Although thiopental is part of the World Health Organization’s “Essential Drugs List,” its use in the United States has been largely replaced with propofol. Nevertheless, thiopental is an ideal anesthesia induction agent with arguably less side effects than propofol. Immediately after intravenous (IV) administration, thiopental distributes to highly perfused tissues such as the brain, lung, liver, heart, kidney, gut, and pancreas. After an anesthetic induction dose, redistribution into muscle depletes thiopental from the brain and terminates the anesthetic effect within 5–10 min. The increased cardiac output associated with morbid obesity has a significant effect on thiopental dose requirement. After a thiopental induction dose of 250 mg, the higher cardiac output of a morbidly obese patient results in peak arterial concentrations up to 50 % lower than those of a lean subject. Thiopental dose adjusted according to lean body mass or the increased cardiac output results in the same peak plasma concentration as for a normal size person.

In current practice, propofol is the induction agent of choice for obese patients. Cardiac output has a significant effect on peak plasma concentration and duration of effect. After a bolus dose for induction of anesthesia, propofol’s peak plasma concentration is inversely related to CO. In addition, a higher CO is associated with a faster wake-up time. For COs of 8.5, 5.5, and 2.5 L/min, recovery of consciousness is predicted to occur at 2.9, 8.6, and 18.7 min, respectively. CO does not affect onset time. LBW is a more appropriate weight-based scalar than TBW for propofol induction of general anesthesia in MO patients. MO patients in whom anesthesia was induced with propofol dose based on LBW required similar doses of propofol and had similar times to LOC compared to nonobese control patients given propofol based on TBW.

Etomidate is less likely to cause a significant decrease in blood pressure than thiopental or propofol. Thus, in patients with significant heart disease or hemodynamically unstable patients, anesthetic induction with etomidate may be a better choice. The pharmacology of etomidate in obese patients has not been studied, but an induction dose based on lean body mass and cardiac output can be justified given the pharmacokinetic and pharmacodynamic similarities of etomidate, thiopental, and propofol.

Etomidate transiently suppresses corticosteroid synthesis in the adrenal cortex by reversibly inhibiting 11-beta-hydroxylase. This suppressant effect on steroid synthesis is probably clinically insignificant after a single dose used for induction of anesthesia. However, in patients with sepsis, the use of etomidate for induction of anesthesia is controversial. Other side effects are pain at injection, myoclonus, and a high incidence of postoperative nausea and vomiting.

Dexmedetomidine is used as a sedative agent with both anxiolytic and analgesic effects. Dexmedetomidine is a selective alpha2-adrenoreceptor agonist. Respiratory depression is minimal but dexmedetomidine potentiates the respiratory depressant effect of opioids and benzodiazepines. The short distribution half-life (8 min) and relatively short elimination half-life (2 h) make it suitable for titration by continuous infusion. The sympatholytic effect of dexmedetomidine decreases norepinephrine release and will decrease arterial blood pressure and heart rate. This may result in severe hypotension in hypovolemic patients and severe bradycardia in patients with heart block. Another side effect is dry mouth, which when used during fiberoptic intubation is an advantage. Postoperatively, dexmedetomidine reduces shivering. During open gastric bypass surgery when used instead of fentanyl to supplement desflurane, a loading dose of dexmedetomidine, 0.5 mcg/kg, given over 10 min followed by an infusion of 0.4 mcg/kg/h, resulted in significantly lower arterial blood pressure and heart rate, shorter time to tracheal extubation, lower pain scores, and less use of morphine and antiemetics in the postanesthesia care unit (PACU). For adjunctive use during laparoscopic bariatric surgery, a lower infusion rate (0.2 mcg/kg/min) is recommended to reduce the risk of cardiovascular side effects.

Fentanyl has a fast onset of effect (5 min) and effectively blocks somatic and autonomic responses during surgery. Fentanyl is probably the most commonly used opioid during bariatric surgery. The higher cardiac output in obese patients will result in significantly lower fentanyl concentrations in the early phase of distribution. Also later on, pharmacokinetic parameters of normal size persons will overpredict measured fentanyl concentrations in obese patients. The clearance of fentanyl is higher in obese patients and increases nonlinear with increasing TBW, but linear with lean body weight (LBW). These data suggest loading and maintenance doses of fentanyl should be based on LBW. However, obesity increases the probability of respiratory depression in the perioperative period, and fentanyl and other opioid administration should be carefully titrated according to individual patient’s need.

Sufentanil is the most potent opioid. It is highly lipophilic and has an onset time of approximately 5 min. Like fentanyl, pharmacokinetic parameters of normal size persons will overpredict measured sufentanil concentrations in morbidly obese patients.

Alfentanil has a fast-onset time of approximately 1 min. The higher cardiac output in obese patients will result in significantly lower alfentanil concentrations in the early phase of distribution. Alfentanil is less lipid soluble than fentanyl or sufentanil and has a smaller volume of distribution. No data on the effects of obesity on the pharmacokinetics of alfentanil have been published.

