Respiratory and Sleep Effects of Remifentanil in Volunteers with Moderate Obstructive Sleep Apnea

There is concern that opioid-based analgesia will worsen sleep-related respiratory insufficiency in patients with obstructive sleep apnea (OSA), resulting in serious morbidity or mortality. However, there are no studies that directly address the merit of this concern. Consequently, the authors designed this study as the first prospective, double-blind, placebo-controlled investigation of opioid pharmacology in patients with documented OSA. Patients (n = 19) with moderate OSA documented by polysomnography (sleep study) were randomized to undergo an additional sleep study while receiving either a saline infusion or a remifentanil infusion (0.075 microg x kg x h). Sleep stages, apneas, hypopneas, and arterial hemoglobin oxygen saturation were continually recorded during saline or remifentanil infusion, and were compared with values obtained during the patients' earlier sleep study. Saline infusion had no effect on sleep or respiratory variables. In contrast, remifentanil increased Stage 1 sleep, markedly decreased rapid eye movement sleep, increased arousals from sleep, and decreased sleep efficiency. Remifentanil actually decreased the number of obstructive apneas, but markedly increased the number of central apneas. Arterial hemoglobin oxygen saturation was also significantly lower in OSA patients receiving remifentanil. The decrease in obstructive apneas likely resulted from the marked decrease in rapid eye movement sleep caused by remifentanil. Despite fewer obstructions, OSA was worse during remifentanil infusion because of a marked increase in the number of central apneas. These data suggest that caution is warranted when administering opioids to subjects with moderate OSA, but that the primary risk may be central apnea, not obstructive apnea.