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Ann Thorac Surg 2002;74:1698-1700
© 2002 The Society of Thoracic Surgeons

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Case report

Heparin-induced hyperkalemia after cardiac surgery

^a Departments of Cardiothoracic Surgery Hammersmith Hospital, London, United Kingdom
^b Renal Medicine, Hammersmith Hospital, London, United Kingdom

Accepted for publication May 1, 2002.

* Address reprint requests to Mr Day, Department of Cardiothoracic Surgery, Hammersmith Hospital, Du Cane Rd, London W12 0HS, United Kingdom.
e-mail: j.day{at}ic.ac.uk

	Abstract

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Surgeons are increasingly faced with patients suffering from complicated pathology in multiple organ systems, to which multiple therapeutic agents with complex adverse effects are often prescribed. We face a daily challenge in maintaining an up-to-date knowledge of these complications. Heparin is widely used in surgical practice, yet our awareness of its adverse effects, other than bleeding and thrombocytopenia, remains poor. We will present an example of heparin-induced hyperkalemia following administration for cardiopulmonary bypass and intraaortic balloon pump prophylaxis. This is a rare but serious complication of heparin therapy, not usually reported in the context of a cardiac surgical patient. We will also discuss the renal physiology leading to hyperkalemia and the options available for its management.

	Introduction

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Hyperkalemia is a rare but serious complication of heparin therapy. We present a case, following cardiac surgery, and discuss the renal physiology leading to hyperkalemia and the options available for its management.

A 55-year-old Asian woman with unstable angina was admitted for coronary revascularization. She had suffered an anterior myocardial infarction 9 months previously, with risk factors including hypercholesterolemia and hypertension. Coronary angiography showed left-sided disease and an unobstructed right side; a ventriculogram showed impaired left ventricular function.

The day after her admission, she underwent coronary artery bypass grafting. After heparinization, cardiopulmonary bypass was established at 32°C, with an ascending aortic cannula and a two-stage venous cannula in the right atrium. The aorta was cross-clamped, and 800 ml of cold blood cardioplegia was instilled into the aortic root. The left internal mammary artery was anastomosed to the left anterior descending artery and a long saphenous vein graft to the first obtuse marginal. After a cross-clamp time of 58 minutes and a bypass time of 81 minutes, she was weaned from cardiopulmonary bypass. Immediate postoperative hypotension was resolved using a low-dose epinephrine infusion and an intraaortic balloon pump. After rewarming in the intensive care unit and exclusion of postoperative bleeding, a low-dose heparin infusion was commenced as prophylaxis for the balloon pump.

She remained ventilated in the intensive care unit and, after 36 hours, developed a persistent hyperkalemia (6.7 to 7.1 µmol/l), resistant to insulin and dextrose therapy, along with a hyperchloremic metabolic acidosis (urinary pH 5.0). Despite the hyperkalemia, no electrocardiographic abnormalities were seen. Preoperatively, the patient was known to have stable chronic mild renal failure (creatinine 139 µmol/l, glomerular filtration rate 35 ml/min). Concurrent with the development of hyperkalemia, her renal function deteriorated with the creatinine rising to 174 µmol/l (glomerular filtration rate 28 ml/min), before subsequently returning to its preoperative level over the next 48 hours. At no time did the patient receive any potassium supplements or nonsteroidal-antiinflammatory drugs, and the angiotensin converting enzyme inhibitor that she was taking preoperatively was stopped at the time of the operation. The patient remained intravascularly replete throughout this period and was not oliguric at any time. The renal cortical collecting tubule transtubular potassium gradient [1] ([urinary K⁺] % [urine osmolality % plasma osmolality] % [plasma K⁺]), was calculated to be 2.72, consistent with a diagnosis of hypoaldosteronism, of which the most likely cause was thought to be the heparin infusion. With this in mind, having achieved hemodynamic stability, the balloon pump was removed and the heparin discontinued. Within 48 hours, the serum potassium level normalized and the patient was successfully extubated.

	Comment

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Heparin, since its clinical introduction by surgeons Gordon Murray [2] in Canada in 1936 and shortly afterwards by Clarence Crafoord [3] with the help of Erik Jorpes in Sweden, has been the mainstay of anticoagulation therapy for more than 50 years, and has been essential to cardiac surgeons since the introduction of cardiopulmonary bypass by Gibbon in 1953. Heparin is a heterogenous mixture of unbranched sulfated polysaccharide polymers. The binding of these anionic groups with positively charged groups on proteins is the mechanism through which most of the biological actions are mediated. Its anticoagulant properties result from binding to the circulating protease inhibitor antithrombin-III, the main physiological inhibitor of thrombin, resulting in a 1,000-fold increase in its efficacy.