Remifentanil’s physicochemical properties result in a fast-onset time of approximately 1 min. Bolus administration in awake patients may result in severe bradycardia, hypotension, and muscle rigidity. Plasma and tissue esterases hydrolyze remifentanil rapidly, resulting in an extraordinary high clearance (3 L/min) unaffected by hepatic or renal insufficiency. The fast-onset time and high clearance make remifentanil especially suitable for administration by continuous infusion. Volumes and clearances not normalized for weight are similar in obese and nonobese patients and do not correlate with TBW but correlate significantly with LBW. Therefore, in the obese, dosing of remifentanil based on TBW will result in concentrations higher than those needed for clinical purposes and an increased incidence of side effects such as hypotension and bradycardia. Remifentanil dosing based on LBW will result in plasma concentration similar to those in normal-weight subjects when dosed according to TBW. After discontinuation of the administration, drug effect terminates rapidly within 5–10 min. Therefore, when postoperative pain is anticipated, alternative analgesics should be administered prior to remifentanil’s discontinuation.

The solubility of inhaled anesthetic agents in fat and the increased fat mass of the obese patient would theoretically result in an increased anesthetic uptake, especially with more fat-soluble anesthetics such as isoflurane. However, blood flow per kg of fat tissue decreases significantly with increasing BMI, therefore limiting uptake. In addition, the time constants (the time to reach 63 % of equilibrium) for equilibrium with fat are long (2,110 and 1,350 min for isoflurane and desflurane, respectively). The decreased fat perfusion and relatively long time constants will diminish the effect of the increased fat mass on the uptake of inhalational agents. During routine clinical practice, the effect of BMI on the uptake of desflurane and the more lipid soluble isoflurane was clinically insignificant.

The concern that isoflurane prolongs emergence from anesthesia in obese patients due to its lipid solubility could also not be substantiated. Obese and nonobese patients emerged from anesthesia similar times (7 min) after 0.6 MAC isoflurane administration for procedures lasting 2–4 h. After termination of isoflurane administration, the time to extubation can be decreased significantly by increasing alveolar ventilation using an isocapnic hyperpnea method.

The effect of BMI on desflurane uptake is insignificant, and obese and nonobese patients emerge from anesthesia equally rapidly (4 min) after 0.6 MAC desflurane administrations for procedures lasting 2–4 h. Several studies in obese patients have compared desflurane and sevoflurane with variable results, finding either a faster awakening with desflurane or no difference.

Sevoflurane appears to provide a slightly more rapid uptake and elimination of anesthetic in morbidly obese patients than does isoflurane. Fluoride, a metabolite of sevoflurane, in concentrations greater than 50 mmol/L, can be nephrotoxic. In addition, sevoflurane is degraded to compound A by carbon dioxide absorbers containing a strong base such as barium hydroxide lime or to a lesser extent by soda lime. Reductions in fresh gas flow as well as an increase in temperature in the gas mixture will increase compound A concentrations. Albuminuria, glycosuria, and enzymuria are associated with inhaled doses of compound A greater than 160 ppm/h. In the few studies in patients with renal impairment, no evidence of further worsening of renal function could be demonstrated after sevoflurane administration. However, the safety of sevoflurane in patients with impaired renal function is unclear.

Succinylcholine is a depolarizing muscle relaxant. It is a nicotinic acetylcholine receptor agonist causing fasciculations followed by flaccid paralysis by depolarization of the motor end plate. Succinylcholine has the fastest onset and shortest duration of action of all muscle relaxants—excellent properties to achieve intubation of the trachea rapidly. If difficulty is encountered managing the airway of the patient, return of neuromuscular function and spontaneous ventilation will occur within 5–7 min. Maximum effect and duration of action are determined by the extracellular fluid volume and elimination by the plasma enzyme butyrylcholinesterase (also known as pseudocholinesterase). Extracellular fluid volume and activity of butyrylcholinesterase both increase with increasing BMI. Therefore, morbidly obese patients have larger succinylcholine requirements than normal size patients. Succinylcholine, 1 mg/kg total body weight, will result in complete neuromuscular blockade and excellent intubation conditions in the obese. Lower doses are associated with poor intubating conditions due to incomplete neuromuscular block. Succinylcholine use is associated with increases in potassium and myalgia. The incidence of succinylcholine-induced myalgia is low in morbidly obese patients.

Rocuronium is a nondepolarizing muscle relaxant that can be used as an alternative to succinylcholine for rapid sequence intubation. A dose of 1.2 mg/kg ideal body weight (IBW) provides excellent or good intubating conditions 60 s after administration. However, the time to reappearance of T1 is 52 min. Rocuronium maintenance dosing based on lean body weight has not been studied, but dosing on the basis of ideal body weight is appropriate. Maximum effect and recovery times of rocuronium and all other muscle relaxants are highly variable; therefore continuous monitoring of the degree of neuromuscular blockade is recommended.