Advertisement

Journal of Medical Toxicology

, Volume 9, Issue 3, pp 242–249 | Cite as

Methylene Blue for Distributive Shock: A Potential New Use of an Old Antidote

  • David H. Jang
  • Lewis S. Nelson
  • Robert S. Hoffman
Review Article

Abstract

Methylene blue is used primarily in the treatment of patients with methemoglobinemia. Most recently, methylene blue has been used as a treatment for refractory distributive shock from a variety of causes such as sepsis and anaphylaxis. Many studies suggest that the nitric oxide–cyclic guanosine monophosphate (NO–cGMP) pathway plays a significant role in the pathophysiology of distributive shock. There are some experimental and clinical experiences with the use of methylene blue as a selective inhibitor of the NO–cGMP pathway. Methylene blue may play a role in the treatment of distributive shock when standard treatment fails.

Keywords

Methylene blue Refractory shock Cardiovascular drug overdoses Calcium channel blockers 

Notes

Acknowledgments

This study was supported in part by grant 5UL1RR029893 from the National Center for Research Resources, National Institutes of Health.

Conflict of Interest

The authors have no conflict of interest to declare.

References

  1. 1.
    Spaeth CS, Robison T, Fan JD et al. (2012) Cellular mechanisms of plasmalemmal sealing and axonal repair by polyethylene glycol and methylene blue. J Neurosci Res 90(5):955–66 doi: 10.1002/jnr.23022 Google Scholar
  2. 2.
    Sohrabnezhad SH (2011) Study of catalytic reduction and photodegradation of methylene blue by heterogeneous catalyst. Spectrochim Acta A Mol Biomol Spectrosc 81(1):228–235PubMedCrossRefGoogle Scholar
  3. 3.
    Kasozi DM, Gromer S, Adler H et al (2011) The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue. Redox Rep 16(4):154–165PubMedCrossRefGoogle Scholar
  4. 4.
    Meissner PE, Mandi G, Coulibaly B et al (2006) Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine. Malar J 8:5–84Google Scholar
  5. 5.
    Adjalley SH, Johnston GL, Li T, Eastman RT et al (2011) Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue. Proc Natl Acad Sci U S A 108(47):E1214–E1223PubMedCrossRefGoogle Scholar
  6. 6.
    Hanzlik PJ (1933) Subject of this letter: Methylene blue as antidote for cyanide poisoning. Cal West Med 38(3):225–226PubMedGoogle Scholar
  7. 7.
    Giovanis P, Garna A, Marcante M et al (2009) Ifosfamide encephalopathy and use of methylene blue. A case report of different sequential neurotoxicity. Tumori 95(4):545–546PubMedGoogle Scholar
  8. 8.
    Richards A, Marshall H, McQuary A (2011) Evaluation of methylene blue, thiamine, and/or albumin in the prevention of ifosfamide-related neurotoxicity. J Oncol Pharm Pract 17(4):372–380PubMedCrossRefGoogle Scholar
  9. 9.
    Barclay JA, Ziemba SE, Ibrahim RB (2011) Dapsone-induced methemoglobinemia: a primer for clinicians. Ann Pharmacother 45(9):1103–1115PubMedCrossRefGoogle Scholar
  10. 10.
    So TY, Farrington E (2008) Topical benzocaine-induced methemoglobinemia in the pediatric population. J Pediatr Health Care 22(6):335–339PubMedCrossRefGoogle Scholar
  11. 11.
    Hahn IH, Hoffman RS, Nelson LS (2004) EMLA-induced methemoglobinemia and systemic topical anesthetic toxicity. J Emerg Med 26(1):85–88PubMedCrossRefGoogle Scholar
  12. 12.
    Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357:593–615PubMedCrossRefGoogle Scholar
  13. 13.
    Schuman EM, Madison DV (1991) A requirement for the intercellular messenger nitric oxide in long-term potentiation. Science 254:1503–1506PubMedCrossRefGoogle Scholar
