Nitroprusside vs. a Nitroprusside-Trimethaphan Mixture for Induced Hypotension

Abstract

Changes in hemodynamic variables and whole blood cyanide and plasma thiocyanate concentrations associated with the infusion of sodium nitroprusside were compared with those during administration of a mixture of sodium nitroprusside (25 mg) and trimethaphan camsylate (250 mg) in a solution of 5% dextrose in water in twenty subjects who required deliberate hypotension for major orthopedic procedures. Subjects were randomly assigned to receive nitroprusside alone (group 1; n = 10) or the nitroprusside-trimethaphan mixture (group 2; n = 10). All subjects received a similar anesthetic technique, consisting of 5 mg/kg thiopental, 1 mg/kg succinylcholine, 1% halothane, 0.2 mg/kg metocurine, and 60% nitrous oxide in oxygen. Mean arterial pressure decreased and was maintained at 55 mm Hg for 258 ± 4 and 266 ± 8 minutes in groups 1 and 2. Arterial hypotension was associated with a rise in cardiac output and heart rate in group 1 but not in group 2. Subjects in group 2 required less nitroprusside than did those in group 1 (1.39 ± 0.3 and 5.82 ± 0.63 µg/kg/min) because of the synergistic or additive action of the combination. After 4 hours of hypotension, the whole blood cyanide level rose from 3.5 ± 1.1 to 96.6 ± 14.0 µg/dl (1.35 ± 0.27 to 37.2 ± 5.4 µmol/L) in group 1 and from 3.7 ± 1.1 to 22.7 ± 4.2 µg/dl (1.42 ± 0.4 to 8.7 ± 1.6 µmol/L) in group 2. Plasma thiocyanate levels rose 2 hours after nitroprusside termination. Significant changes in pH and base deficit occurred late in the course of hypotension in group 1 only; there was a correlation (r = 0.896) between peak blood cyanide levels and decreases in base excess. A rebound increase in mean arterial pressure after termination of hypotension occurred only in group 1. Mean blood pressure increased an average of 13.5 (range 6 to 27) and 21.5 (range 8 to 32) mm Hg over the prehypotension and awake levels. Blood pressure was maximally increased 15 minutes after the end of the infusion and was associated with an increase in systemic vascular resistance; cardiac output did not change. One subject developed ST segment depression and required reinstitution of nitroprusside infusion. There were no adverse effects during or after cessation of the drug mixture. Clinical Pharmacology and Therapeutics (1985) 37, 264–270; doi:10.1038/clpt.1985.38