http://informahealthcare.com/ada ISSN: 0095-2990 (print), 1097-9891 (electronic) Am J Drug Alcohol Abuse, 2014; 40(6): 490–492 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/00952990.2014.965311
LETTER TO THE EDITOR
Methadone induced Torsades de Pointes mimicking seizures in clinical presentation Sameer Raina, MD1, Hakan Paydak, MD1,2, Tawfiq Al-lahham, MD1, and Bashir S. Shihabuddin, MD1,2 1
University of Arkansas for Medical Sciences, Little Rock, Arkansas and 2Central Arkansas Veterans Healthcare System, Little Rock, Arkansas
Torsades de Pointes (TdP) has been associated with high dose methadone use. This usually presents clinically with palpitations, dizziness and syncope. We report a case of methadoneinduced TdP with an unusual clinical presentation mimicking convulsive seizures. This case highlights the importance of being aware of methadone-induced TdP and the possible atypical clinical manifestations of this condition.
Keywords Cardiac arrest, methadone, Torsades de Pointes, seizures History Received 21 April 2014 Revised 6 September 2014 Accepted 8 September 2014 Published online 16 October 2014
Case study A 29-year-old woman with opiate use disorder on 60 mg twice daily of methadone for six years presented with three months history of frequent convulsive episodes. The episodes were occurring up to three times per week and described as sudden clenching of the arms and body jerking while unresponsive for approximately one minute. Afterwards, she was fatigued with no recollection of the events. She denied any premonitory symptoms. Her vital signs, physical examination, metabolic profile and CT scan of the head were normal. ECG, cardiac telemetry and echocardiogram were unrevealing except for a mildly prolonged corrected QT interval (QTc) of 445 ms and prior ECGs were not available for comparison. This was attributed to her sole medication, methadone and thought to be clinically insignificant. She reported recent social stressors and a somatization disorder or new onset seizure disorder was suspected. A diagnostic video EEG monitoring (VEEG) study recorded a typical episode accompanied by remarkable ECG and EEG changes (Figure 1). It manifested with rapid breathing associated with bilateral dystonic arm posturing, whole body myoclonic jerks and noisy breathing before she became completely unresponsive, flaccid and respirations ceased for 54 seconds. Then she resumed breathing and gradually regained awareness. The concomitant ECG showed Torsades de Pointes (TdP) pattern lasting for 139 seconds, while the EEG showed
Address correspondence to Bashir S. Shihabuddin, MD, University of Arkansas for Medical Sciences (UAMS), Department of Neurology, 4301 West Markham Street, Slot #500, Little Rock, AR 72205. E-mail: [email protected]
complete voltage suppression for 48 seconds. She suffered cardiac arrest followed by spontaneous recovery. Repeat ECG showed QTc prolongation at 536 ms and symmetrical T-wave inversions in the anterior and inferior leads. She was transferred to ICU, electrolytes were supplemented and methadone was discontinued. Stress Echocardiogram and Coronary CT scan were normal. Following consultation with cardiology, a cardiac pacemaker was not recommended as the ECG changes gradually normalized and QTc was 442 ms two days later. She was discharged with a plan to start buprenorphine and to follow up closely with cardiology. Unfortunately, this follow-up did not occur at our institution.
Discussion ‘‘Torsades de Pointes’’ represents a distinctive electrocardiographic form of polymorphic ventricular tachycardia. If rapid or prolonged, it can lead to ventricular fibrillation and sudden cardiac death (1). It is caused by a congenital or acquired long QT syndrome (LQTS). The usual clinical manifestations of TdP are palpitations, dizziness and syncope. Certain noncardiac drugs are recognized to increase the propensity for TdP. We report a rare case of methadone-induced TdP mimicking convulsive seizures in clinical presentation. She had a witnessed cardiac arrest with spontaneous recovery during VEEG documenting TdP and concomitant complete suppression of electrocerebral activity. The most common risk factors of methadone-associated QT prolongation and TdP include high dose methadone (460 mg daily), concomitant medications that increase serum methadone levels, HIV
DOI: 10.3109/00952990.2014.965311
Methadone induced Torsades mimicking seizures
491
Figure 1. ECG and EEG changes during the recorded clinical event. (A) Baseline: ECG showing normal sinus rhythm, occasional PVCs, and QT interval prolongation with normal EEG recording. (B) Onset: ECG showing the onset of TdP (up arrow) followed by onset of EEG changes manifesting as high amplitude slow waves (down arrow). (C) Termination: ECG showing TdP termination followed by sinus bradycardia while the EEG activity shows complete voltage suppression (up arrow) followed by restart of the EEG activity with subtle bursts of delta slow waves and subtle muscle artifacts (down arrow). (D) Recovery: ECG showing normal sinus rhythm and occasional PVCs with continued improvement of the EEG activity showing faster frequencies of higher amplitude activity.
infection, hypokalemia, female gender, liver cirrhosis, renal failure and heart disease (2). Wedam et al. reported that almost a quarter of patients on methadone had significant increase in QT interval, while this was not observed in
patients on the partial opioid agonist, buprenorphine (3). To avoid TdP in patients on methadone it is prudent to obtain a baseline and interval ECG, personal and family history of cardiac disease, a list of current medications and using
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S. Raina et al.
Am J Drug Alcohol Abuse, 2014; 40(6): 490–492
Figure 1. Continued.
methadone at the lowest necessary dose. Also, it is essential to consider TdP in patients on methadone even if the clinical presentation is atypical.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.
References 1. Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart 2003;89:1363–1372. 2. Justo D, Gal-Oz A, Paran Y, Goldin Y, Zeltser D. Methadoneassociated torsades de pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. Addiction 2006;101:1333–1338. 3. Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MC. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med 2007;167:2469–2475.