  14. 14.
    Llyengar R, Stuehr DJ, Marietta MA (1987) Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad 84:6369–6373CrossRefGoogle Scholar
  15. 15.
    Hibbs JB, Taintor RR, Vavrin Z (1987) Macrophage cytotoxicity: role of L-argininc deiminasc and imino nitrogen oxidation to nitrite. Science 235:473–476PubMedCrossRefGoogle Scholar
  16. 16.
    Garcin ED, Bruns CM, Lloyd SJ et al (2004) Structural basis for isozyme-specific regulation of electron transfer in nitric-oxide synthase. J Biol Chem 279:37918–37927PubMedCrossRefGoogle Scholar
  17. 17.
    Daff S (2012) NO synthase: structures and mechanisms. Nitric Oxide 23:1–11CrossRefGoogle Scholar
  18. 18.
    Stuehr D, Pou S, Rosen GM (2001) Oxygen reduction by nitric-oxide synthases. J Biol Chem 276:14533–14536PubMedCrossRefGoogle Scholar
  19. 19.
    Tatsumi R, Wuollet AL, Tabata K et al (2009) A role for calcium-calmodulin in regulating nitric oxide production during skeletal muscle satellite cell activation. Am J Physiol Cell Physiol 296(4):C922–C929PubMedCrossRefGoogle Scholar
  20. 20.
    Beckman JS, Beckman TW, Chen J et al (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 87(4):1620–1624PubMedCrossRefGoogle Scholar
  21. 21.
    Beckman JS, Crow JP (1993) Pathological implications of nitric oxide, superoxide and peroxynitrite formation. Biochem Soc Trans 21(2):330–334PubMedGoogle Scholar
  22. 22.
    Ma L (1993) Evidence for nitric oxide-generator cells in the brain. Bull Tokyo Med Dent Univ 40(3):125–134PubMedGoogle Scholar
  23. 23.
    Forstermann U, Closs EI, Pollock JS, Nakane et al (1994) Nitric oxide synthase isozymes: characterization, purification, molecular cloning, and functions. Hypertension 23:1121–1131PubMedCrossRefGoogle Scholar
  24. 24.
    Salemme E, Diano S, Maharajan P, Maharajan V (1996) Nitric oxide, a neuronal messenger. Its role in the hippocampus neuronal plasticity. Riv Biol 89(1):87–107PubMedGoogle Scholar
  25. 25.
    Izumi Y, Clifford DB, Zorumski CF (1992) Inhibition of long-term potentiation by NMDA-mediated nitric oxide release. Science 257:1273–1276PubMedCrossRefGoogle Scholar
  26. 26.
    Handy RL, Wallace P, Moore PK (1996) Inhibition of nitric oxide synthase by isothioureas: cardiovascular and antinociceptive effects. Pharmacol Biochem Behav 55(2):179–184PubMedCrossRefGoogle Scholar
  27. 27.
    Togashi H, Sakuma I, Yoshioka M et al (1992) A central nervous system action of nitric oxide in blood pressure regulation. J Pharmacol Exp Ther 262:343–347PubMedGoogle Scholar
  28. 28.
    Lipton SA, Choi YB, Pan ZH et al (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitrosocompounds. Nature 364:626–632PubMedCrossRefGoogle Scholar
  29. 29.
    Shaul PW (2002) Regulation of endothelial nitric oxide synthase: location, location, location. Annu Rev Physiol 64:749–774PubMedCrossRefGoogle Scholar
  30. 30.
    Venema RC, Sayegh HS, Arnal JF et al (1995) Role of the enzyme calmodulin-binding domain in membrane association and phospholipid inhibition of endothelial nitric oxide synthase. J Biol Chem 270(24):14705–14711PubMedCrossRefGoogle Scholar
  31. 31.
    Zeiher AM, Fisslthaler B, Schray-Utz B et al (1995) Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells. Circ Res 76:980–986PubMedCrossRefGoogle Scholar
  32. 32.
    Alheid U, Frolich JC, Forstermann U (1987) Endothelium-derived relaxing factor from cultured human endothelial cells inhibits aggregation of human platelets. Thromb Res 47:561–571PubMedCrossRefGoogle Scholar
