Cardiac Arrhythmias during Theophylline Toxicity* A Prospective Continuous Electrocardiographic Study Curtis N. Sessler; M.D., F.C.C.E;t Mark D. Cohen, M.D.+
To examine the effects of theophylline toxicity on cardiac rhythm, patients underwent continuous ambulatory ECG recording during acute theophylline toxicity and recovery. The patients, who were recruited from inpatient wards, intensive care units, and emergency departments of a University Medical Center and a Veterans Administration Medical Center, had serum theophylline concentrations (STC) greater than 30 mgIL. There were 14 men and two women with a mean age of 66 years. Fourteen patients had COPD and developed toxicity following long-term theophylline overmedication. Two patients had asthma and ingested an intentional overdose. The STC at the onset of ECG recording ranged from 23 to 67 mgIL. The principal rhythm was sinus in 15 patients; one patient had atrial fibrillation. Sinus tachycardia (heart rate> lOO/min) was common, and heart rate fell in proportion to STC as toxicity resolved. Supraventricular ectopic beats (SVEs) were noted in seven patients with multiple runs of SVE being present in four. One patient developed multifocal atrial tachycardia (MAT) during toxicity that resolved spontaneously. During the II ± 8 hours of recording during toxicity (STC >20 mg! L), 80 percent of patients had ventricular premature beats (VPBs), 44 percent had paired VPBs, and 25 percent had ventricular runs. One elderly patient with heart disease developed sustained ventricular tachycardia (VI') when
STC=66 mgIL. No other patient had ventricular ectopy that required intervention. During the 10±6 hours of recording during the "recovery phase" (STC IO/h) or repetitive VPBs were older (p60 s) episodes of rapid sinus tachycardia (ST) (> 150 beats/min). Heart rate decreased over time and correlated with the reduction in STC (r = 0.47, pets CHEST I 98 I 3 I SEPTEMBER, 1990
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of theophylline in luunan atrial tissue. Int J Cardioll987; 17:28997 Levine JL, Mk-hael JR, (;uarnieri T. ~tulti(()Cal atrial tachycardia: a theophylline indu(.'ed rhythrll. Lan(.'et 1985; 1: 12-4 Paloucek F~ Rodvold KA. Evaluation of theophylline overdoses and toxidties. Ann Emer~ Med 1988; 17:135-44 Sessler eN. Cohen M. Garnett AR. Cardiac arrhytlunias durin~ theophylline toxidty. Chest 1988; 94:85 Mar(.'hlinski FE. ~tiller JM. Atrial arrhytlunias exaeerhated hy theophylline: response to verapmnil and evidence for tri~ered activity in nlan. Chest 1985; 88:931-34 Banner AS. Sund("rrajall E\~ A~al"\\tal MK, Addin~on \V\~ Arrhythm()~enic effects of orally adrninistered hrollchodilators. Arch Intern Med 1979; 139:434-37 Coleman JJ, \'c)lImer \V~1. Barker AF, Schultz CE, Buist AS. Cardiac arrhythrnias dllrill~ the (.'onlhined use of l3-adrener~ic a~onist dru~s and theophylline. Chest 1986; 90:45-51 Cooradson T, Eklundh G, Olofssoll B, Phalm 0, Persson (;. Arrhythrn()~enicity frorn combined bronchodilator therapy in patients \\'ith ohstructive lun~ disease and con(.'omitant ischemic heart disease. Chest 1987; 91 :5-9 Eidelnlilll 011. Sand MH, M(.{;re~()r M. Cosio MG. Combination of theophylline and salhutamol fi)r arrhythmias in sevt."re COPO. Chest 1987~ 91:808-12 Josephson G\V, Kennedy liLt MacKenzie EJ, (;iI)son C. Cardiac dysrhytlunias durin~ the treatment of acute asthma: a , Psychoyos I, Proteau J, Rochemaure J. Cardiae arrhythruias durin~ the (.'()mbined use of intravenous mllinophyllint" and terhutalint- in status asthnulticus. Chest 1988~ 94;496-502 Patel AK, Skatnld JB, Thonlson JII. Cardiac arrhythnlias due to oral aminophylline in patients with chronk obstructive pulrnonary (lisease. Chest 1981; 80:661-65 Shim CS. Scher S~t. \Villiams ~tH. Effect of bronchodilator a~ents on arrhythlnia. NY State J Med 1976; 76:1973-76 Siemons LJ, Parizel G. ProlonJ,!;ed nU1S of ventricular tachyeardia as a (.'()mplication of theophylline intoxication: report of a case. Acta Cardiol 1986; 6:457-64 Hall K\~ Dobson KE. Dalton JG, Ghi~llone Me, Penner 5B. Metabolic ahnonnalities associated \\rith intentional theophylline
