Page 1754 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 125: Critical Care Pharmacology 1223

combined with adequate analgesia and sedation. Rare patients with CHAPTER Critical Care Pharmacology
significant and life-threatening signs and symptoms not responding to
conservative measures should be considered for specific treatment with
equine antivenin. Because of high risk of anaphylactic reaction (quoted 125 Niamh Murphy
as 75% of patients receiving antivenin), skin testing should be consid- Patrick T. Murray
ered prior to antivenin administration, and precautions should be taken
for anaphylaxis. 381
Recluse spider bite (loxoscelism) is characterized by pain and burning
at the bite site followed by localized swelling, erythema, and formation KEY POINTS
of bullae. A bull’s eye–shaped lesion ranging from 1 to 5 cm may develop, • Critical care therapeutics should be individualized to maximize
consisting of an erythematous or hemorrhagic center, surrounded by a therapeutic effect while minimizing the potential for adverse drug
blanched ring that is enclosed in an ecchymotic ring. Central necro- reactions.
sis may develop and last for weeks to months. Some patients develop • The appropriate loading dose is determined primarily by the
systemic symptoms including fever, myalgias, headache, and nausea. volume of distribution of the drug in the patient.
Rare patients develop intravascular hemolysis, disseminated intravas-
cular coagulation, acute renal failure, and the acute respiratory distress • The maintenance dose is proportional to the clearance and the
syndrome. Treatment of loxoscelism is largely supportive. Cool com- desired steady-state plasma concentration.
presses have been recommended for the bite site. Systemic steroids and • Elimination half-life is inversely proportional to clearance and
dapsone have been advocated in severe cases, but evidence support- directly proportional to volume of distribution.
ing their use is lacking, and they should be considered experimental. • Steady-state conditions are obtained after the passage of three to
Antivenin is available in South America. five half-lives.
• Prospective consideration of possible drug-patient and drug-drug
interactions minimizes the potential for undertreatment or adverse
drug reactions.
KEY REFERENCES
• Therapeutic drug monitoring may follow purely pharmacody-
• Ables AZ, Nagubilli R. Prevention, recognition, and mana- namic parameters or additionally use plasma levels to calculate
gement of serotonin syndrome. Am Fam Physician. 2010;81: pharmacokinetic parameters.
1139-1142. • Therapeutic drug monitoring attempts to ensure adequate therapy and
• Annane D, Chadda K, Gajdos P, et al. Hyperbaric oxygen therapy to prevent, detect, and appropriately report adverse drug reactions.
for acute domestic carbon monoxide poisoning: two randomized • Systemwide changes in management of critically ill patients, including
controlled trials. Intensive Care Med. 2010;37(3):486-492. physician order entry systems and dedicated intensivists and pharma-
• Barceloux DG, Bond GR, Krenzelok EP, et al. American Academy cists, can potentially decrease the incidence of adverse drug reactions.
of Clinical Toxicology practice guidelines on the treatment of
methanol poisoning. J Toxicol Clin Toxicol. 2002;40:415-446.
• Hadad E, Weinbroum AA, Ben-Abraham R. Drug-induced hyper-
thermia and muscle rigidity: a practical approach. Eur J Emerg Individualization of critical care therapeutics through the application
Med. 2003;10:149-154. of pharmacologic principles is intended to reconcile important features
• Kuzak N, Brubacher JR, Kennedy JR. Reversal of salicylate- of ICU management including polypharmacy, altered drug disposi-
induced euglycemic delirium with dextrose. Clin Toxicol (Phila). tion, and cost considerations, in the design of a rational drug regimen.
2007;45:526-529. Critically ill patients routinely receive multiple medications, and the
• Lavergne V, Nolin TD, Hoffman RS, et al. The EXTRIP potential for adverse drug reactions (ADRs), particularly drug-drug
interactions, increases in proportion to the number of agents received.
(EXtracorporeal TReatments In Poisoning) workgroup: guideline Furthermore, physiologic changes resulting from critical illness may
methodology. Clin Toxicol (Phila). 2012;50(5):403-413. alter several aspects of drug disposition in a manner that is often dif-
• Meehan TJ, Bryant SM, Aks SE. Drugs of abuse: the highs and lows ficult to predict based on available information. Finally, rational criti-
of altered mental states in the emergency department. Emerg Med cal care therapeutics is a major component of providing cost-effective
Clin North Am. 2010;28:663-682. critical care, because of the substantial fraction of the average hospital
• Ngo AS, Anthony CR, Samuel M, et al. Should a benzodiazepine pharmacy budget consumed by critical care therapeutic agents.
antagonist be used in unconscious patients presenting to the emer- Individualization of pharmacotherapy attempts to avoid ADRs caused
gency department? Resuscitation. 2007;74:27-37. by drug overdosage or undertreatment, including ADRs caused by drug-
• Olson KR. Activated charcoal for acute poisoning: one toxicolo- drug and drug-patient interactions. Correct drug dosing is frequently
complicated in critical illness by alterations in bioavailability, volume of
gist’s journey. J Med Toxicol. 2010;6:190-198. distribution, and elimination. Errors in choosing a therapeutic regimen
1
• Rosman Y, Makarovsky I, Bentur Y, et al. Carbamate poisoning: are frequently poorly tolerated by these patients; rapid efficacy may be
treatment recommendations in the setting of a mass casualties necessary for survival, but physiologic reserve may also be inadequate
event. Am J Emerg Med. 2009;27:1117-1124. to withstand the effects of drug intoxication. Concentrating efforts on
• Saeui C, Charlton N, Brady WJ. Biochemical issues in emergency optimal dosing of drugs that have a low therapeutic index (low ratio of
medicine: diagnostic and therapeutic considerations of selected toxic to therapeutic plasma level) is therefore particularly important.
toxic presentations. Am J Emerg Med. 2012;30(1):231-235. Consideration of pharmacokinetic (PK) and pharmacodynamic (PD)
principles, and their application to design an approximate patient model
for individualized therapeutics, should precede addition of any new
drug to an ICU patient’s regimen. Furthermore, the dynamic physiol-
REFERENCES ogy of these patients mandates frequent reassessment of the accuracy
of this model, updating drug regimens as required. Therapeutic drug
Complete references available online at www.mhprofessional.com/hall monitoring is used to titrate therapy with drugs that have both a low

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