Central sleep apnea in stable methadone maintenance treatment patients

Methadone, a long-acting mu-opioid agonist, is an effective treatment for heroin addiction. Our previous data show that 6 of 10 methadone maintenance treatment (MMT) patients had central sleep apnea (CSA). This study aims to confirm these results and to investigate the pathogenesis of the CSA.

Twenty-five male and 25 female MMT patients and 20 age-, sex-, and body mass index (BMI)-matched normal subjects were tested with polysomnography, blood toxicology, and ventilatory responses to hypoxia and hypercapnia. Resting cardiorespiratory tests were performed in the MMT group

MMT patients and normal subjects were 35 +/- 9 years old (mean +/- SD), and BMI values were 27 +/- 6 kg/m2 and 27 +/- 5 kg/m2, respectively. Thirty percent of MMT patients had a central apnea index (CAI) > 5, and 20% had a CAI > 10. All normal subjects had a CAI < 1, and no difference was found in obstructive apnea-hypopnea index between the two groups. Methadone blood concentration was the only significant variable (t = 2.33, p = 0.025) associated with CAI and explains 12% of the variance. Awake Pa(CO2), antidepressant use, reduced ventilatory response to hypercapnia, and widened awake alveolar-arterial oxygen pressure gradient together explain a further 17% of the CAI variance.

Thirty percent of stable MMT patients have CSA, a minority of which can be explained by blood methadone concentration. Other physiologic variables may also play a role in the pathogenesis of CSA in MMT patients, and further research is indicated in this area.