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

Évora, Paulo Roberto Barbosa; Ribeiro, Patrícia Lisbôa Izetti; Vicente, W. R. R.; Reis, Celso L.; Rodrigues, Alfredo José; Menardi, Antônio Carlos; Alves, Lafaiete; Évora, Patricia Martinez; Bassetto, Solange

doi:10.1590/s0102-76382009000400005

Cited by 72 publications

(66 citation statements)

References 48 publications

(56 reference statements)

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“…If the hypotension persists irresponsive to amines and high CPB flow, MB infusion should be repeated on pump. Therefore, the NO/cGMP pathway blockage is a lifesaving tool for curbing the CPB inflammatory reaction [23][24][25] .…”

Section: Cpb Vasoplegic Syndromementioning

confidence: 99%

Key Points for Curbing Cardiopulmonary Bypass Inflammation

et al. 2016

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PURPOSE: Cardiopulmonary bypass (CPB) procedures are thought to activate systemic inflammatory reaction syndrome (SIRS).Strategies to curb systemic inflammation have been previously described. However, none of them is adequate, since "curbing" the extent of the inflammatory response requires a multimodal approach. The aim of the present mini-review is to discuss the main key points about the main principles in cardiopulmonary bypass curbing inflammation. METHODS:No systematic literature search (MEDLINE) and extracted data from the accumulated experience of the authors. The preconceived idea of an association between severe inflammation and coagulation disorders is reviewed. Also, some fundamental concepts, CPB inflammatory biomarkers, the vasoplegic syndrome and the need forindividual CPB protocols for children, diabetes and old patients, are discussed. CONCLUSION:The ways in which surgical technique (atraumatic vein harvest, biocompatibility and shear resistance of the circuit, monitoring, minimizing organ ischemia, minimal cross-clamping trauma, and blood management) are thought to curb SIRS induced by CPB and affect positively the patient outcome.Improved patient outcomes are strongly associated with these modalities of care, more than single or combinatorial drug strategies (aprotinin, tranexamic acid, pentoxifylline) or CPB modalities (minicircuits, heparin-coated circuits, retrograde autologous prime).

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Section: Cpb Vasoplegic Syndromementioning

confidence: 99%

Key Points for Curbing Cardiopulmonary Bypass Inflammation

et al. 2016

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“…2,3 As a potent guanylyl cyclase inhibitor, MB blocks the release of cyclic guanosine monophosphate (cGMP), thereby preventing vascular smooth muscle relaxation without directly affecting NO synthesis. Nitric oxide synthase inhibitors are not currently in clinical use because of their lack of specificity in inhibiting the different NOS isoforms, with the consequent risk of generalized tissue necrosis and a higher death rate.…”

Section: 3mentioning

confidence: 99%

Methylene Blue Is a Guanylate Cyclase Inhibitor That Does Not Interfere with Nitric Oxide Synthesis

Évora

2016

Texas Heart Institute Journal

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Mangelli and colleagues 1 report the life-saving effectiveness of methylene blue (MB) in treating vasoplegic syndrome in a 75-year-old man, after on-pump cardiac surgery. They present a simplified nitric oxide (NO) pathway that shows methylene blue as a nitric oxide synthase (NOS) inhibitor.In regard to the therapeutic principles for endothelial vasoplegic dysfunction treatment associated with heart surgery, the first and most important concept concerns restrictions on the use of nonspecific inhibitors of NO synthesis (L -NMMA, L -NAME). This approach is prone to controversy, because it involves ethical issues related to the use of new therapies, besides blockingnot only iNOS, but its constitutive enzyme's (eNOS) organic form. 2,3Methylene blue does not interfere with NOS and has played a longstanding beneficial role in many other clinical conditions.2,3 As a potent guanylyl cyclase inhibitor, MB blocks the release of cyclic guanosine monophosphate (cGMP), thereby preventing vascular smooth muscle relaxation without directly affecting NO synthesis. Nitric oxide synthase inhibitors are not currently in clinical use because of their lack of specificity in inhibiting the different NOS isoforms, with the consequent risk of generalized tissue necrosis and a higher death rate. Therefore, we suggest a modification of the diagram, to avoid restrictions upon MB on the basis of NO's detrimental microcirculatory effect:

