PURPOSE: The incidence of adverse events during long term opioid therapy for conditions other than cancer pain is rising. There is an apparent relationship between dose magnitude and the incidence of overdose which suggests that overdose results from the therapy itself, independent of any inappropriate use of the medication. We have noted several patients admitted for acute on chronic respiratory failure which was largely due to high doses of methadone administered for the treatment of opioid dependence. Such respiratory depression could be a contributing factor to death associated with chronic opioid use.
METHODS: 100% of the charts of patients admitted to our institution from 11/1/10 through 2/28/11 were reviewed. All patients using MM were identified. Data on demographics, blood chemistries, echocardiography, methadone dose and concurrent illnesses at the time of admission were recorded for each patient. For each of the MM patients were chosen four age, sex and concurrent disease matched subjects from the non-MM patients admitted during the study period. The data of each matched group was averaged for comparison with that of the corresponding MM patient.
RESULTS: 3063 patients were admitted during the 4 months. 40 were using MM, 90+/-55 mg/day. There were 18 males and 22 females aged 47+/-9.8 yr. Urine testing was uniformly negative for any substance but methadone. Serum HCO3 (a marker for hypercapnea) was 30+/-3.4 meq/l in the MM patients and 25.5+/-1.0 in the controls. The mean pCO2 was 49.4+/- 9.3 torr in the MM patients, 35.5+/-2.2 in the controls. 25/28 echocardiograms of MM patients had enlarged right ventricles. The overall right ventricular diameter (RVD) was 2.5+/-0.25 cm in the MM group and 2.0+/-0.1 in the control group (nl<2.3). Right ventricular systolic pressure (RVSP) was measured in 11 of the methadone patients and was elevated in all. The mean RVSP was 45+/-7mmHg in the MM patients and 27+/-1.8 mm Hg in the controls (nl<30). There was a linear relationship between methadone dose and RVD and RVSP. There was no relationship between any of the parameters and either age or the presence of comorbidities. 6 methadone patients had sleep oximetry and all showed evidence of sleep apnea.
CONCLUSIONS: Patients using high dose methadone maintenance exhibit dose related respiratory depression and signs of pulmonary hypertension.
CLINICAL IMPLICATIONS: Patients using high dose methadone maintenance should be monitored carefully for the development of hypoventilation, pulmonary hypertension and sleep apnea.
DISCLOSURE: The following authors have nothing to disclose: William Marino, Joan Harigopalan
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