title: A systematic analysis of methylene blue for drug-induced shock.
abstract: BACKGROUND
  Pharmacologically induced shock can be refractory to standard resuscitation. Methylene blue (MB) acts to prevent nitric oxide-mediated vasodilation and may be a potential treatment for refractory shock.
  
  
  OBJECTIVE
  A systematic analysis of the literature to evaluate MB in pharmacologically induced shock. Primary outcome was survival and secondary outcome was hemodynamic improvement.
  
  
  METHODS
  A search of MedLine/PubMed, EMBASE, Cochrane Library, TOXLINE, Google Scholar and Google was performed 10 August 2015 using a combination of text words and keywords related to MB, shock and specific drugs. We included primary literature articles reporting clinical outcomes in humans.
  
  
  RESULTS
  The searches yielded 928 citations, with 255 exact duplicates. Of the 673 entries screened, 16 citations met study criteria and comprised 17 cases. Calcium channel blockers (CCBs) represented ten cases (six amlodipine, two verapamil, and two diltiazem), atenolol three cases as coingestant with amlodipine, five metformin, one ibuprofen, and one multidrug (quetiapine, carbamazepine, valproic acid, oxazepam, and fluoxetine). Twelve patients survived and nine had hemodynamic improvement following MB administration. Four did not respond to MB but survived with other advanced resuscitative measures. None of the seven cases had BP improvement and four died when lipid was given prior to MB, compared to one death and nine cases of BP improvement when lipid was not given. In all cases, MB was used after failing several other treatments. Bolus doses ranging from 1 to 3 mg/kg, with repeat boluses or maintenance infusions. Reported adverse events were temporary self-limited blue discolorations.
  
  
  CONCLUSIONS
  While there are compelling cases describing an improved hemodynamic status following MB, there are also several cases without observed change. Currently, there is not enough evidence available to recommend the routine administration of MB in refractory pharmacologically induced shock.
authors.affiliation: a New Mexico Poison and Drug Information Center, University of New Mexico , Albuquerque , NM , USA ;
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Warrick
authors.affiliation: b Faculty of Pharmaceutical Sciences , The University of British Columbia , Vancouver , Canada.
authors.forename: Anita Paula
authors.initials: AP
authors.lastname: Tataru
authors.affiliation: a New Mexico Poison and Drug Information Center, University of New Mexico , Albuquerque , NM , USA ;
authors.forename: Susan
authors.initials: S
authors.lastname: Smolinske
mesh_terms: D002121:Calcium Channel Blockers / Q000633:toxicity*; D016208:Databases, Factual; D019317:Evidence-Based Medicine; D006439:Hemodynamics; D006801:Humans; D008751:Methylene Blue / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic; D012769:Shock / Q000139:chemically induced* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D002121:Calcium Channel Blockers; D009569:Nitric Oxide; D008751:Methylene Blue
keywords: Beta-blocker; calcium channel blocker; hypotension; intoxication; metformin