Copyright of American Journal of Drug & Alcohol Abuse is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
LETTER TO THE EDITOR
Methadone induced Torsades de Pointes mimicking seizures in clinical presentation Sameer Raina, MD1, Hakan Paydak, MD1,2, Tawfiq Al-lahham, MD1, and Bashir S. Shihabuddin, MD1,2 1
University of Arkansas for Medical Sciences, Little Rock, Arkansas and 2Central Arkansas Veterans Healthcare System, Little Rock, Arkansas
Torsades de Pointes (TdP) has been associated with high dose methadone use. This usually presents clinically with palpitations, dizziness and syncope. We report a case of methadoneinduced TdP with an unusual clinical presentation mimicking convulsive seizures. This case highlights the importance of being aware of methadone-induced TdP and the possible atypical clinical manifestations of this condition.
Keywords Cardiac arrest, methadone, Torsades de Pointes, seizures History Received 21 April 2014 Revised 6 September 2014 Accepted 8 September 2014 Published online 16 October 2014
Case study A 29-year-old woman with opiate use disorder on 60 mg twice daily of methadone for six years presented with three months history of frequent convulsive episodes. The episodes were occurring up to three times per week and described as sudden clenching of the arms and body jerking while unresponsive for approximately one minute. Afterwards, she was fatigued with no recollection of the events. She denied any premonitory symptoms. Her vital signs, physical examination, metabolic profile and CT scan of the head were normal. ECG, cardiac telemetry and echocardiogram were unrevealing except for a mildly prolonged corrected QT interval (QTc) of 445 ms and prior ECGs were not available for comparison. This was attributed to her sole medication, methadone and thought to be clinically insignificant. She reported recent social stressors and a somatization disorder or new onset seizure disorder was suspected. A diagnostic video EEG monitoring (VEEG) study recorded a typical episode accompanied by remarkable ECG and EEG changes (Figure 1). It manifested with rapid breathing associated with bilateral dystonic arm posturing, whole body myoclonic jerks and noisy breathing before she became completely unresponsive, flaccid and respirations ceased for 54 seconds. Then she resumed breathing and gradually regained awareness. The concomitant ECG showed Torsades de Pointes (TdP) pattern lasting for 139 seconds, while the EEG showed
Address correspondence to Bashir S. Shihabuddin, MD, University of Arkansas for Medical Sciences (UAMS), Department of Neurology, 4301 West Markham Street, Slot #500, Little Rock, AR 72205. E-mail: [email protected]
complete voltage suppression for 48 seconds. She suffered cardiac arrest followed by spontaneous recovery. Repeat ECG showed QTc prolongation at 536 ms and symmetrical T-wave inversions in the anterior and inferior leads. She was transferred to ICU, electrolytes were supplemented and methadone was discontinued. Stress Echocardiogram and Coronary CT scan were normal. Following consultation with cardiology, a cardiac pacemaker was not recommended as the ECG changes gradually normalized and QTc was 442 ms two days later. She was discharged with a plan to start buprenorphine and to follow up closely with cardiology. Unfortunately, this follow-up did not occur at our institution.
Discussion ‘‘Torsades de Pointes’’ represents a distinctive electrocardiographic form of polymorphic ventricular tachycardia. If rapid or prolonged, it can lead to ventricular fibrillation and sudden cardiac death (1). It is caused by a congenital or acquired long QT syndrome (LQTS). The usual clinical manifestations of TdP are palpitations, dizziness and syncope. Certain noncardiac drugs are recognized to increase the propensity for TdP. We report a rare case of methadone-induced TdP mimicking convulsive seizures in clinical presentation. She had a witnessed cardiac arrest with spontaneous recovery during VEEG documenting TdP and concomitant complete suppression of electrocerebral activity. The most common risk factors of methadone-associated QT prolongation and TdP include high dose methadone (460 mg daily), concomitant medications that increase serum methadone levels, HIV
DOI: 10.3109/00952990.2014.965311
Methadone induced Torsades mimicking seizures
491
Figure 1. ECG and EEG changes during the recorded clinical event. (A) Baseline: ECG showing normal sinus rhythm, occasional PVCs, and QT interval prolongation with normal EEG recording. (B) Onset: ECG showing the onset of TdP (up arrow) followed by onset of EEG changes manifesting as high amplitude slow waves (down arrow). (C) Termination: ECG showing TdP termination followed by sinus bradycardia while the EEG activity shows complete voltage suppression (up arrow) followed by restart of the EEG activity with subtle bursts of delta slow waves and subtle muscle artifacts (down arrow). (D) Recovery: ECG showing normal sinus rhythm and occasional PVCs with continued improvement of the EEG activity showing faster frequencies of higher amplitude activity.
infection, hypokalemia, female gender, liver cirrhosis, renal failure and heart disease (2). Wedam et al. reported that almost a quarter of patients on methadone had significant increase in QT interval, while this was not observed in
patients on the partial opioid agonist, buprenorphine (3). To avoid TdP in patients on methadone it is prudent to obtain a baseline and interval ECG, personal and family history of cardiac disease, a list of current medications and using
492
S. Raina et al.
Am J Drug Alcohol Abuse, 2014; 40(6): 490–492
Figure 1. Continued.
methadone at the lowest necessary dose. Also, it is essential to consider TdP in patients on methadone even if the clinical presentation is atypical.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.
References 1. Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart 2003;89:1363–1372. 2. Justo D, Gal-Oz A, Paran Y, Goldin Y, Zeltser D. Methadoneassociated torsades de pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. Addiction 2006;101:1333–1338. 3. Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MC. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med 2007;167:2469–2475.
Copyright of American Journal of Drug & Alcohol Abuse is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
