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Drug-Induced Sleep Endoscopy (DISE) with Target Controlled Infusion (TCI) and Bispectral Analysis in Obstructive Sleep Apnea
Published on: December 6, 2016
Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea
Anthony G Doufas1, Lu Tian, Kevin A Padrez
1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, USA. agdoufas@stanford.edu
Insights
Obstructive sleep apnea (OSA) increases opioid pain relief sensitivity due to nocturnal hypoxia. Biomarkers like IGFBP-1 and inflammatory mediators predict enhanced opioid effects in at-risk individuals.
Area of Science:
- Anesthesiology
- Sleep Medicine
- Pain Management
Background:
- Obstructive sleep apnea (OSA) involves recurrent nocturnal hypoxia and sleep disruption.
- Sleep fragmentation and hypoxemia can alter pain perception and opioid efficacy.
- Surgical patients with OSA face risks from opioid-induced airway compromise.
Purpose of the Study:
- To investigate pain processing and opioid analgesia in male volunteers at risk for OSA.
- To characterize the relationship between sleep parameters, hypoxia, inflammation, and pain sensitivity.
- To evaluate the impact of OSA risk on remifentanil's analgesic potency.
Main Methods:
- Assessed heat and cold pain thresholds/tolerances via polysomnography (PSG) and pain tests.
- Measured serum pro-inflammatory and hypoxia markers.
- Analyzed pain responses at baseline, placebo, and varying remifentanil concentrations using mixed-effects models.
Main Results:
- Lower lowest oxyhemoglobin saturation (SaO2) correlated with increased remifentanil analgesic sensitivity (P=0.0440).
- Higher insulin growth factor binding protein-1 (IGFBP-1) levels predicted greater opioid analgesic sensitivity (P=0.0013).
- Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) also predicted enhanced opioid potency.
Conclusions:
- Nocturnal hypoxemia in individuals at high risk for OSA enhances opioid analgesic potency.
- Serum hypoxia markers (e.g., IGFBP-1) and pro-inflammatory mediators predict increased opioid efficacy.
- Findings are relevant for managing pain in surgical OSA patients using opioids.
Background:
Obstructive sleep apnea (OSA) is characterized by recurrent nocturnal hypoxia and sleep disruption. Sleep fragmentation caused hyperalgesia in volunteers, while nocturnal hypoxemia enhanced morphine analgesic potency in children with OSA. This evidence directly relates to surgical OSA patients who are at risk for airway compromise due to postoperative use of opioids. Using accepted experimental pain models, we characterized pain processing and opioid analgesia in male volunteers recruited based on their risk for OSA.
Methods:
After approval from the Intitutional Review Board and informed consent, we assessed heat and cold pain thresholds and tolerances in volunteers after overnight polysomnography (PSG). Three pro-inflammatory and 3 hypoxia markers were determined in the serum. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 µg/ml), an μ-opioid agonist. Linear mixed effects regression models were employed to evaluate the association of 3 PSG descriptors [wake after sleep onset, number of sleep stage shifts, and lowest oxyhemoglobin saturation (SaO(2)) during sleep] and all serum markers with pain thresholds and tolerances at baseline, as well as their changes under remifentanil.
Results:
Forty-three volunteers (12 normal and 31 with a PSG-based diagnosis of OSA) were included in the analysis. The lower nadir SaO(2) and higher insulin growth factor binding protein-1 (IGFBP-1) were associated with higher analgesic sensitivity to remifentanil (SaO(2), P = 0.0440; IGFBP-1, P = 0.0013). Other pro-inflammatory mediators like interleukin-1β and tumor necrosis factor-α (TNF-α) were associated with an enhanced sensitivity to the opioid analgesic effect (IL-1β, P = 0.0218; TNF-α, P = 0.0276).
Conclusions:
Nocturnal hypoxemia in subjects at high risk for OSA was associated with an increased potency of opioid analgesia. A serum hypoxia marker (IGFBP-1) was associated with hypoalgesia and increased potency to opioid analgesia; other pro-inflammatory mediators also predicted an enhanced opioid potency.
Trial Registration:
Clinicaltrials.gov NCT00672737.
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