Hydroxocobalamin for Vasodilatory Hypotension in Shock: A Systematic Review With Meta-Analysis for Comparison to Methylene Blue

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. We performed a systematic search of Ovid Medline, Embase, and EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. Meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The ROBINS-I tool was used to assess the risk of bias. Twenty-four studies were identified and comprised of mainly case reports (n = 12) and case series (n = 9), as well as 3 cohort studies. Hydroxocobalamin was mainly applied for cardiac surgery vasoplegia but was also reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and non-cardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure at 1-hour compared to methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in mean arterial pressure (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1-hour when compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42 to 2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to mainly anecdotal reports and a few cohort studies. Hydroxocobalamin appears to have a positive effect on hemodynamics in shock, albeit similar to methylene blue.