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J Thorac Cardiovasc Surg 2004;127:895-896
© 2004 The American Association for Thoracic Surgery
Letter to the editor |
a Laboratory of Cardiovascular Surgical Research and Endothelium Function, Ribeirão Preto Medical School, University of São Paulo and CECORP-Ribeirão Preto Specialized Heart and Lung Center, Ribeirão Preto, SP , Brazil
b Division of Cardiovascular Surgery, Navy Hospital, French Hospital, Swiss-Argentine Clinic, Argentine Institute of Diagnosis and Treatment and Santa Isabel Clinic, Buenos Aires, Argentina
To the Editor:
The excellent article written by Leyh and colleagues motivated this letter.1 We hope to share some of our extensive experience with methylene blue (MB). It is important to observe that Leyh and colleagues examined the results of MB therapy for norepinephrine refractory vasoplegia "after cardiopulmonary bypass (CPB)," although this kind of situation may happen before and even during CPB.
Our ongoing laboratory experiments have proved the usual safe doses of MB in regard to possible endothelium dysfunction. We have performed studies in porcine arteries (coronary, renal, superior mesenteric, and hepatic), rabbit aortas, and canine femoral arteries. By comparing sham animals with animals that received intravenous (IV) MB, we found differences only in intermediary concentrations in dose-response curves to the calcium ionophore (A23187), which causes receptor-independent nitric oxide release.
A single dose of IV MB (2 mg/kg, 20-minute infusion time), as used by Leyh and coworkers, was our first option in 1995.2 We are frequently asked about dose, infusion, and route (venous or arterial). Many colleagues tell us that they only observed a transient effect using a 1 or 2 mg/kg IV bolus. In our opinion, the IV MB bolus is a rescue treatment. It is important to maintain a continuous infusion. In some cases, we use a continuous infusion for more than 48 or 72 hours. Because the lethal doses of MB are well known (40 mg/kg), it is possible to use higher doses if necessary. In regard to the infusion route, in at least 1 anecdotal case, we observed a catastrophic reaction to protamine without response to norepinephrine or an IV MB bolus of 2 mg/kg. CPB was again established with high flow, but we were unable to increase the mean arterial pressure even with norepinephrine infusion. The situation was controlled only by using MB infusion in the CPB arterial line again. Grayling and Deakin3 presented this approach using MB during CPB to treat valve endocarditis in a case of ongoing septicemia.
In Argentina, Levin and colleagues4 performed a prospective, randomized study including 638 patients who underwent cardiac surgery, 56 (8.8%) of whom fulfilled the vasoplegic postoperative criteria. The overall mortality was 27 patients (4.2%), 6 (10.7%) of whom were in the vasoplegic syndrome group and 21 (3.6%) of whom were in the control group (P = .02). The 56 patients with vasoplegic syndrome were randomized to IV MB (1.5 mg/kg, 1-hour infusion time) (28 patients) or placebo (28 patients). The general and surgical characteristics of these 2 populations were quite similar. There were no deaths in the MB group and 6 deaths (21.4%) in the placebo group. The MB resolution vasoplegia time course was approximately 2 hours in all cases. In those treated only with vasopressors (8/28 patients, 28.6%), vasoplegia persisted for more than 48 hours.
Since Gomes and colleagues5 described vasoplegic syndrome, we speculate, as surgeons in undeveloped countries, whether the vasoplegia was caused by some failure in CPB material or drug quality control.
MB is increasingly used, for example in liver transplantation. As there are few papers about its use in cardiac surgery it is possible that cardiac surgical teams do not consider vasoplegic syndrome to be a catastrophic and unexpected problem, and it may be underestimated.
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  P. R. B. Evora and A. J. Rodrigues Methylene blue revised J. Thorac. Cardiovasc. Surg., January 1, 2006; 131(1): 250 - 251. [Full Text] [PDF]
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