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Fever induced by dobutamine infusion
CASE REPORTS
Fever Induced by Dobutamine Infusion Scott A. Chapman, BS, RPh, Tierza Stephan, MD, Kathleen D. Lake, PharmD, Steven W. Sonnesyn, MD, and Robert W. Emery, MD
A
ctive infection is considered an absolute contraindication for heart transplant surgery, and the development of fever in a transplant candidate can result in an extensive infectious disease work-up and possible removal of a patient from the transplant waiting list. As many as 10% of elevated temperatures in hospitalized patients may be druginduced.’ We report a case of dobutamine-induced fever in a patient with heart failure awaiting heart transplantation. To our knowledge, only a single similar case has previously been reported.2 CN is a 51 -year-old white woman with heart failure secondary to idiopathic dilated cardiomyopathy diagnosed in 1981. Other medical history included malignant ventricular arrhythmias and placement of an automatic implantable cardioverter de$brillator (ICD) in 1990 after ventricular fibrillation arrest, chronic atria1 jibrillation, hypothyroidism, cervical cancer, and hysterectomy. She has been on the heart transplant waiting list since October 1992. She had been afebrile during frequent checks of her temperature at home. After a 3-day history of nausea, dyspnea, and fatigue, she presented to the emergency room. There were no associatedfevers, chills, night sweats, chest discomfort, or syncope. Physical examination revealed the patient to be in no acute distress. Vital signs included a blood pressure of 110176 mm Hg, heart rate 80 beatslmin, respiratory rate 20 breathslmin, and temperature 36.4”C. Other sign@ cant @dings were consistent with exacerbated congestive heart failure. Electrocardiogram showed atrialjbrillation. Chest x-ray showed cardioFrom the Minneapolis Heart Institute Foundation, Abbott-Northwestern Hospital and College of Pharmacy, University bf Minnesota, 800 East 28th Street, Suite GGO4, Minneape lis. Minnesota 55407. Manuscript received knuary 27,1994; revised manuscript received and accepted March 1, 1994.
megaly with ICD patches on the heart and mild interstitial pulmonary congestion with peribronchial cufing. The white blood cell count was 8.4 cellslm& on admission. Because of decompensated congestive heart failure, intravenous dobutamine 5 pglkglmin and intravenous bumetanide 4 mg every 6 hours were started. All medications before admission were continued. Core temperatures increased to 38.6”C by the next morning and were associated with headache, chills, temperature intolerance, and a continued chronic cough producing white sputum. The patient recalled a similar episode during a previous hospitalization after the start of a dobutamine infusion. During that episode, no positive sputum, blood, or urine cultures were obtained but empiric clarithromycin was administered for 10 days. During the current hospitalization, blood, sputum, and urine cultures were obtained. No antibiotic therapy was started. Although viral or bacterial infection was suspected, the possibility of dobutamine hypersensitivity was also considered as the cause of her fever and bronchospastic cough. Over 2 days, temperatures remained elevated and the patient experienced nausea, vomiting, rigors, headaches, persistent hacking cough, flushing, and loss of appetite. On the fourth day of hospitalization, the dobutamine infusion was discontinued, and on days 5 to 8 she was afebrile and asymptomatic. All cultures were finally reported negative. During a third previous hospitalization, similar symptoms were observed after starting a dobutamine infision. Culture results were negative and white blood cell counts were within normal limits during that hospitalization. The dobutamine infusion was continued for 13 days; however, the patient did defervesce by day 7 of the dobutamine in&ion.
Although some drugs cause fever, others rarely result in elevated
temperatures. IJP The mechanisms associated with drug-induced fever include hypersensitivity reaction, idiosyncratic reaction, administration-related reaction, pharmacologic action, altered thermoregulation, or unknown reactions.5 Although rarely reported,2 dobutamine-induced fever in a patient awaiting heart transplantation has serious implications and may result in a temporary contraindication to and delay in heart transplantation. Eight separate reports submitted to Eli Lilly and Company have been filed regarding fever associated with DobutrexB. In 7 of these reports, patients had received Dobutrex@ previously without adverse effect. Six of these reports noted fever, which abated on discontinuation of Dobutrex@. In 3, fever recurred on rechallenge with Dobutrex@. Because such reports are voluntary, it is difficult to determine the actual incidence of Dobutrex@associated fever. The package insert for Dobutrex@ warns of the possibility of hypersensitivity reactions from the additive sodium bisulfite which may cause anaphylactic symptoms or asthmatic episodes in susceptible persons (i.e., asthmatics). The patient under discussion had no previous reactions to bisulfite-containing compounds. In patients experiencing drug-induced fever, temperatures typically range from 39°C to 40.6”C, and patients may appear inappropriately well. Drug-induced fever can be associated with low-grade eosinophilia and maculopapular rash. Fever usually normalizes within 48 to 72 hours after discontinuation of the offending drug, although it may persist for several days to weeks if the maculopapular rash presents as a component of the drug reaction.’ Dobutamine should be considered as a cause of fever in patients being treated for heart failure. 1. Chum BA. Drug fever-the importance of recognition. Postgrad Med 1986;80:123-129, 2 Robinson-Strane SR. Bubick JS. Dobutamineinduced fever. Ann Pharmcother 1992.26~1523-1524. 8. Mackowiak PA, LeMaistre CF. Drug fever: a critical appraisal of conventional concepts. Ann Intern Med 1987;106:728-733. 4. Lipsky BA, Hirschmann IV. Drug fever. JAMA 19R1;245:851-854. S. Hanson MA. Drug fever-remember to consider it in diagnosis. Postgrad Med 1991:89:167-173.
