Ph.D. (Pharmacology) Northwestern University, 1982
M.D. Northwestern University, 1982
Massachusetts General Hospital, Residency in Anesthesiology, 1984-86
Massachusetts General Hospital, Research Fellowship in Anesthesiology, 1986-88
Although anesthetics have been given primarily via the inhalational route throughout the history of anesthesiology, I am interested in the pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous anesthetics. I was involved in the initial clinical trial of the opioid remifentanil whose novel pathway of elimination, via tissue esterases, causes it to have an extremely short duration of action. That study demonstrated that the pharmacological effects of the drug can be expected to wear off within a few minutes regardless of the cumulative dose administered. Subsequently I studied remifentanil in persons with severe hepatic failure or with renal failure requiring dialysis. Based on the known pathway of remifentanil metabolism, such organ dysfunction should have no effect on its PK. These experiments, in which the persons with organ dysfunction were studied as volunteers, demonstrated that as expected remifentanil was as short-acting in these persons as in matched control subjects without organ disease. In addition, the PD experiments showed that persons with liver failure were more sensitive to the ventilatory depressant effects of remifentanil.
Despite the use of morphine in medicine for thousands of years, until recently there was no simultaneous PK/PD study of morphine in humans. This study, again performed in volunteers, showed that even after intravenous administration, the time required for the peak morphine effect to occur was approximately 1.5 hr.
Postoperative nausea and vomiting (PONV) remains a significant problem after anesthesia. I have been involved in several studies on two of the antiemetics that are antagonists at the 5-HT3 receptor, ondansetron and dolasetron. In addition, I performed the first detailed dose-response study of ondansetron in preventing PONV.
Droperidol is the most effective single agent in preventing PONV. Unfortunately, since 2001 it has carried a boxed warning because of its alleged risk in causing cardiac arrhythmias. I performed and published a detailed safety analysis using FDA's own safety data showing that the boxed warning is unwarranted when droperidol is given at the usual antiemetic doses.