:
with local anaesthetic agents, as a vasoconstrictor.
Adiabatic change. Volume change of a gas in which in anaphylaxis, cardiac arrest, bronchospasm.
there is no transfer of heat to or from the system. Sudden as an inotropic drug.
compression of a gas without removal of resultant in glaucoma (reduces aqueous humour
heat causes a rise in temperature. This may occur in the production).
gas already present in the valves and pipes of an anaes- in croup.
thetic machine when a cylinder is turned on (hence the Adrenaline may cause cardiac arrhythmias, especially in
danger of explosion if oil or grease is present). Sudden the presence of hypercapnia, hypoxia and certain drugs,
adiabatic expansion of a gas results in cooling, as in the e.g. halothane, cyclopropane and cocaine. During halo-
cryoprobe. thane anaesthesia, suggested maximal dosage of adrena-
See also, Isothermal change line is 10ml 1:100000 solution (100g) in 10min, or
30ml (300g) in 1h. More dilute solutions should be
Adjustable pressure-limiting valves. Valves that open used if possible. Adrenaline should not be used for ring
to allow passage of expired and surplus fresh gas from a blocks of digits or for penile nerve blocks, because of
breathing system, but close to prevent in-drawing of air. possible ischaemia to distal tissues.
-Adrenergic receptor antagonists 13

Dosage: Used to lower BP and reduce afterload by causing

with local anaesthetic agents, 1:200000 concentra- vasodilatation. Compensatory tachycardia may occur.
tion is usual Side effects: postural hypotension, dizziness, tachycar-
anaphylaxis: 50g iv (0.5ml 1:10000 solution), dia (less so with the selective 1-antagonists, possibly
repeated as required. The recommended initial because the negative feedback of noradrenaline at
route in general medical guidelines is usually im 2-receptors is unaffected). Tachyphylaxis may occur.
(0.51.0ml 1:1000 solution), reflecting the risks of
iv administration without appropriate monitoring. -Adrenergic receptor antagonists (-Blockers).
cardiac arrest: 1mg (10ml 1:10000) iv. Competitive antagonists at -adrenergic receptors.
by infusion: 0.010.15g/kg/min initially, increasing Actions:
as required. reduce heart rate, myocardial contractility and O2
croup: 0.5ml/kg (1:1000 solution) nebulised, up to consumption.
5ml maximum, repeated after 30min if required. increase coronary blood flow by increasing diastolic
Subcutaneous injection in shocked patients results in filling time.
unreliable absorption. Tracheal administration in the antiarrhythmic action results from -receptor
absence of iv access is no longer recommended; the antagonism and possibly a membrane-stabilising
intraosseous route is now the suggested alternative. effect at high doses.
See also, Tracheal administration of drugs antihypertensive action (not fully understood but
may involve reductions in cardiac output, central
-Adrenergic receptor agonists. Naturally occurring sympathetic activity and renin levels).
some have partial agonist activity (intrinsic sym
agonists include adrenaline and noradrenaline, which
stimulate both 1- and 2-adrenergic receptors. pathomimetic activity), e.g. pindolol, acebutolol,
Methoxamine and phenylephrine are synthetic 1- celiprolol and oxprenolol.
practolol, atenolol, metoprolol, betaxolol, bisopro-
receptor agonists, used to cause vasoconstriction, e.g. to
correct hypotension in spinal anaesthesia. lol, nebivolol and acebutolol are relatively cardio
Clonidine acts on central 2-receptors. Clonidine and selective, but all will block 2-receptors at high
other 2-receptor agonists (e.g. dexmedetomidine) have doses. Celiprolol has 1-receptor antagonist and 2-
been shown to reduce pain and anaesthetic require- receptor agonist properties, thus causing peripheral
ments, and have also been used for sedation in ICU. vasodilatation in addition to cardiac effects.
labetalol and carvedilol have - and -receptor
Other 2-receptor agonists (e.g. xylazine, detomidine
and medetomidine) have been used in veterinary prac- blocking properties. The former is available for iv
tice as anaesthetic agents for many years. administration and is widely used for acute reduc-
tion in BP.
-Adrenergic receptor agonists. Include adrenaline, esmolol: a few minutes; hydrolysed by red cell
dobutamine and isoprenaline, which stimulate both esterases.
1- and 2-adrenergic receptors to varying degrees. metoprolol, oxprenolol, pindolol, propranolol,
Dopamine acts mainly at 1-receptors. timolol: 24h.
Salbutamol and terbutaline predominantly affect 2- atenolol, practolol, sotalol: 612h.
receptors, and are used clinically to cause bronchodilata- nadolol: 24h.
tion in asthma, and as tocolytic drugs in labour. Most are readily absorbed enterally, and undergo exten-
Formoterol and salmeterol are longer-acting agents sive first-pass metabolism. Practolol, atenolol, celiprolol,
given by inhalation for chronic asthma. Ritodrine is also nadolol and sotalol are water-soluble and largely
used as a tocolytic drug. Some 1-receptor effects are excreted unchanged in the urine; propranolol and meto-
seen at high doses, e.g. tachycardia. They have been used prolol are lipid-soluble and almost completely metabo-
in the treatment of cardiac failure and cardiogenic shock; lised in the liver.
stimulation of vascular 2-receptors causes vasodilata- Uses:
tion and reduces afterload. hypertension, ischaemic heart disease, MI,
arrhythmias, hyperthyroidism, anxiety, migraine
-Adrenergic receptor antagonists (-Blockers). prophylaxis. Have been shown to improve outcome
Usually refer to antagonists that act exclusively at in cardiac failure when added to ACE inhibitor
-adrenergic receptors. therapy. Acute perioperative withdrawal of -
Drugs may be: blockers from patients already receiving them is
selective: known to worsen outcomes; they should therefore
- 1-receptors, e.g. prazosin, doxazosin, terazosin, be continued.
indoramin, phenoxybenzamine. Tamsulosin acts perioperatively: to reduce the hypertensive response
specifically at 1A-receptors and is used in benign to laryngoscopy; to treat perioperative hyperten-
prostatic hypertrophy. sion, tachycardias and myocardial ischaemia; in
- 2-receptors: yohimbine. hypotensive anaesthesia. The use of perioperative
non-selective, e.g. phentolamine. -blockade to reduce perioperative cardiovascular
Labetalol and carvedilol (a drug with similar effects) are morbidity and mortality in high-risk patients under-
antagonists at both - and -receptors. Other drugs may going non-cardiac surgery is no longer advocated as
also act at -receptors as part of a range of effects, e.g. the cardiovascular benefits are outweighed by the
chlorpromazine, droperidol. increased incidence of cerebrovascular accidents.
Antagonism may be competitive, e.g. phentolamine, Side effects:
or non-competitive and therefore longer-lasting, e.g. cardiac failure, especially in combination with other
phenoxybenzamine. negative inotropes.
14 -Adrenergic receptor antagonist poisoning

bronchospasm and peripheral arterial insufficiency,

Table 3 Classification and actions of adrenergic receptors
via blockade of 2-receptors.
increased risk of diabetes when used to treat
hypertension and reduced cardiovascular (1) type Site Effect of stimulation
and metabolic (2) response to hypoglycaemia in
diabetics. 1 Vascular smooth muscle Contraction
depression and sleep disturbance: less likely with Bladder smooth muscle Contraction
water-soluble drugs. (sphincter)
oral practolol was withdrawn because of the oculo- Radial muscle of iris Contraction
mucocutaneous syndrome following its use. The iv Intestinal smooth muscle Relaxation, but contraction
preparation has been withdrawn for commercial of sphincters
Uterus Variable
Salivary glands Viscous secretion
Liver Glycogenolysis
-Adrenergic receptor antagonist poisoning. Uncom- Pancreas Decreased secretion
mon, but overdose is hazardous because of these drugs of enzymes, insulin
low therapeutic ratio. General features include cardiac and glucagon
failure, bradycardia, cardiac conduction defects, hypo- 2 Presynaptic membranes of Reduced release of
tension, bronchospasm, coma and convulsions, the latter adrenergic synapses noradrenaline
two especially with propranolol. Sotalol may cause ven- Postsynaptic membranes Smooth muscle contraction
tricular tachyarrhythmias. Hypoglycaemia is rare. Platelets Aggregation
Treatment: 1 Heart Increased rate and force
of contraction
as for poisoning and overdoses generally.
Adipose tissue Breakdown of stored
CVS effects may require CPR, glucagon (220mg
triglycerides to fatty acids
[50150g/kg in children] iv followed by 50g/ Juxtaglomerular apparatus Increased renin secretion
kg/h) or iv infusion of isoprenaline. Atropine is 2 Vascular smooth muscle Relaxation
often ineffective but should be tried in vagal- (muscle beds)
blocking doses (3mg iv [40g/kg in children]). Bronchial smooth muscle Relaxation
Cardiac pacing may be required. Intestinal smooth muscle Relaxation
Bladder sphincter Relaxation
Adrenergic receptors. G protein-coupled receptors, Uterus Variable; relaxes the
pregnant uterus
activated by adrenaline and other catecholamines, and
Salivary glands Watery secretion
divided into - and -receptors. Further subdivided into Liver Glycogenolysis
1/2/3 and 1/2 receptors (Table 3). Pancreas Increased insulin and
Their effects are mediated by second messengers: glucagon secretion
1-receptor effects by increases in intracellular calcium 3 Adipose tissue Lipolysis
ion concentration, 2-receptor effects by reducing intra-
cellular cAMP, and 1- and 2-receptor effects by
increasing cAMP. There is evidence for mixed receptor
populations at both pre- and postsynaptic membranes.
2-receptors have been further subdivided into 2A
(responsible for central regulation of BP, sympathetic Features:
activity, pain processing and alertness), 2B (causes vaso- acute: hypotension and electrolyte abnormalities
constriction) and 2C (thought to be involved in behav- (hyponatraemia, hyperkalaemia, hypochloraemia,
ioural responses). hypercalcaemia and hypoglycaemia), muscle weak-
See also, -Adrenergic receptor agonists; -Adrenergic ness. In critically ill patients, treatment of occult
receptor agonists; -Adrenergic receptor antagonists; adrenocortical insufficiency may be necessary for
-Adrenergic receptor antagonists; Sympathetic nervous reversal of hypotension that is resistant to vasopres-
system sor drugs.
chronic: weight loss, vomiting, diarrhoea, malaise,
Adrenocortical insufficiency. May be due to: postural hypotension, increased risk of infection,
primary adrenal failure (Addisons disease, high muscle weakness. Dark pigmentation in scars and
ACTH) due to: skin creases occurs in primary disease. Acute insuf-
- autoimmune disease: the most common cause; ficiency (crises) may develop following stress, e.g.
may be associated with other autoimmune disease, infection, surgery, or any critical illness.
e.g. diabetes, thyroid disease, pernicious anaemia, Diagnosed by measurement of plasma cortisol and
vitiligo. ACTH levels, including demonstration of a failed Syn-
- TB, amyloidosis, metastatic infiltration, haemor- acthen test (an impaired cortisol response following
rhage, drugs or infarction, e.g. in shock. Water- administration of tetracosactide, a synthetic analogue of
houseFriderichsen syndrome comprises bilateral ACTH).
adrenal cortical haemorrhage associated with Treatment:
severe meningococcal disease. acute: iv saline, hydrocortisone 100mg iv qds (pref-
secondary adrenal failure (low ACTH) due to: erably as the sodium succinate).
- corticosteroid therapy withdrawal. chronic: hydrocortisone 2030mg/day, fludrocorti-
- ACTH deficiency, e.g. due to surgery, head injury, sone 50300g/day, both orally. Typically, both are
disease of the pituitary or hypothalamus. required in primary insufficiency but only hydrocor-
The term Addisonian describes features of adrenal tisone in secondary insufficiency, although this may
insufficiency irrespective of the cause. not always hold true.
Advanced life support, adult 15

[Thomas Addison (17931860) and Rupert Waterhouse Advanced life support, adult. Component of CPR
(18731958), English physicians; Carl Friderichsen involving specialised equipment, techniques (e.g.
(18861979), Danish paediatrician] tracheal intubation), drugs, monitoring and 100%
oxygen. Airway management may include use of
Adrenocorticotrophic hormone (ACTH). Polypep- tracheal intubation, LMA, Combitube or, rarely,
tide hormone (39 amino acids; mw 4500) secreted by tracheostomy.
corticotropic cells of the anterior pituitary gland in Recommendations of the European Resuscitation
response to corticotropin releasing factor secreted by Council (2010):
the hypothalamus. Release of ACTH is highest in the attention to ABC of basic life support advanced
early morning and is increased by emotional and physi- airway management, if there is a delay in getting
cal stress, including surgery. It increases corticosteroid a defibrillator. Defibrillation should take place
synthesis in the adrenal glands, particularly glucocorti- without delay for a witnessed or in-hospital cardiac
coids but also aldosterone. ACTH production is inhib- arrest. A precordial thump should be considered for
ited by glucocorticoids (i.e. negative feedback). ACTH witnessed, monitored collapse when a defibrillator
or its synthetic analogue tetracosactide (Synacthen) has is not immediately available.
been used in place of corticosteroid therapy in an actions then depend on the initial rhythm:
attempt to reduce adrenocortical suppression, and is - shockable, i.e. VF/pulseless VT:
used for diagnostic tests in endocrinology. They have - defibrillation: a single shock of 150200 J
also been given to treat or prevent post-dural puncture (biphasic) or 360 J (monophasic) followed by
headache. immediate resumption of CPR without reas-
See also, Stress response to surgery sessing the rhythm or feeling for a pulse. After
2min of CPR, reassess and, if indicated, subse-
Adult respiratory distress syndrome, see Acute respi- quent shocks of 150360 J (biphasic) or 360 J
ratory distress syndrome (monophasic). If it is unclear whether the
rhythm is asystole or fine VF, continue basic life
Advance decision (Advance directive; Living will). support and do not attempt defibrillation.
Statement, usually written, that provides for a mentally - adrenaline 1mg iv if VF/VT persists after the
competent person to refuse certain future medical third shock, then 1mg every 35min if it still
treatments, usually involving life-saving therapies, if he/ persists.
she were subsequently to become mentally or physi- - consider and correct potentially reversible
cally incompetent. The directive may be triggered by causes (see below); if not already done, secure
certain background conditions such as dementia, per- the airway, administer oxygen, get iv access.
sistent vegetative state and terminal disease, or acute Cardiac massage and ventilation at 30:2; com-
events including cardiorespiratory arrest, pneumonia, pressions should be uninterrupted once the
acute kidney injury, major CVA or spinal cord injury. airway has been secured.
Legal and ethical issues relate to competence (capacity) - in refractory VF despite three shocks, consider
of the individual, the possibility of changing ones mind, amiodarone 300mg as an iv bolus; 150mg as a
advances in medicine or techniques since the directive second bolus followed by 900mg/24h. Lido-
was written, the refusal of what might be considered caine 1mg/kg is an alternative if amiodarone
basic care (e.g. feeding), difficulties anticipating the is unavailable, but should not be used in addi-
specific circumstances that may arise and therefore tion (maximum 3mg/kg in the first hour). Con-
be covered, and the objections of doctors, other health- sider use of different pad positions/contacts,
care staff and relatives. Previously commonly referred different defibrillator, buffers, if refractory.
to as advance directives, they were renamed advance Magnesium sulphate 8mmol may be indicated
decisions in the Mental Capacity Act 2005, which in hypomagnesaemia, torsades de pointes or
enshrined them into statute for the first time. From digoxin toxicity.
April 2007, in order to be legally valid, an advance deci- - non-shockable, i.e. asystole or pulseless electri-
sion must: cal activity (PEA):
be made by a person 18 years old, with the capac- - adrenaline 1mg as soon as venous access
ity to make it. obtained, repeated every 35min. CPR for
specify the treatment to be refused (can be in lay 2min. Consider and correct potentially revers-
terms) and the circumstances in which this refusal ible causes; cardiac massage and ventilation as
would apply. for VF (see above).
be made freely without the influence of anyone else. - reassess after 2min and repeat if necessary.
be unaltered from when it was made. potentially reversible causes (4 Hs and 4 Ts):
White SM, Baldwin TJ (2006). Anaesthesia; 61: 3819 hypoxaemia, hypovolaemia, electrolyte and meta-
bolic disorders (especially hyper-/hypokalaemia),
Advanced (Cardiac) Life Support (ACLS/ALS). hypothermia, tension pneumothorax, cardiac
System of advanced management of cardiac arrest and tamponade, toxic/therapeutic disturbances (poison-
its training to paramedics, doctors, nurses and other ing and overdoses), thromboembolic/mechanical
healthcare professionals. Also encompasses the recogni- obstruction (PE). A fifth H (hydrogen ions, i.e.
tion and management of periarrest arrhythmias and acidosis) and a fifth T (coronary thrombosis) have
postresuscitation care. In the UK, ALS courses are run also been suggested.
by the Resuscitation Council (UK). In the USA, the drugs are usually given iv, preferably via a central
American Heart Association runs ACLS courses. vein. Peripheral lines should be flushed with 20ml
See also, Advanced life support, adult; Basic life support, saline after each drug. Tracheal administration of
adult; Cardiopulmonary resuscitation drugs is no longer recommended; the intraosseous
16 Advanced Life Support Group

route is now the suggested alternative in the absence in life-saving techniques. Develops and administers
of iv access. several courses such as APLS, MOET, STaR.
consider buffers, e.g. bicarbonate 50ml 8.4% solu-
tion in severe acidosis (pH < 7.1 or base excess Advanced Life Support in Obstetrics (ALSO). Train-
exceeding 10), or specific conditions, e.g. tricyclic ing system developed in the USA and administered by
antidepressant drug poisoning, hyperkalaemia. the American Association of Family Physicians; intro-
if unsuccessful, CPR is generally discontinued after duced in the UK as part of the Maternal and Neonatal
3060min depending on the circumstances (longer Emergency Training (MANET) project. Aimed at
in treatable conditions and in children). training medical and midwifery staff in the practical
post-arrest care: management of maternal and neonatal emergencies and
- checking of arterial blood gases, electrolytes and provision of life support for the mother and child. Similar
CXR. to other CPR training systems (e.g. ACLS, ATLS) in its
- transfer to ICU and cardiorespiratory support as approach and structure.
required. MODS may occur. See also, Cardiopulmonary resuscitation, neonatal
- therapeutic hypothermia to 3234C for 1224h
improves outcome in unconscious adult patients Advanced Paediatric Life Support (APLS). System of
with spontaneous circulation after out-of-hospital management of the sick or injured child, devised by
cardiac arrest due to VF, and possibly for other specialists in paediatrics, accident and emergency medi-
out-of-hospital arrest rhythms or in-hospital cine, anaesthesia and paediatric surgery in the UK and
arrest. administered by the Advanced Life Support Group. The
special situations: system integrates basic and advanced resuscitation tech-
- trauma, choking, near-drowning, electrocution, niques, similar to those employed in ALS/ACLS and
anaphylaxis. ATLS, to permit the assessment and treatment of
- paediatric and neonatal CPR (see Cardiopulmo- paediatric emergencies (e.g. airway obstruction, cardiac
nary resuscitation, paediatric; Cardiopulmonary arrest, hypothermia, convulsions, poisoning and trauma).
resuscitation, neonatal). Incorporates assessment of the airway, breathing and
Recent changes/controversies: circulation with special emphasis on determining if the
importance of effective chest compressions with child has failure of respiration or circulation. Stresses the
minimal interruption is emphasised, to a depth of anatomical and physiological differences between adults
56cm and at a rate of 100120/min; compressions and children whilst emphasising paediatric normal
to continue during defibrillator charging. ranges (e.g. for weight, cardiorespiratory parameters).
atropine is no longer recommended for PEA/ Underlines the usefulness of specific interventions (e.g.
asystole. insertion of an intraosseous needle).
calcium is not recommended routinely because it See also, Cardiopulmonary resuscitation, paediatric
reduces coronary and cerebral blood flow.
hyperglycaemia is thought to worsen the effects of Advanced Trauma Life Support (ATLS). System
cerebral hypoxia. Avoidance of glucose solutions of trauma management devised by physicians in
during CPR has been suggested. Nebraska, USA in 1978 and adopted by the American
the decision to stop CPR may be difficult in certain College of Surgeons in 1979. Based on the concept of
circumstances, as may the decision not to start, reducing morbidity and mortality in the first (golden)
e.g. terminally ill, elderly patients. Routine regular hour following trauma during which patients may die
consideration of do not resuscitate orders has been from potentially survivable injuries (airway obstruction,
suggested. Advance decisions may specify condi- hypovolaemia, pneumothorax, cardiac tamponade), by
tions under which patients do or do not wish to be teaching all members of the trauma team the same
resuscitated. algorithms and procedures which are then carried out
there has been recent controversy over whether by rote on every patient. Has been criticised (mainly by
relatives of cardiac arrest victims should witness senior doctors) because of its very didactic nature,
resuscitation attempts; discomfort of staff and pos- although this is one of its strengths since those most
sible hindrance of CPR may be offset by the benefi- likely to be in the front line of trauma care are tradi-
cial effects of relatives seeing that adequate efforts tionally junior doctors who lack the expertise and
have been expended and their being able to be judgement of their seniors.
present if the patient dies. Consists of the following phases:
manipulation of intrathoracic pressure has been preparation.
suggested in order to improve cardiac output (see triage.
Cardiac massage). primary survey: incorporates assessment of the
Complications include trauma to abdominal organs and integrity and function of the airway, cervical spine,
ribs and those associated with tracheal intubation/ breathing, circulation and neurological status. The
attempted intubation and vascular access. patient is fully exposed to detect all life-threatening
European Resuscitation Council (2010). Resuscitation; injuries, with resuscitation taking place in tandem
81: 121976 with the primary survey. The need for radiographs
See also, Acute Cardiac Life Support; Brainstem death; of the chest, lateral cervical spine and pelvis should
Cough-CPR; Resuscitation Council (UK) be considered during the primary survey but should
not delay resuscitation (the cervical spine is assumed
to require immobilisation for any injury above the
Advanced Life Support Group. UK charity established clavicles until proven otherwise). This takes place
in 1993, aiming to promote and provide both the public simultaneously with the primary survey.
and healthcare professionals with training and education resuscitation of life-threatening conditions.
Afterload 17

secondary survey: the patient is fully examined from and 24h after the reaction if anaphylaxis is sus-
head to toe to exclude injuries to scalp, cranium, pected (99% of plasma tryptase arises from mast
face, neck, shoulders, chest, abdomen, perineum, cells; normal plasma levels < 1ng/ml). A signifi-
long bones, spine and spinal cord. Special pro cant rise is suggestive of anaphylaxis, but its
cedures (e.g. abdominal ultrasound, diagnostic peri- absence does not exclude it; conversely it can
toneal lavage, iv pyelogram, CT of brain) may be occur in non-allergic reactions, albeit to a lesser
undertaken during this phase, before planning of extent. Tryptase is stable in solution and its half-
definitive care. life is 2.5h, so back-calculation to the time of the
continued post-resuscitation monitoring and reaction should still be possible if the samples
re-evaluation. actual times are accurately recorded. Histamine,
definitive care: e.g. surgery, ICU admission or trans- complement and immunoglobulin levels may also
fer to a specialist centre. be useful.
ATLS courses are administered in the USA by the - skin testing is the gold standard for the detection
American College of Surgeons and by the Royal College of IgE-mediated reactions and includes:
of Surgeons of England in the UK. - prick testing (placement of a drop of solution
Carmont MR (2005). Postgrad Med J; 81: 8791 on to the skin of the forearm and gently lifting
the underlying skin with a needle): has been
Adverse drug reactions. Undesired drug effects, usually suggested as the most useful investigation for
divided into: specific agents. Since neat solutions may cause
predictable (type A) dose-related side effects, e.g. flares in normal subjects, 1:10 dilutions or lower
hypotension following thiopental. should also be used. Results are read after 15
unpredictable (type B; idiosyncratic) usually less 20min. A wide range of drugs should be tested.
common reactions. These are unrelated to known Waiting for ~6 months after the reaction has
pharmacological properties of a drug (i.e. not due been suggested in order to allow recovery of the
to common side effects or overdose), usually involv- immune system.
ing the immune system in some way (but not always, - intradermal testing (injection of 0.020.05ml
e.g. MH). dilute solution into the skin of the forearm or
Suspected adverse reactions are voluntarily reported to back) has a higher sensitivity but lower speci
the Medicines and Healthcare products Regulatory ficity and is more likely to trigger a systemic
Agency on yellow cards, introduced in 1964 and updated reaction. Results are read after 2030min.
in 2000. The yellow card system was extended to nurse - patch testing: not useful in suspected periopera-
reporters in 2002. Specific yellow cards for reporting tive anaphylaxis, though useful for contact
anaesthetic drug reactions were introduced in 1988, allergic reactions.
to encourage reporting of serious reactions to estab- - specific IgE antibodies may be assayed using fluo-
lished drugs and any reaction to new drugs. Anaesthe- rescence or (less commonly) radioactive detec-
tists give many different drugs iv to large numbers of tion systems and may be useful in reactions to
patients, and therefore reactions are often seen. Reac- suxamethonium, antibacterial drugs and latex;
tions may be more likely if drugs are given quickly and testing for other anaesthetic drugs is no longer
in combination. considered specific enough. Less sensitive than
Mechanisms: skin testing.
on first exposure: - the role of other tests, e.g. in vitro basophil studies,
- direct histamine release, e.g. tubocurarine, atracu- is controversial.
rium, thiopental, Althesin. It is the anaesthetists responsibility to arrange referral
- alternative pathway complement activation, e.g. to an appropriate centre for further testing after a sus-
Althesin. pected severe reaction, and even after unexplained peri-
apparently on first exposure: prior sensitisation by operative collapse/cardiac arrest.
other (e.g. environmental) antigens may cause Dewachter P, Mouton-Faivre C, Emala CW (2009).
crossover sensitivity to subsequently administered Anesthesiology; 111: 114150
drugs; e.g. reactions to dextrans may involve prior See also, Latex allergy
exposure to bacterial antigens.
requiring prior exposure:
AF, see Atrial fibrillation
- anaphylaxis, e.g. to thiopental.
- classical pathway complement activation, e.g.
Althesin. Other drugs dissolved in Cremophor Affinity. Extent to which a drug binds to a receptor. A
EL may crossreact. drug with high affinity binds more avidly than one with
Features range from mild skin rash to anaphylaxis. First lower affinity, whatever its intrinsic activity.
exposure reactions tend to be milder and more frequent
than those requiring prior exposure. Afterload. Ventricular wall tension required to eject
Reported incidence varies between countries and stroke volume during systole. For the left ventricle, after-
according to definitions but severe allergic reactions are load is increased by:
thought to occur in about 1:10000 to 1:20000 cases. an anatomical obstruction, e.g. aortic stenosis.
Management: raised SVR.
immediate medical management as for decreased elasticity of the aorta and large blood
anaphylaxis. vessels.
testing: increased ventricular wall thickness (greater tension
- a blood sample for mast cell tryptase levels should is needed to produce the necessary pressure
be taken as soon as possible and again at 12h [Laplaces law]).
18 Agonist

Increased afterload results in increased myocardial pass to the systemic circulation via the pulmonary vas-
work/O2 consumption, increased end-systolic ventricular cular bed or cardiac septal defects (a probe-patent
volume and decreased stroke volume. Reduction of foramen ovale exists in 2030% of patients at autopsy).
afterload may be achieved with vasodilator drugs. The bubbles may obstruct the coronary or cerebral
See also, Preload vessels.
Clinical features:
Agonist. Substance that binds to a receptor to cause a reduced cardiac output.
response within the cell. It has high affinity for the recep- tachycardia.
tor and high intrinsic activity. cyanosis.
A partial agonist binds to the receptor, but causes less bronchospasm and pulmonary oedema may occur.
response; it may have high affinity, but it has less intrinsic Dyspnoea, coughing and chest pain are common in
activity. It may therefore act as a competitive antagonist the awake patient.
in the presence of a pure agonist. tinkling sounds on auscultation, e.g. with an oesoph-
An agonistantagonist causes agonism at certain ageal/precordial stethoscope; large amounts of air
receptors and antagonism at others. may cause a mill-wheel murmur. May be detected
See also, Doseresponse curves; Receptor theory by a precordial Doppler probe or transoesophageal
echocardiography, although the extreme sensitivity
Agranulocytosis, see Leucocytes of these techniques may reveal many tiny bubbles
of disputed clinical significance.
AGSS, Anaesthetic gas scavenging system, see sudden reduction of end-tidal CO2 due to increased
Scavenging dead space and decreased cardiac output. End-tidal
nitrogen monitoring has also been used to monitor
AIDS, Acquired immunodeficiency syndrome, see air embolism.
Human immunodeficiency viral infection raised pulmonary artery resistance and pressure.
signs of right ventricular strain on the ECG; ven-
Air. Air contains mostly nitrogen and oxygen, with tricular ectopics or fibrillation may occur.
various other constituents (Table 4). Density is approxi- Treatment:
mately 1.2kg/m3 (1.2g/l). to prevent further embolism:
Medical air may be supplied by a compressor or - seal veins.
in cylinders. The latter (containing air at 137 bar) are - flood the wound with fluid.
grey with black and white shoulders. Piped air is nor- - increase venous pressure using head-down tilt, iv
mally at 4 bar. fluids, jugular venous compression, PEEP. The
See also, individual gases latter and the antigravity suit have been advo-
cated for prevention of air embolism in neurosur-
Air embolism. Introduction of air bubbles into the cir- gery in the traditional sitting position. The use of
culation, usually into veins (although arterial air embo- the modified sitting position with the legs placed
lism has been caused by prolonged flushing of arterial horizontally may decrease the incidence.
lines in neonates). A potential risk when venous pres- once air has entered the circulation:
sure is lower than atmospheric pressure. It may occur - CPR if required.
during any surgery when an open vein is raised above - stop N2O.
the heart; it is particularly likely in neurosurgery with - the head-down, left lateral position is said to
the patient in the sitting position since the dural sinuses increase the likelihood of air remaining in the
do not collapse. May also occur during insertion or right atrium.
removal of a CVP line (minimised by tilting the patient - remove air from the right atrium or ventricle via
head-down during the former and using occlusive dress- a central line. Special wide-bore, multi-holed
ings as opposed to gauze in the latter). Procedures catheters are available for this purpose, although
involving insufflation or injection of gas, e.g. laparo whether these are necessary is controversial.
scopy, epidural anaesthesia using loss of resistance to air, - hyperbaric O2 has been used to reduce the size of
laser surgery with gas-cooled probes, may also lead to the embolism and improve oxygenation.
embolism. N2O diffuses into bubbles, increasing their Mirski MA, Lele AJ, Fitzsimmons L, Toung TJK (2007).
volume and exacerbating their effects. Morbidity and Anesthesiology; 106: 16477
mortality are dependent on the volume of the air
entrained and the rate of accumulation. Airway. The upper airway includes the mouth, nose,
Air in the heart is compressed with each beat and not pharynx and larynx. Maintenance of the airway in the
expelled, causing foaming and interruption of blood unconscious or anaesthetised patient is achieved by
flow. Pulmonary vessels may become obstructed. Small combined flexion of the neck and extension at the
bubbles may have little effect. Paradoxical air emboli atlanto-occipital joint (the sniffing position), and lifting
the angles of the mandible forward. The tongue is lifted
forward by the genioglossus muscle which is attached to
Table 4 Constituents of dry natural air by volume the back of the point of the jaw; the hyoid bone and
larynx are pulled forward by the hyoglossus, mylohyoid,
Nitrogen 78.03% Hydrogen 0.001% geniohyoid and digastric muscles. Upward pressure on
O2 20.99% Helium 0.0005% the soft tissues of the floor of the mouth may cause
Argon 0.93% Krypton 0.0001% obstruction, particularly in children, and should be
CO2 0.03% Xenon 0.000008% avoided. In the lateral (recovery) position, the tongue
Neon 0.0015% and jaw fall forward under gravity, improving the airway.
Airway obstruction during anaesthesia has traditionally
Airway obstruction 19

been attributed to the tongue falling back against the - increasing gas flow: heliumO2 mixtures.
posterior pharyngeal wall. Radiological and electromyo- - bypassing the obstruction: tracheal intubation,
graphic studies suggest that obstruction by the soft tracheostomy or cricothyrotomy. The last two
palate or epiglottis secondary to reduced local muscle may be difficult if the anatomy is distorted.
activity may also be responsible. IPPV:
See also, Airways; Tracheobronchial tree - causes of increased airway pressure and hypoven-
tilation other than obstruction due to equipment
Airway exchange catheter. Device placed into the (e.g. bronchospasm, pneumothorax, inadequate
trachea both to maintain oxygenation after tracheal neuromuscular blockade and coughing) should be
extubation (i.e. inserted through the tracheal tube before considered.
the latter is removed), and to facilitate reintubation - while ventilating by hand, all tubing should be
should it be required. Available devices share similar checked for kinks. A suction catheter will not pass
features: they are long, hollow catheters, able to be down the tracheal tube if the latter is obstructed,
attached to an O2 supply at their proximal end (e.g. using e.g. by kinks, mucus, herniated cuff. If auscultation
a detachable 15-mm connector) and stiff enough to act of the chest does not suggest bronchospasm or
as a guide for a tracheal tube passed over them. The pneumothorax, the cuff should be deflated and
distal end may be angulated, allowing the catheter also the tracheal tube pulled back slightly. If ventila-
to be used as an introducer, e.g. during direct laryngos- tion does not improve, the tube should be removed
copy. A specific type of exchange catheter (the Aintree and ventilation attempted by facemask.
catheter) has been designed for exchanging an LMA Anaesthesia for patients with airway obstruction:
with a tracheal tube via a flexible fibrescope. preoperatively:
- preoperative assessment for the above features
Airway obstruction. Obstruction may occur at the and management as above.
mouth, pharynx, larynx, trachea and large bronchi. It - useful pre-induction investigations include:
may be caused by the tongue, laryngospasm, strictures, - radiography, including tomograms, thoracic
tumours and soft tissue swellings, oedema, infection inlet views and CT scanning.
(e.g. diphtheria, epiglottitis) and foreign objects, includ- - flexible nasendoscopy images.
ing anaesthetic equipment. Hypotonia of the muscles - arterial blood gas interpretation.
involved in upper airway maintenance is common during - flowvolume loops.
anaesthesia. During IPPV, mechanical obstruction may - premedication may aid smooth induction of
occur at any point along the breathing system. anaesthesia but excessive sedation should be
Airway obstruction results in hypoventilation and avoided.
increased work of breathing. It may present as an acute perioperatively:
medical emergency requiring immediate management. - severe/critical obstruction may warrant securing
Features: of the airway using an awake technique (e.g.
spontaneous ventilation: tracheostomy under local anaesthesia or awake
- dyspnoea, noisy respiration, stridor. fibreoptic intubation). The choice depends on
- use of accessory muscles of respiration, with patient compliance, operator experience and
tracheal tug, supraclavicular and intercostal site/severity of the obstruction (e.g. large
indrawing, and paradoxical see-saw movement glottic tumours may be impassable with an
of abdomen and chest. endoscope).
- tachypnoea, tachycardia and other features of - if general anaesthesia is deemed preferable and/
hypoxaemia, hypercapnia and respiratory failure. or necessary it should be induced with full moni-
- pulmonary oedema may occur if negative intra- toring and facilities for resuscitation and trache-
thoracic pressures are excessive. ostomy/cricothyrotomy immediately available.
- during anaesthesia, poor movement of the reser- - patients with proximal airway obstruction usually
voir bag may occur. adopt the optimal head and neck position for
IPPV: maximal air movement; muscle relaxation caused
- increased airway pressures with reduced chest by iv induction may therefore lead to sudden
movement; noisy respiration or wheeze. complete obstruction. It may be impossible to
- features of hypoxaemia and hypercapnia. ventilate the patient by facemask, and tracheal
Management: intubation may be difficult or impossible. IV
O2 therapy (increased FIO2 during anaesthesia). anaesthetic agents and neuromuscular blocking
spontaneous ventilation: drugs should therefore be used with extreme
- general measures in unconscious/anaesthetised caution. Inhalational induction (e.g. sevoflurane in
patients: O2) is traditionally advocated, although induction
- turn to the lateral position if practical. may be slow and difficult. If obstruction worsens,
- correct positioning of the head, elevation of anaesthesia is allowed to lighten. Tracheal intuba-
the jaw, and use of oropharyngeal or nasopha- tion is performed without paralysis; lidocaine
ryngeal airways. Tracheal intubation may be spray may be useful.
required as below. postoperatively: as for difficult intubation (see
- specific treatment, e.g.: Intubation, difficult).
- antibacterial drugs for infection. Classical management of patients with large airway com-
- fresh frozen plasma or C1 esterase inhibitor for pression, e.g. by mediastinal tumours, also employs inha-
hereditary angio-oedema. lational induction and anaesthesia. This avoids acute
- nebulised adrenaline for croup. exacerbation of airway obstruction caused by sudden
- Heimlich manoeuvre for choking. muscle relaxation.
20 Airway pressure

In the recovery room or casualty department, all support the tracheal tube.
unconscious patients should be positioned in the recov- allow suction.
ery position, to protect them from aspiration and airway act as a conduit for fibreoptic intubation.
obstruction. facilitate CPR.
See also, Intubation, awake Thus usually employed during anaesthesia and in uncon-
scious patients.
Airway pressure. Pressure within the breathing system Types:
and tracheobronchial tree. Useful as an indicator of oropharyngeal: Guedel airway is most commonly
mechanical obstruction to expiration during spontane- used. Modifications include a side port for attach-
ous ventilation. During IPPV, changes in airway pressure ment to a fresh gas source (Waters airway), 15mm
may indicate disconnection, dynamic hyperinflation, connectors for attachment to a breathing system,
mechanical obstruction, decreased lung compliance or caps with side ports, and airways used for fibreoptic
increased airway resistance, and the risk of barotrauma. intubation (Fig. 6). A cuffed oropharyngeal airway
The pressure measured at the mouth may considerably (COPA) with a 15mm connector was described in
exceed alveolar pressure during positive pressure 1991 but is not widely used. Oropharyngeal airways
breaths, especially if airway resistance and gas flow rates are the commonest cause of damage to teeth in
are high. During expiration, mouth pressure falls to zero, anaesthetised patients. They must be placed with
but alveolar pressure may lag behind. In some ventila- care, particularly in children where soft tissue
tors airway pressure is measured in the expiratory limb damage can easily occur.
of the breathing system. oral supraglottic: designed to be placed close to,
but above, the larynx, resulting in a better seal
Airway pressure release ventilation (APRV). CPAP and therefore the ability to control ventilation.
with intermittent release to ambient pressure (or a lower Include (Fig. 7):
level of CPAP) causing expiration. Spontaneous venti - LMA: the most widely used.
lation may continue between APRV breaths. Allows - laryngeal tube: requires less mouth opening. Has
reduction of mean airway pressure, and has been used two cuffs, inflated by a single inflation tube. Avail-
to support respiration in ARDS. Weaning is achieved by able in seven sizes, suitable for babies up to adults.
reducing the frequency of CPAP release until the patient Performs better for IPPV in studies than for
is breathing spontaneously with CPAP maintained. spontaneous ventilation. A new double-lumen
Esan A, Hess DR, Raoof S, George L, Sessler CN (2010). version (laryngeal tube Sonda) is similar in func-
Chest; 137: 120316 tion to the Combitube (see Oesophageal obtura-
tors and airways).
Airway resistance - i-gel: similar in function to the LMA but the
cuff is made of soft gel and non-inflatable; incor-
driving pressure porates a gastric channel and bite block. Available
Resistance =
gas flow in sizes 35.
Driving pressure is the difference between alveolar and - others have been described but are not widely
mouth pressures, and may be measured using the body used:
plethysmograph. Alternatively, gas flow may be halted - Airway Management Device (AMD): has a
repeatedly for a tenth of a second at a time with a single lumen and two cuffs, inflated indepen-
shutter; during the brief period of no flow, alveolar pres- dently. The lower cuff compresses the devices
sure may be measured at the mouth. Gas flow can be lumen when inflated; when the cuff is deflated,
measured with a pneumotachograph. a suction catheter may be passed into the
Most of the resistance resides in the large and medium- oesophagus. Available in three adult sizes.
sized bronchi; severe damage to the small airways may - Streamlined Liner of the Pharyngeal Airway
occur before a measurable increase in resistance. (SLIPA): similar to the LMA but with a soft
At low lung volumes, the radial traction produced hollow pharyngeal portion instead of a cuff, that
by lung parenchyma surrounding the airways, and that acts both as a seal and as a sump for collecting
holds them open, is reduced; thus airway calibre is liquid should regurgitation occur. Available in
reduced, and resistance increased. During forced expira- six adult sizes (4757), corresponding to the
tion, some airways may close, causing air trapping. Bron- width of the thyroid cartilage.
choconstriction and increased density or viscosity of the - Cobra: single-use device similar in function to
inspired gas also increase resistance (density because the LMA; available in eight sizes.
flow is not purely laminar in the airways). Resistance is nasopharyngeal: usually smooth non-cuffed tubes
increased in chronic bronchitis due to airway narrowing. with a flange to prevent pushing them completely
In emphysema the airways close because of lung paren- into the nose. Avoids risk to capped teeth, but may
chymal destruction. cause epistaxis. Cuffed nasal airways may be held in
Airway resistance increases during anaesthesia; this place by the inflated cuff, and allow attachment to
may be caused by bronchospasm, reduction in FRC and a breathing system.
lung volume, or by the tubes and connections of the Insertion of an airway may cause gagging, coughing
breathing system. and laryngospasm unless the patient is comatose or
See also, Closing capacity; Compliance adequately anaesthetised; these may also occur on
Airways. Devices placed in the upper airway (but not [Robert Alvin Berman (19141999), US anaesthetist;
into the larynx); used to: Andranik Ovassapian (19362010), Iranian-born US
relieve airway obstruction. anaesthetist; R Tudor Williams, Canadian anaesthetist]
prevent biting and occlusion of the tracheal tube. McIntyre JWR (1996). Can J Anaesth; 43: 62935
Albendazole 21


(b) (b)






Fig. 6 Examples of oropharyngeal airways: (a) Guedel; (b) Berman

intubating; (c) Ovassapian; (d) Williams. The latter three are used for
fibreoptic intubation; the Berman and Ovassapian allow the airway to
be removed without dislodging the tracheal tube once placed

Fig. 7 Examples of supraglottic airways: (a) laryngeal tube; (b) i-gel;

(c) AMD; (d) SLIPA; (e) Cobra. (See Fig. 97 for LMA.)
AIS, see Abbreviated injury scale

AKI, Acute kidney injury, see Renal failure Dose: up to 800mg orally/day in divided doses for 28
days, followed by a 14-day treatment-free period. Up
Albendazole. Agent used (off-licence) in conjunction to three cycles may be given.
with surgery to treat hydatid disease. May be used alone Side effects: GIT upset, headache, dizziness, hepatic
in inoperable cases. impairment, pancytopenia.
22 Albumin

Albumin. The most abundant plasma protein (mw pure methanol may result in permanent blindness,
69000): normal plasma levels: 3550g/l. Important in the with the fatal adult dose around 30ml (methylated
maintenance of plasma oncotic pressure, as a buffer, and spirits contains 5% methanol and 95% ethanol, the
in the transport of various molecules such as bilirubin, latter causing the most toxicity). Blood levels
hormones, fatty acids and drugs. It is synthesised by the greater than 500mg/ml (15mmol/l) indicate severe
liver and removed from the plasma into the interstitial poisoning.
fluid. It may then pass via lymphatics back to the plasma, Management includes gastric lavage if within 2h
or into cells to be metabolised. May have a role as a free of ingestion, administration of bicarbonate, inhibi-
radical scavenger. Depletion occurs in severe illness, tion of further methanol metabolism with ethanol
infection and trauma. Available for transfusion as 4.5% (50g orally/iv followed by 1020g/h iv to produce
and 20% solutions; currently the most expensive non- blood levels of 100200g/dl [2030mmol/l]). More
blood plasma substitute. Has been used as a colloid when recently, fomepizole has gained acceptance as an
providing iv fluid therapy for critically ill patients but alternative to alcohol and may reduce the need for
hypoalbuminaemia in these patients usually results from haemodialysis, which may still be required in severe
increased metabolism of circulating albumin; adminis- cases. Folic acid or its metabolites have also been
tration does not generally result in maintained plasma used (utilised in formate metabolism). Haemodialy-
albumin levels and no improvement in outcome has sis has been used in severe poisoning.
been found when compared with cheaper alternatives. isopropanol: effects are caused by the alcohol itself,
The effect of albumin administration on mortality in not its metabolites. Effects are similar to those of
critically ill patients remains controversial, although ethanol but longer lasting. Gastritis, renal tubular
recent studies suggest mortality is not increased, except acidosis, myopathy and haemolysis may occur.
possibly in patients with traumatic brain injury. The lack Management is with gastric lavage if within 2h
of any clear advantage of using albumin solutions for of ingestion and supportive thereafter.
resuscitation, and its expense, has led to a decline in ethylene glycol: toxicity results from metabolism by
its use. alcohol dehydrogenase to glycoaldehyde and oxalic/
Hartog CS, Bauer M, Reinhart K (2011). Anesth Analg; formic acids. The former causes cerebral impair-
112: 15664 ment, while the latter produce severe metabolic
See also, Blood products; Protein-binding acidosis and acute tubular necrosis. The fatal
adult dose is ~100g, although patients have sur-
Albuterol, see Salbutamol vived much larger doses. Features include intoxica-
tion, vomiting, haematemesis, coma, convulsions,
Alcohol, see Alcohols depressed reflexes, myoclonus, nystagmus, papilloe-
dema and ophthalmoplegia within the first 12h;
Alcohol poisoning. Problems, features and management tachycardia, hypertension, pulmonary oedema and
depend on the alcohols ingested: cardiac failure within the next 12h; and renal failure
ethanol: commonly complicates or precipitates over the subsequent 23 days. Investigations may
acute illness or injury, especially trauma. Results reveal severe lactic acidosis, a large anion gap and
in depressed consciousness (hindering assessment osmolar gap, hypocalcaemia and hyperkalaemia.
of head injury), potentiation of depressant drugs Blood levels exceeding ~200mg/l (~35mmol/l)
and disinhibition. Patients are often uncooperative. indicate severe poisoning.
Other effects of acute intoxication include vaso- Management includes haemodialysis, ethanol
dilatation, tachycardia, arrhythmias, vomiting, and fomepizole; thiamine and pyridoxine have also
reduced lower oesophageal sphincter pressure, gas- been used.
tric irritation, delayed gastric emptying, hypo Jammalamadaka D, Raissi S (2010). Am J Med Sci; 339:
glycaemia (typically 636h after ingestion, especially 27681
in a starved or malnourished individual), metabolic
acidosis, dehydration (due to diuretic effect), coma Alcohol withdrawal syndromes. May be precipitated
and convulsions. Intoxication occurs at blood levels by acute illness or surgery, even if regular intake of
~100150mg/dl (2233mmol/l), loss of muscle alcohol (ethanol) is apparently not excessive and without
coordination at ~150200mg/dl (3343mmol/l), the other features of alcoholism.
decreased level of consciousness at ~200300mg/dl Features:
(4365mmol/l) and death at ~300500mg/dl (65 most commonly, tremulousness, agitation, nausea,
109mmol/l). The fatal adult dose is about 300 vomiting: usually within 68h of abstinence.
500ml absolute alcohol (5001200ml strong spirits) hallucinations: usually visual; occur 1030h after
within 1h. abstinence and in under 10% of cases.
Management is mainly supportive, as for poison- convulsions: occur up to 48h after abstinence and
ing and overdoses. Haemodialysis has been used in in about 5% of cases.
severe poisoning. Features of alcoholism require delirium tremens: includes the above symptoms
attention if present. plus confusion, disorientation, sweating, tachycardia
methanol: toxicity results from hepatic metabo- and hypertension. Occurs up to 23 days after absti-
lism of methanol to formaldehyde and thence nence and in about 5% of cases.
formic acid, the latter being a potent inhibitor of Management includes sedative drugs (e.g. benzodiaze-
mitochondrial cytochrome oxidase. Features occur pines, carbamazepine, clomethiaziole) and reassurance.
after 836h and include intoxication, vomiting, More recently, clonidine has been used successfully to
abdominal pain, coma, visual disturbances, severe smooth withdrawal. Vitamin B6 supplements are usually
metabolic acidosis with a large anion gap and administered, but if there is a risk of encephalopathy a
osmolar gap, and hyperglycaemia. About 10ml mixture of vitamins is best prescribed.
Alfentanil hydrochloride 23

McKeon A, Frye MA, Delanty N (2008). J Neurol Neu- ethylene glycol (glycol; (CH2OH)2): used as an
rosurg Psychiatry; 79: 85462 antifreeze.
propylene glycol (CH3.CHOH.CH2OH): used as a
Alcoholism. Form of substance abuse in which there is solvent in drugs, e.g. etomidate, GTN.
narrowing of the drinking repertoire (loss of day-to-day All are CNS depressants, rapidly absorbed from the
variation in drinking habits), increased tolerance to upper GIT (also by inhalation and, to varying degrees,
alcohol (ethanol), symptoms of alcohol withdrawal syn- percutaneously) and metabolised by hepatic alcohol
dromes when intake is stopped, a craving for alcohol dehydrogenase to the aldehyde; all except isopropanol
and drinking in the early part of the day/middle of the are metabolised further to the corresponding acid by
night. May precipitate admission to hospital as a conse- aldehyde dehydrogenase.
quence of acute alcohol poisoning or intoxication, or See also, Alcohol poisoning; Alcohol withdrawal
impaired organ function resulting from chronic abuse; syndromes
may also complicate the management of incidental
disease or surgery. Alcuronium chloride. Non-depolarising neuromuscular
Effects of chronic alcohol intake:
blocking drug, introduced in 1961 and withdrawn in the
cerebral/cerebellar degeneration, peripheral neu- UK in 1994. Caused mild histamine release and hypoten-
ropathy, psychiatric disturbances (Wernickes sion, but anaphylaxis, when it occurred, was often severe.
encephalopathy, Korsakoffs psychosis).
withdrawal may lead to tremor, anxiety, hallucina-
Aldosterone. Mineralocorticoid hormone secreted by
tions, convulsions, delirium tremens.
the outer layer (zona glomerulosa) of the cortex of the
gastritis, peptic ulcer disease, oesophageal varices;
adrenal gland. Secreted in response to reduced renal
may lead to gastrointestinal haemorrhage.
blood flow (via renin/angiotensin system), trauma and
anxiety (via ACTH release), and hyperkalaemia and
fatty liver, hepatic enzyme induction, cirrhosis
hyponatraemia (direct effect on the adrenal cortex).
causing hepatic failure, coagulopathy.
Increases sodium and water reabsorption from renal
malnutrition, immunodeficiency.
tubular filtrate, sweat and saliva. Acts via mineralocorti-
myopathy, cardiomyopathy.
coid receptors to upregulate basolateral sodium/potas-
[Karl Wernicke (18481904), German neurologist;
sium pumps at the distal renal tubule and collecting duct.
Sergei Korsakoff (18531900), Russian neurologist and
Sodium and water are retained while potassium and
hydrogen ion excretion is increased.
Schuckit MA (2009). Lancet; 373: 492501
Hyperaldosteronism results in hypertension and
hypokalaemia. In cardiac failure and cirrhosis, aldoste-
Alcohols. Group of aliphatic (i.e. non-cyclic) organic
rone levels may be raised, although the mechanism is
chemicals containing one or more hydroxyl (OH)
groups and that form esters (containing the OO
Aldosterone antagonists, e.g. spironolactone, potas-
linkage) with acids. Used as solvents and cleaning agents.
sium canrenoate and eplerenone, cause sodium loss and
Those of particular medical/anaesthetic relevance
potassium retention.
ethanol (ethyl alcohol; C2H5OH): commonly
referred to as alcohol; widely drunk throughout ALERT, see Acute life-threatening events recognition
the world and often abused, resulting in acute toxic- and treatment
ity or alcoholism. Used in the past as an anaesthetic
agent and as a tocolytic drug. May be added to irrig- Alfentanil hydrochloride. Opioid analgesic drug
ant solution to monitor the latters uptake during derived from fentanyl. Developed in 1976. In compari-
TURP. Also used for destructive injection, e.g. into son with fentanyl, alfentanil has a:
neural tissue in chronic pain management. In the faster onset of action (< 1min).
ICU, iv alcohol may be used to treat methanol poi- lower pKa (6.5 vs. 8.4), rendering it mostly (90%)
soning; it may also be useful for sedating alcoholics unionised at body pH.
(110g/h of a 510% solution). shorter elimination half-life due to its lower volume
Metabolised mostly to acetaldehyde, then of distribution (in spite of a lower clearance).
acetate, acetyl coenzyme A and finally CO2 and lower potency (approximately one-tenth).
water via the tricarboxylic acid cycle. Five per cent Has minimal cardiovascular effects, although bradycar-
is excreted unchanged, mostly in the urine but also dia and hypotension may occur. Other effects are similar
in the breath. The rate of metabolism is 10ml/h at to those of fentanyl. Metabolised in the liver to
concentrations above 100mg/dl (22mmol/l); below noralfentanil.
this level it is subject to first-order kinetics with a Dosage:
half-life of about 1h (see MichaelisMenten kinet- for spontaneously breathing patients, up to 500mg
ics). Produces 30 kJ/g (7 Cal/g); it has been used as initially, followed by increments of 250mg. Slow
an iv energy source. injection reduces the incidence of apnoea.
methanol (methyl alcohol; CH3OH): derived from 3050g/kg to obtund the hypertensive response to
distillation of wood or from coal or natural gas. tracheal intubation. Up to 125g/kg is used in
Used in the petroleum and paint industries. Con- cardiac surgery.
tained with ethanol in methylated spirits. Extremely for infusion, a loading dose of 50100g/kg, fol-
toxic if ingested. lowed by 0.51g/kg/min. Higher rates have been
isopropanol (isopropyl alcohol; (CH3)2CHOH): used in TIVA. The infusion is discontinued 10
used as a solvent and to clean the skin before inva- 30min before surgery ends. Also used for sedation
sive procedures. Oxidised in the liver to acetone. in ICU at 3060g/kg/h initially.
24 Alimemazine tartrate

Alimemazine tartrate (Trimeprazine). Phenothiazine- Effects: those of hypocapnia.

derived antihistamine drug, used for premedication in Treatment: of underlying cause.
children. More sedative than other antihistamines. Has See also, Acidbase balance
antiemetic properties.
Dosage: up to 2mg/kg orally 12h preoperatively. Alkylating drugs, see Cytotoxic drugs
Side effects include dry mouth, circumoral pallor and
dizziness. May cause postoperative restlessness due to Allens test. Originally described for assessing arterial
antanalgesia. Has been implicated in causing pro- flow to the hand in thromboangiitis obliterans. Modified
longed respiratory depression on rare occasions. for assessment of ulnar artery flow before radial arterial
cannulation. The ulnar and radial arteries are com-
Aliskiren, see Renin/angiotensin system pressed at the wrist, and the patient is asked to clench
tightly and open the hand, causing blanching. Pressure
Alkalaemia Arterial pH > 7.45 or H+ concentration < over the ulnar artery is released; the colour of the palm
35nmol/l. normally takes less than 510 s to return to normal,
See also, Acidbase balance; Alkalosis with over 15 s considered abnormal. A similar manoeu-
vre may be performed with the radial artery before
Alkalosis. A process in which arterial pH > 7.45 (or ulnar artery cannulation. Although widely performed,
H+ concentration < 35nmol/l), or would be > 7.45 if it is inaccurate in predicting risk from ischaemic
there were no compensatory mechanisms of acidbase damage.
balance. [Edgar Van Nuys Allen (19001961), US physician]
See also, Alkalosis, metabolic; Alkalosis, respiratory Brzezinski M, Luisetti T, London MJ (2009). Anesth
Analg; 109: 176381
Alkalosis, metabolic. Inappropriately high pH for the
measured arterial PCO2. Allergic reactions, see Adverse drug reactions
Caused by:
acid loss, e.g. vomiting, nasogastric aspiration. Allodynia. Pain from a stimulus that is not normally
base ingestion: painful.
- bicarbonate (usually iatrogenic).
- citrate from blood transfusion. Alpha-adrenergic ..., see -Adrenergic
- milk-alkali syndrome.
- forced alkaline diuresis. Alprostadil. Prostaglandin E1, used to maintain patency
potassium/chloride depletion leading to acid urine of a patent ductus arteriosus in neonates with congenital
production. heart disease in whom the ductus is vital for survival, e.g.
Primary change: increased bicarbonate/decreased pulmonary atresia/stenosis, Fallots tetralogy, coarcta-
hydrogen ion. tion, transposition of the great arteries.
Compensation: Dosage: 510ng/kg/min initially via the umbilical
hypoventilation: reaches its maximum within 24h, artery or iv, titrated to a maximum of 100ng/kg/min.
usually with an upper limit for arterial PCO2 of 78 Side effects include apnoea, brady- or tachycardia,
kPa (5060mmHg). Initial increase in HCO3 is hypotension, pyrexia, diarrhoea, convulsions, DIC,
about 0.76mmol/l per kPa change in arterial PCO2 hypokalaemia. Undiluted preparation reacts with
above 5.3 kPa (1mmol/l per 10mmHg above 40), plastic containers, so care in preparation is required.
although the level of compensatory change is less
predictable than in metabolic acidosis. ALS, see Advanced Cardiac Life Support; Advanced life
decreased renal acid secretion. support, adult; Advanced Life Support in Obstetrics;
Effects: Advanced Paediatric Life Support; Advanced Trauma
confusion. Life Support; Neonatal Resuscitation Programme
paraesthesia/tetany (reduced free ionised calcium
concentration due to altered protein-binding). ALSO, see Advanced Life Support in Obstetrics
correction of ECF and potassium depletion. Alteplase (rt-PA, tissue-type plasminogen activator).
rarely, acid therapy, e.g. ammonium chloride or Fibrinolytic drug, used in acute management of MI, PE
hydrochloric acid: deficit = base excess body and acute ischaemic CVA. Becomes active when it binds
weight (kg) mmol. to fibrin, converting plasminogen to plasmin, which dis-
See also, Acidbase balance solves the fibrin. Thought to be non-immunogenic.
Alkalosis, respiratory. Alkalosis due to decreased arte- within 6h of MI: 15mg iv bolus followed by
rial PCO2. Caused by alveolar hyperventilation, e.g. fear, 50mg/30min, then 35mg/60min.
pain, hypoxia, pregnancy, or during IPPV. within 612h of MI: 10mg bolus, then 50mg/60min,
Primary change: decreased arterial PCO2. then 40mg/2h.
Compensation: PE: 10mg followed by 90mg/2h.
initial fall in plasma bicarbonate due to decreased acute stroke (within 3h): 0.9mg/kg (up to 90mg);
carbonic acid formation and dissociation. 10% by iv injection, the remainder by infusion.
decreased acid secretion/increased bicarbonate Maximum dose: 1.5mg/kg if under 65kg body weight.
excretion by the kidneys. Side effects: as for fibrinolytic drugs.
In acute hypocapnia, bicarbonate concentration falls by
about 1.3mmol/l per 1 kPa fall in arterial PCO2. In chronic Althesin. IV anaesthetic agent introduced in 1971, com-
hypocapnia, the fall per 1 kPa is 4.0mmol/l. posed of two corticosteroids, alphaxalone 9mg/ml and
Alveolar gas transfer 25

alphadolone 3mg/ml. Withdrawn in 1984 because of a Alveolar air equation. In its simplified form:
high incidence of adverse drug reactions, mostly minor PA CO2
but occasionally severe. These were thought to be due to alveolar PO2 = FIO2 ( PB PA H 2O)
Cremophor EL, the solubilising agent. Previously widely R
used because of its rapid onset and short duration of PA CO2
or PIO2
action; still used in veterinary practice. R
where PB = ambient barometric pressure
Altitude, high. Problems include: PAH2O = alveolar partial pressure of water (nor-
lack of O2: e.g. atmospheric pressure at 18000 ft mally 6.3 kPa [47mmHg])
(5486m) is half that at sea level. FIO2 is constant, PACO2 = alveolar PCO2; approximately equals
but PO2 is lowered. This effect is offset initially by arterial PCO2
the shape of the oxyhaemoglobin dissociation R = respiratory exchange ratio, normally 0.8
curve, which maintains haemoglobin saturation PIO2 = inspired PO2
above 90% up to 10000 ft (3048m). Compensatory Useful for estimating alveolar PO2, e.g. when determin-
changes due to hypoxia include hyperventilation, ing alveolararterial O2 difference and shunt fractions.
increased erythropoietin secretion resulting in poly- The equation also illustrates how hypercapnia may be
cythaemia, increased 2,3-DPG, proliferation of associated with a lower PAO2. Another form of the equa-
peripheral capillaries and alterations in intracellular tion allows for differences between inspired and expired
oxidative enzymes. Alkalaemia is reduced after a gas volumes, and is unaffected by inert gas exchange:
few days, via increased renal bicarbonate loss. CSF
pH is returned towards normal. Pulmonary vaso- P O PEO 2
alveolar PO2 = PIO2 PA CO 2 I 2
constriction may result in right heart strain. High- PECO 2
altitude illness is thought to be related to acute where PEO2 = mixed expired PO2
hypoxia and alkalosis; it consists of headache, PECO2 = mixed expired PCO2
malaise, nausea and diarrhoea, and may lead to pul-
monary or cerebral oedema. Alveolararterial oxygen difference (AadO2). Alveo-
low temperatures, e.g. ambient temperature is 20C
lar PO2 minus arterial PO2. Useful as a measure of V/Q
at 18000 ft (5486m). mismatch and anatomical shunt. Alveolar PO2 is esti-
expansion of gas-containing cavities, e.g. inner ear.
mated using the alveolar air equation; arterial PO2 is
decompression sickness.
measured directly. The small shunt V /Q and mismatch
anaesthetic apparatus at high altitude:
in normal subjects result in a normal AadO2 of less than
- vaporisers: SVP is unaffected by atmospheric 2.0 kPa (15mmHg) breathing air; this may reach 4.0 kPa
pressure; thus the partial pressure of volatile (30mmHg) in the elderly. It increases when breathing
agent in the vaporiser is the same as at sea level. high O2 concentrations because the shunt component is
Because atmospheric pressure is reduced, the not corrected; i.e. normally up to 15 kPa (115mmHg)
delivered concentration is increased from that breathing 100% O2.
marked on the dial, but since anaesthetic action
depends on alveolar partial pressure, not concen- Alveolar gases. Normal alveolar gas partial pressures
tration, the same settings may be used as at sea and intravascular gas tensions are shown in Table 5. End-
level. However, reduced temperature may alter tidal gas approximates to alveolar gas in normal subjects
vaporisation. and may be monitored, e.g. during anaesthesia.
- flowmeters: since atmospheric pressure is reduced, See also, End-tidal gas sampling
a given amount of gas occupies a greater volume
than at sea level; i.e. has reduced density. Thus a Alveolar gas transfer. Depends on:
greater volume is required to pass through a alveolar ventilation.
Rotameter flowmeter to maintain the bobbin at diffusion across alveolar membrane, fluid interface
a certain height, because it is the number of gas and capillary endothelium (normally less than
molecules hitting the bobbin that support it. The 0.5 m).
flowmeters therefore under-read at high altitudes. solubility of gases in blood.
However, since the clinical effects depend on the cardiac output.
number of molecules, not volume of gas, the flow- For gases transferred from the bloodstream to the alveo-
meters may be used as normal. lus, e.g. CO2, and anaesthetic vapours during recovery,
Leissner KB, Mahmood FU (2009). J Anesth; 23: the same factors apply.

