2025 Southeastern Residency Conference

Title: Vasopressor-Sparing Effects of Methylene Blue versus Hydroxocobalamin for Vasoplegic Syndrome Post-Cardiac Surgery

Authors: Cameron Garramone, Reena Patel, Michael Byers, Deidra Garrett

Objective: Compare vasopressor-sparing effects calculated using the vasoactive-inotropic score (VIS) after the administration of methylene blue or hydroxocobalamin for vasoplegic syndrome (VS) post-cardiac surgery.

Self-Assessment Question: What is the difference between methylene blue and hydroxocobalamin in vasopressor-sparing effects for vasoplegic syndrome post-cardiac surgery?

Background: VS is a life-threatening condition that occurs in 5% to 25% of patients undergoing cardiac surgery using cardiopulmonary bypass (CBP) with a mortality rate as high as 25%. The mainstay of managing VS is catecholamine vasopressors, such as epinephrine and norepinephrine. For VS refractory to vasopressors, second-line therapies such as methylene blue and hydroxocobalamin play a key role in its management. Several studies evaluated the use of these therapies and showed a significant decrease in vasopressor requirements and improvement in hemodynamic parameters. At Piedmont Atlanta Hospital, methylene blue is the initial choice for treating refractory VS unless contraindications, such as concomitant use of serotonergic drugs or those with glucose-6-phoshate dehydrogenase (G6PD) deficiency, are present. The VIS calculation, a commonly used tool in research settings, was utilized to objectively quantify the degree of vasopressor support required to maintain hemodynamic stability. Further research is warranted given the lack of direct comparator studies for treating VS using this scoring tool.

Methodology: This was a retrospective chart review of adult patients who underwent cardiac surgery and received either methylene blue or hydroxocobalamin for the treatment of VS between January 2022 and August 2024. Types of cardiac surgery included coronary artery bypass graft, heart valve procedures, left ventricular assist device implant, and heart transplantation. Patients were excluded if interventions were administered > 24 hours post-cardiac surgery, supported on extracorporeal membrane oxygenation (ECMO) prior to surgery, or received tocilizumab intraoperatively. The primary outcome was percent change in VIS from baseline to 24 hours after methylene blue or hydroxocobalamin administration. Secondary outcomes included percent change in VIS from baseline to each timepoint (1, 2, 6, and 12 hours), percent change in mean arterial pressure (MAP) from baseline to 24 hours, need for additional VS treatment (methylene blue or hydroxocobalamin [if not used initially] and angiotensin II), need for ECMO 24 hours post-cardiac surgery, and number of vasopressors discontinued at 6 hours. Clinical outcomes included length of stay from time of procedure and hospital mortality at 24 hours. Statistical analysis was completed using Wilcoxon Rank Sum or independent t-test and chi-square or Fischer’s exact test where appropriate. A p-value of < 0.05 was considered statistically significant.

Results: In the assessed cohort, 35 patients from each group were included for analysis. When comparing methylene blue to hydroxocobalamin, there was a statistically significant difference noted in the primary outcome of percent change in VIS from baseline to 24 hours (-46.4% vs -64.8%; p=0.027), and percent change in MAP from baseline to 24 hours (12.3% vs 22.2%; p=0.012). No statistical significance was found in need for additional VS treatment (40% vs 25.7%; p=0.203), need for ECMO 24 hours post-cardiac surgery (5.7% vs 11.3%; p=0.238), or number of vasopressors discontinued at 6 hours (22.9% vs 22.9%; p=1). The use of hydroxocobalamin had a numerically higher incidence of 2 or more vasopressors being discontinued at 6 hours (37.5% vs 75%; p=0.137), but not statistically significant. There was a statistically significant difference for percent change in VIS from baseline to 12 hours (-29.4% vs -51.9%; p=0.04), but not at 1 hour (-2% vs -13.6%; p=0.153), 2 hours (-7.3% vs -22.6%; p=0.061), or 6 hours (-22.8% vs -28%; p=0.401).

Conclusions: There was a statistically significant difference noted in the primary outcome as well as the secondary outcomes of percent change in VIS from baseline to 12 hours and percent change in MAP from baseline to 24 hours. However, there were no major differences noted in any other secondary outcomes or clinical outcomes. Study limitations included the retrospective design, small patient population, and non-standardized vasopressor weaning protocol. Prospective trials with a larger sample size are warranted in this population.