Ventilatory responses to hypoxia and hypercapnia in stable methadone maintenance treatment patients

Rationale: Methadone is a long-acting μ-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 HCVH and increased HVR were found in MMT patients compared to normal subjects (HCVR [mean ± SD], 1.27 ± 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 [SpO₂] vs 1.12 ± 0.7 L/min/% SpO₂ [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), PaCO₂ (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 PaCO₂ (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.