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J Thorac Cardiovasc Surg 2000;119:1297-1298
© 2000 The American Association for Thoracic Surgery

LETTERS TO THE EDITOR

Use of intravenous methylene blue for the treatment of refractory hypotension after cardiopulmonary bypass

Sebastian Pagni, MD, Erle H. Austin, MD

Department of Surgery, Division of Thoracic and Cardiovascular Surgery, Jewish Hospital-Rudd Heart and Lung Center, University of Louisville, 201 Abraham Flexner Way, Suite 1200, Louisville, KY 40202

To the Editor:

We read with great interest the article by Yiu, Robin, and PattisonGo 1 titled "Reversal of Refractory Hypotension With Single-Dose Methylene Blue After Coronary Bypass Surgery." The authors reported the successful reversal of post–cardiopulmonary bypass (CPB) vasoplegia (defined as systolic blood pressure < 90 mm Hg associated with low systemic vascular resistance) with the use of a single dose (2 mg/kg) of intravenous methylene blue, achieving hemodynamic stability and rapid weaning (1 hour) from high-dose vasoconstrictor (norepinephrine) support.

We recently used methylene blue in the treatment of a patient with both severe low cardiac output and refractory vasoplegia resulting from a post-CPB severe inflammatory response. Like Yiu, Robin, and Pattison, we noted rapid restoration of peripheral vascular tone, allowing us to discontinue the high-dose norepinephrine drip by the time the infusion dose was completed.

The patient was a 20-year-old man undergoing aortic valve replacement for severe aortic stenosis with severe left ventricular dysfunction and moderate pulmonary hypertension. Fourteen years earlier he had had aggressive radiation therapy and chemotherapy for Hodgkin lymphoma, and he had been on a program of furosemide, digoxin, and enalapril. The operation was conducted under moderate hypothermia (28°C) with antegrade/retrograde cold blood cardioplegia. Operative findings revealed a small, fibrotic, heavily calcified aortic anulus and low-placed stenotic coronary ostia. After extensive debridement and annular enlargement (Manouguian type), a No. 19 St Jude Medical mechanical valve (St Jude Medical, Inc, St Paul, Minn) was implanted and a vein graft was placed to the left anterior descending coronary artery. The patient could not be weaned from CPB despite high-dose inotropic and vasoconstrictor support, resulting in placement of biventricular mechanical assist devices (Thoratec; Thoratec Laboratories, Pleasanton, Calif). The postoperative course at 48 hours showed refractory hypotension, marginal cardiac output, and high pulmonary artery pressures despite the use of high doses of epinephrine, norepinephrine, dobutamine, milrinone, and inhaled nitric oxide. The infusion of 1% methylene blue, 2 mg/kg, over 30 minutes and a second dose given 22 hours later produced the hemodynamic changes listed in Table I.


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  		Table I. Hemodynamic changes
 
The mechanism of systemic inflammatory response syndrome after CPB is not completely understood and seems to be multifactorial. At least part of the inflammatory response is a consequence of substantial nitric oxide release at the endothelial level, accounting for the persistent capillary relaxation and low systemic vascular resistance.Go Go 2,3 The methylene blue inhibits the guanylate cyclase enzyme, blunting the release of nitric oxide and therefore promoting an increase in the peripheral vascular tone. Andrade and associatesGo 4 reported the successful use of methylene blue to control the inflammatory response after cardiac operations and in patients with anaphylactic shock, although those patients had a more distinct vasodilatory shock with increased cardiac output and index. Methylene blue is used clinically for the treatment of methemoglobinemia and the rare cases of nitroprusside toxicity. Few significant secondary effects are described and include cardiac arrhythmias and coronary vasoconstriction with angina. As in the report by Evora, Roselino, and Schiaveto,Go 5 our patient had a transient nodal rhythm (5 minutes) and ventricular ectopy that disappeared after the infusion rate was slowed. Also, different from that report, we used a 1% concentration instead of the 4% described.

Our patient had a mixed disorder with predominant biventricular dysfunction and the inflammatory response resulting from 11 hours of CPB. The infusion of methylene blue allowed rapid (30 minutes) discontinuation of norepinephrine and a substantial decrease in the epinephrine requirement for pressure support. Unfortunately, despite the initial hemodynamic improvement, multiple system organ failure progressively developed and the patient died on postoperative day 10.

We believe methylene blue may be of value as an additional drug for the treatment of patients with refractory vasoplegia after CPB. Further research, of course, is needed.

12/8/105833 doi:10.1067/mtc.2000.105833

References

  1. Yiu P, Robin J, Pattison CW. Reversal of refractory hypotension with single-dose methylene blue after coronary bypass surgery. J Thorac Cardiovasc Surg 1999;118:195-6. [Free Full Text]
  2. Cremer J, Martin M, Redl H, et al. Systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg 1996;61:1714-20. [Abstract/Free Full Text]
  3. Myles PS, Leong CK, Currey J. Endogenous nitric oxide and low vascular resistance after cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1997;11:571-4. [Medline]
  4. Andrade JCS, Batista Filho ML, Evora PB, et al. Methylene blue administration in the treatment of the vasoplegic syndrome after cardiac surgery. Rev Bras Cir Cardiovasc 1996;11:107-14.
  5. Evora PB, Roselino CH, Schiaveto PM. Methylene blue in anaphylactic shock [letter]. Ann Emerg Med 1997;30:2.



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