  33. 33.
    Kurihara N, Alfie ME, Sigmon DH et al (1998) Role of nNOS in blood pressure regulation in eNOS null mutant mice. Hypertension 32(5):856–861PubMedCrossRefGoogle Scholar
  34. 34.
    Triggle CR, Ding H (2010) A review of endothelial dysfunction in diabetes: a focus on the contribution of a dysfunctional eNOS. J Am Soc Hypertens 4(3):102–115PubMedCrossRefGoogle Scholar
  35. 35.
    Nathan CF, Hibbs JB (1991) Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol 3:65–70PubMedCrossRefGoogle Scholar
  36. 36.
    MacNaul KL, Hutchinson NI (1993) Differential expression of iNOS and cNOS mRNA in human vascular smooth muscle cells and endothelial cells under normal and inflammatory conditions. Biochem Biophys Res Commun 196(3):1330–1334PubMedCrossRefGoogle Scholar
  37. 37.
    Tamir S, deRojas-Walker T, Gal A et al (1995) Nitric oxide production in relation to spontaneous B-cell lymphoma and myositis in SJL mice. Cancer Res 55(19):4391–4397PubMedGoogle Scholar
  38. 38.
    Losada AP, Bermúdez R, Faílde LD et al (2012) Quantitative and qualitative evaluation of iNOS expression in turbot (Psetta maxima) infected with Enteromyxum scophthalmi. Fish Shellfish Immunol 32(2):243–248PubMedCrossRefGoogle Scholar
  39. 39.
    Sade K, Schwartz IF, Etkin S et al (2007) Expression of inducible nitric oxide synthase in a mouse model of anaphylaxis. J Investig Allergol Clin Immunol 17(6):379–385PubMedGoogle Scholar
  40. 40.
    Matuschek A, Ulbrich M, Timm S et al (2009) Analysis of parathyroid graft rejection suggests alloantigen-specific production of nitric oxide by iNOS-positive intragraft macrophages. Transpl Immunol 21(4):183–191PubMedCrossRefGoogle Scholar
  41. 41.
    Okamoto I, Abe M, Shibata K et al (2000) Evaluating the role of inducible nitric oxide synthase using a novel and selective inducible nitric oxide synthase inhibitor in septic lung injury produced by cecal ligation and puncture. Am J Respir Crit Care Med 162(2 Pt 1):716–722PubMedCrossRefGoogle Scholar
  42. 42.
    Lucas KA, Pitari GM, Kazerounian S et al (2000) Guanylyl cyclases and signaling by cyclic GMP. Pharmacol Rev 52:375–413PubMedGoogle Scholar
  43. 43.
    Wedel B, Garbers D (2001) The guanylyl cyclase family at Y2K. Annu Rev Physiol 63:215–233PubMedCrossRefGoogle Scholar
  44. 44.
    Mujoo K, Sharin VG, Martin E et al (2010) Role of soluble guanylyl cyclase-cyclic GMP signaling in tumor cell proliferation. Nitric Oxide 22(1):43–50PubMedCrossRefGoogle Scholar
  45. 45.
    Schoeffter P, Lugnier C, Demesy-Waeldele F et al (1987) Role of cyclic AMP- and cyclic GMP-phosphodiesterases in the control of cyclic nucleotide levels and smooth muscle tone in rat isolated aorta. A study with selective inhibitors. Biochem Pharmacol 36(22):3965–3972PubMedCrossRefGoogle Scholar
  46. 46.
    Bensinger RE, Podos SM (1975) Cyclic nucleotide metabolism in the retina. Invest Ophthalmol 14(4):263–266PubMedGoogle Scholar
  47. 47.
    Kumar A, Brar R, Wang P et al (1999) Role of nitric oxide and cGMP in human septic serum-induced depression of cardiac myocyte contractility. Am J Physiol 276:R256–R276Google Scholar
  48. 48.
    Winbery SL, Lieberman PL (2002) Histamine and antihistamines in anaphylaxis. Clin Allergy Immunol 17:287–317PubMedGoogle Scholar
  49. 49.
    Lieberman P (1990) The use of antihistamines in the prevention and treatment of anaphylaxis and anaphylactoid reactions. J Allergy Clin Immunol 86(4 Pt 2):684–686PubMedCrossRefGoogle Scholar
