Association of preoperative nocturnal hypoxaemia nadir and fentanyl ventilatory sensitivity in children with obstructive sleep apnoea undergoing general anaesthesia: a multicentre clinical cohort study

Abstract

Background: Obstructive sleep apnoea (OSA) has been thought to increase the risk of respiratory depression from opioids. The primary aim of this study was to assess whether preoperative hypoxaemia by sleep study pulse oximetry imparts greater opioid sensitivity.

Methods: A multicentre observational cohort study with in-cohort dose randomisation was performed in children 2-8 yr of age with OSA undergoing adenotonsillectomy. Ninety patients were assigned to one of two Spo₂ cohorts by preoperative sleep study Spo₂ nadir of < or ≥85% to receive fentanyl 1.0 or 1.5 μg kg^-1 (maximum 25 μg) after sevoflurane induction. The primary outcome was the extent of opioid-induced central ventilatory depression over time by Spo₂ status as defined by the differences in tidal volume, respiratory rate, end-tidal CO₂, and minute ventilation for 10 min after fentanyl administration when compared with pre-fentanyl baseline values. Secondary outcomes included assessment of body mass index, fentanyl dose, sex, age, and race on opioid-induced central ventilatory depression. Intention-to-treat and per protocol analysis were performed.

Results: Ninety patients underwent in-cohort randomisation (Spo₂ <85%; n=47 and Spo₂ ≥85%; n=43). Final per protocol analysis included 73 subjects, fentanyl 1.0 μg kg^-1 (Spo₂ <85%; n=36 and Spo₂ ≥85%; n=37) and 15 subjects, fentanyl 1.5 μg kg^-1 (Spo₂ <85%; n=9 and Spo₂ ≥85%; n=6). Multivariable mixed effect model for the primary outcomes (tidal volume, respiratory rate, end-tidal CO₂, and minute ventilation) from baseline to 10 min (as % change per minute) were not different between groups by Spo₂ nadir (< or ≥85%) and fentanyl dose for the intention-to-treat and per protocol analyses.

Conclusions: Single-dose fentanyl ventilatory effects in paediatric OSA patients during sevoflurane anaesthesia were not associated with preoperative nocturnal hypoxaemia nadir. Fentanyl dosing in children with OSA should not be determined by sleep study Spo₂ nadir.

Clinical trial registration: NCT05051189.

Keywords: intermittent hypoxaemia; obstructive sleep apnoea; opioid; paediatric anaesthesia.

Fig 1

Flow diagram of screening, enrolment, randomisation, intervention allocation, follow-up, and analysis of participants. Participants were divided into two cohorts based on baseline oxygen saturation: Spo₂ ≥85% (n=43) or Spo₂ <85% (n=47), and underwent within group randomisation to receive fentanyl either 1.0 μg kg⁻¹ or 1.5 μg kg⁻¹. The final intention-to-treat analysis included 39 subjects receiving fentanyl 1.0 μg kg⁻¹ (Spo₂ <85%; n=20 and Spo₂ ≥85%; n=19) and 49 subjects receiving fentanyl 1.5 μg kg⁻¹ (Spo₂ <85%; n=25 and Spo₂ ≥85%; n=24). The final per protocol analysis included 73 subjects receiving fentanyl 1.0 μg kg⁻¹ (Spo₂ <85%; n=36 and Spo₂ ≥85%; n=37) and reported in Table 1. Subjects in the 1.5 μg kg⁻¹ groups receiving the maximum fentanyl dose were reclassified and analysed in the per protocol analysis as described. Spo₂, oxygen saturation. ∗Patients within the Spo₂ <85% randomised to 1.5 μg kg⁻¹ and receiving the maximum dose of 25 μg per protocol, and reclassified and analysed with the Spo₂ <85% fentanyl 1.0 μg kg⁻¹ cohort in the per protocol analysis. ^†Patients within the Spo₂ ≥85% randomised to 1.5 μg kg⁻¹ and receiving the maximum dose of 25 μg per protocol, and reclassified and analysed with the Spo₂ ≥85% fentanyl 1.0 μg kg⁻¹ cohort in the per protocol analysis.

Fig 2

Percent change from baseline through study period for respiratory outcomes, by Spo₂ cohort for fentanyl dose of 1.0 μg kg⁻¹ in the per protocol analysis. CI, confidence interval; ETCO₂, end-tidal CO₂; Spo₂, oxygen saturation.