Principles of intravenous fluid therapy

Jonathan Paddle
Consultant in Intensive Care Medicine Royal Cornwall Hospitals NHS Trust

3rd September 2007

"On the floor lay a girl of slender make and juvenile height, but with the face of a superannuated hag... The colour of her countenance was that of lead - a silver blue, ghastly tint; her eyes were sunk deep into sockets, as though they had been driven an inch behind their natural position; her mouth was squared; her features flattened; her eyelids black; her fingers shrunk, bent, and inky in their hue In short, Sir, that face and form I can never forget, were I to live beyond the period of man's natural age."

WILLIAM BROOKE OSHAUGHNESSY

Edinburgh graduate, age 22 from Limerick

Investigated cholera outbreak in Sunderland: Noted blood ..has lost a large part of its water content.. and.. a great proportion of its neutral saline ingredients.., leading to venalisation (blue, thick and cold); established that the stools contained the missing elements in proportion Therapeutic conclusions: 1. To restore the blood to its natural specific gravity; 2. To restore its deficient saline matters

by the injection of aqueous fluid into the veins.

She had apparently reached the last moment of her earthly existence and now nothing could injure her... Having inserted a tube into the basilic vein, cautiously, anxiously, I watched the effects; ounce after ounce was injected but no visible change was produced. Still persevering, I thought she began to breathe less laboriously, soon the sharpened features, the sunken eye and fallen jaw, pale and cold, bearing the manifest impress of deaths signet, began to glow with returning animation; the pulse, which had long ceased, returned to the wrist; at first small and quick, by degrees it became more distinct, fuller, slower and firmer, and in the short space of half an hour, when six pints had been injected, she expressed in a firm voice that she was free from all uneasiness, actually became jocular, and fancied all she needed was a little sleep; her extremities were warm and every feature bore the aspect of comfort and health. This being my first case, I fancied my patient secure, and from my great need of a little repose, left her in charge of the Hospital surgeon

Thomas A Latta, Leith Physician. Lancet June 18th 1832

.. But I had not been long gone, ere the vomiting and purging recurring, soon reduced her to her former state of disability and she sunk in five and a half hours after I had left her I have no doubt, the case would have issued in complete reaction, had the remedy, which had already produced such effect, been repeated.

Dr Lattas Saline solution

Two to three drachms of muriate of soda (NaCl), two scruples of the bicarbonate of soda in six pints of water and injected it at temperature 112 Fah
( approx 58mmol/l Na, 49 mmol/l Cl, 9 mmol/l bicarbonate) Ten of the first fifteen patients died

The present day

Current controversies in fluid therapy

How much fluid to give Which fluid to use

Assessment of volume status

Look at the patient:
Pulse Blood pressure Capillary refill Mucous membranes Peripheral circulation Thirst

Assessment of volume status

Try a more invasive approach: Urine output Arterial line Central venous line PA catheter Oesophageal doppler

Assessment of volume status

How about blood tests? U&Es Haematocrit Plasma/urine osmolality Arterial blood gases Lactate

Assessment of volume status

OK, so the patient needs fluid

How much should we give?

Trauma
598 adults with penetrating torso injuries Randomised to standard care or no fluids until time of operation
75% 70% 65% 60% 55% 50% Standard Restrictive Mortality

P=0.04

Bickell WH et al. Immediate versus Delayed Fluid Resuscitation for Hypotensive Patients with Penetrating Torso Injuries. NEJM 1994; 331: 1105-9

Trauma
Cochrane Database of Systematic reviews Six randomised controlled studies No evidence in support or against early aggressive fluid resuscitation 52 animal trials hypotensive resuscitation reduced risk of death

Peri-operative
138 patients undergoing major elective abdominal surgery Randomised to one of three groups (one control and two goal directed therapy groups

Wilson J et al. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. BMJ 1999; 318: 1099-103

Peri-operative
Goal-directed therapy was aimed at optimising oxygen delivery to tissues with:
Fluids Inotropes

Extra 1500 ml fluids pre-op

Guided by invasive PA catheter monitoring

Wilson J et al. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. BMJ 1999; 318: 1099-103

Peri-operative

Wilson J et al. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. BMJ 1999; 318: 1099-103

However
RCT 172 patients undergoing elective colorectal resection Restrictive fluid regime (to maintain neutral body weight) vs. standard post-op fluids

Complications: 33% versus 51% (P = 0.013)

Brandstrup B et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg. 2003; 238(5): 641-8.