Although most of the side affects of heparin (bleeding, thrombocytopenia) are familiar to clinicians, the effects of heparin on aldosterone and electrolyte metabolism are less well known. Evidence exists to indicate that heparin and related substances are both aldosterone suppressing and natriuretic [4]. Through this, heparin and heparinoids may increase serum potassium levels leading hyperkalemia [5] and, less frequently, hyponatremia [6] or metabolic acidosis [7]. Heparin-induced hyperkalemia has been described in patients treated with as little as 5,000 units of heparin twice daily [8].

Heparin and urinary electrolytes
In the short term, intravenous administration of heparin may produce a transient increase in urinary potassium, a decrease in urinary sodium, or both [8]. The predominant long-term effects of heparin therapy are enhanced sodium excretion and potassium retention, which may lead to a negative sodium balance [8]. Sodium loss and potassium retention may generally be detected after 1 to 3 days, is maximal after 3 to 5 days, and wanes within 1 to 3 days of discontinuation [8].

Heparin and aldosterone physiology
Inhibition of adrenal aldosterone production by heparin underlies the reduction in renal potassium excretion and ultimately precipitates hyperkalemia. Heparin decreases the number and affinity of angiotensin-II receptors in the adrenal zona glomerulosa, reducing the main stimulus for aldosterone synthesis [8]. Heparin also directly inhibits the final enzymatic steps of aldosterone formation (18-hydroxylation), and prolonged administration in rats has been shown to promote atrophy of the zona glomerulosa [8]. Additionally, excess anticoagulation with heparin may precipitate adrenal hemorrhage and cause adrenal insufficiency [8]. Heparin increases serum potassium levels by 0.2 mEq/liter to as much as 1.7 mEq/liter among patients treated for 3 or more days [8]. Although heparin-associated hyperkalemia has been reported in normal patients, it occurs more frequently in patients (8% to 19%) with preexisting defects in potassium homeostasis [8].

Management
The simplest way to reverse heparin-induced hyperkalemia is to discontinue heparin administration. However, in practice, heparin therapy may often be life saving and must be continued. Therefore, other potassium-lowering measures must be instituted, for example, discontinuing potassium-elevating drugs like angiotensin converting enzyme inhibitors, and enhancing urinary potassium excretion with frusemide. It has been suggested that fludrocortisone may also be therapeutic as it promotes potassium excretion by its direct actions on the remaining distal tubules [9]. In one report, fludrocortisone resulted in a rapid normalization of serum potassium levels despite continued heparin administration [9].

Conclusion
Heparin-induced hyperkalemia may occur in patients with altered renal function. Many patients presenting to cardiac surgeons have other disorders that impair renal potassium handling such as diabetes mellitus, sickle cell nephropathy, lupus nephritis, renal transplantation, and obstructive uropathy. Clinicians need to be familiar with all the possible side effects of heparin, and monitoring of serum potassium levels should be considered routine when this drug is administered in the postoperative period.

	References

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1. Rose B.D. Clinical physiology of acid-base and electrolyte disorders, 4th ed New York: McGraw-Hill, 1994.
2. Murray D.W.G., Jaques L.B., Perrett T.S., Best C.H. Heparin and vascular occlusion. Can Med Assoc J 1936;35:621-622.
3. Crafoord C. Preliminary report on post operative treatment with heparin as a preventive of thrombosis. Acta Chir Scand 1937;79:407-426.
4. Kageyama Y., Suzuki H., Saruta T. Effects of routine heparin therapy on plasma aldosterone concentration. Acta Endocrinol (Copenh) 1991;124:267-270.
5. Siebels M., Andrassy K., Vecsei P., et al. Dose dependent suppression of mineralocorticoid metabolism by different heparin fractions. Thromb Res 1992;66:467-473.[Medline]
6. Aull L., Chao H., Coy K. Heparin induced hyperkalaemia. DICP 1990;24:244-246.[Abstract]
7. Durand D., Ader J.L., Rey J.P., et al. Inducing hyperkalaemia by converting enzyme inhibitors and heparin. Kidney Int 1988;34(Suppl 25):S196.
8. Oster J.R., Singer I., Fishman L.M. Heparin induced aldosterone suppression and hyperkalaemia. Am J Med 1995;98:575-586.[Medline]
9. Sherman D.S., Kass C.L., Fish D.N. Fludracortisone for the treatment of heparin induced hyperkalaemia. Ann Pharmacother 2000;34:606-610.[Abstract]

This article has been cited by other articles:

				G. I Varughese, G. E Robson, J. Aldcroft, D. M Barton, and D. P Warner Heparin therapy and hyperkalaemia in a patient with type 2 diabetes The British Journal of Diabetes & Vascular Disease, September 1, 2004; 4(5): 351 - 352. [PDF]

				V. Mehta and Z. Ahmed Apparent hyperkalaemia from blood sampled from an arterial cannula Br. J. Anaesth., September 1, 2004; 93(3): 456 - 458. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Day, J. R.S. Articles by Taylor, K. M. Search for Related Content PubMed PubMed Citation Articles by Day, J. R.S. Articles by Taylor, K. M. Related Collections Extracorporeal circulation