Altitude, low. Problems are related to high pressure:

those of hyperbaric O2 (see Oxygen, hyperbaric). Table 5 Normal respiratory gas partial pressures and tensions
inert gas narcosis. in kPa (mmHg)
neurological impairment, e.g. tremor,
disorientation. Inspired Alveolar Arterial Venous Expired
pressure reversal of anaesthesia.
effects on equipment: O2 21 (160) 14 (106) 13.3 (100) 5.3 (40) 15 (105)
- implosion of glass ampoules. CO2 0.03 (0.2) 5.3 (40) 5.3 (40) 6.1 (46) 4 (30)
- deflation of air-filled tracheal tube cuffs. Nitrogen 80 (600) 74 (560) 74 (560) 74 (560) 75 (570)
- functioning of vaporisers and flowmeters is H2O Variable 6.3 (47) 6.3 (47) 6.3 (47) 6.3 (47)
normal, as above.
26 Alveolar hypoventilation syndrome

With normal cardiac output, blood cells take about There is no specific treatment, although cortico-
0.75s to pass through pulmonary capillaries. O2 transfer steroids and cyclophosphamide or azathioprine
is usually complete within 0.25s; part of the time is taken may be used. Ciclosporin has theoretical benefits.
for the reaction with haemoglobin. CO2 diffuses 20 times Lung transplantation may be possible.
more quickly through tissue layers; transfer is also com- extrinsic allergic alveolitis (hypersensitivity pneu-
plete within 0.25s. Transfer of highly soluble gases, e.g. monitis): causative agents include aspergillus (farm-
carbon monoxide, is limited by diffusion between alveo- ers lung, malt-workers lung), pituitary extracts
lus and capillary, since large volumes can be taken up by (pituitary snuff takers lung) and avian proteins
the blood once they reach it. Transfer of insoluble gases, (bird-fanciers lung). May be:
e.g. N2O, is limited by blood flow from alveoli, since - acute: requires initial sensitisation to an antigen.
capillary blood is rapidly saturated. Subsequent exposure results in repeated episodes
See also, Carbon dioxide transport; Diffusing capacity; of dyspnoea, cough, malaise, fever, chills, aches
Oxygen transport and lethargy. Wheezing is uncommon. Severity
depends on the dose of antigen; in very severe
Alveolar hypoventilation syndrome, see Obesity cases, life-threatening respiratory failure occurs.
hypoventilation syndrome Recovery is accelerated by corticosteroids.
- chronic: less dramatic onset, with a slow increase
Alveolar recruitment manoeuvre. Technique used in in dyspnoea with minimal other systemic
patients receiving IPPV, aiming to recruit collapsed upset and no acute episodes. May cause cor
alveoli. Typically, CPAP of 3040 cmH2O is applied for pulmonale.
2040s; alternatively, three sighing breaths at a pres- CXR may be normal, but widespread ground-glass
sure of 45 cmH2O may be given. May result in improved appearance in mid and lower zones is common.
oxygenation, although evidence of outcome benefit in Lung function is as above, although it may be
patients with acute lung injury is inconsistent. May result normal between acute attacks. Other investigations
in reduced cardiac output and hypotension due to and treatment as above.
reduced venous return. drug-induced alveolitis: patients may present with
acute cough, fever and dyspnoea or with slowly
Alveolar ventilation. Volume of gas entering the progressive dyspnoea. Causal agents include: O2,
alveoli per minute; normally about 44.5 l/min. Equals nitrofurantoin, paraquat, amiodarone and cytotoxic
(tidal volume minus dead space) respiratory rate; thus drugs.
rapid small breaths result in a much smaller alveolar others: include physical agents (e.g. radiation), con-
ventilation than slow deep breaths, even though minute nective tissue diseases.
ventilation remains constant. In the upright position, All forms may lead to pulmonary fibrosis, which may
apical alveoli receive less ventilation than basal ones, also occur without generalised alveolitis, e.g. following
because the former are already expanded by gravity local disease or aspiration of irritant substances.
and are thus less able to expand further on inspiration.
Since all the exhaled CO2 comes from the alveoli, the Alveolus. Terminal part of the respiratory tree; the
amount exhaled in a minute equals alveolar ventilation site of gas exchange. About 3 108 exist in both lungs,
alveolar concentration of CO2. Thus alveolar (and with estimated total surface area 7080m2. Their walls
hence arterial) CO2 concentration is inversely propor- are composed of a capillary meshwork covered in
tional to alveolar ventilation, at any fixed rate of CO2 cytoplasmic extensions of type I pneumocytes. Tradi
production. tionally thought to conform to the bubble model; i.e.
See also, Ventilation/perfusion mismatch spherical in structure with a thin water lining, with
surfactant molecules preventing collapse. Electron
Alveolitis. Generalised inflammation of lung paren- microscopy, and experimental and mathematical models,
chyma. Classified into: have led to alternative theories, e.g. pooling of water at
cryptogenic fibrosing alveolitis: cause is unknown, septal corners with dry areas of surfactant in between,
therefore a diagnosis of exclusion. Characterised by and surface tension helping return water to interstitial
differing amounts of inflammation and fibrosis of fluid.
the pulmonary air spaces and interstitium. Most
common at 5060 years and in smokers. Possible, Amantadine hydrochloride. Drug with both antipar-
but unproven, triggers include viral infection and kinsonian and antiviral effects. In Parkinsons disease,
exposure to metal dusts or wood fires. Has an it improves tremor, rigidity and mild dyskinesia, but
aggressive course with 50% mortality at 5 years, only in a small percentage of sufferers. Has been used
despite therapy. for the treatment of herpes zoster infections, both
Symptoms include progressive dyspnoea without during the acute phase and in the treatment of posther-
wheeze, dry cough, weight loss and lethargy. Club- petic pain. Has also been used for prophylaxis of influ-
bing occurs in 7080%. Most striking signs are the enza A in very selective groups, but is no longer
very distinctive, fine, end-expiratory crepitations recommended.
heard at the lung bases and mid-axillary lines. Pro- Dosage:
gresses to central cyanosis, pulmonary hyperten- parkinsonism: 100mg orally od (doubled after
sion, cor pulmonale and a restrictive pattern of 1 week).
pulmonary impairment as for pulmonary fibrosis. herpes zoster: 100mg bd for 14 days.
CXR may reveal small lung fields with reticulo- influenza A: 100mg od for 45 days as treatment,
nodular shadowing at lung peripheries and bases. 100mg/day for 6 weeks as prophylaxis.
CT scanning, radioisotope scanning and lung biopsy Side effects: nausea, dizziness, convulsions, hallucina-
may help with the diagnosis. tions, GIT disturbance.
-Aminobutyric acid receptors 27

Ambu-bag, see Self-inflating bags between the amino group of one and the carboxyl group
of another, with the elimination of water.
Ambu-E valve, see Non-rebreathing valves Amino acids from the breakdown of ingested and
endogenous proteins form an amino acid pool from
American Board of Anesthesiology (ABA). Recog- which new proteins are synthesised. Amino acids are
nised as an independent Board by the American Board involved in carbohydrate and fat metabolism; amino
of Medical Specialties in 1941, having been an affiliate groups may be removed or transferred to other mole-
of the American Board of Surgery since 1938. Issues the cules (deamination and transamination respectively).
Diploma of the ABA. Deamination results in the liberation of ammonia, which
may be excreted as urea, or taken up by other amino
American Society of Anesthesiologists (ASA). acids to form amides.
Formed from the American Society of Anesthetists in Eight dietary amino acids are essential for life in
1945, to distinguish medically qualified anesthesiolo- humans: valine, leucine, isoleucine, threonine, methio-
gists from anesthetists. The American Society of Anes- nine, phenylalanine, tryptophan and lysine. Arginine and
thetists had been formed in 1936 from the New York histidine are required for normal growth. Other amino
Society of Anesthetists, which until 1911 had been the acids may be synthesised from carbohydrate and fat
Long Island Society of Anesthetists, founded in 1905. breakdown products.
The ASA is concerned with improving the standards, Glutamine, the most abundant amino acid in the
education and audit of anaesthesia, and publishes the body, has a key role in muscle synthesis and immune
journal Anesthesiology. function, as a neurotransmitter and as a major metabolic
fuel for enterocytes. Inclusion of glutamate in enteral
Amethocaine, see Tetracaine feeds appears to reduce gut permeability and prevents
the mucosal atrophy that occurs when food is not given
Amfetamine poisoning. Overdosage of amfetamines by the enteral route.
may cause anxiety, hyperactivity, tachycardia, hyper Synthetic crystalline amino acid solutions (containing
tension, hallucinations and hyperthermia. Intracranial the l-isomers) are used as a nitrogen source during TPN.
haemorrhage may accompany acute severe hyperten- The composition of solutions varies considerably by
sion. The toxic dose is not well defined, as there is a wide manufacturer, although all provide the essential, and
variation in response related to tolerance in chronic most of the non-essential, amino acids. Enteral feed solu-
abusers. Diagnosis is made on the history and clinical tions also include a mixture of amino acids.
grounds, supported by qualitative laboratory analysis See also, Nitrogen balance
(plasma levels are unhelpful in guiding management).
Patients should have continuous ECG and core tem- -Aminobutyric acid (GABA). Inhibitory neurotrans-
perature monitoring, and urine analysed for myoglobin. mitter found in many parts of the CNS. Binds to specific
Treatment includes general supportive care as for poi- GABA receptors, both pre- and postsynaptic, resulting
soning and overdoses, and the use of chlorpromazine in reduced neuronal excitability by increasing chloride
and -adrenergic receptor antagonists (although 2- conductance. Many anticonvulsant drugs facilitate the
receptor-mediated vasoconstriction in skeletal muscle action of GABA, emphasising its role in epilepsy and the
vessels may increase BP). Forced acid diuresis increases regulation of central activity. It is also an important regu-
excretion but this should not be undertaken if there is lator of muscle tone.
associated rhabdomyolysis.
-Aminobutyric acid (GABA) receptors. Trans
Amfetamines (Amphetamines). Group of drugs membrane receptors activated by GABA, present
that promote the release and inhibit the uptake of throughout the CNS. Two classes have been identified:
noradrenaline, dopamine and serotonin at the synaptic GABAA: pentameric ligand-gated ion channel com-
cleft, thereby causing stimulation of the central and posed of numerous subunit isoforms (e.g , , , ,
sympathetic nervous systems. Commonly abused, ) arranged around a central chloride ion pore (Fig.
they cause addiction and are controlled drugs. Used in 8). GABA binds at the interface between and
narcolepsy. Increase MAC of inhalational anaesthetic subunits, allowing Cl to flow into the cell; this
agents. lowers the membrane potential and therefore neu-
See also, Amfetamine poisoning ronal excitability. Site of action for benzodiazepines,
barbiturates, propofol and volatile anaesthetic
Amikacin. Antibacterial drug; an aminoglycoside with agents, almost all of which potentiate the action
bactericidal activity against some Gram-positive and
many Gram-negative organisms, including pseudo
monas. Indicated for the treatment of serious infections
caused by Gram-negative bacilli resistant to gentamicin. GABA
Not absorbed from the GIT, it must be given parenter-
ally. Excreted via the kidney. Benzodiazepines
Dosage: 7.5mg/kg im or slowly iv bd/tds up to 15g
over 10 days. One-hour (peak) concentration should
not exceed 30mg/l and pre-dose (trough) level should Ethanol
be less than 10mg/l. Volatile anaesthetics
Side effects: as for gentamicin.
Amino acids. Organic acid components of proteins; they
produce polypeptide chains by forming peptide bonds Fig. 8 GABAA receptor showing GABA and drug binding sites
28 Aminoglycosides

of endogenous GABA at low concentrations, hepatic failure, and during therapy with cimetidine,
while directly activating the receptor at higher erythromycin and ciprofloxacin. Phenytoin, carba-
concentrations. mazepine and other enzyme inducers may decrease
GABAB: G protein-coupled receptor, linked to its half-life.
K+ and Ca2+ channels via phospholipase C and ade- Side effects: arrhythmias, agitation and convulsions,
nylate cyclase. Activation results in increased K+ GIT disturbances.
and decreased Ca2+ conductance, reducing neuronal Care should be taken when patients already on oral
excitability. Mediate long-acting, tonic inhibitory treatment are given iv aminophylline, since the drug has
signalling. Site of action for baclofen. a low therapeutic ratio. Plasma levels should be mea-
Franks NP (2008). Nat Rev Neurosci; 9: 37086 sured; therapeutic range is 1020mg/l.

Aminoglycosides. Group of bactericidal antibacterial Aminopyridine. Originally 4-aminopyridine, a drug pre-

drugs. Includes amikacin, gentamicin, neomycin, netilmi- viously used to reverse non-depolarising neuromuscular
cin, streptomycin and tobramycin. blockade, and to treat myasthenic syndrome. Does not
Active against some Gram-positive and many inhibit acetylcholinesterase, but acts presynaptically to
Gram-negative organisms. Amikacin, gentamicin and increase acetylcholine release, thereby increasing the
tobramycin are also active against pseudomonas. force of muscle contraction. It also enters the brain and
Not absorbed from the GIT; must be given parenter- may cause convulsions. Replaced by 3,4-diaminopyri-
ally. Excretion is via the kidney and delayed in renal dine, which does not cross the bloodbrain barrier.
impairment. Side effects include ototoxicity (especially
with concurrent furosemide therapy) and nephrotoxic- Amiodarone hydrochloride. Antiarrhythmic drug,
ity. In pregnancy, they may cross the placenta and cause used for treating SVT, VT and WolffParkinson
fetal ototoxicity. They may also impair neuromuscular White syndrome. Acts by blocking cardiac K+ channels,
function and therefore avoidance has been suggested in thereby prolonging the cardiac action potential and
myasthenia gravis. Monitoring of plasma levels should refractory period. Hence traditionally designated a class
ideally be performed in all cases but is especially impor- III antiarrhythmic, although also demonstrates class I, II
tant in the elderly, children, those with renal impairment, and IV activity. Causes minimal myocardial depression.
the obese, and if high dosage or prolonged treatment is Half-life is over 4 weeks. Acts rapidly following iv
used. Monitored using 1h (peak) and pre-dose (trough) administration.
samples. Dosage:
200mg orally, tds for 1 week, reducing to bd for a
-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate further week, then od for maintenance.
(AMPA) receptors Transmembrane tetrameric ligand- as an iv infusion: 5mg/kg over 20120min followed
gated ion channel, activated by glutamate. Most abun- by up to 1.2g/24h, with ECG monitoring. Brady-
dant receptor in the CNS, it mediates fast synaptic cardia and hypotension may occur. May cause
transmission and has a major role in synaptic plasticity inflammation of peripheral veins. The dose should
and memory formation. Activation by glutamate results be reduced after 12 days.
in channel opening and influx of cations, mainly Na+ and Side effects: prolonged administration commonly
Ca2+ (depending on subunit composition). results in corneal microdeposits (reversible, and
rarely affecting vision), and may cause photosensitiv-
2-Amino-2-hydroxymethyl-1,3-propanediol (THAM/ ity, peripheral neuropathy, hyper- or hypothyroidism,
Tris). Buffer solution that acts both intra- and extracel- hepatitis and pulmonary fibrosis.
lularly, used extensively in molecular biology. Has been
studied for the control of metabolic acidosis (e.g. post Amitriptyline hydrochloride. Tricyclic antidepressant
cardiac arrest) or increased ICP, but not currently rec- drug. Competitively blocks neuronal uptake of nor-
ommended for clinical practice. adrenaline and serotonin. Also has anticholinergic and
Holmdahl M, Wicklund L, Wetterburg T etal (2000). antihistaminergic properties; thus has marked sedative
Acta Anaesthesiol Scand; 44: 5247 effects and is well suited for patients with agitated
depression. Also used in chronic neuropathic pain
Aminophylline. Phosphodiesterase inhibitor, a mixture management, especially when pain prevents sleeping
of theophylline and ethylenediamine. Much more soluble at night. Antidepressant and analgesic effects become
than theophylline alone, hence its use iv. Used as a bron- apparent after 24 weeks treatment.
chodilator drug (but not as first-line therapy), and as an Dosage:
inotropic drug, especially in paediatrics. depression: 75mg orally/day (less in the elderly), in
Causes bronchodilatation, increased diaphragmatic divided doses or as a single dose at night, increased
contractility, vasodilatation, increased cardiac output up to 150200mg/day.
(direct effect on the heart), diuresis (direct effect on the pain: 2575mg at night.
kidney), and CNS stimulation. Side effects: muscarinic effects include arrhythmias,
Dosage: heart block, dry mouth, urinary retention, blurred
100500mg orally bdqds (depending on the prepa- vision, constipation; hypersensitivity, blood dyscrasias,
ration), usually as slow-release preparations. Rectal hepatic impairment, confusion and convulsions may
preparations are no longer used, as they were asso- also occur. Should be avoided in cardiovascular
ciated with proctitis and unpredictable response. disease.
for emergency iv use, injection of 57mg/kg over See also, Tricyclic antidepressant drug poisoning
30min may be followed by an infusion of 0.5mg/
kg/h (up to 1mg/kg/h in smokers), with ECG moni- Ammonia (NH3). Toxic, colourless pungent-smelling
toring. Dosage should be reduced in cardiac and gas, highly soluble in water. Produced in the GIT by the
Amplifiers 29

action of enteric organisms on dietary proteins and Amoxicillin (Amoxycillin). Derivative of ampicillin,
amino acids, and detoxified by transformation in the differing only by one hydroxyl group; has similar anti-
liver into urea. Normal blood level is 100200mg/l; bacterial activity but oral absorption is better and unaf-
levels rise in the presence of severe liver disease or a fected by food in the stomach. Enteral administration
portalsystemic blood shunt. Ammonia intoxication produces higher plasma and tissue levels than ampicillin.
causes tremor, slurred speech, blurred vision and coma. Combined with -lactamase inhibitor clavulanic acid in
There is a weak association between blood ammonia co-amoxiclav.
level and the degree of hepatic encephalopathy in Dosage: 2501000mg orally, 500mg im or 500mg
hepatic failure. Rare genetic disorders of the urea cycle 1g iv tds.
(e.g. ornithine carbamoyltransferase deficiency) lead to Side effects: as for ampicillin.
hyperammonaemia; similarly, treatment with sodium
valproate may result in raised ammonia levels due to AMPA receptors, see -Amino-3-hydroxy-5-methyl-4-
interference with the urea cycle. isoxazolepropionate (AMPA) receptors
Ammonia is also produced in the proximal tubule of
the kidney from the breakdown of glutamine. It com- Ampere. SI unit of current, one of the seven base (fun-
bines intracellularly with H+ to form the ammonium ion damental) units. Defined as the current flowing in two
(NH4+) which is secreted by the proximal tubule cells straight parallel wires of infinite length, 1m apart in a
into the tubular filtrate, thereby facilitating regulation of vacuum, that will produce a force of 2 107 N/m length
acidbase balance and cation conservation. Ammonia on each of the wires. In practical terms, represents the
formed from the dissociation of NH4+ is reabsorbed, amount of charge passing a given point per unit time; a
recycled and resecreted, primarily by the collecting flow of one coulomb of electrons per second equates to
tubule. one ampere of current.
See also, Nitrogen balance [Andre Ampre (17751836), French physicist]

Amnesia. Impairment of memory. May occur with Amphetamine poisoning, see Amfetamine poisoning
intracranial pathology, dementia, metabolic distur-
bances, alcoholism and psychological disturbances. May Amphetamines, see Amfetamines
be caused by head injury and drugs. Patients who recover
from critical illness may have poor recall of events Amphotericin (Amphotericin B). Polyene antifungal
afterwards. drug, active against most fungi and yeasts. Not absorbed
Retrograde amnesia (between the causative agent/ enterally. Highly protein-bound, it penetrates tissues
event and the last memory beforehand) is common after poorly. Administered orally as a treatment for intestinal
head injury. Anterograde amnesia (loss of memory for candidiasis, or iv for systemic fungal infections. Ampho-
the period following the causative agent/event) may tericin is available encapsulated in liposomes or as a
occur after head injury, and is common after admini complex with sodium cholesteryl sulphate, both of which
stration of certain drugs, typically benzodiazepines and reduce its toxicity.
Dosage: 15mg/kg/day iv, depending on the
hyoscine. Awareness during anaesthesia, with amnesia
preventing subsequent conscious recall, may be more formulation.
Side effects: renal and hepatic impairment, nausea
common than previously thought.
and vomiting, electrolyte disturbance, especially
hypokalaemia, arrhythmias, blood dyscrasias, convul-
Amniotic fluid embolism. Condition originally thought sions, peripheral neuropathy, visual and hearing dis-
to be a mechanical embolic phenomenon caused by turbances. A test dose is recommended before iv
entry of amniotic fluid and fetal cells into the maternal administration because of the risk of anaphylaxis.
circulation; now generally accepted to have a major
immunologic component, involving an inflammatory Ampicillin. Broad-spectrum semisynthetic bactericidal
response similar to anaphylaxis. The incidence is quoted penicillin. Active against many Gram-positive and nega-
as 1:80001:80000 deliveries, the wide range reflecting tive organisms; ineffective against -lactamase pro
difficulty in diagnosis. Quoted mortality is 3060%, with ducing bacteria, including Staphylococcus aureus and
many dying within 5h of presentation and a high inci- Escherichia coli. Only moderately well absorbed orally
dence of serious neurological morbidity in survivors. (~50% of dose) and this is further diminished by food
Implicated in 1015% of maternal deaths. in the gut. Excreted into bile and urine.
Usually occurs during labour or delivery, although it Dosage: 250mg1g orally qds; 5002000mg iv or im,
can present up to 48h postpartum and also during cae- 46-hourly, depending on indication.
sarean section. Said to be more common in multiparous, Side effects: nausea, rash, diarrhoea.
older women, and with forceful labour, although this has
been questioned. Amplifiers. Electrical devices used to increase the
Typical features include fetal distress, shock (often power of an input signal using an external energy source.
profound), cardiac arrest, pulmonary hypertension, Widely used in clinical measurement to amplify mea-
pulmonary oedema, acute lung injury, cyanosis, DIC, sured biological electrical potentials (e.g. ECG).
vomiting, drowsiness, convulsions. May be described in terms of:
Management involves aggressive supportive treat- degree of gain (ratio of output to input signal
ment, including correction of DIC. amplitude).
Gist RS, Stafford IP, Leibowitz AB, Beilin Y (2009). bandwidth (range of frequencies over which the
Anesth Analg; 108: 1599602 device provides reliable and constant amplification).
noise compensation (most clinical amplifiers em-
Amoebiasis, see Tropical diseases ploy common-mode rejection, whereby only the
30 Amrinone lactate

difference between two signal sources is amplified, Effects:

and interference that is common to both signals is reduced O2-carrying capacity of blood: fatigue,
rejected). dyspnoea on exertion, angina.
increased cardiac output, to maintain O2 flux: palpi-
Amrinone lactate. Phosphodiesterase inhibitor, used as tations, tachycardia, systolic murmurs, cardiac
an inotropic drug. Active iv and orally. Increases cardiac failure. Reduced viscosity increases flow but turbu-
output and reduces SVR via inhibition of cardiac and lence is more likely.
vascular muscle phosphodiesterase. MAP and heart rate increased 2,3-DPG.
are unaltered. Half-life is 36h. Not available in the UK. maintenance of blood volume by haemodilution.
Milrinone, a more potent derivative, is less likely to Unexpected anaemia should be investigated before
cause side effects (e.g. GIT upset, thrombocytopenia). routine surgery. The traditional minimal safe haemo-
globin concentration for anaesthesia has been 10g/dl,
Amylase. Group of enzymes secreted by salivary glands unless surgery is urgent; below this level, reduced O2
and the pancreas. Salivary amylase (an -amylase carriage was felt to outweigh the advantage of reduced
ptyalin) breaks down starch at an optimal pH of 6.7; blood viscosity and increased flow. More recently, 710g/
consequently it is inactivated by gastric acid. In the small dl has been suggested, reflecting the concerns over the
intestine, both salivary and pancreatic -amylase act on complications of transfusion (except in ischaemic heart
ingested polysaccharides. disease, in which postoperative mortality increases as
Plasma amylase measurements may be useful for preoperative haemoglobin concentration falls below
the diagnosis of numerous conditions, particularly acute around 10g/dl). Reduction of cardiac output during
pancreatitis. About 3540% of total plasma amylase anaesthesia is particularly hazardous. FIO2 of 0.5 is often
activity is contributed by the pancreatic isoenzyme. advocated to reduce risk of perioperative hypoxia by
Amylase levels > 5000U/l are suggestive of acute pan- increasing the O2 reserve within the lungs.
creatitis (peak reached within 2448h); other intra- In the ICU, recent evidence suggests that lowering
abdominal emergencies (e.g. perforated peptic ulcer, the threshold for transfusion from 10g/dl to 7g/dl may
mesenteric infarction) are usually associated with lower decrease mortality, organ dysfunction and cardiac
plasma levels. complications.
See also, Carbohydrates Transfused stored blood takes up to 24h to reach its
full O2-carrying capacity; ideally transfusion should
Anaemia. Reduced haemoglobin concentration; usually occur at least 1 day preoperatively. Slow transfusion also
defined as less than 13g/dl for males, 12g/dl for females. minimises the risk of fluid overload in chronic anaemia.
In children, the figure varies: 18g/dl (12 weeks of age);
11g/dl (6 months6 years); 12g/dl (612 years). Anaerobic infection. Caused by:
Caused by: obligate anaerobes: only grow in the absence of O2.
reduced production: microaerophilic organisms: only grow under condi-
- deficiency of iron, vitamin B12, folate. tions of reduced O2 tension.
- chronic disease, e.g. malignancy, infection. facultative anaerobes: capable of growing aerobi-
- endocrine disease, e.g. hypothyroidism, adreno- cally or anaerobically.
cortical insufficiency. The most clinically important are species of clostridium,
- bone marrow infiltration, e.g. leukaemia, bacteroides and actinomyces. Predisposing factors
myelofibrosis. include disruption of mucosal barriers, impaired blood
- aplastic anaemia, including drug-induced, e.g. supply, tissue injury and necrosis. Most infecting organ-
chloramphenicol. isms are endogenous. Infections are accompanied by foul-
- reduced erythropoietin secretion, e.g. renal failure. smelling, putrid pus. Specimens for analysis of possible
- abnormal red cells/haemoglobin, e.g. sideroblastic anaerobic infections may require special anaerobic trans-
anaemia, thalassaemia. port systems as some anaerobic species die if exposed to
increased haemolysis. O2. Metronidazole is especially active against anaerobes.
Anaerobic threshold. Conventionally defined as the
- acute.
work rate at which metabolic acidosis and associated
- chronic.
Investigated by measuring the size and haemoglobin
changes in gas exchange occur. A theoretical measure of
overall cardiopulmonary function, derived from cardio-
content of erythrocytes:
pulmonary exercise testing. Commonly estimated using
hypochromic, microcytic: e.g. thalassaemia, iron
the inflection point of the oxygen consumption/carbon
deficiency, including chronic haemorrhage, chronic
dioxide production curve (Fig. 9). The sudden increase
in V CO 2 /V O 2 is traditionally ascribed to increased buffer-
normochromic, macrocytic: vitamin B12 or folate
ing of lactic acid by HCO3 (thereby generating excess
deficiency, alcoholism.
CO2), although this is controversial. Has been used to
normochromic, normocytic: chronic disease, e.g.
predict outcome from major surgery, an anaerobic
infection, malignancy, renal failure, endocrine
threshold of < 1011ml/kg/min suggesting a greater risk
disease; aplastic anaemia, bone marrow disease or
of death, especially if associated with high-risk surgery
and/or ischaemic heart disease.
Other investigations include examination of blood
Hopker JG, Jobson SA, Pandit JJ (2011). Anaesthesia;
film (e.g. for sickle cells, parasites, reticulocytes
66: 11123
suggesting increased breakdown or haemorrhage),
measurement of platelets and white cells, bone Anaesthesia. Official journal of the Association of
marrow aspiration and further blood tests, e.g. iron, Anaesthetists of Great Britain and Ireland, first pub-
vitamin B12. lished in 1946.
Anaesthesia, history of 31

Anaesthesia (from Greek: an + aisthesis; without - cerebral function monitor and analysing monitor:
feeling). Term suggested by Oliver Wendell Holmes in easier to use and read, but less informative than
1846 to describe the state of sleep produced by ether; the conventional EEG.
word had been used previously to describe lack of - power spectral analysis: graphic display of compli-
feeling, e.g. due to peripheral neuropathy. He introduced cated data; easier to interpret than conventional
derived terms, e.g. anaesthetic agent. EEG. The bispectral index monitor and entropy
monitor (describing non-linear dynamics) are
Anaesthesia and Intensive Care. Official journal of the now commonly used. These monitors use propri-
Australian Society of Anaesthetists (formed in 1935) etary algorithms to convert raw EEG data into a
since its launch in 1972. Also the official journal of the single number that is claimed to represent global
Australian and New Zealand Intensive Care Society and activity; titration of anaesthesia in order to keep
the New Zealand Society of Anaesthetists. the value within defined limits may thus reduce
both awareness and overdosage, although their
Anaesthesia, balanced, see Balanced anaesthesia place is controversial.
evoked potentials: similar effects are produced by
Anaesthesia crisis resource management, see Crisis different anaesthetic agents.
resource management oesophageal contractility: affected by smooth
muscle relaxants and ganglion blocking drugs, also
Anaesthesia, depth of. Anaesthesia is generally by disease, e.g. achalasia.
accepted as being a continuum in which increasing depth EMG: particularly of the frontalis muscle. Requires
of anaesthesia results in loss of consciousness, recall, and separate monitoring of peripheral neuromuscular
somatic and autonomic reflexes. Some would argue that, blockade in addition.
whilst these are the effects of anaesthetic drugs in Kent CD, Domino KB (2009). Curr Opin Anesthesiol;
increasing dosage, anaesthesia itself occurs at a particu- 22: 7827
lar undefined point, and is therefore either present or
absent. Anaesthesia dolorosa. Pain in an anaesthetic area, typi-
Assessment is important in order to avoid inadequate cally following destructive treatment of trigeminal neu-
anaesthesia with awareness and troublesome reflexes, or ralgia. Unpleasant symptoms, ranging from paraesthesia
overdose. to severe pain, develop in the area of the face rendered
Methods of assessment: anaesthetic, and may be more distressing than the origi-
clinical: nal symptoms. Anaesthesia dolorosa may develop many
- stages of anaesthesia (see Anaesthesia, stages of). months after the lesion, and is often refractory to further
- signs of inadequate anaesthesia: treatment, including surgery. Limited success has been
- lacrimation. reported with gabapentin.
- tachycardia.
- hypertension. Anaesthesia, history of
- sweating. Early attempts at pain relief:
- reactive dilated pupils. opium used for many centuries, especially in the Far
- movement, laryngospasm. East. First injected iv by Wren in 1665.
These signs may be altered by anaesthetic drugs use of other plants and derivatives for many centu-
themselves, and by others, e.g. opioids, atropine, ries, e.g. cocaine (cocada), mandragora, alcohol.
neuromuscular blocking drugs. acupuncture.
- isolated forearm technique. unconsciousness produced by carotid compression.
EEG: analgesia produced by cold (refrigeration anaesthe-
- conventional EEG: bulky and difficult to inter- sia), compression and ischaemia: 15001600s.
pret. Poor correlation between different anaes- mesmerism: 17001800s.
thetic agents. General anaesthesia:
effects of diethyl ether on animals described by
Paracelsus: 1540.
understanding of basic physiology, especially respi-
ratory and cardiovascular, and isolation of many
gases, e.g. O2, CO2, N2O: 16001700s.
5 N2O suggested for analgesia by Davy in 1799.
CO2 inhalation to produce insensibility described
4 by Hickman in 1824.
use of diethyl ether for anaesthesia by Long, Clarke:
VCO2 (l/min)

3 1842.
use of N2O for anaesthesia by Wells, Colton: 1844.
2 first public demonstration of ether anaesthesia in
Boston by Morton: 16 October 1846 (see Bigelow;
1 Holmes; Warren).
first UK use by Scott in Dumfries, Scotland, on 19
0 December 1846, news of Mortons demonstration in
0 1 2 3 4 5 Boston having travelled to Dumfries with Fraser,
VO2 (l/min) ships surgeon aboard the Royal Mail steamship
Acadia. Used in London by Squire 2 days later (see
Fig. 9 Anaerobic threshold (arrowed) Liston).
32 Anaesthesia, mechanism of

chloroform introduced by Simpson: 1847. Previously suggested but now discarded theories:
first deaths, e.g. Greener: 1848. disruption of lipid bilayers/non-specific membrane
development in UK led by Snow, then Clover. expansion; initially suggested by the observation
rectal administration of anaesthetic agents that the potency of volatile agents is related to their
described. lipid solubility (MeyerOverton rule). However,
iv anaesthesia produced with chloral hydrate by this does not explain the cut-off effect or the lack
Or: 1872. of potentiation of anaesthetics by heat.
ether versus chloroform: the former was favoured clathrate theory (water hydrates of anaesthetic
in England and northern USA, the latter in Scot- agents).
land and southern USA. Other agents introduced Fergusons thermodynamic activity theory: related
(see Inhalational anaesthetic agents). Boyle machine activity to the chemical composition of the agent
described 1917. concerned, by determining the energy contained
iv anaesthesia popularised by Weese, Lundy and within the chemical bonds of its molecules. Related
Waters: 1930s (see Intravenous anaesthetic agents). to lipid solubility and other physical properties.
Neuromuscular blockade introduced by Griffith: Bernard suggested that anaesthetics caused intra-
1942. Halothane introduced 1956. cellular protein coagulation.
UK pioneers: Hewitt, Macewen, Magill, Rowbo- [J Ferguson (described 1939), English scientist]
tham, Macintosh (first UK professor), Hewer, Brown EN, Lydic R, Schiff ND (2010). N Engl J Med;
Organe. 363: 263850
USA pioneers: Waters (first university professor),
Guedel, Mckesson, Crile, McMechan, Lundy. Anaesthesia, one-lung, see One-lung anaesthesia
UK: Association of Anaesthetists founded 1932;
DA examination 1935; Faculty of Anaesthetists Anaesthesia Practitioners, see Physicians Assistants
1948; FFARCS examination 1953; College of (Anaesthesia)
Anaesthetists 1988; Royal College of Anaesthetists
1992. Anaesthesia, stages of. In 1847, Snow described five
USA: American Society of Anesthesiologists stages of narcotism, although a less detailed classifica-
founded 1945. tion had already been described. The classic description
World Federation of Societies of Anaesthesiologists of anaesthetic stages was by Guedel in 1937 in unpre-
founded 1955. medicated patients, breathing diethyl ether in air:
Local anaesthesia: stage 1 (analgesia):
cocaine isolated 1860. - normal reflexes.
topical anaesthesia produced by Koller: 1884. - ends with loss of the eyelash reflex and
spinal anaesthesia by Corning: 1885; Bier: 1898. unconsciousness.
epidural anaesthesia 1901. stage 2 (excitement):
pioneers: Braun, Lawen, Labat. - irregular breathing, struggling.
[Sir Christopher Wren (16321723), English scientist - dilated pupils.
and architect; William Scott (18201887) and William - vomiting, coughing and laryngospasm may occur.
Fraser (18191863), Scottish surgeons; Helmut Weese - ends with the onset of automatic breathing and
(18971954), German pharmacologist] loss of the eyelid reflex.
See also, Cardiopulmonary resuscitation; Intermittent stage 3 (surgical anaesthesia):
positive pressure ventilation; Intensive care, history of; - plane I:
Intubation, tracheal; Local anaesthetic agents - until eyes centrally placed with loss of conjunc-
tival reflex.
- swallowing and vomiting depressed.
Anaesthesia, mechanism of. The precise mechanism is - pupils normal/small.
unknown, but theories are as follows: - lacrimation increased.
anatomical level: - plane II:
- ascending reticular activating system, thalamus, - until onset of intercostal paralysis.
and cerebral cortex are considered the most likely - regular deep breathing.
anatomical sites of action. - loss of corneal reflex.
- spinal cord is also affected by anaesthetics. - pupils becoming larger.
- synaptic sites are thought to be more important - lacrimation increased.
than axonal sites, since the former are blocked - plane III:
more easily than the latter at clinically effective - until complete intercostal paralysis.
concentrations of anaesthetic agent. - shallow breathing.
cellular level: - light reflex depressed.
- now accepted to act at specific neuronal protein - laryngeal reflexes depressed.
targets, including: - lacrimation depressed.
- type A GABA receptors: known target for - plane IV:
barbiturates, benzodiazepines, propofol and - until diaphragmatic paralysis.
volatile agents, all of which potentiate GABA- - carinal reflexes depressed.
mediated inhibition of neuronal activity. stage 4 (overdose):
- NMDA receptors: known target for ketamine. - apnoea.
- two-pore domain K+ channels: activated by vol- - dilated pupils.
atile agents, resulting in membrane hyperpolari- With modern agents and techniques, the stages often
sation and reduced excitability. occur too rapidly to be easily distinguished.
Anaesthetic breathing systems 33

The stages may be seen in reverse order on emer-

gence from anaesthesia. A
See also, Anaesthesia, depth of
Anaesthesia, total intravenous, see Total intravenous FGF
Anaesthetic accidents, see Anaesthetic morbidity and
Anaesthetic agents, see Inhalational anaesthetic agents;
Intravenous anaesthetic agents; Local anaesthetic agents
Anaesthetic breathing systems
open: unrestricted ambient air as the fresh gas
semi-open: as above, but some restriction to air
supply, e.g. enclosed mask.
closed: totally closed circle system. FGF
semi-closed: air intake prevented but venting of
excess gases allowed. Divided by Mapleson into five
groups, A to E, in 1954; a sixth (F) was added later
(Fig. 10). Arranged in order of decreasing efficiency
in eliminating carbon dioxide during spontaneous
Maplesons nomenclature (excludes open drop tech-
niques, circle systems, and use of non-rebreathing FGF
Mapleson A (Magill attachment):
- most efficient for spontaneous ventilation, because
exhaled dead-space gas is reused at the next inspi-
ration, and exhaled alveolar gas passes out
through the valve. Thus fresh gas flow (FGF) E FGF
theoretically may equal alveolar minute volume
- inefficient for IPPV, because some fresh gas is lost
through the valve when the bag is squeezed, and
exhaled alveolar gas may be retained in the
system and rebreathed. High gas flows are there- F FGF
fore needed (23 times minute volume).
Mapleson B and C: rarely used, other than for resus-
citation. Inefficient; thus 23 times minute volume
is required.
Mapleson D:
- inefficient for spontaneous ventilation, because Fig. 10 Nomenclature of anaesthetic breathing systems (see text)
exhaled gas passes into the reservoir bag with
fresh gas, and may be rebreathed unless FGF is
high. Suggested values for FGF range from 150 to breathing during spontaneous ventilation. Sug-
300ml/kg/min (i.e. 24 times minute ventilation); gested FGF: 24 times minute volume for spontane-
resistance to breathing may be a problem at ous ventilation. For IPPV, 200ml/kg/min has been
high FGF. suggested, although more complicated formulae
- efficient for IPPV; exhaled dead-space gas passes exist.
into the bag and is reused but when alveolar gas Modifications include:
reaches the bag, the bag is full of fresh gas and coaxial versions of the A and D systems (Lack and
dead-space gas; alveolar gas is thus voided through Bain respectively): the valve is accessible to the
the valve. Theoretically, 70ml/kg/min will main- anaesthetist for adjustment and scavenging, and
tain normocapnia. the tubing is longer and lighter.
Mapleson E (Ayres T-piece): used for children, Humphrey ADE system: valve and bag are at the
because of its low resistance to breathing. To prevent machine end, with a lever incorporated within the
breathing of atmospheric air, the reservoir limb valve block; may be converted into type A, D or E
should exceed tidal volume. A FGF of 24 times systems depending on requirements.
minute volume is required to prevent rebreathing. enclosed afferent reservoir system: resembles the
May be used for IPPV by intermittent occlusion of Mapleson D with an additional reservoir placed on
the reservoir limb outlet. the FGF limb. This reservoir is enclosed within
Mapleson F (JacksonRees modification): adapted a chamber that connects to the main limb such
from Ayres T-piece. The bag allows easier control that compressing the original reservoir bag (e.g.
of ventilation, and its movement demonstrates manually) causes the additional reservoir to be
34 Anaesthetic drug labels

compressed too, increasing the tidal volume deliv- - linkage between N2O and O2 Rotameters, so
ered. The system (in a more sophisticated form, that less than 25% O2 cannot be dialed up, e.g.
including a bellows as the additional reservoir) has Quantiflex apparatus and newer machines.
been incorporated within a ventilator system; - to avoid O2 leak: O2 flowmeter feeds downstream
although it has been shown to be efficient during from the others; thus a cracked CO2 Rotameter
both spontaneous and controlled ventilation, it is leaks N2O in preference to O2.
not widely used. - to avoid risk of O2 delivery failure:
British and International Standard taper sizes of breath- - O2 pressure gauge.
ing system connections are 15mm for tracheal tube con- - O2 failure warning device; preferably switching
nectors and paediatric components, and 22mm for adult off other gas flows and allowing air to be
components. Some components have both external breathed.
tapers of 22mm, and internal tapers of 15mm. Some - O2 analyser.
paediatric equipment has 8.5mm diameter fittings, delivering excessive CO2 (e.g. caused by the CO2
although not standard. Upstream parts of connections flowmeter opened fully, with the bobbin hidden at
are traditionally male, and fit into the female down- the top of the flowmeter tube):
stream parts. - maximal possible CO2 flow is limited, e.g. to
[William W Mapleson, Cardiff physicist; Philip Ayre 500ml/min.
(19021980), Newcastle anaesthetist; Gordon Jackson - bobbin is clearly visible throughout the length of
Rees (19182000), Liverpool anaesthetist; David Hum- the Rotameter tube.
phrey, South African physiologist and anaesthetist] - CO2 cylinder is connected to the machine only
Conway CM (1985). Br J Anaesth; 57: 64957 when specifically required.
See also, Adjustable pressure-limiting valve; Catheter delivering excessive pressures:
mounts; Coaxial anaesthetic breathing systems; Face- - adjustable pressure-limiting valve on breathing
masks; Tracheal tubes; Valveless anaesthetic breathing systems: modern ones allow maximal pressures of
systems ~70 cmH2O when fully closed. Many ventilators
also have cut-off maximal pressures.
Anaesthetic drug labels, see Syringe labels - distensible reservoir bag; maximal pressure attain-
able is about 60 cmH2O. Pressure reaches a
Anaesthetic machines. Term commonly refers to plateau as the bag distends, falling slightly
machines providing continuous flow of anaesthetic gases (Laplaces law) before bursting.
(cf. intermittent-flow anaesthetic machines). The original Other safety features:
Boyle machine was developed in 1917 at St Bar- switches to prevent soda lime being used with tri-
tholomews Hospital, although similar apparatus was chloroethylene (older machines).
already being used in America and France. key filling system for vaporisers.
Usual system: negative and positive pressure relief valves within
piped gas supply or cylinders. scavenging systems.
pressure gauges may indicate pipeline, cylinder antistatic precautions.
or regulated (reduced) pressure (see Pressure Thompson PW, Wilkinson DJ (1985). Br J Anaesth; 57:
measurement). 6408
pressure regulators provide constant gas pressure, See also, Checking of anaesthetic equipment
usually about 400 kPa (4 bar) in the UK. Pipelines
are already at this pressure. Anaesthetic morbidity and mortality. Complications
flowmeters, usually Rotameters. during and following anaesthesia are difficult to quantify,
vaporisers. since many may be related to surgery or other factors.
pressure relief valve downstream from the vaporis- Many are avoidable, and may be more disturbing to the
ers protects the flowmeters from excessive pressure; patient than the surgery itself.
it opens at about 3840 kPa. May be combined with Examples:
a non-return valve. tracheal intubation difficulties (see Intubation, com-
O2 flush; bypasses flowmeters and vaporisers, deliv- plications of).
ering at least 35 l/min. sore throat.
O2 failure warning device. damage to teeth, mouth, eyes, etc.
ventilators, monitoring equipment, suction equip- respiratory complications: hypoventilation, atelec-
ment and various anaesthetic breathing systems tasis, chest infection, PE, pneumothorax, aspiration
may be incorporated. Some machines contain pneumonitis, airway obstruction, bronchospasm.
microprocessors for digitalised control of functions, cardiovascular complications: MI, hypertension/
e.g. gas flow. hypotension, air embolism, arrhythmias.
Modern safety features reduce the risk of: blood transfusion hazards.
delivering hypoxic gas mixtures: thrombophlebitis/pain at injection or infusion sites.
- to avoid incorrect gas delivery: extravasation of injectate/intra-arterial injection.
- pin index system for cylinders and non-inter- severe neurological complications: CVA, brain
changeable connectors for piped gas outlet. damage, spinal cord infarction; they often follow
- colour coding of pipelines and cylinders. severe hypotension/cardiac arrest/hypoxia.
- O2 analyser. awareness.
- O2 flowmeter control is bigger and has a differ- drowsiness, confusion, psychological changes.
ent profile from others; it is positioned in the PONV.
same place on all machines (on the left in the headache: often related to perioperative dehydra-
UK; on the right in the USA). tion and starvation. Post-dural puncture headache.
Analgesic drugs 35

nerve injury and damage related to positioning of monitoring is disconnected during transfer of the
the patient. patient.
muscle pains following suxamethonium. transfer and positioning for surgery are more haz-
backache: especially after lithotomy position. ardous with the patient anaesthetised than when
Reduced by lumbar pillows. awake.
falls during transfer from/to trolleys. equipment, iv fluids and drugs may not be immedi-
burns, e.g. from diathermy. ately available in the operating theatre.
adverse drug reactions, e.g. halothane hepatitis, The above disadvantages lead many anaesthetists to
MH. induce anaesthesia in the operating theatre for high-risk
drug overdose. patients. Continued existence of anaesthetic rooms is
renal impairment, e.g. following uncorrected controversial. Holding areas capable of processing many
hypotension. patients at once (allowing premedication and perfor-
death. mance of regional blocks) have been suggested as an
Mortality may be related to anaesthesia, surgery alternative.
or the medical condition of the patient. Mortality Meyer-Witting M, Wilkinson DJ (1992). Anaesthesia; 47:
studies in the UK, USA, Canada, Scandinavia, 10212
Europe and Australia have all implicated similar
factors: Anaesthetic simulators, see Simulators
- inadequate assessment. Anaesthetists non-technical skills (ANTS). Defined
- hypovolaemia and inadequate resuscitation. as the cognitive, social and personal resource skills that
perioperatively: complement technical skills, contributing to the safe and
- aspiration. efficient delivery of anaesthesia. Long recognised to play
- inadequate monitoring. a major role in crisis management and error prevention;
- intubation difficulties. recent interest in objectively assessing and developing
- delivery of hypoxic gas mixtures and equipment these skills has led to the development of the ANTS
failure. taxonomy. This consists of an assessment system address-
- inexperience/inadequate supervision. ing skills relating to four categories: team working; deci-
postoperatively: sion-making; task management; and situation awareness.
- inadequate observation. Each skill is assessed on a four-point scale.
- hypoventilation due to respiratory depression, Largely used in the simulator setting; elements of the
residual neuromuscular blockade and respiratory system have recently been incorporated into formal
obstruction. workplace-based assessment tools.
Morbidity and mortality are thus reduced by: Flin R, Patey R, Glavin R, Maran N (2010). Br J Anaesth;
thorough preoperative assessment and adequate 105: 3844
resuscitation. See also, Crisis resource management; Fixation error
checking of anaesthetic equipment and drugs.
adequate monitoring. Analeptic drugs. Drugs causing stimulation of the CNS
anticipation of likely problems. as their most prominent action (many other drugs also
attention to detail. have stimulant properties, e.g. aminophylline).
adequate recovery facilities. Mechanism of action:
adequate supervision/assistance. block inhibition, e.g. strychnine (via glycine antago-
Clear contemporaneous record-keeping promotes nism), picrotoxin (via GABA antagonism).
careful perioperative monitoring and assists retrospec- increase excitation, e.g. doxapram, nikethamide.
tive analysis of complications and future anaesthetic Doxapram increases respiration via stimulation of
management. peripheral chemoreceptors. All the analeptics may cause
See also, Audit; Confidential Enquiries into Maternal cardiovascular stimulation, and convulsions at sufficient
Deaths, Report on; Confidential Enquiry into Periopera- doses.
tive Deaths
Analgesia. Lack of sensation of pain from a normally
Anaesthetic rooms (Induction rooms). Usual in the painful stimulus.
UK but not used in many other countries. See also, Analgesic drugs
quiet area for induction of anaesthesia and Analgesic drugs. May be divided into:
teaching. opioid analgesic drugs.
less frightening for the patient than lying on the inhibitors of prostaglandin synthesis:
operating table. Allows parents to be present during - NSAIDs.
induction of anaesthesia in children. - paracetamol.
anaesthetists domain; i.e. without pressure from others:
surgeons. - inhalational anaesthetic agents, e.g. N2O,
store for anaesthetic drugs and equipment. trichloroethylene.
increased throughput of the operating suite, if - ketamine.
another anaesthetist is available to start whilst pre- - clonidine.
vious cases are being completed in theatre. - nefopam, ethoheptazine.
Disadvantages: - local anaesthetic agents.
expensive duplication of equipment is required, e.g. adjuncts: i.e. reduce pain or pain sensation by
anaesthetic machine, monitoring, scavenging. alternative means: e.g. antidepressant drugs,
36 Anaphylaxis

corticosteroids, carbamazepine, gabapentin, muscle adrenaline im (0.51.0ml of 1:1000 every 10min

relaxants, e.g. diazepam. Used widely in chronic as required) or iv (0.51.0ml of 1:10000 slowly,
pain management. Caffeine is often included in oral repeated as required). IV infusion of adrenaline or
analgesic preparations. noradrenaline may be required after initial treat-
Analgesic drugs are distinguished from anaesthetic ment. Alternative vasoconstrictors, e.g. metarami-
agents by their ability to reduce pain sensation without nol, have been successfully used in resistant cases.
inducing sleep; thus N2O is a good analgesic but a poor Bronchodilator drugs, e.g. salbutamol, may be
anaesthetic, and halothane has poor analgesic properties required.
but is a potent anaesthetic. In practice the distinction is Secondary management includes antihistamine drugs,
not precise, as analgesic drugs, e.g. opiates, will cause e.g. chlorphenamine 1020mg slowly iv (H2-receptor
unconsciousness at high doses, and anaesthetic drugs, e.g. antagonists have been suggested but current UK
halothane, will abolish pain sensation at deep planes of guidelines do not support their use), and hydrocorti-
anaesthesia. sone 100200mg iv. Bicarbonate therapy may be
required according to blood gas interpretation.
Anaphylaxis. Severe, life-threatening, generalised or Blood samples should be taken for subsequent testing
systemic hypersensivity reaction. The term has tradition- (see Adverse drug reactions).
ally been reserved for type I immune reactions in which Kroigaard M, Garvey LH, Gillberg L (2007). Acta
cross-linking of two immunoglobulin type-E (reagin) Anaesthesiol Scand; 51: 65570
molecules by an antigen on the surface of mast cells
results in the release of histamine and other vasoactive Aneroid gauge, see Pressure measurement
substances, e.g. kinins, 5-HT and leukotrienes. Type G
immunoglobulin may also be involved. True anaphy- Anesthesia and Analgesia. Oldest current journal of
laxis requires previous exposure to the antigen respon- anaesthesia, first published in 1922 as Current Researches
sible, sometimes many exposures; e.g. anaphylaxis to in Anesthesia and Analgesia (the journal of the National
thiopental classically occurs after more than 10 expo- Anesthesia Research Society, which became the Inter-
sures. However, in 80% of cases no prior exposure is national Anesthesia Research Society in 1925). Also the
evident. official journal of the Society of Cardiovascular Anes-
Reactions not involving IgE cross-linking (and there- thetists, the Society of Pediatric Anesthesia, the Society
fore not requiring prior exposure to the causative agent, of Ambulatory Anesthesia, the International Society
unless the classical complement pathway is involved) for Anaesthetic Pharmacology, the Society for Technol-
have been termed anaphylactoid, but current Euro- ogy in Anesthesia and the Anesthesia Patient Safety
pean guidelines recommend avoidance of this term, Foundation.
since the clinical presentation and management of both Craig DB, Martin JT (1997). Anesth Analg; 85: 23747
types are identical. Such reactions may involve direct
histamine release from mast cells (typically radiological
Anesthesiology. Journal of the American Society of
contrast media, certain neuromuscular blocking drugs,
Anesthesiologists, first published in 1940. Also the offi-
e.g. atracurium, tubocurarine), or activation of comple-
cial journal of the Society of Obstetric Anesthesia and
ment via either classical or alternative pathways (e.g.
Perinatology, and the American Society of Critical Care
More common in women, which has led to the
suggestion that exposure to cosmetics may prime the
reaction. Incidence is estimated at 1 in 1000020000 Anesthesiology. American term describing the
anaesthetics, but with considerable variation between practice of anaesthesia by trained physicians (anesthesi-
countries. More common when drugs are given iv. Agents ologists) as opposed to others who might administer
most commonly implicated are the neuromuscular anaesthetics (e.g. nurse anesthetists). Formally accepted
blocking drugs (6070%), especially suxamethonium, as a specialty by the American Medical Association in
latex (1020%), and antibacterial drugs (1015%; N.B. 1940. In the UK, the term anaesthetist implies medical
current opinion is that patients allergic to penicillin are qualification.
not more likely to react to third- or fourth-generation
cefalosporins). Mortality is approximately 5%. Has been Angina, see Ischaemic heart disease; Myocardial
classified clinically into five grades: ischaemia
I: cutaneous: erythema, urticaria, angio-oedema.
II: as above plus hypotension, tachycardia, Angio-oedema. Tissue swelling resulting from allergic
bronchospasm. reactions. Spread of oedema through subcutaneous
III: as above but severe; collapse, arrhythmias. tissue often involves the periorbital region, lips, tongue
IV: cardiac and/or respiratory arrest. and oropharynx. Life-threatening airway obstruction
V: death. may occur. Common precipitants include plants, food-
Clinical presentation is variable, although 7090% of stuffs (e.g. shellfish, nuts) and drugs (especially angio
patients have cutaneous features and 2040% have tensin converting enzyme inhibitors). Acute swelling
bronchospasm. Hypotension is the only feature in often settles after about 6h, although treatment of a
~10%. severe life-threatening attack should follow the manage-
Immediate management: ment of anaphylaxis.
removal of potential triggers; call for help. Certain forms of angio-oedema result from a defi-
ABC approach to assessment and treatment; intu- ciency of C1-esterase inhibitor, either acquired or hered-
bate if necessary and administer 100% O2 and iv itary. Colicky abdominal pain or severe respiratory
fluids. The patients legs should be raised if there is obstruction often occurs. Treatment of attacks resulting
hypotension. CPR if indicated. from these forms includes androgens, e.g. danazol,
Ankle, nerve blocks 37

plasminogen inhibitors or replacement of C1-esterase Animal bites, see Bites and stings
inhibitor (as fresh frozen plasma or in a synthetic form).
See also, Complement, Hereditary angio-oedema Anion gap. Difference between measured cation and
anion concentrations in the plasma. Sodium concentra-
Angioplasty, see Percutaneous coronary intervention tions exceed chloride plus bicarbonate concentrations
by 411mmol/l (the range has changed in recent years
Angiotensin II receptor antagonists. Antihypertensive as modern methods of measuring electrolytes give rise
drugs, also being investigated for treatment of heart to higher normal values for chloride concentrations).
failure; competitively inhibit angiotensin II at its AT1 Anionic proteins, phosphate and sulphate make up the
receptor subtype on arteriolar smooth muscle, thus less difference. Of use in the differential diagnosis of meta-
likely than angiotensin converting enzyme inhibitors to bolic acidosis; anionic gap increases when organic anions
cause systemic side effects, including those related to accumulate, e.g. in lactic acidosis, ketoacidosis, uraemia.
interaction with other hormone systems (e.g. involving It does not increase in acidosis due to loss of bicarbonate
kinins), or renin/angiotensin system imbalance. However, or intake of hydrochloric acid. Not an infallible tool
may cause hypotension or hyperkalaemia, and should be since other cations such as potassium, calcium and mag-
used with caution in renal artery stenosis. Other side nesium may influence the calculation. Anion gap has
effects include rash, urticaria, angio-oedema, myalgia, also been compared to alterations in plasma bicarbonate
GIT disturbance and dizziness. Losartan was the first to levels (AG/HCO3 ratio). It has also been calculated
be developed, valsartan, candesartan, eprosartan, irbe- for urine electrolytes.
sartan, olmesartan and telmisartan subsequently.
Ankle Brachial Pressure Index (ABPI). Measure of
Angiotensin converting enzyme inhibitors (ACE peripheral vascular disease, calculated by dividing the
inhibitors). Originally isolated from snake venom. Used systolic pressure in the leg (best results are obtained if
in the treatment of hypertension and cardiac failure, the dorsalis pedis and posterior tibial artery pressures
they have been shown to reduce mortality in cardiac are averaged) by the systolic pressure in the arms
failure associated with MI. They block the action of (average of left and right brachial artery pressures). Nor-
angiotensin converting enzyme; apart from converting mally 0.911.3, with values > 1.3 suggesting poor arterial
angiotensin I to angiotensin II, this enzyme breaks down compressibility due to medial arterial calcification while
kinins, naturally occurring vasodilators. The ACE inhibi- values of < 0.9, < 0.7 and < 0.4 indicate mild, moderate
tors cause vasodilatation and a drop in BP that may be and severe disease respectively. Has been used to predict
profound after the first dose. Side effects include hypo- cardiovascular morbidity and mortality and distinguish
tension, rashes, leucopenia, renal and hepatic damage, atherosclerosis from other causes of leg pain.
loss of taste, angio-oedema, pancreatitis, GIT distur-
bance, myalgia, dizziness, headache and cough. Severe Ankle, nerve blocks. Useful for surgery distal to the
hypotension may follow induction of anaesthesia or ankle.
perioperative haemorrhage, especially if the patient is Nerves to be blocked are as follows (Fig. 11):
fluid- and/or sodium-depleted (e.g. taking diuretics). tibial nerve (L5S3): lies posterior to the posterior
Should be used with caution in patients with renovascu- tibial artery, between flexor digitorum longus and
lar disease. flexor hallucis longus tendons. Divides into lateral
Captopril and enalapril were the first and second and medial plantar nerves behind the medial mal-
ACE inhibitor introduced respectively; newer ones leolus. Supplies the anterior and medial parts of the
include cilazapril, fosinopril, lisinopril, moexipril, perin- sole of the foot. A needle is inserted lateral to the
dopril, quinapril, ramipril and trandolapril. posterior tibial artery at the level of the medial mal-
See also, Renin/angiotensin system leolus, or medial to the Achilles tendon if the artery
cannot be felt. It is passed anteriorly and 510ml
Angiotensins, see Renin/angiotensin system local anaesthetic agent injected as it is withdrawn.

