Histamine plasma concentration and cardiovascular effects of non-depolarising muscle relaxants: Comparison of atracurium, vecuronium, pancuronium and pipecuronium in coronary surgery risk patients.

Objective: Cardiovascular effects of four commonly used non-depolarising muscle relaxants and their ability to increase histamine plasma concentrations were studied in patients scheduled for coronary artery bypass grafting. Methods: 40 patients were included in the study after informed consent. After premedication with Flunitrazepam (2 mg p.o.) on the evening before and 1 hour prior to surgery anaesthesia was induced with Flunitrazepam (4-6 mu g kg(-1)), Fentanyl (3 mu g kg(-1)) und Etomidate (150 mu g kg(-1)) and the patients were ventilated via face mask with 50% N2O in oxygen. Patients were randomly allocated to one of four groups, and, 15 min after induction of anaesthesia, received equipotent doses of either Pancuronium (0.09 mg kg(-1), n = 10), Pipecuronium (0,08 mg kg(-1), n = 10), Atracurium (0,6 mg kg(-1), n = 10), or Vecuronium (0,1 mg kg(-1), n =10) injected over 20 seconds via a central venous catheter. Cardiovascular variables were determined in the awake patient, 15 min after induction of anaesthesia and following administration of the respective muscle relaxant. In addition, plasma histamine concentrations were assessed before and after relaxation. Evoked muscular response to TOF simulation of the ulnar nerve (plethysmo-mechanogram) was continuously recorded to determine the onset of neuromuscular blockade. Results: Heart rate, mean arterial pressure and cardiac index significantly decreased in all patients following induction of anaesthesia while systemic vascular resistance remained unchanged. Only Pancuronium caused a significant increase in heart rate (53 +/- 11 to 61 +/- 15 min(-1)) whereas cardiac index and mean arterial pressure did not change significantly. No other neuromuscular blocking agent caused any changes in the cardiovascular variables measured and histamine plasma concentrations remained within the reference range in all of the four groups with no differences detectable between groups. Conclusion: All investigated neuromuscular blocking agents exhibited marked cardiovascular stability which permits their use, being based exclusively on pharmacodynamic and pharmakokinetic considerations even in patients with coronary heart disease. If an increase in heart rate appears beneficial Pancuronium may be advantageous.