Ann Thorac Surg 1999;68:1072-1074
© 1999 The Society of Thoracic Surgeons
Case Reports
Procainamide-induced postoperative pyrexia
Kevin D. Murray, MDa,
Jon J. Vlasnik, PharmDa
a Division of Cardiothoracic Surgery, Washington University School of Medicine, and Department of Pharmacology, Barnes-Jewish Hospital, St. Louis, Missouri, USA
Address reprint requests to Dr Murray, Division of Cardiothoracic Surgery, University of Nevada School of Medicine, 2040 W Charleston Blvd, Suite 601, Las Vegas, NV 89102
e-mail: kmurray{at}med.unr.edu
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Abstract
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Procainamide is an effective antiarrhythmic that is often used to convert atrial fibrillation to normal sinus rhythm. A side effect of procainamide, rarely reported in the surgical literature, is pyrexia. The pyrexia is a manifestation of an allergic response to this medication. If unrecognized, procainamide-induced pyrexia can lead to unnecessary testing, hospitalization, and treatment. We present a case of a post-coronary artery bypass surgery patient who repeatedly displayed pyrexia when reexposed to procainamide indicating an allergic response to this drug.
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Introduction
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Cardiac surgery patients infrequently develop a postoperative fever greater than 38.5°C. When this problem arises, the differential diagnosis is extensive. The timing of the temperature elevation, the degree of pyrexia, and the associated signs and symptoms are all factors that help identify the cause. The presentation of pyrexia (
38.5°C), chills, rigors, and lassitude more than 1 week after coronary artery bypass surgery is most commonly associated with an infectious etiology. This report describes an unusual case where a patient’s postoperative fever and associated clinical findings were caused by a hypersensitivity reaction to the antiarrhythmic drug procainamide (PROC).
The patient was a 64-year-old man who presented with xertional chest pain. The clinical diagnosis of cardiac ischemia was confirmed using an exercise thallium test. A cardiac catheterization demonstrated triple-vessel coronary artery disease with impaired left ventricular function. Coronary artery bypass surgery was performed using the left internal mammary artery and three saphenous vein grafts.
He was weaned from cardiopulmonary bypass in normal sinus rhythm (NSR). After extubation on the first postoperative day (POD), he developed atrial fibrillation (AF) with a ventricular response of 105–115 beats per minute. One gram of PROC was infused intravenously with a rapid conversion to NSR. Simultaneously, he was started on an oral regimen of sustained released PROC (1.5 g Procanbid, twice daily). This dose was reduced (1 g twice daily) on the second POD secondary to nausea. His nausea resolved, and serum PROC levels on the third POD were in the low therapeutic range. He was discharged on POD 5 in NSR, afebrile, and with a white blood cell (WBC) count of 14.4.
He returned to the emergency department (ED) on POD 9 with chills, lassitude, and a temperature of 39°C. He had no localizing symptoms, his wounds were unremarkable, the WBC was 8.6, the chest radiograph was without infiltrates, and cultures (both blood and urine) had no growth. Since there was no evidence of infection and he was in NSR, the PROC was stopped and the patient was discharged home. He became afebrile within 24 hours.
He returned to the ED on POD 13 in AF. His temperature was 36.8°C. He was restarted on sustained release PROC (1 g Procanbid twice daily). He converted to NSR within 24 hours, however, after the second dose, his temperature reached 40.2°C, with associated rigors, chills, and a normal WBC. Multiple blood and urine cultures were obtained over the next 48 hours but all were without growth. A chest radiograph was normal and his wounds had no evidence of infection. Within 24 hours after stopping the PROC on POD 15, his temperature returned to normal. Subsequently, he reverted to AF and was restarted a third time on oral PROC. After receiving the first dose, his temperature reached 39.1°C with rigors and chills. This third episode of fever, rigors, and chills after PROC administration were ascribed to a hypersensitivity reaction, and the drug was stopped. There were no further episodes of hyperpyrexia. He converted to NSR using ß-blockers and amiodarone. All cultures remained without growth and he subsequently recovered without evidence of infection.
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Comment
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Allergic reactions account for 6%–18% of all adverse ffects of medications [1]. Only 3%–4% of these allergic reactions are manifested primarily by fever. The cause of these fevers is most frequently a hypersensitivity response to the drug. The pyrexia is ascribed to an immune mechanism involving an antigen/antibody interaction. The sequence for a classic hypersensitivity response after the initial drug exposure is an induction period of approximately 10–14 days before the patient becomes febrile. The temperature elevation usually is low grade, although PROC is more likely to cause significant pyrexia ( 38.5°C) [1]. After discontinuation of the offending medication, the fever abates over 1–2 days, but it reappears within hours if the drug is reintroduced to the patient. Generally, the patient does not feel ill, although clinical reports of PROC hypersensitivity frequently describe associated malaise, chills, nausea, and vomiting [2, 3]. The development of the allergic response is not influenced by the route of administration or the dose. The antiarrhythmic effects of PROC are not affected by the febrile reaction, however, discontinuation of the drug is necessary to alleviate the adverse hypersensitivity response.
This patient manifested all the classic, albeit rare, findings for a hypersensitivity response to PROC. The etiology of the postoperative fever, as an allergic response to the drug, was not proven by its resolution after the initial discontinuation of the PROC. The patient’s recent surgery, high fever, and associated symptoms strongly suggested an infection. However, the recurrence of the significant pyrexia and the associated symptoms after each reexposure to PROC plus the lack of clinical signs indicating an infectious etiology suggested the diagnosis as a hypersensitivity reaction to the drug.
There are only a small number of published reports describing patients receiving PROC who develop a hypersensitivity response, manifested primarily as significant pyrexia [2, 3]. The majority of these cases involved nonsurgical patients. Procainamide is frequently used in cardiac surgery patients for the treatment of postoperative atrial arrhythmias. This Vaughn Williams’ class IA agent has particular effectiveness in the conversion of atrial fibrillation to normal sinus rhythm. Despite its widespread use, we could find no reports of the hypersensitivity response to PROC in the cardiac surgical literature. Procainamide hypersensitivity should be considered in the differential diagnosis of cardiac surgery patients who develop pyrexia (38.5°C), chills, rigors, and lassitude 7 to 14 days after the initiation of drug treatment. This allergic response is treated by the discontinuation of the drug and the avoidance of PROC in the future.
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Acknowledgments
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We thank Yalonda J. Norris for her expert assistance in the preparation of this manuscript.
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References
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Tabor P.A. Drug fever. Drug Intell Clin Pharm 1986;20:413-420.[Abstract]
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Larvson D.H., Jick H. Advanced reactions to procainamide. Br J Clin Pharmacol 1977;4:507-511.[Medline]
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Shapiro M.S., Teitler A., Grab D. Procainamide hydrochloride sensitivity. Minnesota Med 1973;56:1041-1044.[Medline]
Accepted for publication February 13, 1999.
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Abstract
Introduction
