Mark Dershwitz, M.D., Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Anesthesiology

Joint Faculty In:
   Biochemistry and Molecular Pharmacology

Clinical Pharmacology of Intravenous Anesthetics and Antiemetics

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 new antiemetics that are antagonists at the 5-HT3 receptor, ondansetron and dolasetron.  I performed the first detailed dose-response study of ondansetron in preventing PONV, the results of which had significant economic implications considering the expense of the drug and the frequency with which it is used.  Most recently, I have been interested in demonstrating the safety of droperidol, an older antiemetic that has been unfarly burdened with a "black box" warning by the FDA.

Selected Recent Publications

Dershwitz M, Henthorn TK.  The pharmacokinetics and pharmacodynamics of thiopental as used in lethal injection.  Fordham Urban Law J 2008; 35:931-56.

Cooper JB, Blum RH, Carroll JS, Dershwitz M, Feinstein DM, Gaba DM, Morey JC, Singla AK.  Differences in safety climate among hospital anesthesia departments and the effect of a realistic simulation-based training program.  Anesth Analg 2008; 106:574-84.

Dershwitz M.   Is droperidol safe?   Probably…  Semin Anesth Periop Med Pain 2004; 23:291-301.

Dershwitz M.   Droperidol:   should the black box be light gray?   J Clin Anesth 2002; 14:598-603.

Dershwitz M, Michałowski P, Chang YC, Rosow CE, Conlay LA.  Postoperative nausea and vomiting following total intravenous anesthesia with propofol and remifentanil or alfentanil.  How important is the opioid?  J Clin Anesth 2002; 14:275-78.

Dershwitz M, Walsh JL, Morishige RJ, Connors PM, Rubsamen RM, Shafer, SL, Rosow C.   Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in healthy volunteers.  Anesthesiology 2000; 93:619-28.

Dershwitz M, Conant JA, Chang YC, Rosow CE, Connors PM.   A randomized double-blind dose-response study of ondansetron in the prevention of postoperative nausea and vomiting.   J Clin Anesth 1998; 10:314-20.

Kearse LA, Rosow C, Zaslavsky A, Connors P, Dershwitz M, Denman W.  Bispectral analysis of the electroencephalogram predicts conscious processing of information during propofol sedation and hypnosis.  Anesthesiology 1998; 88:25-34.

Hoke JF, Shlugman D, Dershwitz M, Michałowski P, Malthouse-Dufore S, Connors PM, Marten D, Rosow CE, Muir KT, Rubin N, Glass PSA.   Pharmacokinetics and pharmacodynamics of remifentanil in subjects with renal failure compared to healthy volunteers.   Anesthesiology 1997; 87:533-41.

Dershwitz M, Hoke JF, Rosow CE, Michałowski P, Connors PM, Muir KT, Dienstag JL.   Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease.   Anesthesiology 1996; 84:812-20.

Dershwitz M, Randel GI, Rosow CE, Fragen RJ, Connors PM, Librojo ES, Shaw DL, Peng AW, Jamerson BD.   Initial clinical experience with remifentanil, a new opioid metabolized by esterases.   Anesth Analg 1995; 81:619-23.

Dershwitz M, Di Biase PM, Rosow CE, Wilson RS, Sanderson PE, Joslyn AF.   Ondansetron does not affect alfentanil-induced ventilatory depression or sedation.   Anesthesiology 1992; 77:447-52.

Dershwitz M, Rosow CE, Di Biase PM, Joslyn AF, Sanderson PE.   Ondansetron is effective in decreasing postoperative nausea and vomiting.   Clin Pharmacol Ther 1992; 52:96-101.

Dershwitz M, Rosow CE, Di Biase PM, Zaslavsky A.   Comparison of the sedative effects of butorphanol and midazolam.   Anesthesiology 1991; 74:717-24.

Academic Background

B.A. (Departmental Honors in Chemistry) Oakland University, 1974
Ph.D. (Pharmacology) Northwestern University, 1982
M.D. Northwestern University, 1982

Postdoctoral Training

Carney Hospital, Transitional Internship, 1983
Massachusetts General Hospital, Residency in Anesthesiology, 1984-86
Massachusetts General Hospital, Research Fellowship in Anesthesiology, 1986-88

Office: S2-743
Phone: 508-856-2480
E-mail: Mark.Dershwitz@umassmed.edu

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