A team of Massachusetts General Hospital (MGH) physicians has developed a new general anesthetic that may be safer for critically ill patients. In the August issue of Anesthesiology, they describe preclinical studies of the drug called MOC-etomidate - a chemically altered version of an exiting anesthetic - which does not cause the sudden drop in blood pressure seen with most anesthetics or prolonged suppression of adrenal gland activity, a problem with the original version of the drug.
"We have shown that making a version of etomidate that is broken down very quickly in the body reduces the duration of adrenal suppression while retaining etomidate’s benefit of keeping blood pressure much more stable than other anesthetics do," says Douglas Raines, MD, of the MGH Department of Anesthesia, Critical Care and Pain Medicine, who led the study.
Almost all general anethetic 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 such patients, etomidate is often used to induce anesthesia, but since adrenal suppression sets in quickly and can last for several hours to days, other agents are used to maintain anesthesia during a procedure, requiring very careful monitoring to avoid dangerous blood pressure drops.
In their search for a safer version of etomidate, the research team mimicked 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, 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 note that, since the study only examined the effect of a single dose of MOC-etomidate, their next step will be to study continuous infusion of the drug. Additional data must be gathered from animal studies before testing the agent in human patients is feasible. "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," Raines says. "We also anticipate that patients will wake more quickly and with less sedation after surgery and anesthesia."
Raines is an associate professor of anesthesia at Harvard Medical School. Co-authors of the Anesthesiology study - supported by grants from the National Institutes of Health and the Foundation for Anesthesia Education and Research - are lead author Joseph Cotton, MD; Shaukat Husain, DPhil; Stuart Forman, MD, PhD, Keith Miller, DPhil; Elizabeth Kelly and Hieu Nguyen, all of the MGH Department of Anesthesia, Critical Care and Pain Medicine. The MGH has filed a patent application for MOC-etomidate and other etomidate analogues.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.