The QTc effect of low-dose methadone for chronic pain: a prospective pilot study.

OBJECTIVE: Methadone is associated with QT prolongation and serious cardiac complications, but this has been primarily demonstrated in opioid dependent patients receiving moderate to high doses. This study investigates the effect of low-dose methadone on the QTc interval in a chronic pain population. DESIGN AND SUBJECTS: We conducted a prospective cohort study in a chronic pain clinic including 82 patients receiving methadone and 102 patients receiving non-methadone opioid therapy. METHODS: We analyzed automated QTc calculations from 12-lead electrocardiograms at baseline and during the subsequent 6 months. The primary outcome of interest was the incidence of QTc greater than 470 milliseconds or an increase from baseline of greater than 60 milliseconds. RESULTS: The methadone group did not manifest an overall higher frequency of QTc > 470 milliseconds (6% for the methadone group vs 5% for controls, P = 0.722) or an increase in the QTc of > 60 milliseconds (4% for the methadone group vs 4% for controls, P = 0.94). In the first month after initiating methadone, patients demonstrated an increase in QTc compared to controls (5% for the methadone group vs 0% for the controls, P = 0.073) but the difference disappeared in the third and sixth months. CONCLUSION: Data from our chronic pain clinic support a potential association of QTc prolongation during the initiation of methadone, but this effect is small and short lived. We believe larger scale studies to further characterize the safety profile of low-dose methadone are warranted.

Protocol adherence when managing massive bleeding following complex cardiac surgery: a study design pilot.

OBJECTIVE: High-quality prospective trials of hemostatic "rescue" therapy to control massive bleeding in cardiac surgery are lacking. Wide variability in the care of patients with severe bleeding following cardiopulmonary bypass has precluded accurate comparison of treatment groups in previous studies. This study identified the use of a management protocol for early identification and uniform treatment of patients with massive bleeding for application in future trials of hemostatic rescue agents. DESIGN: A prospective, nonblinded, interventional feasibility study. SETTING: A university teaching hospital. PARTICIPANTS: Forty-three adult patients undergoing complex cardiac surgery. INTERVENTIONS: Study participants undergoing high-risk cardiac surgery received standardized treatment in accordance with a bleeding management protocol. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients (63%) had severe bleeding following heparin reversal and received conventional hemostatic resuscitation per protocol. Six patients had massive refractory bleeding. Compliance with protocol tasks was≥90% in 4 of 5 categories (anticoagulation, hemostasis scoring, recording blood loss, protocol transfusion) with the exception being submission of laboratory samples (76%). Measured bleeding rates (mL/h) following heparin reversal were clearly differentiated in those with hemostasis scores≥3 compared to those with scores≤2 (1,420±957 v 147±96; p<0.001). CONCLUSIONS: Adherence to a management protocol for massive bleeding is feasible and allows for homogenous treatment of patients before study arm randomization in future "rescue" therapy trials. The authors' protocol allowed for prompt and accurate identification of patients with severe bleeding refractory to conventional therapy. This review resolved several key barriers in the design of severe bleeding management trials.