Chapter 44: IV Drugs, Fluids, and Antidotes

Central lines have some disadvantages - higher risk of bleeding, infection and VTE, and harder to place
PVC has 2 problems - leaching and sorption
Leaching - DHEP can leach from PVC - need to use non-PVC bags and polyethylene lined tubing
Drugs w/ Leaching Issues - Tacrolimus, temsirolimus, trniposide, cabazitaxel, docetaxel,
paclitaxel, amiodarone
Tic Tac Toe, craving delicious pho!
Sorption is when the PVC bag pulls in some of the drug - instead use polyolefin or glass containers
Drugs w/ Sorption issues - amiodarone (for infusions >2hrs), caramustine,
lorazepam, sufentanil, thiopental, regular insulin, and NTG
ACLS TIN
IV Fluids
Crystalloids = Salt Solutions: NS, 1/2 NS, 1/4 NS, (may add KCl), hypertonic saline (3%,
7.5%, 23.4%), and LR. Good for maintaining hydration and keeping IV lines open/patent
All hypertonic solutions should be given through a CENTRAL line
Have low osmotic pressure, so only 25%ish will stay intravascular
Colloids - used to increase osmotic pressure - way more expensive than crystalloids and
risk of hypersensitivity rxns and bleeding
Albumin 5% & 25%, hexastarch 6%, pentastarch 6%, dextran, etc
Conditions in the ICU
Shock Syndromes - hypoperfusion and lack of O2 - signs are hypotension (SBP < 90)
4 Types - Hypovolemic (hemorrhagic), Cardiogenic, Distributive (Septic), Obstructive (PE)
Treatment - require fluids (crystalloids, colloids, or blood), and vasorpressors and/or inotropes
Inotropes increase contractility = increased CO - by B-stimulation or inhibiting PDE
Vasopressors work via vasoconstriction (Pressing down on vasculature) - increasing SVR
Dobutamine - B agonist causing increased CO and HR - for cardiogenic shock
Milrinone - selective PDE inhibitor
Monitoring- continuous BP, HR, ECG, CVP, MAP, urine output
SE - hypo/hypertension, tachycardia, arrhythmias, thrombocytopenia (w/ milrinone)
Dopamine - precursor for NE - stimulates diff receptors based on dose (L-D1, M-B1, H-a1)
Epinephrine - B agonist at low doses, and alpha agonist at high doses
Norepinephrine (levophed) - preferred drug in septic shock - Stimulates a > B
Phenylephrine (Neo-syneohrine) - pure alpha agonist
SE - arrhythmias, tachycardia (Esp DA and EPI), bradycardia w/ phenyl,
peripheral ischemia and tissue necrosis, etc
Monitoring - continuous BP, HR, MAP, urine output, infusion site for extravasation
Vasopressin - ADH analog - causes vasoconstriction and increases SVR
SE - may increase BP, arrhythmias, necrosis, etc
Extravasation or leakage of vasopressors into surrounding tissue of vasopressors/inotropes
can cause tissue damage/necrosis - medical emergency
With NE treat w/ Phentolamine (Regitine) an alpha blocker that antagonizes NE
ICU Sedation and Analgesia
Combination of opioids, BZDs, antipsychotics, and/or hypnotics (propofol, dexmedetomidine)
Must administer and optimize analgesia first - fentanyl is preferred for fast analgesia
BZDs (lorazepam, midazolam) and Propofol recommended for sedation (propofol for
procedural and when fast awakening is needed)
Midazolam has shorter half life than lorazepam (for short term sedation <48h), but is
highly lipophilic and can accumulate in obese, and has active metabolite that is bad if
renal prob. Also has many drug interactions (3A4)
Propofol (Diprivan) - lipid emulsion 1.1 kcal/mL
Limit dose to avoid infusion syndrome which could cause arrhythmias/death
SE - hypotension, hypertrigs, apnea, pancreatitis
Use strict aseptic technique d/t risk of bacterial growth (only good for 12hrs)
Sedation scale should be used frequently to assess response and agitation over time
 Dexmedetomidine (Precedex) - mix with NS only
Duration of infusion NTE 24hrs, patients are arousable and alert when
stimulated (does not cause resp depression)
Morphine - has active metabolite which can accumulate in renal impairment
Preferred agent if hemodynamically stable
Causes a histamine release = pruritis
Fentanyl - causes less hypotension than morphine b/c no histamine release
Fast onset, short duration, 100x more potent than morphine
Preferred if unstable hemodynamics
