Etomidate Effects on the Body PDF

Etomidate has been associated with grand mal seizures and produces increased EEG activity in epileptogenic foci. This feature has proven useful for intraoperative mapping of seizure foci before surgical ablation. BIS monitor values decrease after etomidate bolus administration and return to baseli...

Etomidate has been associated with grand mal seizures and produces increased EEG activity in epileptogenic foci. This feature has proven useful for intraoperative mapping of seizure foci before surgical ablation. BIS monitor values decrease after etomidate bolus administration and return to baseline during recovery. During etomidate infusion, the BIS values reliably predict the depth of sedation and hypnosis. Effects on the Respiratory System Etomidate has less effect on ventilation than other anesthetics used to induce anesthesia. It does not induce histamine release in healthy patients or in patients with reactive airway disease.357 Ventilatory response to carbon dioxide is depressed by etomidate, but the ventilatory drive at any given carbon dioxide tension is greater than that following an equipotent dose of methohexital.171 Induction with etomidate produces a brief period of hyperventilation, sometimes followed by a similarly brief period of apnea,358 which results in a slight (±15%) increase in PaCO2, but no change in the partial pressure of arterial oxygen (PaO2).359 Etomidate's action on pulmonary vascular tone is similar to the actions observed with ketamine and propofol; that is, they attenuate the vasorelaxant responses to acetylcholine and bradykinine.360 Effects on the Cardiovascular System The hemodynamic stability associated with administration of etomidate is due to its lack of effect on the sympathetic nervous system and on the function of the baroreceptor. The effect of etomidate on the α2-adrenoceptors generates an increase in blood pressure in vivo; this may contribute to the cardiovascular stability after induction of anesthesia. The minimal effect of etomidate on cardiovascular function sets it apart from other rapid-onset anesthetics.361,362 Etomidate has proven useful in patients with valvular or ischemic heart disease undergoing noncardiac surgery and in patients with poor cardiac function.363,364 In patients receiving etomidate during induction of anesthesia, more hypertension and tachycardia occurs after etomidate compared to propofol.365 The myocardial oxygen supply-to-demand ratio is well maintained.366 Etomidate lacks analgesic efficacy, however, and needs to be combined with an opiate to prevent hemodynamic perturbations in response to painful stimuli such as laryngoscopy and intubation. In the setting of a hemorrhagic shock, etomidate provides advantages for induction of anesthesia. In contrast to other drugs, in a pig model of hemorrhagic shock the pharmacodynamics and pharmacokinetics of etomidate were minimally altered.337 Endocrine Effects In 1983 Ledingham and Watt reported retrospective data showing increased mortality among intensive care patients receiving longterm etomidate infusion compared to patients receiving benzodiazepines.330 They postulated that adrenal cortical suppression could be the cause of this increased mortality. Soon after this publication, clinical investigators confirmed the adrenocortical suppression by etomidate.331,367 The specific endocrine effects manifested by etomidate are a dosedependent reversible inhibition of the enzyme 11β-hydroxylase, which results in decreased biosynthesis of cortisol. The blockade of the cytochrome P450-dependent enzyme 11β-hydroxylase also results in decreased mineralocorticoid production and an increased formation of intermediaries (11-deoxycorticosterone) (Fig. 21.18). Subsequent research showed that etomidate is far more potent as an inhibitor of steroid synthesis than as a sedative hypnotic agent.367,368 The etomidate concentrations associated with adrenal cortical suppression are less than 10 ng/mL, which are much lower than the concentrations needed for hypnosis (more than 200 ng/mL). The disparate concentrations for hypnosis and adrenotoxicity may explain the dramatic difference in duration of these two actions.61 A Cochrane review in 2015 of single-dose etomidate versus other induction agents for endotracheal intubation in critically ill patients reveals no conclusive evidence that etomidate increases mortality.369 As indicated earlier, etomidate is associated with suppression of adrenal steroidogenesis, which can last up to 72 hours. However, the clinical impact of this adrenal suppressive effect is not certain.370 The Corticosteroid Therapy of Septic Shock (CORTICUS) study followed 500 patients with septic shock, who were randomized to receive either low-dose corticosteroid therapy or placebo. Twenty percent of the patients received etomidate. The study concluded that there was no benefit of low-dose corticosteroid therapy to long-term outcome.371 Retrospective analyses of the CORTICUS population suggest that patients receiving etomidate before enrollment had a 28-day mortality significantly higher and that steroid supplements provided no benefit.372,373 A meta-analysis on adrenal insufficiency by etomidate and mortality published in 2021 concluded that relative death rates linked to etomidate grew steadily and were most common in critically ill patients. Etomidate has a greater relative fatality rate (20%) in severely ill patients with a projected mortality \>44% than comparable anesthetic induction drugs. The necessity for glucocorticoid supplementation following etomidate in patients with severe critical illness and those who have suddenly deteriorated vital signs should be anticipated by intensivists.