CASE REPORTS 517
Fever Induced by Dobutamine Infusion Scott A. Chapman, BS, RPh, Tierza Stephan, MD, Kathleen D. Lake, PharmD, Steven W. Sonnesyn, MD, and Robert W. Emery, MD
A
ctive infection is considered an absolute contraindication for heart transplant surgery, and the development of fever in a transplant candidate can result in an extensive infectious disease work-up and possible removal of a patient from the transplant waiting list. As many as 10% of elevated temperatures in hospitalized patients may be druginduced.’ We report a case of dobutamine-induced fever in a patient with heart failure awaiting heart transplantation. To our knowledge, only a single similar case has previously been reported.2 CN is a 51 -year-old white woman with heart failure secondary to idiopathic dilated cardiomyopathy diagnosed in 1981. Other medical history included malignant ventricular arrhythmias and placement of an automatic implantable cardioverter de$brillator (ICD) in 1990 after ventricular fibrillation arrest, chronic atria1 jibrillation, hypothyroidism, cervical cancer, and hysterectomy. She has been on the heart transplant waiting list since October 1992. She had been afebrile during frequent checks of her temperature at home. After a 3-day history of nausea, dyspnea, and fatigue, she presented to the emergency room. There were no associatedfevers, chills, night sweats, chest discomfort, or syncope. Physical examination revealed the patient to be in no acute distress. Vital signs included a blood pressure of 110176 mm Hg, heart rate 80 beatslmin, respiratory rate 20 breathslmin, and temperature 36.4”C. Other sign@ cant @dings were consistent with exacerbated congestive heart failure. Electrocardiogram showed atrialjbrillation. Chest x-ray showed cardioFrom the Minneapolis Heart Institute Foundation, Abbott-Northwestern Hospital and College of Pharmacy, University bf Minnesota, 800 East 28th Street, Suite GGO4, Minneape lis. Minnesota 55407. Manuscript received knuary 27,1994; revised manuscript received and accepted March 1, 1994.
megaly with ICD patches on the heart and mild interstitial pulmonary congestion with peribronchial cufing. The white blood cell count was 8.4 cellslm& on admission. Because of decompensated congestive heart failure, intravenous dobutamine 5 pglkglmin and intravenous bumetanide 4 mg every 6 hours were started. All medications before admission were continued. Core temperatures increased to 38.6”C by the next morning and were associated with headache, chills, temperature intolerance, and a continued chronic cough producing white sputum. The patient recalled a similar episode during a previous hospitalization after the start of a dobutamine infusion. During that episode, no positive sputum, blood, or urine cultures were obtained but empiric clarithromycin was administered for 10 days. During the current hospitalization, blood, sputum, and urine cultures were obtained. No antibiotic therapy was started. Although viral or bacterial infection was suspected, the possibility of dobutamine hypersensitivity was also considered as the cause of her fever and bronchospastic cough. Over 2 days, temperatures remained elevated and the patient experienced nausea, vomiting, rigors, headaches, persistent hacking cough, flushing, and loss of appetite. On the fourth day of hospitalization, the dobutamine infusion was discontinued, and on days 5 to 8 she was afebrile and asymptomatic. All cultures were finally reported negative. During a third previous hospitalization, similar symptoms were observed after starting a dobutamine infision. Culture results were negative and white blood cell counts were within normal limits during that hospitalization. The dobutamine infusion was continued for 13 days; however, the patient did defervesce by day 7 of the dobutamine in&ion.
Although some drugs cause fever, others rarely result in elevated
temperatures. IJP The mechanisms associated with drug-induced fever include hypersensitivity reaction, idiosyncratic reaction, administration-related reaction, pharmacologic action, altered thermoregulation, or unknown reactions.5 Although rarely reported,2 dobutamine-induced fever in a patient awaiting heart transplantation has serious implications and may result in a temporary contraindication to and delay in heart transplantation. Eight separate reports submitted to Eli Lilly and Company have been filed regarding fever associated with DobutrexB. In 7 of these reports, patients had received Dobutrex@ previously without adverse effect. Six of these reports noted fever, which abated on discontinuation of Dobutrex@. In 3, fever recurred on rechallenge with Dobutrex@. Because such reports are voluntary, it is difficult to determine the actual incidence of Dobutrex@associated fever. The package insert for Dobutrex@ warns of the possibility of hypersensitivity reactions from the additive sodium bisulfite which may cause anaphylactic symptoms or asthmatic episodes in susceptible persons (i.e., asthmatics). The patient under discussion had no previous reactions to bisulfite-containing compounds. In patients experiencing drug-induced fever, temperatures typically range from 39°C to 40.6”C, and patients may appear inappropriately well. Drug-induced fever can be associated with low-grade eosinophilia and maculopapular rash. Fever usually normalizes within 48 to 72 hours after discontinuation of the offending drug, although it may persist for several days to weeks if the maculopapular rash presents as a component of the drug reaction.’ Dobutamine should be considered as a cause of fever in patients being treated for heart failure. 1. Chum BA. Drug fever-the importance of recognition. Postgrad Med 1986;80:123-129, 2 Robinson-Strane SR. Bubick JS. Dobutamineinduced fever. Ann Pharmcother 1992.26~1523-1524. 8. Mackowiak PA, LeMaistre CF. Drug fever: a critical appraisal of conventional concepts. Ann Intern Med 1987;106:728-733. 4. Lipsky BA, Hirschmann IV. Drug fever. JAMA 19R1;245:851-854. S. Hanson MA. Drug fever-remember to consider it in diagnosis. Postgrad Med 1991:89:167-173.
CASE REPORTS 517