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“…The consequences of this include cytokine storm and vasodilatation refractory to vasoconstrictors with reduced myocardial contractility and increased endothelial permeability [15][16][17].…”

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confidence: 99%

“…Mortality for the severe forms of vasoplegic shock reaches 25% in spite of employing adequate treatment [1,15,17].…”

mentioning

confidence: 99%

“…Using methylene blue in treating post-CPB vasoplegia has a well-grounded position in modern intensive cardiosurgical therapy. Methylene blue is a drug that directly inhibits the production of nitric oxide (iNOs) and blocks cGMP, which enables the restart of the mechanism related to cAMP and ATP via dependent potassium channels, therefore enabling the normalization of cellular calcium metabolism and the regaining of the physiological properties of myocytes [15]. Methylene blue is not a directly vasoconstrictive drug, as it does not constrict the vessels when vasoplegia is not present (in the absence of iNOs activation and NO -cGMP excess).…”

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confidence: 99%

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Vasoplegic versus septic shock in cardiac surgery. Possibilities of differentiating between them and implementing appropriate therapy

Kudliński¹,

Marczak²,

Cichoń³

2013

kitp

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Among patients undergoing on-pump cardiac surgery (cardiopulmonary bypass -CPB), there is a population of patients who, shortly after the end of the procedure (and CPB), exhibit symptoms of generalized hypotension related to very low systemic vascular resistance, the treatment of which requires very large doses of vasoconstrictors. This clinical condition is known as vasodilatation or vasoplegic shock (a distributive shock). Risk factors of postoperative vasoplegia such as initial patient condition, preoperative pharmacotherapy, cardiac procedure type, extracorporeal perfusion, the activation of intrinsic mechanisms leading to vasodilatation, and infectious factors (complicating the previously "sterile" vasoplegia course) should be taken into consideration when planning the treatment and aiming to improve the postoperative outcome. Whether vasoplegia is of infectious or sterile etiology remains the big issue which dictates postoperative therapy: empirical antibiotic de-escalation therapy vs. standard perioperative antibiotic prophylaxis. Key words: vasoplegia, septic shock, CPB, antibiotic prophylaxis. StreszczenieW kardiochirurgii z użyciem krążenia pozaustrojowego (cardiopulmonary bypass -CPB) obserwuje się populację pacjentów, u których w krótkim okresie po zakończeniu zabiegu (oraz CPB) występują objawy uogólnionej hipotensji związanej z bardzo niskim oporem obwodowym wymagającym zastosowania w terapii bardzo dużych dawek leków wazokonstrykcyjnych. Taki stan kliniczny określa się mianem wstrząsu wazodylatacyjnego lub wazoplegicznego (wstrząs dystrybucyjny). Istotnym problemem w leczeniu tego zespołu jest identyfikacja czynników ryzyka związanych z przedoperacyjnym stanem klinicznym pacjenta, prowadzoną terapią lekową, samym zabiegiem kardiochirurgicznym i jego rodzajem, prowadzeniem perfuzji w krążeniu pozaustrojowym, jak również aktywacją wewnątrzustrojowych mechanizmów powodujących wazodylatację oraz czynnikami infekcyjnymi wikłającymi "sterylny" przebieg wazoplegii. Odpowiedź na pytanie, czy jest to wstrząs wazodylatacyjny czy już wstrząs septyczny, implikuje wdrożenie adekwatnej terapii -empirycznej antybiotykoterapii deeskalacyjnej lub standardowej profilaktyki okołooperacyjnej. Słowa kluczowe: wazoplegia, wstrząs septyczny, krążenie pozaustrojowe, antybiotykoterapia.

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

Cited by 72 publications

References 48 publications

Key Points for Curbing Cardiopulmonary Bypass Inflammation

Key Points for Curbing Cardiopulmonary Bypass Inflammation

Methylene Blue Is a Guanylate Cyclase Inhibitor That Does Not Interfere with Nitric Oxide Synthesis

Vasoplegic versus septic shock in cardiac surgery. Possibilities of differentiating between them and implementing appropriate therapy

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