ANESTH ANALG 1053 1984;63 053-8 Effe ct s o f Intravenous Bupivacaine on Cardiovascu lar Function an d Plasma Catecholamine Levels in Humans Lars J. Hasselstrom, MD, Torben Mogensen, MD, Henrik Kehlet, MD, an d Niels J. Christensen, MD HASSELSTR0M LJ, MOGENSEN T, KEHLET H, CHRISTENSEN NJ. Effects of intravenous bupivacaine on cardiovascular function and plasma catecholamine levels in humans. Anesth Analg 1984;63:1053-8. The effects of the intravenous infus ion of bupi vacaine (2 mglmin for 3 h r) on cardiovascular function and various endocrine metabolic parameters were studied in a random- ized single-blind crossover stud y in eight normal subjects. Bupivacaine infusion resulted in plasma conc entrations about 1-2 pglml. Heart rate increased significantly from approx- imately 60 to 70 beatslmin. Mean arterial blood pressure increased from 87 to about 10 0 mm Hg, and cardiac output decreased about 20%, both o f these statistically sign ificant . Oxygen consumption did not change significantly. Plasma epinephrine concentrations increased signijicantly from 0.03 to 0.08 ng/ml, but plasma norepinephrine levels did not change sjgnificantly, nor did blood concentrations of cose, lactate and plasma cortisol, and free fa tt y acids. The se results demonstrate that systematically administered bu- pivacaine results in plasma concentrations of bupivacaine comparable to those that may be observed during regional anesthesia, including a positive chronotrop ic and an arterial vasoconstrictiv eeffect. Theseeffects areprobnbly cause d ma inly by a direct effect of bupivacaine on the cardiovascular sys- tem, because only quantitatively minor changes in plasma catecholamines and other endocrine metabolic parameters were observed. Ke y Words: LOCAL ANESTHETICS-bupivacaine. Studies o f the effects of systematically admini stered bupivacaine on cardiovascular function in animals have shown a decrease in contractility in a rabbit heart preparation (l), constrictive effe ct on the portal vein (2), and vasodilatation in the dog hind limb after in- traarterial injection (3). In humans, the infusion of bupivacaine has been associated with either no sig- nific ant changes or increa ses in heart rate, blood pres- sure, and cardiac output (4,5). Systemic vascular re- sistance has been reported to increase at low concentrations (6) and decrease at high concentrations of plasma bupivacaine (6). Infusion studies resulting in plasma bupivacaine concentrations comparable to either a slight increase (4) or decrease in peripheral vascula r resistance (5). In addition, oxygen consump- tion and splan chnic uptak e of glycerol and l actate increased (7), effect s that were hypothesized as being This study was supported by a grant from AB Astra, Sweden. Received from the Departments of Anesthesia and Internal Medicine and Endocrinology, Herlev Hospital, University o f Co- penhagen, and Hvidare Hospital, Klampenborg, Denmark. Ac- cepted for publication August 21, 1984. Address correspondence to Dr. Hasselstrem, Department of Anesthesia, Herlev Hospital, DK 2730 Herlev, Denmark. elated to (unm easu red) increases in plasma levels o f epinephrine. Because o f the unce rtainty su rro undi ng the phys- iologi c and biochemical consequences o f th e prese nce of bupivacaine in peripheral blood, we studied the effects o f intra ven ous infusion o f bu pivac aine on heart rate, blood pressure, cardiac output, oxygen con- sumption, and plasma concentrations o f epinephrine, norepinephrine, glucose, lactate, free fatty acids, and cortis ol in normal volunteers in a randomized single- blind crossover study. Mate rial and Methods Subjects Eight healthy v olunteers, four o f each sex, took part in the stud y after informed consen t was obtained. Age was 28 yr (median), range 23-44 yr; weight was 71 kg (media n), range 56 -79 kg. The investigat ion was Experimental Protocol The protocol consisted of a randomiz ed single -blind crossover design with a t least one week between each 0 1984 by the International Anesthesia Research Society
