Methylene Blue Utilization for Refractory Septic Shock in the Setting of Cirrhosis as a Bridge to Successful Liver-Kidney Transplant: Case Report and Review of the Literature

Abstract

SESSION TITLE: Critical Care Cases I SESSION TYPE: Affiliate Case Report Slide PRESENTED ON: Sunday, October 25, 2015 at 03:15 PM - 04:15 PM INTRODUCTION: While routinely used for methemoglobinemia, methylene blue's utility in septic shock is less clear despite being described more than two decades ago. Its hemodynamic effects occur via selective inhibition of nitric oxide in the cyclic guanosine monophosphate (cGMP) pathway, resulting in increased vascular tone. CASE PRESENTATION: We present a case of a 60 year old woman with decompensated alcoholic cirrhosis recovering from pneumonia, Enterococcal urinary infection, and renal failure requiring continuous veno-venous hemofiltration. She was awaiting liver and kidney transplant with a model for end-stage liver disease (MELD) score of 40. On hospital day 36, she developed a new vasopressor requirement and rising leukocytosis from 10,400 to 22,800 cells/mL with 25% bands over three days. Antibiotics were broadened to include meropenem and micafungin in addition to continuing daptomycin for Enterococcus. The following day, she tested positive for Clostridium difficile and was started on intravenous metronidazole and oral vancomycin. Over the next two days, she developed shock refractory to fluid resuscitation, vasopressin, norepinephrine, epinephrine, phenylephrine and hydrocortisone. For pressor-refractory shock, methylene blue (2 mg/kg) was bolused, followed by a continuous infusion (0.5 mg/kg/h for six hours titrated to 0.3 mg/kg/h). Within 6 hours and without other remarkable interventions, her hemodynamics markedly improved such that epinephrine and phenylephrine were discontinued. Within 24 hours, she required only 7 mcg/min of norepinephrine, and methylene blue was stopped at 48 hours. With sustained hemodynamic improvements, she was deemed a transplant candidate again and underwent successful liver and kidney transplant 3 days post-infusion. DISCUSSION: Prior case reports and clinical studies have suggested transient hemodynamic benefit in septic shock but no improvement in patient-centered outcomes. These mixed results reflect the inability to identify the subpopulation of shock likely to benefit. Given its mechanism of action, we reasoned methylene blue might be effective in treating septic shock in the setting of cirrhosis, which also exhibits nitric oxide-mediated vasodilation. CONCLUSIONS: To our knowledge, this is the first report of methylene blue as a bridge to liver transplant. This case suggests an effective treatment option in septic shock with concomitant nitric oxide dysregulation such as in cirrhosis. Reference #1: Jang DH. J Med Toxicol. 2013; 9:242-249. Reference #2: Dumbarton TC. Can J Anesth. 2011; 58:401-05. DISCLOSURE: The following authors have nothing to disclose: Michael Kavanaugh, Jennifer Berumen, Frank Chu, Jeffrey Yin, Jeremy Beitler No Product/Research Disclosure Information