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overdose. Ann Intern Med 1984; 101:457-62 21 TaniJttlchi A, Ohe T, Shimontra K. Theophylline-induced ventricular tachycardia in a patient with chronic Illn~ disease: sensitivity to verapamil. Chest 1989; 96:958-59 22 Camarata SJ, \Veil MH, lIanashiro PK, Shubin H. Cardiac arrest in the critically ill, I: a study of the predisposin~ causes in 132 patients. Circulation 1971~ 44:688-95 23 Bresnick E, \\hodward WK t Sa~eman CB. Fatal reactions to the intravenous administration of aminophylline. JAMA 1948; 136:397-98 24 Merrill GA. Aminophylline deaths. JAMA 1943; 123: 1115 25 Olson KR, Benowitz NL, Woo OF, Pond SM. Theophylline overdose: acute sin~le in~estion versus chronic repeated overmedication. Am J Emer~ Med 1985; 3:386-94 26 Bertino JS, Walker JW Reassessment of theophylline toxicity: senlm concentrations, clinical (..'()urse, and treatment. Arch Intern Med 1987; 147:757-60 27 Greenber~ A, Piraino BH, Kroboth PO, Weiss J. Severe theophylline toxicity: role of(.'()nservative measures. antiarrhythmic agents, and charcoal hemoperfusion. Am J Med 1984; 76:854-60 28 Hendeles L, Bi~hley L, Richardson RH, IIepler CD, Cannichael J. Frequent toxicity from IV arninophylline infusions in critically ill patients. Drtl~ Intel) Clin Pharm 1977; 11-12-7 29 Sessler eN. Theophylline toxicity and overdose: predisp()sin~ factors, clinical features, and outcome of 116 consecutive cases. Am Rev Respir Dis 1989; 139:A435 30 Mountain RD, NefTTA. Oral theophylline intoxication: a serious error of patient and physician understandin~. Arch Intern Med 1984; 144:724-27 31 Benchimol A, Li~ett MS. Cardiac hemodynamics durin~ stirnulation of the right atrium, ri~ht ventricle, and left ventricle in normal and abnomlal hearts. Circulation 1966; 33:933-44 32 Klei~er RE, Senior RM. L()n~-term electrocardioJ,!;raphic monitorin~ of ambulatory patients with chronic airway obstnlction. Chest 1974; 65:483-87 33 Shih liT, \Vehh CR, Conway WA, Peterson E, Tilley B, Goldstein S. Frequency and siJtnificance of cardiac arrhythnlias in chronic obstructive lun~ disease. Chest 1988; 94:44-8 34 Holford FD, Mithoefer. Cardiac arrhythnlias in hospitalized patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1973; 108:879-85 35 Aitken ML, Martin TR. Life-threatenin~ theophylline toxicity is not predictable by serum levels. Chest 1987; 91:10-4 36 Helliwell M, Berry D. Theophylline p()isonin~ in adults. Br Med J 1979; 2: 114
Cardiac Arrhythmias during Theophylline Toxicity (Sessler, Cohen)
To examine the effects of theophylline toxicity on cardiac rhythm, patients underwent continuous ambulatory ECG recording during acute theophylline toxicity and recovery. The patients, who were recruited from inpatient wards, intensive care units, and emergency departments of a University Medical Center and a Veterans Administration Medical Center, had serum theophylline concentrations (STC) greater than 30 mgIL. There were 14 men and two women with a mean age of 66 years. Fourteen patients had COPD and developed toxicity following long-term theophylline overmedication. Two patients had asthma and ingested an intentional overdose. The STC at the onset of ECG recording ranged from 23 to 67 mgIL. The principal rhythm was sinus in 15 patients; one patient had atrial fibrillation. Sinus tachycardia (heart rate> lOO/min) was common, and heart rate fell in proportion to STC as toxicity resolved. Supraventricular ectopic beats (SVEs) were noted in seven patients with multiple runs of SVE being present in four. One patient developed multifocal atrial tachycardia (MAT) during toxicity that resolved spontaneously. During the II ± 8 hours of recording during toxicity (STC >20 mg! L), 80 percent of patients had ventricular premature beats (VPBs), 44 percent had paired VPBs, and 25 percent had ventricular runs. One elderly patient with heart disease developed sustained ventricular tachycardia (VI') when
STC=66 mgIL. No other patient had ventricular ectopy that required intervention. During the 10±6 hours of recording during the "recovery phase" (STC IO/h) or repetitive VPBs were older (p60 s) episodes of rapid sinus tachycardia (ST) (> 150 beats/min). Heart rate decreased over time and correlated with the reduction in STC (r = 0.47, pets CHEST I 98 I 3 I SEPTEMBER, 1990
677
6 7
8 9
10
11 12
13
14
15
16
17
18 19
20
