Until recently, obese subjects have been routinely excluded from clinical trials to obtain regulatory approval for investigational drugs. This has resulted in package insert dosage recommendations valid for normal weight patients but not for the obese. Obesity is not only associated with an increase in tissue mass but also changes in body composition and tissue perfusion. Fat mass and lean body mass both increase, but the increase is not proportional. The percentage of lean body mass as a percentage of total body weight decreases (Fig. 19.1). The different ratio of lean body weight to fat weight at different BMIs will have a significant impact on drug distribution. Fat perfusion is also altered at different BMIs. At low BMIs fat is relatively well perfused, at high BMIs fat is poorly perfused. Because of the different ratio of fat to lean body weight at different BMIs and changes in fat perfusion, the effect of obesity on drug distribution into the different tissues is poorly understood. The increased cardiac output of the obese decreases the fraction of drug distributed to the brain and increases the rate of redistribution, which may result in lower peak concentrations. In obese patients with normal cardiac function, cardiac output is highly correlated to lean body weight, more so than total body weight or other variables. Therefore, lean body weight and cardiac output are more appropriate dosing scalars than total body weight. Total body weight dosing will result in overdosing and side effects.

Numerous pharmacokinetic studies have shown that clearance, the most relevant pharmacokinetic parameter for maintenance dosing is linearly related to lean body weight but not total body weight. This implies that lean body weight is the appropriate dosing scalar, not only for determining loading doses, but also for maintenance doses.

Ideally administration of sedatives should be minimized or avoided. Respiratory depression caused by benzodiazepines and opioids is more pronounced in the obese, especially in those with obstructive sleep apnea . Upper airway collapsibility and decreased arousal response to airway occlusion make these patients particularly sensitive to drug-induced respiratory depression. Benzodiazepines decrease upper airway muscle activity with consequent obstruction and cause central apnea during the initial postadministration minutes. If very anxious, patients need premedication. Small doses of midazolam and opioids can be administered under continued monitoring. Recommend dosing scalars for several anesthetic agents used for sedation during block placement are summarized in Table 19.2.

Local anesthetics have a well-characterized side effect profile that includes the risk of CNS and cardiovascular toxicity and other adverse effects such as nerve injury and chondrolysis. There is no evidence that these side effects occur more often in the obese. In diabetic rats, an increase in nerve damage occurs after nerve block with traditional local anesthetics such as ropivacaine [16]. Some have suggested that patients with diabetes, a very common comorbidity associated with obesity, may increase the likelihood of nerve injury [17].

Studies specifically addressing the effect of obesity on local anesthetics are nonexisting, and consequently, the optimal dosing scalar for the administration of local anesthetics in obesity is not known. Because the clearance of many drugs in the obese is proportional to lean body weight, lean body weight dosing is probably more appropriate than total body weight dosing [18]. Continuous infusion regimens using total body weight may result in overdosing.

The recommendation when a local anesthetic overdose is suspected is to administer 20 % lipid emulsion based on lean body weight: A dose of 1.5 mL/kg lean body weight of 20 % lipid emulsion delivered as a bolus over 1 min followed by a continuous infusion of 0.25 mL/kg/min for at least 10 min after return of spontaneous circulation. The bolus could be repeated once or the infusion doubled for continued hypotension, but the total dose, including both bolus and infusion, should not exceed 12 mL/kg [19].