Measurement of QTc in Patients Receiving Chronic Methadone Therapy

Cruciani, Ricardo A.; Sekine, Ryuichi; Homel, Peter; Lussier, David; Yap, Y.; Suzuki, Y.; Schweitzer, Paul; Yancovitz, Stanley R.; Lapin, Jeanne; Shaiova, Lauren; Sheu, Robert; Portenoy, Russell K.

doi:10.1016/j.jpainsymman.2004.06.012

Cited by 103 publications

(73 citation statements)

References 16 publications

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“…8 Our findings are inconsistent with data in adults, in whom methadone has been associated with varying degrees of QTc prolongation (16%-23% change in QTc interval), and with torsades de pointes in up to 4% of patients. [14][15][16][21][22][23][24][25][26] Further, methadone dose, presence of interacting or other QTc-prolonging drugs, electrolyte abnormalities, and underlying cardiovascular disease have been identified as risk factors for QTc prolongation in adults, but we did not identify these associations in our population. [14][15][16][21][22][23][24][25][26] The observed differences in methadone-associated QTc prolongation may be due to physiologic differences between children and adults.…”

Section: Discussionmentioning

confidence: 81%

“…11 Furthermore, critically ill children are likely to receive other QTc-prolonging drugs, have electrolyte derangements, and have end-organ dysfunction known to be associated with increased risk for QTc prolongation. [12][13][14][15][16][17] Because methadone administration is prevalent in pediatric intensive care units, we must ensure that existing clinical practice of methadone administration does not cause undue, life-threatening harm. Therefore, we aimed to determine the effects of methadone initiation on QTc interval in critically ill children, including those with underlying cardiac disease.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Methadone on Corrected Q-T Interval Prolongation in Critically Ill Children

Heath

Greenberg

Hupp

et al. 2018

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVESThis study aimed to determine the association between methadone use and corrected Q-T interval (QTc) prolongation in critically ill children METHODS A retrospective cohort study of critically ill children receiving methadone at a tertiary care pediatric hospital was conducted. Patients younger than 19 years who had been admitted to the intensive care unit between January 1, 2009, and June 21, 2013, who had received methadone while inpatients, and who had had electrocardiograms (ECGs) performed within 30 days before and after methadone initiation were included. The primary outcome was the net change in QTc interval between baseline and postmethadone ECGs. Secondary outcomes included percent change in QTc interval and the proportion of patients whose QTc intervals changed from normal to prolonged following methadone initiation. We also evaluated potential predictors of QTc interval prolongation, including age, sex, admission diagnosis category, exposure to other QTc-prolonging medications, presence of congenital heart disease or known arrhythmias, and methadone daily dose and route of administration.RESULTS Sixty-four patients met the inclusion criteria. The median (25th, 75th percentiles) change in QTc interval following methadone initiation was −8 msec (−34, 13.5 msec; p = 0.19). Five patients (8%) had a baseline normal QTc interval that became prolonged after methadone initiation. We identified no statistically significant predictors of QTc prolongation after methadone initiation.CONCLUSIONS In this dedicated pediatric safety study, methadone initiation did not result in prolongation of the QTc interval. Although these findings suggest methadone initiation may not have a substantial effect of QTc prolongation in critically ill children, a controlled, prospective evaluation in this population remains warranted.

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Effects of Methadone on Corrected Q-T Interval Prolongation in Critically Ill Children

Heath

Greenberg

Hupp

et al. 2018

The Journal of Pediatric Pharmacology and Therapeutics

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“…In patients with non-malignant pain, minor increases and fluctuations in QTc during a prolonged treatment with methadone in doses of less than 100 mg/day were found [5]. In a mixed population of patients with chronic pain or maintenance therapy receiving methadone with median doses of 110 mg/day, 33 % of patients had QTc prolongation related to methadone dose, but no patient had a QTc longer than 500 ms [2].…”

