title: Methadone and Corrected QT Prolongation in Pain and Palliative Care Patients: A Case-Control Study.
abstract: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients.
  
  
  
  Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool.
  
  
  
  We performed a case-control study of adult inpatients receiving ME for pain management. Settings/Subjects: Adult inpatients receiving ME with a QTc >470 msec (males) and >480 msec (females) were matched 1:2 according to age, history of QTc prolongation, and gender with ME patients who did not have a prolonged QTc interval. QTc prolongation risk factors were collected for both groups. Covariates were analyzed using conditional logistic regression. Classification and regression tree analysis was used to identify the ME dose associated with QTc prolongation.
  
  
  
  Predictors of QTc prolongation included congestive heart failure (CHF) (OR: 11.9; 95% CI: 3.7-38.2; p < 0.00), peptic ulcer disease (PUD) (odds ratio [OR]: 8.3; 95% confidence interval [95% CI]: 2.4-28.9; p < 0.00), hypokalemia (OR: 6.5; 95% CI: 1.5-28.2; p < 0.01), rheumatologic diseases (OR: 4.7; 95% CI: 1.6-13.9; p < 0.00), taking medications with a known torsades de pointes (TdP) risk (OR: 4.4; 95% CI: 1.8-10.7; p < 0.01), malignancy (OR: 3.3; 95% CI: 1.2-9.3; p < 0.03), hypocalcemia (OR: 2.1; 95% CI: 0.9-4.8; p < 0.07), and ME doses >45 mg per day (OR: 1.9; 95% CI: 0.8-4.8; p < 0.16). Mild liver disease was protective against QTc prolongation (OR: 0.05; 95% CI: 0.0-0.46; p < 0.01).
  
  
  
  Predictors of QTc prolongation in our multivariate conditional logistic regression model included CHF, PUD, hypokalemia, rheumatologic disorders, use of medications with a known TdP risk, malignancy, hypocalcemia, and ME doses >45 mg per day.
authors.affiliation: 1 Department of Pharmacy Practice, Wegmans School of Pharmacy, St. John Fisher College , Rochester, New York.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Juba
authors.affiliation: 2 Department of Pharmacy, University of Rochester Medical Center-Strong Memorial Hospital , Rochester, New York.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Khadem
authors.affiliation: 1 Department of Pharmacy Practice, Wegmans School of Pharmacy, St. John Fisher College , Rochester, New York.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hutchinson
authors.affiliation: 1 Department of Pharmacy Practice, Wegmans School of Pharmacy, St. John Fisher College , Rochester, New York.
authors.forename: Jack E
authors.initials: JE
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use*; D000072716:Cancer Pain / Q000188:drug therapy*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D058850:Opiate Substitution Treatment; D010166:Palliative Care / Q000379:methods; D012307:Risk Factors
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone
keywords: QTc prolongation; methadone; pain; palliative care; risk factors