Ann Thorac Surg 1999;67:1158-1159
© 1999 The Society of Thoracic Surgeons
Case Reports
Nicorandil-induced peripheral vasodilatation during cardiopulmonary bypass
Bode A. Falase, FRCSa,
Balwinder S. Bajaj, MRCPa,
Tracey J. Wall, FRCAa,
Vincenzo Argano, FRCSa,
Aprim Y. Youhana, FRCSa
a Department of Cardiothoracic Surgery, Cardiology, and Anaesthetics, Regional Cardiac Centre, Morriston Hospital, Swansea, Wales, United Kingdom
Accepted for publication September 23, 1998.
Address reprint requests to Mr Falase, Department of Cardiothoracic Surgery, Regional Cardiac Centre, Morriston Hospital, Swansea, SA6 6NL, Wales, United Kingdom
e-mail: bode{at}bfalase.freeserve.co.uk
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Abstract
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Nicorandil is an antianginal agent with actions at epicardial coronary arteries and arterioles, systemic arterioles, and veins. We report our experience with 7 patients taking oral Nicorandil who had severe vasodilation and hypotension requiring significant vasoconstrictor support after cardiopulmonary bypass. Although the mechanism for this phenomenon remains unknown Nicorandil might be interacting with other factors present during cardiopulmonary bypass, as it has relatively mild hemodynamic effects outside this situation.
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Introduction
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Nicorandil is a derivative of nicotinamide, incorporating a nitrate moiety, which is increasingly being used as an antianginal agent. Its novel mechanism of action is believed to be its ability to open adenosine triphosphate–sensitive potassium channels in vascular smooth muscle cells. This action causes increased transmembrane potassium conductance and membrane hyperpolarization, with the result that the voltage-dependent ion channels close, and there is a reduction in free intracellular calcium ions. This process leads to a relaxation of vascular smooth muscle [1]. Analogous to nitrates, Nicorandil also causes an increase in cyclic guanosine monophosphate levels in vascular smooth muscle cells (through activation of soluble guanylate cyclase by its nitro-group). The resultant hemodynamic effect is to cause dilation of epicardial coronary arteries and arterioles (with a reduction in the coronary vascular resistance), systemic resistance vessels, and veins. This agent also improves blood flow within collateral vessels; its net effect is improved myocardial blood flow, which results in decreased systemic vascular resistance and systemic blood pressure, pulmonary capillary wedge, and left ventricular end-diastolic pressures [1].
A single intravenous dose of 4 to 12 mg of Nicorandil can decrease the mean arterial blood pressure 5% to 15%, but its effects on patients who subsequently undergo cardiopulmonary bypass has not been investigated [1]. However, one study found severe peripheral vasodilatation after cardiopulmonary bypass in a patient taking Nicorandil [2]. We report our experience with 7 patients taking oral Nicorandil who had cardiopulmonary bypass and developed severe vasodilatation requiring significant vasoconstrictor support during, and in 5 patients, also after cardiopulmonary bypass.
The case notes of 7 patients were retrospectively analyzed. They all had an open-heart operation using cardiopulmonary bypass. Unanticipated intraoperative or postoperative vasodilatation and hypotension requiring support with vasoconstrictors or inotropic agents was necessary to maintain systemic blood pressure. All 7 patients had coronary artery bypass grafting, and 1 (patient 4) also had repair of a postmyocardial infarction ventricular septal defect. The angiographic assessment of the severity of coronary disease and left ventricular function are summarized in Table 1. All patients were taking Nicorandil (10 to 20 mg twice daily orally). This was the only drug common to all patients.
All the patients required phenylephrine support in excess of usual doses (more than 1,000 µg) intraoperatively to maintain perfusion pressures over 55 mm Hg on bypass (Table 1). There was no direct relationship between the bypass or ischemic times and requirements for vasoconstrictors for maintenance of systemic blood pressure. The mode of myocardial preservation or the general anesthetic used did not appear to influence requirements for vasoconstrictors. Five of the 7 patients also required intropic support with intravenous adrenaline, noradrenaline, or both, postoperatively for 4 to 72 hours.
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Comment
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Nicorandil is a balanced arterial and venous dilator that also has cardioprotective properties. It is relatively well tolerated when used orally or intravenously, both in healthy volunteers and patients with long-term, stable ischemic heart disease. Its main reported side effect in such studies is headache, with less frequently reported dizziness and gastrointestinal disorders [3].
The effects of Nicorandil during cardiopulmonary bypass are not well documented. In 7 patients who were taking Nicorandil preoperatively, all required unusual and excessive support with phenylephrine and inotropic agents perioperatively during and after (in 5 of the 7 patients) cardiopulmonary bypass. When other possible variables that could cause this effect are accounted for, we conclude that preoperative treatment with Nicorandil is the one common factor that might be responsible. Indeed, severe peripheral vasodilation after cardiopulmonary bypass in a patient taking Nicorandil has been reported previously [2]. Nicorandil could be interacting with other factors present during cardiopulmonary bypass as it has relatively mild hemodynamic effects outside this situation. One proposed mechanism is that the hemodynamic effects of Nicorandil are exaggerated by the depletion of adenosine triphosphate, which is known to occur during cardiopulmonary bypass [2]. Not all patients taking Nicorandil had these complications; 4 patients did not have vasodilatation and hypotension. All 7 patients ultimately had a favorable outcome. The future maintenance of Nicorandil therapy before cardiopulmonary bypass must take into account the potential benefits in terms of myocardial cytoprotection and difficulties in treating intraoperative and postoperative hypotension.
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References
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Kato K. Haemodynamic and clinical effects of an intravenous potassium channel opener—a review. Eur Heart J 1993;14(Supp B):40-47.[Abstract/Free Full Text]
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Montgomery H., Sumeray M., Carr C., Singer M. Sinus arrest and severe peripheral vasodilatation following cardiopulmonary bypass in a patient taking Nicorandil. Cardiovasc Drugs Ther 1997;11:81.[Medline]
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Witchitz S, Darmon JY. Nicorandil safety in the long-term treatment of coronary heart disease. Cardiovasc Drugs Ther 1995;9(Suppl 2):2:237–43.
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Abstract
Introduction