Hydromorphone (Dilaudid) - not used much for ICU sedation - no active metabolites
Remifentanil (Ultiva)
Haloperidol
SE - hypotension, QT, tachycardia, EPS, anticholinergic, NMS, etc
Antipsychotics are used for ICU delerium
Acid-Base Homeostasis
An acid donates protons, and a base receives protons - the pH and [H+] are inversely related
Normal pH of blood is 7.4 (7.35-7.45) - controlled by bicarbonate which is regulated by the
kidney and acts as a buffer/base, and carbon dioxide which is regulated by lungs and acts as
buffer/acid
Diet and cellular metabolism produces large amounts of H+ ions that must be excreted
to maintain proper pH
Classified as acidosis/alkalosis and metabolic/respiratory
Metabolic involves changes in HCO3 (normal is 24 mEq/L)
Metabolic Acidosis (low HCO3) may be associated with an anion gap, elevated is >12
Anion Gap = Na - (Cl + HCO3)
Respiratory involves changes in PaCO2 (normal is 40mmHg)
Etiologies of Acid/Base Disorders
Metabolic Acidosis
Elevated anion gap - CUTE DIMPLES - cyanide, uremia, toluene, ethanol, DKA,
isoniazid, menthol, propylene gylcol, lactic acidosis, ethylene glycol, salicylates
Non-elevated anion gap - renal tubular acidosis, diarrhea, administration of acidic substanc
Metabolic Alkalosis - loop and thiazide diuretics, high dose PCNs, vomiting, CF
Resp Acidosis - opioids, sedatives, anesthetics, stroke, asthma/COPD
Resp Alkalosis - pain, fever, brain tumors, salicylates, catecholamines, theophylline
Electrolyte Disorders in ICU
Do not correct sodium disorders too quickly - NTE 12 mEq/L of Na per 24hrs
Stress Ulcer Prophylaxis - critically ill have reduced blood flow to the gut - results in breakdown
of gastric mucosa and defenses
Risk Factors - mechanical ventilation, coagulopathy, spesis, TBI, burn pts, ARF, High dose CS
Treatment:
H2RAs - can cause thrombocytopenia, mental status changes (elderly), tachyphylaxis
PPIs - risk of C.diff and pneumonia
VTE Prophylaxis
Risk Factors - surgery, trauma, immobility, cancer, previous VTE, increasing age, pregnancy/post-
partum, acute mental illnes, thrombophilia, LV dysfunction, acute MI, catheter, estrogen therapy
Low Dose UFH - 5000u SC BID-TID
LMWH - Enoxeparin 30 mg SC BID or 40 mg SC QD (If CrCl < 30, give 30 mg SC QD)
Fondaparinux - 2.5 mg SC QD (do not use if CrCl < 30 or Wt < 50kg)
Rivaroxaban 20 mg PO QD (do not use if CrCl < 30)
Anesthetics
SE - hypotension, bradycardia, N/V, mild drop in body temp - OD causes resp dep and card arrest
Inhaled anesthetics can cause malignant hyperthermia (rare) - treat W/ dantrolene
Inhaled anesthetics = desflurane, sevoflurane, isoflurane, NO
Neuromuscular Blocking Agents - cause skele muscle paralysis
 NMBAs do not provide sedation or analgesia - must provide adequately before
starting NMBA, and these paralyze the diaphragm so must be under mechanical
ventilation
High risk med - must labele with red label WARNING PARALYZING AGENT
Non-Depolarizing NMBAs - Atracurium, Cisatracurium (Nimbex), Vecuronium, Pancuronium,
Rocuronium
Hemostatic Agents
Systemic Hemostatic Agents:
Most common AE or systemic agents is hypersensitivity rxns and thrombosis
Aminocaproic Acid (Amicar) - for excessive bleeding in cardiac surg, liver cirrhosis
Tranexamic Acid (Lysteda oral and Cyklokapron inj) - for hemophilia associated bleeding and
heavy menstrual bleeding
Recombinant Factor VIIa (NovoSeven RT) - BBW for clotting risk (sometimes fatal)
Topical Hemostatic Agents:
Thrombin - All can cause thrombosis via systemic absorption
Bovine-derived is Thrombin-JMI which has risk of antibody formation = can
cause coagulopathies and thrombosis
Human-derived is Evicel has a (low) risk of dz transmission
Recombinant Thrombin is Recothrom - no dz risk and less immunogenic
Fibrin Sealants - Tisseel, Evicel, Crosseal contain fibrinogen and thrombin -
thrombin cleaves fibrinogen to fibrin which form clots
Risks depend on source - like thrombin products above
Acrylates - Dermabond, Liquid Bandage
Gelatin Products - Gelfoam, Gelfilm, Surgiflo, Surgifoam - cannot be used in closed spaces
Floseal combination thrombin and gelatin
