Infusion of methylene blue in human septic shock: A pilot, randomized, controlled study

Киров, М. Ю.; Evgenov, Oleg V.; Evgenov, Natalia V.; Egorina, Elena M.; Sovershaev, Mikhail A.; Sveinbjørnsson, Baldur; Nedashkovsky, E.; Bjertnæs, Lars J.

doi:10.1097/00003246-200110000-00002

Cited by 223 publications

(191 citation statements)

References 36 publications

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“…When compared to the control group, methylene blue reduced pressor requirement. Although 5/10 patients treated with methylene blue survived as opposed to 3/10 patients who received conventional treatment, this study was not powered to find a mortality difference [83].…”

Section: The No-cgmp Pathway In Anaphylaxis and The Role Of Methylenementioning

confidence: 92%

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

2013

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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 oxidecyclic 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.

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Section: The No-cgmp Pathway In Anaphylaxis and The Role Of Methylenementioning

confidence: 92%

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

2013

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“…In this case, we report the need for a prolonged infusion of MB over a period of 120 hr in a patient with intractable septic shock. Previous research has demonstrated that MB may be efficacious in septic shock when given by intravenous bolus or short-term (B6 h) infusions, 3,4,9,11,[16][17][18] although a case report of a longer-term infusion of 44 hr has been described. 12 Despite standard treatment for septic shock with early goal-directed therapy, conventional vasopressors, including norepinephrine, epinephrine, and vasopressin, our patient responded only to the administration of MB.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10][11][12] Little is known about the clinical utility, optimal dose, or duration of MB administration in patients with septic shock. The relatively few reports available on the use of MB in septic shock describe relatively short infusions.…”

Section: Résumémentioning

confidence: 99%

“…The relatively few reports available on the use of MB in septic shock describe relatively short infusions. Most reports describe infusions less than six hours in length, 7,9,11,13 with the longest reported infusion less than 44 hr. 12 We report the administration of MB to a patient with profound hemodynamic instability secondary to septic shock that was refractory to conventional vasopressor support.…”

Section: Résumémentioning

confidence: 99%

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Prolonged methylene blue infusion in refractory septic shock: a case report

Dumbarton

Minor

Yeung

et al. 2011

Can J Anesth/J Can Anesth

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Purpose Methylene blue (MB) has been advocated for the treatment of refractory hemodynamic instability in patients with septic shock. However, the use of MB infusions in septic shock is not considered standard treatment, and the available literature describes infusions of short duration, typically less than six hours. Clinical features We report a case of septic shock in a 67-yr-old male who required maximal vasopressor support with norepinephrine, epinephrine, and vasopressin. Despite standard protocols for the treatment of septic shock, the patient's hemodynamic status was refractory 80 hr post admission. However, initiation of a MB infusion resulted in the rapid restoration of hemodynamic stability and a subsequent decrease in vasopressor requirements.Multiple attempts to discontinue the MB infusion resulted in immediate and repeated increases in vasopressor requirements, necessitating a continuous infusion with a slow taper of MB for 120 hr. Ultimately, the patient survived the illness and was discharged home. We observed no adverse events that could be attributed to the use of MB. Conclusion In our patient, the use of MB resulted in hemodynamic stability unattained with standard vasopressor support. Further research is warranted on the use of MB in patients with septic shock. RésuméObjectif Le bleu de me´thyle`ne (BM) a e´te´propose´par certains chercheurs comme traitement de l'instabiliteh e´modynamique re´fractaire chez les patients en choc septique. La perfusion de BM n'est toutefois pas conside´re´e comme un traitement standard du choc septique, et la litte´rature publie´e de´crit des perfusions de courte dure´e, en ge´ne´ral de moins de six heures. É léments cliniques Nous rapportons un cas de choc septique chez un homme de 67 ans qui a eu besoin d'un soutien vasopresseur maximal avec de la nore´pine´phrine, de l'e´pine´phrine et de la vasopressine. Malgre´l'application des protocoles normalise´s pour le traitement du choc septique, l'e´tat he´modynamique du patient demeurait re´fractaire 80 h apre`s son admission. L'amorce d'une perfusion de BM a toutefois permis de re´tablir rapidement la stabilite´he´modynamique du patient et a entraıˆne´une re´duction subse´quente de ses besoins en vasopresseurs. Les nombreuses tentatives d'interruption de la perfusion de BM ont entraıˆne´des augmentations imme´diates et re´pe´te´es des besoins en vasopresseurs, c'est pourquoi une perfusion continue a`un de´bit plus bas de BM durant 120 h a e´te´mise en place. Le patient a finalement surve´cu a`la maladie et reçu son conge´de l'hôpital. Nous

