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Preoperative methylene blue administration in patients at high risk for vasoplegic syndrome during cardiac surgery.Ozal E, Kuralay E, Yildirim V, Kilic S, Bolcal C, Kucukarslan N, Gunay C, Demirkilic U, Tatar H. Ann Thorac Surg 79:1615-1619, 2005. Reviewer: Mark A. Chaney, MD Abstract: Specific preoperative medications (angiotensin-converting enzyme inhibitors, calcium channel blockers, heparin) have been shown to increase risk of vasoplegic syndrome in patients following cardiac surgery. These investigators prospectively studied whether preoperative methylene blue administration would prevent the vasoplegic syndrome in these high-risk patients. One hundred patients scheduled for coronary artery bypass graft surgery with assist of cardiopulmonary bypass and deemed at high risk for postoperative vasoplegia (preoperative angiotensin-converting enzyme inhibitors, calcium channel blockers, heparin) were randomly assigned to either receive preoperative methylene blue (n = 50) or not receive it (n = 50). When given, methylene blue (1% solution) was administered intravenously at a dose of 2 mg/kg over thirty minutes approximately one hour prior to surgery. Although similar in terms of all demographic and operative variables, patients receiving methylene blue experienced significantly less postoperative vasoplegia than patients not receiving methylene blue (0 of 50 versus 13 of 50, respectively, p < 0.001). In six patients, vasoplegic syndrome was refractory to norepinephrine (four survived, two remained refractory to aggressive vasopressor therapy and ultimately died of multiorgan failure). Patients receiving methylene blue also had shorter intensive care unit stays (1.2 ± 0.5 days versus 2.1 ± 1.2 days, respectively, p < 0.001) and left the hospital sooner ( 6.1 ± 1.7 days versus 8.4 ± 2.0 days, respectively, p< 0.001) when compared to patients not receiving methylene blue. These investigators conclude that their results suggest that preoperative methylene blue administration reduces the incidence and severity of vasoplegic syndrome in high risk patients, ensuring adequate systemic vascular resistance during the intraoperative and postoperative periods and also shortens both intensive care unit stays and hospitals stays. Comments: Cardiopulmonary bypass may induce a vasoplegic syndrome that occurs in the immediate postoperative period (incidence may be as high at 10%) that is characterized by severe hypotension, decreased systemic vascular resistance, decreased arteriolar reactivity, and increased requirements for filling volume and vasopressive therapy, despite adequate cardiac output. Recent clinical work has established that preoperative angiotensin-converting enzyme inhibitors, calcium channel blockers, and heparin increase risk for postoperative vasoplegic syndrome and its presentation worsens overall prognosis. Nitric oxide appears to play an important role via guanylate cyclase enzyme activation, cyclic guanosine monophosphate production, and smooth muscle vascular relaxation. Thus, inhibiting nitric oxide may limit or prevent the vasoplegic syndrome. Recent clinical work has revealed that methylene blue (via nitric oxide inhibition) administration in response to the vasoplegic syndrome can restore systemic vascular resistance. These investigators found that preoperative methylene blue administration, in patients at high risk for vasoplegic syndrome, decreased incidence and severity of the syndrome, a potentially important finding. The rennin-angiotensin system plays an important role in vascular tone changes that occur postoperatively. Angiotensin-converting enzyme inhibitors decrease angiotensin II levels and increase plasma levels of bradykinin, a vasodilator. The increase in plasma bradykinin is due to the fact that cardiopulmonary bypass excludes the lungs, the major site of bradykinin catabolism. Angiotensin-converting enzyme inhibitors certainly play a major role in initiating vasoplegic syndrome. As more and more patients scheduled for cardiac surgery are taking these drugs, this represents a real clinical problem. Conventional treatment of vasoplegic syndrome usually involves phenylephrine, norepinephrine, or vasopressin. While these drugs increase blood pressure, they also have potential adverse effects (unwanted vasoconstriction to major organs). Thus, it would be advantageous to avoid these drugs, if possible. Over the last decade, methylene blue has emerged as a useful drug to treat vasoplegic syndrome that is unresponsive to conventional treatment. This is the first clinical study to use preoperative methylene blue to ward off development of the syndrome. It appears to work. It should be noted, however, that methylene blue, like all vasoconstrictors, also has potential adverse effects. The drug may cause cardiac arrhythmias, coronary vasoconstriction, decreased cardiac output, decreased renal blood flow, decreased mesenteric blood flow, increased pulmonary vascular pressure, increased pulmonary vascular resistance, and gas exchange deterioration. Methylene blue is also well known to turn the urine greenish-blue and may initiate mild skin discoloration (observed in this study's patients). While one cannot at this time recommend routine preoperative use, all cardiac anesthesiologists should be aware of the emerging beneficial effects of methylene blue in the treatment of vasoplegic syndrome. Table of Contents:
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