Saphenous Cutaneous branch of

common peroneal

Lateral Medial plantar


Superficial peroneal Superficial peroneal

Sural Medial plantar Sural

Fig. 11 Cutaneous innervation of the ankle and foot

38 Ankylosing spondylitis

sural nerve (L5S2): formed from branches of the dilatation. Treatment includes behavioural and psy-
tibial and common peroneal nerves. Accompanies chotherapy; chlorpromazine has also been used.
the short saphenous vein behind the lateral malleo- Seller CA, Ravalia A (2003). Anaesthesia; 58: 43743
lus and supplies the posterior part of the sole, the
back of the lower leg, the heel and lateral side of Anrep effect. Intrinsic regulatory mechanism of the
the foot. Subcutaneous infiltration is performed heart; contractility increases in response to acute
from the Achilles tendon to the lateral malleolus, increases in afterload. Initial reduction in stroke volume
using 510ml solution. and increase in left ventricular diastolic pressure are
deep and superficial peroneal nerves (both L4S2): followed by restoration to near original values. May be
the deep peroneal nerve supplies the area between related to changes in myocardial perfusion.
the first and second toes. It lies between anterior [Gleb V Anrep (18901955), Russian-born Egyptian
tibial (medially) and extensor hallucis longus (later- physiologist]
ally) tendons, lateral to the anterior tibial artery. A Yentis SM (1998). J Roy Soc Med; 91: 20912
needle is inserted between these tendons; a click
may be felt as it penetrates the extensor retinacu- Anrep, Vassily (18521927). Russian scientist and med-
lum. 5ml solution is injected. The superficial pero- ico-politician. Described the pharmacology of cocaine in
neal nerve is blocked by subcutaneous infiltration 1880 and was the first person to describe the numbing
from the lateral malleolus to the front of the tibia. effect of sc injection; he went on to perform the first
It supplies the dorsum of the foot. nerve blocks (intercostal), publishing his results in
saphenous nerve (L34): the terminal branch of the Russian in 1884 but failing to publicise his work more
femoral nerve; blocked by subcutaneous infiltration widely. His son Gleb described the Anrep effect.
above and anterior to the medial malleolus. It sup- Yentis SM (1999). Anesthesiology; 90: 8905
plies the medial side of the ankle joint.
Antacids. Used to relieve pain in peptic ulcer disease,
hiatus hernia and gastro-oesophageal reflux by increas-
Ankylosing spondylitis. Disease characterised by ing gastric pH. Used preoperatively in patients at high
inflammation and fusion of the sacroiliac joints and risk of aspiration of gastric contents (e.g. in obstetrics)
lumbar vertebrae; may also involve the thoracic and cer- to reduce the risk/severity of ensuing pneumonitis,
vical spine. Commonest in males, with a high proportion should aspiration occur. Also used on ICU as prophy-
carrying tissue type antigen HLA B27. laxis against stress ulcers. Many preparations are avail-
Features: able; sodium citrate is most commonly used in anaesthetic
backache and stiffness. Spinal cord compression practice. Chronic overuse of antacids may result in alka-
may occur; atlantoaxial subluxation or cervical frac- losis, hypercalcaemia (calcium salts), constipation (alu-
ture may also occur. Spinal/epidural anaesthesia minium salts) and diarrhoea (magnesium salts).
may be difficult.
restricted ventilation if thoracic spine or costover- Antagonist. Substance that opposes the action of an
tebral joints are severely affected; increased dia- agonist.
phragmatic movement usually preserves good lung Antagonism may be:
function. Pulmonary fibrosis is rare. competitive: the substance reversibly binds to a
tracheal intubation may be difficult due to a receptor, and causes no direct response within the
stiff or rigid neck, or temporomandibular joint cell (i.e. has no intrinsic activity), but may cause a
involvement. response by displacing an agonist, e.g. naloxone.
aortitis may occur (in less than 5% of chronic suf- non-competitive: as above, but with irreversible
ferers), causing aortic regurgitation. Cardiomyopa- binding, e.g. phenoxybenzamine.
thy and conduction defects are rare. physiological: opposing actions are produced by
amyloidosis may occur. binding at different receptors, e.g. histamine and
Woodward JL, Kam PCA (2009). Anaesthesia; 64: adrenaline causing bronchoconstriction and bron-
5408 chodilatation respectively.
See also, Doseresponse curves; Receptor theory

Anorexia nervosa. Psychiatric condition, most common Antanalgesia. Increased sensitivity to painful stimuli
in young women. Characterised by loss of weight, distor- caused by small doses of depressant drugs, e.g. thiopen-
tion of body image and amenorrhoea; the last results tal. Thought to result from suppression of the inhibitory
from weight loss, and psychological and endocrine action of the ascending reticular activating system,
factors. Quoted mortality is 418% the highest of any allowing increased cortical responsiveness (decreased
psychiatric condition. pain threshold). Larger doses depress the activating
Anaesthetic considerations: system and induce sleep. Antanalgesia may also occur as
electrolyte disturbances, especially hypokalaemia, blood drug levels fall, e.g. causing postoperative restless-
are associated with laxative abuse or self-induced ness when barbiturates or alimemazine are used as pre-
vomiting. medication, especially in children.
tendency towards hypothermia, hypotension and
bradycardia. Antecubital fossa (Cubital fossa). Triangular fossa,
reduced lean body mass. anterior to the elbow joint (Fig. 12).
anaemia. Borders:
psychiatric co-morbidity, including depression. proximal: a line between the humeral epicondyles.
rarer complications: myopathy, cardiomyopathy, lateral: brachioradialis muscle.
peripheral neuritis, hepatic impairment, gastric medial: pronator teres.
Antiarrhythmic drugs 39

risk if associated with abnormal placentation; the

Biceps muscle Medial epicondyle placenta may invade (placenta accreta) or even
Brachialis muscle penetrate (placenta percreta) the uterine wall.
Brachial artery Haemorrhage may be torrential, requiring hysterec-
tomy. Placenta accreta/percreta is more common if
Medial cutaneous
there has been prior uterine surgery, e.g. myomec-
nerve of the forearm
tomy or caesarean section, the risk increasing with
Lateral epicondyle each previous procedure.
placental abruption: haemorrhage behind the pla-
centa. May present with abdominal pain and fetal
Lateral cutaneous distress, usually in the third trimester; vaginal bleed-
nerve of the forearm ing is not always present. Caesarean section should
not be delayed since there is a risk of developing
Radial artery DIC if the fetus is not delivered, this risk increasing
the longer the wait. Has been associated with renal
Brachioradialis muscle cortical necrosis.
Anaesthetic management includes standard resuscita-
Radial nerve tion and techniques of obstetric analgesia and anaes-
(under brachioradialis)
thesia; the choice of regional versus general anaesthesia
depends on the cardiovascular stability, estimated
Deep head of
pronator teres
blood loss, presence of fetal distress, whether there is a
coagulopathy and the preferences of the anaesthetist,
Median nerve obstetrician and patient. Postpartum observation is
important since adequate fluid balance and urine
Ulnar artery output must be maintained; in addition placenta
praevia in particular predisposes to postpartum haem-
Ulnar nerve
orrhage since the uterine lower segment is not able to
Fig. 12 Anatomy of the antecubital fossa contract as effectively as the more muscular upper
Walfish M, Neuman A, Wlody D (2009). Br J Anaesth;
103: i4756

floor: supinator and brachialis muscles, with the Anterior spinal artery syndrome. Infarction of the
joint capsule behind. spinal cord due to anterior spinal artery insufficiency.
roof: deep fascia with the median cubital vein and
May follow profound hypotension, e.g. in spinal or epi-
medial cutaneous nerve on top. dural anaesthesia. May also occur after aortic surgery.
Contents from medial to lateral (embedded in fat):
Results in lower motor neurone paralysis at the level of
median nerve.
the lesion, and spastic paraplegia with reduced pain and
brachial artery, dividing into radial and ulnar
temperature sensation below the level. Because the pos-
arteries. terior spinal arteries supply the dorsal columns and pos-
biceps tendon.
terior horns, joint position sense and vibration sensation
posterior interosseus and radial nerves.
are preserved.
The bicipital aponeurosis lies between the superficial
veins and deeper structures, protecting the latter during
venepuncture. Damage may still be caused to nerves and Anthrax, see Biological weapons
arteries during this procedure; anomalous branches are
relatively common. Accidental intra-arterial injection of Antiarrhythmic drugs. Classified by Vaughan Williams
drugs is a particular hazard. into four classes, depending on their effects on the action
See also, Venous drainage of arm potential in vitro. A fifth class has been suggested that
includes a number of miscellaneous drugs (e.g. digoxin,
Antepartum haemorrhage (APH). Defined as vaginal and other cardiac glycosides, adenosine, magnesium)
bleeding after 22 weeks gestation. Occurs in up to 5% that do not fit into the standard four classes (Table 6).
of all pregnancies. Most cases are not severe and are More usefully classified for clinical purposes according
associated with various conditions, including infection. to their site of action:
Two conditions affecting the placenta are of particular atrioventricular node: calcium channel blocking
importance to the anaesthetist since they may cause drugs, digoxin, -adrenergic receptor antagonists,
sudden and severe collapse and rapid exsanguination, adenosine (used for supraventricular arrhythmias).
although this extreme is fortunately rare: atria, ventricles and accessory pathways: quini-
placenta praevia: the placenta encroaches upon or dine, procainamide, disopyramide, amiodarone
covers the cervical os. Presents with vaginal bleed- (used for supraventricular and ventricular
ing, usually in the third trimester; there may be fetal arrhythmias) and dronedarone (used to maintain
distress. Unless the mother is at risk of exsanguina- sinus rhythm after successful cardioversion for
tion, delivery of the fetus by caesarean section atrial fibrillation).
should wait until adequate blood has been obtained ventricles only: lidocaine (lignocaine), mexiletine,
and appropriate staff are present, since the mother phenytoin (used for ventricular arrhythmias).
is not at risk of developing coagulopathy unless [EM Vaughan Williams, English pharmacologist]
massive transfusion is required. Particularly high See also, individual arrhythmias
40 Antibacterial drugs

Antibiotics, see Antibacterial drugs

Table 6 Classification of antiarrhythmic drugs

Class Action Examples Antibodies, see Immunoglobulins

I Slow depolarisation rate by
inhibiting sodium influx Anticholinergic drugs. Strictly, should include all
a Prolong action potential Quinidine drugs impairing cholinergic transmission, although the
Procainamide term usually refers to antagonists at muscarinic acetyl-
Disopyramide choline receptors. Antagonists at nicotinic receptors
b Shorten action potential Lidocaine are classified as either ganglion blocking drugs or
Mexiletine neuromuscular blocking drugs. In general effects are
antiparasympathetic, and include tachycardia, bron-
c No effect on action Flecainide
chodilatation, mydriasis, reduced gland secretion, smooth
Propafenone muscle relaxation, and sedation or restlessness. Anaes-
Encainide thetic uses include the treatment of bradycardia, as a
II Diminish effect of -adrenergic receptor component of premedication and antagonism of the
catecholamines antagonists cardiac effects of acetylcholinesterase inhibitors.
Bretylium In anaesthesia, the most commonly used agents are
III Prolong action potential, Amiodarone atropine, hyoscine and glycopyrronium. Comparison
without affecting Sotalol of actions:
depolarisation rate Bretylium atropine:
IV Inhibit calcium influx Calcium channel blocking drugs
- central excitation.
V Miscellaneous Digoxin
- greater action than hyoscine on the heart, bron-
Magnesium chial smooth muscle and GIT.
- central depression; amnesia (may cause excite-
ment in the elderly).
- greater action than atropine on the pupil and
sweat, salivary and bronchial glands.
Antibacterial drugs. Drugs used to kill bacteria (bacte- glycopyrronium:
ricidal) or inhibit bacterial replication (bacteriostatic). - minimal central effects (quaternary ammonium
Antibiotics are synthesised by micro-organisms and ion; crosses the bloodbrain barrier less readily
kill or inhibit other micro-organisms. Drugs synthesised than atropine and hyoscine, both tertiary ions).
in vitro, e.g. sulphonamides, are not antibiotics. - similar peripheral actions to atropine, but with
Main groups: greater antisialagogue effect and less effect on the
-lactams: bactericidal; act by inhibiting cell wall heart. Less antiemetic action than hyoscine and
synthesis. Include penicillins, cephalosporins, aztre- atropine.
onam, carbapenems. - longer duration of action.
macrolides: bacteriostatic; act by inhibiting protein Other uses of anticholinergic drugs include:
synthesis. Include erythromycin and related drugs. antispasmodic effect (on bowel and bladder), e.g.
aminoglycosides: bactericidal; inhibit protein syn- propantheline.
thesis. Include gentamicinh, netilmicin. ulcer healing, e.g. pirenzepine.
tetracyclines: bacteriostatic; inhibit protein bronchodilatation, e.g. ipratropium.
synthesis. mydriasis and cycloplegia (dilatation of pupil and
sulphonamides and trimethoprim: each alone is paralysis of accommodation), e.g. atropine.
bacteriostatic; the combination (cotrimazole) is Anticholinergic antiparkinsonian drugs, e.g. benzatro-
bactericidal. pine, procyclidine, orphenadrine, are used for their
4-quinolones: bactericidal; impair nucleic acid rep- central effects.
lication. Include nalidixic acid and ciprofloxacin. See also, Central anticholinergic syndrome
glycopeptides, e.g. teicoplanin and vancomycin:
Anticholinesterases, see Acetylcholinesterase inhibitors
others, e.g. clindamycin, chloramphenicol, metroni-
dazole, polymyxins, fusidic acid, linezolid, quinu-
pristin/dalfopristin. Anticoagulant drugs. Mechanisms of action:
antituberculous drugs. prevent synthesis of coagulation factors, e.g.
Choice of antibacterial drug depends on the organism warfarin.
involved (or suspected), the severity of the condition and inhibit existing factors, e.g. heparin, factor Xa inhib-
the site of the infection. In many conditions, initial itors, thrombin inhibitors.
therapy is based on a best guess principle with broad- inhibit platelet aggregation, i.e. antiplatelet drugs.
spectrum drugs, narrower therapy being continued break down circulating fibrinogen, e.g. ancrod
when the results of culture and sensitivity studies are (snake venom derivative; not commonly used).
known. The requirement for prompt treatment in severe Fibrinolytic drugs break down thrombus once formed.
illness may conflict with the need to obtain adequate Warfarin and heparin are more effective at preventing
samples for culture before therapy is started. Much venous thrombus than arterial thrombus, as the former
concern exists about the increasing problem of bacterial contains relatively more fibrin. Antiplatelet drugs are
resistance. more effective in arterial blood, where thrombus con-
See also, Antifungal drugs; Antiviral drugs tains many platelets and little fibrin.
Antiemetic drugs 41

Anticonvulsant drugs. Heterogeneous group of drugs deficiency. Further evidence is that central depletion
used to treat epilepsy classified according to their main (e.g. by reserpine) may cause depression.
mechanism of action, although many act in several ways: May be classified thus:
neuronal sodium channel blockade, e.g. sodium val- tricyclic antidepressant drugs: block noradrenaline
proate, phenytoin, carbamazepine, oxcarbazepine, and 5-HT uptake from synapses.
lamotrigine, zonisamide, lacosamide. selective serotonin reuptake inhibitors (SSRIs):
calcium channel blockade, e.g. carbamazepine, specifically block reuptake of 5-HT, e.g. fluoxetine.
ethosuximide. Nefazodone blocks serotonin uptake and its recep-
increase in GABA levels: tors, whilst venlafaxine is a serotonin and noradren-
- GABAA receptor agonists, e.g. benzodiazepines, aline reuptake inhibitor.
barbiturates. monoamine oxidase inhibitors (MAOIs): prevent
- GABA transaminase inhibitors, e.g. vigabatrin. catecholamine breakdown.
- GABA uptake inhibitors, e.g. tiagabine. others, e.g. lithium (mechanism of action is
- glutamic acid decarboxylase inhibitors, e.g. gaba- unknown), reboxetine (selective noradrenaline
pentin, sodium valproate. reuptake inhibitor), mirtazapine (presynaptic
glutamate receptor blockers, e.g. felbamate, 2-antagonist).
topiramate Perioperative problems arising from concurrent antide-
unknown action: levetiracetam. pressant therapy may occur, particularly with MAOIs.
Choice of drug depends on the type of seizures,
absence of side effects and teratogenesis in women of
Antidiuretic hormone, see Vasopressin
child-bearing age:
broad-spectrum agents, e.g. sodium valproate,
lamotrigine, levetiracetam: used to treat generalised Antiemetic drugs.
epilepsy (tonic-clonic or absence seizures). Absence Site of action (Fig. 13):
seizures may also respond to ethosuximide and vomiting centre: anticholinergic and antihistamine
myoclonic epilepsy to clonazepam. drugs.
narrow-spectrum agents, e.g. carbamazepine, phe- chemoreceptor trigger zone (CTZ): dopamine
nytoin, vigabatrin, gabapentin: reserved for simple receptor antagonists (e.g. phenothiazines, butyro-
or complex partial seizures. phenones and metoclopramide) and 5-HT3 receptor
About 50% of epileptic patients can be managed with antagonists.
one anticonvulsant drug. GIT: metoclopramide increases lower oesophageal
First-line management of status epilepticus involves sphincter tone and gastric emptying by a peripheral
use of iv lorazepam. Diazepam, phenytoin, fosphenytoin action.
and thiopental are also used. neurokinin-1 receptor antagonists (e.g. aprepi-
For patients undergoing surgery, anticonvulsant tant): originally developed for use in cancer
therapy should continue up to operation, and recom- chemotherapy.
mence as soon as possible postoperatively. If oral therapy others:
is delayed postoperatively, parenteral administration - dexamethasone: mechanism of action is
may be substituted. Phenobarbital and phenytoin cause uncertain.
hepatic enzyme induction, increasing the metabolism of - cannabis derivatives have been used in the treat-
certain drugs. ment of chemotherapy-induced emesis.
See also, -Aminobutyric acid (GABA) receptors - midazolam on induction of anaesthesia has been
shown to reduce PONV.
Antidepressant drugs. Most increase central amine Dopamine antagonists are suitable for treatment of
concentrations (e.g. dopamine, noradrenaline, 5-HT), vomiting associated with morphine, which stimulates the
supporting the theory that depression results from amine CTZ. Increased vestibular stimulation of the vomiting

trigger zone 5-HT3, dopamine and
5-HT3, dopamine and emetic agents
neurokinin-1 antagonists
neurokinin-1 receptors

Vomiting centre Anticholinergic drugs

muscarinic cholinergic and
histamine receptors Antihistamine drugs

5-HT3 and neurokinin-1

receptor antagonists
Gastrointestinal tract
5-HT3 and neurokinin-1

Fig. 13 Sites of action of different antiemetic drugs

42 Anti-endotoxin antibodies

centre, e.g. in motion sickness, is best treated with drugs prevention/treatment of nausea and vomiting, e.g.
acting on the vomiting centre, e.g. hyoscine. Sedation is cinnarizine, cyclizine (act on vomiting centre).
a common side effect, particularly of antihistamines, They have anticholinergic effects (e.g. dry mouth, blur-
anticholinergic drugs and phenothiazines. In addition, ring of vision, urinary retention). Newer drugs, e.g. terf-
phenothiazines may cause hypotension, and all dopa- enadine, cross the bloodbrain barrier to a lesser extent,
mine antagonists may cause dystonic reactions. causing less sedation.
See also, H2 receptor antagonists
Anti-endotoxin antibodies. Antibodies directed against
various parts of Gram-negative endotoxins; they have Antihypertensive drugs. Drugs used to reduce BP may
been investigated as possible treatments of severe act at different sites (Fig. 14):
sepsis. Theoretically, antibodies against the inner core of diuretics: reduce ECF volume initially and also
endotoxin (which is conserved among many different cause vasodilatation (1).
bacteria) should be useful in protecting against many vasodilator drugs: act on the vascular smooth muscle
organisms. They have conferred protection against (2), either directly, e.g. hydralazine, sodium nitro-
Gram-negative infection in animal models, but their prusside, or indirectly, e.g. -adrenergic receptor
place in clinical practice is controversial. One (HA-1A; antagonists, calcium channel blocking drugs, angio-
Centoxin) was introduced in 1991 for use in humans, but tensin II receptor antagonists, potassium channel
was withdrawn in 1993 following evidence that it might activators. Angiotensin converting enzyme inhibi-
increase mortality in patients without Gram-negative tors also decrease water and sodium retention.
bacteraemia. Another, E5, produced conflicting results -adrenergic receptor antagonists: lower cardiac
in human trials and was never released. output (3).
adrenergic neurone blocking drugs (4): e.g. gua-
Antifibrinolytic drugs. Drugs that prevent dissolution of nethidine depletes nerve endings of noradrenaline,
fibrin. Include -aminocaproic acid (no longer available preventing its release. Reserpine prevents storage
in the UK) and tranexamic acid, which inhibit plasmino- and release of noradrenaline. -Methyl-p-tyrosine
gen activation and thus reduce fibrinolysis. Used periop- inhibits dopa formation from tyrosine.
eratively to reduce surgical blood loss (e.g. in cardiac ganglion blocking drugs (5).
surgery and obstetric haemorrhage), and in trauma. centrally acting drugs (6): reduce sympathetic
Cardone D, Klein AA (2009). Eur J Anaesthesiol; 26: activity, e.g. reserpine, -methyldopa, clonidine,
7229 moxonidine.
See also, Coagulation In addition, anaesthetic agents and techniques may
reduce BP; e.g. halothane depresses baroreceptor activ-
Antifungal drugs. Heterogeneous group of drugs active ity (7) and also reduces sympathetic activity and cardiac
against fungi; includes: output; spinal and epidural anaesthesia block sympa-
polyenes (amphotericin, nystatin). thetic outflow (8).
imidazoles (e.g. clotrimazole, ketoconazole, In the treatment of hypertension, thiazide diuretics,
miconazole). -adrenergic receptor antagonists and oral vasodilators
triazoles (fluconazole, itraconazole, voriconazole).
others (caspofungin, flucytosine, griseofulvin).

Antigen. Substance that may provoke an immune Vasomotor centre

response, then react with the cells or antibodies pro-
duced. Usually a protein or carbohydrate molecule.
Some substances (called haptens), too small to provoke
immune reactions alone, may combine with host
molecules, e.g. proteins, to form a larger antigenic
Antigravity suit. Garment used to apply pressure to the 6
lower half of the body, in order to increase blood volume
in the upper half and prevent hypotension, e.g. in the
sitting position in neurosurgery. Systolic BP and CVP
are increased; the latter may aid prevention of air embo- 8
lism. Modern suits are inflated pneumatically around the
legs and abdomen, to a pressure of 28 kPa.
Military antishock trousers (MAST) have been used 5
in trauma to produce similar effects. They also splint 4
broken bones and apply pressure to bleeding points. 3

Antihistamine drugs. Refers to H1 histamine receptor

prevention or treatment of allergic disorders, 2
e.g. hayfever, urticaria, drug reactions, e.g.
chlorphenamine. 1
for sedation or in premedication, e.g. promethazine
and alimemazine. Fig. 14 Sites of action of antihypertensive drugs (see text)
Antipsychotic drugs 43

(except for -adrenergic receptor antagonists) are used - bromocriptine, lisuride, pergolide and apomor-
most commonly. More recently, the AB/CD algorithm phine: dopamine agonists. Ropinirole is a selec-
has been suggested: ACE inhibitors or -antagonists for tive D2 receptor agonist. Pramipexole is a D2 and
high-renin hypertension, typically younger and non- D3 agonist.
black patients, and calcium channel blocking drugs and/or - amantadine: increases release of endogenous
diuretics for low-renin hypertension, typically older and dopamine.
black patients. NICE guidelines suggest an ACE inhibitor - selegiline: monoamine oxidase inhibitor type B.
or angiotensin-II receptor blocker initially for young - amfetamines have been used.
patients, and a thiazide-like diuretic or calcium blocker anticholinergic drugs, e.g. atropine, benzatropine,
in older or black patients, with combination therapy if trihexyphenidyl, procyclidine: most effective for
required (- and -antagonists as fourth-line drugs). rigidity, tremor and treatment of drug-induced par-
Ganglion blockers, adrenergic neurone blocking kinsonism. For acute drug-induced dystonic reac-
drugs and the centrally acting drugs are seldom used, tions, benzatropine 12mg or procyclidine 510mg
because of their side effects. may be given iv. There is a higher risk of intraopera-
In the treatment of a hypertensive crisis, vasodilator tive arrhythmias and labile BP in patients taking
drugs are often given iv. For patients undergoing surgery, these drugs.
antihypertensive drugs should be continued up to
operation, and recommenced as soon as possible Antiphospholipid syndrome, see Coagulation
postoperatively. disorders
See also, Hypotensive anaesthesia

Anti-inflammatory drugs, see Non-steroidal anti- Antiplatelet drugs. Reduce platelet adhesion and
inflammatory drugs; Corticosteroids aggregation, thereby inhibiting intraluminal thrombus
formation. May act via different mechanisms:
inhibition of platelet cyclo-oxygenase and throm-
Antimalarial drugs. Used for:
prophylaxis: no drugs give absolute protection
boxane 2 production; may be reversible, e.g. pros-
against malaria. Treatment should begin at least 1 tacyclin, or irreversible, e.g. low-dose aspirin, and
week before travel to an endemic area (to ensure other NSAIDs.
patient tolerance) and continued for at least 4 increased intraplatelet cAMP levels, e.g.
weeks after leaving. Drugs used depend upon the dipyridamole.
glycoprotein IIb/IIIa receptor antagonists (e.g.
area to be visited and include chloroquine, progua-
nil, mefloquine and doxycycline. abciximab, eptifibatide, tirofiban); block the site at
which fibrinogen, von Willebrand factor and adhe-
- falciparum malaria: chloroquine is not used sive proteins bind to platelets. Reversible and
because of worldwide resistance. Quinine, meflo- short-acting.
platelet ADP receptor antagonists, e.g. clopidogrel,
quine and halofantrine are the main treatments.
Halofantrine is rarely used today; it can cause prasugrel, ticagrelor, ticlopidine. Inhibition blocks
prolonged QT syndrome. Mefloquine is contra- the glycoprotein IIb/IIIa pathway. Irreversible and
indicated in epilepsy. Artemether with lumefan- long-acting.
trine has recently been introduced. Used to improve cerebral, peripheral and coronary
- benign malaria: chloroquine is the drug of choice blood supply in vascular disease, and to prevent throm-
primaquine. boembolism. Glycoprotein IIb/IIIa inhibitors are recom-
Baird JK (2005). N Engl J Med; 352: 156577 mended for high-risk patients with unstable angina or
non-Q wave MI and for those undergoing percutaneous
Antimitotic drugs, see Cytotoxic drugs transluminal coronary angioplasty. Dextran also has an
antiplatelet action and has been used to prevent postop-
Antiparkinsonian drugs. Treatment of Parkinsons erative DVT and PE.
disease is directed towards increasing central dopami- Patients receiving these drugs who present for surgery
nergic activity, or decreasing cholinergic activity: may be at increased risk of bleeding. The place of
increasing dopamine:
regional anaesthesia in such patients is controversial
- levodopa: crosses the bloodbrain barrier and is because of the possibly increased risk of spinal
converted to dopamine by dopa decarboxylase. haematoma.
Decarboxylase inhibitors (carbidopa, bensera- Hall R, Mazer CD (2011). Anesth Analg; 112: 292318
zide), which do not cross the bloodbrain barrier, See also, Anticoagulant drugs; Coagulation
prevent peripheral dopamine formation, thus
reducing the dose of levodopa required and the Antipsychotic drugs (Neuroleptics). Drugs used for the
incidence of side effects. Entacapone prevents management of psychosis (e.g. hallucinations, delusions,
peripheral breakdown of levodopa by inhibiting thought disorder) and acute agitation. Previously termed
catechol-O-methyl transferase and is used in com- major tranquillisers. All act via antagonism of D2 dopa-
bination with decarboxylase inhibitors in severe mine receptors, with other effects (e.g. sedation, anti-
cases. muscarinic effects) mediated via antagonism of other
Levodopa is most effective for bradykinesia. receptors, e.g. histamine receptors, 5-HT2 receptors, mus-
Its use may be limited by nausea and vomiting, carinic acetylcholine receptors). Other side effects
dystonic movements, postural hypotension and include: prolonged QT syndromes; dystonic reactions;
psychiatric disturbances. Improvement is usually parkinsonian symptoms; hyperglycaemia; and neurolep-
only temporary and may exhibit onoff tic malignant syndrome. Should be used with caution
effectiveness. and at lower dosage in the elderly, in whom they have
44 Antispasmodic drugs

been shown to be associated with a slightly increased Antituberculous drugs. Used for:
mortality and increased risk of CVA. prophylaxis: advised for susceptible close contacts
Classification: or following treatment of TB in immunocompro-
phenothiazines (e.g. prochlorperazine, chlorpro mised patients. Comprises isoniazid alone daily for
mazine). 6 months, or combined with rifampicin daily for
butyrophenones (e.g. haloperidolh, droperidol). 3 months.
atypical (e.g. olanzapine, risperidone, quetiapine). treatment is carried out in two phases:
There is no evidence that any one agent is superior to - initial phase (2 months) using four drugs: intended
any other; choice of drug is determined by individual to reduce the number of viable organisms as
response and tolerability of side effects. quickly as possible to avoid resistance. Usually
includes isoniazid, rifampicin, pyrazinamide and
Antispasmodic drugs. Used as adjunctive therapy in ethambutol. Streptomycin is rarely used today
the management of non-ulcer dyspepsia, irritable bowel but sometimes added if resistance to isoniazid is
syndrome and diverticular disease. Also administered present.
during GIT endoscopy and radiology, and when con- - continuation phase (further 4 months) using two
structing bowel anastomoses. drugs: intended to eradicate the bacteria from the
Include: body (longer treatment may be required in bone,
antimuscarinic agents (e.g. atropine, dicycloverine, joint, CNS and resistant infections). Usually com-
hyoscine, propantheline). Produce dry mouth, prises continuation of isoniazid and rifampicin
blurred vision, urinary retention and constipation. therapy.
Also relax the oesophageal sphincter, causing gas- Other drugs used in resistant cases or when side effects
tro-oesophageal reflux. are limiting include capreomycin, cycloserine, azithro-
others: e.g. alverine, mebeverine, peppermint oil: mycin, clarithromycin, 4-quinolones and rifabutin.
direct intestinal smooth muscle relaxants. Treatment must be supervised if non-compliance is
Antispasmodics should not be used in patients with ileus. suspected since partial completion of treatment courses
is a major factor in producing resistance. During use of
Antistatic precautions. Employed in operating suites, antituberculous drugs (especially pyrazinamide, isonia-
to prevent build-up of static electricity with possible zid and rifampicin), monitoring of liver function is man-
sparks, explosions and fires. Surfaces and materials datory. Streptomycin and ethambutol should be avoided
should have relatively low electrical resistance, to allow in patients with renal impairment.
leakage of charge to earth, but not so low as to allow
electrocution and electrical burns.
Precautions include: Antiviral drugs. Heterogeneous group of drugs with
avoidance of wool, nylon and silk, which may generally non-specific actions. Parenteral use is usually
generate static charge. Cotton blankets and clothing reserved for severe life-threatening systemic infections,
are suitable (resistance is very low in moist especially in immunocompromised patients. Available
atmospheres). drugs can best be classified according to the infections
antistatic rubber (containing carbon) for tubing. in which they are used:
Coloured black with yellow labels for identification. herpes simplex/varicella zoster:
Resistance is 10000010000000 ohms/cm. - aciclovir: purine nucleoside analogue; after
terrazzo floor (stone pieces embedded in cement phosphorylation, it inhibits viral DNA poly-
and polished): resistance should be 200005 000000 merase. Phosphorylated by, and therefore active
ohms between two points 60cm apart. against, herpes simplex and varicella zoster
trolleys and other equipment have conducting viruses. Early initiation of treatment is important.
wheels; staff wear antistatic footwear. May also be useful in HIV infection. May be given
Sparks are more likely in cold dry atmospheres, there- topically, orally or iv; side effects include GIT
fore relative humidity should exceed 50% and tempera- upset, rashes, and deteriorating renal and liver
ture exceed 20C. function.
The requirement for expensive antistatic flooring and - famciclovir, valaciclovir, idoxuridine, inosine,
other precautions are rarely followed in modern UK amantadine: used for simplex and zoster infection
operating suites, since the use of flammable anaesthetic of the skin and mucous membranes.
agents such as cyclopropane and diethyl ether has ceased HIV:
in the UK, and although fires may still occur with other - nucleoside reverse transcriptase inhibitors: e.g.
substances (e.g. alcohol skin cleansers), ignition is usually zidovudine, abacavir, zalcitabine, didanosine,
caused by a high-energy source such as diathermy or stavudine, lamivudine, tenofovir.
laser rather than static electricity. - protease inhibitors: e.g. indinavir, ritonavir, lopi-
navir, nelfinavir, amprenavir, saquinavir. May
Antithrombin III. Cofactor of heparin and natural cause metabolic derangement, including hyper-
inhibitor of coagulation. Often deficient in critical illness lipidaemia and redistribution of body fat, insulin
such as sepsis; hence its investigation as a possible treat- resistance and hyperglycaemia.
ment, though evidence suggests that therapy causes no - non-nucleoside reverse transcriptase inhibitors:
improvement in outcome whilst increasing bleeding e.g. efavirenz, nevirapine. May cause severe skin
complications. A hereditary antithrombin III deficiency reactions and hepatic impairment.
may result in recurrent thromboembolism; patients with cytomegalovirus: ganciclovir, valganciclovir,
the deficiency require higher doses of heparin. foscarnet.
Torossian A, Graf J, Bauhofer (2007). Br Med J; 335: respiratory syncytial virus: tribavirin.
121920 In addition, interferons are used in hepatitis infections.
Aortic dissection 45

Antoine equation. Describes the theoretical variation often given before aortic clamping, to encour-
of SVP with temperature. Empirically relates SVP to age diuresis.
three constants, derived from experimental data for - GIT ischaemia and infarction may occur if the
each substance. mesenteric arterial supply is interrupted. The
[Louis Charles Antoine (described 1888), French anterior spinal artery syndrome may also occur.
scientist] Attempts to reduce the effects of renal and GIT
ischaemia have also included hypothermia and
ANTS, see Anaesthetists Non-Technical Skills use of metabolic precursors, e.g. inosine.
postoperatively: ICU or HDU. Elective IPPV may
Aortic aneurysm, abdominal. Manifestation of periph- be required. Epidural analgesia is often used.
eral vascular disease, most often due to atherosclerosis. For emergency surgery, prognosis is generally poor;
Usually occurs in males over 60 years old. Often presents 50% die in the prehospital setting, and a further 50%
with abdominal or back pain, or as an asymptomatic, die in hospital. The following are important:
pulsatile abdominal swelling, increasingly detected by wide-bore peripheral venous access (and ideally an
ultrasound screening. May rupture or dissect acutely, arterial line) pre-induction; insertion of invasive
leading to death; leakage is amenable to urgent surgical monitoring should not delay surgery
intervention. Elective surgery is indicated when the preparation and draping of the patient before
diameter of the aneurysm exceeds 5cm. The traditional induction.
open procedure is usually performed via an abdominal availability of blood, O negative if necessary.
incision from xiphisternum to pubis. Alternatives include rapid sequence induction. Etomidate or ketamine is
endoluminal repair, in which a graft is placed via per often used.
cutaneous arterial puncture, or a semi-laparoscopic Abdominal muscular relaxation following induction
method, in which much of the mobilisation is achieved of anaesthesia may result in decreased abdominal tam-
via small incisions before grafting. Preparation should be ponade of the leaking aneurysm, resulting in further
as for the open technique since the risk of proceeding or haemorrhage and hypotension.
of severe, sudden haemorrhage is always present. Endo- Vaughn SB, LeMaire SA, Collard CD (2011). Anesthe-
luminal repair in particular has been shown to reduce siology; 115: 1093102
blood loss, organ dysfunction, hospital stay and early See also, Aortic aneurysm, thoracic; Blood transfusion,
mortality, although mortality at 1 year is thought to be massive; Induction, rapid sequence
the same as after open repair.
Anaesthetic considerations for elective repair: Aortic aneurysm, thoracic. Usually results from aortic
preoperative assessment is particularly directed to dissection. Surgical approach is via left thoracotomy;
the effects of widespread atherosclerosis, i.e. affect- one-lung anaesthesia facilitates surgery. Concurrent
ing coronary, renal, cerebral and peripheral arteries. aortic valve replacement may be required. General
Hypertension is also common. anaesthetic management is as for abdominal aneurysm
perioperatively: repair. Cardiovascular instability may be more dramatic
- monitoring: ECG; direct arterial, central venous because of the proximity of the aortic clamp to the heart,
and possibly pulmonary artery pressure measure- and the reduction of venous return and cardiac output
ment; temperature; urine output. during surgical manoeuvres. Complications include
- at least two large-bore iv cannulae. haemorrhage and infarction of spinal cord, liver, gut,
- warming blanket and warming of iv fluids. Humid- kidneys and heart. Perioperative drainage of CSF is
ification of inspired gases. commonly performed to reduce spinal cord ischaemia.
- cardiovascular responses: Operative techniques include atriofemoral cardiopul-
- hypertension during tracheal intubation. monary bypass, or use of a shunt across the clamped
- increased afterload caused by aortic cross- aortic section.
clamping. Hypertension and left ventricular See also, Aortic aneurysm, abdominal
failure may occur. Anticipatory use of vasodila-
tor drugs may help to reduce hypertension and Aortic bodies. Peripheral chemoreceptors near the
left ventricular strain. aortic arch. Similar in structure and function to the
- reduction of afterload, return of vasodilator carotid bodies. Afferents pass to the medulla via
metabolites from lower part of the body, and the vagus.
possible haemorrhage following aortic unclamp-
ing (declamping syndrome). Myocardial con- Aortic coarctation, see Coarctation of aorta
tractility is reduced by the acidotic venous
return. Anticipatory volume loading before Aortic counter-pulsation balloon pump, see Intra-
unclamping, with termination of vasodilator aortic counter-pulsation balloon pump
therapy before slow controlled release of the
clamp, may reduce hypotension. Bicarbonate Aortic dissection. Passage of blood into the aortic wall,
therapy is guided by arterial acidbase analysis; usually involving the media of the vessel. Degeneration
it is often not required if clamping time is less of this layer is usually caused by atherosclerosis but is
than 11.5h. also seen in Marfans syndrome and EhlersDanlos syn-
- blood loss and effects of massive blood drome. Often associated with hypertension. Dissection
transfusion. may involve branches of the aorta, including the coro-
- postoperative visceral dysfunction: nary arteries. Additionally, rupture into pericardium,
- renal failure may follow aortic surgery; it is pleural cavity, mediastinum or abdomen may occur. May
more likely to occur after suprarenal cross- also follow chest trauma. Classified thus (DeBakey
clamping. Mannitol, furosemide or dopamine is classification):
46 Aortic regurgitation

type I: starts in the ascending aorta, extending prox- enlargement/failure. Echocardiography and cardiac
imally to the aortic valve and distally around the catheterisation are also useful.
aortic arch (least common). Anaesthetic management:
type II: limited to the ascending aorta. antibiotic prophylaxis as for congenital heart
type IIIa: starts distal to the left subclavian artery, disease.
extending proximally and distally, but remaining general principles: as for cardiac surgery/ischaemic
above the diaphragm. heart disease. Myocardial ischaemia and left ven-
type IIIb: starts near the left subclavian artery, tricular failure may occur.
extending distally only, and continuing below the the following should be avoided:
diaphragm (i.e. intra-abdominally). - bradycardia: increases time for regurgitation.
Features: - peripheral vasoconstriction and increased dia-
severe tearing central chest pain; may mimic MI. stolic pressure: increases afterload and therefore
May radiate to the back or abdomen. regurgitation. Peripheral vasodilatation reduces
signs of aortic regurgitation. regurgitation and increases forward flow.
signs of haemorrhage or cardiac tamponade. cardioplegia solution is infused directly into the
progressive loss of radial pulses and CVA may indi- coronary arteries during cardiac surgery, since if
cate extension along the aortic arch. Coronary injected into the aortic root it will enter the
artery involvement may cause MI. Renal vessels ventricle.
may be involved. left ventricular end-diastolic pressure may be much
CXR may reveal a widened mediastinum or pleural greater than measured pulmonary capillary wedge
effusion. Echocardiography, CT/MRI scanning and pressure, if the mitral valve is closed early by the
aortography may be used in diagnosis. regurgitant backflow.
Management: postoperative hypertension may occur.
analgesia. [Alfred de Musset (18101857), French poet; Austin
control of BP, e.g. using vasodilator drugs. Flint (18121886), US physician]
surgery is increasingly employed, especially if the See also, Heart murmurs; Preoperative assessment;
aortic valve is involved, dissection progresses or Valvular heart disease
rupture occurs. Management: as for thoracic aortic
aneurysm. Aortic stenosis. Narrowed aortic valve with obstruction
[Edward Ehlers (18631937), Danish dermatologist; to the left ventricular outflow, resulting in a pressure
Henri Alexandre Danlos (18441912), French derma- gradient between the left ventricle and aortic root. Ini-
tologist; Michael E DeBakey (19082008), US cardiac tially, left ventricular hypertrophy and increased force of
surgeon] contraction maintain stroke volume. Compliance is
Karthikesalingam A, Holt PJ, Hinchliffe RJ, Thompson decreased. Coronary blood flow is decreased due to
MM, Loftus IM (2010). Vasc Endovascular Surg; 44: increased left ventricular end-diastolic pressure and
1659 involvement of the coronary sinuses, whilst left ventricu-
See also, Aortic aneurysm, thoracic lar work increases. Ultimately, contractility falls, with left
ventricular dilatation and reduced cardiac output.
Aortic regurgitation. Retrograde flow of blood through Caused by:
the aortic valve during diastole. Causes left ventricular rheumatic fever: may present at any age (usually
hypertrophy and dilatation, with greatly increased stroke also involves the mitral valve).
volume. Later, compliance decreases and end-diastolic congenital bicuspid valve: usually presents in middle
pressure increases, with ventricular failure. age.
Caused by: degenerative calcification: usually in the elderly.
rheumatic fever; usually affects the mitral value too. Features:
aortic dissection. angina (3040%), syncope, left ventricular failure.
endocarditis (especially acute regurgitation). sudden death.
Marfans syndrome. low-volume slow-rising pulse with reduced pulse
congenital defect (associated with aortic stenosis). pressure (plateau pulse). AF usually signifies coex-
chest trauma, ankylosing spondylitis, rheumatoid istent mitral disease.
disease, syphilis, SLE. ejection systolic murmur, radiating to the neck.
Features: Loudest in the aortic area, with the patient sitting
collapsing pulse with widened pulse pressure (water forward in expiration. The second heart sound
hammer). Bobbing of the head in synchrony with is quiet, with reversed splitting if stenosis is
the pulse (Mussets sign) may occur. severe (due to delayed left ventricular emptying).
early diastolic murmur, high-pitched and blowing. A thrill, fourth sound and ejection click may
Loudest in expiration and with the patient leaning be present.
forward, and heard at the left sternal edge, some- investigations: ECG may show left ventricular
times at the apex. The third heart sound may be hypertrophy; CXR may show ventricular enlarge-
present. A thrill is absent. An aortic ejection murmur ment/failure, possibly with calcification and postste-
is usually present, radiating to the neck; a mid-dia- notic dilatation. Echocardiography and cardiac
stolic mitral murmur may be present due to obstruc- catheterisation are especially useful. The gradient
tion by aortic backflow (Austin Flint murmur). across the valve exceeds 50mmHg in severe steno-
left ventricular failure. sis, falling as left ventricular failure supervenes.
angina is usually late. Normal valve area is 2.63.5cm2; in moderate and
investigations: ECG may show left ventricular severe stenosis the area is reduced to < 1.0 and <
hypertrophy; CXR may show ventricular 0.7cm2 respectively.
APACHE IV scoring system 47

Anaesthetic management: each physiological parameter in the first 24h after ICU
antibiotic prophylaxis as for congenital heart admission (range 04), age and chronic health (Table 7);
disease. selection of criteria and weightings is based upon the
general principles: as for cardiac surgery/ischaemic opinions of a panel of experts. Definitions of chronic
heart disease. Myocardial ischaemia, ventricular health are more specific than in the original APACHE
arrhythmias and left ventricular failure may occur. system. The assigned weights for all physiological mea-
Percutaneous transcatheter valve replacements are surements, age and chronic health are summated to give
now being performed. an APACHE II score (maximum 71), which is further
the following should be avoided: integrated with the patients diagnosis to calculate the
- loss of sinus rhythm: atrial contraction is vital to predicted mortality.
maintain adequate ventricular filling. APACHE II has been validated in many large centres
- peripheral vasodilatation: cardiac output is rela- and is thought to be a reliable method for estimating
tively fixed, therefore BP may fall dramatically, group outcome amongst ICU patients. Survival rates of
causing myocardial ischaemia. 50% have been reported for an admission score of about
- excessive peripheral vasoconstriction: further 25 points, with 80% mortality for scores above 35 points.
reduces left ventricular outflow. More recently, repeated assessments (i.e. change in
- tachycardia: ventricular filling is impaired and APACHE II score over time) have been used to chart
coronary blood flow reduced. patients progress.
- myocardial depression. Vincent JL, Moreno R (2010). Crit Care; 14: 20715
postoperative hypertension may occur. See also, APACHE III scoring system; APACHE IV
See also, Heart murmurs; Preoperative assessment; Val- scoring system; Mortality/survival prediction on intensive
vular heart disease care unit

Aortocaval compression (Supine hypotension syn-

APACHE III scoring system (Acute physiology, age
drome). Compression of the great vessels against the
and chronic health evaluation). Further development of
vertebral bodies by the gravid uterus in the supine posi-
the APACHE II scoring system, introduced in 1991.
tion in mid- to late-pregnancy. Vena caval compression
Consists of a numerical score (range 0299) reflecting
reduces venous return and cardiac output with a com-
the weights assigned to the variables of three principal
pensatory increase in SVR; this may be symptomless
data categories: physiological measurements, chrono-
(concealed), or associated with hypotension, bradycar-
logical age (the emphasis on age reflected in the reas-
dia or syncope (revealed). Reduced placental blood
signment of the second A in APACHE) and chronic
flow may result from the reduced cardiac output, vaso-
health status. APACHE III uses data from 16 physio-
constriction and compression of the aorta. During
logical measurements. Unlike earlier versions, weight-
uterine contractions, the compression may worsen
ing of physiological abnormalities is derived from
(Poseiro effect). Reduced cardiac output is more likely
multiple logistic regression. Physiological abnormalities
to occur if vasoconstrictor reflexes are impaired, e.g.
have a greater relative importance in the APACHE
during regional or general anaesthesia. May be reduced
III score and predictive equations. The chronic health
by manual displacement of the uterus or tilting the
component has been modified and is based on seven
mother to one side (usually the left is preferred), e.g.
variables referring to the presence or absence of hae-
with a wedge. Up to 45 tilt may be required.
matological malignancies, lymphoma, AIDS, metastatic
See also, Obstetric analgesia and anaesthesia
cancer, immunosuppression, hepatic failure and liver
Aortovelography. Use of a Doppler ultrasound probe
APACHE III uses 78 mutually exclusive disease defi-
in the suprasternal notch to measure blood velocity and
nitions to group patients according to the principal
acceleration in the ascending aorta. Used for cardiac
reason for ICU admission. Patients admitted directly
output measurement.
from the operating or recovery room are classified as
operative (surgical), and are further subdivided accord-
APACHE scoring system (Acute physiology and
ing to the urgency of the operation (elective versus
chronic health evaluation). Tool described in 1981 for
emergency). All other patients are classified as non-
assessing the severity of illness of individual patients
operative (medical). The APACHE III score is inte-
and predicting the risk of hospital mortality for groups
grated with the patients diagnosis and source before
of patients treated in ICUs. Consists of two parts: an
ICU to calculate the estimate of hospital mortality and
acute physiology score (APS) and an assessment of the
length of ICU stay. Although its performance is slightly
patients pre-illness health status. Rarely used now
better than that of APACHE II, APACHE III is less
because of acknowledged superiority of other systems,
widely used because the predictive equations it employs
are commercially protected.
Vincent JL, Moreno R (2010). Crit Care; 14: 20715
Vincent JL, Moreno R (2010). Crit Care; 14: 20715
See also, Mortality/survival prediction on intensive
See also, Mortality/survival prediction on intensive
care unit
care unit

APACHE II scoring system (Acute physiology and APACHE IV scoring system (Acute physiology, age
chronic health evaluation; version II). Revised version and chronic health evaluation). Further development of
of the prototype APACHE scoring system, described in the APACHE III scoring system, published in 2006.
1985. The number of physiological measurements used Derived from a more refined statistical analysis of
in the acute physiology score is reduced to 12, with data from 100 ICUs and > 110000 patients. Like the
weightings allocated for the degree of derangement of APACHE III, it utilises multiple logistic regression and
Table 7 APACHE II scoring system

High abnormal range Low abnormal range

Physiological variable +4 +3 +2 +1 0 +1 +2 +3 +4

Temperature rectal
(C) 41 3940.9 38.538.9 3638.4 3435.9 32.233.9 3031.9 29.9
Mean arterial pressure
(mmHg) >160 130159 110129 70109 5069 49
Heart rate
(ventricular response) 180 140179 110139 70109 5569 4054 39
Respiratory rate
(non-ventilated or ventilated) 50 3549 2534 1224 1011 69 5
Oxygenation: AadO2 or PaO2
(kPa [mmHg])

(a) FIO2 0.5 record AadO2 >67 4766.9 2746.9 <27

(>500) (350499) (300349) (<200)

(b) FIO2 <0.5 record only >9.3 8.19.3 7.38.0 < 7.3
PaO2 (>70) (6170) (5560) (<55)
Arterial pH
7.7 7.67.69 7.57.59 7.337.49 7.257.32 7.157.24 <7.15
Serum sodium
(mmol/l) 180 160179 155159 150154 130149 120129 111119 110
Serum potassium
(mmol/l) 7 66.9 5.55.9 3.55.4 33.4 2.52.9 <2.5
Serum creatinine (mol/l
[mg/100 ml]) (double point >301 170300 130169 50129 <50
score for acute kidney injury) (3.5) (23.4) (1.51.9) (0.61.4) (<0.6)
(%) 60 5059.9 4649.9 3045.9 2029.9 <20
White blood count
(total/mm3) (in 1000s) 40 2039.9 1519.9 314.9 12.9 <1
Glasgow coma scale (GCS)
Score = 15 minus actual
A Total acute physiology
score (APS): a sum of
the 12 individual variable
Serum HCO3 (venous
mmol/l) (not preferred, 52 4151.9 3240.9 2231.9 1821.9 1517.9 <15
use if no arterial blood

B Age points C Chronic health points APACHE II SCORE

Assign points to age If the patient has a history of severe organ system insufficiency or is
as follows: immunocompromised, assign points as follows: Sum of:
Age (years) Points (a) for non-operative or emergency postoperative patients +5 points or A APS points
(b) for elective postoperative patients +2 points
44 0 B Age points
4554 2 Organ insufficiency or immunocompromised state must have been evident C Chronic health points
5564 5 before this hospital admission and conform to the following criteria:
Liver: Biopsy-proven cirrhosis and documented portal hypertension; episodes Total APACHE II
6574 5
of past upper gastrointestinal bleeding attributed to portal hypertension, or prior
75 6 episodes of hepatic failure/encephalopathy/coma
Cardiovascular: New York Heart Association Class IV (inability to perform
physical activity)
Respiratory: Chronic restrictive, obstructive, or vascular disease resulting in severe
exercise restriction, i.e. unable to climb stairs or perform household duties, or
documented chronic hypoxia, hypercapnia, secondary polycythaemia, severe
pulmonary hypertension (> 40 mmHg), or respiratory dependency
Renal: Receiving chronic dialysis
Immunocompromised: The patient has received therapy that suppresses
resistance to infection, e.g. immunosuppression, chemotherapy, radiation, long-term
or recent high-dose corticosteroids, or has a disease that is sufficiently advanced
to suppress resistance to infection, e.g. leukaemia, lymphoma, AIDS
Apudomas 49

gasping and possibly spontaneous respiration may be

Table 8 Apgar scoring system
induced by stimulation; the gasp reflex is also active.
Sign Score 0 Score 1 Score 2
During secondary apnoea, active resuscitation and oxy-
genation are required to restore breathing.
Heart rate (beats/min) Absent <100 >100 See also, Cardiopulmonary resuscitation, neonatal; Sleep
Respiratory effort Absent Weak cry Strong cry apnoea
Muscle tone Limp Poor tone Good tone
Reflex irritability No response Some Strong Apnoeahypopnoea index, see Sleep apnoea/
movement withdrawal hypopnoea
Colour Blue, pale Pink body, Pink
blue Apnoeic oxygenation. Method of delivering O2 to the
lungs by insufflation during apnoea. A catheter is passed
into the trachea, its tip lying at the carina. O2 passed
through it at 46 l/min reaches the alveoli mainly by
mass diffusion, with O2 utilised faster than CO2 is pro-
generates an estimate of predicted mortality and length duced. The technique does not remove CO2, which rises
of ICU stay. at a rate of approximately 0.5 kPa/min (3.8mmHg/min)
Vincent JL, Moreno R (2010). Crit Care; 14: 20715 at normal rates of CO2 production. Hypercapnia may
therefore occur during prolonged procedures.
Apgar scoring system. Widely used method of evaluat- May be used to maintain oxygenation, e.g. during
ing the condition of the neonate, described in 1953. bronchoscopy, or during the diagnosis of brainstem
Points are awarded up to a maximum total of 10 accord- death.
ing to clinical findings (Table 8). Assessments are com- See also, Insufflation techniques
monly performed at 1 and 5min after birth, but may be
repeated as necessary. Colour may be omitted from the Apomorphine hydrochloride. Alkaloid derived from
observed signs to give a maximum score of 8 (Apgar morphine, with a powerful agonist action at both D1 and
minus colour score). D2 dopamine receptors. Used to treat refractory motor
[Virginia Apgar (19091975), US anaesthetist] fluctuations in Parkinsons disease that are inadequately
controlled by levodopa or other dopaminergic drugs.
Apixaban. Orally active direct factor Xa inhibitor, Overdosage causes respiratory depression that is
licensed in adults for DVT prophylaxis after elective hip reversed by naloxone. Causes intense stimulation of the
or knee replacement surgery. More effective than enoxa- chemoreceptor trigger zone, resulting in vomiting. Needs
parin at preventing DVT and PE, with comparable risks to be prescribed with an antiemetic drug. Previously
of haemorrhagic side effects. used as an emetic drug to empty the stomach.
Rapidly absorbed via the oral route (peak plasma Dosage: 330mg/day as sc boluses (max 10mg per
concentration within 34h), with 50% oral bioavailabil- bolus) or 14mg/h sc by infusion, up to 100mg/day
ity. Half-life is ~12h; 70% undergoes hepatic metabo- (changing the injection site every 12h).
lism (by the cytochrome P450 system) to inactive products, Side effects: vomiting, salivation, worsening dyskine-
and 30% is excreted unchanged in urine. Thus, caution sia, sedation, local ulceration.
is required in patients with severe hepatic or renal
failure, or those taking drugs that cause hepatic enzyme Aprepitant. Neurokinin-1 receptor antagonist, licensed
induction/inhibition. Bleeding risk is increased with con- as an antiemetic drug as part of combination therapy
comitant antiplatelet drugs. (with a corticosteroid and a 5-HT3 receptor antagonist)
Dosage: 2.5mg orally bd, starting 1224h after in cancer chemotherapy. Has been studied in PONV.
surgery, for 2 (knee) or 5 (hip) weeks after surgery Dosage: 125mg, 80mg and 80mg orally on 3 succes-
respectively. sive days.
Side effects: nausea, haemorrhage. Side effects: hiccups, fatigue.