  50. 50.
    Enjeti S, Bleecker ER, Smith PL et al (1983) Hemodynamic mechanisms in anaphylaxis. Circ Shock 11:297–309PubMedGoogle Scholar
  51. 51.
    Toda N (1984) Endothelium-dependent relaxation induced by angiotensin II and histamine in isolated arteries of dog. Br J Pharmacol 81:301–307PubMedCrossRefGoogle Scholar
  52. 52.
    Krstic MK, Stepanovic RM, Krstic SK et al (1989) Endothelium-dependent relaxation of the rat renal artery caused by activation of histamine H1-receptors. Pharmacology 38:113–120PubMedCrossRefGoogle Scholar
  53. 53.
    Rosenkranz-Weiss P, Sessa WC, Milstien S et al (1994) Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells: elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity. J Clin Invest 93:2236–2243PubMedCrossRefGoogle Scholar
  54. 54.
    Li H, Burkhardt C, Heinrich UR et al (2003) Histamine upregulates gene expression of endothelial nitric oxide synthase in human vascular endothelial cells. Circulation 107:2348–2354PubMedCrossRefGoogle Scholar
  55. 55.
    Champion HC, Kadowitz PJ (1997) NO release and the opening of K + ATP channels mediate vasodilator responses to histamine in the cat. Am J Physiol 273(2 pt 2):H928–H937PubMedGoogle Scholar
  56. 56.
    Buzato MA, Viaro F, Piccinato CE et al (2005) The use of methylene blue in the treatment of anaphylactic shock induced by compound 48/80: experimental studies in rabbits. Shock 23(6):582–587PubMedGoogle Scholar
  57. 57.
    Oliveira Neto AM, Duarte NM, Vicente WV et al (2003) Methylene blue: an effective treatment for contrast medium-induced anaphylaxis. Med Sci Monit 9(11):CS102–CS106PubMedGoogle Scholar
  58. 58.
    Del Duca D, Sheth SS, Clarke AE et al (2009) Use of methylene blue for catecholamine-refractory vasoplegia from protamine and aprotinin. Ann Thorac Surg 87(2):640–642PubMedCrossRefGoogle Scholar
  59. 59.
    Levy MM, Fink MP, Marshall JC et al (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250–1256PubMedCrossRefGoogle Scholar
  60. 60.
    Angus DC, Linde-Zwirble WT, Lidicker J et al (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310PubMedCrossRefGoogle Scholar
  61. 61.
    Dellinger RP (2003) Inflammation and coagulation: implications for the septic patient. Clin Infect Dis 36:1259–1265PubMedCrossRefGoogle Scholar
  62. 62.
    Kumar A, Brar R, Wang P et al (1999) Role of nitric oxide and cGMP in human septic serum-induced depression of cardiac myocyte contractility. Am J Physiol 276(1 Pt 2):R265–R276PubMedGoogle Scholar
  63. 63.
    Symeonides S, Balk RA (1999) Nitric oxide in the pathogenesis of sepsis. Infect Dis Clin North Am 13(2):449–63 xGoogle Scholar
  64. 64.
    Fleming I, Julou-Schaeffer G, Gray GA et al (1991) Evidence that an L-arginine/nitric oxide dependent elevation of tissue cyclic GMP content is involved in depression of vascular reactivity by endotoxin. Br J Pharmacol 103(1):1047–1052PubMedCrossRefGoogle Scholar
  65. 65.
    Schott CA, Gray GA, Stoclet JC (1993) Dependence of endotoxin-induced vascular hyporeactivity on extracellular L-arginine. Br J Pharmacol 108(1):38–43PubMedCrossRefGoogle Scholar
  66. 66.
    Julou-Schaeffer G, Gray GA, Fleming I et al (1990) Loss of vascular responsiveness induced by endotoxin involves L-arginine pathway. Am J Physiol 259(4 Pt 2):H1038–H1043PubMedGoogle Scholar
  67. 67.
    Schuller F, Fleming I, Stoclet JC et al (1992) Effect of endotoxin on circulating cyclic GMP in the rat. Eur J Pharmacol 212(1):93–96PubMedCrossRefGoogle Scholar
