[Interactions of H2 antagonists and non-depolarizing muscle relaxants]

Many drugs potentiate the action of non depolarizing relaxants. These interactions are of clinical importance if such drugs are administered during the perioperative period. H2 Antagonists are increasingly often used for premedication. Cimetidine inhibits the elimination of a number of drugs used in the perioperative period. We therefore investigated whether H2 antagonists enhanced neuromuscular blockade by vecuronium, a medium short acting non depolarizing muscle relaxant. METHODS. The study was carried out in 24 female patients (ASA class I or II) scheduled for microsurgical procedures. Neuromuscular transmission was recorded electromyographically using four stimulations every 20 s to the ulnar nerve. After induction with thiopentone, anesthesia was maintained with fixed concentrations of volatile anesthetics. Fentanyl was administered for additional analgesia. Vecuronium was used as the sole muscle relaxant. Fixed repetitive doses of vecuronium (0.8-1.2 mg) were injected whenever the T1 returned to 25%. This time interval was defined as the T1-25 period. The study proper started when the T1-25 period had stabilized. After two control periods, six patients in each group received either 200 or 400 mg cimetidine or 100 mg ranitidine. The fourth group was the control group. The T1-25 periods and the maximal EMG depression were recorded automatically for at least two further periods. The first measured period was recorded as 100% and the length of each other periods was calculated as a percentage of the control period. This method enables an intraindividual comparison of the length of the T1-25 period and the maximal EMG depression before and after administration of the H2 antagonists. A two-tailed Student's t-test was used to test statistical significance, P less than 0.05 being accepted as significant. RESULTS. In the control group and in the group with 200 mg cimetidine or 100 mg ranitidine no statistical significant prolongation of the T1-25 period or of the maximal EMG depression could be observed, while after 400 mg cimetidine there was significant prolongation (mean 161 +/- 14.8%) of the T1-25 period and significantly greater EMG depression compared with the pre-cimetidine values. In the groups with 200 mg cimetidine or 100 mg ranitidine few patients showed prolongation of the T1-25 period up to 130%. DISCUSSION. Our results confirm experimental studies that have shown cimetidine to enhance aminoglycoside--relaxant interactions. Because we found an immediate response to the administration of the H2 antagonists, the interaction cannot be on the elimination side; it must be at the neuromuscular junction. Experimental investigation has shown that calcium reverses the cimetidine effects. It is therefore probable that the cimetidine--relaxant interaction occurs at the presynaptic level. Careful observation seems to be necessary if H2 antagonists, especially cimetidine, are administered intraoperatively at the same time as drugs that also enhance