Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery

Levín, Ricardo; Degrange, Marcela; Bruno, Gustavo F; Mazo, Carlos Del; Taborda, Daniel J; Griotti, Jorge J; Boullón, Fernando

doi:10.1016/s0003-4975(03)01510-8

Cited by 258 publications

(222 citation statements)

References 14 publications

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“…As its plasma concentration declines sharply during the first 40 minutes of bolus infusion, we have been maintaining the same dose in continuous infusion on the next hour. There are personal reports of its use on up to 7 mg/kg without side effects [8][9][10]. As the lethal dosage, determined in goats, is 40 mg/kg, we believe that there is, in extreme cases, the total dosage use of up to 10 mg/kg.…”

Section: Discussionmentioning

confidence: 89%

“…Among the 60 papers that appear in the bibliography of this text, through a laborious and error subjected evaluation, the existence of varied types of publications is evidenced: 1) a first series (1.67%) of six non-randomized patients [5]; 2) a series (1.67%) of 60 patients submitted the CPB and randomized to study the inflammatory reaction [12]; 3) a series (1.67%) of 54 non-randomized patients [6,7]; 4) a series (1.67%) of 56 randomized patients in which 28 had received MB to treat VS in cardiac surgery´s postoperative [8][9][10] and; 5) a series (1.67%) of 100 patients with VS risk factors that had been randomized and 50 patients that received MB before the CPB [11]. Observing the other 55 studies we can find: 1) one study (1.67%) based on evidences through metanalysis of literature [13]; 2) seven review articles (11.67%) [4,14,23].…”

Section: Resultsmentioning

confidence: 99%

“…The largest series of prospective studies indicate an incidence of 8% to 12% [6,10,11] The mortality is high, ranging from 16 to 27% [6,10,11], and therefore has been the subject of several studies aimed on improving the outcomes of these patients. MB has been used as a therapeutic option in these situations.…”

Section: Discussionmentioning

confidence: 99%

“…Three studies involving a higher number of patients deserve particular citations: 1) In 2003, Leyh et al [6,7] reported, in Germany, 54 cases of cardiac surgery patients not carrying bacterial endocarditis who had been treated with MB, with over 90% of the patients responding to the treatment; 2) Levin et al [8][9][10], in Argentina, reported the incidence of 8.8% of VS in 638 patients. Among the 56 vasoplegic patients randomly receiving MB or placebo there was no mortality in the group treated with MB and it was possible to discontinue vasoconstrictors in a short period time, with less consequential morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

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Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties

Évora¹,

Ribeiro

Vicente³

et al. 2009

Rev Bras Cir Cardiovasc

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Azul de metileno no tratamento da síndrome vasoplégica em cirurgia cardíaca. Quinze anos de perguntas, respostas, dúvidas e certezasMethylene blue for vasoplegic syndrome treatment in heart surgery. Fifteen years of questions, answers, doubts and certainties AbstractObjective: There is strong evidence that methylene blue (MB), an inhibitor of guanylate cyclase, is an excellent therapeutic option for vasoplegic syndrome (VS) treatment in heart surgery. The aim of this article is to review the MB's therapeutic function in the vasoplegic syndrome treatment.Methods: Fifteen years of literature review.Results: 1) Heparin and ACE inhibitors are risk factors; 2) In the recommended doses it is safe (the lethal dose is 40 mg/ kg); 3) The use of MB does not cause endothelial dysfunction; 4) The MB effect appears in cases of nitric oxide (NO) upregulation; 5) MB is not a vasoconstrictor, by blocking of the GMPc system it releases the AMPc system, facilitating the norepinephrine vasoconstrictor effect; 6) The most used dosage is 2 mg/kg as IV bolus followed by the same continuous infusion because plasmatic concentrations strongly decays in the first 40 minutes; 7) There is a possible "window of opportunity" for the MB's effectiveness.Conclusions: Although there are no definitive multicentric studies, the MB used to treat heart surgery VS, at the present time, is the best, safest and cheapest option, being a Brazilian contribution for the heart surgery.

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Section: Discussionmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties

Évora¹,

Ribeiro

Vicente³

et al. 2009

Rev Bras Cir Cardiovasc

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“…Peroxynitrite depresses myocardial contractility by decreasing the ability of Ca 2+ to trigger contraction, an effect that is partly mediated by the cGMP/cGMP-dependent protein kinase pathway [194]. The presence of MB significantly inhibits the relaxation induced by peroxynitrite [195], and it promotes myocardial contraction [89].…”

Section: Methylene Blue and Hemodynamicsmentioning

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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Anesthesia in Cardiac Transplantation

Hartmann,

Wavrin,

Leff

2023

Textbook of Transplantation and Mechanical Support for End‐Stage Heart and Lung Disease

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Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery

Cited by 258 publications

References 14 publications

Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties

Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties

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

Anesthesia in Cardiac Transplantation

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