Opioid Sensitivity in Children with and without Obstructive Sleep Apnea

Abstract

C hildhood 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 aBStract 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 nonobstructive sleep apnea and obstructive sleep apnea patients. No differences in the relationship between remifentanil concentra...

Opioids for acute pain management in children

“…Obstructive sleep apnoea, defined as partial or complete obstruction of the upper airway during sleep, is common in children, and is the main indication for children undergoing adenoidectomy with or without tonsillectomy. 57 Most children in Australia and New Zealand do not undergo pre-tonsillectomy polysomnography and only the very severe will be on continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) support. Children with OSA are more likely to have post-tonsillectomy respiratory complications including oxygen desaturations, obstructive episodes and apnoeic adverse events when compared with children without OSA.…”

“…Children with OSA are more likely to have post-tonsillectomy respiratory complications including oxygen desaturations, obstructive episodes and apnoeic adverse events when compared with children without OSA. 57,58 This has implications for postoperative disposition and monitoring, opioid dosing and discharge opioid prescribing. While CPAP or BiPAP can mitigate these risks, it is often poorly tolerated by children and difficult to introduce de novo postoperatively without sedation.…”

“…58 If these children are overweight or obese, a pharmacokinetic discrepancy between the expected and actual opioid plasma concentrations may also play a role. 57 The synergistic effect of the opioids combined with hypno-sedative medications used for general anaesthesia (both for tonsillectomy and other operations) is clinically relevant when loading and re-dosing postoperative opioids in children with OSA. Judicious titration is therefore warranted, particularly when managing these children for other procedures and in the outpatient environment.…”

Influence of genetic variants on remifentanil sensitivity in Chinese women

“…Remifentanil was infused at a constant rate of 0.2 μg/(kg min) for 15 min. 20,23 The PPT and PPTO were measured before and after the infusion. Meanwhile, the OAA/S score was recorded every 60s after infusion and the changes in SpO 2 were observed closely.…”

Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression

“…However, we ask whether nociceptive or conversational stimulation might obscure recognizable indicators of opioid toxicity, rendering common clinical parameters inadequately sensitive. We propose that an approach involving pupillary testing [ 6 – 8 ] may be more reliable than conventional measures in assessing opioid effect.…”