Potentially Safer General Anesthetic for Critically Ill Patients

A chemically altered version of the general anesthetic (GA) etomidate does not cause the sudden drop in blood pressure or prolonged suppression of adrenal gland activity seen with the original version of the drug.

Researchers at Massachusetts General Hospital (MGH, Boston, USA), in a search for a safer version of etomidate, decided to mimic the chemical structure of other "soft analogue" drugs--derivatives of parent drugs designed to be rapidly metabolized--by adding a molecule that causes the drug to broken down by natural enzymes soon after producing its effects. Experiments in tadpoles and rats showed that the new agent, Methoxycarbonyl (MOC)-etomidate, quickly produced anesthesia from which the animals recovered rapidly after administration ceased. The rat study verified that MOC-etomidate had little effect on blood pressure levels and no effect on adrenal activity, even when administered at twice the dosage required to produce anesthesia. The researchers noted that since the study only examined the effect of a single dose of MOC-etomidate, the next step would be to study continuous infusion of the drug.

Further data from animal studies needs to be gathered before testing the agent in human patients is feasible. The study was published in the August 2009 issue of Anesthesiology.

"If all goes well, we expect that we could give a large dose of MOC-etomidate to induce anesthesia and then run a continuous infusion to maintain anesthesia without reducing blood pressure in even very sick patients,” said lead author Douglas Raines, M.D., of the department of anesthesia, critical care, and pain medicine. "We also anticipate that patients will wake more quickly and with less sedation after surgery and anesthesia.”

Almost all GA agents reduce blood pressure immediately after they are administered, which is not a problem for young and healthy patients but can have serious consequences for those who are elderly, critically ill, or suffering from blood loss. For these patients, etomidate, a rapidly acting sedative-hypnotic that provides hemodynamic stability is often used. However, it causes prolonged suppression of adrenocortical steroid synthesis, and therefore its clinical utility and safety are limited, and require very careful monitoring to avoid dangerous blood pressure drops.

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