1. REVIEW Obstructive Sleep Apnea Syndrome and Perioperative Complications: A Systematic Review of the Literature J Clin Sleep Med 2012;8:199-207. Vasu TS, Grewal R, Doghramji K. 호흡기 내과 / R4 이민혜

2. Introduction Obstructive sleep apnea syndrome (OSAS) –Intermittent and recurrent episodes of partial or complete obstruction of the upper airway during sleep –Disrupt sleep architecture  fragmented sleep and daytime sleepiness –Associated with various health-related consequences: increased rate of motor vehicle accidents, hypertension, diabetes mellitus, congestive heart failure, stroke, and all-cause mortality Surgical patients with sleep apnea  increased risk of perioperative complications –Hypoxemia –Pneumonia –Difficult intubation –Myocardial infarction –Pulmonary embolism –Atelectasis –Cardiac arrhythmias –Unanticipated admission to the ICU

3. Epidemiology Prevalence: 2%~25% in the general population –Young et al. Defined as apnea-hypopnea index (AHI) ≥ 5/h  9%(women) and 24%(men) Defined as AHI ≥ 5/h and daytime sleepiness  2%(women) and 4%(men) –The National Sleep Foundation (NSF) Sleep in America 2005 Poll 1/4 Americans are at high risk of having sleep apnea based on the Berlin Questionnaire The prevalence of sleep apnea is much higher in surgical patients and depends on the type of surgery –Bariatric surgery population: > 70%  formal sleep evaluation recommended –Patients who are coming for general surgery: higher prevalence of sleep apnea –Chung et al.: Berlin Questionnaire, 24% of surgical patients were at high risk for sleep apnea –Vasu et al.: STOP-BANG Questionnaire, elective surgery  41%(high risk for sleep apnea) –In a cross-sectional study, 39 patients underwent nocturnal polysomnography (NPSG) prior to undergoing epilepsy surgery  1/3 patients had sleep apnea –In another study, the prevalence of sleep apnea was found to be 64% in a small population of patients undergoing surgery for intracranial tumor –In an observational study, Finkel et al. noted that > 80% of surgical patients were unaware that they had sleep apnea prior to undergoing surgery

4. Pathophysiology Impact of Sedation, Anesthesia, and Opioids Surgical patients receive sedation, anesthesia, and opioids during the perioperative period –Increase pharyngeal collapse –Decrease ventilatory response –Impair the arousal response –Leading to worsening of sleep apnea Sleep apnea: negative pressure of inspiratory muscles exceeds the upper airway dilator muscle activity (critical airway pressure) General anesthetics: decrease the upper airway dilator muscle activity in a dose-dependent manner  increase upper airway collapsibility Increased upper airway collapsibility  secondary to progressive decrease in the genioglossus muscle activity Upper airway collapsibility  worsening of the sleep apnea  increase the risk of hypoxemia, cardiac arrhythmias, and postoperative complications

5. Pathophysiology Impact of Sedation, Anesthesia, and Opioids Anesthetic medicines: impair the arousal response Anesthetics, opioids, hypnotics, and benzodiazepines: respiratory depression, decrease the minute ventilation Halothane reduces the ventilatory response to hypoxemia and hypercapnia in humans: selective effect of halothane on the peripheral chemoreflex loop Similarly, a subanesthetic dose of isoflurane: reduce the hypoxemic ventilatory response via peripheral chemoreceptors Opioids: impair ventilatory function by affecting both peripheral and central carbon dioxide chemoreflex loops Small doses of narcotics administered epidurally: depress the respiratory function, even in healthy adults Morphine has been shown to reduce hypoxic and hypercapnic ventilatory response in women, but not in men/ On the other hand, it raises the apneic threshold in men with no effect in women The combination of opiates and benzodiazepines: cause more significant episodes of hypoxemia and apnea

