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A systematic review of the literature was conducted to determine if the administration of methylene blue in humans improves hemodynamic status and/or outcome in patients with septic shock. Studies were identified from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials database. The review included human studies of patients with septic shock treated with methylene blue in which hemodynamic variables or mortality rates were reported. An electronic form was used to extract items including study design, population characteristics, intervention details, and outcomes. No meta-analysis was performed. Methylene blue administration in patients with septic shock increases mean arterial pressure and systemic vascular resistance while decreasing vasopressor requirements. Increased pulmonary vascular resistance has been reported with bolus administration but might be avoided by continuous infusion. No other ill effects were reported. Effects on mortality have not been adequately evaluated in the literature.