LAUSR

BACKGROUND Protamine administration post-cardiopulmonary bypass (CPB) can potentially cause hemodynamic instability. Histamine released from mast cells is believed to be responsible for hypotension after protamine administration. The aim of this study was to examine the effects of pretreatment with H1 and H2 antihistamines on changes in systemic arterial pressure following protamine administration. METHODS This study was a randomized, triple-blinded, placebo-controlled study, conducted at a university hospital. Forty adult patients undergoing elective coronary bypass graft surgery (CABG) or single valve surgery were included. The patients were randomly allocated (20 patients in each group) to receive a single dose of combined chlorpheniramine 10 mg and ranitidine 50 mg or normal saline intravenously immediately after separation from CPB prior to protamine administration. Trajectory changes in systolic blood pressure (SBP), mean arterial pressure (MAP), and vasoactive-inotropic score (VIS) from baseline until 35 minutes following protamine administration (24-time points) were compared between the two groups. Serial serum tryptase levels were also obtained at baseline, 30 and 60 minutes after protamine was given. RESULTS Forty patients were included in the analysis. Demographic and baseline blood pressure were similar between the two groups. At 30 minutes after protamine administration, there were no significant differences in both crude SBP [mean difference: -7.1 mmHg, 95% confidence interval (CI), -1.1 to 15.3 mmHg, P=0.09] and SBP after adjustment for the European System for Cardiac Operative Risk Evaluation (EuroSCORE II), CPB time, and VIS (mean difference: -3.9 mmHg, 95% CI, -11.9 to 4.0 mmHg, P=0.33). There were also no significant differences in crude MAP (mean difference: -2.1 mmHg, 95% CI, -6.9 to 2.7 mmHg, P=0.39) and adjusted MAP (mean difference: -0.7 mmHg, -5.9 to 4.4 mmHg, P=0.78) between the two groups. None of the patients in both groups had a significant increase in serum tryptase from baseline. No differences in median serum tryptase levels at baseline, 30 and 60 minutes were demonstrated between the two groups. CONCLUSIONS Pretreatment with H1 and H2 antihistamines does not attenuate blood pressure responses to protamine administration in patients after CPB. Mechanisms other than histamine release from mast cells might be responsible for protamine-induced cardiovascular changes. TRIAL REGISTRATION ClinicalTrials.gov NCT03583567.