APLS, see Advanced Paediatric Life Support Aprotinin. Proteolytic enzyme inhibitor. Inhibits:
plasmin (at low dose, causing reduced fibrinolysis).
Apneustic centre, see Breathing, control of kallikrein (at higher dose, causing reduced
Apnoea. Absence of breathing. Causes are as for trypsin.
hypoventilation. Results in hypercapnia and hypoxae- Intermediate doses cause reduced platelet aggregation.
mia. The rate of onset and severity of hypoxaemia Previously used to reduce perioperative blood loss
are related to the FIO2, FRC and O2 consumption. Thus cardiac surgery; subsequently shown to increase mortal-
preoxygenation delays the onset of hypoxaemia follow- ity in this setting, when compared with tranexamic acid
ing apnoea. In pregnancy, hypoxaemia develops more and aminocaproic acid. No longer available.
quickly, due to reduced FRC and increased O2 Kay WA, Stein CM (2008). N Engl J Med; 358:
consumption. 2398400
Alveolar PCO2 rises at about 0.5 kPa/min (3.8mmHg/
min) when CO2 production is normal. APRV, see Airway pressure release ventilation
In paediatrics, prematurity is a major cause of recur-
rent apnoea. In newborn animals, induced hypoxaemia APS, see Acute physiology score
results in vigorous efforts to breathe, followed by primary
apnoea and bradycardia, then secondary (terminal) Apudomas. Tumours of amine precursor uptake and
apnoea after a few gasps. During primary apnoea, decarboxylation (APUD) cells. APUD cells are present
50 Arachidonic acid

Phospholipids Arachidonic acid Prostaglandins
Steroids Endoperoxides Prostacyclin

Indicates inhibition NSAIDs

Fig. 15 Arachidonic acid pathways

in the anterior pituitary gland, thyroid gland, adrenal prolonged when cardiac output is reduced). Useful con-
gland medulla, GIT, pancreatic islets, carotid body and ceptually when comparing different iv induction agents;
lung. Originally thought to arise from neural crest tissue; thus thiopental acts within one armbrain circulation
now thought to be derived from endoderm. They have time, whereas midazolam takes longer.
similar structural and biochemical properties, secreting
polypeptides and amines. They may secrete hormones
that cause systemic disturbances, e.g. insulin, glucagon, Arrhythmias. Deviation from normal sinus rhythm.
catecholamines, 5-HT, somatostatin, gastrin and vasoac-
disorders of impulse formation:
tive intestinal peptide.
See also, Carcinoid syndrome; Multiple endocrine adeno- - supraventricular:
matosis; Phaeochromocytoma - sinus arrhythmia, bradycardia and tachycardia.
- SVT.
- sick sinus syndrome.
Arachidonic acid. Essential fatty acid synthesised from
- AF, atrial flutter, atrial ectopic beats.
phospholipids and metabolised by lipoxygenase and
- junctional arrhythmias.
cyclo-oxygenase to leukotrienes and endoperoxides
- VF, ventricular tachycardia, ventricular ectopic
respectively (Fig. 15). Endoperoxides form prostaglan-
dins, prostacyclin and thromboxanes via separate path-
disorders of impulse conduction:
ways. The pathways are inhibited by corticosteroids and
- slowed/blocked conduction (e.g. heart block).
NSAIDs as shown.
- abnormal pathway of conduction (e.g. Wolff
Arachidonic acid may also undergo peroxidation
ParkinsonWhite syndrome).
during oxidative stress, under the action of free radicals,
Arrhythmias, especially tachycardias, are common in
with the production of isoprostanes.
acute illness. During anaesthesia, ECG monitoring is
mandatory. Bradycardia, junctional rhythm and ventric-
Arachnoiditis. Inflammation of the arachnoid and pial ular ectopic beats (including bigeminy) are common, but
meninges. Has occurred after spinal and epidural anaes- usually not serious.
thesia; antiseptic solutions and preservatives in drug Arrhythmias are more likely with:
solutions (e.g. sodium bisulphite) have been implicated. pre-existing cardiac disease.
Also occurs after radiotherapy, trauma and myelography hypoxaemia and hypercapnia.
with oil-based contrast media. May occur months or acidbase disturbances.
years after the insult. Progressive fibrosis may cause electrolyte abnormalities, especially of potassium,
spinal canal narrowing, ischaemia and permanent nerve calcium, magnesium.
damage. The cauda equina is usually affected, with pain, drugs, e.g. inotropic drugs, antiarrhythmic
muscle weakness and loss of sphincter control. May drugs, theophylline, cocaine. During anaesthesia,
rarely spread cranially. Response to treatment is gener- halothane sensitises the myocardium to
ally poor. catecholamines.
See also, Cauda equina syndrome mechanical stimulation of heart chambers (e.g.
central venous/pulmonary artery catheterisation).
ARAS, see Ascending reticular activating system pacemaker malfunction.
certain diseases, e.g. thyrotoxicosis, subarachnoid
ARDS, see Acute respiratory distress syndrome haemorrhage.
manoeuvres that activate powerful reflex pathways,
Argatroban. Hirudin, studied as an alternative to e.g. during dental surgery, oculocardiac reflex, vis-
heparin. Similar to lepirudin but excreted via the liver as ceral manipulation, tracheobronchial suctioning.
opposed to the kidneys. Half-life is 3060min, thus
requiring administration by continuous infusion.
Arterial blood pressure. The pulsatile ejection of the
stroke volume gives rise to the arterial waveform, from
Arginine vasopressin/argipressin, see Vasopressin
which systolic, diastolic and mean arterial pressures may
be determined.
Armbrain circulation time. Time taken for a sub-
stance injected into an arm vein (traditionally ante- MAP = cardiac output SVR
cubital) to reach the brain. If a bile salt is injected, Thus arterial pressure may vary with changes in cardiac
the time until arrival of the bitter taste at the tongue output (stroke volume heart rate) and vascular
may be measured (normally 1020s; this may be greatly resistance.
Arterial waveform 51

Control of BP: - continuous arterial tonometry: a pressure trans-

short-term: ducer is positioned over the radial artery, com-
- intrinsic regulatory properties of the heart: Anrep pressing it against the radius. The transducer
effect, Bowditch effect, Starlings law. output voltage is proportional to the arterial BP,
- autonomic pathways involving baroreceptors, which is displayed as a continuous trace. Periodic
vasomotor centre and cardioinhibitory centre. calibration is performed using an automatic oscil-
- hormonal mechanisms: lometric cuff on the arm.
- renin/angiotensin system. [Stephen Hales (16771761), English curate and
- vasopressin. naturalist; Scipione Riva-Rocci (18631937), Italian
- adrenaline and noradrenaline as part of the physician]
sympathetic response. See also, Pressure measurement
intermediate/long-term: renin/angiotensin system,
aldosterone, vasopressin, atrial natriuretic peptide, Arterial cannulation. Used for direct arterial BP mea-
endocannibinoids. surement, and to allow repeated arterial blood gas inter-
See also, Arterial blood pressure measurement; Diastolic pretation. Peripheral cannulation, e.g. of radial and
blood pressure; Hypertension dorsalis pedis arteries, produces higher peak systolic
pressure than more central cannulation, but is usually
Arterial blood pressure measurement. First attempted preferred because of reduced complication rates. Other
by Hales in 1733, who inserted pipes several feet long sites available include brachial, ulnar, posterior tibial
into the arteries of animals. The BP cuff was introduced and femoral arteries. Allens test is sometimes per-
by Riva-Rocci in 1896. Measurement and recording of formed before radial artery catheterisation, but is of
BP were introduced into anaesthetic practice by Cushing doubtful value. Continuous slow flushing with heparin-
in 1901. ised saline (34ml/h) reduces blockage and is preferable
May be direct or indirect:
to intermittent injection. The need for addition of
heparin has been questioned. Flushing with excessive
- gives a continuous reading; i.e. changes may be volumes of solution may introduce air into the carotid
noticed rapidly. circulation, especially in children.
- provides additional information from the shape of System consists of:
the arterial waveform. cannula: ischaemia, emboli and tissue necrosis are
- requires arterial cannulation. uncommon if a 2022 G parallel-sided Teflon
- requires calibration and zeroing of the monitoring cannula is used, and removed within 2448h.
system. connecting catheter: short and stiff to reduce
- resonance and damping may cause inaccuracy. resonance.
transducer placed level with the heart. Requires
- palpation (unreliable). calibration and zeroing.
- mercury or aneroid manometer attached to a electrical monitor and connections. An adequate
cuff: the brachial artery is palpated and the cuff frequency response of less than 40Hz is required.
inflated to 3060 mmHg above the pressure at Bubbles, clots and kinks may cause damping.
which the pulsation disappears. Cuff pressure is Intravascular transducers may be placed within large
released at 23 mmHg/s, and pressure measured arteries, but are expensive and not routinely used.
by detecting pulsation by using the Korotkoff
sounds, a pulse detector or Doppler probe. The
cuff width must be 20% greater than the arms Arterial gas tensions, see Blood gas interpretation
diameter or half its circumference; narrower
cuffs will over-read. Error may arise between dif- Arterial waveform. The shape of the pressure wave
ferent observers. BP should be recorded to the recorded directly from the aorta differs from that
nearest 2 mmHg. recorded from smaller arteries; the peak systolic pres-
- oscillotonometer. sure and pulse pressure increase, and the dicrotic notch
- automatic oscillometry devices that use the same becomes more apparent, peripherally (Fig. 16a). The
cuff for inflation and detection of movement of aorta and large arteries are distended by the stroke
the arterial walls. Systolic pressure and diastolic volume during its ejection; during diastole, elastic recoil
pressures correspond to onset and offset of pulsa- maintains diastolic blood flow (Windkessel effect).
tions respectively; MAP to the maximum oscilla- Smaller vessels are less compliant and therefore less
tion amplitude. Some devices measure only distensible; thus the pressure peaks are higher and travel
systolic and mean pressures while calculating faster peripherally. In the elderly, decreased aortic com-
diastolic pressure. Tend to under-read when pres- pliance results in higher peak pressures.
sures are high and over-read when low. Inconsis- Abnormal waveforms (Fig. 16b):
tencies occur if the cardiac cycle is irregular, e.g. anacrotic: aortic stenosis.
in atrial fibrillation. collapsing:
- plethysmographic methods: a cuff is inflated - hyperdynamic circulation, e.g. pregnancy, fever,
around a finger, and its pressure varied continu- anaemia, hyperthyroidism, arteriovenous fistula.
ously to keep its volume constant, using photo - aortic regurgitation.
metry/oximetry to measure volume. Cuff pressure bisferiens: aortic stenosis + aortic regurgitation.
is proportional to finger arterial pressure; a con- alternans: left ventricular failure.
tinuous display of the arterial pressure waveform excessive damping: e.g. air bubble.
is obtained. May be unreliable if peripheral vas- excessive resonance: e.g. catheter too long or
cular disease is present. flexible.
52 Arteriovenous oxygen difference

Information that may be derived from the normal

Aorta arterial BP.
stroke volume and cardiac output, from the area
under the systolic part of the waveform.
myocardial contractility, as indicated by rate of
pressure change per unit time (dP/dt).
outflow resistance; estimated by the slope of the
Radial artery diastolic decay. A slow fall may occur in vasocon-
striction, a rapid fall in vasodilatation.
hypovolaemia is suggested by a low dicrotic notch,
narrow width of the waveform and large falls in
peak pressure with IPPV breaths.
[Windkessel, German, wind chamber]
See also, Arterial blood pressure; Cardiac cycle; Mean
Dorsalis pedis artery arterial pressure

Arteriovenous oxygen difference. Difference between

arterial and mixed venous O2 content, normally 5ml
O2/100ml blood. Increased with low cardiac ouput or
exercise (high O2 extraction). Decreased with peripheral
arteriovenous shunting, or when tissue O2 extraction is
Time impaired, e.g. sepsis or cyanide poisoning.
(b) See also, Oxygen transport

Anacrotic Arthritis, see Connective tissue diseases; Rheumatoid


Articaine hydrochloride (Carticaine). Local anaes-

Collapsing thetic agent containing both ester and amide groups, first
used clinically in 1974. Although used in Canada and
continental Europe for several years, was only intro-
duced in the UK (only in combination with adrenaline)
in 2001. Chemically similar to prilocaine and of similar
potency. Suggested as being particularly suitable for
dental anaesthesia because of its low toxicity (maximal
safe dose 7mg/kg), an ability to diffuse readily through
Bisferiens tissues and its metabolism by blood and tissue esterases.
Elimination half-life is about 1.6h, with 50% excreted
in the urine. Duration of action is about 24h.

Artificial heart, see Heart, artificial

Artificial hibernation, see Lytic cocktail

Alternans Artificial ventilation, see Expired air ventilation; Inter-

mittent positive pressure ventilation

ASA physical status. Classification system adopted by

the American Society of Anesthesiologists in 1941 for
categorising preoperative physical status. Originally with
six categories (the last two referring to emergency cases),
Damped trace a seventh (moribund patient) was later added and in
1962 the ASA adopted a modified five-category system
with the postscript E indicating emergency surgery. A
sixth category was added in 1984/5 in the ASAs relative
Resonance value guide for billing purposes:
1: normal healthy patient.
2: mild systemic disease.
3: severe systemic disease.
4: severe systemic disease that is a constant threat
to life.
5: moribund patient; not expected to survive without
the operation.
Fig. 16 (a) Arterial tracing from different sites. (b) Abnormal arterial 6: declared brain-dead organ donor.
waveforms Extremes of age, smoking and late pregnancy are some-
times taken as criteria for category 2.
Aspiration pneumonitis 53

Although not an indicator of anaesthetic or operative - hiatus hernia.

risk, there is reasonable correlation with overall outcome. - drugs, e.g. opioid analgesic drugs.
Widely used in clinical trials to standardise fitness of - pregnancy.
patients. However, use of the scoring system may be inefficient lower oesophageal sphincter:
inconsistent between anaesthetists. - hiatus hernia.
See also, Preoperative assessment - drugs, e.g. opioids, atropine.
- pregnancy with heartburn.
Ascending cholangitis, see Cholangitis, acute - presence of a nasogastric tube.
raised intra-abdominal pressure:
Ascending reticular activating system (ARAS). - pregnancy.
Group of neuronal circuits extending from medulla to - lithotomy position.
midbrain, implicated in regulating sleepwake transi- - obesity.
tions and level of cortical arousal. Its main pathway is oesophagus not empty:
the central tegmental tract, conveying impulses to the - achalasia.
hypothalamus and thalamus and thence to the cortex. - strictures.
Any lesion interrupting the ARAS tends to cause coma. - pharyngeal pouch.
Because of close proximity to other brainstem nuclei, ineffective laryngeal reflexes:
lesions often cause cardiovascular or respiratory distur- - general anaesthesia/sedation.
bances. A possible site of action for general anaesthetic - topical anaesthesia.
agents. - neurological disease.
May result in:
Ascites. Excessive free fluid within the abdominal cavity; stimulation of the airway(s), causing breath-
may exceed 2030 l in extreme cases. Initially asymptom- holding, cough, bronchospasm.
atic but features include weight gain, abdominal discom- impaired laryngoscopy if it occurs during induction
fort, fullness in the patients flanks, shifting dullness to of anaesthesia.
percussion and a fluid thrill. May be sufficient to restrict obstruction of the upper airway by solid or semi-
ventilation if gross, via increased intra-abdominal pres- solid matter, causing complete or partial airway
sure or pleural effusions. There may be dependent obstruction.
oedema despite evidence of hypovolaemia. obstruction of smaller airways causing distal
Causes include hepatic failure, cardiac failure, abdom- atelectasis.
inal malignancy, hepatic vein or portal vein occlusion, aspiration pneumonitis. Silent and continuous aspi-
constrictive pericarditis, nephrotic syndrome, malnutri- ration of small amounts of material may cause
tion, pancreatitis, trauma (haemoperitoneum), ovarian repeated episodes of moderate respiratory impair-
hyperstimulation syndrome and bacterial peritonitis. ment, especially in patients with chronically
Analysis of the ascitic fluid may help in the differential impaired protective reflexes. The diagnosis may be
diagnosis, as for pleural effusion. easy to confuse with other conditions, e.g. repeated
Management includes treatment of the underlying small PEs or chest infections.
cause, reducing sodium intake, diuretics (traditionally Measures to reduce risk:
spironolactone and furosemide) and paracentesis. Fluid starvation.
often reaccumulates; if losses are severe and continuous empty stomach:
the fluid may be recirculated into the venous system via - via nasogastric tube.
a simple shunt or following filtration in an extracorpo- - metoclopramide.
real circuit. increase lower oesophageal sphincter tone, e.g. with
Hou W, Sanyal AJ (2009). Med Clin North Am; 93: metoclopramide, prochlorperazine.
80117 rapid sequence induction of anaesthesia.
induction in the lateral or sitting position.
ASCOT, see A severity characterisation of trauma reduction of the severity of aspiration pneumonitis:
e.g. H2 receptor antagonists, antacids, proton pump
Aspiration of gastric contents. Potentially a risk in all inhibitors.
unconscious, sedated or anaesthetised patients, as lower If aspiration occurs:
oesophageal sphincter tone decreases and laryngeal the patient should be placed in the head-down
reflexes are depressed. Aspiration may follow passive lateral position.
regurgitation of gastric contents or vomiting, and is not material is aspirated from the pharynx and larynx,
necessarily prevented by the presence of a cuffed tra- and O2 administered.
cheal or tracheostomy tube. tracheal intubation may be necessary to protect the
Factors predisposing to aspiration: airway, and to allow tracheobronchial suction.
full stomach: further management is as for aspiration
- recent oral intake. In all but extreme emergencies, pneumonitis.
patients are starved of food for 46h before Apfel CC, Roewer N (2005). Curr Opin Anesth; 18:
anaesthesia, although recent evidence suggests 15762
that total fluid restriction may be unnecessary. See also, Induction, rapid sequence
- gastrointestinal obstruction.
- gastrointestinal bleeding. Aspiration pneumonitis (Mendelsons syndrome).
- ileus. Inflammatory reaction of lung parenchyma following
- trauma/shock/anxiety/pain. After trauma, gastric aspiration of gastric contents, originally described in
emptying may be delayed for several hours, espe- obstetric patients. A critical volume of 25ml of aspirate,
cially in children. of pH 2.5, has been suggested to be required to produce
54 Aspirin

the syndrome, although these figures have been disputed Association of Anaesthetists of Great Britain and
since they are based on animal studies. The more acidic Ireland. Founded in 1932 to represent anaesthetists
the inhaled material, the less volume is required to interests and to establish a diploma in anaesthetics (DA
produce pneumonitis. examination). Before this, the London Society of Anaes-
Particulate antacids, e.g. magnesium trisilicate, thetists (founded 1893) had formed the Anaesthetic
may themselves be associated with pneumonitis if Section of the Royal Society of Medicine in 1908, its
aspirated. purpose to advance the science and art of anaesthesia.
The acid gastric contents cause chemical injury and Also publishes the journal Anaesthesia and regular
loss of surfactant. Pneumonitis occurs within hours of guidelines on various aspects of anaesthetic practice.
aspiration, with decreased FRC and pulmonary compli- Has over 10000 members. The Group of Anaesthetists
ance, pulmonary hypertension, shunt and increased in Training (GAT; formerly the Junior Anaesthetists
extravascular lung water. Features include dyspnoea, Group; JAG) has over 3500 members.
tachypnoea, tachycardia, hypoxia and bronchospasm, Helliwell PJ (1982). Anaesthesia; 37: 91323
with or without pyrexia. Crepitations and wheezes may
be heard on chest auscultation. Irregular fluffy densities Asthma. Reversible airways obstruction, resulting from
may appear on the CXR from 8 to 24h. Movement of bronchoconstriction, bronchial mucosal oedema and
fluid into the lungs results in hypovolaemia and hypoten- mucus plugging. Causes high airways resistance, hypox-
sion. The syndrome is often considered part of the aemia, air trapping and increased work of breathing. Two
ARDS spectrum. Differential diagnosis includes cardiac main forms exist:
failure, sepsis, PE, amniotic fluid embolism and fat extrinsic allergic: begins in childhood; may have an
embolism. associated family history of atopy (e.g. hayfever,
Treatment is mainly supportive, with O2 therapy, eczema), is episodic and tends to respond to therapy.
bronchodilator drugs, and removal of aspirate and secre- intrinsic: adult onset; no allergic family history.
tions by physiotherapy and suction. Bronchoscopy may Nasal polyps are common and exacerbations occur
be required to remove large particulate matter. Second- with infection and aspirin. Less responsive to
ary infection may occur, and prophylactic antibacterial treatment.
drugs are sometimes given, although this is controversial. Patients bronchi show increased sensitivity to triggering
Use of high-dose corticosteroids is declining but inhaled agents, constricting when normal bronchi may not.
corticosteroids may be beneficial for treatment of bron- During anaesthesia, surgical stimulation or stimulation
chospasm. CPAP or IPPV with PEEP may be required of the pharynx or larynx may cause bronchospasm.
in severe cases. Mortality is high. Chronic drug treatment:
[Curtis L Mendelson (19132002), US obstetrician] 2-adrenergic receptor agonists, e.g. salbutamol.
Marik PE (2001). N Engl J Med; 344: 66571 aminophylline and related drugs.
Aspirin. Acetylsalicylic acid, synthesised in the early sodium cromoglicate.
1900s in Germany. Commonest salicylate in use. Uses, anticholinergic drugs, e.g. ipratropium.
effects and pharmacokinetics as for salicylates. Used leukotriene receptor antagonists.
widely as an antiplatelet drug. Should not be given to Acute severe asthma:
children under 16 years of age, and inadvisable in ado- signs of a severe attack:
lescents, because of the risk of Reyes syndrome. - inability to talk.
Dosage: - tachycardia > 110 beats/min.
analgesia: 300900mg orally 46-hourly, up to a - tachypnoea > 25 breaths/min.
total of 4g daily. - pulsus paradoxus > 10mmHg.
secondary prevention of thrombotic cerebrovascu- - peak expiratory flow rate (PEFR) < 50% of pre-
lar or CVS disease: 75100mg orally od. dicted normal.
acute coronary syndromes: 150300mg orally od. signs of life-threatening attack:
following cardiac surgery: 75100mg orally od. - silent chest on auscultation.
Over-the-counter sale of 300mg tablets/capsules in the - cyanosis.
UK is limited to packs of 32 (packs of 100 tablets/cap- - bradycardia.
sules may be purchased from pharmacists in special - exhausted, confused or unconscious patient.
circumstances). arterial blood gas measurement: hypoxaemia,
See also, Salicylate poisoning largely from V/Q mismatch, may be severe. It may
worsen following bronchodilator treatment due to
Assisted ventilation. Positive pressure ventilation sup- increased dead space and mismatch. Arterial PCO2
plementing each spontaneous breath made by the V /Q is usually reduced because of hyperventilation,
patient. May be useful during transient hypoventilation but may rise in severe cases, indicating requirement
caused by respiratory-depressant drugs in spontaneously for IPPV. There is poor correlation between FEV1
breathing anaesthetised patients. Also used in ICU, e.g. and arterial PCO2.
in weaning from ventilators. other problems: pneumothorax, infection, dehydra-
Different modes: tion. Hypokalaemia is common due to corticoste-
assist mode ventilation: delivery of positive pres- roids, catecholamine administration and respiratory
sure breaths triggered by inspiratory effort. alkalosis.
assist-control mode ventilation: assist mode ventila- general medical and ICU management:
tion against a background of regular IPPV. - first-line therapies:
inspiratory pressure support. - humidified O2 with high FIO2 is required.
inspiratory volume support. - nebulised salbutamol 2.55mg or terbutaline
proportional assist ventilation. 510mg 4-hourly (may be given continuously
Atenolol 55

in severe asthma); iv salbutamol 250g may Tubocurarine and atracurium may cause hista-
be given, followed by 520g/min, although mine release, whilst vecuronium, pancuronium,
in general, iv administration of 2-agonists is rocuronium and fentanyl do not.
thought to have no advantage over the inhaled - although many opioid analgesic drugs may release
route. histamine, they are commonly given. For patient-
- nebulised ipratropium 0.10.5mg is tradition- controlled analgesia fentanyl may be a good
ally alternated with 2-agonists, although in alternative if morphine has previously provoked
modern practice they are often combined in the bronchospasm.
same nebuliser. - tracheal intubation and the presence of a tracheal
- corticosteroids; e.g. hydrocortisone 100200mg tube may cause bronchospasm. This may be
4-hourly iv, or by infusion. reduced by spraying the larynx and trachea with
- second-line therapies: lidocaine; iv lidocaine, 12mg/kg, has been used
- magnesium sulphate 1.22.0g iv over 20min as to reduce the incidence of bronchospasm on intu-
a single dose has recently been introduced to bation and extubation. Alternatively, techniques
UK guidelines. avoiding tracheal intubation may be employed.
- aminophylline 36mg/kg iv, followed by 0.5mg/ - -adrenergic receptor antagonists should be
kg/h (with caution if the patient is already avoided.
taking theophyllines). - dehydration should be avoided.
- diethyl ether, halothane, ketamine and adrena- Sellers WFS (2013). Br J Anaesth; 110: 18390
line have been used in resistant cases. See also, Bronchodilator drugs
supportive therapies:
- antibacterial drugs, physiotherapy, iv rehydration. Astrup method. Used for the analysis of blood acid
- IPPV: base status. The pH of a blood sample is measured, and
- intubation may provoke cardiac arrhythmias in the sample equilibrated with two gases of different CO2
severe hypoxia/hypercapnia. concentration, usually 4% and 8%. pH is measured after
- sedation and muscle relaxation are required to each equilibration, and the standard bicarbonate and
aid IPPV. base excess calculated. The original CO2 tension is cal-
- high inflation pressures risk barotrauma and culated from the pH of the original sample, using the
decreased cardiac output. Siggaard-Andersen nomogram.
- a flow generator ventilator is required, to ensure [Poul Astrup (19152000), Danish chemist]
adequate tidal volumes.
- because expiration may not be complete before Asystole. Absent cardiac electrical activity. Common in
the next breath, FRC increases with gas trap- cardiac arrest due to hypoxia or exsanguination, espe-
ping, usually reaching equilibrium after 510 cially in children. Must be distinguished from accidental
breaths. Despite the resultant auto-PEEP ECG disconnection. Management: as in CPR.
(intrinsic PEEP) and traditional teaching that
PEEP should not be used in asthma because of Atelectasis. Collapse of lung tissue affecting all or part
the increased risk of barotrauma, PEEP has of the lung. Caused by inadequate aeration of alveoli,
been applied to good effect and may actually with subsequent absorption of gas. The latter occurs
reduce FRC by an unknown mechanism. because the total partial pressure of dissolved gases in
- adequate ventilation may be difficult; permis- venous blood is less than atmospheric pressure; gas
sive hypercapnia is often practised. Gas trapped behind obstructed airways, e.g. by secretions, is
exchange may be improved by a slow inspira- therefore slowly absorbed. Nitrogen, being relatively
tory flow rate, low minute volume (68 l/min) insoluble in blood, tends to splint alveoli open when
and low ventilatory rate (1214 breaths/min). breathing air. Absorption atelectasis may follow high
Expiration should occupy at least 50% of the FIO2, since O2 is readily absorbed into the blood and the
ventilatory cycle duration. nitrogen has been washed out of the alveoli.
bronchoalveolar lavage has been used. Has been shown by CT scanning to occur in depen-
Anaesthetic management of patients with asthma: dent parts of the lung during anaesthesia in normal
preoperatively: patients, contributing to impaired gas exchange. May
- preoperative assessment is directed towards also follow accidental endobronchial placement of a tra-
respiratory function, frequency and severity cheal tube. It may persist postoperatively, particularly in
of attacks, and drug therapy (including patients with poor lung function and sputum retention,
corticosteroids). and when chest movement is reduced, e.g. by pain after
- investigations: CXR; PEFR/spirometry (espe- upper abdominal surgery or fractured ribs. Hypoxaemia,
cially pre- and postbronchodilator); arterial blood tachypnoea and tachycardia result, with reduced air
gas interpretation. entry to the affected area of lung that may then become
- premedication: nebulised bronchodilators may be infected. Treatment of atelectasis includes physiother-
given with premedication. Preoperative physio- apy, incentive spirometry, humidification, intermittent
therapy may also be useful. Steroid cover may be lung inflations using a ventilator, CPAP and, occasion-
required. ally, bronchoscopy.
perioperatively: Duggan M, Kavanagh BP (2005). Anesthesiology; 102:
- regional anaesthesia is often suitable. 83854
- thiopental has been implicated as causing
bronchospasm, although this is controversial. Pro- Atenolol. Water-soluble -adrenergic receptor antago-
pofol, etomidate and ketamine are suitable alter- nist, available for oral and iv administration. Relatively
natives. Volatile agents cause bronchodilatation. selective for 1-receptors. Uses and side effects are as for
56 Atherosclerosis

-adrenergic receptor antagonists in general. properties but causes less histamine release). At body
Dosage: temperature and pH, undergoes spontaneous Hofmann
hypertension: 50mg/day orally; angina and arrhyth- elimination to laudanosine. Up to 50% ester hydrolysis
mias: 50100mg/day. also occurs. Often considered the drug of choice in renal
acute arrhythmias: 150g/kg iv over 20min, or hepatic impairment. Its cardiostability, low risk of
repeated 12-hourly as required. accumulation and spontaneous reversal are also advan-
after acute MI: 510mg slowly iv, then 50mg iv tages. Stored at 28C; at room temperature, activity
after 15min and 12h, then 100mg/day orally. decreases by only a few per cent per month.
perioperatively in patients at risk from ischaemic
heart disease: 510mg iv before surgery, then 50 Atrial ectopic beats. Impulses arising from abnormal
100mg orally during the hospital stay (up to a pacemaker sites within the atria. The P waves are usually
week). abnormal, and arise early in the cardiac cycle. They are
Side effects: as for -adrenergic receptor usually conducted to the ventricles in the normal way,
antagonists. producing normal QRS complexes (Fig. 17). Very early
ectopics may produce abnormal QRS complexes,
Atherosclerosis. Disease involving the intima of because the ventricular conducting system may still be
medium and large arteries, resulting in fat accumulation refractory when the ectopic impulse reaches it. The
and fibrous plaques that narrow the vessel lumen. resultant QRS may then be mistaken for a ventricular
Further stenosis may follow thrombosis and haemor- ectopic beat. Several ectopic sites may give rise to the
rhage. Thought to be at least partly inflammatory in aeti- wandering pacemaker, producing differently shaped P
ology, although the precise roles of proinflammatory and waves with differing PR intervals. Rarely require
prothrombotic mediators are uncertain. Causes isch- treatment.
aemic heart disease, cerebrovascular disease and periph- See also, Arrhythmias; Electrocardiography
eral arterial insufficiency, especially in the legs. Thus
patients with peripheral vascular disease frequently Atrial fibrillation (AF). Lack of coordinated atrial con-
have occult atherosclerotic disease involving other traction, resulting in impulses from many different parts
organs. of the atria reaching the atrioventricular (AV) node in
A rigid arterial tree results in a high systolic arterial quick succession, only some of which are transmitted.
BP with normal diastolic pressure, a common finding in Ventricular response may be fast, resulting in inadequate
the elderly, since virtually all elderly patients have some ventricular filling, and reduced stroke volume and
atherosclerosis. cardiac output. Cardiac failure, hypotension and sys-
Hansson GK (2005). N Engl J Med; 352: 168595 temic emboli from intra-atrial thrombus may occur.
ATLS, see Advanced Trauma Life Support irregularly irregular pulse. Ventricular rate depends
upon the conducting ability of the AV node; usually
Atmosphere. Unit of pressure. One atmosphere equals rapid, the ventricular activity is slow and regular if
760mmHg (101.33 kPa), the average barometric pres- complete heart block exists.
sure at sea level. no P waves on the ECG (Fig. 18).
See also, Bar May be idiopathic or caused by:
ischaemic heart disease (most common cause),
ATN, Acute tubular necrosis, see Renal failure including acute MI.
mitral valve disease.
Atopy. Tendency to asthma, hayfever, eczema and other hyperthyroidism.
allergic conditions, including adverse drug reactions. Suf- PE.
ferers are sensitive to antigens that usually cause no cardiomyopathy.
reaction in normal subjects. May be familial. IgE levels thoracic surgery/central venous cannulation.
may be raised. Drugs associated with histamine release acute hypovolaemia.
should be avoided. Treatment:
drug therapy is aimed at reducing AV node conduc-
Atorvastatin, see Statins tion and ventricular rate. Sinus rhythm may be
restored. Examples include digoxin, -adrenergic
ATP, see Adenosine triphosphate and diphosphate receptor antagonists, verapamil, diltiazem, amioda-
rone and disopyramide.
ATPD and ATPS. Ambient temperature and pressure, cardioversion if haemodynamically unstable or
dry; and ambient temperature and pressure, saturated recent onset (< 3 days).
with water vapour. Used for standardising gas volume catheter ablation of the AV node or atrial foci
measurements. where AF originates; largely reserved for cases
intolerant of or refractory to other treatment.
Atracurium besylate. Non-depolarising neuromuscular anticoagulation should be considered if AF has per-
blocking drug, first used in 1980. A bisquaternary nitrog- sisted for more than 23 days, especially before car-
enous plant derivative. Initial dose: 0.30.6mg/kg. Intu- dioversion. In chronic AF, aspirin or warfarin is
bation is possible approximately 90s after a dose of used depending on the absence or presence of other
0.5mg/kg. Effects last 2030min. Supplementary dose: risk factors, e.g. age > 75, diabetes, hypertension,
0.10.2mg/kg. Has been given by iv infusion at 0.3 previous CVA.
0.6mg/kg/h. May cause histamine release, usually mild, Somasundaram K, Ball J (2013). Anaesthesia; 68 s1:
but severe reactions have been reported (an isomer of 84101
atracurium, cisatracurium, has similar neuromuscular See also, Arrhythmias
Atrioventricular dissociation 57

increases GFR, and urinary sodium and water
excretion. Decreases reabsorption of sodium ions in
the proximal convoluted tubule of the nephron.
relaxes vascular smooth muscle; renal vessels are
more sensitive than others.
inhibits plasma renin activity and aldosterone
Fig. 17 Example of an atrial ectopic beat (arrowed)
releases free fatty acids from adipose tissue.
Thought to act via specific receptors. ANP and
related peptides have been investigated as markers
of cardiac failure and myocardial ischaemia. Inhibi-
tion of their breakdown has been investigated as
possible therapy in hypertension, cardiac failure
and myocardial ischaemia, whilst infusion of
ANP has been investigated for its renal protective
effect in oliguric acute tubular necrosis. A synthetic
ANP is available for treatment of advanced heart
de Lemos JA, McGuire DK, Drazner MH (2003). Lancet;
Fig. 18 Atrial fibrillation
362: 31622
See also, B-type natriuretic hormone

Atrial septal defect (ASD). Accounts for up to 15% of

congenital heart disease.
Normal septal development is as follows:
the septum primum grows down from the top of the
F F F F heart, separating the right and left halves of the
common atrium.
the foramen secundum appears in its upper part.
the septum secundum grows down to the right

F, flutter waves
of the septum primum, usually just covering the
foramen secundum.
Fig. 19 Atrial flutter the foramen ovale is formed from the foramen
secundum and overlapping septum secundum.
Features of ASD:
pulmonary flow murmur with or without a tricuspid
murmur, increasing on inspiration. Fixed splitting of
Atrial flutter. Arrhythmia resulting from rapid atrial the second heart sound.
discharge (usually 300/min), caused by a re-entrant right ventricular hypertrophy, right bundle branch
circuit within the atria and usually initiated by an atrial block and right axis deviation may be present.
ectopic beat. May be paroxysmal or sustained. Com- pulmonary hypertension.
monly occurs with 4:1 or 2:1 atrioventricular block; i.e. Over 90% of defects are secundum ASDs; they may
with ventricular rates 75/min or 150/min respectively. present in later life with pulmonary hypertension, right-
Features: sided cardiac failure, Eisenmengers syndrome and AF.
usually regular pulse. Suturing of the defect is usually quick if a patch is not
saw-tooth flutter (F) waves on the ECG (Fig. 19); required.
with 2:1 block the second flutter wave of each pair Ostium primum defects may involve the atrioven-
may be hidden in the QRS or T waves, leading to tricular valves; they often present early. Repair is more
the incorrect diagnosis of sinus tachycardia. Carotid complicated. Valve regurgitation and conduction defects
sinus massage may slow the ventricular rate enough may follow surgery.
to reveal rapid flutter waves. Anaesthetic management: as for congenital heart
Causes: as for AF. disease and cardiac surgery.
Treatment: See also, Heart murmurs; Preoperative assessment
aimed at restoring sinus rhythm: cardioversion
using low-energy (2550 J), rapid atrial pacing, and Atrial stretch receptors, see Baroreceptors
drug therapy as for AF.
digoxin may convert flutter to AF. Atrioventricular block, see Heart block
See also, Cardiac pacing
Atrioventricular dissociation. Unrelated ventricular
Atrial natriuretic peptide (ANP). Hormone isolated and atrial activity. The term is usually reserved for when
from myocytes of the right atrium; similar peptides are the ventricular rate exceeds the atrial rate, to distinguish
present in the cardiac ventricles and vascular endothe- it from complete heart block (in which the reverse
lium. Released in response to atrial stretching, e.g. in occurs). Ventricular activity may arise from the atrioven-
fluid overload (i.e. not to increased atrial pressure tricular node or an ectopic pacemaker. It may occur
per se), sympathetic stimulation and presence of angio- during bradycardia as an escape mechanism, and during
tensin II. anaesthesia. On the ECG, P waves and QRS complexes
58 Atrioventricular node

of a particular aspect of practice (e.g. reducing

assessment of how that practice is carried out
P P P (e.g. measuring nausea scores, recording usage of
judgement by peer review whether certain stan-
dards are being met (e.g. deciding in advance that
Fig. 20 Atrioventricular dissociation
more than 10% of patients suffering severe nausea
is unacceptable. National standards exist for many
areas of practice, e.g. issued by professional bodies).
are unrelated, the former more widely spaced than the identification of areas for improvement where prac-
latter (Fig. 20). Rarely clinically significant. tice is substandard (e.g. prophylactic antiemetics
See also, Arrhythmias not being given for high-risk surgery).
addressing the deficiency (e.g. education, institution
Atrioventricular node, see Heart, conducting system of protocols).
reassessment after a period to check that practice
Atropine sulphate. Anticholinergic drug (competitive has improved and standards are being met; i.e.
antagonist at muscarinic acetylcholine receptors), an closing the audit loop. In order to be effective,
ester of tropic acid and tropine. Found in deadly night- specific audits require repeating regularly.
shade. Used to reduce muscarinic effects of acetylcho- Audit (is the correct management being used?) should
linesterase inhibitors, for premedication and in the be distinguished from research (what is the correct man-
treatment of bradycardia. Has also been used as an anti- agement?), although both may involve similar methods
spasmodic drug and as a mydriatic. of data collection and analysis.
Effects: Anaesthetic/ICU applications include monitoring:
CVS: organisation of services, e.g. appropriate allocation
- tachycardia (may cause bradycardia initially; of trainees, cancellation of surgery because of insuf-
thought to be due to central vagal stimulation). ficient staff, leave allocations and costs.
- cutaneous vasodilatation (cause unknown). management of patients drug usage and clinical
CNS: policies.
- excitement, hallucinations and hyperthermia, complications, e.g. unplanned admission to ICU,
especially in children. specific events. Methods include analysis of cur-
- antiparkinsonian effect. rently held data (e.g. anaesthetic record-keeping)
RS: or specific studies into particular aspects of care
- bronchodilatation and increased dead space. (e.g. National Confidential Enquiry into Patient
- reduced secretions. Outcome and Death and Confidential Enquiries
GIT: into Maternal Deaths). Audit is now a mandatory
- reduced salivation. part of medical practice in the UK, despite contro-
- reduced motility. versy over its value in relation to costs.
- reduced secretion. See also, Quality assurance; Risk management
- reduced lower oesophageal sphincter tone.
others: Auriculotemporal nerve block, see Mandibular nerve
- reduced sweating. blocks
- mydriasis and cycloplegia.
- reduced bladder and ureteric tone. Auscultatory gap. During auscultatory arterial BP
Standard doses: measurement, the Korotkoff sounds may disappear at
0.10.6mg increments iv for bradycardia. A larger a point below systolic pressure, to reappear at a
maximum dose (3mg) is no longer recommended lower pressure before disappearing again at diastolic
for the management of asystole/pulseless electrical pressure. The significance is unknown, but it emphasises
activity. the importance of palpating the artery before ausculta-
0.30.6mg im as premedication; 0.010.02mg/kg tion, in order to ensure that the absence of sounds is
for children. because the pressure is above systolic, and not within the
0.010.02mg/kg when given with acetylcholinester- silent gap.
ase inhibitors.
0.61.2mg orally at night in irritable bowel disease, Australia antigen, see Hepatitis
Atropine should be avoided in pyrexial patients, particu- Autoimmune disease. Characterised by activation of
larly children. the immune system, directed against host tissue. May
Applied directly to the eye, it may provoke closed- involve antibody production, attacking intracellular,
angle glaucoma in susceptible patients, the iris obstruct- extracellular or cell membrane antigens. Pathogenesis is
ing drainage of aqueous humour when the pupil is not fully understood, but involves imbalance of suppres-
dilated. sor and helper T lymphocyte cell function. May affect
See also, Anticholinergic drugs, for comparison with specific organs, e.g. adrenocortical insufficiency, or many
hyoscine and glycopyrronium; Tracheal administration tissues, e.g. connective tissue diseases.
of drugs May follow triggering agents, e.g.:
drugs: SLE-like syndrome after procainamide or
Audit. Systematic process by which medical practice is hydralazine therapy, haemolytic anaemia after
assessed and improved. Involves the following steps: -methyldopa therapy.
Avogadros hypothesis 59

infection: haemolysis following mycoplasma pneu- Autonomic neuropathy. May be:

monia, rheumatic fever following streptococcal central:
infection. Viral infections are often implicated. - primary, e.g. progressive autonomic failure (Shy
Genetic factors are also important, hence the association Drager syndrome).
between certain diseases and HLA types, e.g. myasthenia - secondary to CVA, infection or drugs.
gravis, thyroid disease, pernicious anaemia and vitiligo. peripheral, e.g. due to diabetes mellitus, amyloido-
More than one of these diseases may occur in the same sis, autoimmune diseases, porphyria, GuillainBarr
patient, suggesting common mechanisms. Testing for syndrome, myasthenic syndrome.
autoantibodies may be useful in the diagnosis and treat- Results in postural hypotension, cardiac conduction
ment of these conditions. defects, bladder dysfunction and GIT disturbances,
including delayed gastric emptying. Diabetics with auto-
nomic neuropathy have increased risk of perioperative
Autologous blood transfusion, see Blood transfusion, cardiac or respiratory arrest.
autologous Useful bedside tests of autonomic function include:
pulse and BP measurement lying and standing; a

Autonomic hyperreflexia. Increased sensitivity of sym- postural drop of over 30mmHg indicates auto-
pathetic reflexes in patients with spinal cord injury nomic dysfunction.
Valsalva manoeuvre.
above T5/6. Cutaneous or visceral stimuli below the level
effect of breathing on pulse rate (normally slows on
of the lesion may result in mass discharge of sympathetic
nerves, causing sweating, vasoconstriction and hyper expiration).
sustained hand grip (normal response: tachycardia
tension, with high levels of circulating catecholamines.
Baroreceptor stimulation results in compensatory brady and over 15mmHg increase in diastolic BP).
cardia. Distension of hollow viscera, especially of the ECG is useful for the latter two tests. Other tests
bladder, is a potent stimulus. It may also occur during include observation of sweating and pupillary
abdominal surgery and labour. Onset of susceptibility is responses, and catecholamine studies.
usually within a few weeks of injury. Patients with autonomic neuropathy are at risk of devel-
In anaesthesia, both general and regional techniques oping severe hypotension during anaesthesia, particu-
have been used; spinal anaesthesia has been suggested larly with spinal or epidural anaesthesia, and IPPV. They
as the technique of choice, if appropriate. Control of may also show reduced response to hypoglycaemia.
hypertension has been successfully achieved with vaso- There may be increased risk of aspiration of gastric
dilator drugs. Hypotension may also occur. contents.
[George Shy (19191967) and Glenn Drager (1917
1967), US neurologists]
Autonomic nervous system. System that regulates See also, Peripheral neuropathy
non-voluntary bodily functions, by means of reflex path-
ways. Efferent nerves contain medullated fibres that Autoregulation. Mechanism by which an organ, e.g.
leave the brain and spinal cord to synapse with non- kidney, brain, heart, maintains a constant blood flow
medullated fibres in peripheral ganglia. Closely related despite variations in the mean arterial pressure perfus-
to the CNS, anatomically and functionally; thus, sensory ing the organ.
input may affect autonomic activity and also conscious- Several theories exist:
ness and voluntary behaviour, e.g. pain, temperature and myogenic theory: postulates that muscle in the
sensation. vessel wall contracts as intraluminal pressure
Divided into the parasympathetic and sympathetic
increases, thus maintaining wall tension by reducing
nervous systems, on the basis of anatomical, pharma- radius, in accordance with Laplaces law.
cological and functional differences (Fig. 21): metabolic theory: argues that vasodilator substances
parasympathetic: (nitric oxide, hydrogen ions, CO2, adenosine) accu-
- output in cranial and sacral nerves; ganglia near mulate in the tissues at low blood flow; the resultant
to target organs. vasodilatation results in increased flow and the
- acetylcholine released as a transmitter at pre- and vasodilator metabolites are washed away.
postganglionic nerve endings. tissue theory: states that, as blood flow increases, the
- increases GIT activity, and reduces arousal and vessels are compressed by the increased amount of
cardiovascular activity. interstitial fluid that has accumulated. Usually
sympathetic: occurs at MAP of 60160mmHg in normotensive
- output in thoracic and lumbar segments of subjects; it may be impaired by volatile anaesthetic
the spinal cord; ganglia form the sympathetic agents, vasodilator drugs or disease states (e.g. cere-
trunk. bral blood flow in head injury).
- acetylcholine released at preganglionic nerve See also, Systemic vascular resistance
endings, adrenaline and noradrenaline (in general)
at postganglionic nerve endings.
Autotransfusion, see Blood transfusion, autologous
- increases arousal and cardiovascular activity
(fight or flight reaction), reduces visceral
activity. Average, see Mean
Some organs receive only sympathetic innervation (e.g.
piloerector muscles, adipose tissue, juxtaglomerular Avogadros hypothesis. At constant temperature and
apparatus), others only parasympathetic innervation pressure, equal volumes of all ideal gases contain the
(e.g. lacrimal glands); most are under dual control. same number of molecules. One mole of a substance at
See also, Acetylcholine receptors standard temperature and pressure contains 6.023 1023
60 AVP

Parasympathetic Sympathetic

Eye III Midbrain

Ciliary ganglion

Submandibular, sublingual
+ lacrimal glands
Pterygopalatine +
submandibular ganglia

Lungs, larynx,
tracheobronchial tree
Otic ganglion
Eye, salivary glands
Heart X

Parotid gland T1
Heart, lungs, larynx, tracheobronchial tree
Proximal GIT


Coeliac ganglion
Proximal GIT + blood vessels
Adrenal medulla
T12 Superior mesenteric
Distal GIT + blood vessels
bladder, genitalia
L3 Inferior mesenteric

Distal GIT
Bladder S3

Fig. 21 Autonomic nervous system

particles (Avogadros number), and one mole of a gas painful (P) stimuli, or unresponsive (U). Easier and
occupies 22.4 litres. faster to perform than other more complicated trauma
[Count Amedeo Avogadro (17761856), Italian scales and systems such as the Glasgow coma scale.
Awareness. Postoperative recall of events occurring
AVP, Arginine vasopressin, see Vasopressin during general anaesthesia. Ranges from being fully con-
scious and in pain intraoperatively with explicit recall,
AVPU scale. Simple scale of responsiveness, commonly to non-specific postoperative psychological symptoms
used to assess the neurological status of patients, e.g. with only vague recollections or dreams. Signs of inad-
following trauma, cardiac arrest. Records whether the equate anaesthesia (tachycardia, sweating, hypertension,
patient is alert (A), responsive only to vocal (V) or large pupils, lacrimation) may not be present. Quoted
Azumolene sodium 61

incidence is 0.010.2%; its rarity and diagnostic variabil- pulsation in the axilla. The medial cutaneous nerve
ity contribute to the wide range. Importantly, in most may be at risk with this approach.
cases patients do not report awareness while in the
recovery room. Ayres T-piece, see Anaesthetic breathing systems
Associated with significant psychological and psychi-
atric morbidity, including post-traumatic stress disorder.
Azathioprine. Non-specific cytotoxic drug, used as an
Postoperative interview or hypnosis may reveal recall
immunosuppressive drug in organ transplantation,
of pain, events, comments or specific messages played
myasthenia gravis and inflammatory disease. Metabo-
to patients. The significance of non-conscious recall is
lised to mercaptopurine.
unknown. Dose: 35mg/kg orally/iv initially; maintenance
Risk factors and associations:
14mg/kg per day.
previous history of awareness under anaesthesia.
Side effects: myelosuppression, fever, rigors, arthral-
administration of low doses (< 0.8 MAC) of volatile
gia, myalgia, interstitial nephritis, liver toxicity. Moni-
anaesthetic agents (e.g. in caesarean section, major
toring of therapy requires regular full blood counts.
trauma, cardiac surgery or anaesthesia for mori-
The iv preparation is alkaline and very irritant.
bund patients), especially in combination with neu-
romuscular blocking drugs.
reliance on iv agents given by bolus without inhala- Azeotrope. Mixture of two or more liquids whose com-
tional agents, leading to awareness between doses; ponents cannot be separated by distillation. The boiling
e.g. during bronchoscopy, or repeated attempts at point of each is altered by the presence of the other
difficult intubation. substance; thus the components share the same boiling
equipment failure. point, and the vapour contains the components in the
Use of high-dose opioid drugs may not prevent aware- same proportions as in the liquid mixture. Halothane
ness, although the patient may not feel pain. and ether form an azeotrope when mixed in the ratio of
May be reduced by: 2:1 by volume.
ensuring adequate administration of anaesthetic
agent, including use of end-expiratory gas monitor- Azidothymidine, see Zidovudine
ing (with alarms enabled).
thorough checking of equipment. Azithromycin. Macrolide, similar to erythromycin but
avoidance of neuromuscular blocking drugs. less active against Gram-positive bacteria and more
use of amnesic drugs, e.g. benzodiazepines. active against certain Gram-negative ones. Used in
use of cerebral function monitors (e.g. bispectral respiratory and other infections and as an antituber
index monitor). culous drug in resistant TB. Extensively tissue-bound.
All cases of possible or confirmed awareness should be Dosage: 500mg orally od for 3 days.
adequately followed up, with counselling and psychiatric Side effects: as for clarithromycin.
referral if indicated.
Mashour GA, Orser BA, Avidan MS (2011). Anesthesi-
AZT, Azidothymidine, see Zidovudine
ology; 114: 121833
See also, Anaesthesia, depth of; Isolated forearm tech-
nique; Traumatic neurotic syndrome Aztreonam. Monocyclic -lactam (monobactam) active
against Gram-negative aerobes (including Pseudomo-
Axillary venous cannulation. Route of central venous nas) but not Gram-positive or anaerobic organisms; thus
cannulation, usually used when alternative sites are reserved for specific (as opposed to blind) therapy.
unsuitable. Advantages include venous puncture outside Resistant to some, but not all, -lactamases. Synergistic
the ribcage, thus reducing the risk of pneumothorax, and with aminoglycosides against many bacteria.
Dosage: 0.51.0g iv over 35min or by deep im injec-
the ability to compress the axillary artery directly if acci-
dentally punctured. A number of techniques have been tion tds/qds (or 2g iv bd); in severe infections 2g iv
described, classified into: tds/qds.
Side effects: as for penicillin. May cause phlebitis and
proximal: with the arm abducted to 45, a needle is
introduced three fingers breadth (5cm) below the pain on injection.
coracoid process and directed at the junction of the
medial one-quarter and lateral three-quarters of Azumolene sodium. Analogue of dantrolene; has
the clavicle. been investigated as an alternative because of its
distal: with the arm abducted to 90, a needle is greater water solubility and a smaller volume of
introduced 1cm medial to the axillary arterial administration.
BACCN, see British Association of Critical Care Nurses - aerobes:
- cocci, e.g. neisseria species.
Backward failure, see Cardiac failure - bacilli, e.g. enterobacteria (enterobacter,
escherichia, klebsiella, proteus, salmonella, ser-
Baclofen. Synthetic GABAB receptor agonist and skel- ratia, shigella, yersinia), vibrio, acinetobacter,
etal muscle relaxant, used to treat muscle spasticity, e.g. pseudomonas, brucella, bordetella, campylo-
following spinal injury and in multiple sclerosis. Acts at bacter, haemophilus, helicobacter, legionella,
both spinal and supraspinal levels. Has also been used chlamydia, rickettsia, mycoplasma, leptospira,
to treat alcohol withdrawal syndromes. treponema species.
Dosage: 5mg orally tds, increased slowly up to - anaerobes:
100mg/day. Has also been given intrathecally: 25 - cocci, e.g. veillonella species.
50g over 1min, increased by 25g/24h up to - bacilli, e.g. bacteroides species.
100g to determine an effective dose, then 12 Bacteria may also be classified according to antigenic
2000g/day by infusion for maintenance. properties of the cell surface, and by their susceptibility
Side effects: sedation, nausea, confusion, convulsions, to various viral phages and antibiotics.
hypotension, GIT upset, visual disturbances, rarely [Hans Gram (18531938), Danish physician]
hepatic impairment. See also, individual infections
See also, -Aminobutyric acid receptors
Bacterial contamination of breathing equipment, see
Bacteraemia. Presence of bacteria in the blood. May be Contamination of anaesthetic equipment
present in SIRS and sepsis, but is not necessary for either
diagnosis to be made. Bacterial resistance. Ability of bacteria to survive in
See also, Blood cultures; Endotoxins the presence of antibacterial drugs. An increasingly sig-
nificant problem in terms of cost, pressure on develop-
Bacteria. Micro-organisms with a bilayered cytoplasmic ment of new antibiotics and impaired ability to treat
membrane, a double-stranded loop of DNA and, in most infections both in critically ill patients and the commu-
cases, an outer cell wall containing muramic acid. nity as a whole.
Responsible for many diseases; mechanisms include the Mechanisms:
initiation of inflammatory pathways by endotoxins or impermeability of the cell wall to the drug, e.g. pseu-
exotoxins; direct toxic effects on/destruction of tissues domonas and many antibiotics.
or organ systems; impairment of host defensive mecha- lack of intracellular binding site for the antibiotic,
nisms; invasion of host cells; and provocation of auto e.g. Streptococcus pneumoniae and penicillin
immune processes. Early claims that bacterial infections resistance.
had been conquered by the development of antibacterial lack of target metabolic pathways, e.g. vancomycin
drugs are now seen as premature in light of the increas- is only effective against Gram-positive organisms
ing problem of bacterial resistance. Classified according because it affects synthesis of the peptidoglycan cell
to their ability to be stained by crystal violet after wall components that Gram-negative bacteria do
iodine fixation and alcohol decolorisation (Gram stain- not possess.
ing), various aspects of their metabolism and their production of specific enzymes against the drug, e.g.
morphology: penicillinase.
Gram-positive: cell wall consists of peptidoglycan the presence of bacterial biofilms communities of
(made up of glucosamine, muramic acid and amino bacteria held within a polysaccharide and protein
acids), lipoteichoic acid and polysaccharides; matrix that make them resistant to normal treat-
include: ment regimens of antibacterial agents.
- aerobes: Resistance may be a natural or acquired property.
- cocci (spherical-shaped), e.g. staphylococci, Bacteria may acquire resistance via activation of a
enterococci, streptococci species. dormant gene or transfer of the responsible gene from
- bacilli (rod-shaped), e.g. bacillus, corynebacte- other bacteria (horizontal evolution).
rium, mycobacterium species. Factors that increase the likelihood of resistance
- anaerobes: occurring include indiscriminate use of antibacterial
- cocci, e.g. peptococcus species. drugs, inappropriate choice of drug and use of subopti-
- bacilli, e.g. actinomyces, propionibacterium, mal dosage regimens (including poor compliance by
clostridium species. users, e.g. long-term anti-TB drug therapy). Regular
Gram-negative: have an additional outer cell consultation with microbiologists, use of antibiotic
wall layer containing lipopolysaccharide (endo- guidelines and infection control procedures, and micro-
toxin); include: biological surveillance may limit the problem. In the UK,

