Pharmacology in Emergency Medicine A REVIEW OF METHYLENE BLUE TREATMENT FOR CARDIOVASCULAR COLLAPSE Jean C. Y. Lo, MD, Michael A. Darracq, MD, MPH, and Richard F. Clark, MD Department of Toxicology, University of California, San Diego, San Diego, California Reprint Address: Jean C. Y. Lo, MD, Department of Toxicology, University of California, San Diego, 135 Dickinson Street, San Diego, CA 92103 , Abstract—Background: Historically, methylene blue (MB) has been used for multiple purposes, including as an antidote for toxin-induced and hereditary methemoglobi- nemia, ifosfamide-induced encephalopathy, and ackee fruit and cyanide poisoning; as an aniline dye derivative, antima- larial agent, and antidepressant. Discussion: Most recently, the use of MB has been advocated as a potential adjunct in the treatment of shock states. Our article reviews the role of MB in septic shock, anaphylactic shock, and toxin- induced shock. MB is proposed to increase blood pressure in these shock states by interfering with guanylate cyclase activity, and preventing cyclic guanosine monophosphate production and vasodilatation. Summary: MB may be an adjunct in the treatment of septic shock, anaphylactic shock, and toxin-induced shock. Ó 2014 Elsevier Inc. , Keywords—methylene blue; septic shock; anaphylactic shock; shock due to toxin INTRODUCTION Shock is a condition with the potential for significant morbidity and mortality for patients in the emergency department (ED) and throughout the hospital. Despite multiple causative etiologies, the insufficient delivery of oxygen to organs and tissue results in organ dysfunction and potential organ necrosis. Much effort and attention has been directed at the appropriate treatment of shock in the ED to correct the mismatch between oxygen deliv- ery and oxygen demand, to reverse tissue hypoxia, and limit or prevent organ dysfunction and death. Treatment protocols that emphasize intravascular volume and central venous pressure restoration, optimization of oxygen- carrying capacity via exogenous oxygen delivery and blood transfusion, and vasopressors to improve inotropy, chronotropy, and peripheral vascular resistance have been advocated and implemented with positive results. The use of methylene blue (methylthioninium chloride [MB]) has been advocated as a potential adjunct in the treatment of shock states. This article will review the liter- ature on MB for the treatment of shock. HISTORICAL BACKGROUND MB was the first fully synthetic drug used in medicine. This chemical was first developed as an aniline dye deriv- ative for the textile industry by Heinrich Caro in 1876, and Robert Koch used MB as a stain for microscopic visu- alization of the tuberculosis bacilli in 1870. After observing that bacteria and parasites were seen with MB-containing stains, Paul Ehrlich argued this might suggest a harmful effect on the microorganism by MB that could be used in the prevention and treating of dis- ease (1–3). As a result of these observations and arguments, Ehrlich and Guttman applied MB to the treatment of malaria starting in 1891 (4). MB was used as an antimalarial agent through the end of World War II by U.S. service members but was not well liked, as it resulted in characteristic but reversible blue-green urine and blue sclera (5). More recently, interest has been re- newed in MB as an antimalarial agent (6,7). In the 1920s, MB was observed to be a potent treatment for RECEIVED: 28 February 2012; FINAL SUBMISSION RECEIVED: 7 May 2013; ACCEPTED: 18 August 2013 670 The Journal of Emergency Medicine, Vol. 46, No. 5, pp. 670–679, 2014 Copyright Ó 2014 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter http://dx.doi.org/10.1016/j.jemermed.2013.08.102