RATIONALE: Methadone is a long-acting mu-opioid and is an effective treatment for heroin addiction. Opioids depress respiration, and patients receiving methadone maintenance treatment (MMT) have higher mortality than the general population. Few studies have investigated ventilatory responses to both hypercapnia and hypoxia in these patients. STUDY OBJECTIVES: We measured hypercapnic ventilatory response (HCVR) and hypoxic ventilatory response (HVR) and investigated possible factors associated with both in clinically stable patients receiving MMT. DESIGN AND SETTING: Patients receiving long-term, stable doses of methadone recruited from a statewide MMT program, and normal, non-opioid-using subjects matched for age, sex, height, and body mass index were studied with HCVR and HVR. RESULTS: Fifty MMT patients and 20 normal subjects were studied, and significantly decreased HCVR and increased HVR were found in MMT patients compared to normal subjects (HCVR [mean +/- SD], l.27 +/- 0.61 L/min/mm Hg vs 1.64 +/- 0.57 L/min/mm Hg [p = 0.01]; HVR, 2.14 +/- 1.58 L/min/% arterial oxygen saturation measured by pulse oximetry [Sp(O2)] vs 1.12 +/- 0.7 L/min/% Sp(O2) [p = 0.008]). Respiratory rate and not tidal volume changes were the major physiologic responses contributing to both HCVR and HVR differences between the groups. Variables associated with HCVR in the MMT patients are as follows: obstructive sleep apnea/hypopnea index (t = 5.1, p = 0.00001), Pa(CO2) (t = - 3.6, p = 0.001), body height (t = 2.6, p = 0.01) and alveolar-arterial oxygen pressure gradient (t = 2.5, p = 0.02). Variables associated with HVR in MMT patients are body height (t = 3.2, p = 0.002) and Pa(CO2) (t = - 2.8, p = 0.008). CONCLUSIONS: Stable long-term MMT patients have blunted central and elevated peripheral chemoreceptor responses. The mechanisms and clinical significance of these findings need further investigation.
"In general, it is thought that for most patients the respiratory depressive effect of opioids dissipates over the first few days of exposure. Yet there is some evidence that patients who have been receiving long-term opioid therapy continue to exhibit signs of respiratory depression, specifically sleep-disordered breathing (Teichtahl et al., 2005; D. Wang & Teichtahl, 2007; D. Wang et al., 2008; J. Wang et al., 2006; Webster, Choi, Desai, Webster, & Grant, 2008). Additionally, when these patients are exposed to increased doses or a different opioid, they remain at risk of further respiratory compromise (Athanasos et al., 2006; Stoermer et al., 2003). "
"Cependant, cette tolérance semble partielle même après une longue durée d'usage. À cet effet, une série d'études a été réalisée afin de déterminer l'effet de la méthadone sur un certain nombre de paramètres respiratoires chez des patients traités chroniquement avec ce médicament, donc considérés pleinement tolérants (Teichtahl & al., 2005). Ainsi, 50 patients sous méthadone ont été comparés à 20 sujets témoins. "
"SDB, including obstructive and central sleep apnea, results in oxygen desaturations and sleep fragmentation and is associated with increased risk of coronary artery disease (Peker et al., 2006), hypertension (Peppard et al., 2000), stroke (Arzt et al., 2005), depression (Peppard et al., 2006), and death (Young et al., 2008). Central sleep apnea (CSA) – mediated by hypoventilation and reduced hypercapnic and hypoxic ventilatory responsiveness (Teichtahl et al., 2005) – has been reported to occur in 30-60% of MMT patients (Teichtahl et al., 2001; Wang et al., 2005). CSA has been associated with methadone dose and concomitant benzodiazepine use in a study of chronic pain patients taking methadone (Webster et al., 2008) and with methadone blood concentration in a sample of Australian MMT patients (Wang et al., 2005). "
[Show abstract][Hide abstract] ABSTRACT: Opioid-dependent patients treated with methadone have subjective sleep complaints and disrupted sleep on polysomnography (PSG). Previous studies of sleep-disordered breathing (SDB) in this population have focused on central sleep apnea (CSA). Our objectives were to: (1) characterize obstructive sleep apnea (OSA) and CSA in patients in methadone maintenance treatment (MMT) for opioid dependence; (2) examine factors associated with SDB in this population; and (3) investigate whether SDB was related to severity of subjective sleep complaints in MMT patients with subjective sleep disturbances.
We analyzed OSA and CSA from one night of home PSG in 71 patients who were in MMT for at least 3 months and had a Pittsburgh Sleep Quality Inventory (PSQI) score >5.
OSA (defined as obstructive apnea-hypopnea index (OAHI) > or = 5) was observed in 35.2% of our sample. OSA was associated with higher body mass index, longer duration in MMT, and non-Caucasian race. CSA (defined as central apnea index (CAI) > or = 5) was observed in 14.1% of the sample. CSA was not associated with methadone dose or concomitant drug use. Subjective sleep disturbance measured with the PSQI was not related to OSA or CSA.
SDB was common in this sample of MMT patients and OSA was more common than CSA. Given the lack of association between presence of SDB and severity of subjective sleep difficulties, factors other than sleep apnea must account for complaints of disturbed sleep in this population.
Drug and alcohol dependence 04/2010; 108(1-2):77-83. DOI:10.1016/j.drugalcdep.2009.11.019 · 3.42 Impact Factor
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