64 Bacterial translocation

the Department of Health has run several campaigns to of anociassociation in 1911, and Lundys refinement
increase awareness of the problem and encourage sen- in 1926.
sible prescribing of antibiotics. Antimicrobial steward-
ship programmes (particularly in ITUs) strive to reduce Ballistocardiography. Obsolete method for measure-
the emergence of bacterial resistance, improve clinical ment of measure cardiac output and stroke volume via
outcomes and control costs, through the logical prescrib- detection of body motion resulting from movement of
ing of antibacterial drugs. blood within the body with each heartbeat.
Resistance may also occur in other micro-
organisms, although the problem is greatest in bacteria. Balloon pump, see Intra-aortic counter-pulsation balloon
Gandhi TN, DePestel DD, Collins CD, Nagel J, Washer pump
LL (2010). Crit Care Med; 38 (Suppl.): S31523
Bar. Unit of pressure. Although not an SI unit, com-
Bacterial translocation. Passage of bacteria across the monly used when referring to the pressures at which
bowel wall via lymphatics into the hepatic portal circula- anaesthetic gases are delivered from cylinders and piped
tion, and thence possibly into the systemic circulation. gas supplies.
Implicated in the pathophysiology of intra-abdominal or 1 bar = 10 5 N/m 2 (Pa) = 100 kPa = 10 6 dyn/cm 2
generalised sepsis and MODS, with increased bowel wall
permeability resulting from inadequate oxygen delivery = 14.5 lb/in 2 1 atmosphere
allowing bacteria or their components (e.g. endotoxins)
to enter the circulation and activate various inflamma- Baralyme. Calcium hydroxide 80% and barium octahy-
tory mediator pathways, including cytokines. The inflam- drate 20%. Used to absorb CO2. Although less efficient
matory response may thus be initiated or maintained. than soda lime, it produces less heat and is more stable
Resting the bowel is thought to increase the chances of in dry atmospheres. Used in spacecraft. Carbon monox-
bacterial translocation; therefore early enteral feeding ide production may occur when volatile agents contain-
of critically ill patients (especially with a glutamine- ing the CHF2 moiety (desflurane, enflurane or isoflurane)
enriched feed) is believed to be beneficial. are passed over dry warm baralyme, e.g. at the start of a
Although much evidence supports the occurrence of Monday morning operating session following prolonged
bacterial translocation, its actual significance in SIRS passage of dry gas through the absorber.
and MODS is disputed.
Tsujimoto H, Ono S, Mochizuki H (2009). Dig Surg; 26: Barbiturate poisoning. Causes CNS depression with
1009 hypoventilation, hypotension, hypothermia and coma.
Skin blisters and muscle necrosis may also occur.
Bactericidal/permeability-increasing protein. Protein Treatment:

normally released by activated polymorphonuclear leu- general measures as for poisoning and overdoses.
cocytes. Binds to and neutralises endotoxin and is bac- of the above complications.
tericidal against Gram-negative organisms (by increasing forced alkaline diuresis, dialysis or haemoperfusion
permeability of bacterial cell walls). May have a role in may be indicated.
the future treatment of severe Gram-negative infections, Now rare, with the declining use of barbiturates.
e.g. meningococcal disease. Lipopolysaccharide-binding See also, Forced diuresis
protein is closely related.
See also, Sepsis; Sepsis syndrome; Septic shock; Systemic Barbiturates. Drugs derived from barbituric acid, itself
inflammatory response syndrome derived from urea and malonic acid and first synthesised
in 1864. The first sedative barbiturate, diethyl barbituric
Bain breathing system, see Coaxial anaesthetic breath- acid, was synthesised in 1903. Many others have been
ing systems developed since, including phenobarbital in 1912, hexo-
barbital in 1932 (the first widely used iv barbiturate),
Bainbridge reflex. Reflex tachycardia following an thiopental in 1934, and methohexital (methohexitone)
increase in central venous pressure, e.g. after rapid infu- in 1957.
sion of fluid. Activation of atrial stretch receptors results Substitutions at certain positions of the molecule

in reduced vagal tone and tachycardia. Absent or dimin- confer hypnotic or other properties to the compound
ished if the initial heart rate is high. Of uncertain signifi- (Fig. 22). Chemical classification:
cance but has been proposed to be involved in respiratory oxybarbiturates: as shown. Slow onset and pro-
sinus arrhythmia and to act as a counterbalance to the longed action, e.g. phenobarbital.
baroreceptor reflex.
[Francis Bainbridge (18741921), English physiologist]
Crystal GJ, Salem MR (2012). Anesth Analg; 114:
52032 O H
BAL, see Bronchoalveolar lavage C N
R 6 1
Balanced anaesthesia. Concept of using a combination C 5 2 O
of drugs and techniques (e.g. general and regional 4 3
anaesthesia) to provide adequate analgesia, anaesthesia R
and muscle relaxation (triad of anaesthesia). Each drug
reduces the requirement for the others, thereby reduc- O R
ing side effects due to any single agent, while also allow-
ing faster recovery. Arose from Criles description Fig. 22 Structure of the barbiturate ring
Baroreceptors 65

thiobarbiturates: sulphur atom at position 2. Rapid measures have failed and patients are fit enough for
onset, smooth action, and rapid recovery, e.g. anaesthesia and surgery.
BMI > 50kg/m as first-line treatment, if patients
methylbarbiturates: methyl group at position 1. are fit enough for anaesthesia and surgery.
Rapid onset and recovery, with excitatory phenom- Patients must be able to receive intensive specialist
ena, e.g. methohexital. management and be committed to the need for long-
methylthiobarbiturates: both substitutions. Very term follow-up.
rapid, but too high an incidence of excitatory Surgical techniques:
phenomena to be useful clinically. restrictive: laparoscopic adjustable gastric band-
Long side groups are associated with greater potency ing (AGB), sleeve gastrectomy, gastric balloon
and convulsant properties. Phenyl groups confer anti- insertion.
convulsant action. malabsorptive: biliopancreatic diversion duodenal
Exist in two structural isomers, the enol and keto forms. switch.
The enol form is water-soluble at alkaline pH and under- restrictive/malabsorptive: Roux-en-Y gastric bypass
goes dynamic structural isomerism to the lipid-soluble (laparoscopic or open).
keto form upon exposure to physiological pH (e.g. after Of these, laparoscopic AGB and Roux-en-Y bypass
injection). constitute the vast majority of performed procedures.
Divided clinically into: Some evidence suggests that the latter is more effec-
long-acting, e.g. phenobarbital. tive in severely obese patients, although there is
medium-acting, e.g. amobarbital. increased potential for serious surgical complications.
very short-acting, e.g. thiopental. AGB is quicker and easier to perform and its adjust-
Speed of onset of action reflects lipid solubility, and ability and reversibility confer specific advantages.
thus brain penetration. The actions of long- and May achieve losses of 50% of excess weight and
medium-acting drugs are terminated by metabolism; improvement of associated morbidity (e.g. hyperten-
the shorter duration of action of thiopental and sion, diabetes mellitus).
methohexital is due to redistribution within Anaesthetic considerations are as for all patients with
the body. morbid obesity.
Bind avidly to the alpha subunit of the GABAA [Jean Charles Roux (18571934), French surgeon]
receptor, potentiating the effects of endogenous
GABA. Antagonism of AMPA-type glutamate
receptors (-amino-3-hydroxy-5-methyl-4-isoxazo Barker, Arthur E (18501916). English Professor of
lepropionic acid receptors) also contributes to CNS Surgery at University of London. Helped popularise
depression. Actions: spinal anaesthesia in the UK. In 1907, became the first
general CNS depression, especially cerebral cortex
to use hyperbaric solutions of local anaesthetic agents,
and ascending reticular activating system. combined with alterations in the patients posture, to
central respiratory depression (dose-related).
vary the height of block achieved. Studied the effects of
baricity of various local anaesthetic preparations by
reduction of rapid eye movement sleep (with
developing a glass spine model. Used specially prepared
rebound increase after cessation of chronic use). solutions of stovaine (combined with 5% glucose)
anticonvulsant or convulsant properties according
from Paris.
to structure. Lee JA (1979). Anaesthesia; 34: 88591
cardiovascular depression. Central depression is
usually mild; the hypotension seen after thiopental Baroreceptor reflex (Pressoreceptor, Carotid sinus or
is largely due to direct myocardial depression and Depressor reflex). Reflex involved in the short-term
venodilatation. control of arterial BP. Increased BP stimulates barore-
ceptors in the carotid sinus and aortic arch, increasing
Oxidative and conjugative hepatic metabolism is fol- afferent discharge in the glossopharyngeal and vagus
lowed by renal excretion. Cause hepatic enzyme nerves respectively, that is inhibitory to the vasomotor
induction. centre and excitatory to the cardioinhibitory centre in
Contraindicated in porphyria. the medulla. Vasomotor inhibition (reduced sympathetic
Used mainly for induction of anaesthesia, and as anti- activity) and increased cardioinhibitory activity (vagal
convulsant drugs. Have been replaced by benzodiaze- stimulation) result in a lowering of BP and heart rate.
pines for use as sedatives and hypnotics, as the latter The opposite changes occur following a fall in BP, with
drugs are safer. sympathetic stimulation and parasympathetic inhibition.
See also, -Aminobutyric acid receptors; Barbiturate Resultant peripheral vasoconstriction occurs mainly in
poisoning non-vital vascular beds, e.g. skin, muscle, GIT.
The reflex is reset within 30min if the change in BP
Bariatric surgery. Performed to induce significant is sustained. It may be depressed by certain drugs, e.g.
and sustained weight loss in severe obesity, thereby halothane and possibly propofol.
preventing and indirectly treating the complications of Guyenet PG (2006). Nat Rev Neurosci; 7: 33546
obesity. Delivered as part of a multidisciplinary pro- See also, Valsalva manoeuvre
gramme including diet/lifestyle modifications drug
Indications (issued by NICE): Baroreceptors. Stretch mechanoreceptors in the walls
body mass index (BMI) 40kg/m or 3540kg/m
2 2
of blood vessels and heart chambers. Respond to disten-
in the presence of related significant disease sion caused by increased pressure, and are involved in
(e.g. diabetes, hypertension), where non-surgical control of arterial BP.
66 Barotrauma

Exist at many sites: O2 consumption: the subject breathes via a sealed

carotid sinus and aortic arch: circuit (containing a CO2 absorber) from an O2-
- at normal BP, discharge slowly. Rate of discharge filled spirometer. As O2 is consumed, the volume
is increased by a rise in BP, and by increased rate inside the spirometer falls, and a graph of volume
of rise. against time is obtained. O2 consumption per unit
- send afferent impulses via the carotid sinus nerve time is corrected to standard temperature and pres-
(branch of glossopharyngeal nerve) and vagus sure. Average energy liberated per litre of O2 con-
(afferents from aortic arch) to the vasomotor sumed = 20.1kJ (4.82Cal; some variation occurs
centre and cardioinhibitory centre in the medulla. with different food sources); thus BMR may be cal-
Raised BP invokes the baroreceptor reflex. culated. A similar derivation can be obtained elec-
atrial stretch receptors: tronically by the bedside metabolic cart, e.g. when
- found in both atria. Involved in both short-term calculating energy balance in critically ill patients.
neural control of cardiac output and long-term Normal BMR (adult male) is 197kJ/m2/h (40Cal/m2/h).
humoral control of ECF volume. BMR values are often expressed as percentages above
- some discharge during atrial systole while others or below normal values obtained from charts or tables.
discharge during diastolic distension (more so Metabolic rate is increased by:
when venous return is increased or during IPPV). circulating catecholamines, e.g. due to stress.
The latter may be involved in the Bainbridge muscle activity.
reflex. Discharge also results in increased urine raised temperature.
production via stimulation of ANP secretion and hyperthyroidism.
inhibition of vasopressin release. pregnancy.
ventricular stretch receptors: stimulation causes recent feeding (specific dynamic action of foods).
reduced sympathetic activity in animals, but the age and sex (higher in males and children).
clinical significance is doubtful. May also respond to Measurement of metabolic rate under basal conditions
chemical stimulation (BezoldJarisch reflex). eliminates many of these variables.
coronary baroreceptors: importance is uncertain. See also, Metabolism
Other baroreceptors may be present in the mesentery,
affecting local blood flow. Basal narcosis, see Rectal administration of anaesthetic
Barotrauma. Physical injury caused by an excessive
pressure differential across the wall of a body cavity; in
anaesthesia, the term usually refers to pneumothorax, Base. Substance that can accept hydrogen ions, thereby
pneumomediastinum, pneumoperitoneum or subcuta- reducing hydrogen ion concentration.
neous emphysema resulting from passage of air from
the tracheobronchial tree and alveoli into adjacent Base excess/deficit. Amount of acid or base (in mmol)
tissues. Risk of barotrauma is increased by raised airway required to restore 1 litre of blood to normal pH at PCO2
pressures, e.g. with IPPV and PEEP (especially if exces- of 5.3kPa (40mmHg) and at body temperature. By con-
sive tidal volume or air flow is delivered, or if the vention, its value is negative in acidosis and positive in
patient fails to synchronise with the ventilator). High alkalosis. May be read from the Siggaard-Andersen
frequency ventilation may reduce the risk. Diseased nomogram. Useful as an indication of severity of the
lungs with reduced compliance are more at risk of metabolic component of acidbase disturbance, and in
developing barotrauma, e.g. in asthma, ARDS; limiting the calculation of the appropriate dose of acid or base
inspiratory pressures at the expense of reduced minute in its treatment. For example, in acidosis:
volume and increased arterial PCO2 is increasingly used
to reduce the risk of barotrauma in these patients (per- Total bicarbonate deficit (mmol) = base deficit (mmol/l)
missive hypercapnia). Evidence of pulmonary intersti- treatable fluid compartment (l);
tial emphysema may be seen on the CXR (perivascular estimated to be 30% of body weight, composed of
air, hilar air streaks and subpleural air cysts) before
development of severe pneumothorax. In all cases, N2O ECF and exchangeable intracellular fluid:
will aggravate the problem. body weight
Risk of barotrauma during anaesthesia is reduced = base deficit
by various pressure-limiting features of anaesthetic
machines and breathing systems. Because of problems associated with bicarbonate admin-
See also, Emphysema, subcutaneous; Ventilator-associated istration, half the calculated deficit is given initially.
lung injury See also, Acidbase balance; Blood gas analyser; Blood
gas interpretation
Basal metabolic rate (BMR). Amount of energy liber-
ated by catabolism of food per unit time, under stan- Basic life support, adult (BLS). Component of CPR
dardised conditions (i.e. a relaxed subject at comfortable without any equipment or drugs (i.e. suitable for anyone
temperature, 1214h after a meal). May be expressed to administer). Known as the ABC of resuscitation. Use
corrected for body surface area. with simple equipment, e.g. airways, facemasks, self-
Determined by measuring: inflating bags, oesophageal obturators, LMA; it has been
heat produced by the subject enclosed in an insu- defined as basic life support with airway adjuncts.
lated room, the outside walls of which are main- Latest European recommendations (2010):
tained at constant temperature. The heat produced ensure own safety and that of the victim.
raises the temperature of water passing through assess: e.g. shake the victim, ask if he/she is all right.
coils in the ceiling, allowing calculation of BMR. If responsive, leave the patient in the same position
Bellows 67

(provided safe) and get help. If unresponsive, shout of the posterior surface of each vertebral body, and with
for help, turn the patient on to his/her back, open sacral, lumbar, thoracic and cervical veins. It thus con-
the airway and remove any obstruction. nects pelvic veins with intracranial veins. Provides an
Airway: tilt the head back and lift the chin. Remove alternative route for venous blood to reach the heart
food and dentures from the airway. Use airway from the legs. Originally described to explain a route for
adjuncts if available. metastatic spread of tumours. Distends when vena caval
Breathing: check first look, listen and feel for up venous return is obstructed, e.g. in pregnancy, thus
to 10s. If breathing, turn into the recovery position, reducing the space available for local anaesthetic solu-
unless spinal cord injury is suspected. Summon help, tion in epidural anaesthesia.
asking for an automated external defibrillator [Oscar V Batson (18941979), US otolaryngologist]
(AED) if one is available; a solo rescuer should See also, Epidural space
phone first since the chance of successful defibril-
lation falls with increasing delay (although children, Beclometasone dipropionate (Beclomethasone).
trauma or drowning victims, and poisoned or Inhaled corticosteroid, used to prevent bronchospasm in
choking patients may benefit from 1min of CPR asthma by reducing airway inflammation.
before calling for help). If not breathing, summon Dosage: 0.20.8mg bd, depending on clinical severity
help and, on returning, start cardiac massage; after and drug preparation. A nebuliser preparation is
30 compressions give two slow effective breaths available but is relatively inefficient since the drug is
(7001000ml, each over 1s) followed by another 30 poorly soluble.
compressions. Rapid breaths are more likely to Side effects: as for corticosteroids, although systemic
inflate the stomach. Cricoid pressure should be uptake is low. Hoarse voice and oral candidiasis may
applied if additional help is available. Risk of HIV occur with high dosage.
infection and hepatitis is considered negligible.
Inflating equipment and 100% O2 should be used if Becquerel. SI unit of radioactivity. One becquerel =
available. amount of radioactivity produced when one nucleus dis-
Circulation: apply external cardiac massage (56cm integrates per second.
chest depressions) at 100120/min, with the hands [Antoine Becquerel (18521908), French physicist]
in the centre of the chest, stopping only if the patient
starts breathing. It is important to deliver uninter- Bed sores, see Decubitus ulcers
rupted compressions since this improves chances of
survival. Do not stop to check the victim or discon-
tinue CPR unless the victim starts to show signs of Bee stings, see Bites and stings
regaining consciousness, e.g. coughing, eye opening,
speaking or moving purposefully. External bleeding BeerLambert law. Combination of two laws describ-
should be stopped and the feet raised. ing absorption of monochromatic light by a transparent
if there is a second rescuer, the two rescuers substance through which it passes:
Beers law: intensity of transmitted light de
should swap every 12min to minimise fatigue. The
recommended ratio of compressions:breaths is creases exponentially as concentration of substance
30:2 for both single- and two-operator CPR. Chest- increases.
Lamberts law: intensity of transmitted light
compression-only CPR is acceptable if the rescuer
is unable or unwilling to give rescue breaths. decreases exponentially as distance travelled
in cases of choking, encourage coughing in
through the substance increases.
conscious patients; clear the airway manually and Forms the basis for spectrophotometric techniques, e.g.
use 5 back slaps then 5 abdominal thrusts enzyme assays, oximetry, near infrared spectroscopy.
(Heimlich manoeuvre) if not breathing or unable [August Beer (18251863) and Johann Lambert (1728
to speak, repeated as necessary; use basic life 1777), German physicists]
support (as above) if the patient becomes
unconscious. BellMagendie law. The dorsal roots of the spinal cord
All medical and paramedical personnel should be able are sensory, the ventral roots motor.
to administer basic life support (ideally every member [Sir Charles Bell (17741842), Scottish surgeon; Franois
of the public). Ability of hospital staff has been consis- Magendie (17831855), French physiologist]
tently shown to be poor. Regular training sessions are
thought to be necessary, using training mannikins. Bellows. Expansible container used to deliver controlled
European Resuscitation Council Guidelines (2010). volumes of pressurised gas. May describe bellows incor-
Resuscitation; 81: 121976 porated into ventilators or hand-operated devices. The
See also Advanced life support, adult; Cardiac arrest; latter have been used in CPR and animal experiments
Cardiopulmonary resuscitation, neonatal; Cardiopulmo- for several centuries. More modern devices allow
nary resuscitation, paediatric; International Liaison manual-controlled ventilation, and are either applied
Committee on Resuscitation; Resuscitation Council (UK) directly to the patients face or used in draw-over
BASICS, see British Association for Immediate Care Examples:
Cardiff bellows: mainly used for resuscitation
Batsons plexus. Valveless epidural venous plexus com- (rarely used now, self-inflating bags being pre-
posed of anterior and posterior longitudinal veins, com- ferred). Design:
municating at each vertebral level with venous rings that - concertina bellows with a facemask at one end.
pass transversely around the dural sac. Also communi- - non-rebreathing valve between the bellows and
cates with basivertebral veins passing from the middle facemask.
68 Bends

- one-way valve at the other end of the bellows that

prevents air or O2 leaks during compression,
whilst allowing fresh gas entry during expansion.
Oxford bellows (Fig. 23): used for resuscitation or
draw-over anaesthesia. Design:
- concertina bellows mounted on a block contain-
ing one-way valves.
- held open by an internal spring, but may be manu-
ally compressed. Expansion draws in air or O2
through a side port.
- unidirectional gas flow is ensured by the one-way To
valves, one on either side of the bellows. A non- patient
rebreathing valve is required between the bellows
and patient.
In earlier models, an O2 inlet opened directly into
the closed bellows system. This could allow build-up
of excessive pressure, with risk of barotrauma.

Bends, see Decompression sickness

Benzatropine mesylate (Benztropine). Anticholinergic

drug, used to treat acute dystonic reactions and parkin- Oxygen
sonism, especially drug-induced.
Fig. 23 Oxford bellows
14mg orally od.
12mg iv/im, repeated as required.
Side effects: sedation, dry mouth, blurred vision, GIT
lorazepam: 12h.
upset, urinary retention, tachycardia. May worsen diazepam, clonazepam: 2448h.
tardive dyskinesia. Metabolism often produces active products with long
half-lives that depend upon renal excretion, e.g. diaze-
Benzodiazepine poisoning. Commonest overdose pam to temazepam and nordiazepam (the latter has a
involving prescription drugs. Generally considered to be half-life of up to 900h and is itself metabolised to oxaz-
less serious than overdose with other sedatives, although epam). In chronic use, benzodiazepines have largely
death may occur, usually due to respiratory depression replaced barbiturates as hypnotics and anxiolytics, since
and aspiration of gastric contents. Of the benzodiaze- they cause fewer and less serious side effects. Overdos-
pines, temazepam is most sedating, and oxazepam least age is also less dangerous, usually requiring supportive
sedating, when taken in overdose. Often accompanied treatment only. Hepatic enzyme induction is rare. A
by alcohol poisoning. chronic dependence state may occur, with withdrawal
Features are mainly those of CNS depression; featuring tremor, anxiety and confusion. Flumazenil is a
hypoventilation and hypotension may also be present. specific benzodiazepine antagonist.
Treatment is largely supportive. Flumazenil may be used See also, -Aminobutyric acid receptors; Benzodiazepine
but large doses may be required and the effects may be poisoning
temporary; acute withdrawal and convulsions may be
provoked in patients on chronic benzodiazepine therapy,
Benztropine, see Benzatropine
those with alcohol dependence, or in cases of mixed drug
overdoses (tricyclic antidepressants drug poisoning in
particular). Benzylpenicillin (Penicillin G). Antibacterial drug,
the first penicillin. Used mainly in infections caused
Benzodiazepines. Group of drugs with sedative, anxio- by Gram-positive and -negative cocci, although its use is
lytic and anticonvulsant properties. Also cause amnesia hampered by increasing bacterial resistance. The drug of
and muscle relaxation. Bind to the and subunits of choice in meningococcal disease, gas gangrene, tetanus,
the GABAA receptor complex, potentiating the increase anthrax and diphtheria. Inactivated by gastric acid, thus
in chloride ion conductance caused by endogenous poorly absorbed orally.
Dosage: 0.61.2g im/iv qds; up to 2.4g 46-hourly in
GABA. They thus enhance GABA-mediated inhibition
in the brain and spinal cord, especially the limbic system meningococcal meningitis or anthrax.
Side effects: allergic reactions, convulsions following
and ascending reticular activating system.
Anaesthetic uses: high doses or in renal failure.
premedication, e.g. diazepam, temazepam,
lorazepam. Bernard, Claude (18131878). French physiologist,
sedation, e.g. diazepam, midazolam. whose many contributions to modern physiology include:
as anticonvulsant drugs, e.g. diazepam, lorazepam, demonstrating hepatic gluconeogenesis; proving that
clonazepam. pancreatic secretions could digest food; discovering
induction of anaesthesia, e.g. midazolam. vasomotor nerves; and investigating the effects of curare
Half-life: at the neuromuscular junction. Also suggested the
midazolam: 13h. concept of the internal environment (milieu intrieur)
oxazepam: 38h. and homeostasis.
temazepam: 68h. Lee JA (1978). Anaesthesia; 33: 7417
Bioavailability 69

Bernoulli effect. Reduction of pressure when a fluid Presented as 8.4%, 4.2% and 1.26% solutions
accelerates through a constriction. As velocity increases (1000mmol/l, 500mmol/l and 150mmol/l respectively).
during passage through the constriction, kinetic energy See also, Base excess/deficit
increases. Total energy must remain the same, therefore
potential energy (hence pressure) falls. Beyond the con- Bier, Karl August Gustav (18611949). Renowned
striction, the pressure rises again. A second fluid may German surgeon, Professor in Bonn and then Berlin.
be entrained through a side arm into the area of lower Introduced spinal anaesthesia using cocaine, describing
pressure, causing mixing of the two fluids (Venturi its use on himself, his assistant and a series of patients,
principle). in 1899. Gave a classic description of the post-dural
[Daniel Bernoulli (17001782), Swiss mathematician] puncture headache he later suffered, and suggested CSF
leakage during/after the injection as a possible cause.
Bert effect. Convulsions caused by acute O2 toxicity, Also introduced IVRA, using procaine, in 1908. As con-
seen with hyperbaric O2 therapy (3 atm). sulting surgeon during World War I, he introduced the
[Paul Bert (18331896), French physiologist] German steel helmet.
See also, Oxygen therapy, hyperbaric van Zundert A, Goerig M (2000). Reg Anesth Pain Med;
25: 2633
Beta-adrenergic , see -Adrenergic
Biers block, see Intravenous regional anaesthesia
Beta-lactams, see -Lactams
Bigelow, Henry Jacob (18181890). US surgeon at the
BezoldJarisch reflex. Bradycardia, vasodilatation and Massachusetts General Hospital, Boston, he sponsored
hypotension following stimulation of ventricular recep- Wells abortive attempt at anaesthesia in 1845 and
tors by ischaemia or drugs, e.g. nicotine and veratridine. promoted and published the first account of Mortons
Thought to involve inhibition of the baroreceptor use of diethyl ether anaesthesia for surgery in 1846.
reflex. Although of disputed clinical significance, a role Described several operations and the intraoperative
in regulation of BP and the response to hypovolaemia events that occurred during them. Later, as a Professor,
has been suggested. The reflex may be activated during he became renowned for many contributions to surgery,
myocardial ischaemia or MI, and in rare cases of including inventing a urological evacuator.
unexplained cardiovascular collapse following spinal/
epidural anaesthesia. Biguanides. Hypoglycaemic drugs, used to treat non-
[Albert von Bezold (18361868), German physiologist; insulin-dependent diabetes mellitus. Act by decreasing
Adolf Jarisch (18501902), Austrian dermatologist] gluconeogenesis and by increasing glucose utilisation
Campagna JA, Carter C (2003). Anesthesiology; 98: peripherally. Require some pancreatic islet cell function
125060 to be effective. May cause lactic acidosis, especially in
renal or hepatic impairment. Lactic acidosis is particu-
Bicarbonate. Anion present in plasma at a concentra- larly likely with phenformin, which is now unavailable
tion of 2433mmol/l, formed from dissociation of car- in the UK. Metformin, the remaining biguanide, is used
bonic acid. Intimately involved with acidbase balance, as first-line treatment in obese patients in whom diet
as part of the major plasma buffer system. Filtered in the alone is unsuccessful, or when a sulphonylurea alone is
kidneys and reabsorbed to a variable extent, according inadequate.
to acidbase status. 80% of filtered bicarbonate is reab-
sorbed in the proximal tubule via formation of carbonic Biliary tract. Bile produced by the liver passes to the
acid, which in turn forms CO2 and water aided by car- right and left hepatic ducts, which unite to form the
bonic anhydrase. The bicarbonate ion itself does not pass common hepatic duct. This is joined by the cystic duct,
easily across cell membranes. which drains the gallbladder, to form the common bile
Sodium bicarbonate may be administered iv to raise
duct; the latter drains into the duodenum (with the pan-
blood pH in severe acidosis, but with potentially creatic duct) through the ampulla of Vater, the lumen of
undesirable effects: which is controlled by the sphincter of Oddi. Both infec-
increased formation of CO2, which passes readily
tion of the biliary tree (cholangitis) and inflammation of
into cells (unlike bicarbonate), worsening intracel- the gallbladder (cholecystitis) may occur during critical
lular acidosis. illness.
increased blood pH shifts the oxyhaemoglobin dis-
[Ruggero Oddi (18451906), Italian physiologist and
sociation curve to the left, with increased affinity of anatomist; Abraham Vater (16841751), German anato-
haemoglobin for O2 and impaired O2 delivery to the mist and botanist]
tissues. See also, Jaundice
solutions contain 1mmol sodium ions per mmol
bicarbonate ions, representing a significant sodium Binding of drugs, see Pharmacokinetics; Protein-
load. binding
8.4% solution is hypertonic: increased plasma
osmolality may cause arterial vasodilatation and Bioavailability. Fraction of an administered dose of
hypotension. a drug that reaches the systemic circulation unchanged;
severe tissue necrosis may follow extravasation.
iv injection thus provides 100% bioavailability. For
For these reasons, treatment is usually reserved for pH an orally administered dose, it equals the area under
below 7.17.2. the resultant concentration-against-time curve divided
base deficit body weight (kg) by that for an iv dose (Fig. 24). Low values of bioavail-
Dose: mmol ability occur with poorly absorbed oral drugs, or those
Half of this dose is given initially. that undergo extensive first-pass metabolism. Various
70 Biofeedback

pneumonic plague: Gram-negative bacillus causing

mucopurulent sputum, chest pain and hemoptysis.
If untreated, mortality approaches 100%.
Bioavailability = AUCpo x 100
tularaemia: Gram-negative coccobacillus causing
bronchopneumonia, pleuritis and hilar lymphade-
nopathy. Overall mortality for virulent strains is
515%, but up to 3060% in pulmonic or septicae-
mic tularaemia without antibiotics.
iv viral haemorrhagic fevers: influenza-like illness with
Plasma haemorrhage, petechiae and ecchymoses or multi-
[drug] ple organ failure. Mortality approaches 100% for
the most virulent forms.
botulism: a paralytic illness characterised by sym-

oral metric, descending flaccid paralysis of motor and

autonomic nerves, usually beginning with the cranial
nerves. Mortality is approximately 6% if appropri-
Time ately treated.
smallpox: febrile illness followed by a generalised
Fig. 24 Bioavailability
macular or papular-vesicular-pustular eruption.
Mortality is approximately 30%.
Management includes specific and general supportive
formulations of the same drug may have different measures; consideration should also be directed towards
bioavailability. Bioinequivalence is a statistically signifi- protection of staff, decontamination of clinical areas and
cant difference in bioavailability, whereas therapeutic equipment, disposal of bodies and other aspects of major
inequivalence is a clinically important difference, e.g. as incidents.
may occur with different preparations of digoxin. White SM (2002). Br J Anaesth; 89: 30624
See also, Pharmacokinetics See also, Incident, major; Chemical weapons

Biofeedback. Technique whereby bodily processes Biotransformation, see Pharmacokinetics

normally under involuntary control, e.g. heart rate,
are displayed to the subject, enabling voluntary control BIPAP. Bi-level positive airway pressure, see Non-
to be learnt. Has been used to aid relaxation, and in invasive positive pressure ventilation
chronic pain management when increased muscle
tension is present, using the EMG as the displayed Bispectral index monitor. Cerebral function monitor
signal. that uses a processed EEG obtained from a single
frontal electrode to provide a measure of cerebral activ-
Bioimpedance cardiac output measurement, see ity. Used to monitor anaesthetic depth in an attempt to
Impedance plethysmography prevent awareness. Produces a dimensionless number
(the BIS number) ranging from 100 (fully awake) to 0
Biological weapons. Living organisms or infected mate- (no cerebral activity). The algorithm used to calculate
rial derived from them, used for hostile purposes, either the BIS value is commercially protected but is based on
by certain nations in legitimate biological warfare or by power spectral analysis of the EEG, the synchrony of
(bio)terrorists. The agents depend for their effects on slow and fast wave activity and the burst suppression
their ability to multiply in the person, animal or plant ratio. Targeting a BIS number of 4060 is advocated to
attacked. Although not pathognomonic of a bioterrorist reduce awareness and allow more rapid emergence
attack, the following should raise suspicion: from anaesthesia, although the evidence does not
an unusual clustering of illness in time or space. support its routine use.
an unusual age distribution of a common illness (e.g. See also, Anaesthesia, depth of
apparent chickenpox in adults).
a large epidemic. Bisphosphonates. Group of drugs that inhibit osteoclast
disease that is more severe than expected. activity; used in Pagets disease, osteoporosis, metastatic
an unusual route of exposure. bone disease and hypercalcaemia. They are adsorbed on
disease outside its normal transmission season. to hydroxyapatite crystals, interfering with bone turn-
multiple simultaneous epidemics of different over and thus slowing the rate of calcium mobilisation.
diseases. May be given orally or by slow iv infusion, e.g. in severe
unusual strains or variants of organisms or antimi- hypercalcaemia of malignancy:
crobial resistance patterns. disodium pamidronate: 1560mg, given once or
Potential diseases include: divided over 24 days, up to a maximum of 90mg
anthrax: Gram-negative bacillus causing fever, skin in total.
eschars (dry scabs) and associated lymphadenopa- ibandronic acid: 24mg by a single infusion.
thy, chest pain, dry cough, nausea and abdominal sodium clodronate: 300mg/day for 710 days or
pain, followed by sepsis, shock, widened mediasti- 1.5g by a single infusion.
num, hemorrhagic pleural effusions and respiratory zoledronic acid: 45mg (depending on the prepara-
failure. Mortality rates vary depending on exposure: tion) over 15min by a single infusion.
approximately 20% for cutaneous anthrax without Side effects include hypocalcaemia, hypophosphatae-
antibiotics, 2575% for gastrointestinal anthrax and mia, pyrexia, flu-like illness, vomiting and headache.
over 80% for inhalation anthrax. Blood dyscrasias, hyper- or hypotension, renal and
Blood 71

hepatic dysfunction may rarely occur, especially with assessment of all systems and degree of swelling
disodium pamidronate. Osteonecrosis of the jaw and are important. Antitetanus immunisation should be
atypical femoral fractures have also been reported, given. Broad-spectrum antibacterial drugs are often
mainly associated with long-term administration. given.
[Sir James Paget (18141899), English surgeon] Singletary EM, Rochman AS, Bodmer JC, Holstege CP
(2005). Med Clin North Am; 89: 1195224
Bites and stings. May include animal bites, and animal
or plant stings. Problems are related to: Bivalirudin. Recombinant hirudin used as anticoagulant
local tissue trauma itself: damage to vital organs, in acute coronary syndromes.
haemorrhage, oedema. Importance varies with the Dosage:
size, location and number of the wound(s). in patients undergoing percutaneous coronary
effect of venom or toxin delivered: may cause an intervention (PCI), including those with S-T
intense immune and inflammatory reaction, usually segment elevation MI: 750g/kg iv initially fol-
with severe pain and swelling. Systemic features lowed by 1.75mg/kg/h for up to 4h after
usually present within 14h; they may vary but procedure.
typically include: in patients with unstable angina or non S-T segment
- respiratory: bronchospasm, pulmonary oedema, elevation MI: 100g/kg iv initially followed by
respiratory failure (type I or II), airway obstruc- 250g/kg/h for up to 72h. For those proceeding to
tion (from oedema). PCI, an additional bolus dose of 500g is given
- cardiovascular: hypertension (from neuro followed by an infusion of 1.75mg/kg/h.
transmitter release), hypotension (from cardiac Side effects: bleeding, hypotension, angina,
depression, hypovolaemia, vasodilatation), headache.
- neurological: confusion, coma, convulsions. Bladder washouts. Main types used in ICU:
- neuromuscular: cranial nerve palsies and periph- to remove debris and exclude catheter blockage as
eral paralysis (from pre- or postsynaptic neuro- a cause of oliguria: sterile saline. Various solutions
muscular junction blockade), muscle spasms are available to remove phosphate deposits.
(from neurotransmitter release), rhabdomyolysis. to dissolve blood clots: sterile saline or sodium
- gastrointestinal: nausea, vomiting. citrate 3% irrigation. Streptokinase-streptodornase
- haematological: coagulation disorders, haemo enzyme preparation may also be used (allergic reac-
lysis. tions and burning may occur).
- renal: impairment from myoglobinuria, hypoten- for urinary tract infection: chlorhexidine 1:5000
sion and direct nephrotoxicity. (may cause burning and haemorrhage); ineffective
wound infection, either introduced at the time of in pseudomonal infections. Saline may also be used.
injury or acquired secondarily. Amphotericin may be used in fungal infection.
systemic transmitted disease, e.g. tetanus, rabies, Also used to treat local malignancy.
Venoms are typically mixtures of several compounds, Blast injury, see Chest trauma
including enzymes and other proteins, amino acids, pep-
tides, carbohydrates and lipids. The age and health of the Bleeding time, see Coagulation studies
victim, and the site and route of envenomation, may
affect the severity of the injury. Identification of the Bleomycin. Antibacterial cytotoxic drug, given iv or im
offending animal or plant is particularly important, since to treat lymphomas and certain other solid tumours. Side
prognosis and management may vary considerably effects include alveolitis, dose-dependent progressive
between species. Certain venoms may be identified by pulmonary fibrosis, skin and allergic reactions (common)
blood testing. and myelosuppression (rare). Pulmonary fibrosis is
Management: thought to be exacerbated if high concentrations of O2
initial resuscitation as for trauma, anaphylaxis. are administered, e.g. for anaesthesia. Suspicion of fibro-
Rapid transfer of victims of envenomation to hos- sis (CXR changes or basal crepitations) is an indication
pital is the most important prehospital measure. to stop therapy.
Jewellery should be removed from the affected limb
as swelling may be marked. Blood. Circulating body fluid composed of blood cells
specific management: (red cells, white cells and platelets) suspended in plasma.
- application of a pressure dressing and immobilisa- Normal adult blood volume is 7080ml/kg, of which
tion of the affected body part in order to reduce ~45% is cellular. Cell formation occurs in the liver,
systemic absorption. spleen and bone marrow before birth, after which it
- neutralisation of venom already absorbed. Many occurs in bone marrow only. In adults, active bone
antivenoms are derived from horses, and severe marrow is confined to vertebrae, ribs, sternum, ilia and
allergic reactions may occur. humeral and femoral heads. Stem cells differentiate into
- previously employed measures, now agreed to be mature cells over many divisions. Primary stem cells
unhelpful or harmful, include suction to remove may give rise to the lymphocyte series of stem cells or
venom from the wound and application of limb to secondary stem cells. The secondary stem cells may
tourniquets. give rise to the erythrocyte, granulocyte, monocyte or
general supportive management according to the megakaryocyte series of stem cells (the latter forming
system affected. IV fluids are usually required. platelets).
Blood should be taken early as certain venoms and See also, Blood volume; Erythrocytes; Leucocytes;
antivenoms may interfere with grouping. Frequent Plasma; Platelets
72 Blood, artificial

Blood, artificial. Synthetic solutions capable of O2 trans- neuromuscular blocking drugs and glycopyrronium, are
port and delivery to the tissues. Circumvent many of the permanently charged, and cross to a very limited extent
complications of blood transfusion and avoid the need (cf. atropine).
for blood compatibility testing. Two types have been The effectiveness of the barrier is reduced in neo-
investigated: nates compared with adults: hence the increased passage
haemoglobin solutions: of drugs (e.g. opioid analgesic drugs) and other sub-
- must be free of red cell debris (stroma-free) to stances (e.g. bile salts, causing kernicterus). Localised
avoid renal damage, that has also occurred with pathology, e.g. trauma, malignancy and infection, may
certain stroma-free solutions. Other effects may also reduce the integrity of the barrier.
include impairment of macrophage activity, vaso-
constriction and activation of various inflamma- Blood compatibility testing. Procedures performed on
tory pathways. Free haemoglobin solutions are donor and recipient blood before blood transfusion, to
also hyperosmotic and are quickly broken down determine compatibility. Necessary to avoid reactions
in the blood. caused by transfusion of red cells into a recipient whose
- the oxyhaemoglobin dissociation curve of free plasma contains antibodies against them. ABO and
haemoglobin is markedly shifted to the left of that Rhesus are the most relevant blood group systems clini-
for intraerythrocyte haemoglobin, reducing its cally, although others may be important.
usefulness. Antibodies may be intrinsic (e.g. ABO system) or
- must be stored in O2-free atmosphere to avoid develop only after exposure to antigen (e.g. Rhesus).
oxidisation to methaemoglobin. Methods:
Various modifications of the haemoglobin molecule group and screen: if red cells have serum added that
have been made in order to prolong its half-life contains antibody against them, agglutination of the
from under 1h to over 24h, including polymerisa- cells occurs; serum of known identity is thus used to
tion with glutaraldehyde, linking haemoglobin with identify the recipients ABO blood group and
hydroxyethyl starch or dextran, cross-linking the Rhesus status. The recipients serum is also screened
or chains, and fusing the chains end to end (the for atypical antibodies against other groups. Usually
latter has been done with recombinant human hae- takes 3040min.
moglobin). Bovine haemoglobin, and encapsulation cross-match: in addition to group and screen, the
of haemoglobin within liposomes, has also been recipients serum is added to red cells from each
used. Many of these preparations are currently donor unit to confirm compatibility. Usually takes
undergoing clinical trials. 4560min.
perfluorocarbon solutions (e.g. Fluosol DA20) carry computer cross-match (electronic issue): uncross-
dissolved O2 in an amount directly proportional to matched ABO and Rhesus-compatible blood may
its partial pressure, and have been used to supple- be issued within a few minutes with no further
ment O2 delivery in organ ischaemia due to shock, testing, provided the patient does not have irregular
arterial (including coronary) insufficiency and antibodies.
haemorrhage. Have been used for liquid ventilation. Uncross-matched O Rhesus-negative blood is reserved
Even with high FIO2, O2 content is less than that of for life-threatening emergencies. Fresh frozen plasma is
haemoglobin (newer compounds may be more effi- not cross-matched, but chosen as type-specific (ABO) so
cient at O2 carriage). Accumulation in the reticulo- that antibodies are not infused into a recipient who
endothelial system is of unknown significance. might have the corresponding antigens on his or her
Clinical trials are continuing. cells. Platelets are suspended in plasma, so are also
Spiess BD (2009). J Appl Physiol; 106: 144452 selected as type-specific, but in this case according to
Rhesus typing too.
Bloodbrain barrier. Physiological boundary between
the bloodstream and CNS, preventing transfer of hydro- Blood cultures. Microbiological culture of blood, per-
philic substances from plasma to brain. The original formed to detect circulating micro-organisms. Blood is
concept was suggested by the lack of staining of brain taken under aseptic conditions and injected into (usually
tissue by aniline dyes given systemically. Passage of two) bottles containing culture medium, for aerobic and
hydrophilic molecules is impeded by tight junctions anaerobic incubation. Diluting the sample at least 45
between capillary endothelial cells in the brain and epi- times in the culture broth reduces the antimicrobial
thelial cells in the choroid plexus; glial cells also con activity of serum and of any circulating drugs. Changing
tribute. Active transport may still occur for specific the hypodermic needle between taking blood and injec-
molecules, e.g. glucose. Certain areas of the brain lie tion into the bottles is not now thought to be necessary,
outside the barrier, e.g. the hypothalamus and areas although contamination of the needle and bottles must
lining the third and fourth ventricles (including the che- be avoided. Sensitivity depends on the type of infection,
moreceptor trigger zone). the number of cultures and volume of blood taken. At
In the absence of active transport, the ability of chem- least 23 cultures, each using at least 1030ml blood, are
icals to cross the barrier is proportional to their lipid usually recommended. More samples may be required
solubility, and inversely proportional to molecular size when there is concurrent antibacterial drug therapy (the
and charge. Water, O2 and CO2 cross freely; charged ions sample may be diluted several times or the drug removed
and larger molecules take longer to cross, unless lipid- in the laboratory to increase the yield) or when endo-
soluble. All substances eventually penetrate the brain; carditis is suspected. False-positive results may be sug-
the rate of penetration is important clinically. Some gested by the organism recovered (e.g. bacillus species,
drugs only cross the barrier in their unionised, non- coagulase-negative staphylococci, diphtheroids) and
protein-bound form, i.e. a small proportion of the their presence in only a single culture out of many and
injected dose, e.g. thiopental. Quaternary amines, such as after prolonged incubation.
Blood gas interpretation 73

Many different culture systems exist, some directed

Table 9 Blood flow to and O2 consumption of heart, brain,
at particular organisms. Different systems may be used
liver and kidneys
together to increase their yield. Modern microbiological
techniques may involve automatic alerting of staff when Blood flow O2 consumption
significant microbial growth interrupts passage of light
through the bottles. The organisms may then be identi- (ml/100g (ml/100g
fied and sensitivity to antimicrobials determined. Organ (ml/min) tissue/min) (ml/min) tissue/min)
Thompson F, Madeo M (2009). J Infect Prevention; 10:
s246 Heart 250 80 30 10
Brain 700 50 50 3
See also, Sepsis
Liver 1400 50 50 2
Kidneys 1200 400 20 6
Blood filters. Devices for removing microaggregates
during blood transfusion. Platelet microaggregates form
early in stored blood, with leucocytes and fibrin aggre-
gates occurring after 7 days storage. Pulmonary micro- arteries and in the hyperdynamic circulation, particu-
embolism has been suggested as a cause of pulmonary larly in anaemia, when viscosity is reduced (see Reyn-
dysfunction following transfusion. olds number).
Types of filters: Measurement:
screen filters: sieves with pores of a certain size. direct measurement of blood from the arterial
depth filters: remove particles mainly by adsorption. supply.
Pore size varies, and effective filtration may be electromagnetic flow measurement.
reduced by channel formation within the filter. Doppler measurement.
combination filters. indirect methods:
Most contain woven fibre meshes, e.g. of polyester or - Fick principle.
nylon. Filtration results from both a physical sieving - dilution techniques.
effect and the presence of a positive or negative charge - plethysmography.
on the surface of the material that traps cellular compo- Approximate blood flow to, and O2 consumption of,
nents and large molecules. various organs are shown in Table 9.
Standard iv giving sets suitable for blood transfusion
contain screen filters of 170m pore size. Filtration of Blood/gas partition coefficients, see Partition
microaggregates requires microfilters of 2040m pore coefficients
size. The general use of microfilters is controversial; by
activating complement in transfused blood they may Blood gas analyser. Device used to measure blood gas
increase formation of microaggregates within the recipi- tensions, pH, electrolytes, metabolites and haemoglobin
ents bloodstream. They add to expense, increase resis- derivatives. Incorporates a series of measuring elec-
tance to flow and may cause haemolysis. They have, trodes a co-oximeter. Directly measured parameters
however, been shown to be of use in extracorporeal include pH, PO2, PCO2. Bicarbonate, standard bicarbon-
circulation. ate and base excess are derived. Inaccuracy may result
Leucodepletion filters are used in cell salvage, e.g. to from excess heparin (acidic), bubbles within the sample
remove cellular fragments, but their routine use has been and metabolism by blood cells. The latter is reduced by
questioned because of rare reports of severe hypoten- rapid analysis after taking the sample, or storage of the
sion in recipients, possibly related to release of bradyki- sample on ice. O2, CO2 and pH electrodes require regular
nin and/or other mediators when blood is passed over maintenance and two-point calibration.
filters with a negative charge. See also Blood gas interpretation; Carbon dioxide mea-
A filter capable of removing prion proteins that cause surement; Oxygen measurement; pH measurement
CreutzfeldtJakob disease is under evaluation.
Blood gas interpretation. Normal ranges are shown in
Blood flow. For any organ: Table 10.
Suggested plan for interpretation:
perfusion pressure
flow = oxygenation:
resistance - knowledge of the FIO2 is required before interpre-
thus the haemodynamic correlate of Ohms law. tation is possible.
Perfusion pressure depends not only on arterial and - calculation of the alveolar PO2 (from alveolar gas
venous pressures but also on local pressures within the equation).
capillary circulation. - calculation of the alveolararterial O2 difference.
Resistance depends on: acidbase balance:
vessel radius, controlled by humoral, neural and - identification of acidaemia or alkalaemia, repre-
local mechanisms (autoregulation). senting acidosis or alkalosis respectively.
vessel length. - identification of a respiratory component by
blood viscosity. Reduced peripherally due to plasma referring to the CO2 tension.
skimming, which results in blood with reduced hae- - identification of a metabolic component by refer-
matocrit leaving vessels via side branches. Reduced ring to the base excess/deficit or standard bicar-
in anaemia. bonate (both are corrected to a normal CO2
Flow is normally laminar; i.e. it roughly obeys the tension, thus eliminating respiratory factors).
HagenPoiseuille equation, although blood vessels are - knowledge of the clinical situation helps to decide
not rigid, arterial flow is pulsatile and blood is not an whether the respiratory or metabolic component
ideal fluid. Turbulent flow may occur in constricted represents the primary change.
74 Blood groups

solutions (the latter in about 23 times the volume of the

Table 10 Normal values (ranges or mean 2 SD) for blood gas
interpretation, for young adults breathing room air at sea level
Blood loss may be reduced by:
hypotensive anaesthesia.
Arterial pH 7.357.45
PO2 10.613.3kPa (80100mmHg) tourniquets.
PCO2 4.66.0kPa (3545mmHg) local infiltration with vasopressor drugs.
HCO3 2226mmol/l appropriate positioning, e.g. head-up for ENT
SaO2 95100% surgery.
spinal and epidural anaesthesia.
Mixed venous pH 7.327.36
Bleeding may be increased by:
PO2 4.75.3kPa (3540mmHg)
PCO2 5.66.1kPa (4246mmHg) raised venous pressure:
HCO3 2428mmol/l - raised intrathoracic pressure, e.g. due to respira-
S v O2 6080% tory obstruction, coughing, straining.
- fluid overload and cardiac failure.
- inappropriate positioning.
- venous obstruction.
See also, Blood gas analyser; Carbon dioxide measure- hypercapnia.
ment; Carbon dioxide transport; Oxygen measurement; coagulation disorders:
Oxygen transport; pH measurement - pre-existing.
- dilutional coagulopathy.
Blood groups. Each individuals red cells bear certain - incompatible blood transfusion.
antigens capable of producing an antibody response in - anticoagulant drugs.
another person. Some are only present on red cells, e.g. - DIC.
Rhesus antigens; others are also present on other tissue hypertension.
cells, e.g. ABO antigens. Immunoglobulins may be poor surgical technique.
present intrinsically, e.g. ABO and Lewis, or following See also, Blood transfusion, massive; Haemorrhage
exposure to the antigen, e.g. Rhesus; they are usually IgG
or IgM. Administration of blood cells to a recipient who Blood patch, epidural. Procedure for the relief of post-
has the corresponding antibody causes haemolysis and dural puncture headache. 1020ml of the patients blood
a severe reaction. is drawn from a peripheral vein under sterile conditions,
Minor blood groups may be important clinically fol- and injected immediately into the epidural space. Blood
lowing ABO-typed uncross-matched blood transfusion, is thought to seal the dura, thus preventing further CSF
or multiple transfusions; an atypical antibody in a recipi- leak, although cranial displacement of CSF resulting
ent makes the finding of suitable donor blood difficult. from epidural injection may also be important, at least
Minor groups include the Kell, Duffy, Lewis and Kidd initially. Maintaining the supine position for at least
systems. Many more have been described; the signifi- 24h after patching is recommended to increase the
cance of such diversity is unclear. chance of success, by reducing dislodgement of the clot
See also, Blood compatibility testing from the dural puncture site. Should be avoided if the
patient is febrile, in case of bacteraemia and subsequent
Blood loss, perioperative. Important as a guide to peri- epidural abscess. The sending of blood for culture at the
operative fluid requirements, and also as indicator of time of patching has been suggested, in case infection
potential development of a coagulation disorder related does occur.
to major haemorrhage. Effective in 70100% of cases, although symptoms
Methods of estimation: may recur in 3050%, sometimes necessitating a repeat
clinical judgement of the patients volume status. blood patch. Relief of headache may occur immediately
observation of wound and swabs. or within 24h. Spectacular results have been claimed,
weighing swabs and subtracting their dry weight. even when performed up to several months after dural
Weighing swabs may underestimate blood loss if puncture. Prophylactic use has been less consistently
fluid is lost by evaporation or soaked into drapes. successful. Complications are rare, and include transient
Overestimation may occur if saline is weighed bradycardia, back and neck ache, root pain, pyrexia, tin-
without correction. nitus and vertigo. Subsequent epidural anaesthesia is
measuring the volume removed by suction devices. thought to be unaffected.
washing of all swabs and drapes in a known volume
of water and measuring haemoglobin concentra- Blood pressure, see Arterial blood pressure; Diastolic
tion. Volume of blood lost may then be calculated. blood pressure; Mean blood pressure; Systolic blood
Measurement of potassium released from lysed pressure
cells has also been used.
measurement of blood volume. Blood products. Many products may be obtained from
Replacement with blood has been suggested if losses donated blood (Fig. 25), including:
exceed 1520% of blood volume in adults, or 10% in whole blood: stored at 26C for up to 35 days.
children, although greater losses may be allowed if the 70ml citrate preservative solution is added to
preoperative haemoglobin concentration is high. Recent 420ml blood. The use of whole blood for blood
guidelines suggest that, under stable conditions, a hae- transfusion is restricted in the UK. Heparinised
moglobin concentration of 710g/dl should be a general whole blood (lasts for 2 days) has been used for
indication for blood transfusion, depending on the cir- paediatric cardiac surgery.
cumstances. Until blood transfusion becomes neces- packed red cells (plasma reduced): stored at
sary, losses may be replaced with colloid or crystalloid 26C for up to 35 days. Should be kept at room
Blood products 75

temperature for no more than 24h. Haematocrit is or kept at room temperature and given within 4h.
approximately 0.55. Produced by removing all but Contains all clotting factors, including fibrinogen,
20ml residual plasma from a unit of whole blood and is also a source of plasma cholinesterase. Con-
and suspending the cells in 100ml SAG-M (saline tains added citrate. Viral infection risk is as for
adenineglucosemannitol) solution to give a mean whole blood. In the UK, one unit of FFP is derived
volume per unit of 280ml. Since 1998, routinely from plasma from a single donor, and FFP for chil-
depleted of leucocytes to decrease the risk of trans- dren born after 1995 is derived from unpaid US
mitting variant CreutzfeldtJakob disease. One unit donors. Indicated for treatment of various coagu-
typically increases haemoglobin concentration in a lopathies e.g. multifactor deficiencies associated
70-kg adult by 1g/dl. with major haemorrhage and/or DIC. One adult
microaggregate-free blood: leucocytes, platelets therapeutic dose is 1215ml/kg or 4 units for a
and debris removed (i.e. the buffy coat). Used 70-kg adult, and would typically increase the fibrin-
to prevent reactions to leucocyte and platelet ogen concentration by 1g/l.
antigens. cryoprecipitate: obtained by controlled thawing of
leucocytes: separated from blood donated by FFP to precipitate high-molecular-weight proteins
patients whose leucocyte count has been increased (e.g. factor VIII, fibrinogen and von Willebrands
by pretreatment with corticosteroids, or those with factor). Frozen and stored at 20C; thawed imme-
chronic granulocytic leukaemia. diately before use. Indicated for the treatment of
frozen blood: used by the armed forces but too ongoing bleeding in the presence of low fibrinogen
expensive and time-consuming for routine use. levels (< 1g/l). A typical adult dose is two 5-unit
Glycerol is added to prevent haemolysis. Requires pools, in total containing 36g fibrinogen in 200
thawing and washing. May be stored for many 500ml; this would increase fibrinogen levels by
years. ~1g/l. Viral infection risk is as for whole blood.
platelets: stored at 22C for up to 5 days. Obtained human albumin solution (HAS; previously called
either from a single donor by plateletpheresis plasma protein fraction, PPF): stored at room
(one donation yielding 13 therapeutic dose units) temperature for 25 years depending on the prepa-
or from multiple units of donated whole blood ration. Heat-treated to kill viruses. Contains virtu-
(one unit of platelets derived from four donors). ally no clotting factors. Available as 4.5% and
Transfusion thresholds vary according to the clinical 20% (salt-poor albumin) solutions; both contain
situation, the level of platelet function and labora- 140150mmol/l sodium but the latter contains less
tory evidence of coagulopathy, but typically include sodium per gram of albumin. Licensed for blood
a platelet count of 50 109/l or less for surgery, volume expansion with or without hypoalbuminae-
unless platelet function is abnormal. One therapeu- mia. Use is controversial owing to its high cost and
tic dose unit (approximate volume 210310ml) nor- the absence of evidence demonstrating its superior-
mally increases the platelet count by 2040 109/l, ity to other colloids. UK supplies are now sourced
although some patients may exhibit refractoriness from the USA.
(e.g. those with circulating antiplatelet antibodies). factor concentrates, e.g. VIII and IX: now obtained
Filtered by microfilters; ordinary iv giving sets are by recombinant gene engineering, removing the risk
suitable. Preferably should be ABO-compatible. of viral infection. Recombinant activated factor VII
Contains added citrate. (rFVIIa) is licensed for the treatment of patients
fresh frozen plasma (FFP): stored at 30C for up with acquired or congenital haemophilia, von
to 2 years. Must be ABO-compatible. Once thawed, Willebrands disease and inhibitors to factors VIII
can be stored at 4C and must be given within 24h, or IX of the clotting cascade. Factor VIIa enhances

Whole blood


Frozen red cells Packed red cells Platelet-rich plasma

Freezing/microfiltration Centrifuge 20C

Leucocyte-poor red cells Leucocytes Plasma Platelets

Freezing 20C FFP

70C and rapid thawing

Cryoprecipitate Supernatant

Factor IX
Factor VIII
Products obtained from pooled plasma Albumin

Fig. 25 Blood products available from whole blood

76 Blood storage

thrombin generation on the surfaces of activated transfused within 4h or discarded. Details of each unit
platelets, thus having a mainly local effect with little given and the total volume transfused should be recorded
impact on systemic coagulation. Increasingly used in the patients notes and/or anaesthetic record.
off-licence for arresting major traumatic, surgical See also, Blood products; Blood transfusion
and obstetric haemorrhage, although use is restricted
owing to extremely high cost. Blood substitutes, see Blood, artificial
See also, Blood, artificial; Blood storage
Blood tests, preoperative, see Investigations,
Blood storage. Viability of red cells is defined as at least preoperative
70% survival 24h post-transfusion.
The following occur in stored blood: Blood transfusion. Reports of transfusion between
reduced pH, as low as 6.77.0, mainly due to high animals, and between animals and humans, date from the
PCO2. seventeenth century. Transfusions between humans were
increased lactic acid. performed in the early nineteenth century. Adverse
increased potassium ion concentration, up to reactions in recipients, and clotting of blood, were major
30mmol/l. problems. ABO blood groups were discovered in 1900;
reduced ATP and glucose consumption. improvements in blood compatibility testing and antico-
shift to the left of oxyhaemoglobin dissociation agulation followed.
curve (ValtisKennedy effect). In the UK, NHS Blood and Transplant, a Special
reduced 2,3-DPG levels. Health Authority, relies on voluntary donors, and is
reduced viability of other blood constituents, e.g. increasingly hard-pressed to meet demand for blood
platelets and leucocytes, and formation of microag- products. Perioperative use accounts for about 50% of
gregates. Coagulation factors V and VIII are almost total blood usage. Recent guidelines suggest that, under
completely destroyed, XI is reduced, and IX and X stable conditions, a perioperative haemoglobin concen-
are reduced after 7 days. tration of 710g/dl should be maintained, depending on
Storage solutions: the circumstances.
SAG-M (saline 140mmol/l, adenine 1.5mmol/l, Complications of transfusion:
glucose 50mmol/l and mannitol 30mmol/l). The immunological (reactions are associated with 2% of
standard solution used in the UK. Used to resus- all transfusions):
pend concentrated red cells after removal of plasma - immediate haemolysis (e.g. ABO incompatibil-
from CPD anticoagulated blood (see below), allow- ity). Incidence is 1in 2500001 000000. Features
ing a greater amount of plasma to be removed for include rapid onset of fever, back pain, skin rash,
other blood products. Has similar preserving prop- hypotension and dyspnoea. DIC and renal failure
erties to CPD-A. Mannitol prevents haemolysis. may occur. Hypotension and increased oozing
BAGPM (bicarbonate-added glucosephosphate of blood from wounds may be the only indication
mannitol) is similar. of incompatible transfusion in an anaesthetised
ACD (acidcitratedextrose): trisodium citrate, patient. Immediate treatment is as for anaphy-
citric acid and dextrose. Introduced in the 1940s. laxis, although the underlying mechanisms are
Red cell survival is 21 days. 2,3-DPG is greatly different. Samples of recipient and donor blood
reduced after 7 days. should be taken for analysis. Mortality is up to
CPD (citratephosphatedextrose): citrate, sodium 50%. Most cases arise from clerical errors (e.g.
dihydrogen phosphate and dextrose. Described in incorrect labelling or administration to the wrong
the late 1950s. Red cell survival: 28 days. 2,3-DPG patient).
is greatly reduced after 14 days. - delayed haemolysis (e.g. minor groups). Usually
CPD-A. Addition of adenine increases red cell ATP occurs 710 days after transfusion, with fever,
levels. Red cell survival: 35 days. 2,3-DPG is low anaemia and jaundice. Renal failure may occur.
after 14 days. Used for whole blood. - reactions to platelets and leucocytes (HLA anti-
Storage at 26C is optimum for red cells but reduces gens). Slow onset of fever, dyspnoea and tachy-
platelets and clotting factors. 22C is optimum for plate- cardia; shock is rare.
lets (survival time 35 days). Freezing of blood is expen- - reactions to donor plasma proteins (often IgA).
sive and time-consuming, but allows storage for many May cause anaphylaxis. Transfusion-related
years. It requires 2h of thawing, and removal of glycerol acute lung injury (TRALI), a form of ALI
(used to prevent haemolysis). caused by donor antibodies reacting with recipi-
After rewarming and transfusion, potassium is taken ent leucocyte antigens and defined as occurring
up by red cells. 2,3-DPG levels are restored within 24h. within 6h of transfusion, occurs in 1:500010000
Plastic collection bags, permeable to CO2 without transfusions.
altering the blood itself, were introduced in the 1960s. - graft-versus-host disease in immunosuppressed
In the closed triple-bag system, blood passes from patients.
the donor to the first collection bag, from which plasma - febrile reactions of unknown aetiology, with or
and red cells are passed into separate bags if required. without urticaria.
The closed system prevents exposure to air and - infusion of Rhesus-positive blood into Rhesus-
infection. negative women of child-bearing age may cause
Before transfusion, the correct identity of the unit of haemolytic disease of the newborn in future
blood (including expiry date) and the patient must be pregnancies.
confirmed (by checking against an identification band). - increased tumour recurrence has been reported
The integrity of the bag should be checked. Blood left in patients undergoing surgery for colonic, ovarian
out of the fridge for more than 30min should be and prostatic cancer, who receive perioperative
Blood transfusion 77