Cellulose - Surgicel, Fibrillar, Surgicel Nu-Kit - have low pH = topical pain/inflammation
Cannot be used with other biologics b/c of pH
IVIgG - plasma protein replacement for immunodeficient (ITP, B-cel lymphocytic leukemia, Guillian-
Barre), as well as anti-inflammatory (SLE, RA)
IVIG is a blood product and is subject to supply shortages and infectious dz risks
Expensive - most pharm depts have guidelines for use
8 Products available - diff volumes, osmolarity, IgA content, sodium, sugar, stabilizing
agents, and pH - must match to the patient
Products - Carimune NF, Flebogamma DIF, Gammagard, Gammagard S/D, Gammaplex,
Gammunex-C, Octagam, Privigen
Well tolerated but SE include fever, nausea, chills, hypotension, facial flushing, HA, myalgias, chest
pain, tachycardia
FDA requires that all samples be screened for HIV, HepB, HepC
Considerations
Renal Disease - BBW if renal damage - avoid nephrotoxic drugs, ensure
hydration, choose isotonic product and slow infusion
Cardiac Dz
Diabetes - stabilizers can increase BG (sorbitol, maltose, L-proline and glycine do not)
Stabilizers - Sorbitol is metabolized to fructose (caution fructose intolerance), maltose is
derived from corn (caution corn allergy), L-proline dangerous in pts w/ hyperprolinemia
AEs to watch for
Aseptic Meningitis - severe HA and nuchal rigidity w/o signs of infxn
Hemolysis - watch for hematuria within few hours after infusion
Thromboembolic disorders
Pharmacy must track lot numbers
Preparation/Administration:
Must dose adjust for renal impairment
Come already in solution or require reconstitution with the provided diluent
Always inspect for particles, and do not shake
Infuse separately
 Select IV Drugs:
Amiodarone - stable for 24hrs in polyolefin or glass, or 2hrs in PVC. Light sensitive, use D5W
Amphotericin B - dilute in D5W only, infuse over 2-6hrs, light sensitive
Furosemide - store at room temp! Light sensitive, do not use if soln is yellow
IV: PO ratio is 1:2
Levothyroxine - give immediately after reconstitution, protect from light
IV: PO ratio is 1:2
Metronidazole - store at room temp, protect from light, IV:PO is 1:1
Phenytoin - further dilution is controversial (if so use NS), use ASAP (within 4hrs), do
not refrigerate
Use in-line filter and follow w/ saline flush to prevent vein irritation
IV:PO is 1:1, max infusion rate is 50mg/min
SMX/TMP - dilute with D5W only, infuse over 60-90mins, adjust for renal impairment
Store at room temp, protect from light, stability based on concentration (2-6hrs)
IV:PO is 1:1
Resources - IV drug compatibility - Trissels and Kings Guide
Trissels has 4 different types of tables - solution compatibility, additive compatibility, drugs
in syringe compatibility, and y-site injection comp
Drugs that require protection from light - amiodarone, amphotericin, ceftriaxone, cefepime,
cipro, dopamine, doxy, EPI, fentanyl, furosemide, HC, hydromorphone, levoflox, levothyroxine,
linezolid, methylpred, metronidazole, nor-epi, ondansetron, pentamidine, phytonadione,
SMX/TMP, sodium nitroprusside
Antidotes for Select Toxicities
Warfarin - Phytonadione (AquaMephyton, Mephyton)
Anticholinesterase insecticides/organophosphates (nerve agents) -
Atropine/Pralidoxime (Protopam)
BZDs - Flumazenil (Romazicom)
BBs - Glucagon (GlucaGen)
Digoxin - Digoxin Immune Fab (DigiBind, DigiFab)
Ethylene Glycol, Methanol - Ethanol or Fomepizole (Antizole)
Heavy Metals - Dimercaprol
Heparin - Protamine
Iron - Deferoxamine (Desferal) or Deferiprine for overload from blood transfusions
Isoniazid - Pyridoxine (B6)
Opioids - Naloxone
Snake Bites - Crotalidea polyvalent (Antivenin, Crofab)
 IV Drugs, Fluids, and Antidotes:
Peripheral IV: placed in a small vein
Central IV: placed in a
large vein. Example is
a peripherally inserted
central catheter (PICC).
Can give meds that
would be overly
irritating to peripheral
veins like higher doses
or greater volumes.
Disadvantages:
higher bleeding
risk, infection,
thromboembolism,
and more difcult to
insert.
Concern with PVC:
Leaching:
Drugs pull out
DEHP from bag:
tacrolimus,
temsirolimus,
teniposide,
cabazitaxel,
docetaxel,
ixacabepilone,
and
paclitaxel.

