Methylene Blue for Septic Shock: A Systematic Review and Meta-analysis of Randomized and Prospective Observational Studies

Background The impact of methylene blue (MB) on critical patient outcomes, including overall mortality, hemodynamic stability, and organ function has been inconsistently described across studies. This study aims to evaluate the efficacy of MB therapy in adult patients with septic shock in the intensive care unit (ICU). Methods The systematic search of PubMed/MEDLINE, EMBASE and Cochrane Library databases up to February 2024 included randomized controlled trials and prospective observational studies involving adult septic shock patients who received intravenous MB therapy. The primary outcome was all-cause mortality, with secondary outcomes on hemodynamics and ICU length of stay. Results Fifteen studies (5 randomized, 10 non-randomized) involving a total of 441 patients, met the inclusion criteria. The meta-analysis showed statistically significant reduction in mortality rates among septic shock patients treated with MB (mortality rate 0.52; 95% CI 0.38 to 0.66; P < .001). In a sub-analysis of only randomized trials, the results remained statistically significant (risk ratio 0.66; 95% CI 0.47 to 0.94; P = .023). A significant increase in mean arterial pressure post-infusion was observed in three studies. Two studies showed no substantial difference in heart rate and two studies showed no difference in cardiac index following MB administration. Only one study showed a reduction in the length of ICU stay with MB use, while another observed a decrease in overall hospital length of stay. Conclusions The review and meta-analysis suggest that MB may be associated with a significant reduction in mortality in septic shock patients though findings are limited by sample size and heterogeneity. Further robust studies are needed to validate these results.