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Abstract

Introduction: Septic shock is a major cause of morbidity and mortality in the intensive care unit, and effective therapies are limited. An increasing body of literature continues to show the benefits of methylene blue (MB) in cases of refractory hypotension caused by the systemic inflammatory response syndrome (SIRS), septic shock, or vasoplegic syndrome. The use of MB or tetramethylthionine chloride to treat septic shock is not considered a standard of care and often remains a therapy of last resort. The author reports the successful use of MB in a patient with refractory septic shock. A 64 years old female with significant past medical history for toxic colitis requiring total colectomy a year ago presented to our institution with symptoms of abdominal pain, nausea and decreased ostomy output. On admission, she was hemodynamically stable however later on she developed progressive lactic acidosis. Subsequently she was diagnosed with a small bowel obstruction and an exploratory laparotomy with lyses of adhesions was performed. After admission to the ICU, the patient became progressively hypotensive with mean arterial pressures of approximately 60 mm of Hg. Her arterial lactate levels continued to climb. During this time, multiple boluses of crystalloids were given in an effort to alleviate her hypotension. Epinephrine, nor-epinephrine and vasopressin infusions were titrated up to the maximum dose. Six hours after surgery her Esophageal Doppler monitor showed normal to high cardiac output, and a low calculated systemic vascular resistance (SVR) with a CVP of approximately 20 mm of Hg. A loading dose of MB (1mg/kg) was administered over 10-20 minutes followed by a continuous infusion of 0.5 mg/kg/hour for more than 8 hours (Fig.1). The immediate effect of the infusion was a rapid restoration of hemodynamic stability and a subsequent decrease in vasopressor requirements. Unlike what it has been reported before, the author was able to discontinue the MB infusion without further need of vasopressors. Patient was found to have Clostridium difficile colitis in the remaining small bowel which was treated with metronidazole and oral vancomycin. Ultimately, the patient survived the illness and was discharged without any further hemodynamic complications. No adverse events that could be attributed to the use of MB were observed apart from significant blue/green discoloration of the skin and mucosa. MB is often used in patients with vasoplegia after cardio-pulmonary bypass. 3 Its indication for sepsis has been considered the therapy of last resort. In this case, the author reports more than 8 hours of MB infusion in a patient with refractory septic shock. MB is an inhibitor of both inducible nitric oxide (NO) synthase and guanylate cyclase in vascular smooth muscle cells. Inhibition of these enzymes often results in decreased production of NO. 2 Cytokines and inflammatory factors present during sepsis are thought to induce endothelial NO production in smooth muscle cells, leading to systemic vasodilatation and shock. By blocking the production of NO in the vasculature, MB is believed to mitigate the vasodilatory response in refractory septic shock. The use of MB in patients with septic shock results in increased MAP and SVR while decreasing vasopressor requirements, increased pulmonary vascular resistance has been noticed with bolus administration but could be avoided by continuous infusion of the drug. Although a randomized trial of MB in post cardiac surgery vasoplegia demonstrated a clinical significant 31% absolute reduction in mortality, MB effect on oxygen delivery and mortality remains unknown. 4 A recent case report has shown in the setting of severe sepsis in an immunosuppressed patient, MB should be considered early as a therapeutic option for treatment of refractory vasoplegia. 5 Further research is warranted to explore the efficacy and safety of MB in patients with refractory septic shock.