of theophylline in luunan atrial tissue. Int J Cardioll987; 17:28997 Levine JL, Mk-hael JR, (;uarnieri T. ~tulti(()Cal atrial tachycardia: a theophylline indu(.'ed rhythrll. Lan(.'et 1985; 1: 12-4 Paloucek F~ Rodvold KA. Evaluation of theophylline overdoses and toxidties. Ann Emer~ Med 1988; 17:135-44 Sessler eN. Cohen M. Garnett AR. Cardiac arrhytlunias durin~ theophylline toxidty. Chest 1988; 94:85 Mar(.'hlinski FE. ~tiller JM. Atrial arrhytlunias exaeerhated hy theophylline: response to verapmnil and evidence for tri~ered activity in nlan. Chest 1985; 88:931-34 Banner AS. Sund("rrajall E\~ A~al"\\tal MK, Addin~on \V\~ Arrhythm()~enic effects of orally adrninistered hrollchodilators. Arch Intern Med 1979; 139:434-37 Coleman JJ, \'c)lImer \V~1. Barker AF, Schultz CE, Buist AS. Cardiac arrhythrnias dllrill~ the (.'onlhined use of l3-adrener~ic a~onist dru~s and theophylline. Chest 1986; 90:45-51 Cooradson T, Eklundh G, Olofssoll B, Phalm 0, Persson (;. Arrhythrn()~enicity frorn combined bronchodilator therapy in patients \\'ith ohstructive lun~ disease and con(.'omitant ischemic heart disease. Chest 1987; 91 :5-9 Eidelnlilll 011. Sand MH, M(.{;re~()r M. Cosio MG. Combination of theophylline and salhutamol fi)r arrhythmias in sevt."re COPO. Chest 1987~ 91:808-12 Josephson G\V, Kennedy liLt MacKenzie EJ, (;iI)son C. Cardiac dysrhytlunias durin~ the treatment of acute asthma: a , Psychoyos I, Proteau J, Rochemaure J. Cardiae arrhythruias durin~ the (.'()mbined use of intravenous mllinophyllint" and terhutalint- in status asthnulticus. Chest 1988~ 94;496-502 Patel AK, Skatnld JB, Thonlson JII. Cardiac arrhythnlias due to oral aminophylline in patients with chronk obstructive pulrnonary (lisease. Chest 1981; 80:661-65 Shim CS. Scher S~t. \Villiams ~tH. Effect of bronchodilator a~ents on arrhythlnia. NY State J Med 1976; 76:1973-76 Siemons LJ, Parizel G. ProlonJ,!;ed nU1S of ventricular tachyeardia as a (.'()mplication of theophylline intoxication: report of a case. Acta Cardiol 1986; 6:457-64 Hall K\~ Dobson KE. Dalton JG, Ghi~llone Me, Penner 5B. Metabolic ahnonnalities associated \\rith intentional theophylline
678
overdose. Ann Intern Med 1984; 101:457-62 21 TaniJttlchi A, Ohe T, Shimontra K. Theophylline-induced ventricular tachycardia in a patient with chronic Illn~ disease: sensitivity to verapamil. Chest 1989; 96:958-59 22 Camarata SJ, \Veil MH, lIanashiro PK, Shubin H. Cardiac arrest in the critically ill, I: a study of the predisposin~ causes in 132 patients. Circulation 1971~ 44:688-95 23 Bresnick E, \\hodward WK t Sa~eman CB. Fatal reactions to the intravenous administration of aminophylline. JAMA 1948; 136:397-98 24 Merrill GA. Aminophylline deaths. JAMA 1943; 123: 1115 25 Olson KR, Benowitz NL, Woo OF, Pond SM. Theophylline overdose: acute sin~le in~estion versus chronic repeated overmedication. Am J Emer~ Med 1985; 3:386-94 26 Bertino JS, Walker JW Reassessment of theophylline toxicity: senlm concentrations, clinical (..'()urse, and treatment. Arch Intern Med 1987; 147:757-60 27 Greenber~ A, Piraino BH, Kroboth PO, Weiss J. Severe theophylline toxicity: role of(.'()nservative measures. antiarrhythmic agents, and charcoal hemoperfusion. Am J Med 1984; 76:854-60 28 Hendeles L, Bi~hley L, Richardson RH, IIepler CD, Cannichael J. Frequent toxicity from IV arninophylline infusions in critically ill patients. Drtl~ Intel) Clin Pharm 1977; 11-12-7 29 Sessler eN. Theophylline toxicity and overdose: predisp()sin~ factors, clinical features, and outcome of 116 consecutive cases. Am Rev Respir Dis 1989; 139:A435 30 Mountain RD, NefTTA. Oral theophylline intoxication: a serious error of patient and physician understandin~. Arch Intern Med 1984; 144:724-27 31 Benchimol A, Li~ett MS. Cardiac hemodynamics durin~ stirnulation of the right atrium, ri~ht ventricle, and left ventricle in normal and abnomlal hearts. Circulation 1966; 33:933-44 32 Klei~er RE, Senior RM. L()n~-term electrocardioJ,!;raphic monitorin~ of ambulatory patients with chronic airway obstnlction. Chest 1974; 65:483-87 33 Shih liT, \Vehh CR, Conway WA, Peterson E, Tilley B, Goldstein S. Frequency and siJtnificance of cardiac arrhythnlias in chronic obstructive lun~ disease. Chest 1988; 94:44-8 34 Holford FD, Mithoefer. Cardiac arrhythnlias in hospitalized patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1973; 108:879-85 35 Aitken ML, Martin TR. Life-threatenin~ theophylline toxicity is not predictable by serum levels. Chest 1987; 91:10-4 36 Helliwell M, Berry D. Theophylline p()isonin~ in adults. Br Med J 1979; 2: 114
Cardiac Arrhythmias during Theophylline Toxicity (Sessler, Cohen)