Sorption: PVC
bag pulls in
drug:
Amiodarone,
carmustine,
lorazepam,
sufentanil,
thiopental,
insulin,
nitroglycerin.
Colloids and Crystalloids: Colloids do not readily
cross capillaries (stay in
veins) and may provide
more intravascular
 volume expansion than
equal volumes of
crystalloids, but they
are expensive.
Crystalloids are less
costly and safer.
Shock: (Hypovelemic, Cardiogenic, Distribuitive, Obstructive, Neurogenic)
Fluid Resuscitation is 1st line
Vasopressors: not effective without adequate fluid.
Dobutamine: B1 Inotrope that increases
HR, Contractility, and CO.
Dopamine: At medium doses B1 (SV/CO), at higher doses a1
(vasoconstriction)
Epinephrine (Adrenaline): alpha and beta.
Norepinephrine(Levophed): a1 (mostly) and beta
Phenylephrine (Neo-Synephrine): all a1
(vasoconstriction)
Vasopressin: V1 and V2 agonist (vasoconstriction)
***The vasoconstrictors can cause peripheral ischemia and necrosis
(gangrene)
***If extravasation, treat with phentolamine (alpha blocker)
ICU sedation, analgesia, and delirium:
Optimize analgesia first, usually fentanyl, morphine, hydromorphone
Sedation usually with benzos (midazolam),
propofol, or dexmedetomidine (Precedex). Propofol can cause infusion reactions that
result in cardiac arrhythmias and death.
Patients should frequently be assessed
with a validated sedation scale to adjust therapies.
The ACCM recommends using Precedex to
sedate patients with delirium.

