Several acute toxicities are associated with inhaled anesthetics. One serious complication is carbon monoxide (CO) poisoning, which is most commonly linked to desflurane. Carbon monoxide can form when desflurane interacts with dry CO₂ absorbers used in anesthesia machines during perioperative care. If these absorbers are not replaced, CO can accumulate, potentially leading to CO poisoning. Absorbent dries out when fresh gas is left flowing through an idle circuit, classically over a weekend, so the first case of the day after the machine sat unused is the typical setting. CO production is highest with desflurane, then isoflurane, and lowest with sevoflurane; prevention is turning fresh gas off when the machine is idle, replacing suspect absorbent, and choosing absorbents without strong bases (potassium and sodium hydroxide).
Another concern is nephrotoxicity, historically linked to sevoflurane. Sevoflurane is metabolized more than the other modern agents, producing inorganic fluoride ions, and fluoride was the cause of the renal injury seen with methoxyflurane; sevoflurane's fluoride peaks are brief, however, and have not produced clinical renal injury. The second concern is compound A, a breakdown product formed when sevoflurane meets carbon dioxide absorbent, more so at low fresh gas flows, with warm or desiccated absorbent, and with strong-base absorbents. Compound A injures the kidney in rats, but studies in humans, including volunteers given prolonged low-flow sevoflurane, have not shown lasting renal injury. The FDA label still advises fresh gas flows of at least 1 L/min, limits exposure at flows of 1 to 2 L/min to 2 MAC-hours, and states that safety in renal insufficiency has not been established, so many providers keep flows at 2 L/min or more, or choose another agent, in patients with kidney disease.
Hepatotoxicity is another rare but serious side effect, primarily associated with halothane. Some patients, particularly those who have been repeatedly exposed to halothane, may develop halothane-induced hepatitis, which can progress to acute liver failure. This risk has led to a decrease in halothane’s use in modern practice. While hepatotoxicity is less common with newer inhaled anesthetics, it remains a potential risk with prolonged or repeated exposure.
All volatile anesthetics (and succinylcholine) trigger malignant hyperthermia, an acute hypermetabolic crisis of skeletal muscle in genetically susceptible patients; nitrous oxide is not a trigger. The earliest sign is usually a rising end-tidal carbon dioxide that does not respond to increased ventilation, followed by tachycardia, muscle rigidity, and later hyperthermia. Treatment is to stop the triggering agent, hyperventilate with 100% oxygen at high fresh gas flow, give dantrolene 2.5 mg/kg IV and repeat until the crisis settles, and treat hyperkalemia, acidosis, and the temperature; the MHAUS hotline (1-800-644-9737) is available around the clock.
