Obstructive Sleep Apnea Predicts Adverse Perioperative Outcome: Evidence for an Association between Obstructive Sleep Apnea and Delirium

Delirium is an acute, fluctuating impairment in attention and cognition. POD affects up to 70% of patients older than 65 yr undergoing surgery, with rates varying by the type of patients, surgery and diagnostic instrument.2A particularly high incidence of POD has been reported following hip surgery and cardiac surgery, where it is a strong independent predictor of mortality up to 10 yr postoperatively.3Consequently, it is critical to identify potentially reversible causes of POD and to further elucidate the mechanisms that underlie it.

Although obesity has clearly been linked with an increased incidence of perioperative complications, including wound infections and breakdown, venous thromboembolism, adverse cardiac events, and respiratory complications, some (but not all) data support the view that OSA, independent of obesity, increases perioperative risks. Potential mechanism underlying the increased risk of perioperative complications in OSA include, but are not limited to, drug effects, inflammation, and hypercoagulobility, as well as perioperative changes in sleep architecture.4 

The mechanism of the potential link between OSA and POD cannot be directly addressed in the present study, but it is tempting to speculate on possible pathways (fig. 1). Frequent episodes of airway collapse in OSA lead to hypoxia, disrupted sleep, sleep inertia, daytime sleepiness, and increased arousal threshold from sleep, all of which may be considered as potential precipitating and/or augmenting factors of delirium.2,5Indeed, it is intriguing to note that OSA patients appear to be most vulnerable to hypoxia on postoperative night 2 or 3, the time interval during which postoperative delirium most typically presents.

OSA is also, in part, an inflammatory disorder.6Evidence suggests that chronic intermittent hypoxia and, possibly, sleep loss and fragmentation associated with OSA, increase the levels of various markers of inflammation and oxidative stress.6Inflammation has been implicated in the pathophysiology of delirium, based on increased levels of proinflammatory cytokines and increased levels of C-reactive protein.7Accordingly, it is possible that perioperative inflammation in combination with the baseline hyperinflammatory state associated with OSA may lead to delirium.

Previous work including studies using serum markers of neuronal damage also suggest that delirium may also be ischemically mediated. OSA patients show distinct reversible brain structural changes,8and OSA is an independent risk factor for stroke.9It may be that patients with OSA are more vulnerable to perioperative brain ischemia leading to POD. Also, along this line, sleep disorder breathing has recently been linked to the development of cognitive impairment. Patients with cognitive impairment have significantly higher rates of delirium, another possible pathway linking OSA and POD.10 

All of this said, there are significant methodologic limitations to the present study, suggesting that the observed association between OSA and POD should be considered “hypothesis-generating” rather than “proven.” The association was not a prespecified hypothesis, but rather arose in the setting of screening approximately 20 different patient characteristics/comorbidities for an association with POD. This approach increases the chance of making a type-1 error. Also, as the sample size is relatively small and the number of outcomes few, it is not possible for the authors to perform a rigorous multivariate regression analysis to fully account for the factors that might confound a causal relationship between OSA and POD. Further, there are important known risk factors for POD, including postoperative anemia, electrolyte abnormalities, renal dysfunction, infection, benzodiazepine and opiate use, and postoperative pain scores that were not collected in the present study and which therefore could not be analyzed as potential confounders.

The present study does, however, provide a strong rationale for adequately powered investigations specifically designed to test the hypothesis that OSA contributes to POD. Future studies will also need to establish whether strategies that mitigate the perioperative consequences of OSA, including titrating narcotics and neuromuscular blocking agents carefully to minimize residual effects on upper airway muscle strength, as well as promoting early mobilization, and utilizing continous positive airway pressure,11,– 13decrease the occurrence of POD. If it turns out that OSA does cause POD and that there are effective strategies to prevent it from doing so, than the paper by Flink et al.  will be a landmark in the quest to address this most challenging perioperative complication.