Assessment of Risk Factors for Vasoplegic Syndrome in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass

Vasoplegic syndrome (VS), a common complication of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), can be defined as an abnormally low systemic vascular resistance presenting as profound hypotension and vasodilatory shock despite adequate cardiac output. Multiple risk factors for the development of VS post-CPB have been explored. The purpose of this study is to identify additional patient-specific risk factors associated with VS, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, angiotensin receptor/neprilysin inhibitor, beta blockers, dihydropyridine calcium channel blockers, dobutamine, milrinone, HMG-CoA reductase inhibitors, aspirin, P2Y12 inhibitors, scheduled phosphodiesterase 5 inhibitors, intravenous treprostinil, hydralazine, sulfonylureas, continuous infusion loop diuretics, vasopressors, other anti-hypertensive agents, amiodarone, and steroid use.

This single-center, retrospective, case-control study includes adult patients ≥19 years old admitted to the cardiovascular intensive care unit (ICU) following cardiothoracic surgery with CPB. Patients in the VS group were identified as having received methylene blue, hydroxocobalamin, or angiotensin II within 48 hours of CPB initiation. Patients were excluded if they were pregnant, incarcerated, or <19 years old. Controls were matched by procedure type, age within five years, and patient sex. The primary outcome is a correlation of risk factors of VS. Secondary outcomes include vasopressor utilization at pre-specified time points, ICU length of stay, hospital length of stay, and survival to hospital discharge. Statistical analyses used Fisher's exact test for categorical data and the Wilcoxon rank-sum test or independent samples t-test for continuous data (PC SAS v9.4, significance at p<0.05).  Results: Of 63 patients identified as having received methylene blue, hydroxocobalamin, or angiotensin II, 38 patients met the inclusion criteria. After matching, 114 patients were included in the analysis. Baseline characteristics were similar, with 83% male patients and a median age of 57.5 years, except for a difference in CPB duration (189 minutes vs. 142.5 minutes, p=0.017). When assessing risk factors for the primary outcome, there was no difference between groups except with hydralazine (9 (23.7%) vs. 7 (9.2%), p=0.047). There were differences observed in ICU length of stay (7 vs. 4 days, p=0.004), hospital length of stay (25 vs. 22.5 days, p=0.028), and survival to hospital discharge (28 (73.7%) vs. 75 (98.7%), p<0.001).

Hydralazine was the only pre-operative factor identified with a higher incidence of usage in the VS group. Further research is needed to determine the clinical significance of this association.