Table 11 Exclusions and screening applying to donation of blood (NB primarily applies to the UK, though similar procedures apply to other
Western countries)

Donors excluded Blood screening Comments

Brucellosis Past history of infection

Cytomegalovirus For immunocompromised About 55% of the population are
(CMV) patients only CMV-positive
Glandular fever Infection within last 2 years
Hepatitis Hepatitis or jaundice within last year Hepatitis B surface antigen: No carrier state for hepatitis A, therefore
Acupuncture (unless by registered routine not screened for
practitioner), tattoo or other skin Hepatitis C antibodies/RNA: If post-transfusion hepatitis occurs,
piercing within 6 months routine the donor may be traced and further
Risk of transmission ~1:500000 units
for hepatitis B and 1:32 million for
hepatitis C
HIV At-risk groups: either permanent (iv drug HIV-1 and HIV-2 antibodies: Risk of transmission ~1:45 million units
users, sex workers, previous HIV-positive routine
test) or within 1 year of sex with
someone from an at-risk group
HTLV-I Past history of infection Antibodies: routine Infection may result in adult T-cell leukaemia
Malaria Visit to endemic areas within last 6 months,
with only plasma collected for next 5
years unless cleared by antibody testing
vCJD Recipients of: transfusion in the UK after Leucodepletion (removal of white cells) of
1980; iv immunoglobulins prepared from all blood components
UK plasma; human pituitary extract Plasma for fractionation to make plasma
Donors whose blood has been tranfused to derivatives imported from outside the UK
recipients who later develop vCJD FFP for patients < 16 years old imported
without other explanation from outside the UK
Family member with vCJD A filter that removes the prion protein
responsible for vCJD is under investigation
Syphilis Past history of infection Antibodies: routine
Others Blood donation within last 12 weeks Trypanosoma cruzi antibodies
Chesty cough, sore throat, active cold sore and West Nile virus RNA
or any infection within last 2 weeks if recent travel to
Antibiotic medication within last week endemic areas
Currently pregnant or 9 months

HTLV-I, human T-cell leukaemia and lymphoma virus type I; vCJD, variant CreutzfeldtJakob disease.

transfusion, possibly via immunosuppression due - citrate toxicity: citrate is normally metabo-
to transfused leucocytes. Leucodepleted blood lised to bicarbonate within a few minutes. Rapid
has been suggested as a better alternative to transfusion of citrated blood may cause hypo
whole blood, if transfusion is absolutely necessary calcaemia, and calcium administration may be
in these groups. required. Alkalosis may follow citrate metabolism
infective: transmission of infective agents is reduced/ to bicarbonate. With the modern practice of using
prevented by excluding certain groups from donat- SAG-M (salineadenineglucosemannitol) solu-
ing blood, and screening donated blood (Table 11). tion, citrate toxicity is rare unless large volumes
Bacterial contamination of donor units, typically of plasma or platelet preparations are given, since
with Gram-negative organisms, e.g. pseudomonas these do contain citrate.
or coliforms, may result in fever and cardiovascular - acidosis due to transfused blood is rarely a
collapse. Risk is 1 in 500000 units transfused. problem (see above).
Platelet concentrates harbouring staphylococcus, circulatory overload and cardiac failure. More likely
yersinia and salmonella have been reported. Risk is in the elderly, and in the correction of chronic
about 1 in 50000. anaemia. Diuretics (e.g. furosemide 40mg) may be
metabolic: given with transfusion.
- hyperkalaemia: rarely a problem, unless with hypothermia. Rapid infusion of cold blood may
rapid transfusion in hyperkalaemic patients, as cause cardiac arrest. All transfused blood should be
potassium is rapidly taken up by red cells after warmed, especially when infused rapidly. Excessive
infusion and warming. heat may cause haemolysis.
78 Blood transfusion, autologous

in the ICU, recent evidence suggests that lowering impaired O2 delivery to tissues.
the threshold for transfusion from 10g/dl to 7g/dl impaired coagulation. Fresh frozen plasma and
may decrease mortality, organ dysfunction and platelets should be given only when there is clinical
cardiac complications. and laboratory evidence of abnormal coagulation.
impaired O2 delivery to tissues, due to the leftward hypothermia.
shift of oxyhaemoglobin dissociation curve in stored hypocalcaemia (if rapid transfusion).
blood that lasts up to 24h. In addition, red cells in hyperkalaemia may occur, although this is rarely a
stored blood are thought to be more likely to cause problem; hypokalaemia may follow potassium
blockage of capillaries owing to their reduced phys- uptake by red cells.
ical flexibility, further impairing O2 delivery. metabolic acidosis may occur initially; alkalosis may
impaired coagulation caused by dilution and/or follow as citrate is metabolised to bicarbonate (rare
consumption of circulating clotting factors and with modern blood products).
platelets. DIC is rare. hypovolaemia or fluid overload.
microaggregates (see Blood filters). ARDS may follow many situations where large
thrombophlebitis and extravasation. blood transfusions are required.
air embolism. Sihler KC, Napolitano LM (2010). Chest; 137: 20920
iron overload (chronic transfusions). See also, Blood products; Blood storage
interaction when stored blood is administered
following iv fluids, e.g. clotting (gelatin solu- Blood urea nitrogen (BUN). Nitrogen component of
tions, Hartmanns solution), haemolysis (dextrose blood urea. Gives an indication of renal function in a
solutions). similar way to urea measurement. Normally 1.5
Klein HG, Spahn DR, Carson JL (2007). Lancet; 370: 3.3mmol/l (1020mg/dl).
See also, Blood groups; Blood storage; Blood transfusion, Blood volume. Total blood volume is approximately
massive; Intravenous fluid administration; Rhesus blood 70ml/kg in adults, 80ml/kg in children and 90ml/kg in
groups neonates (although the latter may vary widely, depend-
ing on how much blood is returned from the placenta at
Blood transfusion, autologous. Transfusion of a birth. The formula: [% haematocrit + 50]ml/kg has been
patients own blood. Interest in it has increased over the suggested for neonates).
last two decades because of the risks of infection and Distribution (approximate):
transfusion reactions, and an increasing shortfall between 6070% venous
the demand and supply of donated blood. 15% arterial
Different methods used: 10% within the heart
26 units are taken over a period of days or 5% capillary.
weeks before surgery. Concurrent oral iron therapy Measured by dilution techniques; plasma volume is
ensures an adequate bone marrow response. Eryth- found by injecting a known dose of marker (e.g. albumin
ropoietin has been used. Pretransfusion testing labelled with dyes or radioactive iodine) into the blood
varies between centres, from ABO grouping to full and measuring plasma concentrations. Rapid exchange
cross-matching. Labelling of blood must be meticu- of albumin between plasma and interstitial fluid leads to
lous and this requirement, together with wastage of slight overestimation using this method; larger mole-
unused blood (which may be up to 20%), results cules, e.g. immunoglobulin, may be used.
in the administration costs being higher than for
Total blood volume
allogeneic transfusion. Only suitable for elective
surgery. 100
= plasma volume
perioperative haemodilution: simultaneous collec- 100 %haematocrit
tion of blood and replacement of removed volume
Red cell volume may be found by labelling erythrocytes
with colloid or crystalloid. The collected blood is
with radioactive markers, e.g. 51Cr.
available for transfusion when required, usually
during or shortly after blood loss has stopped.
peri- or postoperative retransfusion of blood sal-
Bloody tap, see Epidural anaesthesia
vaged from the operation site during surgery.
Washing and filtering remove debris and contami- Blow-off valve, see Adjustable pressure-limiting valve
nants. Methods range from simple closed collecting/
reperfusion systems to expensive centrifuging BMI, see Body mass index
machines (the latter referred to as cell salvage).
Ashworth A, Klein AA (2010). Br J Anaesth; 105: BMR, see Basal metabolic rate
See also, Blood transfusion Bodok seal. Metal-edged rubber bonded disk, used to
prevent gas leaks from the cylinder/yoke interface on
Blood transfusion, massive. Definitions vary but anaesthetic machines.
transfusion of 10 units of blood within 6h. Body mass index (BMI). Indication of body fat derived
transfusion of 5 units of blood within 1h. from a persons weight and height: BMI = weight (kg)
replacement of blood volume with transfused blood height (m)2. Widely used as a measure of obesity,
within 24h. although it doesnt account for body build and muscle
Adverse effects are those of blood transfusion gener- mass. Also used to refer to degrees of underweight. Has
ally; in particular: been incorporated into most international and national
Bone marrow harvest 79

Bohr effect. Shift to the right of the oxyhaemoglobin

Table 12World Health Organization classification of obesity dissociation curve associated with a rise in blood PCO2
according to body mass index (kg/m2)
and/or fall in pH. Results in lower affinity of haemoglo-
Underweight < 18.5 bin for O2, favouring O2 delivery to the tissues, where
CO2 levels are high.
Normal 18.524.99 The double Bohr effect refers to pregnancy, when
Overweight 25.029.9 CO2 passes from fetal to maternal blood at the placenta,
Obese: class I 30.034.9 causing the following changes:
class II 35.039.9 maternal blood: CO2 rises, i.e. shift of curve to right
class III 40.0 and reduced O2 affinity.
fetal blood: CO2 falls, i.e. shift of curve to left and
increased O2 affinity.
The net effect is to favour O2 transfer from maternal to
classifications of obesity (Table 12), although some fetal blood.
national variations in definitions exist. [Christian Bohr (18551911), Danish physiologist]
See also, Oxygen transport
Body plethysmograph. Airtight box, large enough to
enclose a human, used to study lung volumes and pres- Bohr equation. Equation used to derive physiological
sures. Once a subject is inside, air pressure and volume dead space.
may be measured before and during respiration. Expired CO2 = inspired CO 2 + CO2 given out by lungs,
May be used to measure: or: FE VT = (FI VT ) + (FA VA )
FRC: the subject makes inspiratory effort against a
where FE = fractional concentration of CO2 in expired
shutter. Box volume is decreased due to lung expan-
sion, and box pressure increased because of the
FI = fractional concentration of CO2 in inspired
decrease in volume. Applying Boyles law:
original pressure volume FA = fractional concentration of CO2 in alveolar
= new pressure new volume gas
where new volume = original volume change in VT = tidal volume
lung volume. VA = alveolar component of tidal volume.
Thus change in lung volume may be calculated. If
Since inspired CO2 is negligible, it may be ignored:
airway pressures are also measured:
i.e. FE VT = FA VA
original airway pressure resting lung volume
= new airway pressure new lung volume But VA = VT VD, where VD = dead space
where resting lung volume = FRC
and new volume = FRC + change in lung volume FE VT = FA (VT VD )
= (FA VT ) (FA VD )
Thus FRC may be calculated.
airway resistance: or: FA VD = (FA VT ) (FE VT )
= VT (FA FE )
alveolar pressure mouth pressure
airflow Therefore =
The subject breathes the air in the box. Box volume
is reduced by the change in alveolar volume during Since partial pressure is proportional to concentration:
inspiration, measured as above. Lung volume may VD PA CO2 PECO2
be measured at the same time, as above: =
lung volume starting alveolar pressure where PACO2 = alveolar partial pressure of CO2
= new lung volume new alveolar pressure; PECO2 = mixed expired partial pressure of CO2
where starting alveolar pressure = box pressure, and
Since alveolar PCO2 approximately equals arterial PCO2,
new lung volume = lung volume + alveolar volume
Alveolar pressure may thus be calculated. Also, =
mouth pressure = box pressure, and flow may be VT Pa CO2
measured using a pneumotachograph. where PaCO2 = arterial partial pressure of CO2.
pulmonary blood flow: the subject breathes from a
See also, Bohr effect
bag containing N2O and O2 within the box. As the
N2O is taken up by the blood, the volume of the Boiling point (bp). Temperature of a substance at which
bag decreases. Since N2O uptake is flow-limited its SVP equals external atmospheric pressure. Addi-
(see Alveolar gas transfer), uptake occurs in steps tional heat does not raise the temperature further, but
with each heartbeat. The decrease in bag size provides the latent heat of vaporisation necessary for the
therefore occurs in steps, and is calculated by mea- liquid to evaporate. If external pressure is raised, e.g.
suring bag pressure, and box volume and pressure. within a pressure cooker, bp is also raised; thus the
If the N2O-carrying capacity of blood is known, maximal temperature attainable is raised, and food
pulmonary blood flow may be calculated and dis- cooks more quickly.
played as a continuous trace showing pulsatile flow.
Bone marrow harvest. Taking of bone marrow for
Body surface area, see Surface area, body bone marrow transplantation, from either a healthy
80 Bone marrow transplantation

donor (allograft) or the patient recipient before radio- may be especially prolonged after allogeneic
or chemotherapy (autograft). Usually performed under transplantation, when prolonged immunosup-
general anaesthesia, especially in children, although pressive therapy is required. Antibacterial and
local anaesthetic techniques may be used. antiviral drugs are often given prophylactically;
Anaesthetic considerations: immunoglobulins have also been used (see
preoperatively: Immunoglobulins, intravenous). Blood products
- allografts: donors are usually fit. are often required to restore red cell, white
- autografts: usually performed for blood malig- cell and platelet numbers. Recently, macrophage
nancy; i.e. patients may be anaemic or thrombo- and granulocyte colony-stimulating factors have
cytopenic and prone to infections. Cardiovascular, been used.
respiratory and renal function may be impaired. rejection: may require repeat transplantation.
Drug treatment may include cytotoxic drugs and graft-versus-host disease.
corticosteroids. interstitial pneumonitis may occur; it may be unclear
perioperatively: whether this is related to cytomegalovirus or other
- marrow is usually taken from the posterior atypical infection, or directly related to radiother-
and anterior iliac crests and sternum, requiring apy. Mortality is up to 80%.
positioning first supine, then prone, although
the lateral position may suffice. Tracheal intuba- Boott, Francis (17921863). US-born London physician;
tion and IPPV are usually employed. Avoid- qualified in Edinburgh. Having read a letter from Big-
ance of N2O has been suggested, but this is elows father about Mortons demonstration of diethyl
controversial. ether, he arranged a dental extraction by Robinson (who
- large-bore iv cannulation is required, since there also administered the ether) on 19 December 1846 at his
may be large volume losses. Autologous blood house in Gower Street, London (now a nursing home
transfusion is usually performed, especially for and formerly the location of part of the FCAnaes exami-
allografts. Non-autologous blood is irradiated nation). He then informed Liston, who operated using
before transfusion to kill any leucocytes present. ether 2 days later.
The volume of marrow harvested is up to 2030% [James Robinson (18131861), English dentist]
of estimated blood volume, to provide the required Ellis RH (1977). Anaesthesia; 32: 197208
leucocyte count.
- heparin may be given to stop the marrow clotting; Bosentan monohydrate. Endothelin receptor antago-
it may also protect against fat embolism, which nist (both type A and type B) licensed as a treatment for
may occur during harvesting. pulmonary hypertension. Decreases both pulmonary
postoperatively: large volumes of iv fluids are often and systemic BP without affecting heart rate. May cause
required. hepatic impairment. Sitaxsentan is similar but has greater
action at type A receptors and is less hepatotoxic.
Bone marrow transplantation. Performed for leukae-
mias, lymphomas, certain solid tumours, and various Bosun warning device, see Oxygen failure warning
non-malignant disorders including aplastic anaemia, devices
haemoglobinopathies and rare genetic diseases. Involves
donation of bone marrow (usually under general anaes- Botulinum toxins. Group of exotoxins responsible for
thesia), and its subsequent infusion via a central vein botulism. Act on presynaptic cholinergic nerve terminals
into the recipient, whose own bone marrow has been blocking release of acetylcholine. Eight have been char-
ablated with chemotherapy + radiotherapy. acterised (labelled AH), each produced by a distinct
May be one of three types: strain of Clostridium botulinum. Types A, B and E
autologous: the recipients own bone marrow is (rarely, F and G) cause disease in humans. Types A and
taken and treated to remove neoplastic cells before B have been used therapeutically in minute quantities in
being frozen and stored while ablation is performed. order to cause selective muscle weakness that may last
Mortality is up to 10%. for several months, e.g. in strabismus, blepharospasm,
syngeneic: the donor and recipient are identical hemifacial spasm, torticollis, dystonias, spasmodic dys-
twins. Treatment of the collected cells is not phonia and as a cosmetic procedure. Also used as a tool
required. to investigate neurotransmitter function.
allogeneic: the donor is HLA-matched as closely
as possible to the recipient; they usually come from Botulism. Clinical syndrome caused by ingestion of
the same family or racial group. Mortality is up exotoxins (botulinum toxins) produced by the anaerobic
to 30%. Gram-positive bacillus Clostridium botulinum. Exotoxin
Problems occur with all three types but to different binds irreversibly to cholinergic nerve endings, prevent-
extents, and may be related to: ing acetylcholine release. Affects the neuromuscular
the procedure itself: junction, autonomic ganglia and parasympathetic post-
- ablative therapy includes cyclophosphamide, ganglionic fibres. Classified according to the source of
busulfan and other cytotoxic and immuno infection:
suppressive drugs. Toxic effects include vomiting, foodborne botulism: caused by ingestion of Clos-
cardiomyopathy, convulsions, pulmonary fibrosis, tridium spores or exotoxin produced under anaero-
GIT mucositis and hepatic veno-occlusive disease. bic conditions (e.g. home canning).
- impaired bone marrow function: bacterial, viral, wound botulism: due to contamination of surgical
fungal and pneumocystis infections may be prob- or other wounds. Also seen in drug abusers
lems in the first 46 months after autologous injecting black-tar heroin subcutaneously (skin-
and syngeneic transplantation; immunodeficiency popping).
Brachial plexus 81

infant botulism: due to absorption of exotoxin pro- Treatment:

duced within the GIT, classically after eating con- supportive measures, including antibacterial drugs,
taminated honey. restoration of cardiac output vasodilator drugs.
adult infectious botulism: similar to the infant form intra-arterial infusion of vasodilators, e.g. papaver-
but follows GIT surgery. ine 3060mg/h, has been used via the angiography
inadvertent botulism: follows accidental overdose catheter.
of botulinum toxin given for treatment of move- surgery to resect necrotic bowel remove embolus
ment disorders (e.g. dystonia). or thrombus.
Features occur within 1272h:
nausea, vomiting and abdominal pain. Boyle, Henry Edmund Gaskin (18751941). English
symmetrical descending paralysis initially affecting anaesthetist, best known for the anaesthetic machine
cranial nerves, with diplopia, facial weakness, dys- named after him. Originally introduced in 1917, it con-
phagia, dysarthria, limb weakness and respiratory sisted of N2O and O2 cylinders, pressure gauges, water-
difficulty. sight flowmeters and ether vaporiser (Boyles bottle)
autonomic disturbance: ileus, unresponsive pupils, set in a wooden case. Being left-handed, he placed all
dry mouth, urinary retention. controls on the left side of the machine, a practice that
sensory deficit, mental disturbance and fever do not continues today. His name is also attached to the instru-
occur. ment used to maintain jaw opening during tonsillectomy
Diagnosed by inoculation of the patients serum into (BoyleDavis gag). Boyle practised at St Bartholomews
mice that have been treated or untreated with antitoxin. Hospital, London, was involved in the advancement and
Different strains of toxin may be identified. EMG improvement of anaesthesia in the UK, and performed
studies may aid diagnosis while waiting for inoculation much work into the use of N2O, including under battle
studies. conditions.
[John S Davis (18241885), US surgeon]
supportive. IPPV may be necessary. Hadfield CF (1950). Br J Anaesth; 22: 10717
wound debridement if indicated.
antitoxin to neutralise circulating exotoxin. Hyper-
Boyles law. At constant temperature, the volume of
sensitivity may occur. A human botulism immuno-
a fixed mass of a perfect gas varies inversely with
globulin is used for treatment of infant botulism and
those allergic to the antitoxin.
[Robert Boyle (16271691), English chemist]
penicillin to kill live bacilli.
See also, Charles law; Ideal gas law
Complete recovery may take months.
See also, Biological weapons, Paralysis, acute
Brachial artery. Continuation of the axillary artery,
Bougie, see Intubation aids running from the lower border of teres minor to the
antecubital fossa, where it divides into the radial and
Bourdon gauge, see Pressure measurement ulnar arteries. Lies at first medial, then anterior to the
humerus. Around its midpoint, crossed from lateral to
Bovie machine, see Diathermy medial by the median nerve. Protected from the medial
cubital vein in the antecubital fossa by the bicipital apo-
Bowditch effect. Intrinsic regulatory mechanism of neurosis. Occasionally divides in the upper arm.
cardiac muscle in response to increased rate of stimula- May be used for arterial cannulation, although seldom
tion. As rate increases, contractility increases. Also called as the site of first choice because of possible distal
the treppe effect. ischaemia.
[Henry Bowditch (18401911), US physiologist; Treppe,
German for steps] Brachial plexus. Nerve plexus supplying the arm. Arises
from the ventral rami of the lower cervical and first
Bowel ischaemia. May affect any part of the GIT thoracic spinal nerves, and emerges between the scalene
(although rarely stomach) but usually affects the large muscles in the neck. The plexus invaginates the scalene
bowel. May be caused by thrombus, embolism (e.g. from fascia and passes down over the first rib (Fig. 26a). It
mural thrombus after MI), vascular spasm or low mes- accompanies the subclavian artery (which becomes the
enteric perfusion with vasoconstriction (non-occlusive axillary artery) within a perivascular sheath of connec-
mesenteric ischaemia [NOMI]). May occur in patients tive tissue.
with intra-abdominal pathology, especially following Anatomy of the scalene muscles:
vascular surgery, or in any patient with low cardiac scalenus anterior arises from the anterior tubercles
output. May also occur in severe intestinal obstruction. of the 3rd6th cervical transverse processes, and
Vasoconstriction often persists after correction of the inserts into the scalene tubercle on the first rib.
initial insult. Bowel infarction may follow as a result of scalenus medius arises from the posterior tubercles
reduced tissue oxygenation or reperfusion injury. of the 2nd6th cervical transverse processes and
Associated with high mortality because diagnosis inserts into the first rib behind the groove for the
may be difficult, and bowel infarction may continue subclavian artery.
despite treatment. Gastric tonometry has been used to scalenus posterior is the portion of the previous
monitor GIT perfusion in critical illness. muscle attached to the second rib.
Features include abdominal pain and distension, GIT The roots lie in the interscalene groove; the trunks
bleeding, nausea and vomiting, tachycardia, pyrexia, leu- cross the posterior triangle of the neck; the divisions
cocytosis and metabolic acidosis. Angiography may be lie behind the clavicle; the cords lie in the axilla.
useful to diagnose ischaemia and differentiate its causes. Branches arise at different levels (Fig. 26b):
82 Brachial plexus

roots: nerves to the rhomboids, scalene muscles and - medial:

serratus anterior (long thoracic nerve), and a con- - medial pectoral nerve to pectoralis major and
tribution to the phrenic nerve (C5). minor.
trunks: nerve to subclavius, and the suprascapular - medial cutaneous nerves of the arm and forearm:
nerve (to supraspinatus and infraspinatus). supply the medial aspect of the upper arm and
cords: forearm respectively.
- lateral: - ulnar nerve.
- lateral pectoral nerve to pectoralis major. - medial part of median nerve.
- musculocutaneous nerve: passes through the - posterior:
belly of coracobrachialis in the upper arm, sup- - subscapular nerves to subscapularis and teres
plying coracobrachialis, biceps and brachialis major.
muscles and the elbow joint. Continues as the - nerve to latissimus dorsi.
lateral cutaneous nerve of the forearm, supply- - axillary nerve: passes posterior to the neck of
ing the radial surface of the forearm. the humerus. Supplies deltoid and teres minor
- lateral part of the median nerve. and the shoulder joint, and continues as the


Cervical vertebrae


Scalenus medius muscle
C4 Scalenus anterior muscle
C5 Brachial plexus
Subclavian artery

Subclavian vein

1st rib 2nd rib

Roots Trunks Divisions Cords

To rhomboids
Suprascapular Lateral pectoral pectoralis major
Upper Lateral

To subclavius Musculocutaneous

Middle Posterior
C7 Radial Median

To latissimus dorsi
Subscapular Ulnar
Lower Medial
Medial cutaneous of forearm
Medial cutaneous of arm
T1 Medial pectoral

Long thoracic

Fig. 26 (a) Relations of the upper brachial plexus.

Brachial plexus block 83

Anterior Posterior

Upper lateral cutaneous n Upper lateral cutaneous n

of the arm (from axillary nerve) of the arm

Lower lateral cutaneous n Medial cutaneous n Posterior cutaneous n of the

of the arm (from radial nerve) of the arm arm (from radial nerve)

Lateral cutaneous n of forearm Medial cutaneous n Lateral cutaneous n

(from musculocutaneous nerve) of the forearm of the forearm

Radial nerve Radial nerve

Ulnar nerve

Median nerve

Fig. 26 (Continued) (b) Plan of the brachial plexus. (c) Cutaneous nerve supply of the arm

upper lateral cutaneous nerve of the arm, - produces adequate block for shoulder
supplying the skin of the outer shoulder. manipulations.
- radial nerve. - ulnar nerve may be missed.
The plexus thus supplies the skin of the upper limb - complications include phrenic nerve block, recur-
(Fig. 26c). rent laryngeal nerve block, Horners syndrome,
Characteristic motor lesions of the plexus: inadvertent epidural or spinal block and injection
upper roots: waiters tip position; arm internally into the vertebral artery. Bilateral blocks, or
rotated and pronated, with wrist flexed (Erbs blocks in patients with contralateral phrenic nerve
paralysis). palsy, should be avoided.
lower roots: claw hand (Klumpkes paralysis). supraclavicular:
[Wilhelm Erb (18401921), German physician; Augusta - with the patients head turned away from the side
Klumpke (18591927), French neurologist] to be blocked, a needle is inserted immediately
See also, Brachial plexus block; Dermatomes posterior and lateral to the subclavian pulsation
behind the mid-clavicle. In the classic technique,
Brachial plexus block. May be performed by injecting it is directed caudally, medially and posteriorly to
local anaesthetic solution into the fascial compartment the upper surface of first rib, and walked along
surrounding the brachial plexus at several levels. Needle the rib until the needle position is confirmed;
placement is routinely guided by use of a nerve stimula- 810ml solution is injected per division.
tor (eliciting contractions in the appropriate muscle - median nerve may be missed.
group) or ultrasound imaging: - complications: phrenic and recurrent laryngeal
interscalene: nerve blocks, Horners syndrome, subclavian
- with the patients head turned away from the side puncture, pneumothorax. Bilateral blocks should
to be blocked, a needle is inserted in the intersca- be avoided.
lene groove, lateral to the sternomastoid, and subclavian perivascular:
level with the cricoid cartilage. It is directed - with the patients head turned away from the side
towards the transverse process of C6 (medially, to be blocked, a needle is inserted in the intersca-
caudally and posteriorly). Accidental epidural, lene groove, caudal to the level of the cricoid
intrathecal or intravascular injections are more cartilage, and cranial and posterior to a finger pal-
likely if the needle is directed cranially. pating the subclavian artery. It is directed caudally
- 3040ml solution is injected when the needle only, until the needle position is confirmed (for
position is confirmed. If a nerve stimulator is used, nerve stimulation, contractions elicited in the
contractions should be sought in the shoulder, arm/hand, not in the shoulder, which may be
arm or forearm. caused by stimulation of the suprascapular nerve).
84 Bradycardia

- 2030ml solution is injected. been described, with injection of 2040ml solu-

- complications: as for supraclavicular block, but tion at a depth of 57cm. Horners syndrome is
pneumothorax is less likely. common; difficulty breathing may also occur and
axillary: epidural and spinal blockade have been reported.
- with the patients head turned away, the arm Suitable solutions:
abducted to 90 and the hand under the head, a prilocaine or lidocaine 11.5% with adrenaline:
needle is inserted just above the axillary artery onset within 2030min and lasts for 1.52h.
pulsation, as high in the axilla as possible. A click bupivacaine 0.3750.5%: onset up to 1h; lasts for
is felt as the perivascular sheath is entered. up to 12h. Combination with 1% lidocaine speeds
- 2550ml solution is injected, with digital pres- onset.
sure or a tourniquet below the injection site to The area blocked is increased by using larger volumes
encourage upward spread of solution. Careful of solution. Motor block is increased by increasing con-
aspiration before application of digital pressure centration, and intensity of block by increasing total
excludes placement of the needle in the axillary dose. Although maximal safe doses have been exceeded
vein. The arm is returned to the patients side without serious effects or high blood levels of agent, this
after injection, to avoid compression of the proxi- cannot be recommended routinely. Systemic uptake of
mal sheath by the humeral head, or before injec- agent is greatest following interscalene block, and least
tion if a cannula technique is used. following axillary block. Incidence of neurological
- a cannula, e.g. iv type 1820G, may be inserted damage is thought to be reduced by using short bevelled
and used for repeated injection. needles, and using a nerve stimulator rather than elicit-
- may miss the musculocutaneous and axillary ing paraesthesia as the end-point for localisation.
nerves. See also, Regional anaesthesia
The former may be blocked thus:
- upper arm: at the time of axillary block, 510ml Bradycardia, see Heart block; Junctional arrhythmias;
is injected above the perivascular sheath, into Sinus bradycardia
coracobrachialis muscle. Bradykinin, see Kinins
- elbow: 10ml is injected in the groove between
biceps tendon and brachioradialis in the ante- Brain. Intracranial part of the CNS. Forms from
cubital fossa, and infiltrated subcutaneously tubular neural tissue, developing into hindbrain (rhomb-
around the lateral elbow. encephalon), midbrain (mesencephalon) and forebrain
the intercostobrachial nerve, supplying the inner (prosencephalon):
upper arm, may be blocked by superficial infiltra- hindbrain:
tion as the needle is withdrawn from the axillary - medulla: continuous with the spinal cord. Com-
block. municates with the cerebellum via the inferior
fascial sheets within the neurovascular sheath may cerebellar peduncle. Forms the posterior part of
cause a patchy block. Puncture both above and the fourth ventricle floor. Contains the decussa-
below the artery has been suggested as a remedy. tion of pyramidal tracts, gracile and cuneate
Alternatively, separate identification of the differ- nuclei, nuclei of cranial nerves IX, X, XI and XII,
ent nerves with a nerve stimulator has been advo- and vital centres, e.g. for respiration and cardio-
cated (median: causes contraction of flexor carpi vascular homeostasis.
radialis; ulnar: flexor carpi ulnaris; radial: extensor - pons: communicates with the cerebellum via the
muscles of hand/wrist; musculocutaneous: biceps), middle cerebellar peduncle. Forms the anterior
with the total dose divided between them. Inten- part of the fourth ventricle floor. Contains the
tional transfixion of the artery has also been nuclei of cranial nerves V, VI, VII and VIII, and
described: blood is aspirated as the needle is pontine nuclei. Also houses the apneustic and
advanced through the artery; when aspiration pneumotactic centres of breathing control.
ceases, solution is deposited posterior to the artery. - cerebellum: occupies the posterior cranial fossa.
infraclavicular: Consists of grey cortex covering white matter.
- with the patients arm abducted, a needle is Communicates via the medulla, pons and mid-
inserted 23cm caudal to the midpoint of a line brain with the thalamus, cerebral cortex and
drawn between the medial head of the clavicle spinal cord. Regulates posture, coordination and
and the coracoid process. The needle is advanced muscle tone. Lesions cause ipsilateral effects.
laterally parallel to this line and at 45 to the midbrain: communicates with the cerebellum via
skin until twitches are seen in the hand (pectoral the superior cerebellar peduncle. Contains the
contraction indicates superficial placement of pineal body and cranial nerve nuclei III and IV.
the needle, and biceps contraction may be forebrain:
achieved by stimulating the musculocutaneous - diencephalon: consists of the hypothalamus
nerve outside the plexus sheath). Has also been (forming the floor of the lateral wall of the third
described with the needle directed directly poste- ventricle) with the pituitary gland below, and
riorly at a point 1cm medial and 2cm caudal to thalamus (lateral to the third ventricle). The thal-
the coracoid process. amus integrates sensory pathways.
- 3045ml solution is injected. - basal ganglia: grey matter within cerebral hemi-
posterior: spheres. The internal capsule, containing the
- with the patient sitting or lying, and the cervical major ascending and descending pathways to and
spine flexed, a needle is inserted 3cm from the from the cerebral cortex, passes between the
midline level with the C67 interspace. A loss of basal ganglia. They receive and relay information
resistance technique or nerve stimulation has concerned with fine motor control.
Breathing, control of 85

- cerebral cortex: water into the ear canal (normal response is a

- frontal lobes: contain motor cortices, including tonic deviation of the eyes towards the side
areas for speech and eye movement; areas being irrigated followed by a faster phase back
for intellectual and emotional functions lie towards the midline). Each ear is tested in turn,
anteriorly. having checked that the canal is not blocked. (In
- parietal lobes: contain sensory cortices, and the UK, testing for dolls eye movements is not
areas for association and integration of sensory used as a component of brainstem testing.)
input. - gag reflex (CN IX and X).
- temporal lobes: contain auditory cortices, and - cough reflex (CN X).
areas for integration and association of auditory - absent motor responses within cranial nerve dis-
input and memory. Also constitutes part of the tribution, to any peripheral stimuli (corticospinal
limbic system, which integrates endocrine, auto- tract runs through the brainstem).
nomic and motivational functions. - absent respiratory efforts despite arterial PCO2 of
- occipital lobes: contain the visual cortices, and 6.6kPa (50mmHg), and adequate oxygenation
areas for association and integration of visual (e.g. with apnoeic oxygenation). Must be con-
sensory input. firmed using blood gas interpretation.
See also, Ascending reticular activating system; Brain- All the above requirements must be met for the diagno-
stem; Cerebral circulation; Cerebrospinal fluid; Motor sis of brainstem death to be made. Two sets of tests
pathways; Sensory pathways should be performed by two doctors (registered for 5
years) who have skill in the field, one of whom is a con-
Brainstem. Composed of midbrain, pons and medulla. sultant, neither of whom should be part of the organ
Contains neurone groups involved in the control of donation team.
breathing, cardiovascular homeostasis, GIT function, The tests may be carried out together or separately.
balance and equilibrium, and eye movement. Also inte- No specific time interval has been recommended
grates ascending and descending pathways between the between testing. Although EEG, cerebral angiography
spinal cord, cranial nerves, cerebellum and higher and oesophageal contractility testing are performed in
centres, partly via the ascending reticular activating some countries, they are not required to make the diag-
system. nosis of brainstem death in the UK. The legal time of
See also, Brain; Brainstem death; Breathing, control of death is recorded as the time the first set of tests shows
no activity.
Brainstem death. Irreversible absence of brainstem Although the clinical criteria remain unchanged
function despite artificial maintenance of circulation and for paediatric patients, the interval between the two
gas exchange. Clinical experience has shown that, once tests differs. No UK recommendations exist; therefore
it is diagnosed, cardiac arrest is inevitable, usually within the US ones are usually followed for children of differ-
a few days. Guidelines have been established for the ent ages:
withdrawal of artificial support and, where appropriate, newborn to 2 months (usually performed for medi-
arrangement for organ donation. These guidelines colegal reasons): interval 48h.
include: 212 months: 24h.
necessary preconditions: 118 years: 12h.
- apnoeic coma (i.e. the patient is unresponsive and Vegetative state associated with absent cortical function
requiring IPPV). or cortical disconnection may occur with intact brain-
- irreversible structural brain damage caused stem reflexes. Such patients may have spontaneous res-
by a disorder that can lead to brain death piration and may live for years without recovery, and do
(e.g. subarachnoid haemorrhage, head injury, not satisfy the criteria for brainstem death.
meningitis). Gardiner D, Shemie S, Manara A, Opdam H (2012). Br
necessary exclusions: J Anaesth; 108: i1428
- absence of primary hypothermia, i.e. core tem-
perature > 35C (N.B. secondary hypothermia Braun, Heinrich Friedrich Wilhelm (18621934).
often follows brainstem death). German surgeon who also practised and investigated
- absence of primary metabolic or endocrine distur- anaesthesia. One of the pioneers of local anaesthesia,
bance (N.B. secondary endocrine abnormalities he described many local blocks, and published exten-
often follow brainstem death, e.g. diabetes insipi- sively on the subject. Introduced adrenaline to local
dus, hypothyroidism, hypoprolactinaemia). anaesthetic solutions to prolong their action in 1902
- absence of drug intoxication, including sedatives and in 1903 suggested its possible use in resuscitation.
given in ICU. Popularised procaine in 1905.
- absence of paralysis caused by neuromuscular
blocking drugs (neuromuscular blockade moni- Breathing, control of. The exact origin of the signal
toring is useful) or neuromuscular disorders (e.g. for regular breathing is unknown. Brainstem centres
GuillainBarr syndrome). involved in the control of breathing have been identified;
- absence of abnormal posturing (e.g. decorticate or their precise roles are unclear. There are three such
decerebrate) or convulsions. centres:
necessary clinical findings: medullary centre:
- absent cranial nerve (CN) reflexes: - dorsal respiratory group neurones arising from
- pupillary light reflex (CN II and III). the nucleus tractus solitarius are involved in inspi-
- corneal reflex (CN V and VII). ration; when stimulated they cause diaphragmatic
- oculovestibular reflex (CN VIII), i.e. no eye contraction via contralateral phrenic nerves; they
movement following injection of 4060ml icy also project to ventral neurones.
86 Breathing, muscles of

- ventral respiratory group neurones arising the area enclosed by the broken line represents
from the nucleus ambiguous are predominantly work done to overcome elastic forces.
involved in expiration, causing contraction of ipsi- area A represents work done to overcome resis-
lateral accessory muscles (via vagus nerves) and tance during inspiration.
intercostal muscles. They also inhibit the apneus- area B represents work done to overcome resis-
tic centre. tance during expiration.
apneustic centre in the lower pons: causes excitation The greater the tidal volume or lung volume, the more
of medullary dorsal respiratory group neurones work is required to overcome elastic recoil. The faster
causing inspiration whilst inhibiting ventral respira- the flow rates, the greater the amount of work required
tory group neurones. Surgical section above it to overcome resistance. Normally, energy is provided for
causes prolonged pauses at end-inspiration. expiration by potential energy stored in the stretched
pneumotactic centre (nucleus parabrachialis) in the elastic tissues (i.e. area B lies within the broken line), but
upper pons: curtails inspiration and thus regulates extra energy may be required in airway obstruction.
respiratory rate. Total work of breathing is difficult to measure in
The respiratory centre composed of these groups of spontaneous respiration. Volume may be measured with
neurones receives afferents from chemoreceptors and a pneumotachograph; oesophageal pressure, indicating
other structures: intrapleural pressure, may be measured with an oesoph-
chemoreceptors : ageal balloon. Normally, the work of breathing accounts
- peripheral (aortic and carotid bodies): afferents for less than 3% of the total body O2 consumption at
pass via the vagus and glossopharyngeal nerves rest, but may be much higher in disease states, e.g.
respectively. Stimulated by a fall in arterial PO2, COPD, cardiac failure and during exercise.
also by a rise in PCO2 and hydrogen ion concentra- Expiratory valves in anaesthetic breathing systems
tion. Their response to reduced O2 increases increase work of expiration, particularly when not fully
markedly below 810kPa (6075mmHg). The open. Coaxial anaesthetic breathing systems increase
response to increased CO2 is roughly linear. expiratory resistance, the Lack by virtue of its small-
- central: present on the ventral surface of the calibre expiratory tube, and the Bain because of the high
medulla, but separate from the respiratory centre. flow rate of fresh gas directed at the patients mouth.
Stimulated by a rise in hydrogen ion concentra- Banner MJ, Jaeger MJ, Kirby RR (1994). Crit Care Med;
tion in CSF, due to increased PCO2 or metabolic 22: 51523
acidosis. See also, Airway resistance; Compliance
Hypoxaemia increases the sensitivity of the chemo-
receptors to hypercapnia, and vice versa. Hypoxae- Bretylium tosylate. Class II and III antiarrhythmic
mia causes direct depression of the respiratory drug, originally introduced as an antihypertensive drug.
centres, in addition to reflex stimulation. In chronic Reduces sympathetic drive to the heart and prolongs the
lung disease, the central chemoreceptors may not action potential. Taken up by adrenergic nerve endings,
respond to increased CO2 levels, either due to che- causing release of noradrenaline followed by inhibition
moreceptor resetting or due to correction of CSF of release. Excreted largely unchanged in the urine. Pre-
pH. Hypoxaemia then becomes the main drive to viously reserved for treatment of resistant ventricular
respiration (of importance in O2 therapy). arrhythmias, now no longer available in the UK.
other structures: Dosage: 510mg/kg iv by slow infusion, repeated
- lungs: 12hlater up to 30mg/kg. Followed by 12mg/min
- pulmonary stretch receptors, involved in the or 510mg/kg tds/qds. May also be given im.
HeringBreuer and deflation reflexes. Initial hypertension may be followed by severe hypoten-
- juxtapulmonary capillary receptors, involved in sion. May cause nausea and vomiting.
dyspnoea due to pulmonary disease and pulmo-
nary oedema.
- pulmonary irritant receptors, responding to
noxious stimuli.
- proprioceptors in joints and muscles, thought to
be important during exercise.
- baroreceptors; hypertension inhibits ventilation,
but this is of little clinical significance.
- higher centres, responding to pain and fear.
During anaesthesia, the responses to hypercapnia and
Lung volume

hypoxaemia are depressed, the latter severely.

See also, Carbon dioxide response curve; Expiration
Hypoventilation B A
Breathing, muscles of, see Respiratory muscles

Breathing systems, see Anaesthetic breathing systems

Breathing, work of. Equals the product of pressure FRC

change across the lung and volume of gas moved. During Negative intrapleural pressure
inspiration, most of the work of breathing is done to
overcome elastic recoil of the thorax and lungs, and the Fig. 27 Graph of intrapleural pressure against lung volume during
resistance of the airways and non-elastic tissues (Fig. 27): breathing (see text)
Bronchiectasis 87

BrewerLuckhardt reflex. Laryngospasm in response Types:

to remote stimulation, e.g. anal or cervical dilatation. small cell (~20%): may arise from APUD cells (see
[Nathan R Brewer (19042009)and Arno B Luckhardt Apudomas), and secrete hormones. Extensive
(18851957), US physiologists] spread is usual at presentation. Extremely poor
British Association for Immediate Care (BASICS). non-small cell:
Voluntary charitable organisation, formed in 1977, - adenocarcinoma (~40%).
whose members provide medical assistance at the scene - squamous cell (~30%): most present with bron-
of an accident or medical emergency or during primary chial obstruction. Better prognosis than the other
transport to hospital. Acts as the national coordinating common forms.
body for schemes and individual doctors providing - large cell (~10%); particularly related to smoking.
immediate care throughout the UK. Organises educa- - others:
tional courses for doctors, nurses, paramedics, occupa- - bronchiolar alveolar, carcinoid: least related to
tional health professionals, the emergency services and smoking.
those involved in healthcare at sporting and other events. - carcinoma in situ.
British Association of Critical Care Nurses (BACCN). local:
Formed in 1984 from the amalgamation of various - haemoptysis, cough, dyspnoea.
groups of UK critical care nurses. Exists to support per- - wheeze, stridor, chest discomfort.
sonal and professional development of members (who - chest infection, pleural effusion.
include nurses, managers, educationalists, researchers invasion of:
and others with an interest in critical care) and to - mediastinum, chest wall. May cause superior vena
promote the art and science of critical care nursing. Its caval obstruction, dysphagia, cardiac arrhythmias,
official journal is Nursing in Critical Care. pericardial effusion.
- vertebrae.
British Journal of Anaesthesia. Second oldest journal of - recurrent laryngeal nerve, usually on the left.
anaesthesia (first published in 1923), and the first to be - sympathetic trunk at C8/T1, causing Horners
published monthly (in 1955). Previously unaffiliated with syndrome.
any association, institution or society, it became the offi- - brachial plexus at lung apex, causing pain and
cial journal of the College of Anaesthetists in 1990. wasting in the hand/arm (with Horners syndrome,
Spence AA (1988). Br J Anaesth; 60: 6057 rib or vertebral erosion, superior vena caval
obstruction, = Pancoast syndrome).
Bromage scale. Scoring system used to assess the metastases: commonly lymph nodes, bone, liver,
degree of motor block, originally described in the context brain.
of epidural anaesthesia for surgery. Consists of four other features:
grades (Table 13). Various modifications have been - fatigue, anorexia, weight loss, anaemia.
described (e.g. with or without detectable weak hip - hormone secretion, e.g. causing the syndrome
flexion); in some modifications a score of 1 indicates no of inappropriate antidiuretic hormone secretion,
block instead of complete block, as in the original Cushings syndrome, hypercalcaemia due to para-
scale. thyroid hormone secretion, carcinoid syndrome.
[Philip Bromage, English-born Canadian/US Most common with small cell tumours. Thyroid
anaesthetist] and sex hormone secretion may occur.
- sensory or motor neuropathy; cerebellar atrophy.
Bromethol (Tribromethanol; Avertin). CBr3CH2OH. - myasthenic syndrome, muscle weakness, dermato-
Obsolete rectal and iv sedative drug introduced in 1927 myositis.
and used for deep sedation or anaesthesia. - finger clubbing and hypertrophic pulmonary
Bronchial blockers, see Endobronchial blockers May present for bronchoscopy, mediastinoscopy or tho-
racic surgery. Anaesthetic considerations are related to
Bronchial carcinoma. Commonest cause of death from the above features, effects of smoking and malignancy;
cancer in Western men and women. Mostly associated thus preoperative assessment of respiratory, cardiovas-
with smoking, but also occurs following exposure to cular and neurological systems, and hormonal and meta-
asbestos, and certain industrial chemical and radioactive bolic status, is particularly important.
substances. Air pollution may also be a causative factor. Radiotherapy is used mainly for palliative treatment
Five-year survival in the UK is less than 10%; in the of pain and obstructive lesions (e.g. superior vena
USA and certain parts of Europe it is ~15%. caval obstruction), especially due to small cell carci-
noma. Chemotherapy is also used, particularly in small
cell carcinoma.
[Henry Pancoast (18751939), US radiologist]
Sculier JP, Berghmans T, Meert AP (2010). Am J Respir
Table 13 Bromage scale for motor block Crit Care Med; 181: 77381
See also, Polymyositis
1 Complete Unable to move legs or feet
2 Almost complete Able to move feet only Bronchial tree, see Tracheobronchial tree
3 Partial Just able to flex knees only
4 None Full movement of legs and feet Bronchiectasis. Permanent abnormal bronchial dilata-
tion, usually suppurative. May follow pneumonia,
88 Bronchiolitis

bronchial obstruction, chronic repeated chest infections, Postulated mechanisms of action:

e.g. in cystic fibrosis and immunological impairment. 2-adrenergic receptor agonists, e.g. salbutamol:
Features: - inhibit degranulation of mast cells.
haemoptysis. - stimulate adenylate cyclase in smooth muscle
chronic cough with purulent sputum. cells, increasing cAMP levels and thus causing
chronic respiratory insufficiency, of restrictive and/ reduced intracellular calcium and relaxation.
or obstructive pattern. phosphodiesterase inhibitors, e.g. theophylline,
empyema, abscesses, cor pulmonale, clubbing. aminophylline:
CXR: increased lung markings, patchy shadowing, - inhibit the breakdown of cAMP in smooth muscle
thick-walled dilated bronchi. cells.
Treatment includes antibiotic therapy, physiotherapy - possible effect via release of catecholamines via
and postural drainage, and lung resection if disease is adenosine inhibition.
localised. - possible effect on myosin light chains, reducing
Anaesthetic management: contraction.
preoperatively: anticholinergic drugs, e.g. ipratropium:
- early admission for preoperative assessment, - block muscarinic acetylcholine receptors, decreas-
medical treatment and physiotherapy. ing intracellular guanine monophosphate (cGMP;
- CXR, arterial blood gas interpretation, lung func- opposes the bronchodilating action of cAMP).
tion tests as appropriate. - possible effect via reduction in intracellular
perioperatively: soiling of the unaffected lung is calcium.
reduced by appropriate positioning. Double-lumen corticosteroids:
endobronchial tubes may assist surgery and allow - anti-inflammatory action.
isolation and suction of copious secretions. - reduced capillary permeability.
postoperatively: adequate analgesia and physio- - possibly increase the effects of -adrenergic
therapy to reduce risk of respiratory complications. receptor agonists.
ODonnell AE (2008). Chest; 134: 81523 Sodium cromoglicate and leukotriene receptor antago-
nists are not bronchodilators, but help to prevent bron-
Bronchiolitis. Inflammation of the bronchioles; usually choconstriction by reducing inflammation.
refers to acute infection in children but may also occur See also, Asthma; Bronchospasm
chronically in early COPD in adults. In children, respira-
tory syncytial virus accounts for 70% of cases, but many Bronchopleural fistula. Abnormal connection between
other viruses may also be responsible. Usually affects the tracheobronchial tree and pleura. Most commonly
children under 1 year old, causing non-specific upper occurs 210 days after pneumonectomy, although it may
respiratory tract symptoms that may progress over 12 follow trauma, chronic infection and erosion by tumour.
days to respiratory distress with diffuse crackles per- Features:
sistent wheezing. Hypoxaemia results from hypoventila- fever, productive cough, malaise.
tion and V/Q mismatch. May be associated with apnoea, X-ray evidence of infection in the remaining lung
especially in premature babies. Treatment is supportive, with fall in fluid level on the affected side.
including humidified O2 therapy, fluid replacement and Problems caused:
occasionally IPPV. Inhaled adrenaline and dexametha- source of (usually) infected material in one pleural
sone are also used. Ribavirin may reduce the severity of cavity, with potential contamination of the normal
illness if given early. lung through the fistula. Repeated spillage may
Usually self-limiting, lasting under 10 days; mortality cause pulmonary function impairment before cor-
in infants admitted to hospital is about 1% if previously rective surgery.
fit. Has been implicated in the development of subse- IPPV may force fresh gas through the fistula,
quent asthma. without inflating the remaining lung. Increased pres-
Ducharme FM (2011). Br Med J; 342: 7734 sure in the affected pleura increases the likelihood
See also, Tracheobronchial tree of contamination, and may impair cardiac output.
Bronchoalveolar lavage (BAL). Performed for pulmo- chest drainage.
nary alveolar proteinosis, to remove accumulated lipo- sitting the patient up, with affected side lowermost.
proteinaceous material. Has also been used in asthma classical method for induction of anaesthesia: inha-
and cystic fibrosis. Usually performed under general lational induction and intubation with a double-
anaesthesia, and involves instillation and drainage under lumen endobronchial tube, with spontaneous
gravity of 2040 litres warm buffered saline (heparin ventilation. IPPV may be started once the affected
may be added) through one lumen of a double-lumen side has been isolated. However, deep anaesthesia
endobronchial tube, whilst ventilating via the other. The with volatile agents may cause profound cardiovas-
other lung is treated after a few days. Main problems are cular effects, and coughing may increase contamina-
related to the pre-existing state of the patient, one-lung tion risk. Alternatives include awake intubation
anaesthesia and avoidance of soiling of the ventilated under local anaesthesia, or preoxygenation, iv
lung. Cardiopulmonary bypass has also been used. induction and intubation using suxamethonium
Lavage using small volumes is sometimes used to aid (only advocated by, and for, experienced thoracic
diagnosis of atypical chest infections, and may be carried anaesthetists).
out via flexible bronchoscopy under local anaesthesia. postoperatively, IPPV may be necessary. High-
frequency ventilation and differential lung ventila-
Bronchodilator drugs. Drugs that increase bronchial tion have been used.
diameter. See also, Thoracic surgery
Bronchoscopy 89

Bronchopulmonary lavage, see Bronchoalveolar lavage - airway management:

- tracheal intubation in airway obstruction. Also
Bronchoscopy. Inspection of the tracheobronchial tree useful for changing tracheal tubes.
by passing an instrument down its lumen. May be: - confirmation of correct placement of tra-
rigid: usually performed in the operating theatre cheal/tracheostomy/endobronchial tubes. Also
for diagnosis of bronchial disease, removal of used in percutaneous tracheostomy.
foreign bodies and management of haemoptysis. - assessment of the tracheobronchial tree before
Anaesthetic management: extubation. In cases of potential postextubation
- preoperatively: airway obstruction, e.g. caused by oedema, the
- preoperative assessment is directed at the fibreoptic bronchoscope can be left in situ whilst
respiratory and cardiovascular systems. Many the tracheal tube is removed and the airway
patients will have bronchial carcinoma or other assessed; the tube may be resited over the bron-
smoking-related diseases. Secretions may be choscope if required.
improved by preoperative physiotherapy. Neck - diagnostic:
mobility and the teeth should be assessed. - chest infection, especially atypical. Washings,
- premedication reduces awareness. The antisial- brushings or transbronchial/endobronchial
agogue effects of anticholinergic drugs may be biopsies or needle aspiration may be used.
useful. Repeated instillation of 20ml sterile saline with
- perioperatively: subsequent aspiration (bronchoalveolar lavage)
- in the absence of a foreign body in the airway, may be useful in both infective and non-infective
iv induction of anaesthesia is usual. Inhalational processes.
induction may be indicated if airway obstruc- - other lesions, e.g. tumours, tears, thermal
tion is present, particularly in children. Neuro- damage. May be used to investigate abnormali-
muscular blockade is usually achieved with a ties on CXR.
short-acting neuromuscular blocking drug. - therapeutic:
- spraying of the larynx with lidocaine may reduce - aspiration of sputum and aspirated material.
perioperative and postoperative coughing and Mucolytic drugs can be instilled on to mucus
laryngospasm. plugs. Bronchoalveolar lavage has been used in
- ventilation: several methods may be used: severe asthma.
- injector techniques; air entrainment through - removal of foreign body.
the bronchoscope using intermittent jets of - for haemoptysis; saline lavage may be useful for
O2. Automatic jet ventilators have been used small areas of bleeding; the bronchoscope itself
for long procedures. can be used to compress bleeding points; or it
- IPPV via a side arm on the bronchoscope, may facilitate passage of a balloon-tipped cath-
the proximal end of which is occluded by a eter into the affected segment.
window or the operators thumb. Management for bronchoscopy in the ICU:
- deep anaesthesia with spontaneous ventila- coagulation studies should be performed if biopsies
tion. Often used in children, classically using are planned. Electrolyte imbalance should be
diethyl ether, then halothane, but now sevo- corrected.
flurane. Anaesthetic gases may be delivered secretions may be improved by physiotherapy.
via a side arm on the bronchoscope; before Anticholinergic drugs may reduce secretions
these ventilating bronchoscopes became but may also make them thick and difficult to
available, the patient breathed air and bron- aspirate.
choscopy was performed as anaesthesia light- awake patients may be managed under local anaes-
ened (a possible disadvantage of sevoflurane thesia as for awake intubation. In those with tra-
being that anaesthesia might lighten too cheal tubes, the bronchoscope may be passed
quickly). through a rubber-sealed connector at the tubes
- insufflation techniques, particularly apnoeic proximal end and IPPV continued. Leaks may
oxygenation. Suitable for short procedures occur around the scope, especially if airway pres-
only. sures are high; a swab coated in lubricant jelly
- intermittent IPPV via a tracheal tube placed wrapped around the leak may improve the seal.
in the proximal end of the bronchoscope. 5.0mm diameter bronchoscopes require an 8.0mm
- high-frequency ventilation has been used. tracheal tube to ensure adequate gas flow around
- monitoring as standard. the bronchoscope. Passage of the bronchoscope
- awareness is a particular problem, especially alongside the tracheal tube has also been used, as
with jet ventilation using 100% O2, or apnoeic has high-frequency ventilation.
oxygenation. Regular supplements or continu- increased sedation and neuromuscular blockade
ous infusion of iv anaesthetic agents, typically are usually required in ventilated patients.
propofol, reduce the incidence, as does premed- hypoxaemia may worsen during bronchoscopy;
ication, or the use of midazolam. 100% O2 is usually administered. Severe hypoxae-
- recovery should be in the lateral, head-down mia is usually considered a contraindication.
position, to encourage drainage of blood and arrhythmias, hypertension, coughing, broncho-
secretions. spasm or laryngospasm may occur during and after
fibreoptic: commonly performed for diagnostic pur- stimulation of the tracheobronchial tree. Topical
poses under local anaesthesia as for awake intuba- lidocaine may reduce airway irritation. Bleeding
tion, but also used by anaesthetists and intensivists and pneumothorax may also occur.
during general anaesthesia and on the ICU. Uses: See also, Foreign body, inhaled; Intubation, awake
90 Bronchospasm

