Methylene blue in the critical care setting

Table 2 Summary of systematic reviews and meta-analyses on the use of methylene blue in shock and vasoplegic syndromes

Author	Type of study	Indication	Dose for studies	Results
Cadd et al[33], 2024	4 retrospective studies	263	Vasoplegic shock post-cardiopulmonary bypass	Hydroxocobalamin vs MB: Hydroxocobalamin was associated with a significant improvement in mean arterial pressure at 1 hour (MD: 5.30 mmHg, 95%CI: 2.98-7.62), total vasopressor dose at 1 hour (MD: -0.13 mcg/kg/minute NEE, 95%CI: -0.25 to -0.01) and total vasopressor dose at 6 hours (MD: -0.15 mcg/kg/minute NEE, 95%CI: -0.21 to -0.08) compared to MB
				No differences were observed in SVR or mortality between groups
Huang et al[39], 2024	6 RCTs	265	Septic shock, vasoplegic syndrome after cardiac surgery and ischemic reperfusion	MB reduced the duration of mechanical ventilation (MD: -0.68; 95%CI: -1.23 to -0.14), ICU LOS and (MD: -1.54, 95%CI: -2.61 to -0.48); hospital LOS (MD: -1.97; 95%CI: -3.92 to -0.11)
			Syndrome due to liver transplantation	No significant difference in mortality between the MB and placebo groups (ORs = 0.59; 95%CI: 0.32 to -1.06)
Zhao et al[4], 2022	10 RCT	832	Septic shock, vasoplegic syndrome and ischemic reperfusion	Mortality decreased (OR = 0.54, 95%CI: 0.34-0.85, P = 0.008); vasopressor use decreased (MD: -0.77, 95%CI: -1.26 to -0.28, P = 0.002)
	5 observational studies			MB increased MAP, HR and SVR. MB was associated with a lower incidence of renal failure. MB was linked to reduced lactate levels
Brokmeier et al[34], 2023	3 retrospective cohort studies	-	Vasoplegic shock post-cardiopulmonary bypass	Hydroxocobalamin vs MB: Hydroxocobalamin was associated with a higher MAP at 1 hour (MD: 7.80, 95%CI: 2.63-12.98); no difference in mortality (OR = 0.92, 95%CI: 0.42-2.03)
Ng et al[26], 2025	5 RCTs	257	Septic shock	MAP increased (MD: 8.4 mmHg, 95%CI: 5.01-11.75); mortality decreased (OR = 0.49, 95%CI: 0.27-0.88) reduced LOS (MD: -1.94 days, 95%CI: -3.79 to -0.08, P = 0.04, and increased PaO2/FiO2 (MD: 34.78, 95%CI: 8.94 to 60.61, P = 0.008)
Alkazemi et al[27], 2024	15 (5 RCTs, 10 observational studies)	441	Septic shock	Mortality decreased (OR = 0.52, 95%CI: 0.38-0.66, P < 0.001); ICU LOS decreased in 1 study; MAP increased post-infusion in 3 studies
Ballarin et al[12], 2024	3 RCTs	141	Septic shock	ICU LOS decreased (MD: -1.58, 95%CI: -2.97 to -0.20, P = 0.03); ventilation days decreased (MD: -0.72, 95%CI: -1.26 to -0.17, P = 0.01); time to vasopressor discontinuation decreased (MD: -31.49 hours, 95%CI: -46.02 to -16.96, P < 0.0001)

MB: Methylene blue; MAP: Mean arterial pressure; MD: Mean difference; CI: Confidence interval; NEE: Norepinephrine equivalent; SVR: Systemic vascular resistance; ICU: Intensive care unit; LOS: Length of stay; OR: Odds ratio; RCT: Randomized controlled trial; HR: Heart rate; PaO₂/FiO₂: Ratio of arterial oxygen partial pressure to fraction of inspired oxygen.