Commonly used agents for agitation and

sedation:

Shock: (Hypovelemic, Cardiogenic, Distribuitive, Obstructive, Neurogenic)

Fluid Resuscitation is 1st line
Vasopressors: not effective without adequate fluid.
Dobutamine: B1 Inotrope that increases
HR, Contractility, and CO.
Dopamine: At medium doses B1 (SV/CO), at higher doses a1
(vasoconstriction)
Epinephrine (Adrenaline): alpha and beta.
Norepinephrine(Levophed): a1 (mostly) and beta
Phenylephrine (Neo-Synephrine): all a1
(vasoconstriction)
Vasopressin: V1 and V2 agonist (vasoconstriction)
***The vasoconstrictors can cause peripheral ischemia and necrosis
(gangrene)
***If extravasation, treat with phentolamine (alpha blocker)
ICU sedation, analgesia, and delirium:
Optimize analgesia first, usually fentanyl, morphine, hydromorphone
Sedation usually with benzos (midazolam),
propofol, or dexmedetomidine (Precedex). Propofol can cause infusion reactions that
result in cardiac arrhythmias and death.
Patients should frequently be assessed
with a validated sedation scale to adjust therapies.
The ACCM recommends using Precedex to
sedate patients with delirium.

Commonly used agents for agitation and

sedation:

lorazepam (Ativan)
midazolam
propolol (Diprivan): propofol infusion related syndrome(PRIS), rare but can
be fatal.
Hypertriglycerides
dexmedetomidine (Precedex): **Sedation without Respiratory
Depression
morphine: has active metabolite M6G,
hypotension from histamine release
fentanyl: less hypotension than morphine b/c no histamine release
hydromorphone (Dilaudid)
haloperidol (Haldol): QT prolongation, EPS Acid-Base Homeostasis:
pH < 7.35 is acidosis, pH > 7.45 is alkalosis
Metabolic or Respiratory

Electrolyte Disorders:

Sodium: Dont correct more than 12mEq/L

hours
in 24to prevent central pontine myelinosis which is a devastating neurological
complication.
Potassium: IV potassium should not be faster than
10-20 mEq/hr.
Stress Ulcer Prophylaxis:
Critical illness leads to reduced blood flow to gut which results in breakdown
of gastric mucosal defense mechanisms
Patients without risk factors should not receive
prophylaxis (Mechanical Vent, Coagulopathy, Sepsis, Brain Injury, Burns, Renal
Failure, High Dose Steroids)
H2 blockers
VTE prevention:
High Risk: Surgery, trauma, immobility, cancer, previous VTE, pregnancy,
estrogen etc..
 UFH: 5,000 units SC BID-TID
LMWH: Enoxapin 30mg SC BID or 40mg SC Daily.
If CrCl<30, use 30mg SQ Daily Anesthesia:
must be closely monitored
Inhaled anesthetics can cause malignant hyperthermia and should be
given dantrolene.
Neuromuscular blockers: cisatracurium (Nimbex)
and Vecuronium . Do not provide sedation or analgesia.
IV compatibility resources:
Trissels
King Guide Poison Management:
Insecticide Poisoning/Nerve Agents: Organophosphates that inhibit
acetlycholinesterase, leads to increase Ach. MUDDLES: miosis (pinpoint
pupils), urination, diarrhea, diaphoresis, lacrimation, excitation, salivation
Antidotes for select toxicities:
APAP: N-acetylcysteine
Anticholinesterase: Atropine
Benzos: Flumazenil (Romazicon)
Beta Blockers: Glucagon
Digoxin: Digoxin Immune Fab (Digifab)
Heparin: Protamine
Iron: deferoxamine (Desferal)
Isoniazid: (Pyridoxine Vit B6)
Opioids: Naloxone
Warfarin: phytonadione (Mephyton) = Vitamin K