Sepsis and the critically ill

Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock
Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D., Suzanne Havstad, M.A., Julie Ressler, B.S., Alexandria Muzzin, B.S., Bernhard Knoblich, M.D., Edward Peterson, Ph.D., Michael Tomlanovich, M.D., for the Early Goal-Directed Therapy Collaborative Group

Volume 345: 1368-1377

November 8, 2001

Sepsis and the critically ill

263 patients presenting with severe sepsis Single-centre: large American Emergency department

Randomised to standard therapy or goaldirected therapy

Rivers E et al. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. NEJM 2001; 345: 1368-77

Protocol group

Treatment given
0-6 hours EGDT Fluids (ml) Standard 4991 3499 7-72 hours 8625 10602 0-72 hours 13443 13358

P value
EGDT RBC transfusion (%) Standard P value EGDT Standard P value EGDT Dobutamine use (%) Standard P value EGDT Mechanical ventilation (%) Standard P value EGDT PA Catheter use (%) Standard P value

<0.001
64.1 18.5 <0.001 27.4 30.3 0.62 13.7 0.8 <0.001 53.0 53.8 0.90 0 3.4 0.12

0.01
11.1 32.8 <0.001 29.1 42.9 0.03 14.5 8.4 0.14 2.6 16.8 <0.01 18.0 28.6 0.04

0.73
68.4 44.5 <0.001 36.8 51.3 0.02 15.4 9.2 0.15 55.6 70.6 0.02 18.0 31.9 0.01

Vasopressor use (%)

The take-home message!

Resuscitate with fluids early and aggressively
They wont get overloaded They wont get pulmonary oedema They will be less likely to need ICU

Be guided by markers of tissue perfusion

Urine output Lactate Consider central venous oxygen saturations

FACTT Study
Comparison of two fluid management strategies in acute lung injury Randomised controlled trial 1001 patients with ARDS or ALI Conservative v liberal fluid therapy Also compared PAC or CVC Mortality at 60 days, vent free days, organ failure free days
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-2575

FACTT
Fluid restriction 43 hrs post admission 24 hours post ALI/ARDS Renal failure pts excluded Volume replete patients

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-2575

FACTT
No significant difference in mortality Restrictive fluid group had:
Better oxygenation indexes More ventilator free days Less renal failure in conservative group

Recommendations: Conservative fluid approach without PAC But..

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-2575

FACTT
Increase in cardiovascular failure days in patients in conservative group Caution in fluid depleted patients. Relative young age of patients ? Realistic study population

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-2575

Now for which fluid

What is the choice?

Crystalloids
Saline Dextrose Hartmanns

Colloids
Albumin Gelatins Starches

Fluid distribution

Cell membrane

Capillary wall

Practical differences
Roberts I, Alderson P, Bunn F, P Chinnock, K Ker and Schierhout G.
Colloids versus crystalloids for fluid resuscitation in critically ill patients (Cochrane Review).
The Cochrane Library, Issue 4, August 24th, 2004

Albumin vs. crystalloid

HES vs. crystalloid

Gelatin vs. crystalloid

Dextran vs. crystalloid

There is no evidence from randomised controlled trials that resuscitation with colloids reduces the risk of death compared to crystalloids in patients with trauma, burns and following surgery. As colloids are not associated with an improvement in survival, and as they are more expensive than crystalloids, it is hard to see how their continued use in these patient types can be justified outside the context of randomised controlled trials

A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit

The SAFE Study Investigators

2004; 350: 2247-2256

Study design
16 centres in Australia and New Zealand Randomised, double-blind, trial of 4% albumin compared to 0.9% Saline for fluid resuscitation in the ICU Study fluid given until death, discharge or 28 days

Study design
6997 Patients enrolled 90% power to detect 3% difference in mortality from baseline of 15% mortality A priori sub-groups identified:
Trauma Severe Sepsis ARDS

Fluids administered and effect

Total administered study fluid Albumin 2247 ml Saline 3096 ml Ratio 1 : 1.4

Outcome
ALBUMIN 28 day mortality ICU LOS (days) Hospital LOS (days) Duration of mech. Vent. Duration of RRT 726/3473 (20.9%) 6.5 6.6 SALINE 729/3460 (21.1%) 6.2 6.2 Relative risk (95% CI) 0.99 (0.91 to 1.09) 0.24 (-0.06 to 0.54) -0.24 (-0.70 to 0.21) 0.19 (-0.08 to 0.47) 0.09 (-0.0 to 0.19) Absolute diff (95% CI) P value 0.87 0.44