Bronchospasm. May occur during anaesthesia due to: [A ]

surgical stimulation.
pH = pK + log
presence of airway adjunct or tracheal tube.
pharyngeal/laryngeal/bronchial secretions or When pH equals pK of the buffer system, maximal buff-
blood. ering may occur, because HA and A exist in equal
aspiration of gastric contents.
Body buffer systems:
pulmonary oedema.
use of -adrenergic receptor antagonists.
- carbonic acid/bicarbonate: H2CO3 H+ + HCO3.
Particularly likely in smokers or in patients with asthma The pK is 6.1; i.e. the system is not very efficient
or COPD, and if anaesthesia is inadequate. at buffering alkaline at body pH (although it is
Features: quite efficient at buffering acid, efficiency increas-
polyphonic expiratory wheeze.
ing as pH falls). However, because there is a large
reduced movement of reservoir bag.
reservoir of plasma bicarbonate, and CO2 may
increased expiratory time.
be readily eliminated via the lungs and bicarbon-
increased airway pressures.
ate excretion can be regulated via the kidneys,
Must be distinguished from: this system constitutes the main buffer system in
the blood.
mechanical obstruction.
- haemoglobin: dissociation of histidine residues
gives haemoglobin six times the buffering capac-
pulmonary oedema.
ity of plasma proteins. Deoxygenated haemoglo-
Treatment: bin is a better buffer than oxygenated haemoglobin
of primary cause.
(Haldane effect).
increased FIO2.
- plasma proteins: carboxyl and amino groups dis-
increased inspired concentration of volatile inhala-
sociate to form anions; this accounts for a small
tional anaesthetic agent. amount of buffering capacity.
salbutamol 250500g sc/im or 250g iv slowly.
- phosphate: H2PO4 H+ + HPO42. Plays a small
Delivery by nebuliser or aerosol may also be used part in buffering in the ECF.
but may be technically difficult.
aminophylline 36mg/kg iv slowly, followed by
- proteins.
0.5mg/kg/h infusion. - phosphate.
further management as for asthma.
See also, Acidbase balance

Bumetanide. Loop diuretic, similar to furosemide in its

Brown fat. Specialised adipose tissue used for thermo- actions. 1mg is approximately equivalent to 40mg furo-
genesis because of its chemical make-up and structural semide. Diuresis begins within minutes of an iv dose and
composition. Of particular importance in temperature lasts for 2h.
regulation in neonates. Laid down from about 22 weeks Dosage:
of gestation around the base of the neck, axillae, medi- 15mg orally odtds.
astinum and between the scapulae; gradually replaced 12mg iv, repeated after 20min if required. May
by adult white adipose tissue after birth, the process also be given by infusion at 15mg/h.
taking several years. Fat breakdown and thermogenesis Side effects: as for furosemide; myalgia may also
are increased by -adrenergic neurone activity. occur, especially with high doses.
Enerbck S (2009). N Engl J Med; 360: 20213
BUN, see Blood urea nitrogen
BTPS. Body temperature and pressure, saturated with
water vapour. Bundle branch block (BBB). Interruption of impulse
propagation in the heart conducting system distal to the
Buccal nerve block, see Mandibular nerve blocks atrioventricular node. Causes are as for heart block.
May involve right or left bundles:
right BBB:
Buffer base. Blood anions that can act as bases and - common; usually clinically insignificant.
accept hydrogen ions. Mainly composed of bicarbonate, - ECG findings (Fig. 28a):
haemoglobin and negatively charged proteins. - QRS duration > 0.12s.
See also, Acidbase balance; Buffers - large S wave, lead I.
- RSR pattern, lead V1.
Buffers. Substances that resist a change in pH by absorb- - incomplete BBB may be due to an enlarged right
ing or releasing hydrogen ions when acid or base is ventricle, e.g. due to cor pulmonale or ASD.
added to the solution. In aqueous solutions this com- left BBB:
prises either a weak acid and its conjugate base (see - represents more widespread disease, as the left
below), or a weak base and its conjugate acid. bundle is a bigger and less discrete structure, con-
For the equation HA H+ + A, where HA = undis- sisting of anterior and posterior fascicles. If
sociated acid and A = anion, the equation shifts to the present preoperatively, it serves as an indicator of
left if acid is added, and to the right if base is added; existing heart disease.
changes in H+ concentration are thus minimised. - ECG findings (Fig. 28b):
The HendersonHasselbalch equation describes - QRS duration > 0.12s.
these relationships: - wide R waves, leads I and V46.
Burns 91

- may be due to left ventricular hypertrophy, e.g. Bupivacaine hydrochloride. Amide local anaesthetic
due to hypertension or valvular heart disease. agent, introduced in 1963. Widely used for peripheral
hemiblock (involving individual fascicles of the left nerve/plexus blocks, spinal and epidural anaesthesia. In
bundle): comparison with lidocaine, bupivicaine:
- left anterior hemiblock: has a slower onset of action (pKa 8.1).
- QRS may be normal or slightly widened. is more potent (~6 more lipid-soluble); 0.5%
- left axis deviation > 60. bupivicaine is equivalent to 2% lidocaine.
- left posterior hemiblock: causes less vasodilatation; addition of adrenaline
- less common, because the posterior fascicle is neither prolongs the effect nor restricts systemic
better perfused than the anterior. absorption of bupivacaine.
- QRS normal or slightly widened. is extensively bound to tissue and plasma proteins
- right axis deviation > 120. (95%); thus has a longer duration of action
bifascicular block: (34hfor epidural block and up to 12hfor some
- composed of right BBB and one hemiblock: nerve blocks, e.g. brachial plexus).
- anterior: is more cardiotoxic.
- right BBB ECG pattern and left axis Mainly metabolised by the liver, a small amount is
deviation. excreted unchanged in the urine. 0.250.5% solutions
- may lead to complete heart block later in life, are used for most purposes. 0.75% produces more
but this is rare during anaesthesia. prolonged motor block when given epidurally; this con-
- posterior: centration is contraindicated in obstetric practice
- right BBB ECG pattern and right axis because of toxicity. Contraindicated for use in IVRA
deviation. because of its cardiotoxicity. A hyperbaric 0.5% solution
- rare. (with glucose 8%) spinal administration was introduced
- at risk of developing complete heart block. in 1982. Maximal safe dose: 2mg/kg; toxic plasma levels:
- bifascicular block plus prolonged PR interval > 24g/ml.
(i.e. partial trifascicular block) is particularly The original preparation of bupivacaine is a racemic
likely to progress to complete heart block. mixture of l- and d-isomers. A preparation of the pure
BBB itself is not a contraindication to anaesthesia, but enantiomer l-bupivacaine (levobupivacaine) was devel-
progression to complete heart block during anaesthesia oped in 1997 and is equivalent to the racemic mixture in
remains the main risk. Temporary perioperative cardiac terms of action and potency, whilst having reduced pro-
pacing should be considered if BBB is associated with pensity to CVS and CNS toxicity. It is available in the
either a history of syncope or a prolonged PR interval. same concentrations as the racemic preparation.
Anaesthetic management is as for heart block. See also, Isomerism; individual blocks

Bungarotoxins. Snake venom neurotoxins. -

Buprenorphine hydrochloride. Opioid analgesic drug
Bungarotoxin binds irreversibly to postsynaptic acetyl-
derived from thebaine, with partial agonist properties.
choline receptors at the neuromuscular junction; -
Synthesised in 1968. 0.4mg is equivalent to 10mg mor-
bungarotoxin acts presynaptically to block acetylcholine
phine; it has slower onset and its effects last longer
release. They have been used to study neuromuscular
(about 8h). May be given iv or im (0.30.6mg), or sub-
lingually (0.20.4mg) 68-hourly. A slow-release patch
(3570g/h, equivalent to 0.841.68mg/day) has been
produced for severe chronic pain. Respiratory depres-
sion does occur, but reaches a plateau that cannot be
(a) (b)
exceeded by increasing the dose. Respiratory depression
I I is not readily reversed by naloxone. Carries a low risk of
dependence and has been used in the treatment of drug
See also, Opioid receptors

Burns. Burned patients may suffer from:

V1 V1 direct thermal injury to body and airway.
smoke inhalation, with e.g. carbon monoxide (CO)
or cyanide (CN) poisoning.
extensive fluid loss into the dermis, into blisters and
from skin surfaces.
Patients suffering from electrocution and electrical
burns may have suffered widespread internal tissue
injury, whilst those suffering from chemical burns may
V6 V6 also have features of systemic toxicity/metabolic distur-
bance. General management of electrical and chemical
burns is similar to that for thermal burns.
high FIO2 O2 therapy. Tracheal intubation and IPPV
are required in:
Fig. 28 ECG findings in bundle branch block: (a) right BBB; (b) left - severe CO or CN poisoning. It has been suggested
BBB that CN poisoning should be assumed if there
92 Burns, during anaesthesia

is unexplained severe metabolic acidosis, and prevention of Curling ulcers, e.g. with H2 receptor
treated accordingly. antagonists.
- apparent or impending upper airway obstruction tetanus toxoid as necessary.
due to inhalational injury. Obstruction due to consider transfer to a specialist burns unit if:
oedema may develop over a few hours; thus tra- - burn > 10% total body surface area (adult) or >
cheal intubation with an uncut tube should be 5% (child), or any full-thickness burn > 5%.
performed early if burns to the airway are present. - burn to face, hands, genitalia, major joints.
The latter may be indicated by burns or soot - significant inhalational injury.
around the face and in the mouth, and are con- - < 5 and > 60 years of age (poorer prognosis).
firmed by fibreoptic bronchoscopy. Obstruction - circumferential burn to limbs or chest.
usually resolves within 24 days. - high-voltage electrical or chemical burn > 5%
- an unconscious patient. total body surface area.
- respiratory failure. Complications:
Measurement of blood gas tensions, carboxyhaemo- infection and sepsis.
globin and possibly cyanide levels, should be per- respiratory failure and ARDS.
formed. A CXR is mandatory. renal failure, with myoglobinuria or haemoglobin-
assessment of the extent of burns (rule of nines is uria. Suggested by low urine osmolarity and urine/
appropriate for adults; a paediatric burn chart is blood urea ratio < 10.
used for children). hypercatabolism.
fluid replacement: many different regimens exist, Mortality is related to the extent and site of burn, and
using colloid, crystalloid or hypertonic solutions. age. Recent evidence suggests that area of burn > 40%,
Average total requirements = water 24ml/kg/% age > 60 years and the presence of inhalational injury
burn and sodium 0.5mmol/kg/% burn. Constant are the three risk factors most strongly associated with
reassessment is the most important factor. Common death; absence of these risk factors is associated with
UK regimen: 0.3% mortality; a single risk factor with 3% mortality,
- replacement volume (V) in ml: two risk factors with 33% mortality, and all three risk
body weight (kg) %surface area burnt factors with 90% mortality.
V= Anaesthetic considerations in patients with burns:
2 patients often require repeat anaesthetics, e.g. for
3 V is infused in the first 12 h from the time change of dressings, plastic surgery.
of burn; difficult airway and/or intubation if burns exist

2 V in the next 12 h; around the head and neck, especially if contractures

1 V in the next 12 h. a life-threatening enhanced increase in plasma
- choice of fluid: colloid is thought to be best. Blood potassium may follow use of suxamethonium;
is given to keep haematocrit 3545%. Rough cardiac arrest has been reported. Most likely 310
guide: 1 unit per 10% burn, excluding the first 10%. weeks after the burn, but has been reported between
Normal maintenance fluids are given in addition. 9 days and 2 months. An increased number of extra-
- alternative regimen, using crystalloid: junctional acetylcholine receptors is thought to be
2 weight % burn in first 8 h (ml); responsible.
increased requirement for non-depolarising neuro-
2 weight % burn in next 16 h. muscular blocking drugs. The mechanism is unclear
Frequent reassessment is crucial. Urine output but may involve altered pharmacokinetics, e.g.
should be maintained at 0.51 ml/kg/h with osmo- changes in protein-binding, clearance, volume of
lality 6001000 mosmol/kg (high due to high circu- distribution. An alternative theory suggests the
lating levels of vasopressin). Low urine flow with release of a specific, yet undiscovered, substance fol-
high osmolality indicates under-replacement; high lowing burns that reduces drug interaction with the
flow with low osmolality indicates over-replacement, neuromuscular junction, or affects the latter directly.
in the absence of renal failure. The fluid regimen limited venous access.
is altered as necessary. hypermetabolism/catabolism.
Oral rehydration is acceptable in burns of up to heat loss during prolonged surgery.
10% (children) to 15% (adults). Oral rehydration extensive blood loss is possible; e.g. during grafting
fluid mixtures are suitable for children. For adults, procedures approximately 2% blood volume lost
water containing 75mmol/l sodium chloride and per 1% surface burn.
15mmol/l sodium bicarbonate has been suggested, suggested techniques:
at 23 times normal water intake. - iv opioid analgesic drugs, traditionally combined
escharotomy (incision of contracted full-thickness with butyrophenones (neuroleptanaesthesia),
burn that prevents ventilation or limb perfusion) though this is less common now.
may be necessary. - inhalational analgesia with Entonox or volatile
monitoring of: agents.
- urine output (via catheter if > 25% burn). - ketamine other iv agents, e.g. midazolam,
- haematocrit and plasma electrolytes. propofol.
- respiratory function. - standard general anaesthesia.
- CVP. Latenser BA (2009). Crit Care Med; 37: 281926
analgesia: opioid infusions are often required.
adequate nutrition (enteral if possible via a naso- Burns, during anaesthesia, see Diathermy; Electrocution
gastric or -jejunal tube). and electrical burns; Explosions and fires; Laser surgery
Bypass, cardiopulmonary 93

BURP, Backward, upward and rightward pressure, see tranquillisers (a term no longer used). They produce a
Intubation, difficult state of detachment from the environment and inhibit
purposeful movement via GABA receptor antagonism.
Burst suppression, see Electroencephalography They may cause distressing inner restlessness that may
be masked by outward calmness. They are powerful anti-
Busulfan (Busulphan). Alkylating agent cytotoxic drug, emetic drugs, acting as dopamine antagonists at the che-
given orally to treat chronic myeloid leukaemia. Causes moreceptor trigger zone. Although some -adrenergic
myelosuppression that may be irreversible, and, rarely, blocking effect has been shown, cardiovascular effects
pulmonary fibrosis. Thus important in patients present- are minimal. May cause extrapyramidal side effects, and
ing for bone marrow transplantation. the neuroleptic malignant syndrome, especially after
chronic usage. Used to treat psychoses (especially
Butorphanol tartrate. Obsolete opioid analgesic drug schizophrenia and mania), in neuroleptanaesthesia and
with partial agonist properties, withdrawn in the UK in as antiemetics. Droperidol has a faster onset of action
1983, similar in actions to pentazocine. and shorter half-life than haloperidol.
See also, Opioid receptors

Butyrophenones. Group of centrally acting drugs, Bypass, cardiopulmonary, see Cardiopulmonary

originally described with phenothiazines as major bypass
CABG, see Coronary artery bypass graft The above points inform the decision to employ general
or regional anaesthesia.
Regimens used to reduce the risk of aspiration
Cachectin, see Cytokines
fasting during labour: this practice has been ques-
Cachexia, see Malnutrition tioned, and many centres allow clear fluids or
certain foods (low fat and sugar content) for low-
Caesarean section (CS). Operative delivery of a fetus risk women in labour (if not receiving opioids),
by surgical incision through the abdominal wall and although this is still controversial.
uterus. Unless specifically indicated, the classical midline antacid therapy: 0.3M sodium citrate (30ml)
upper uterine segment approach has been largely directly neutralises gastric acidity; it has a short
replaced by the transverse lower segment incision; the duration of action and should be given immediately
latter is associated with lower rates of ileus, infection and before induction of anaesthesia.
bleeding. The CS rate in the UK has steadily increased H2 receptor antagonists: different regimens are
to ~25%, from ~810% in the 1980s. employed in different units, with most reserving
Indications include: previous CS; pre-existing mater- prophylaxis, e.g. with ranitidine, for women at risk
nal morbidity (e.g. cardiac disease); complications of of operative intervention or receiving pethidine
pregnancy (e.g. pre-eclampsia); obstetric disorders (causing reduced gastric emptying). For elective CS,
(e.g. placenta praevia); fetal compromise; failure to ranitidine 150mg orally the night before and 2h
progress. before surgery is often given. For emergency CS,
Specific anaesthetic considerations: ranitidine 50mg iv may be given; cimetidine 200mg
physiological changes of pregnancy. im is an alternative as it has a more rapid onset than
difficult tracheal intubation and aspiration of gastric ranitidine.
contents associated with general anaesthesia (GA) omeprazole and metoclopramide have also been
have been major anaesthetic causes of maternal used, to reduce gastric acidity and increase gastric
mortality. Mortality is higher for emergency CS emptying, respectively.
than for elective CS. Sedative premedication is usually avoided because of
aortocaval compression must be minimised by the risk of neonatal respiratory depression and difficul-
avoiding the supine position at all times. ties over timing.
uterine tone is decreased by volatile anaesthetic Anaesthetic techniques:
agents; however, consideration of this should for all types of anaesthesia:
not result in the administration of inadequate - wide-bore iv access (16G or larger).
anaesthesia. - cross-matched blood available within 30min.
placental perfusion may be reduced by severe and/ - routine monitoring and skilled anaesthetic assis-
or prolonged hypotension and/or reduction in tance, with all necessary equipment and resuscita-
cardiac output. tive drugs available and checked.
contraction of the uterus upon delivery results in - aortocaval compression is reduced by positioning
autotransfusion of about 500ml blood, helping to the patient laterally during transport to theatre
offset the average blood loss of 5001500ml (GA) and surgery.
or 300700ml (regional anaesthesia). - ergometrine has been superseded by oxytocin as
neonatal depression should be avoided, but mater- the first-line uterotonic following delivery because
nal awareness may occur if depth of anaesthesia is of the formers side effects (e.g. hypertension and
inadequate. vomiting).
The usual preoperative assessment should be made, general anaesthesia:
with particular attention to: - rapid sequence induction with an adequate dose
the indication for CS (e.g. pre-eclampsia) and other of anaesthetic agent is required to prevent aware-
obstetric or medical conditions. ness; a maximal allowed dose based on weight
whether CS is elective or emergency, and whether may be insufficient. Neonatal depression due to
the fetus is compromised. iv induction agents is minimal. Suxamethonium
assessment of the airway. is still considered the neuromuscular blocking
maternal preference for general or regional drug of choice by most authorities, although
anaesthesia. rocuronium (especially with the advent of sugam-
if used in labour, the quality of existing epidural madex) is an alternative.
analgesia should be assessed. - difficult and failed intubation (the latter ~1:300
assessment of the lumbar spine and any contraindi- 500) is more likely in obstetric patients than in the
cations to regional anaesthesia. general population. Contributory factors include

96 Caesarean section

a full set of teeth, increased fat deposition, (e.g. fentanyl) is common (though may not be
enlarged breasts and the hand applying cricoid necessary if many epidural doses have been given
pressure hindering insertion of the laryngoscope during labour). Bicarbonate has also been added
blade into the mouth. Laryngeal oedema may be to shorten the onset time, (e.g. 2ml 8.4% added
present in pre-eclampsia. Apnoea rapidly results to 20ml lidocaine or lidocaine/bupivacaine
in hypoxaemia because of reduced FRC and mixture), but risks errors from mixing up to 45
increased O2 demand. different drugs, especially in an emergency.
- IPPV with 50% O2 in N2O is commonly recom- Commercial premixed solutions of lidocaine/
mended until delivery; however, in the absence of bupivacaine and adrenaline may be unsuitable as
fetal distress, 33% O2 is associated with similar they have a low pH (3.55.5) and contain preser-
neonatal outcomes. vatives. Ropivacaine 0.50.75% or levobupiva-
- 0.50.6 MAC of volatile agents (with 50% N2O) caine 0.5% is also used. 0.75% bupivacaine is
reduces the incidence of awareness to 1% without associated with a high incidence of toxicity, and
increasing uterine atony and bleeding, or neonatal has been withdrawn from obstetric use. Chloro-
depression; however, at 0.81.0 MAC, awareness procaine is available in the USA and a small
falls to 0.2% and the uterus remains responsive to number of European countries (but not the UK);
uterotonics. Placental blood flow is thought to it has a rapid onset and offset. Etidocaine has also
be maintained by vasodilatation caused by the been used in the USA.
volatile agents, and high levels of vasoconstricting - L34 interspace is usually chosen.
catecholamines associated with awareness are - on average, 1520ml solution is required for ade-
avoided. Delivery of higher concentrations of quate blockade (from S5 to T46). Loss of normal
volatile agents (overpressure) in 66% N2O has light touch sensation is a stronger predictor of
been suggested for the first 35min whilst alveo- intraoperative comfort than loss of cold sensation,
lar concentrations are low, to reduce awareness. although either may be used to assess the block.
Factors increasing the likelihood of awareness Smaller volumes are required for a specified level
include lack of premedication, reduced con of block than in non-pregnant patients, as dilated
centrations of N2O and volatile agents, and with- epidural veins reduce the available volume in the
holding opioid analgesic drugs until delivery. epidural space.
Up to 26% awareness was reported in early - injection of solution in 5-ml increments at 5-min
studies using 50% N2O and no volatile anaes- intervals reduces the risk of hypotension and
thetic agent. extensive blockade (e.g. due to accidental spinal
- normocapnia (4 kPa/30mmHg in pregnancy) is injection), but increases anaesthetic time and
considered ideal; excessive hyperventilation may total dose. A single injection of 1520ml is advo-
be associated with fetal hypoxaemia and acidosis cated by some as producing a more rapid block.
due to placental vasoconstriction, impairment of A catheter technique is used most frequently,
O2 transfer associated with low PCO2, and reduced although injection through the epidural needle
venous return caused by excessive IPPV. may be performed.
- all neuromuscular blocking drugs cross the pla- - opioids (e.g. diamorphine 24mg or fentanyl
centa to a very small extent. Shorter-acting drugs 50100g) are routinely given epidurally for peri-
(e.g. vecuronium and atracurium), are usually and postoperative analgesia; maternal respiratory
employed, since postoperative residual paralysis depression has been reported, albeit rarely.
associated with longer-lasting drugs has been a - hypotension associated with blockade of sympa-
significant factor in some maternal deaths. thetic tone may be reduced by preloading with iv
- opioid analgesic drugs are withheld until delivery fluid; however, the use of vasopressors to prevent
of the infant, to avoid neonatal respiratory and treat hypotension in the euvolaemic patient
depression. is thought to be a more effective and rational
- aspiration may also occur during recovery from approach. Ephedrine 36mg or phenylephrine
anaesthesia (when the effect of sodium citrate 50100g is commonly given by intermittent
may have worn off). Routine gastric aspiration bolus; continuous infusions are also effective.
during anaesthesia has been suggested, especially Phenylephrine appears to be associated with a
in emergency cases. Before tracheal extubation, better neonatal acidbase profile than large doses
the patient should be awake and on her side. of ephedrine (thought to be due to ephedrine
- advantages: usually quicker to perform in emer- crossing the placenta and causing increased
gencies. May be used when regional techniques anaerobic glycolysis in the fetus via -adrenergic
are inadequate or contraindicated, e.g. in coagula- stimulation).
tion disorders. Safer in hypovolaemia. - nausea and vomiting may be caused by hypoten-
- disadvantages: risk of aspiration, difficult intuba- sion and/or bradycardia.
tion, awareness and neonatal depression. Hypo- - routine administration of O2 by facemask has
tension and reduced cardiac output may result been questioned on the grounds of being ineffec-
from anaesthetic drugs and IPPV. Postoperative tive and even possibly harmful to the fetus, due to
pain, drowsiness, PONV, blood loss and DVT risk generation of free radicals.
all tend to be greater. - during surgery many women feel pressure and
epidural anaesthesia (EA): movement, which may be unpleasant; all women
- facilities for GA should be available. should be warned of this possibility and of the
- bupivacaine 0.5% or lidocaine 2% (the latter with potential requirement for general anaesthesia.
adrenaline 1:200000) is most commonly used in Inhaled N2O, further epidural top-ups, small doses
the UK, often in combination. Addition of opioids of iv opioid drugs (e.g. fentanyl or alfentanil), iv
Calcium 97

paracetamol and ketamine may be useful. Shoul- as a last resort if other techniques are unavailable or
der tip pain may result from blood tracking up to unsuccessful. It may also be used to supplement inhala-
the diaphragm and may be reduced by head-up tional anaesthesia following failed intubation. Trans-
tilt. Good communication between mother, anaes- verse abdominis plane block has been used, e.g. for
thetist and obstetrician is especially important postoperative analgesia.
when performing CS under regional anaesthesia, [Julius Caesar (10044 BC), Roman Emperor; said to
and the obstetrician should warn the anaesthetist have been born by the abdominal route; his name alleg-
before exteriorising the uterus or swabbing the edly derived from caedare, to cut. An alternative sugges-
paracolic gutters. tion is related to a law enforced under the Caesars
- advantages: the risks of GA are avoided. Onset of concerning abdominal section following death in late
hypotension is usually slow, the mother may be pregnancy]
able to warn of it early and it may be corrected See also, Confidential Enquiries into Maternal Deaths;
before becoming severe. Minimal neonatal Fetus, effects of anaesthetic agents on; ID interval;
depression occurs compared with GA. The mother Induction, rapid sequence; Intubation, difficult; Intuba-
is not drowsy and is able to hold the baby soon tion, failed; Obstetric analgesia and anaesthesia; UD
after delivery. Her partner is able to be present interval
during the procedure. Epidural analgesia pro-
vided in labour can be extended for operative Caffeine. Xanthine present in tea, coffee and certain soft
delivery. The catheter can be used for further top- drinks; the worlds most widely used psychoactive sub-
up during surgery if required, and for postopera- stance. Also used as an adjunct to many oral analgesic
tive analgesia. drug preparations, although not analgesic itself. Causes
- disadvantages: risk of dural tap, total spinal block- CNS stimulation; traditionally thought to improve per-
ade, local anaesthetic toxicity, severe hypotension. formance and mood, whilst reducing fatigue. Increases
It may be slow to achieve adequate blockade with cerebral vascular resistance and decreases cerebral
a risk of patchy block. Inability to move the legs blood flow. Half-life is about 6h. Has been used iv and
may be disturbing. orally for treatment of post-dural puncture headache.
spinal anaesthesia (SA): Acts via inhibition of phosphodiesterase, increasing
- general considerations as for EA. levels of cAMP and as an antagonist at adenosine
- 0.5% bupivacaine is used in the UK; plain bupi- receptors.
vacaine (e.g. 3ml) produces a more variable block Dosage: up to 30mg in compound oral preparations.
than hyperbaric bupivacaine (e.g. 1.82.8ml), 150300mg orally tds/qds for post-dural puncture
which is the only form licensed for spinal anaes- headache; 250mg iv (with 250mg sodium
thesia. Plain levobupivacaine is also licensed in benzoate).
the UK. Hyperbaric tetracaine (amethocaine) Side effects: as for aminophylline, especially CNS and
0.5% (1.21.6ml) is used in the USA. cardiac stimulation.
- injection is usually at the L34/L45 interspace.
- advantages: as for EA, but of quicker onset. Caisson disease, see Decompression sickness
Blockade is more intense and not patchy. Smaller
doses of local anaesthetic drug are used. Calcitonin. Hormone (mw 3500) secreted from the
- disadvantages: single shot; i.e. may not last long parafollicular (C) cells of the thyroid gland. Involved in
enough if surgery is prolonged. Spinal catheter calcium homeostasis; secretion is stimulated by hyper-
techniques allow more control over spread and calcaemia, catecholamines and gastrin. Decreases serum
duration but are technically more difficult. Risk calcium by inhibiting mobilisation of bone calcium,
of post-dural puncture headache (reduced to decreasing intestinal absorption and increasing renal
under 1% if 2527G pencil-point needles are calcium and phosphate excretion. Acts via a G protein-
used). Hypotension is of faster onset and thus coupled receptor on osteoclasts. Calcitonin derived from
may be more difficult to control; has been associ- salmon is used in the treatment of severe hypercalcae-
ated with poorer neonatal acidbase status com- mia, postmenopausal osteoporosis, Pagets disease and
pared with EA/GA. Remains the most popular intractable pain from bony metastases.
anaesthetic technique for CS in the UK. [Sir James Paget (18141899), English surgeon]
combined spinalepidural anaesthesia (CSE): See also, Procalcitonin
- general considerations as for EA and SA.
- allows the fast onset and dense block of SA but Calcium. 99% of body calcium is contained in bone;
with the flexibility of EA. Also allows a small plasma calcium consists of free ionised calcium (50%)
subarachnoid injection to be extended by epidu- and calcium bound to proteins (mainly albumin) and
ral injection of either saline (thought to act via a other ions. The free ionised form is a second messenger
volume effect) or local anaesthetic, with greater in many cellular processes, including neuromuscular
cardiovascular stability. transmission, muscle contraction, coagulation, cell
- usually performed at a single vertebral interspace division/movement and certain oxidative pathways.
(needle-through-needle method) Binds to intracellular proteins (e.g. calmodulin), causing
(For contraindications and methods, see individual configurational changes and enzyme activation. Intracel-
techniques) lular calcium levels are much higher than extracellular,
CS is possible using local anaesthetic infiltration of due to relative membrane impermeability and active
the abdominal wall (e.g. with 0.5% lidocaine or prilo- transport mechanisms. Calcium entry via specific chan-
caine). Large volumes are required, with risk of toxicity. nels leads to direct effects (e.g. neurotransmitter release
Infiltration of each layer is performed in stages. The pro- in neurones), or further calcium release from intracel-
cedure is lengthy and uncomfortable, but may be used lular organelles (e.g. in cardiac and skeletal muscle).
98 Calcium channel blocking drugs

Extracellular hypocalcaemia has a net excitatory effect Classified according to pharmacological effects in
on nerve and muscle; hypocalcaemic tetany can result in vitro and in vivo:
life-threatening laryngospasm. class I: potent negative inotropic and chronotropic
Ionised calcium increases with acidosis, and decreases effects, e.g. verapamil. Acts mainly on the myocar-
with alkalosis. Thus for accurate measurement, blood dium and conduction system; reduces myocardial
should be taken without a tourniquet (which causes contractility and O2 consumption and slows conduc-
local acidosis), and without hyper-/hypoventilation. tion of the action potential at the SA/AV nodes.
Ionised calcium is measured in some centres, but total Thus mainly used to treat angina and SVT (less
plasma calcium is easier to measure; normal value is useful in hypertension). Severe myocardial depres-
2.122.65mmol/l. Varies with the plasma protein level; sion may occur, especially in combination with
corrected by adding 0.02mmol/l calcium for each g/l -adrenergic receptor antagonists.
albumin below 40g/l, or subtracting for each g/l above class II: acts on vascular smooth muscle, reducing
40g/l. vascular tone; minimal direct myocardial activity
Regulation: (although may cause reflex tachycardia):
vitamin D: group of related sterols. Cholecal- - nifedipine: acts mainly on coronary and periph-
ciferol is formed in the skin by the action of ultra- eral arteries, with little myocardial depression.
violet light, and is converted in the liver to Used in angina, hypertension and Reynauds syn-
25-hydroxycholecalciferol (in turn converted to drome. Systemic vasodilatation may cause flush-
1,25-dihydroxycholecalciferol in the proximal renal ing and headache, especially for the first few days
tubules). Formation is increased by parathyroid of treatment.
hormone and decreased by hyperphosphataemia. - nicardipine: as nifedipine, but with even less myo-
Actions: cardial depression.
- increases intestinal calcium absorption. - amlodipine and felodipine: similar to nifedipine
- increases renal calcium reabsorption. and nicardipine, but with longer duration of action
- increases bone mineralisation. and therefore taken once daily.
parathyroid hormone: secretion is increased - nimodipine: particularly active on cerebral vascu-
by hypocalcaemia and hypomagnesaemia, and lar smooth muscle, it is used to relieve cerebral
decreased by hypercalcaemia and hypermagnesae- vasospasm following subarachnoid haemorrhage.
mia. Actions: class III: slight negative inotropic effects, without
- mobilises bone calcium. reflex tachycardia: diltiazem is used in angina and
- increases renal calcium reabsorption. hypertension.
- increases renal phosphate excretion. The above drugs act mainly on the L-type calcium (long-
- increases formation of 1,25-dihydroxy- lasting) channels; these are more widely distributed than
cholecalciferol. the T-type (transient) channels which are confined to the
calcitonin: secreted by the parafollicular cells of the sinoatrial node, vascular smooth muscle and renal neu-
thyroid gland. Secretion is increased by hypercal- roendocrine cells. N-type calcium channels are concen-
caemia, catecholamines and gastrin. Actions: trated in neural tissue and are the binding site of omega
- decreases intestinal absorption of dietary calcium. toxins produced by certain venomous spiders and cone
- inhibits mobilisation of bone calcium. snails. A derivative of the latter, ziconotide, is available
- increases renal calcium and phosphate excretion. for the treatment of chronic pain.
Calcium is used clinically to treat hypocalcaemia, e.g. Additive effects might be expected between these
during massive blood transfusion. It is also used as an drugs and the volatile anaesthetic agents, all of which
inotropic drug. Although ionised calcium concentration decrease calcium entry into cells. Reduction in cardiac
may be low after cardiac arrest, its use during CPR is no output, decreased atrioventricular conduction and
longer recommended unless persistent hypocalcaemia, vasodilatation may occur to different degrees, but
hyperkalaemia or overdose of calcium channel blocking severe interactions are rarely a problem in practice.
drugs is involved. This is because of its adverse effects Non-depolarising neuromuscular blockade may be
on ischaemic myocardium and on coronary and cerebral potentiated.
circulations. Overdose causes hypotension, bradycardia and heart
Calcium chloride 10% contains 6.8mmol/10ml and block. Treatment includes iv calcium chloride, glucagon
14.7% contains 10mmol/10ml; calcium gluconate 10% and catecholamines. Heart block is usually resistant to
contains 2.22.3mmol/10ml, depending on the formula- atropine and hypotension may not respond to inotropes
tion. 510ml calcium chloride or 1020ml calcium glu- or vasopressors. High-dose insulin has been successful in
conate is usually recommended by slow iv bolus. The reversing refractory hypotension.
chloride preparation is usually recommended for CPR,
although equal rises in plasma calcium are produced Calcium resonium, see Polystyrene sulphonate resins
by gluconate, if equal amounts of calcium are given.
Arrhythmias and prolonged hypercalcaemia may follow Calcium sensitisers. New class of inotropic drugs, now
their use. established as effective treatment of acute heart failure;
Aguilera IM, Vaughan RS (2000). Anaesthesia; 55: examples include levosimendan and pimobendan. Act
77990 directly on cardiac myofilaments without increasing
intracellular calcium, thus improving myocardial con-
Calcium channel blocking drugs. Structurally diverse tractility without impairing ventricular relaxation. Levo-
group of drugs that block Ca2+ flux via specific Ca2+ chan- simendan also has vasodilatory effects through opening
nels (largely L-type, slow inward current). Effects vary of K+ channels.
according to relative affinity for cardiac or vascular Parissis JT, Rafouli-Stergiou P, Mebazaa A etal (2010).
smooth muscle Ca2+ channels. Curr Opin Crit Care; 16: 43241
Capreomycin 99

Calibration. Process of standardising the output of a Capacitance. Ability to retain electrical charge; defined
measuring device against another measurement of as the charge stored by an object per voltage difference
known and constant magnitude. Reduces measurement across it. The unit of capacitance is the farad (F), 1 farad
error due to drift. One-point calibration is sufficient to being the capacity to store 1 coulomb of charge for an
address offset drift; two-point calibration is required for applied potential difference of 1 volt.
the mitigation of gradient drift. Essential for the accu- A capacitor composed of conductors separated by
rate functioning of many measurement devices (e.g. arte- an insulator may be charged by a potential difference
rial blood pressure monitor, blood gas analyser, expired across it, but will not allow direct current to flow. Its
gas analyser). stored charge may subsequently be discharged, e.g. in
defibrillation. Repeated charging and discharging
Calorie. Unit of energy. Although not an SI unit, widely induced by an alternating current results in current flow
used, especially when describing energy content of food. across a capacitor.
[Michael Faraday (17911867), English chemist]
1 cal = energy required to heat 1g water by 1C.
1kcal (1 Cal) = energy required to heat 1kg water Capacitance vessels. Composed of venae cavae and
by 1C = 1000 cal. large veins; normally only partially distended, they may
1 cal = 4.18 joules. expand to accommodate a large volume of blood before
venous pressure is increased. Innervated by the sympa-
Calorimetry, indirect, see Energy balance thetic nervous system in the same way as the arterial
system (resistance vessels), they act as a blood reservoir.
CAM-ICU, see Confusion in the intensive care unit 6070% of blood volume is within the veins normally.

cAMP, see Adenosine monophoshate, cyclic Capacitor, see Capacitance

CampbellHowell method, see Carbon dioxide Capillary circulation. Contains 5% of circulating blood
measurement volume, which passes from arterioles to venules via cap-
illaries, usually within 2s. Controlled by local autoregu-
Canadian Journal of Anesthesia. Official journal of the latory mechanisms, and possibly by autonomic neural
Canadian Anesthetists Society. Launched in 1954 as reflexes. Substances that readily cross the capillary walls
the Canadian Anaesthetists Society Journal. Became the (mainly by diffusion) include water, O2, CO2, glucose and
Canadian Journal of Anaesthesia in 1987 and the Cana- urea. Hydrostatic pressure falls from about 30mmHg
dian Journal of Anesthesia in 1999. (arteriolar end) to 15mmHg (venous end) within the
capillary. Direction of fluid flow across capillary walls is
Candela. SI unit of luminous intensity, one of the base determined by hydrostatic and osmotic pressure gradi-
(fundamental) units. Definition relates to the luminous ents (Starling forces).
intensity of a radiating black body at the freezing point
of platinum. Capillary refill time. Time taken for capillaries to refill
after blanching pressure is applied for 5s. Normally
Cannabis. Hallucinogenic drug obtained from the < 2s; prolonged in hypoperfusion and hypothermia. May
Cannabis sativa plant. A mixture of at least 60 chemicals be measured centrally, over the sternum, or peripherally,
(cannabinoids) including the main psychoactive -9- on the soft pad of a digit.
tetra-hydrocannibinol. Cannabinoid receptors have
been identified in central and peripheral neurones (CB1 Capnography. Continuous measurement and pictorial
receptors) and lymphoid tissue (e.g. spleen) and macro- display of CO2 concentration (capnometry refers to
phages (CB2); both types are G protein-coupled measurement only). During anaesthesia, used to display
receptors. end-tidal CO2; this may be achieved using:
Therapeutic uses include treatment of glaucoma and spectroscopy (most commonly infrared).
as an antiemetic agent during chemotherapy. Also has mass spectrometer.
analgesic, anticonvulsant and possibly antispasmodic The equipment used must have a very short response
properties, hence its use in chronic pain and multiple time in order to produce a continuous display (for
sclerosis. Mild psychological dependence is common, uses and capnography traces, see Carbon dioxide,
although physiological withdrawal states do not occur. end-tidal).
Cognitive impairment, including psychosis with chronic Whitaker DK (2011). Anaesthesia; 66: 5449
usage, has been reported. Usually combined with tobacco See also, Carbon dioxide measurement
and smoked; anaesthetic concerns are as for smoking
generally. Capreomycin. Cyclic polypeptide antibacterial drug
Present law prohibits prescription of cannabis used to treat TB resistant to other therapy (especially
without a Home Office Licence and has hampered in immunocompromised patients). Also used in other
clinical trials; there has been pressure to allow freer mycobacterial infections. Poorly absorbed orally, peak
administration in certain chronic conditions and even to levels occur within 2h of im injection. Excreted
decriminalise it altogether. Reclassified as a Class C unchanged in the urine.
drug under the Misuse of Drugs Act 1971 in 2004. Nabi- Dosage: 1g/day by deep im injection for 24 months,
lone is a synthetic cannabinoid used as an antiemetic in then 1g 23 times weekly, reduced in renal failure.
chemotherapy-induced nausea and vomiting. Side effects: renal and hepatic impairment, ocular dis-
Hosking RD, Zajicek JP (2008). Br J Anaesth; 101: turbances, ototoxicity, blood dyscrasias, electrolyte
5968 disturbances, neuromuscular blockade.
100 Capsaicin

Capsaicin. Component of hot chilli peppers; activates although they are not true hydrates. a usually exceeds 3,
heat-sensitive Ca2+ channels (vanilloid receptors), and may or not equal b. Notable examples of monosac-
located on A and C pain fibres, producing a burning charides are ribose and glucose, where a = 5 and 6
sensation. Initial stimulation is followed by depletion of respectively (pentoses and hexoses). Disaccharides are
substance P by reducing its synthesis, storage and trans- formed from condensation reactions between two
port. Applied topically for the treatment of neuralgias monosaccharides (e.g. sucrose = glucose + fructose).
(e.g. postherpetic neuralgia) and arthritis. Should be Large polysaccharides include starch, cellulose and gly-
applied 68-hourly. Takes 14 weeks to produce its cogen. Metabolites often contain phosphorus. Some
effect. Application of a single high-concentration (8%) polysaccharides are combined with proteins, e.g. muco-
capsaicin patch can produce 3 months relief from neu- polysaccharides. Act as a source of energy in food, e.g.:
ropathic pain. C 6 H 12O6 + 6O2 6CO2 + 6 H 2O + energy
Captopril. Angiotensin converting enzyme inhibitor, 1g carbohydrate yields about 17 kJ energy (4 Cal).
Ingested carbohydrates are broken down thus:
used to treat hypertension and cardiac failure (including
mouth: salivary amylase: starch smaller units
following MI), and diabetic nephropathy. Shorter acting
small intestine:
than enalapril; onset is within 15min, with peak effect
at 3060min. Half-life is 2h. Interferes with renal auto- - pancreatic amylase: starch as above.
regulation; therefore contraindicated in renal artery ste- - maltase: maltose glucose.
nosis or pre-existing renal impairment. - lactase: lactose glucose + galactose.
Dosage: 6.2550mg orally bd/tds. - sucrase: sucrose glucose + fructose.
Side effects: severe hypotension after the first dose, Hexoses and pentoses absorbed from the GIT pass to
cough, taste disturbances, rash, abdominal pain, the liver for storage molecule synthesis or use in alterna-
agranulocytosis, hyperkalaemia, renal impairment. tive metabolic pathways.
Severe hypotension may occur after induction of See also, Metabolism
anaesthesia and in hypovolaemia.
Contraindicated in pregnancy and porphyria. Carbon dioxide (CO2). Gas produced by oxidation of
carbon-containing substances. Average rate of produc-
Carbamazepine. Anticonvulsant drug, used to treat all tion under basal conditions in adults is about 200ml/
types of epilepsy, except petit mal. Acts by stabilising min, although it varies with the energy source (see Respi-
the inactivated state of voltage-gated sodium channels. ratory quotient).
Has fewer side effects than phenytoin, and has a greater Partial pressures of CO2:

therapeutic index. Also used for pain management inspired: 0.03 kPa (0.2mmHg).
(e.g. in trigeminal neuralgia) and in manic-depressive alveolar: 5.3 kPa (40mmHg).
disease. arterial: 5.3 kPa (40mmHg).
Dosage: initially 100200mg orally od/bd, increasing venous: 6.1 kPa (46mmHg).
to up to 1.6g/day in divided doses. Monitoring plasma expired: 4 kPa (30mmHg).
levels may help determination of optimal dosage Isolated in 1757 by Black. CO2 narcosis was used for
(target levels 2050mol/l). anaesthesia in animals by Hickman in 1824. Used to
Side effects: dizziness, visual disturbances, GIT upset, stimulate respiration during anaesthesia in the early
rash, hyponatraemia, cholestatic jaundice, hepatitis, 1900s, to maintain ventilation and speed uptake of vola-
syndrome of inappropriate ADH secretion. Blood tile agents during induction; also used to assist blind
dyscrasias may occur rarely. Enzyme induction may nasal tracheal intubation. Administration is now gener-
cause reduced effects of other drugs, e.g. warfarin. ally considered hazardous because of the adverse effects
Contraindicated in atrioventricular conduction defects of hypercapnia; CO2 cylinders have now been largely
and porphyria. removed from anaesthetic machines. Manufactured by
heating calcium or magnesium carbonate, producing
Carbapenems. Group of bactericidal antibacterial CO2 and calcium/magnesium oxide.
drugs; contain the -lactam ring and thus, like the peni- Properties:

cillins, impair bacterial cell wall synthesis. Include imipe- colourless gas, 1.5 times denser than air.
nem, meropenem and ertapenem. mw 44.
boiling point 79C.
Carbetocin. Analogue of human oxytocin, licensed for critical temperature 31C.
prevention of uterine atony after delivery by caesarean non-flammable and non-explosive.
section under regional anaesthesia. Acts within 2min of supplied in grey cylinders; pressure is 50 bar at 15C,
injection, its effects lasting over an hour. about 57 bar at room temperature.
Dosage: 100g iv. Effects: as for hypercapnia.
Side effects: as for oxytocin. [Joseph Black (17281799), Scottish chemist]
See also, Acidbase balance; Alveolar gas transfer;
Carbicarb. Experimental buffer composed of 0.3M Carbon dioxide absorption, in anaesthetic breathing
sodium carbonate and 0.3M sodium bicarbonate; unlike systems; Carbon dioxide dissociation curve; Carbon
bicarbonate, there is no net generation of CO2, when dioxide, end-tidal; Carbon dioxide measurement; Carbon
treating acidosis. dioxide response curve; Carbon dioxide transport

Carbocisteine, see Mucolytic drugs Carbon dioxide absorption, in anaesthetic breathing

systems. Investigated and described by Waters in the
Carbohydrates (Saccharides). Class of compounds early 1920s, although used earlier. Exhaled gases
with the general formula Ca(H2O)b, hence their name, are passed over soda lime or a similar material (e.g.
Carbon dioxide measurement 101

baralyme) and reused. In closed systems, only basal O2 Carbon dioxide, end-tidal. Partial pressure of CO2
requirements need be supplied; absorption may also be measured in the final portion of exhaled gas. Approxi-
used with low fresh gas flows and a leak through an mates to alveolar PCO2 in normal anaesthetised subjects;
expiratory valve. the difference is normally 0.40.7 kPa (35mmHg),
Advantages: increasing with V/Q mismatch and increased CO2 pro-
less wastage of inhalational agent. duction. Continuous monitoring (e.g. using infrared cap-
less pollution. nography or mass spectrometry) is considered mandatory
warms and humidifies inhaled gases. during general anaesthesia.
Disadvantages: Measurement is useful for assessing adequacy of
if N2O is also used, risk of hypoxic gas mixtures ventilation, whether controlled or spontaneous, and
makes an O2 analyser mandatory. allows normo- or hypocapnia to be produced as
failure of CO2 absorption may be due to exhaustion required during IPPV. Measurement also aids detec-
of soda lime or inefficient equipment; thus capnog- tion of:
raphy is required. efficient cardiac massage or return of spontaneous
resistance and dead space may be high with some cardiac output in CPR.
systems, and inhalation of dust is possible. oesophageal intubation, since CO2 is only present
trichloroethylene is incompatible with soda lime. in the oesophagus and stomach in small amounts, if
chemical reactions between the volatile agent and at all.
soda lime if the latter dries out excessively (see Soda PE (including fat and air embolism): PECO2 falls due
lime). to increased alveolar dead space and reduced
Methods: cardiac output.
circle systems. rebreathing.
Waters canister: cylindrical drum containing 0.45kg disconnection.
soda lime. Reservoir bag at one end, facemask with MH: PECO2 rises as muscle metabolism increases.
fresh gas supply and expiratory valve at the other; Display of a continuous trace is more useful than
exhaled gases pass to and fro through it. Most effi- values alone (Fig. 30a):
cient when tidal volume equals the contained air phase 1: zero baseline during inspiration; a raised
space (400450ml). Smaller canisters are used for baseline indicates rebreathing (Fig. 30b).
children. Dead space equals the volume between phase 2: dead-space gas (containing no CO2) is
the patient and soda lime; it increases during use as followed by alveolar gas, represented by a sudden
the soda lime nearest the patient is exhausted. Effi- rise to a plateau. Excessive sloping of the upstroke
ciency is also reduced by channelling of exhaled may indicate obstruction to expiration (Fig. 30c).
gases through gaps in the soda lime if loosely packed phase 3: near-horizontal plateau indicates mixing
and allowed to settle. Also heavy and bulky to use. of alveolar gas. A steep upwards slope indicates
obstruction to expiration or unequal mixing, e.g.
Carbon dioxide dissociation curve. Graph of blood COPD (Fig. 30c).
CO2 content against its PCO2 (Fig. 29). The curve is much phase 4: rapid fall to zero at the onset of
steeper than the oxyhaemoglobin dissociation curve, and inspiration.
more linear. Different curves are obtained for oxygen- additional features may be present:
ated and deoxygenated blood, the latter able to carry - superimposed regular oscillations corresponding
more CO2 (Haldane effect). The difference between the to the heartbeat (Fig. 30d).
dissolved CO2 and the oxygenated haemoglobin curves - small waves representing spontaneous breaths
represents the CO2 carried as bicarbonate ion and carb- between ventilator breaths, e.g. if neuromuscular
amino compounds. blockade is insufficient (Fig. 30e).
See also, Carbon dioxide measurement

Carbon dioxide measurement. Estimation of arterial

CO2 content (ml/100 ml blood)

60 PCO2:
direct: Severinghaus CO2 electrode consisting of a
50 glass pH electrode separated from arterial blood
40 sample by a thin membrane. CO2 diffuses into bicar-
bonate solution surrounding the glass electrode,
30 lowering pH. pH is measured and displayed in
terms of PCO2. Requires maintenance at 37C, and
20 calibration with known mixtures of CO2/O2 before
use. Samples are stored on ice or analysed immedi-
ately, to reduce inaccuracy due to blood cell
0 metabolism.
0 1 2 3 4 5 6 7 8 9 10 Indwelling intravascular CO2 electrodes are available
Pco2 (kPa) for continuous monitoring of PCO2.
Deoxygenated - from gas:
Oxygenated - to obtain gas for analysis:
Dissolved CO2 - end-tidal gas sampling (end-tidal PCO2
approximates to alveolar PCO2, which approx-
Fig. 29 Carbon dioxide dissociation curve imates to arterial PCO2).
102 Carbon dioxide narcosis

- rebreathing technique of Campbell and

(a) Howell: rebreathing from a 2 litre bag con-
taining 50% O2 for 90s, then a further 30s
after 3min rest. Bag PCO2 then approximates
3 to mixed venous PCO2. Arterial PCO2 is nor-

mally 0.8 kPa (6mmHg) less than mixed

venous PCO2.
2 4 - subsequent gas analysis:
- chemical: formation of non-gaseous com-
1 pounds, with reduction of overall volume of
the gas mixture (Haldane apparatus).
- physical: capnography and mass spectrometry
Time are most widely used. An interferometer or
I, inspiration gas chromatography may also be used.
E, expiration - from blood/tissues:
- transcutaneous electrode: requires heating of
(b) the skin; relatively inaccurate and slowly
- measurement of venous PCO2 and capillary
PCO2: inaccurate and unreliable.
- Siggaard-Andersen nomogram: equilibration of

the blood sample with gases of known PCO2.

- van Slyke apparatus: liberation of gas from
blood sample with subsequent chemical
- fibreoptic sensors: under development.
Time [John W Severinghaus, San Francisco anaesthetist; EJ
Moran Campbell (19252004), English-born Canadian
(c) physiologist; John BL Howell, Southampton physician]

Carbon dioxide narcosis. Loss of consciousness caused

by severe hypercapnia, i.e. arterial PCO2 exceeding
approximately 25 kPa (200mmHg). Thought to be due

to a profound fall in pH of CSF (under 6.9). Increasing

central depression is seen at arterial PCO2 greater than
13 kPa (100mmHg), and CSF pH under 7.1. Other fea-
tures of hypercapnia may be present.
Used by Hickman in 1824 to enable painless surgery
Time on animals.

(d) Carbon dioxide response curve. Graph defining the

relationship between minute ventilation and arterial CO2
tension. May be obtained by rebreathing from a 6 litre
bag containing 50% O2 and 7% CO2, measuring minute
ventilation and bag PCO2 periodically. This is easier than

increasing inspired CO2 levels and measuring the

response after equilibration at each new level. The curve
may be used to indicate depression of respiratory drive
(Fig. 31); increased threshold is represented by a shift of
the curve to the right (1), and decreased sensitivity by
Time depression of the slope (2). Both may follow administra-
tion of opioid and other depressant drugs, and in chronic
(e) hypercapnia; the opposite occurs in hypoxaemia.
See also, Breathing, control of

Carbon dioxide transport. In arterial blood, approxi-


mately 50ml CO2 is carried per 100ml blood, as:

bicarbonate: 45ml.
carbonic acid: 2.5ml.
carbamino compounds with proteins, mainly hae-
moglobin: 2.5ml.
In venous blood, 54ml is carried per 100ml blood, as:
bicarbonate: 47.5ml.

Fig. 30 End-tidal PCO2 traces: (a) normal; (b) rebreathing; carbonic acid: 3.0ml.
(c) expiratory obstruction; (d) superimposed heartbeats; carbamino compounds: 3.5ml.
(e) spontaneous breaths CO2 is rapidly converted by carbonic anhydrase in red
cells to carbonic acid, which dissociates to bicarbonate
Carboxyhaemoglobin 103

O2 saturation measured by pulse oximetry may be

misleading because carboxyhaemoglobin (which
has a unique spectrophotometric profile) is inter-
preted as oxygenated haemoglobin by some devices.
Newer co-oximeters (e.g. Masimo Rainbow) are
Minute ventilation

specifically able to determine blood carboxyhaemo-

1 globin levels by measuring the absorbance of light
across a range of wavelengths, thus distinguishing
2 between different species of haemoglobin.
neurological symptoms (e.g. dystonia, ataxia, par-
kinsonism), personality changes and impaired
memory may follow recovery from CO coma.
O2 therapy: speeds carboxyhaemoglobin dissocia-
Alveolar Pco2 tion. Tracheal intubation and IPPV may be neces-
sary. Elimination half-life of carbon monoxide is
Fig. 31 Carbon dioxide response curve (see text) reduced from 4h to under 1h with 100% O2; it is
reduced further to under 30min with hyperbaric O2
at 2.53 atm. At this pressure, dissolved O2 alone
satisfies tissue O2 requirements. Hyperbaric O2 has
and hydrogen ions. Bicarbonate passes into plasma in been suggested if the patient is unconscious, has
exchange for chloride ions (chloride shift); hydrogen arrhythmias, is pregnant or has carboxyhaemoglo-
ions are buffered mainly by haemoglobin. Haemoglo- bin levels above 40%.
bins buffering ability increases as it becomes deoxygen- carboxyhaemoglobin levels correlate poorly with
ated, as does its ability to form carbamino groups severity of symptoms, because of variable effects of
(Haldane effect). tissue toxicity. Values often quoted:
See also, Acidbase balance; Buffers; Carbon dioxide dis- - 0.32%: normal non-smokers (some CO from
sociation curve pollution, some formed endogenously).
- 56%: normal smokers.
Carbon monoxide (CO). Colourless, odourless and - 1030%: mild symptoms common.
tasteless gas produced by the partial oxidation of carbon- - above 60%: severe symptoms common.
containing substances. Produced endogenously from the Hampson NB, Piantadosi CA, Thom SR, Weaver LK
breakdown of haemoglobin, it acts as a neurotransmitter (2012). Am J Respir Crit Care Med; 186: 1095101
and may have a role in modulating inflammation and
mitochondrial activity. Carbon monoxide poisoning may
Carbon monoxide transfer factor, see Diffusing
result from exposure to high levels of exogenous CO.
Carbon monoxide diffusing capacity, see Diffusing
capacity Carbonic anhydrase. Zinc-containing enzyme catalys-
ing the reaction of CO2 and water to form carbonic acid,
Carbon monoxide poisoning. May result from inhala- which rapidly dissociates to bicarbonate and hydrogen
tion of fumes from car exhausts, fires, heating systems or ions. Absent from plasma, but present in high concentra-
coal gas supplies. Often coexists with cyanide poisoning. tions in:
Although not directly toxic to the lungs, carbon monox- red blood cells: important in buffering, CO2 trans-
ide (CO) binds to haemoglobin with 200250 times the port and O2 transport.
affinity of O2, forming carboxyhaemoglobin, which dis- renal tubular cells: important for maintaining acid
sociates very slowly. The amount of carboxyhaemoglo- base balance.
bin formed depends on inspired CO concentration and gastric mucosa: important in hydrochloric acid
duration of exposure. production.
Production of CO in circle systems has been reported ciliary body: involved in aqueous humour formation.
under certain circumstances. Inhibited by acetazolamide and sulphonamides.
reduced capacity for O2 transport.
Carboprost. Prostaglandin F2 analogue, used for the
oxyhaemoglobin dissociation curve shifted to the
induction of second-trimester abortion; also used to
treat postpartum haemorrhage unresponsive to first-line
inhibition of the cellular cytochrome oxidase
therapy. Given as the trometamol salt.
system; tissue toxicity is proportional to the length Dosage: 250g by deep im injection repeated as
of exposure.
required every 1590min, up to 2mg. May also be
aortic and carotid bodies do not detect hypoxia,
injected directly into the myometrium, although this
since the arterial PO2 is unaffected.
carries increased risk of accidental iv administration
and represents off-licence use.
non-specific if chronic, e.g. headache, weakness, diz-
Side effects: vomiting, diarrhoea, leucocytosis, fever,
ziness, GIT disturbances.
bronchospasm, uterine rupture.
if acute: as above, with hypoxia, convulsions and
coma if severe.
the cherry red colour of carboxyhaemoglobin may Carboxyhaemoglobin, see Carbon monoxide
be apparent. poisoning
104 Carcinogenicity of anaesthetic agents

Carcinogenicity of anaesthetic agents, see Environ- electromechanical dissociation (EMD)/pulseless

mental safety of anaesthetists; Fetus, effects of anaesthetic electrical activity (PEA). May occur in widespread
agents on myocardial damage. The least common ECG
finding, with the worst prognosis, unless due to
Carcinoid syndrome. Results from secretion of vasoac- mechanical causes of circulatory collapse, e.g. PE,
tive and other substances from certain tumours, found cardiac tamponade, pneumothorax.
in the GIT (70%) or the bronchopulmonary system. Asystole and EMD/PEA may convert to VF,
Secreted compounds are metabolised by the liver so that which eventually converts to asystole if untreated.
symptoms are absent until hepatic metastases are Only 1520% of patients leave hospital after cardiac
present. May be associated with neurofibromatosis. arrest. Up to 3040% survival is thought to be possible
Features: if prompt CPR is instituted. Permanent hypoxic brain
flushing, mainly of the head and neck. May be asso- damage usually occurs within 45min unless CPR
ciated with vasodilatation, hypotension, wheezing, is instituted. The prognosis is better if the patient
skin wheals and sweating. regains consciousness within 10min of the circulation
diarrhoea, sometimes with nausea and vomiting. restarting.
Typically episodic, along with flushing. Weight loss See also, Advanced life support, adult; Basic life support,
is common. adult; Cerebral ischaemia
endocardial fibrosis involving the tricuspid and
pulmonary valves may cause right-sided cardiac Cardiac asthma. Acute pulmonary oedema resembling
failure. asthma. Both may feature dyspnoea, decreased lung
Symptoms are traditionally ascribed to secretion of compliance and widespread rhonchi, although pink
5-HT (diarrhoea) and kinins (flushing), but many more frothy sputum is suggestive of pulmonary oedema.
substances have been implicated, e.g. dopamine, sub- Increased airway resistance may result from true bron-
stance P, prostaglandins, histamine and vasoactive chospasm or from bronchial oedema.
intestinal peptide. Diagnosis includes measurement of
urinary 5-hydroxyindole acetic acid, a breakdown Cardiac catheterisation. Passage of a catheter into the
product of 5-HT. heart chambers for measurement of intracardiac pres-
Anaesthetic management: sures and O2 saturations, or for injection of radiological
perioperative treatment with various drugs has contrast media for radiological imaging (angiocardiog-
been used to reduce hyper-/hypotensive episodes raphy). Used to investigate ischaemic heart disease, val-
and bronchospasm: vular heart disease and congenital heart disease; also
- somatostatin analogues, e.g. octreotide: inhibits used therapeutically (e.g. balloon valvotomy, atrial sep-
release of inflammatory mediators and has tostomy for transposition of the great arteries and per-
become the first-line treatment of many cutaneous transluminal coronary angioplasty).
authorities. Technique:
- 5-HT antagonists: ketanserin, cyproheptadine, commonly performed under local anaesthesia
methysergide. except in small children, in whom general anaesthe-
- antihistamine drugs. sia is required.
invasive cardiovascular monitoring and careful fluid access is via a peripheral vein or artery, e.g.
balance. femoral or brachial vessels, using either a cut-down
use of cardiostable drugs where possible; avoidance technique or percutaneous guidewire (Seldinger
of drugs causing histamine release. technique).
suxamethonium has been claimed to increase medi- the right side of the heart is approached as for pul-
ator release via fasciculations but this is uncertain. monary artery catheterisation.
drugs should be prepared for treatment of broncho- the left side of the heart is approached retrogradely
spasm and hyper-/hypotension. under X-ray control, via a peripheral artery or from
admission to HDU/ICU postoperatively. the right side through the atrial septum or a defect
Kinney MA, Warner ME, Nagorney DM, etal (2001). Br thereof.
J Anaesth; 87: 44752 Information gained:
pressure values, waveforms and gradients between
Cardiac arrest. Sudden circulatory standstill. Common chambers.
cause of death in cardiovascular disease, especially saturation values; greater than expected values on
ischaemic heart disease. May also be caused by PE, elec- the right side indicate a left-to-right shunt.
trolyte disturbances (e.g. of potassium or calcium), cardiac output may be measured using the Fick
hypoxaemia, hypercapnia, hypotension, vagal reflexes, principle.
hypothermia, anaphylaxis, electrocution, drugs (e.g. angiocardiography: cardiac function may be
adrenaline) and instrumentation of the heart. assessed on cine film, or the coronary vessels filled
Features: unconsciousness within 1530s, apnoea or with dye to assess patency.
gasping respiration, pallor, cyanosis, absent pulses. Approximate normal pressures and measurements are
Pupillary dilatation is usual. shown in Table 14.
May be due to:
VF: usually associated with myocardial ischaemia. Cardiac compressions, see Cardiac massage
The most common ECG finding (about 60%), with
the best prognosis. Cardiac contractility, see Myocardial contractility
asystole: occurs in about 30%. More likely in hypo-
volaemia and hypoxia, especially in children. May Cardiac cycle. Sequence of events occurring during
also follow vagally mediated bradycardia. cardiac activity; often represented by the Wiggers
Cardiac failure 105

phase 5: passive ventricular filling: most rapid at the

Table 14 Normal pressures and O2 saturations obtained during
start of diastole.
cardiac catheterisation
May also be described in terms of the changes in pres-

Site Pressure (mmHg) Saturation (%) sure and volume within the left ventricle during the
cardiac cycle the left ventricular pressurevolume
Right atrium 14 75 loop (Fig. 33):
Right ventricle 25/4 75 consists of four phases corresponding to phases 25
Pulmonary artery 25/12 75 of the Wiggers diagram, as described above the
Left atrium 210 97 transition between phases is marked by opening/
Left ventricle 120/10 97 closure of mitral/aortic valves (MV/AV) (Fig. 33a).
Aorta 120/70 97 stroke volume (SV) is the difference between end-
diastolic volume (EDV) and end-systolic volume
stroke work corresponds to the area within the loop.
changes in preload, afterload and myocardial con-
Systole tractility result in predictable changes in the shape
of the loop, with corresponding changes in SV and
work (Fig. 33bd):
P R T - increased preload or EDV results in increased
force of contraction (see Starlings law); SV and
Q S work increase.
- increased afterload results in increased ESV; SV
100 decreases.
Pressure (mmHg)

- increased contractility results in decreased ESV;

stroke volume and work are increased.
[Carl J Wiggers (18831963), US physiologist]
See also, Arterial waveform; Pulse; Venous waveform

Cardiac enzymes. Enzymes normally within cardiac

a v y cells; released into the blood after injury (e.g. after MI
0 or cardiac contusion), thus aiding diagnosis:
x creatine kinase (CK or CPK):
- normally < 190 iu/l.
A P - rises 46h after MI, peaks at 12h, falls at 23
S1 S2
- three specific isoenzymes exist for skeletal muscle
(CKMM), brain (CKBB) and myocardium
Time (0.1 s) (CKMB). Presence of CKMB in the plasma indi-
cates myocardial necrosis.
Phases 1 2 3 4 5 aspartate aminotransferase (AST):

ECG P/Q/R/S/T: see ECG - normally < 35 iu/l.

