Central Sleep Apnea in Stable Methadone Maintenance Treatment Patients

doi:10.1378/chest.128.3.1348

Chest

Volume 128, Issue 3, September 2005, Pages 1348-1356

https://doi.org/10.1378/chest.128.3.1348 Get rights and content

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.

Section snippets

Subject Selection

MMT patients and control subjects were recruited through advertisements placed in pharmacies licensed for distributing methadone across the inner suburbs of Melbourne, Australia. The advertisement did not mention the research topic. Patients included for study had been in an MMT program for ≥ 2 months and receiving a stable dose of methadone. Normal subjects did not have a history of substance abuse, and none were receiving opioids at the time of study. All patients underwent a screening

Results

Sixty-two MMT patients consented to take part in the study. Three patients were excluded due to poorly controlled asthma. One patient was excluded because of previous severe head injury. Another patient was excluded because of pregnancy. In addition, two patients withdrew from the study due to family commitments. Four patients were unable to be contacted after consenting to participate in the study. One MMT patient died of drug overdose prior to performing study tests. This left 50 MMT patients

Discussion

To our knowledge, this is the first study to assess the prevalence of SDB in clinically stable MMT patients in a large number of patients and to have compared the data with a matched non-opioid-using control group. We have confirmed our previous findings of a high prevalence of CSA in stable MMT patients.¹⁷ Our study has also shown that clinically stable MMT patients do not have significantly different obstructive SDB when compared to control subjects and that the difference in AHI found

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This study was supported by the Australian Postgraduate Awards (D.W.), the Western Hospital Education, Equipment and Research Fund, and the Western Hospital Liver Research Fund.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

This study was supported by the Australian Postgraduate Awards (D.W.), the Western Hospital Education, Equipment and Research Fund, and the Western Hospital Liver Research Fund.

View full text

Chest

Clinical InvestigationsCentral Sleep Apnea in Stable Methadone Maintenance Treatment Patients

Study objectives

Methods

Results

Conclusions

Section snippets

Subject Selection

Results

Discussion

Chest

Clin Chest Med

Forensic Sci Int

J Emerg Med

Biol Psychiatry

Psychiatry Res

Respir Physiol

J Pediatr

Effective medical treatment of opiate addiction. National Consensus Development Panel on Effective Medical Treatment of Opiate Addiction

JAMA

Methadone maintenance in Australia

J Drug Issues

Retention in methadone maintenance and heroin addicts’ risk of death

Addiction

All-cause mortality rate and risk of dying in methadone maintenance treatment in New South Wales in 1990–95. International Opioid Overdose Symposium

Deaths in the first two weeks of maintenance treatment in NSW in 1994: identifying cases of iatrogenic toxicity

Drug Alcohol Rev

Mechanisms of fatal opioid overdose

Addiction

Mortality associated with New South Wales methadone programs in 1994: lives lost and saved

Med J Aust

Intravenous opioid anesthetics

Diminished ventilatory response to hypoxia and hypercapnia after morphine in normal man

N Engl J Med

Influences of morphine on the ventilatory response to isocapnic hypoxia

Anesthesiology

Effects of intrathecal morphine on the ventilatory response to hypoxia

N Engl J Med

Decreased carbon dioxide sensitivity in infants of substance-abusing mothers

Pediatrics

Sudden infant death syndrome in infants of substance-abusing mothers

J Pediatr

Responses to hypoxia and hypercapnia in infants of substance-abusing mothers

J Pediatr

Sleep-disordered breathing in stable methadone programme patients: a pilot study

Addiction

A new method for measuring daytime sleepiness: the Epworth sleepiness scale

Sleep

AASM Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement technique in clinical research

Sleep

American Sleep Disorders Association. EEG arousals: scoring rules and examples; a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association

Sleep

A clinical method for assessing the ventilatory response to hypoxia

Am Rev Respir Dis

Clinical Investigations
Central Sleep Apnea in Stable Methadone Maintenance Treatment Patients