Opioid Sensitivity in Children With and Without Obstructive Sleep Apnea

Michael C. Montana, M.D., Ph.D.; Lindsay Juriga, B.S.; Anshuman Sharma, M.D.; Evan D. Kharasch, M.D., Ph.D.


Anesthesiology. 2019;130(6):936-945. 

In This Article

Abstract and Introduction


Background: Opioids are a mainstay of perioperative analgesia. Opioid use in children with obstructive sleep apnea is challenging because of assumptions for increased opioid sensitivity and assumed risk for opioid-induced respiratory depression compared to children without obstructive sleep apnea. These assumptions have not been rigorously tested. This investigation tested the hypothesis that children with obstructive sleep apnea have an increased pharmacodynamic sensitivity to the miotic and respiratory depressant effects of the prototypic μ-opioid agonist remifentanil.

Methods: Children (8 to 14 yr) with or without obstructive sleep apnea were administered a 15-min, fixed-rate remifentanil infusion (0.05, 0.1, or 0.15 μg · kg−1 · min−1). Each dose group had five patients with and five without obstructive sleep apnea. Plasma remifentanil concentrations were measured by tandem liquid chromatography mass spectrometry. Remifentanil effects were measured via miosis, respiratory rate, and end-expired carbon dioxide. Remifentanil pharmacodynamics (miosis vs. plasma concentration) were compared in children with or without obstructive sleep apnea.

Results: Remifentanil administration resulted in miosis in both non-obstructive sleep apnea and obstructive sleep apnea patients. No differences in the relationship between remifentanil concentration and miosis were seen between the two groups at any of the doses administered. The administered dose of remifentanil did not affect respiratory rate or end-expired carbon dioxide in either group.

Conclusions: No differences in the remifentanil concentration–miosis relation were seen in children with or without obstructive sleep apnea. The dose and duration of remifentanil administered did not alter ventilatory parameters in either group.


Childhood obstructive sleep apnea, defined by periodic, partial or complete obstruction of the upper airway during sleep, is a common disorder in pediatric patients, with a prevalence as high as 5.7%.[1,2] Children with obstructive sleep apnea often present for surgery and other procedures that require general anesthesia. In fact, the treatment of obstructive sleep apnea is the primary indication for more than 75% of children undergoing tonsillectomy with or without adenoidectomy.[3] Tonsillectomy is the most common pediatric operation performed in the United States, with more than 500,000 tonsillectomies performed annually.[4] Unfortunately, children at high risk for obstructive sleep apnea are three times more likely to have posttonsillectomy respiratory complications and apneic adverse events than children at low risk for obstructive sleep apnea,[5,6] and the rate of complications in patients with obstructive sleep apnea posttonsillectomy (16 to 27%) is substantially increased compared to that of the general pediatric postoperative population (0 to 1.3%).[7–11] These complications include oxygen desaturation, hypercapnia, obstructive apneas requiring continuous positive airway pressure or airway instrumentation, unexpected intensive care unit admission, and in rare cases, death.

Concerns for a heightened risk of opioid induced respiratory depression make the perioperative use of opioids in children with obstructive sleep apnea particularly challenging, if not controversial. It has been suggested that they may be at risk from overdose if administered what would otherwise be considered a normal dose of opioid.[6] Indeed, some pediatric surgical centers automatically reduce by half the opioid dose of patients undergoing tonsillectomy for a diagnosis of obstructive sleep apnea; published guidelines recommend decreasing opioid doses in all patients with sleep apnea, for fear of respiratory depression.[13]

Despite the widespread belief that obstructive sleep apnea increases opioid sensitivity, evidence to support this claim comes largely from either animal studies, or from human studies that are limited by their reliance on behavioral scores, rather than using objective markers of opioid sensitivity.[6,9,14–17] There is an unmet need to quantify whether there is opioid sensitivity in children with obstructive sleep apnea as compared to children without obstructive sleep apnea. The purpose of this study was to evaluate opioid pharmacodynamics in pediatric patients with and without obstructive sleep apnea, using remifentanil as the prototype opioid. We tested the hypothesis that children with obstructive sleep apnea have increased pharmacodynamic sensitivity to remifentanil, compared to those without obstructive sleep apnea. Pupil constriction (miosis) is the most sensitive measure of opioid effects at subanesthetic drug concentrations, and was used as an objective measure of opioid effect. Sensitivity to remifentanil was assessed using pupillometry, and also respiratory rate and end-expired carbon dioxide in pediatric patients with and without obstructive sleep apnea.