Aorta a/c/x/v/y: see Venous waveform - rises after 12h, peaks at 12 days.
Left atrium S1/S2: 1st/2nd heart sounds lactate dehydrogenase (LDH):
Left ventricle A/P: aortic/pulmonary valve closure - normally < 300 iu/l (depends on the assay).
Phonocardiography - rises after 12h, peaks at 23 days, falls after 57
Fig. 32 Cardiac cycle (see text) - five isoenzymes exist; an increase in the level of
LDH1 or the ratio of LDH1:LDH2 indicates
myocardial necrosis.
diagram, which details changes in vascular pressures Have been largely replaced by troponins as indicators of
(especially arterial BP), heart chamber pressures, ECG myocardial damage (see Acute coronary syndromes).
and phonocardiography tracings during normal sinus
rhythm (Fig. 32). Cardiac failure. Usually defined as inability of the heart
Divided into five phases: to produce sufficient output for the bodys requirements.
phase 1: atrial contraction: responsible for about The diagnosis is clinical, ranging from mild symptoms on
30% of ventricular filling. Some blood regurgitates exertion only to cardiogenic shock. Several terms have
into the venae cavae and pulmonary veins. been used to describe different forms of cardiac failure:
phase 2: isometric ventricular contraction: lasts left or right ventricular failure (the most commonly
from the closing of the tricuspid and mitral valves used classification). The left ventricle is usually
until ventricular pressures exceed aortic and pulmo- affected by general disease because its workload is
nary artery pressures, and the aortic and pulmonary much greater than that of the right.
valves open. forward or backward failure: the former refers to
phase 3: ventricular ejection: most rapid at the start failure with reduced cardiac output; the latter refers
of systole. Lasts until the aortic and pulmonary to failure with venous congestion.
valves close. congestive cardiac failure: the term sometimes
phase 4: isometric ventricular relaxation: lasts until refers to backward failure, but is often reserved for
the tricuspid and mitral valves open. left-sided failure leading to right-sided failure.
106 Cardiac failure

(a) (b)
200 200
Left ventricular pressure (mmHg)

Left ventricular pressure (mmHg)

100 AV closes 3 100
AV opens
4 SV

MV opens 5 MV closes
0 0
0 100 200 0 100 200
Left ventricular volume (ml)
Left ventricular volume (ml)
(c) (d)
200 200
Left ventricular pressure (mmHg)

Left ventricular pressure (mmHg)

100 100

0 0
0 100 200 0 100 200
Left ventricular volume (ml) Left ventricular volume (ml)

Fig. 33 Left ventricular pressurevolume loops (see text): (a) baseline; (b) increased preload; (c) increased afterload; (d) increased contractility
(shaded loops show the effect of changes)

high-output failure: associated with increased reduced filling:
preload and increased cardiac output. - tricuspid/mitral stenosis.
diastolic failure: recently recognised form in which - cardiac tamponade, constrictive pericarditis (right
the ejection fraction may be normal but ventricular side).
filling is impaired. - reduced ventricular compliance, e.g. amyloid
Caused by: infiltration.
increased workload: Effects:
- preload: ventricular end-diastolic pressure increases, leading
- aortic/mitral regurgitation. to compensatory mechanisms:
- ASD/VSD. - ventricular hypertrophy.
- severe anaemia, fluid overload, hyper - increased force of contraction (Starlings law).
thyroidism. - neuroendocrine response: mainly increased sym-
- afterload: pathetic activity, with tachycardia, vasoconstric-
- hypertension. tion and increased contractility. Aldosterone,
- pulmonary/aortic stenosis, hypertrophic renin/angiotensin and vasopressin activity are
obstructive cardiomyopathy. increased, especially in chronic failure, but mecha-
- pulmonary hypertension, PE. nisms are unclear. Salt and water retention result.
reduced force of contraction: ventricular compliance is reduced, leading to
- MI, ischaemic heart disease. increased atrial pressure and atrial hypertrophy.
- cardiomyopathy. Eventually, ventricular dilatation occurs, with higher
- arrhythmias. wall tension required to produce a given pressure
- myocarditis. (Laplaces law).
Cardiac glycosides 107

coronary blood flow is reduced by tachycardia,

raised end-diastolic pressure and increased muscle - drug combinations, e.g. inotropes + vasodilators;
mass. often produce the greatest improvement
left-sided failure may lead to pulmonary oedema, - intra-aortic counter-pulsation balloon pump.
pulmonary hypertension, V/Q mismatch, decreased Anaesthetic considerations:
lung compliance and right-sided failure. cardiac failure is consistently associated with
right ventricular failure: CVP and JVP increase, increased perioperative morbidity and mortality; it
with peripheral oedema and hepatic engorgement. should therefore be treated preoperatively when-
reduced peripheral blood flow leads to increased O2 ever possible.
uptake and reduction of mixed venous PO2. treatment as above. Electrolyte disturbances and
sodium and water retention exacerbate oedema. digoxin toxicity may occur.
Features: anaesthetic drugs should be given in small doses
reduced cardiac output may result in hypotension, and slowly, because:
confusion and coma. - armbrain circulation time is increased.
left-sided failure: - increased proportion of cardiac output goes to
- dyspnoea, typically worse on lying flat (orthop- vital organs, e.g. brain and heart; thus greater
noea) and sometimes waking the patient at night effects are seen on these organs than in normal
(paroxysmal nocturnal dyspnoea). cardiac output states.
- peripheral shutdown, basal crepitations, left danger of myocardial depression, hypoxia,
ventricular hypertrophy. Extra heart sounds, e.g. arrhythmias.
gallop rhythm and heart murmurs, may be present. use of epidural/spinal anaesthesia is controversial;
CheyneStokes respiration may accompany low the benefit of reduction of SVR may be offset by
output. the risk of hypotension. Perioperative risk is not
- acute pulmonary oedema. diminished.
right-sided failure: McMurray JJV (2010). N Engl J Med; 362: 22838
- raised JVP.
- dependent oedema, e.g. ankles if ambulant, Cardiac glycosides. Drugs derived from plant extracts;
sacrum if bed-bound. used to control ventricular rate in atrial fibrillation and
- hepatomegaly/ascites; the liver may be tender. atrial flutter and for symptomatic relief in cardiac failure.
- right ventricular hypertrophy. Actions are due to inhibition of the sodium/potassium
CXR may reveal cardiomegaly, upper-lobe blood pump and increased calcium mobilisation. The drugs
diversion, fluid in the pulmonary fissures, Kerley have long half-lives (e.g. ouabain 20h; digoxin 36h; digi-
lines, pleural effusion and pulmonary oedema. toxin 4 days), large volumes of distribution (e.g. digoxin
ECG may reveal ventricular hypertrophy and strain 700 litres) and low therapeutic index.
and arrhythmias. Actions:
Management: increase myocardial contractility and stroke volume.
general: of underlying cause, rest, sodium restric- decrease heart rate via direct effects on atrioven-
tion; O2 therapy if acute. tricular conduction and sinus node discharge; also
ACE inhibitors: inhibit ventricular remodelling, act indirectly by increasing vagal tone.
reducing mortality and morbidity. Angiotensin II Side effects: as for digoxin. They are increased by
receptor antagonists have similar efficacy. hypokalaemia, hypercalcaemia and hypomagnesae-
diuretics: reduce salt and water retention, pro mia. Toxicity is also more likely in renal failure and
viding symptomatic relief; a thiazide in combina- pulmonary disease.
tion with a loop diuretic is frequently used.
Spironolactone may be added in low dosage to
ACE inhibitor/diuretic therapy in severe, non-
responsive failure.
-adrenergic receptor antagonists (e.g. carvedilol,
bisoprolol): first-line agents in stable left ventricular Normal
systolic failure, reducing mortality and morbidity.
other vasodilator drugs (e.g. nitrates, hydralazine)
have been used in patients unable to tolerate ACE 3
Cardiac output

inotropic drugs: oral drugs are mostly disappointing. Failure

The most effective drugs are administered by iv 2
digoxin: may improve symptoms and performance
but not mortality.
calcium sensitisers, e.g. levosimendan.
atrial-synchronised biventricular pacemakers have
been shown to improve symptoms and mortality in
patients with severe failure.
emergency treatment: as for pulmonary oedema
and cardiogenic shock. Left ventricular end-diastolic pressure
Response to treatment (Fig. 34):
1: inotropic drugs/arterial vasodilators. Fig. 34 Response to treatment of cardiac failure by Starlings curve
2: diuretics/venous vasodilators. (see text)
108 Cardiac index

Digoxin is most widely used. Ouabain is more rapidly Intrathoracic pressures may be maximised by syn
acting. chronising compressions with IPPV breaths, with or
without abdominal binding or compression (new
Cardiac index (CI). Cardiac output corrected for body CPR). Devices used to augment the thoracic pump
size, expressed in terms of body surface area: mechanism include:
cardiac output (1/ min) - automatic chest compressor (chest thumper).
CI = - active compression/decompression device:
surface area (m 2 ) applies suction to the chest wall between com-
Normal value is 2.54.2 l/min/m2. pressions to increase venous return.
- impedance valve inserted in the ventilating
Cardiac massage. Periodic compression of the heart or system: impedes passive inspiration during the
chest in order to maintain cardiac output, e.g. during release phase, thus increasing intrathoracic neg-
CPR. Both open (internal) and closed (external) cardiac ative pressure and increasing venous return.
massage were developed in the late 1800s. The latter During compression the extra venous return
became more popular in the 1960s following clear dem- results in greater cardiac output.
onstration of its value in dogs and humans, and was Improved blood flows and outcome have been
subsequently adopted by the American Heart Associa- claimed but further studies are awaited.
tion and the Resuscitation Council (UK) as method Open cardiac massage:
of choice. increasingly used, because blood flows and cardiac
Closed cardiac massage: output are greater than with closed massage. Also,
with the patient supine on a rigid surface, the heel direct vision and palpation are useful in assessing
of one hand is placed on the lower half of the cardiac rhythm and filling, and defibrillation and
sternum. The other hand is placed on the first, intracardiac injection are easier.
with fingers clear of the chest. With elbows skin and muscle are incised in an arc under the left
straight and shoulders vertically above the hands, nipple in the fourth or fifth intercostal space, stop-
regular compressions are applied, with a compres- ping 23cm from the sternum to avoid the internal
sion:relaxation ratio of 1:1. The sternum should be thoracic artery. Pericardium is exposed using blunt
depressed 56cm at each compression, at a rate of dissection and pulling the ribs apart. The heart is
100120/min. squeezed from the patients left side using the left
efficacy is assessed by feeling the femoral or carotid hand, with fingers anteriorly over the right ventricle
pulse, although palpable peak pressures may not and thumb posteriorly over the left ventricle. The
reflect blood flow. End-tidal CO2 measurement rate of compressions is determined by cardiac
has been used to assess adequacy of massage; an filling. The descending aorta may be compressed
increase reflects improved cardiac output. with the other hand. The pericardium is opened for
may produce up to 30% of normal cardiac output defibrillation or intracardiac injection. Because of
with corresponding carotid and cerebral blood flow. the emergency nature of the procedure and the low
Coronary flow is low during cardiac massage, and risk of infection, sterile precautions are usually
falls rapidly when massage is stopped. waived.
Technique in children up to 8 years: may also be performed per abdomen through the
- under 1 year: tips of two fingers placed on the intact diaphragm; the heart is compressed against
sternum, one fingers breadth below a line joining the sternum. Minimally invasive direct cardiac
the nipples. The sternum is depressed by one-third massage via a small thoracostomy has recently been
of the depth of the childs chest at a rate of 100 described.
120/min. usually reserved for trauma, perioperative use,
- up to 8 years: heel of one hand placed over the intra-abdominal or thoracic haemorrhage, massive
lower half of the sternum, the fingers lifted to PE, hypothermia, chest deformity and ineffective
avoid applying pressure on the ribs. The sternum closed massage.
is depressed by one-third of the depth of the European Resuscitation Council (2010). Resuscitation;
childs chest at a rate of 100120/min. 81: 121976
theories of mechanism (both may occur): See also, Cardiac output measurement
- cardiac pump (as originally suggested): the heart
is squeezed between sternum and vertebrae
during compressions, expelling blood from the Cardiac output (CO). Volume of blood ejected by the
ventricles. During relaxation, blood is drawn into left ventricle into the aortic root per minute. Equals
the chest by negative intrathoracic pressure, and stroke volume (litres) heart rate (beats/min). Normally
the ventricles fill from the atria (thoracic dias- about 5 l/min (0.07 litres 70 beats/min) in a fit 70-kg
tole). Thought to be more important in children man at rest; may increase up to 30 l/min, e.g. on vigorous
and when the heart is large. exercise. Often corrected for body surface area (cardiac
- thoracic pump: the theory arose from arterial and index).
cardiac chamber pressure measurements during Of central importance in maintaining arterial BP
CPR, and from the phenomenon of cough-CPR. (equals cardiac output SVR) and O2 delivery to the
Positive intrathoracic pressure pushes blood out tissues (O2 flux).
of heart and chest during compressions; reverse Affected by metabolic rate (e.g. increased in preg-
flow is prevented by cardiac and venous valves, nancy, sepsis, hyperthyroidism and exercise), drugs, and
and collapse of the thin-walled veins. During many other physiological and pathological processes
relaxation, blood is drawn into the chest by nega- that affect heart rate, preload, myocardial contractility
tive intrathoracic pressure. and afterload.
Cardiac output measurement 109

Distribution of normal CO (approximate values): measured by a thermistor at the catheter tip.

heart: 5%. Injection is usually performed at end-expiration.
brain: 15%. A plot of temperature drop against time is pro-
muscle: 20%. duced as for dye dilution but without the sec-
kidneys: 20%. ondary peak. Cardiac output is calculated by a
liver: 25%. bedside computer using the StewartHamilton
rest: 15%. equation and an average of at least three mea-
(for comparisons of blood flow and oxygen consumption, surements. Sources of inaccuracy include: the
see Blood flow) presence of intracardiac shunts or tricuspid
Effects of iv anaesthetic agents on CO: regurgitation; inaccurate measurement of injec-
reduced by propofol > thiopental > etomidate, tate volume or temperature; variation in the
mostly via decreased contractility, though propofol speed of injection; or if the thermistor is against
may also cause vasodilatation and bradycardia. a vessel wall. Repeated measurements are not
increased by ketamine. affected by previous ones.
Effects of inhalational anaesthetic agents on CO: In transpulmonary thermodilution cardiac output
reduced by enflurane > halothane > isoflurane/ measurement, ice-cold saline is injected via a
desflurane > sevoflurane > N2O. Proposed mecha- central venous catheter and is dispersed into both
nisms include direct myocardial depression (via intra- and extravascular spaces during passage
reduced concentration or modified activity of intra- through the lungs. Pulse contour cardiac output
cellular calcium ions during systole), inhibition of derived from rapid beat-to-beat analysis of the
central or peripheral sympathetic nervous system arterial (aortic) pressure wave is calibrated with
outflow, and altered baroreceptor activity. an arterial thermodilution measurement to give a
maintained by diethyl ether via sympathetic stimu- continuous indication of cardiac output. Use of an
lation despite a direct myocardial depressant effect. intra-arterial fibreoptic catheter and injection of
See also, Cardiac output measurement; Cardiac cycle cold dye allows measurement of intrathoracic
blood volume and extravascular lung water. If
Cardiac output measurement. Methods that have indocyanine green is used, the intravascular dye
been used include: distribution volume during the first cardiopulmo-
Fick principle: most commonly O2 consumption is nary passage equals intrathoracic blood volume;
measured using samples of mixed venous and arte- indocyanine green is extracted selectively from the
rial blood. Alternatively, CO2 production may be blood by the liver and this can therefore be used
measured, deriving arterial PCO2 from end-tidal as a liver function test. Total circulating blood
expired partial pressure. Mixed venous PCO2 may volume can be calculated after complete mixing of
be derived from analysis of expired gas collected the indocyanine green with the blood has occurred.
in a closed rebreathing bag, using a mass spectrom- - continuous: employs a specially modified pulmo-
eter. Both methods are lengthy, complicated and nary artery catheter, containing a thermal fila-
unsuitable for routine use. A new technique, ment extending 1425cm from its distal tip (thus
NiCO, employs partial PCO2 rebreathing and end- lying within both the right atrium and the right
expiratory CO2 measurement. ventricle during use), which adds an average of
dilution techniques: 7.5 W heat to the blood in a repetitive onoff
- dye dilution: a known amount of dye is injected sequence every 3060s. Changes in blood tem-
into the pulmonary artery, and its concentration perature are measured by a thermistor 4cm
measured peripherally using a photoelectric spec- from the catheter tip. A typical thermodilution
trometer. Indocyanine green is used because of its washout curve is constructed by applying a
low toxicity, short half-life and absorption charac- formula to correlate the thermistor temperature
teristics (i.e. unaffected by changes in O2 satura- with the thermal energy input sequence. Cardiac
tion). Semilogarithmic plotting of the data curve output is computed from the curve as above.
is required, with extrapolation of the straight line
obtained to correct for recirculation of the dye
(Fig. 35). Cardiac output is calculated from the
injected dose, the area under the curve within the
extrapolated line and its duration. Curves of short
Concentration of dye

duration are produced by high cardiac output; Secondary peak, due to

curves of long duration are produced by low recirculation of dye
cardiac output. Recirculation of dye may cause
data from repeated injections to be affected by
previous ones.
Lithium is an alternative to indocyanine green;
it is injected via a central venous catheter and
measured by a lithium-sensitive electrode incor-
porated into an arterial cannula, e.g. placed in the
radial artery.
- thermodilution: suitable for use in the ICU or
operating theatre: Ordinary plot
- intermittent: 510ml cold dextrose or saline is Semilogarithmic plot
injected through the proximal port of a pulmo-
nary artery catheter, with temperature changes Fig. 35 Dilution technique for measuring cardiac output
110 Cardiac pacing

- PiCCO: a technique combining transpulmonary repositioned if necessary. Dual-chamber pacing

thermodilution and arterial pulse contour may be achieved using a special atrial wire in
analysis. addition to the ventricular one.
echocardiography: two-dimensional echocar - tachyarrhythmias, e.g. SVT, atrial flutter: A00
diography can be used to measure left ventricular pacing is used, stimulating via a right atrial lead.
ejection fraction and subsequent derivation of The rate is slowly increased from 60/min to the
stroke volume. This relies on the shape of the spontaneous rate, held for 30s, and pacing
ventricular cavity being ellipsoid, which may not stopped. If unsuccessful, pacing at 400800/min
always be the case. Three-dimensional and trans may be used to provoke AF, which usually reverts
oesophageal echocardiography may produce better spontaneously to sinus rhythm. VT may be treated
results. by slow ventricular V00 pacing, atrial pacing or
a Doppler probe (oesophageal or suprasternal) may ventricular pacing at 1030% faster rate than
be used; the velocity of blood in the ascending aorta spontaneous for 510 beats only (burst pacing),
is measured using the Doppler effect, allowing esti- with defibrillation available. Advantages over car-
mation of the length of a column of blood passing dioversion include avoidance of anaesthesia and
through the aorta per unit time. This is multiplied the adverse effects of electrical shock, easier rep-
by the cross-sectional area of the aorta to give etition if unsuccessful and availability of pacing if
cardiac output. bradycardia or asystole occurs.
cardiac catheterisation and angiography allow esti- - the pacing wire may conduct extraneous currents
mation of left ventricular volume and ejection frac- directly to the heart (e.g. from diathermy) with
tion, as does radioisotope scanning. risk of electrocution (microshock).
impedance plethysmography and induction cardi- - transthoracic pacing may also be used, with large
ography: thought to be useful in estimating changes surface area skin electrodes (e.g. one over the
in individual subjects, but not useful for absolute cardiac apex, one over the right scapula or clavi-
measurements. cle) and pulse duration of up to 50 ms to reduce
aortovelography and ballistocardiography: cutaneous nerve and muscle stimulation. Avoids
inaccurate. complications of transvenous pacing, and quicker
electromagnetic flow measurement may be achieved to perform.
during surgery by placing a probe around the root - transoesophageal pacing has also been used but
of the aorta, but its use is obviously limited. is less reliable.
de Waal EE, Wappler F, Buhre WF (2009). Curr Opin permanent: a pulse generator (pacemaker) is
Anesth; 22: 717 implanted subcutaneously. Electrodes are usually
unipolar, i.e. one intracardiac electrode, with current
Cardiac pacing. Repetitive electrical stimulation of returning to the pacemaker via the body. The heart
myocardium, used to treat brady- or tachyarrhythmias. electrode is usually endocardial, passed via a central
May be: vein; epicardial electrodes have been used.
- transvenous: pacing wire passed via a central vein
to the right ventricle under X-ray control. Usually Cardiac risk indices. Scoring systems for preoperative
bipolar, with two electrodes at the end of the wire; identification of patients at risk from major periopera-
current passes from the distal to the proximal tive cardiovascular complications. The first, described by
electrode, stimulating adjacent myocardium. Goldman in 1977, was derived retrospectively from data
Wires may be rigid, or flexible and balloon-tipped. from 1001 patients undergoing non-cardiac surgery;
Complications and technique of insertion are as analysis identified nine differentially weighted variables
for central venous cannulation; the procedure correlating with increased risk:
may be technically difficult. In biventricular third heart sound/elevated JVP: 11 points.
pacing (for heart failure) a lead is also placed in MI within 6 months: 10 points.
the left ventricle via the coronary sinus. ventricular ectopic beats > 5/min: 7 points.
Indications include acute MI (inferior MI often rhythm other than sinus: 7 points.
requires temporary pacing; anterior often requires age > 70 years: 5 points.
permanent pacing). Preoperative use should be emergency operation: 4 points.
considered in: severe aortic stenosis: 3 points.
- heart block: third-degree, sometimes second- poor medical condition of patient: 3 points.
degree (e.g. if Mobitz type II, associated with abdominal or thoracic operation: 3 points.
symptoms or intended surgery is extensive). Patients with scores above 25 points had 56% incidence
- bundle branch block, e.g. symptomatic bifas- of death, with 22% incidence of severe cardiovascular
cicular block or PR prolongation. complications. Corresponding figures for scores below
- bradyarrhythmias. 26 points were 4% and 17% respectively, with 0.2% and
Technique of pacing: 0.7% for scores less than 6.
- bradyarrhythmias: once the wire is in place, the The more recent Revised Cardiac Risk Index identi-
pacemaker box is set to V00 (see below) and the fies six independent predictors of major cardiac compli-
minimal current is determined (usually about cations following non-cardiac surgery:
12mA). The pacing output is set 23 times high-risk surgery (intraperitoneal, intrathoracic or
higher and the system changed to VVI. Failure suprainguinal vascular surgery).
to pace may result from disconnections, over- history of ischaemic heart disease.
sensing or failure to capture. The pacing box history of heart failure.
should be converted to V00 and the wire cerebrovascular disease.
Cardiac surgery 111

insulin-dependent diabetes mellitus. commonly used. Ketamine is usually avoided.

preoperative serum creatinine > 177mol/l. Benzodiazepines have been used.
Relative risk of major cardiac events for no factors is standard neuromuscular blocking drugs are suit-
~0.4%; for one factor it is ~1%, for two factors ~2% and able; pancuronium is often used as it is long-
for three or more factors ~6%. acting and maintains BP, although it may cause
Confirmed by other studies as having high specificity tachycardia.
but low sensitivity; i.e. high-scoring patients are high risk, opioid analgesic drugs are used to provide a smooth
but not all high-risk patients are identified. induction and avoid the hypertensive response to
Other scoring systems are used for patients undergo- intubation, e.g. fentanyl 510g/kg, alfentanil 30
ing cardiac surgery (e.g. Parsonnet risk stratification 50g/kg or remifentanil 1g/kg followed by 0.05
scheme). 2g/kg/min. High-dose techniques (e.g. fentanyl or
[Lee B Goldman, Boston cardiologist; Victor Parsonnet, alfentanil up to 100125g/kg) have been used but
New Jersey cardiac surgeon] may necessitate prolonged postoperative IPPV.
Ford MK, Beattie S, Wijeysundera DN (2010). Ann N2O is often avoided because of myocardial depres-
Intern Med; 152: 2635 sion, especially in combination with high-dose
See also, Ischaemic heart disease; Preoperative opioids. It may also increase SVR and the size of air
assessment bubbles. Volatile inhalational anaesthetic agents are
commonly used. Isoflurane was found to cause cor-
onary steal in early animal models, but this concern
Cardiac surgery. First performed in the late 1800s but has been refuted; there is now good evidence that
limited by the effects of circulatory interruption. Use of volatile agents (including isoflurane) protect against
hypothermia increased the range of surgery possible, but subsequent ischaemic injury (anaesthetic precondi-
open heart surgery, i.e. employing cardiopulmonary tioning). TIVA with propofol is also commonly
bypass (CPB), was not developed until the 1950s. used. No primary anaesthetic agent has been found
Indications: to be superior to any other.
requiring CPB: maintenance of myocardial oxygen balance and
- ischaemic heart disease, i.e. coronary artery minimisation of ischaemia are of overriding impor-
bypass graft (CABG; but see below). tance; aims include avoidance of tachycardia, main-
- congenital heart disease, e.g. VSD, ASD, Fallots tenance of oxygenation and adequate diastolic
tetralogy. coronary perfusion pressure.
- others, e.g. heart transplantation, pulmonary Monitoring:
embolectomy for PE, chest trauma. 5-lead ECG.
not requiring CPB: patent ductus arteriosus, aortic direct arterial BP measurement.
coarctation, pericarditis, cardiac tamponade. CABG CVP measurement.
is increasingly performed off-pump. pulmonary artery catheterisation may be used in
percutaneous procedures, e.g. percutaneous translu- complex cases. Left-sided pressures may be mea-
minal coronary angioplasty and stent insertion and sured directly via a needle during surgery.
pacemaker insertion, are usually performed under transoesophageal echocardiography is routinely
local anaesthesia. General anaesthesia is required used. An oesophageal Doppler probe may be used
for electrophysiological studies and insertion of to assess perioperative myocardial workload and
implantable defibrillators. myocardial ischaemia.
Preoperative assessment and management: temperature measurement (core and peripheral).
as for ischaemic and congenital heart disease. electrolyte and blood gas interpretation should be
Cardiac risk index may be used for assessing risk. readily available. Activated clotting time (ACT)
Cardiac failure is particularly important. Respira- may be determined in the operating theatre (see
tory and cerebrovascular disease is common. Inves- Coagulation studies).
tigations include assessment of respiratory, renal, a urinary catheter is usual unless surgery is straight-
and liver function and coagulation studies. CXR, forward and short.
ECG, cardiac catheterisation studies and echocar- Pre-CPB management:
diography are routine. Carotid Doppler studies may stimulation during sternotomy may require further
be indicated. analgesia to prevent tachycardia and hypertension.
most cardiovascular drugs are continued. Oral anti- after baseline ACT measurement, heparin 23mg/
coagulant drugs are usually stopped or changed to kg (90mg/m2 surface area) is injected via a tested
heparin. central line. Prostacyclin has been used but is
traditional heavy premedication regimens have expensive and its role is uncertain. ACT measured
largely been replaced with single-agent anxiolysis after 1min should be > 480s or three times base-
(e.g. temazepam) if required. Premedication is often line; aortic and right atrial cannulation may then be
omitted in emergency surgery. Antibiotic prophy- performed for CPB.
laxis is usual. Management during CPB:
Induction and maintenance of anaesthesia: circulation is gradually taken over by the pump.
preoxygenation is usually employed. drugs are diluted by the crystalloid prime, thus
venous and arterial cannulation is usually per- further iv boluses are often required, e.g. opioid,
formed under local anaesthesia. Central venous benzodiazepine, induction agent, neuromuscular
cannulation is often reserved until the patient is blocking drug. Fentanyl may be taken up by the
anaesthetised. oxygenator membrane. Drugs, including inhala-
iv induction employs standard agents in small tional agents, may be added to the CPB circuit.
doses, as for ischaemic heart disease. Etomidate is haemodilution occurs.
112 Cardiac tamponade

hypothermia is used to reduce myocardial O2 - vasodilators (often combined with inotropes).

requirements and provide neuroprotection; the - correction of potassium/acidbase imbalance.
aorta is cross-clamped and cardioplegia used, low- - intra-aortic counter-pulsation balloon pump is
ering heart temperature to 1015C. Intentional occasionally required.
fibrillation is sometimes used, avoiding cardiople- heparin is reversed with protamine, injected slowly
gia. Mild hypothermia (3235C) is often used to reduce side effects, especially pulmonary hyper-
to provide some neuroprotection while avoiding tension. 1mg/mg heparin is usually used.
problems of moderate (2832C) and profound hypertension is common if left ventricular function
(2227C) hypothermia, especially disturbed coagu- is good, especially in aortic valve disease; vasodila-
lation. Lower temperatures (1520C) are used tors may be required.
during circulatory arrest. temperature may fall as core heat is transferred to
IPPV is stopped; continuous positive pressure is the periphery.
sometimes applied to maintain some lung expan- arrhythmias and heart block may occur.
sion. Air is thought to be better than 100% O2 pericardial and pleural drains are inserted before
because of increased atelectasis with the latter; N2O sternal closure.
is avoided because of the risk of air embolism. transfer to ICU must be carefully managed because
optimal perfusion pressure is controversial; of the potential dangers from interrupted monitor-
50mmHg is generally thought to be the minimum. ing and infusions, and movement.
CPB details are also controversial, e.g. type of oxy- specific postoperative concerns include:
genator, pulsatile/non-pulsatile flow. - bleeding: may be surgical, or caused by consump-
SVR decreases as haemodilution occurs; vasopres- tion or dilution of platelet and coagulation
sor drugs (e.g. phenylephrine or metaraminol) may factors during CPB, the effects of massive blood
be needed to maintain perfusion pressure. SVR transfusion, or inadequate reversal of heparin.
then slowly increases due to absorption of the Perioperative aprotinin, antifibrinolytic drugs and
crystalloid and vasodilatation with GTN or phentol- desmopressin have been used to reduce blood
amine may be needed. Some cardiovascular drugs requirements.
such as nicorandil and angiotensin converting - treatment of hyper-/hypotension and
enzyme inhibitors may exacerbate hypotension. arrhythmias.
ACT is checked every 30min, with further heparin - low-output state, as above. Cardiac tamponade
given if necessary, e.g. one-quarter to one-half initial may necessitate thoracotomy on ICU.
dose. Potassium is added as required. Arterial - maintenance of fluid balance and urine output.
blood gas analysis is performed at 37C in most The crystalloid load from CPB usually causes
machines; values have been traditionally corrected diuresis but pulmonary oedema may occur, espe-
to body temperature to account for increased cially if cardiac output is low.
solubility of CO2 at low temperatures (pH stat), - rewarming; central/peripheral temperature differ-
but this is now considered unnecessary and man- ence is a useful indication.
agement conducted according to uncorrected - maintenance of electrolyte, acidbase and blood
values (alpha stat). Bicarbonate is usually not gas balance. Hypokalaemia is common.
administered unless base deficit exceeds 78mmol/l. - IPPV is usually continued for a few hours,
Blood is transfused to keep the haematocrit above sometimes overnight. Opioid/benzodiazepine
0.20.3. boluses are commonly used for sedation. Immedi-
after repair of the lesion, the cross-clamp is removed ate extubation after surgery is increasingly per-
and rewarming undertaken. Cardiac activity (usually formed in appropriately selected cases. Usual
VF but sometimes sinus rhythm) usually returns criteria for weaning include cardiovascular and
spontaneously. Internal defibrillation is performed respiratory stability, adequate warming and
at 3032C, and normal PO2, pH and electrolyte perfusion, good urine output, minimal blood loss
concentration. 2050 J is usually used. Cardiac and good conscious level. Impaired gas exchange
pacing is sometimes required; epicardial wires may may be associated with pre-existing lung disease,
be inserted prophylactically for postoperative use. atelectasis, and CPB-related factors (e.g. emboli-
CPB blood flow is gradually decreased as cardiac sation with bubbles and platelet aggregates,
output increases. Drug boluses are given iv as complement activation), especially if CPB was
before. Manual IPPV helps expel air from the pul- prolonged.
monary vessels. - CNS changes: CVA occurs in less than 2% of
Post-CPB and postoperative care: patients undergoing open-heart surgery, but
left atrial pressure is optimised to 812mmHg; subtle changes are found in up to 60%, thought
vasodilators are used to accommodate CPB fluid to be related to embolisation (e.g. bubbles, aggre-
volume. gates during CPB) and/or inadequate perfusion.
a low-output state may occur, especially if ventricu- Effects are possibly reduced by filtering the arte-
lar function was poor preoperatively and ischaemia rial inflow line.
time was prolonged. It may be improved by:
- inotropic drugs: calcium is often used as a tempo-
rary measure but may worsen reperfusion injury. Cardiac tamponade. Compression of the heart by
Others include dopamine, dobutamine, adrena- fluid (e.g. blood) within the pericardium, restricting
line and isoprenaline; more recently enoximone, ventricular filling and reducing stroke volume and
milrinone and dopexamine. The choice is accord- cardiac output.
ing to individual patient and drug characteristics, Myocardial O2 supply is reduced by hypotension,
and personal experience. increased end-diastolic pressure, tachycardia and
Cardiomyopathy 113

compression of epicardial vessels. Tamponade should be Cardioinhibitory centre (Cardioinhibitory area). Con-
differentiated from pneumothorax and cardiac failure. sists of the nucleus ambiguus and adjacent neurones in
Features: the ventral medulla, with some input from the dorsal
dyspnoea, restlessness, oliguria, hypotension, motor nucleus and nucleus of the tractus solitarius. Pro-
peripheral vasoconstriction. JVP, CVP and left duces vagal tone, increased by baroreceptor discharge.
atrial pressure are raised, and pulsus paradoxus is Also receives afferents from higher centres. Efferents
present. Jugular venous distension may occur during pass to the vasomotor centre, inhibiting it, and thence to
inspiration or when pressure is applied over the the heart via the vagus nerve. Thus involved centrally in
liver (Kussmauls sign). Cardiovascular collapse and controlling arterial BP.
death may occur, especially if acute (e.g. following
chest trauma).
ECG complexes may be small, and the heart shadow Cardiomyopathy. Encompasses disorders of myocar-
globular and enlarged on the CXR. Confirmed by dial function from any cause, categorised by the World
echocardiography. Health Organization as either extrinsic (specific pathol-
Immediate management is pericardiocentesis; surgery ogy secondary to a well-defined cause, e.g. ischaemic,
may be required subsequently. hypertensive, valvular, inflammatory) or intrinsic (gen-
Anaesthetic considerations: drugs or manoeuvres eralised pathology with less discrete aetiology).
which reduce venous return, heart rate or myocardial Intrinsic myocardial disorders are defined according
contractility should be avoided, especially with to pathophysiology:
coexistent hypovolaemia. IPPV should be performed dilated (congestive):
cautiously. - reduced contractility and ejection fraction, with
[Adolf Kussmaul (18221909), German physician] ventricular dilatation.
See also, Cardiac surgery - causes cardiac failure, arrhythmias, angina and
systemic embolism from mural thrombus.
Cardiogenic shock. Shock due to primary cardiac pump - prognosis is poor; death is usually within a few
failure. Diagnosis is suggested by acute haemodynamic years of cardiac failure.
changes, including: - may be associated with alcoholism, viral infection,
systolic BP 30mmHg below basal levels for more cytotoxic drugs, connective tissue diseases, and
than 30min. metabolic and infiltrative disorders, e.g. sarcoid-
cardiac index < 2.2 l/min/m .
osis. Peripartum cardiomyopathy is defined as
arteriovenous oxygen difference > 5.5ml/100ml. that occurring in the absence of other causes and
pulmonary capillary wedge pressure (PCWP) > in the last month (the last trimester has been sug-
15mmHg. gested) of pregnancy or the first 5 months after
Most commonly caused by acute MI affecting either pregnancy. It typically presents as cardiac failure
right or left ventricle, but it may also follow cardiac and may recur in subsequent pregnancies.
surgery, chest trauma and acute myocarditis. Heart - treatment includes digoxin, diuretics, antiarrhyth-
rate and SVR are usually increased to compensate for mic drugs, vasodilator drugs and anticoagulant
hypotension, exacerbating myocardial O2 supply/ drugs.
demand imbalance. Acidosis resulting from poor perfu- - anaesthetic management: as for ischaemic heart
sion further impairs myocardial contractility. disease and cardiac failure. Myocardial depres-
Features: sion, hypovolaemia and increased SVR are par-
as for shock. ticularly hazardous.
increased left ventricular end-diastolic pressure and hypertrophic (obstructive; HOCM):
pulmonary oedema are usual. However, relative - familial disorder, with left ventricular hypertro-
hypovolaemia may be present due to redistribution phy especially affecting the upper interventricular
of fluid to lungs, previous fluid restriction, diuretic septum, causing left ventricular outflow obstruc-
therapy and sweating. Right-sided failure may tion. Epidemiological screening studies suggest a
occur, e.g. in right ventricular infarction. prevalence of 1 in 500 in the general population,
Management: with the majority undiagnosed.
treatment of underlying cause; if caused by coro- - causes arrhythmias, syncope, angina, cardiac
nary artery occlusion, early percutaneous translu- failure and sudden cardiac death. Infective endo-
minal coronary angioplasty or coronary artery carditis may occur.
bypass graft improves prognosis. - treatment includes diuretics, antiarrhythmics
optimising left ventricular end-diastolic pressure; and -adrenergic receptor antagonists; the last
PCWP is a more useful guide than CVP, unless reduce force and rate of contraction, reducing
failure is predominantly right-sided. A PCWP of outflow obstruction. Conversely, digoxin should
1822mmHg is thought to be optimal for the failing be avoided. Anticoagulants are often used in sus-
heart, even though this is higher than normal. tained arrhythmias. Surgical myectomy or alcohol
Colloid is usually given if PCWP is low; inotropic ablation is used to relieve obstruction and severe
and vasodilator drugs if PCWP is high. refractory symptoms.
intra-aortic counter-pulsation balloon pump and - anaesthetic management includes avoidance of
cardiac surgery may be required. tachycardia and increased myocardial work,
Prognosis is generally poor, especially after MI (mortal- arrhythmias, hypovolaemia and reduced SVR.
ity 7090%) and without aggressive therapy. restrictive:
Topalian S, Ginsberg F, Parillo JE (2008). Crit Care Med; - very rare; due to fibrosis or infiltration.
36: S6674 - effects and management are as for constrictive
See also, Cardiac failure pericarditis.
114 Cardioplegia

ECG is usually non-specific, showing arrhythmias, Usual solution pH is 5.57.8 and osmolality 285300
bundle branch block, ventricular hypertrophy and isch- mosmol/kg.
aemia. CXR may show cardiac enlargement and pulmo-
nary oedema. Echocardiography, cardiac catheterisation Cardiopulmonary bypass (CPB). Developed largely by
and nuclear cardiology may be useful. Gibbon in the 1950s from animal experiments performed
Davies MJ (2000). Heart; 83: 46974 in 1937. Haemolysis was caused by initial disc/bubble
oxygenators; improved membrane oxygenators were
developed in the late 1950s. Used in cardiac surgery;
Cardioplegia. Intentional cardiac arrest caused by coro- similar techniques are used for extracorporeal mem-
nary perfusion with cold electrolyte solution, to allow brane oxygenation and extracorporeal CO2 removal in
cardiac surgery. After establishment of cardiopulmonary respiratory failure.
bypass, a cannula is inserted into the ascending aorta and Principles:
connected to a bag of solution (traditionally at 4C), venous drainage: under gravity via a right atrial
having excluded air bubbles. After aortic cross-clamping cannula or separate superior/inferior vena caval can-
distal to the cannula, the solution is passed under 200 nulae if the right atrium is opened. Blood also drains
300mmHg pressure into the aortic root, closing the via right atrial and left heart suckers/vents to avoid
aortic valve and perfusing the coronary arteries. In aortic pooling of blood in the operative field. Blood passes
valve incompetence, individual coronary artery cannula- through a filter and defoaming chamber, which may
tion may be required. Severe coronary stenosis may be combined with a reservoir and/or oxygenator.
require further injection of solution through the bypass oxygenator: older bubble oxygenators have been
graft or retrograde perfusion via the coronary sinus. replaced by membrane oxygenators since the 1980s,
Asystole usually occurs after 100200ml, but 1 litre is the latter being associated with greater haemody-
used (20ml/kg in children) in order to cool the heart to namic stability, reduced coagulopathy and fewer
1012C. embolic phenomena.
Further infusion may be required in prolonged Consist of hollow capillary fibres through which
surgery. Cold saline is placed around the heart to main- blood passes, with gas exchange across their walls.
tain hypothermia. Flat membrane oxygenators are also available. Can
Solutions used may contain: also be used for concurrent ultrafiltration. Most
NaCl 110140mmol/l: prevents excess water accu- incorporate temperature exchangers, and may
mulation. May increase calcium entry if sodium therefore be used in the treatment of severe, refrac-
concentration is too high. tory hypothermia. CO2 and O2 are supplied inde-
KCl 1020mmol/l: causes depolarisation and pendently to the oxygenator as required, e.g. 2.5%
cardiac arrest in diastole, reducing myocardial O2 CO2 in O2.
demand. Higher concentrations may cause arterial pumps: usually rotating roller pumps using wide
spasm. tubing. Rotating chambers (centrifugal pumps) are
MgCl2 16mmol/l and CaCl2 1.22.2mmol/l: reduce also used, reducing damage to blood components.
automatic rhythmogenicity and protect against Flow is traditionally non-pulsatile but pulsatile flow
potassium-induced damage post-bypass. Excessive may provide better organ perfusion, with lower
calcium may cause persistent myocardial contrac- vasopressin and angiotensin levels; however, the
tion (stone heart). Magnesium reduces calcium equipment required is more complex and expen-
entry. sive. Pulsations may be synchronised with the ECG
NaHCO3 010mmol/l. if the heart is pumping. Flows used vary between
procaine 01mmol/l: membrane stabiliser, reducing centres but are usually 1.02.4 l/min/m2 surface area
arrhythmias post-bypass. (up to 80ml/min/kg).
other additives are more controversial, and arterial return: via ascending aorta (rarely, femoral
include: artery) using a short wide cannula to reduce resis-
- buffers, e.g. histidine and tromethamine: help tance and avoid accidental cannulation of aortic
maintain normal intracellular pH and encourage branches. The return is filtered to remove platelet
ATP generation. aggregates, fibrin and debris. 5-40 m filters are
- metabolic substrates, e.g. glucose and amino acids: standard; the smaller filters reduce microemboli but
increase ATP generation. increase platelet consumption and risk of comple-
- mannitol: reduces water accumulation and may ment activation.
improve cardiac function. Use:
- free radical scavengers. disposable systems are usually employed.
- corticosteroids. the system is primed with 1.52.5 litres crystalloid
- calcium channel blocking drugs. usually, although colloid may be used. The resulting
Other controversies: haemodilution improves perfusion at low tempera-
use of blood instead of crystalloid: improved oxy- tures, and is usually corrected postoperatively by an
genation with optimal osmotic, buffer and meta- appropriate diuresis.
bolic make-up, but increased viscosity limits the use anticoagulation, introduction and termination of
of hypothermia. CPB: as for cardiac surgery.
oxygenation of the solution. Complications:
use of warm solution: may cause better myo technical, e.g. leaks, bubbles, disconnections, obstruc-
cardial relaxation, with reduced membrane tion, coagulation, power failure. Vascular damage
and protein damage associated with low tempera- may occur during cannulation.
tures. embolisation with clot, debris, bubbles and defoam-
continuous versus intermittent injection. ing agent. Bubbles may enter via the heart cavity
Cardiopulmonary resuscitation, neonatal 115

during surgery, especially at end of bypass. Subtle advanced life support: as above, plus use of spe-
neurological changes are thought to be related to cialised equipment, techniques (e.g. tracheal intuba-
microembolisation. tion), drugs and monitoring.
related to surgery or anticoagulation. Regular updates on guidelines are provided by the
[John H Gibbon (19031974), US surgeon] Resuscitation Council (UK), European Resuscitation
Council, International Liaison Committee on Resuscita-
Cardiopulmonary exercise testing (CPX/CPEX tion and the American Heart Association (see Basic life
testing; CPET). Integrated assessment of cardiopulmo- support, adult; Advanced life support, adult).
nary function at rest and during incrementally increasing See also, Brainstem death; Cardiopulmonary resuscita-
levels of exercise. BP, ECG, ventilatory parameters and tion, neonatal; Cardiopulmonary resuscitation, paediat-
respiratory gases are measured throughout, and used to ric; Cough-CPR
derive two major indicators of cardiopulmonary func-
tion: maximum oxygen uptake (V O2 max ) and anaerobic Cardiopulmonary resuscitation, neonatal. Prompt
threshold. Several protocols exist, most utilising a tread- resuscitation is important in order to prevent permanent
mill or exercise bicycle for approximately 10min. A mental or physical disability. Neonatal cardiac arrest
bicycle is most commonly used for perioperative assess- is almost always caused by hypoxaemia and thus
ment as it is more stable and measurements are less prompt management of apnoea and airway obstruction
prone to movement artefact. is vital.
Indications include: Equipment required includes:
preoperative evaluation and risk stratification. a tilting resuscitation surface, with radiant heater,
evaluation for heart/lung transplantation. clock and pulse oximetry.
investigation of undiagnosed exercise intolerance. suction equipment.
evaluation of exercise tolerance, functional capacity, O2 with funnel and facemasks.
disability or response to treatment. self-inflating bag (volume 250ml, with pressure
Thought to predict the patients capacity to respond relief valve set at 3035 cmH2O).
to the physiological stress of major surgery. Estab- pharyngeal airways (sizes 000, 00 and 0).
lished predictor of perioperative morbidity and mortal- tracheal tubes (uncuffed). Suitable sizes:
ity in patients undergoing pulmonary resection. More - 2.02.5mm for babies under 750g weight or 26
recent evidence suggests that testing may also be useful weeks gestation.
in other contexts (e.g. aortic aneurysm repair, laparot- - 2.53.0mm for 7502000g or 2634 weeks.
omy in elderly patients), both for initial patient - 3.03.5mm for over 2000g or 34 weeks.
selection and guiding the level of postoperative care laryngoscope, usually with straight blade (size 01).
required. iv cannulae, including umbilical venous and arterial
Smith TB, Stonell C, Purkayastha S, Paraskevas P (2009). catheters.
Anaesthesia; 64: 88393 Requirement for resuscitation may be anticipated from
the course of pregnancy and labour and fetal monitoring.
Cardiopulmonary resuscitation (CPR). Over many Elements of the Apgar score may also be useful.
centuries, numerous techniques have been tried in Greater emphasis is placed on maintaining a patent
order to restore life; early attempts included use of airway and providing adequate ventilation than for adult
heat, smoke, cold water, beating and suspension from CPR; cardiac massage is only started once adequate ven-
ropes. tilation has been achieved:
Artificial ventilation was developed within the last dry, stimulate and wrap the baby. Babies < 30 weeks
400 years: gestation should be wrapped in food-grade plastic
use of bellows via the mouth or nose is attributed without drying; all neonates should be placed under
to Paracelsus in the early 1500s. Used via tracheal a radiant heater in the first instance.
tubes in the 1700s, e.g. by Kite. airway management: early aggressive suctioning of
postural techniques, e.g. compressing the chest and pharynx and trachea is no longer recommended.
abdomen from behind with the victim prone, Suction is only indicated if there is copious thick
moving the arms, or using tilting boards: used from meconium visible in the mouth and the baby is non-
the 1850s. vigorous. To open the airway the head should be
expired air ventilation: developed in the 1700s, placed in the neutral position (with the aid of a
although reported earlier. towel placed under the shoulders) and a jaw thrust
Cardiac massage, external and internal, was first manoeuvre applied if required.
attempted in the late 1800s; external massage was initial assessment of the respiratory effort, heart
popularised in the early 1960s. rate, colour and tone:
Defibrillation was investigated in animals in the - adequate respiration, heart rate > 100 beats/min,
1700s/1800s; internal defibrillation was performed in the baby is centrally pink with good tone: no
humans in the 1940s and external defibrillation in further treatment required.
the 1950s. - heart rate < 100 beats/min or absent/inadequate
CPR is divided into: respiration: 5 inflation breaths lasting for 23s, to
basic life support (BLS): traditionally without any aid lung expansion. Airway pressures should not
equipment, and therefore suitable for lay-person exceed 3035 cmH2O (20 cmH2O in the preterm
resuscitation. Increasingly includes the use of neonate). Air should be used in the first instance,
simple equipment (although this has been defined switching to oxygen if there is poor initial response.
as basic life support with airway adjuncts), e.g. If there is no response, adequacy of ventilation
airways, face-pieces, self-inflating bags, oesopha- (i.e. good chest wall movement) should be checked
geal obturators, LMAs. and a further five inflations attempted, with
116 Cardiopulmonary resuscitation, paediatric

airway adjuncts if appropriate. If still no response, two fingers; in older children the heel of the
tracheal intubation should be considered. palm or both hands may be used. Whatever the
if heart rate < 60 beats/min despite good ventilation, technique, compressions should be applied to
cardiac massage should be instituted, with both the lower half of the sternum, compressing the
hands encircling the chest or using two fingers (see chest by one-third of its total depth.
Cardiopulmonary resuscitation, paediatric). Com- - ratio for cardiac massage:breaths of 15:2.
pressions should occur at 120 beats/min, depressing advanced life support:
the sternum one-third of the depth of the chest, and - iv access/monitoring/airway management as for
with a compression:ventilation ratio of 3:1. Stan- adults. An intraosseous needle should be used if
dard ventilation breaths are 1s in duration. Cardiac venous access is difficult (see Intraosseous fluid
massage is futile unless adequate ventilation is administration). For monitoring small children via
provided. the defibrillator, it may be easier to apply the
if heart rate remains < 60 beats/min after 30s of paddles to the front and back of the chest.
cardiac massage, drugs should be given: - asystole/pulseless electrical activity:
- umbilical venous catheterisation is usually the - adrenaline 10g/kg iv/im, repeated every
most accessible route for iv administration of 35min. Tracheal administration is no longer
drugs (N.B. the umbilical cord contains a single recommended, but was previously given at 10
vein and two arteries). times the iv dose.
- initial iv drugs: adrenaline 1:10000: 0.1ml/kg ini- - BLS for a further 2min.
tially, then 0.3ml/kg, then 1ml/kg after 4.2% - VF/VT:
bicarbonate 12ml/kg (higher concentrations - defibrillation using 4 J/kg (one paddle below the
have been associated with intraventricular haem- right clavicle, the other at the left anterior axil-
orrhages). The cannula should be flushed with lary line).
saline after each drug. - BLS for further 2min, then repeat the above.
- administration of adrenaline via the tracheal tube - repeat as necessary; after the third shock give
is not recommended, but if it is given would amiodarone 5mg/kg and an immediate fourth
require doses of 0.51ml/kg. Bicarbonate must shock. Consider reversible causes of cardiac
not be given via the tracheal route. arrest.
- others: Special situations: choking, electrocution, near-
- crystalloid (e.g. NaCl 0.9%) 10ml/kg if hypovo- drowning, trauma, neonatal CPR (see Cardiopulmo-
laemia or sepsis is suspected. nary resuscitation, neonatal).
- 10% dextrose 22.5ml/kg if hypoglycaemia is Other drugs:
present. atropine is no longer recommended for non-
- naloxone 10mg/kg im, iv or sc, repeated shockable rhythms.
every 23min or 60g/kg im as a single injec- bicarbonate: 1mmol/kg iv (1ml/kg 8.4%
tion, if the mother has received opioids during solution).
labour. calcium chloride: 0.2mmol/kg iv (0.3ml/kg 10%
Congenital abnormalities (e.g. diaphragmatic hernia, solution).
tracheo-oesophageal fistula) should be considered in glucose 10%: 1g/kg iv (10ml/kg).
babies who do not respond to resuscitation. Fluid bolus in hypovolaemia: 10ml/kg colloid (tradi-
European Resuscitation Council (2010). Resuscitation; tionally 4.5% albumin initially).
81: 121976 European Resuscitation Council (2010). Resuscitation;
See also, Pugh, Benjamin 81: 121976
See also, Paediatric anaesthesia
Cardiopulmonary resuscitation, paediatric. The same
principles apply as for adult CPR, but primary cardiac Cardioversion, electrical. Restoration of sinus rhythm
disease is uncommon. Sinus bradycardia progressing to by application of synchronised DC current across
asystole is more common, especially if due to hypoxae- the heart. Current delivery is synchronised to occur
mia or haemorrhage. Thus cardiac arrest is often second- with the R wave of the ECG, since delivery during
ary to respiratory arrest or exsanguination, and usually ventricular repolarisation may produce VF (R on T
represents a severe insult. phenomenon).
2010 Recommendations of the Resuscitation Council Used for:
(UK), adapted from European Resuscitation Council AF, particularly of recent onset.
Guidelines: atrial flutter; usually successful with low energy.
basic life support (BLS): VT, usually successful with low energy.
- assess as for adults. a lone rescuer should continue SVT.
for about a minute before seeking help. Energy levels of 20200 J are usually used.
- ABC of resuscitation: Digoxin-induced arrhythmias may convert to serious
- Airway: as for adults. ventricular arrhythmias; therefore digoxin is usually
- Breathing: 5 initial rescue breaths by expired air withheld for at least 24h.
ventilation, each over 11.5s; mouth to mouth In chronic atrial arrhythmias, anticoagulation is often
and nose if < 1 year, mouth to mouth otherwise. administered to reduce risk of systemic embolisation.
Only 5 breaths should be attempted; if unsuc- Preparation of the patient, drugs and equipment, and
cessful, move on to circulation. monitoring should be as for any anaesthetic. The proce-
- Circulation: up to 10s to check for pulse or dure is painful, therefore requiring brief sedation/
signs of life, then external cardiac massage at anaesthesia. A single iv agent is commonly used, e.g.
100/min. In infants this may be delivered using thiopental, etomidate, propofol or diazepam. Further
Carotid endarterectomy 117

injections may be required if repeated shocks are - branches, from below upwards:
delivered. - ascending pharyngeal.
See also, Defibrillation