6. Pathophysiology REM Sleep Rebound Surgical patients: highly fragmented sleep on postoperative nights 1 or 2, with a significant reduction in REM sleep, slow wave sleep, and increased stage 2 NREM sleep These sleep disturbances usually occur secondary to surgical stress, pain, and the use of anesthetic and pain medications The stress of surgical trauma: increased level of cortisol, and cortisol has been shown to cause significant reduction in REM sleep Surgical trauma: induce significant inflammatory response, increased level of pro-inflammatory markers like TNF-α, IL-1, and IL-6  especially IL-1 and TNF-α: suppress REM sleep

7. Pathophysiology REM Sleep Rebound REM sleep is usually absent on postoperative nights 1 and 2 Profound increase in the amount and density of REM sleep(REM sleep rebound) during recovery nights 3 to 5 The episodes of sleep disordered breathing and hypoxemia are usually worse during REM sleep due to hypotonia and unstable breathing REM sleep: increased sympathetic discharge leading to tachycardia, hemodynamic instability, and myocardial ischemia Most complications after the surgery occur in the first postoperative week, especially between postoperative days 2 and 5, corresponding to periods of REM rebound Episodes of hypoxemia after surgery: mostly between postoperative nights 2 to 5  may increase the risk of wound infection, cerebral dysfunction, and cardiac arrhythmias In an observational study at Mayo Clinic, the incidence of acute myocardial infarction peaked on day 3 after surgery Similarly, episodes of delirium, nightmares, and psychomotor dysfunction: occur between postoperative nights 3 to 5

8. Evidence on Sleep Apnea as a Risk Factor for Perioperative Complications

9. How to Identify Patients with Sleep Apnea Nocturnal polysomnography (NPSG): gold standard to identify patients with obstructive sleep apnea –Difficult to implement due to a variety of factors, including its prolongation of the process of surgery and contribution to the overall cost –In many hospital settings: not be readily available Other methods –Questionnaires –Nocturnal pulse oximetry –Home sleep testing

10. How to Identify Patients with Sleep Apnea Questionnaires 3 of these questionnaires have been validated in the surgical population –Berlin Questionnaire –ASA checklist –STOP-BANG questionnaire Abrishami et al. conducted a systematic review to identify and evaluate the different screening questionnaires for sleep apnea –Berlin and STOP-BANG questionnaires: high sensitivities and specificities in predicting moderate or severe sleep apnea –STOP and STOP-BANG questionnaires: highest methodological validity, and these questionnaires are very easy to use Korean J Otorhinolaryngol-Head Neck Surg 2010;53:768-72.

11. How to Identify Patients with Sleep Apnea Questionnaires Berlin questionnaire: most widely used questionnaire –Sensitivity of 86% and positive predictive value of 89% for identifying patients with respiratory disturbance index (RDI) > 5/h in the primary care clinic –Chung et al. validated the Berlin questionnaire in surgical population: sensitivity of 74.3% to 79.5% and a negative predictive value of 76% to 89.3% in identifying patients with moderate-to-severe OSA –However, complex scoring system and time consuming Korean J Otorhinolaryngol-Head Neck Surg 2010;53:768-72.

12. How to Identify Patients with Sleep Apnea Questionnaires American Society of Anesthesiologists (ASA) checklist –12 items for adults and 14 items for children –Sensitivity of 78.6% to 87.2% and a negative predictive value of 72.7% to 90.9% in identifying surgical patients with moderate-to severe OSA STOP-BANG (Snoring, Tiredness during daytime, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, Gender) questionnaire –Concise, self-administered, and easy-to-use questionnaire that consists of 8 yes/no questions –The sensitivity: AHI > 5, > 15, and > 30 cutoff values was 83.6%, 92.9%, and 100%, respectively; corresponding negative predictive values (NPV) were 60.8%, 90.2%, and 100% Anesthesiology.2008;108:812- 21

13. How to Identify Patients with Sleep Apnea Nocturnal Pulse Oximetry Used for the screening of OSA Malbois et al. compared the sensitivity of nocturnal oximetry to ambulatory monitoring in order to identify patients with sleep apnea prior to undergoing bariatric surgery –Nocturnal oximetry with a 3% desaturation index as a screening tool for OSA could rule out significant OSA (AHI > 10) and also detect patients with severe OSA This cheap and widely available technique could accelerate preoperative work-up of these patients

