Refractory hyperkalaemia associated with use of epsilon-aminocaproic acid during coronary bypass in a dialysis patient

Chike Magnus Nzerue,1 and Babajide Falana2

1 Renal Service 2 Department of Medicine, Morehouse School of Medicine, Atlanta Georgia, USA

Sir,

Epsilon-aminocaproic acid ({varepsilon}ACA) is a lysine analogue that inhibits fibrinolysis and thus reduces blood loss during cardiac surgery [13]. The potential of this drug to induce hyperkalaemia is not widely appreciated. We report a case where the use of this agent during coronary bypass surgery in a dialysis patient was associated with intractable hyperkalaemia that persisted in spite of conservative measures until haemodialysis was performed post-operatively.

Case.

A 34-year-old woman with end-stage renal disease, due to idiopathic rapidly progressive glomerulonephritis, presented with a 4-week history of intermittent chest pain associated with dyspnea. She denied any history of trauma, fever or chills in association with the chest pain. She had been on maintenance haemodialysis through a right subclavian vein permanent catheter for 8 months prior to the onset of the pain, but failed to keep previous appointments for the placement of arterio-venous access for dialysis. Her medications included amlodipine 5 mg/day, atenolol 100 mg/day and oral calcium carbonate 1250 mg twice daily. On examination, she was afebrile with a blood pressure of 150/86 mmHg, a pulse of 86 beats/min, and a respiratory rate of 18 breaths/min. Her cardiac examination revealed a grade II/VI systolic murmur, heard loudest over the base of the heart, without significant radiation. Her chest radiography and ECG were normal. Cardiac iso-enzymes of creatine kinase, and trophin levels were normal. A trans-oesophageal echocardiogram showed an intracardiac mass in the right atrium, which was suspected to be a clot so anti-coagulation was recommended.

Over a 3-month period, an international normalized ration of 3.5 was achieved, but the patient's symptoms worsened with an onset of orthopnea. Repeat echocardiographic findings revealed an interval change in the contour of the intracardiac mass, with the appearance of a second mass that resembled a clot, although a myxoma could not be excluded. Surgical excision of the mass was recommended. A day prior to the operation, haemodialysis was performed with transfusion of 2 units of packed red blood cells, fresh frozen plasma and 20 µg of desmopressin administered to curtail bleeding during surgery. Her laboratory data a few hours prior to surgery are shown in Table 1Go. During surgery, frozen sections confirmed the masses to be organized clots and they were excised under a cardiopulmonary bypass. The patient received {varepsilon}ACA 10 g i.v. bolus and a second 5 g dose given in a carrier. The time on cardiopulmonary bypass was 49 min and aortic cross-clamp time was 24 min. The patient received 2500 ml of physiological saline and 2 units of packed red blood cells during the operation. Her urine output was 450 ml during the operation. No potassium was given during the operation. Intraoperatively it was observed that the patient's plasma potassium increased progressively to a level of 7.2 mmol/l, at which time 25 g of dextrose and 10 units of regular insulin were given. The patient was transferred to the recovery unit after surgery.


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Table 1.  Laboratory results showing serial changes of electrolytes over time

 
In spite of sequential treatment with repeated doses of glucose and insulin, i.v. albuterol 20 mg and sodium polystyrene sulphonate (kayexalate) 30 g as a retention enema, hyperkalaemia persisted, with the development of ECG changes necessitating i.v. calcium gluconate, until haemodialysis was performed 12 h later.

Comment.

The differential diagnosis of persistent hyperkalaemia in our patient included the effects of heparin, the cardiopulmonary bypass [4], the effect of transfused blood, and the use of {varepsilon}ACA [5]. We do not think that the hyperkalaemia was caused by heparin because this patient had frequently received heparin with previous dialysis sessions without this hyperkalaemic response occurring. Other possible causes of post-operative hyperkalaemia such as metabolic acidosis, haemolysis and use of succinyl choline were excluded in this patient. We postulate that the use of {varepsilon}ACA was the most likely cause of hyperkalaemia in this patient. The plasma potassium began to rise 90 min after receiving {varepsilon}ACA, and progressively worsened in spite of conservative therapeutic measures. Perazella and Biswas [5] recently reported a case of hyperkalaemia after the administration of {varepsilon}ACA to a patient with chronic renal failure. In that case the hyperkalaemia resolved 4 h post-operatively after the administration of glucose, insulin and furosemide. {varepsilon}ACA is a structural analogue of lysine- and arginine-cationic amino acids. Infusion of these cationic amino acids in both human and animal studies has been shown to induce hyperkalaemia [57]. The intriguing persistence of the hyperkalaemia in spite of therapeutic measures probably reflects the impact of reduced clearance of this drug in a functionally anephric dialysis patient.

Our case suggests that caution should be exercised with use of {varepsilon}ACA in patients with renal failure, with close monitoring of plasma potassium levels and arrangements for post-operative dialysis.

Notes

Email: CMNzerue{at}aol.com Back

References

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  2. Vander Salm TJ, Kaur S, Lancey RA et al. Reduction of bleeding after heart operations through the prophylactic use of epsilon-aminocaproic acid. J Thorac Cardiovasc Surg1996; 112: 1098–1107[Abstract/Free Full Text]
  3. Troianos CA, Sypula RW, Lucas DM et al. The effect of prophylactic epsilon-aminocaproic acid on bleeding, transfusions, platelet function, and fibrinolysis during coronary artery bypass grafting. Anesthesiol1999; 91: 430–435[ISI][Medline]
  4. Lim M, Linton RAF, Band DM. Rise in plasma potassium during rewarming in open-heart surgery. Lancet1983; 1: 241–242
  5. Perazella MA, Biswas P. Acute hyperkalemia associated with intravenous epsilon-aminocaproic acid therapy. Am J Kid Dis1999; 33: 782–785[ISI][Medline]
  6. Bushinsky DA, Gennari FJ. Life-threatening hyperkalemia induced by arginine. Ann Intern Med1978; 89: 632–634[ISI][Medline]
  7. Dickerman HW, Walker WG. Effect of cationic amino acid infusion on potassium metabolism in vivo. Am J Physiol1964; 206: 403–404[Abstract/Free Full Text]




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