The effect of high dose morphine compared to fentanyl infusion on serum levels of mast cell tryptase during cardiac surgery

[摘要] Background: Morphine directly activates cutaneous mast cells in a seemingly dose-dependent manner, resulting in the release of both histamine and tryptase into the bloodstream. Tryptase is almost exclusively stored in mast cells. Elevated serum tryptase concentrations serve as an indicator of mast cell activation and have become the most frequently used laboratory investigation in anaphylaxis. Following a clinical diagnostic dilemma our study was aimed at answering whether mast cell tryptase concentration remains useful in supporting the diagnosis of anaphylaxis even after administration of high dose morphine.Methods:We conducted a non-blinded, randomized controlled trial comparing the effects of fentanyl and high dose morphine, on serum mast cell tryptase concentrations. A power analysis was performed. Twenty adults undergoing cardiac surgery were randomly assigned to one oftwo opioid regimens. Both groups received a fentanyl bolus of 3 to 8 mcg/kg at induction. In the fentanyl group this was followed by a fentanyl infusion of 5 to 10 mcg/kg/hr until completion of surgery. Patients in the morphine group received morphine 1 mg/kg infused over thirty minutes.Baseline serum mast cell tryptase concentrations were determined directly prior to induction of anaesthesia and again 90 minutes after the start of the opioid infusion. The primary endpoint was statistical differences in tryptase concentrations between the morphine and fentanyl groups at the two time periods.Results: Ten patients of similar demographics were enrolled in each group. In the fentanyl groupthe second, 90-minute mast cell tryptase concentration was statistically significantly (10.1%)lower (p = 0.006) than baseline. Despite the 95% confidence interval of the difference between the means (-1.06 to -0.34 mcg/L) not including zero , this was not a clinically importantdifference.In the morphine group serum mast cell tryptase concentrations in the second (90 minute)sample were not statistically different from baseline values, the 95% confidence interval including zero. No between-group differences in tryptase concentration were detected. One patient in the morphine group exhibited a clinically significant 50,4% increase in tryptase concentrations, albeit from a high baseline of 11.9 mcg/L, which in this small study constitutes a prevalence of 10% (95% CI 1.8% to 40.4.)Conclusion: In this small pilot study, serum mast cell tryptase concentrations were unaffected by whether fentanyl or high dose morphine was administered. The null hypothesis, that there is no significant increase in serum mast cell concentrations after high dose morphine compared tofentanyl during cardiac anaesthesia and surgery, was therefore accepted. Larger studies are however needed to ensure a robust result, especially in the morphine group

[发布机构] Stellenbosch University