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“…Dose-related neurotoxicity of MB affecting the central nervous system with higher doses (between 5 mg/kg and 50 mg/kg) than those used in the present study, as well as possible interspecies differences [97,100], have been described. The clinical efficacy and safety of MB are well documented with both intermittent [189,190] and continuous administration [91]. Further, the cost-effectiveness ratio of MB could be more advantageous than for the newer compounds with inhibitory effect on NOS.…”

Section: The Dose Of Methylene Bluementioning

confidence: 99%

Cerebral protection in experimental cardiopulmonary resuscitation (with special reference to the effects of methylene blue)

Miclescu¹

2010

Acta Anaesthesiol Scand

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Although survival rates are increasing, brain injury continues to be a leading cause of death after cardiac arrest (CA). Permanent brain damage after CA is determined by limited tolerance to ischemia from CA and cardiopulmonary resuscitation (CPR), as well as the unique cerebral response to reperfusion after return of spontaneous circulation (ROSC). A major pathway leading to neurotoxic cascade and neuronal injury after CA involves the increased presence of reactive oxygen and nitrogen species generated during ischemia and reperfusion. The magnitude of cerebral oxidative injury induced by free radicals increased with the duration of CA (Paper I). Nitric oxide (NO), a free radical responsible for the formation of reactive nitrogen species, is increased during global ischemia from CA and reperfusion (Paper IV). Hypothetically, the administration of a drug that counteracts the overproduction of NO and also acts as a scavenger of oxygen free radicals might be warranted in order to reduce the damage caused by nitrosative and oxidative stress. For these purposes we used methylene blue (MB), an old dye that has been used in medicine for almost half a century, and an experimental pig model of 20 min of ventricular fibrillation (VF) to reflect a clinical scenario of ischemia/reperfusion injury. Administration of MB added to a hypertonic-hyperoncotic solution (MBHSD) that was started during CPR and continued for 50 min after ROSC increased short-term survival by decreasing myocardial damage, as well as cerebral peroxidation and inflammatory injury (Paper II). Immunostaining of cerebral tissue collected at different time points after CA and ROSC (Paper IV) provided experimental evidence that cortical blood-brain barrier (BBB) disruption begins as early as during the initial phase of untreated as well as treated CA. The results indicated that MB administration reduced the neurologic injury and BBB disruption considerably, but did not reverse the ongoing detrimental processes. The demonstrated positive effects of MB were related to a decrease of nitrite/nitrate tissue content, and thus to a decrease of excess NO due to the MB inhibitory effects on NOS isoforms. A mixture of MB in hypertonic sodium lactate (MBL) was investigated to facilitate administration of MB in "the field." Based on findings that MBL cardio-and neuroprotective properties were similar to those of MBHSD, there is reason to believe that the use of MBL might be extended during ongoing CPR and after ROSC (Paper III). It would therefore make sense to try using MB as a pharmacological neuroprotectant during or after clinical CPR in order to expand the temporal therapeutic window before other measures for neuroprotection such as hypothermia are available. Keywords: Cardiac arrest, cardiopulmonary resuscitation, reperfusion injury, methylene blue, nitric oxide, nitric oxide synthases, blood-brain barrier

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Infusion of methylene blue in human septic shock: A pilot, randomized, controlled study

Abstract: In human septic shock, continuously infused MB counteracts myocardial depression, maintains oxygen transport, and reduces concurrent adrenergic support. Infusion of MB appears to have no significant adverse effects on the selected organ function variables.

Cited by 223 publications

References 36 publications

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

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

Prolonged methylene blue infusion in refractory septic shock: a case report

Cerebral protection in experimental cardiopulmonary resuscitation (with special reference to the effects of methylene blue)

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