Administration of methylene blue in septic shock: pros and cons

Abstract

Septic shock typically requires the administration of vasopressors. Adrenergic agents remain the first choice, namely norepinephrine. However, their use to counteract life-threatening hypotension comes with potential adverse effects, so that non-adrenergic vasopressors may also be considered. The use of agents that act through different mechanisms may also provide an advantage. Nitric oxide (NO) is the main driver of the vasodilation that leads to hypotension in septic shock, so several agents have been tested to counteract its effects. The use of non-selective NO synthase inhibitors has been of questionable benefit. Methylene blue, an inhibitor of soluble guanylate cyclase, an important enzyme involved in the NO signaling pathway in the vascular smooth muscle cell, has also been proposed. However, more than 25 years since the first clinical evaluation of MB administration in septic shock, the safety and benefits of its use are still not fully established, and it should not be used routinely in clinical practice until further evidence of its efficacy is available.

Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis

“…Although this review highlights the potential of MB as a therapeutic strategy in septic shock, the inherent uncertainty in the literature suggests that clinical equipoise regarding its utility may exist ( 10 ). Given the limited data describing the current use of MB in septic shock, a practice audit and clinician survey would be particularly useful components of a future research program on this topic.…”

“…Despite this, evidence examining the use of MB in septic shock remains sparse, including only small randomized clinical trials (RCTs). Furthermore, the risk of MB-associated adverse effects is unclear ( 10 ). To address this critical knowledge gap, we conducted a systematic review and meta-analysis summarizing the efficacy and safety of MB in adult patients with septic shock.…”

Methylene blue in sepsis and septic shock: a systematic review and meta-analysis

“…In this context, strategies that prioritize decatecholaminization have been proposed for the management of patients with septic shock; however, as additional vasopressor agents, including vasopressin, terlipressin, and angiotensin-2, are similarly linked to an increased likelihood of tachyarrhythmias, organic ischemia, and immune dysfunction ( 9 , 10 ), methylene blue (MB) has been explored as a potential alternative to reach the hemodynamic targets ( 14 ). MB acts by blocking the enzyme guanylate cyclase, reducing excessive nitric oxide production, and alleviating its vasorelaxant effect in vascular smooth muscle, restoring vascular tone and increasing blood pressure ( 10 , 15 , 16 ).…”

“…Although MB effectively increases vascular tone and arterial pressure, its affordability and widespread availability notwithstanding, the absence of randomized clinical trials poses challenges in evaluating its effectiveness in patients with sepsis ( 10 ). While several systematic reviews have previously been published on this subject matter, recently, a randomized controlled trial (RCT) with a larger sample was published ( 17 ).…”