Section: Discussionmentioning

confidence: 98%

Changes of QTc interval after opioid switching to oral methadone

Mercadante

Prestia

Adile

et al. 2013

Support Care Cancer

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A consecutive sample of patients who were switched from strong opioids to methadone in a period of 1 year was surveyed. QTc was assessed before switching (T0) and after achieving adequate analgesia and an acceptable level of adverse effects (Ts). Twenty-eight of 33 patients were switched to methadone successfully. The mean initial methadone doses at T0 were 67.1 mg/day (SD ±80.2, range 12-390). The mean QTc interval at T0 was 400 ms (SD ±30, range 330-450). The mean QTc interval at Ts (median 5 days) was 430 ms (SD ±26, range 390-500). The difference (7.7 %) was significant (p <0.0005). Only two patients had a QTc of 500 ms. No serious arrhythmia was observed. At the linear regression analysis, there was no significant association between mean opioid doses expressed as oral morphine equivalents and QTc at T0 (p =0.428), nor between mean methadone doses and QTc at Ts (p =0.315). No age differences were found with previous opioid doses (p =0.917), methadone doses (p =0.613), QTc at T0 (p =0.173), QTc at Ts (p = 0.297), and final opioid-methadone conversion ratio (p = 0.064). While methadone used for opioids switching seems to be an optimal choice to improve the opioid response in patients poorly responsive to the previous opioid, the possible QTc prolongation should be of concern despite not producing clinical consequences in this group of patients. A larger number of patients should be assessed to quantify the risk of serious arrhythmia.Keywords Cancer pain . Methadone . QT prolongation . Toxicity . Opioid switching Methadone has specific pharmacokinetic and pharmacodynamic properties which could be attractive in several pain conditions. However, dosing of this drug can be challenging for the practicing physicians. Despite lack of reliable equianalgesic conversion ratios, the large interindividual variability in methadone pharmacokinetics, as well as the potential for pharmacological interaction with other drugs, in a selected setting, methadone is an invaluable drug for resolving difficult pain conditions [19]. Early research with methadonemaintained patients revealed that methadone fatalities occur primarily due to respiratory arrest during methadone induction and in the context of polysubstance use. Recent reports of methadone deaths emphasize the role of methadone-related QT prolongation, and the possibility of inducing torsades de pointes, a potentially fatal ventricular arrhythmia [3,22].Recent recommendations suggest that methadone should be used by experienced physicians [1]. For these reasons, methadone is commonly used as a second-line drug, for opioid substitution with remarkable advantages from the clinical point of view [17,18].The aim of this study was to assess the QTc interval changes in the context of opioid switching, which is the most frequent occasion in daily practice to use methadone in advanced cancer patients unresponsive to previous opioids. MethodsA consecutive sample of patients who were switched from strong opioids to methadone in a period of 1 year was surveyed. Informed cons...

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“…In another study, female sex, medications interfering, hypomagnesemia, structural cardiac disorder and hypokalemia were considered as the risk factors for QTc prolongation and TdP (24). Cruciani et al (25) showed that 33% had QTc prolongation (males 40%, females 20%; P = 0.03) and a marked dose response was obtained in males on methadone < 12 months (r = 0.60, P = 0.02). They also suggested that methadone may prolong the QTc interval in specific subpopulations but it poses little risk of serious prolongation.…”

Section: Discussionmentioning

confidence: 98%

Relationship between Corrected-QT Intervals and Other ECG Characteristics with Methadone Dose in Methadone Maintenance Treatment (MMT) Patients and Healthy Subjects: A Case- Control Study

et al. 2017

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Background: In this study we assessed the relationship between corrected-QT intervals and other ECG characteristics with methadone dose and other parameters in MMT patients and healthy subjects. Methods: This was a case-control study which was carried out on patients underwent MMT and healthy control group who had been referred to Ebne-Sina academic hospital, Mashhad during 2014 -2015. At the time of the study, 40 patients who received MMT therapy for at least 6 months and 40 voluntary healthy subjects who matched on age and sex enrolled in the study. 12-lead ECG was performed for all the patients. Mean QT interval, PR interval and QRS duration in every 12 leads were documented for each patient in maximum. Results: To evaluate the patients, we divided 80 patients into two groups: 40 patients under treatment with Methadone and 40

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Measurement of QTc in Patients Receiving Chronic Methadone Therapy

Cited by 103 publications

References 16 publications

Effects of Methadone on Corrected Q-T Interval Prolongation in Critically Ill Children

Effects of Methadone on Corrected Q-T Interval Prolongation in Critically Ill Children

Changes of QTc interval after opioid switching to oral methadone

Relationship between Corrected-QT Intervals and Other ECG Characteristics with Methadone Dose in Methadone Maintenance Treatment (MMT) Patients and Healthy Subjects: A Case- Control Study

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