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Central Sleep Apnea in Stable Methadone Maintenance Treatment Patients^*

^* From the Department of Respiratory & Sleep Disorders Medicine (Drs. Wang, Teichtahl, and Cunnington, and Ms. Cherry), Drug and Alcohol Service (Dr. Kronborg and Ms. Goodman), Western Hospital; and Victorian Institute of Forensic Medicine (Dr. Drummer), Victoria, Australia.

Correspondence to: Harry Teichtahl, MBBS, Department of Respiratory & Sleep Disorders Medicine, Western Hospital, Gordon St, Footscray, Victoria, Australia 3011; e-mail: harry.teichtahl{at}wh.org.au

Study objectives: Methadone, a long-acting µ-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.

Methods: 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

Results: 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 PaCO₂, antidepressant use, reduced ventilatory response to hypercapnia, and widened awake alveolar-arterial oxygen pressure gradient together explain a further 17% of the CAI variance.

Conclusions: 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.

Key Words: central sleep apnea • hypercapnic ventilatory response • hypoxic ventilatory response • methadone

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