  68. 68.
    Rivers E, Nguyen B, Havstad S et al (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377PubMedCrossRefGoogle Scholar
  69. 69.
    Watson D, Grover R, Anzueto A et al (2004) Cardiovascular effects of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) in patients with septic shock: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144–002). Crit Care Med 32(1):13–20PubMedCrossRefGoogle Scholar
  70. 70.
    Cheng X, Pang CC (1998) Pressor and vasoconstrictor effects of methylene blue in endotoxaemic rats. Naunyn Schmiedebergs Arch Pharmacol 357(6):648–653PubMedCrossRefGoogle Scholar
  71. 71.
    Fernandes D, Sordi R, Pacheco LK et al (2009) Late, but not early, inhibition of soluble guanylate cyclase decreases mortality in a rat sepsis model. J Pharmacol Exp Ther 328(3):991–999PubMedCrossRefGoogle Scholar
  72. 72.
    Demirbilek S, Sizanli E, Karadag N et al (2006) The effects of methylene blue on lung injury in septic rats. Eur Surg Res 38(1):35–41PubMedCrossRefGoogle Scholar
  73. 73.
    Menardi AC, Viaro F, Vicente WV et al (2006) Hemodynamic and vascular endothelium function studies in healthy pigs after intravenous bolus infusion of methylene blue. Arq Bras Cardiol 87(4):525–532PubMedCrossRefGoogle Scholar
  74. 74.
    Evgenov OV, Sveinbjørnsson B, Bjertnaes LJ (2001) Continuously infused methylene blue modulates the early cardiopulmonary response to endotoxin in awake sheep. Acta Anaesthesiol Scand 45(10):1246–1254PubMedCrossRefGoogle Scholar
  75. 75.
    Evgenov OV, Sager G, Bjertnaes LJ (2001) Methylene blue reduces lung fluid filtration during the early phase of endotoxemia in awake sheep. Crit Care Med 29(2):374–379PubMedCrossRefGoogle Scholar
  76. 76.
    Galili Y, Kluger Y, Mianski Z et al (1997) Methylene blue—a promising treatment modality in sepsis induced by bowel perforation. Eur Surg Res 29(5):390–395PubMedCrossRefGoogle Scholar
  77. 77.
    Dumbarton TC, Minor S, Yeung CK et al (2011) Prolonged methylene blue infusion in refractory septic shock: a case report. Can J Anaesth 58(4):401–405PubMedCrossRefGoogle Scholar
  78. 78.
    van Haren FM, Pickkers P, Foudraine N et al. (2010) The effects of methylene blue infusion on gastric tonometry and intestinal fatty acid binding protein levels in septic shock patients. J Crit Care 25(2):358.e1-7Google Scholar
  79. 79.
    Brown G, Frankl D, Phang T (1996) Continuous infusion of methylene blue for septic shock. Postgrad Med J 72(852):612–614PubMedCrossRefGoogle Scholar
  80. 80.
    Heemskerk S, van Haren FM, Foudraine NA et al (2008) Short-term beneficial effects of methylene blue on kidney damage in septic shock patients. Intensive Care Med 34(2):350–354PubMedCrossRefGoogle Scholar
  81. 81.
    Park BK, Shim TS, Lim CM et al (2005) The effects of methylene blue on hemodynamic parameters and cytokine levels in refractory septic shock. Korean J Intern Med 20(2):123–128PubMedCrossRefGoogle Scholar
  82. 82.
    Donati A, Conti G, Loggi S et al (2002) Does methylene blue administration to septic shock patients affect vascular permeability and blood volume? Crit Care Med 30(10):2271–2277PubMedCrossRefGoogle Scholar
  83. 83.
    Kirov MY, Evgenov OV, Evgenov NV et al (2001) Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med 29(10):1860–1867PubMedCrossRefGoogle Scholar
  84. 84.
    Memis D, Karamanlioglu B, Yuksel M et al (2002) The influence of methylene blue infusion on cytokine levels during severe sepsis. Anaesth Intensive Care 30(6):755–762PubMedGoogle Scholar