15.3 9.6
4.5 6.1 0.48 2.28

15.6 9.6
4.3 5.7 0.39 2.0

0.30
0.74 0.41

Outcome

Subgroup Outcome: 28 day mortality

ALBUMIN Trauma 81/596 (13.6%)

SALINE 59/590 (10.0%)

Relative risk (95% CI) 1.36 (0.99 to 1.86)

P value 0.06

Severe Sepsis
ARDS

185/603 (30.7%)
24/61 (39.3%)

217/615 (35.3%)
28/66 (42.4%)

0.87 (0.74 to 1.02)

0.93 (0.61 to 1.41)

0.09
0.72

What about starches?

Starches are polymers of glucose 1,6 linkages produce branched chains called amylopectins Hydroxyethyl radicals can be substituted on glucose units, hence
HYDROXYETHYL STARCH

Why might they be useful?

Large molecules, so retained in the plasma Stable molecules, so have a sustained effect Some evidence of specific antiinflammatory properties that may be therapeutic

Endothelial properties
Prospective RCT, single centre 66 patients >65 years old Major abdominal surgery
Ringers lactate (n=22) Normal saline (n=22) HES 130/0.4 (n=22)

From induction of anaesthesia until 1st post-op day to keep CVP 8-12mmHg
Boldt J. Int Care Med 2004; 30: 416-22

Endothelial properties

Boldt J. Int Care Med 2004; 30: 416-22

Why might they be bad?

Potential risk of anaphylaxis Some starch solutions cause coagulation disorders Risk of renal impairment Known incidence of pruritis

Incidence of anaphylaxis
%age of anaphylactoid reactions

French multicentre study 49 hospitals 19593 patients Overall 1 in 456 had an anaphylactoid reaction

0.50

0.40

0.30

0.20

0.10

0.00
Gelatin Dextran Albumin Starch

Laxenaire MC. Ann Fr Anesth Reanim 1994; 13: 301-10

Coagulation disorders
2000

Small RCT, 21 patients per group

1500 1000 500 0 Post op RL

* * *

Major abdominal surgery for malignancy

Compared blood transfusion requirements according to fluid given

5 hr

1st day

2 day (tot)

HES 140/0.4

Hextend

Boldt J et al. Br J Anaesth 2002; 89: 722-8

Renal Impairment
Schortgen F, Lacherade J-C, Bruneel F et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 2001; 357: 911-6

129 patients in three centres Severe sepsis / septic shock 6%HES 200/0.6 vs. 3% Gelatin Prospective RCT

Renal Impairment

OR 2.57 (1.13 5.83) P=0.026

Schortgen F et al. Lancet 2001; 357: 911-6

Renal Impairment
Boldt J, Brenner T, Lehmann A et al. Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new starch preparation with gelatin. Int Care Med 2003; 29: 763-9

40 patients, single centre HES 130/0.4 vs. Gelatin Prospective RCT

Renal Impairment

No significant differences

Boldt J et al. Int Care Med 2003; 29: 763-9

Pruritis
Morgan PW and Berridge JC. Giving long-persistent starch as volume replacement can cause pruritis after cardiac surgery. Br J Anaesth 2000; 85: 696-9.

85 consecutive cardiac patients Structured interview 58 received EloHAES 27 received no HES

Pruritis
Morgan PW and Berridge JC. Giving long-persistent starch as volume replacement can cause pruritis after cardiac surgery. Br J Anaesth 2000; 85: 696-9.

Pruritis experienced in:

13 (22%) of EloHAES patients 0 (0%) of non-HES patients (P=0.007)

Median onset (range) 4 (1-12) weeks Greatest duration >9 months

Time to put it all together!

How much fluid

Trauma
Restrictive fluid strategy until bleeding controlled

Peri-operative
Fluids early (?pre-op), then cut back

Sepsis
Early aggressive fluids to restore perfusion Restrict fluids late to avoid oedema

Which fluid
It probably doesnt matter! Avoid dextrose (water) as large volumes will be required, worsening tissue oedema If using crystalloid, the patient will require 1.4 times the volume compared to colloid Crystalloid may be better in trauma Colloid (or possibly starches) may be better in critically ill / sepsis