Association of obstructive sleep apnea and opioids use on adverse health outcomes: A population study of health administrative data

Abstract

Rationale Despite the high prevalence of obstructive sleep apnea (OSA) and concurrent use of opioid therapy, no large-scale population studies have investigated whether opioid use and pre-existing OSA may interact synergistically to increase the risk of adverse health consequences. To address this knowledge gap, we conducted a retrospective cohort study using provincial health administrative data to evaluate whether the combined presence of opioid use and OSA increases the risk of adverse health consequences, such as mortality, hospitalizations, and emergency department (ED) visits; and if it does, whether this co-occurrence has synergistic clinical relevance. Methods We included all adults who underwent a diagnostic sleep study in Ontario, Canada, between 2013 and 2016. Individuals were considered exposed to opioids if they filled a prescription that overlapped with the date of their sleep study (Opioid+). Individuals with at least a 50% probability of having a diagnosis of moderate to severe OSA (OSA+) were identified using a previously externally validated case-ascertainment model. The primary outcome was all-cause mortality; secondary outcomes were all-cause or ischemic heart disease hospitalizations, all-cause ED visits, and motor vehicle collisions (MVC) requiring hospital or ED visit. We used multivariable Cox regression models to compare hazards between four mutually exclusive groups: (1) Opioid+ OSA+; (2) Opioid+ OSA-; (3) Opioid- OSA+, and (4) OSA- Opioid- (reference for comparison). Relative excess risks due to interaction (RERI) were calculated to test for additive interaction. Results Of 300,663 adults who underwent a sleep study, 15,713 (5.2%) were considered as Opioid+ and 128,351 (42.7%) as OSA+. Over a median of two years, 6,223 (2.1%) died from any cause. Regardless of OSA status, opioid use at the date of the sleep study was associated with an increased hazard for all-cause mortality with the greatest hazard associated with Opioid+ OSA- (adjusted hazard ratio [aHR]: 1.75, 95% CI 1.57–1.94), but not Opioid+ OSA+ (aHR: 1.14, 95% CI 1.02–1.27) as hypothesized. Regardless of OSA status, opioid use at the date of the sleep study was associated with an increased hazard for all secondary outcomes. Opioid+ OSA+ was associated with the greatest hazards of all-cause hospitalizations (aHR 1.55, 95% CI 1.49–1.61) and MVC (aHR of 1.39; 95% CI 1.09–1.77); however, no statistically significant synergistic effects were observed. Conclusions Adults referred for sleep disorder assessment who used opioids had a significantly increased hazard of adverse health outcomes than those who did not, regardless of whether they had a high probability of moderate to severe OSA. The use of opioids and OSA was associated with the greatest hazard of all-cause hospitalizations and MVC requiring hospital or ED visit. The interaction of opioids and OSA did not confer a synergistic risk for poor outcomes.

Association between opioid prescription profiles and adverse health outcomes in opioid users referred for sleep disorder assessment: a secondary analysis of health administrative data

“…For example, clinical indications for the opioid prescription and results of the sleep study to identify a specific sleep disorder were not available. However, we showed previously a significantly increased hazard of all-cause mortality, hospitalizations and ED visits associated with opioid prescription vs. not, regardless of SDB presence (Kendzerska et al, 2022). Importantly, we demonstrated a higher prevalence of opioid use with a large proportion on longacting opioids, higher opioid dosages, and on benzodiazepines among adults referred for a sleep disorder assessment than the general population (Kendzerska et al, 2020), suggesting that these individuals are more susceptible to opioid-related adverse health consequences regardless of clinical indications for the opioid prescription or sleep disorder assessment.…”

“…Previously, we found that adults referred for a sleep disorder assessment who used prescription opioids had a significantly increased hazard of all-cause mortality, hospitalizations and ED visits compared to non-opioid users, regardless of SDB presence (Kendzerska et al, 2022). We also demonstrated a higher prevalence of opioid use with a large proportion on longacting opioids and higher opioid dosages, and a higher use of benzodiazepines among adults referred for a sleep disorder assessment than the general population (Kendzerska et al, 2020), suggesting that these individuals are more at risk for opioidrelated adverse health consequences.…”

“…SDBrelated treatment (positive airway pressure therapy or surgical interventions) in follow-up was considered as a time-varying covariate since the index date. Details on definitions are provided in the Supplementary Table 1 and our previous work (Kendzerska et al, 2020(Kendzerska et al, , 2022.…”

“…We also demonstrated a higher prevalence of opioid use with a large proportion on longacting opioids and higher opioid dosages, and a higher use of benzodiazepines among adults referred for a sleep disorder assessment than the general population (Kendzerska et al, 2020), suggesting that these individuals are more at risk for opioidrelated adverse health consequences. However, there is a need to further explore specific opioid characteristics associated with the greatest risk for both general and opioid-related adverse outcomes in opioid users referred for sleep disorder assessment (Kendzerska et al, 2022). Although the best therapeutic option for opioidrelated adverse health outcomes may be the withdrawal of opioids, health providers, especially primary care physicians, are often faced with the challenge of effectively managing the underlying disorder while ensuring individual safety, which requires evidence of a safe prescribing of opioids in this population.…”

Perioperative management of Obstructive Sleep Apnoea: Present themes and future directions

“…In a general surgical population, 3 months after surgery, around 7% of patients still use opioids that were initiated for postoperative pain [43]. Use of opioids in patients with OSA is associated with negative long-term health outcomes [44 ▪▪ ] and use of multimodal analgesia and engagement from specialist pain services are key in this patient group.…”