  85. 85.
    Juffermans NP, Vervloet MG, Daemen-Gubbels CR et al (2010) A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock. Nitric Oxide 22(4):275–280PubMedCrossRefGoogle Scholar
  86. 86.
    Weingartner R, Oliveira E, Oliveira ES et al (1999) Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue. Braz J Med Biol Res 32(12):1505–1513PubMedCrossRefGoogle Scholar
  87. 87.
    Gachot B, Bedos JP, Veber B et al (1995) Short-term effects of methylene blue on hemodynamics and gas exchange in humans with septic shock. Intensive Care Med 21(12):1027–1031PubMedCrossRefGoogle Scholar
  88. 88.
    Goluboff N, Wheaton R (1961) Methylene blue-induced cyanosis and acute hemolytic anemia complicating the treatment of methemoglobinemia. J Pediatr 58:86–89PubMedCrossRefGoogle Scholar
  89. 89.
    Héritier Barras AC, Walder B, Seeck M (2010) Serotonin syndrome following methylene blue infusion: a rare complication of antidepressant therapy. J Neurol Neurosurg Psychiatry 81(12):1412–1413PubMedCrossRefGoogle Scholar
  90. 90.
    McDonnell AM, Rybak I, Wadleigh M et al. (2012) Suspected serotonin syndrome in a patient being treated with methylene blue for ifosfamide encephalopathy. J Oncol Pharm Pract 18(4):436–9Google Scholar
  91. 91.
    Boyer EW, Shannon M (2005) The serotonin syndrome. N Engl J Med 352(11):1112–1120PubMedCrossRefGoogle Scholar
  92. 92.
    Petzer A, Harvey BH, Wegener G et al (2012) Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase. Toxicol Appl Pharmacol 258(3):403–409PubMedCrossRefGoogle Scholar
  93. 93.
    Jang DH, Nelson LS, Hoffman RS (2011) Methylene blue in the treatment of refractory shock from an amlodipine overdose. Ann Emerg Med 58(6):565–567PubMedCrossRefGoogle Scholar
  94. 94.
    Zhang X, Hintze TH (1998) Amlodipine releases nitric oxide from canine coronary microvessels, an unexpected mechanism of action of a calcium channel-blocking agent. Circulation 97:576–580PubMedCrossRefGoogle Scholar
  95. 95.
    Zhang X, Loke KE, Mital S et al (2002) Paradoxical release of nitric oxide by an L-type calcium channel antagonist, the R+ enantiomer of amlodipine. J Cardiovasc Pharmacol 39:208–214PubMedCrossRefGoogle Scholar
  96. 96.
    Lensai H et al (2003) Amlodipine activates the endothelial nitric oxide synthase by altering phosphorylation on Ser and Thr. Cardiovasc Res 59:844–853CrossRefGoogle Scholar
  97. 97.
    Xu B, Xiao-hung L, Lin G et al (2002) Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide- and kinin-dependent mechanism. Br J Pharmacol 136:375–382PubMedCrossRefGoogle Scholar
  98. 98.
    Rodrigues JM, Pazin Filho A, Rodrigues AJ et al (2007) Methylene blue for clinical anaphylaxis treatment: a case report. Sao Paulo Med J 125:60–62PubMedCrossRefGoogle Scholar
  99. 99.
    Weissgerber AJ (2008) Methylene blue for refractory hypotension: a case report. AANA J 76(4):271–274PubMedGoogle Scholar
  100. 100.
    Grayling M, Deakin CD (2003) Methylene blue during cardiopulmonary bypass to treat refractory hypotension in septic endocarditis. J Thorac Cardiovasc Surg 125(2):426–427PubMedCrossRefGoogle Scholar

Copyright information

© American College of Medical Toxicology 2013

Authors and Affiliations

  • David H. Jang
    • 1
  • Lewis S. Nelson
    • 1
  • Robert S. Hoffman
    • 1
  1. 1.Division of Medical Toxicology, Department of Emergency MedicineNew York University School of Medicine, Bellevue Hospital CenterNew YorkUSA

Personalised recommendations