Perioperative pharmacology in morbid obesity.
OBJECTIVE
Morbid obesity alters drug dose requirement and time course of drug response. In addition, morbid obesity's impact on many organ systems decreases the margin of safety of anesthetic drugs. Consequently, incorrect dosing will increase the rate of perioperative complications. In this review, we will discuss factors that affect the pharmacokinetics and pharmacodynamics of anesthetic agents in the obese population, we specify certain dosing scalars, and we relate our current knowledge of obesity's effects on the clinical pharmacology of anesthetic drugs.


RESULTS
A morbidly obese individual's increased cardiac output requires administration of higher drug doses than would be required for a standard-size person to attain the same peak-plasma concentration. Lean body weight (LBW) is highly correlated with the increased cardiac output, more so than fat mass or other variables. For most drugs, clearance increases nonlinearly with total body weight but linearly with LBW. Morbid obesity has no clinically significant impact on the uptake of the inhalation anesthetics isoflurane, sevoflurane, and desflurane when used in routine clinical practice. Total body weight dosing of neuromuscular blocking agents will result in a prolonged effect.


CONCLUSIONS
For the induction dose of hypnotics and the initial dose of other drugs that have a fast onset of effect, cardiac output or LBW are relevant dosing scalars. For maintenance dosing, LBW seems to be a more appropriate dosing scalar than total body weight.
Department of Anesthesia, Stanford University Medical Center, Stanford University School of Medicine, Stanford, California 94305, USA. hlemmens@stanford.edu
Hendrikus J m
HJ
Lemmens
D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology; D000777:Anesthetics / Q000493:pharmacokinetics / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009125:Muscle Relaxants, Central / Q000493:pharmacokinetics / Q000494:pharmacology; D009388:Neostigmine / Q000493:pharmacokinetics / Q000494:pharmacology; D009767:Obesity, Morbid / Q000378:metabolism*; D019990:Perioperative Care; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D010599:Pharmacokinetics; D010600:Pharmacology
D000701:Analgesics, Opioid; D000777:Anesthetics; D018685:Anesthetics, Inhalation; D002800:Cholinesterase Inhibitors; D009125:Muscle Relaxants, Central; D004364:Pharmaceutical Preparations; D009388:Neostigmine