MGH researchers develop potentially safer general anesthetic

News release — Mass. General team develops potentially safer general anesthetic

A team of Harvard Medical School (HMS) researchers at  Massachusetts General
Hospital (MGH) 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 existing 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,” said HMS associate professor of anesthesia Douglas Raines
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.”

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, Shaukat Husain, Stuart Forman, Keith Miller, Elizabeth Kelly, and Hieu Nguyen, all of the MGH Department of Anesthesia,
Critical Care and Pain Medicine.  MGH has filed a patent application for
MOC-etomidate and other etomidate analogues.