Once used only as third-line therapy for chronic pain management, methadone is now being used as first- and second-line therapy in palliative care. The risks and stigma associated with methadone use are known, but difficulties with dosing methadone and lack of an established conversion protocol from other opiates have limited the access for patient populations who could potentially benefit from this medication. For palliative care patients, the benefits of methadone can far outweigh its risks. This article provides an overview and specific recommendations on the use of parenteral methadone in pain and palliative care, with a focus on the transition from hospital to home/hospice care. The goal of this consensus guideline is to assist clinicians who are providing chronic pain management in acute care hospital and nonhospital settings (i.e., hospice, long-term care facilities, and community) for patients with life-limiting illnesses, where the goals of care are focused on comfort (i.e., palliative care). The recommendations in this article intend to promote a standard of care involving the use of intravenous methadone with the aim of reaching a broader population of patients for whom this drug would provide important benefits.
Recent reports suggest that methadone may prolong the QTc interval and cause torsades de pointes. This study was conducted to evaluate the prevalence of QTc prolongation during oral methadone therapy and identify factors associated with prolongation. Patients receiving oral methadone as treatment for chronic pain or addiction were eligible for the study. One hundred four patients who were receiving > or = 20 mg methadone per day for > or = 2 weeks underwent electrocardiograms to measure QTc interval duration. Sixty-three (61%) patients were male and 63 (61%) were receiving methadone maintenance for opioid addiction. The mean (+/- SD) age was 45.3 +/- 9.4 years. The median (range) methadone dose was 110 mg/day (20-1200 mg/day); median (range) number of months on methadone was 12.5 months (1-444 months). The median (range) QTc interval was 428 msec (396-494 msec). Thirty-three percent had QTc prolongation (males 40%, females 20%; P=0.03). No patient had a QTc longer than 500 msec. Significant dose response was observed in males on methadone <12 months (rho=0.60, P=0.02). Our study suggests that methadone may prolong the QTc interval in specific subpopulations but poses little risk of serious prolongation.
Nutritional factors are among the postulated causes of fatigue, a highly prevalent symptom in the cancer population, with serious impact on patients' quality of life. Deficiency of the micronutrient carnitine may play a role by reducing energy production through fatty acid oxidation. We present preliminary data of an open-label, dose-finding study to determine safety and maximally tolerated dose (MTD) of 1 week of L-carnitine supplementation in cancer patients with fatigue and carnitine deficiency. Patients who met inclusion/exclusion criteria underwent carnitine level determination. Eighty-three percent of these patients (15/18) had carnitine deficiency. Preliminary data analysis of 13 patients showed that total carnitine increased from 30.0 +/- 6.9 to 41.0 +/- 12.1 (mean +/- SD) after 1 week of supplementation (P = 0.01), and free carnitine increased from 24.3 +/- 6.1 to 33.8 +/- 9.8 (P = 0.004). Outcome measures were fatigue (BFI score), depression (CES-D), sleep disruption (ESS), and performance status (Karnofsky). Median (min, max) BFI score at baseline was 73 (46, 82) versus 50 (3, 82) after 1-week supplementation (P = 0.009). CES-D score at baseline was 29 (16, 42) and 22 (8, 32) after 1 week (P = 0.028). ESS at baseline was 46.5 (0, 69) and 30.4 (0, 72) after 1 week (P = 0.015). Karnofsky score did not change significantly (P = 0.38). We are currently conducting a randomized, double-blind, placebo-controlled study to rigorously assess the role of L-carnitine for the treatment of fatigue and depression in cancer patients.
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