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British Journal of Anaesthesia, 1992, Vol. 69, No. 5 492-497
© 1992 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

ENHANCEMENT OF BUPIVACAINE TOXICITY BY DILTIAZEM IN ANAESTHETIZED DOGS{dagger}

B. A. FINEGAN, M.B., F.R.C.P.C1, R. W. WHITING, M.B., F.F.A.R.A.C.S.1, Y. K. TAM, PH.D.2 and A. S. CLANACHAN, PH.D.3,

1Department of AnaesthesiaUniversity of Alberta Edmonton, Canada T6G 2H7
3Department of Pharmacology, University of Alberta Edmonton, Canada T6G 2H7
2Faculty of Pharmacy and Pharmaceutical Sciences University of Alberta Edmonton, Canada T6G 2H7

Correspondence to A.S.C.

We have studied the cardiovascular effects of graded doses of bupivacaine in the absence or presence of clinical concentrations (approximately 250 ng litre–1) of diltiazem in fentanyl-pentobarbi-tone anaesthetized dogs. Bupivacaine was given, increasing in a stepwise manner, as a loading dose (200, 400 or 600 pig kg–1) followed by a 30-min i. v. infusion (25, WO or 200 pig kg–1 min–1, respectively). Thereafter, bupivacaine was infused at 400 pig kg–1 min–1 until each animal died. Group AB (n= 5) 7 2 fig kg–1(n = 7) received bupivacaine, group diltiazem (400 fig kg–1 followed bymin–1) and group C (n = 7) received diltiazem followed by bupivacaine given as in group A. Lethal plasma concentrations of bupivacaine were significantly smaller (P < 0.01) in group C (7.1 (SEM 0.7) vs 12.6 (1.5) mg litre–1). Bupivacaine produced similar decreases in cardiac index, left ventricular (LV) segmental work and the first derivative of LV pressure (LV dP/dX) in the absence and presence of diltiazem. In group A, bivacaine increased systemic vascular resistance index (SVRI) and thus mean arterial pressure (MAP) was maintained. In group C, SVRI, reduced by diltiazem per se, did not increase in response to bupivacaine, so MAP was not maintained. Death resulted from a progressive decrease in cardiac contractility and MAP. Plasma concentrations of bupivacaine attained at the three doses were similar in the absence and presence of diltiazem. This study has shown that the toxicity of bupivacaine was increased approximately two-fold by diltiazem. (Br. J. Anaesth. 1992; 69:492–497)

{dagger}Presented in part to the Anaesthesia Research Society, April 1990[1]


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