14. How to Identify Patients with Sleep Apnea Home Sleep Testing Ambulatory monitoring is another modality that can be employed in patients at high risk for sleep apnea However, this is recommended only in patients with a high pre-test probability of sleep apnea and is not recommended in patients with coexisting cardiopulmonary complications Limitations in terms of ease of use by the patients It would be helpful to evaluate this modality of diagnosing OSAS in specific surgical patient population

15. Perioperative Management

16. Evidence for Perioperative use of CPAP CPAP –Act as a pneumatic splint and helps in opening the collapsed upper airway at night –Improves functional residual capacity (FRC) and oxygenation with reduction in work of breathing –Improve excessive daytime sleepiness in patients with OSAS Some evidence that the perioperative use of CPAP may help in reducing postoperative complications –Gupta et al.: case control study, CPAP had reduced rate of complications and also decreased hospital length of stay –Liao et al.: not compliant with their CPAP, greatest risk of having postoperative complications –Squadron et al.: use of CPAP, reduction in the incidence of endotracheal intubation and other severe complications in patients who develop hypoxemia after elective major abdominal surgery –Kingen-Milles et al.: randomized controlled trial, prophylactic use of nasal CPAP, reduction in pulmonary complications and hospital length of stay in patients undergoing thoracoabdominal aortic aneurysm repair –Zarbock et al.: significant reduction in the rate of pulmonary complications with the prophylactic use of nasal CPAP in patients undergoing elective cardiac surgery –A recent meta-analysis of nine randomized controlled trials in the abdominal surgical population, reduction in the rate of atelectasis, postoperative pulmonary complications, and pneumonia with the perioperative use of CPAP

17. Conclusions Obstructive sleep apnea syndrome (OSAS) is a common type of sleep disordered breathing, with a high prevalence in the surgical population The majority of patients with sleep apnea are undiagnosed and are therefore unaware of their OSAS at the time of the surgery These patients are at increased risk for perioperative complications Sedation, anesthesia, opioids, and REM sleep rebound have been shown to cause worsening of sleep apnea in the perioperative period that may lead to increase in the rate of perioperative complications It is important to identify these patients preoperatively so that appropriate actions can be taken during their perioperative care Screening questionnaires such as the Berlin, STOP-BANG, or ASA checklist are easy to administer preoperatively and have been shown to identify high-risk patients There should be a standard protocol for the perioperative management of high-risk patients in order to reduce the rate of complications These high-risk patients should also have a formal sleep evaluation for the long-term management of their sleep apnea after the discharge from the hospital

18. Editorials Empiric Postoperative Autotitrating Positive Airway Pressure Therapy: Generating Evidence in the Perioperative Care of Patients at Risk for Obstructive Sleep Apnea Chest 2013;144:5-7. Mokhlesi B.

19. –Enrolled 86 CPAP-naive patients, elective total knee or total hip arthroplasty, high risk for having OSA –Standard care vs. Standard care + empirical APAP therapy –Primary end point: hospital length of stay (LOS) –Secondary end points: postoperative complications –Intention-to-treat analysis: no significant difference in the primary or secondary outcomes –Post hoc analyses: moderate or severe OSA (AHI ≥ 15), the LOS increased by 1 day in patients treated with APAP (4 days vs 5 days; P =.02) –The LOS increased by 1 day in patients with usage > 4 h per night compared with those with < 4 h per night ( P =.04) –APAP therapy group: significantly longer period of time with oxygen saturation below 90% on the first postoperative day –Although the cause of the hypoxemia remains unclear, may have been related to poor blending of supplemental oxygen with air while on APAP compared with supplemental oxygen delivered by nasal cannula in the standard of care group Chest. 2013;144(1):72-78.

20. First and foremost, the authors are to be commended for undertaking the monumental task of screening 2,375 patients over a 4-year period and implementing a rigorous and well- designed research protocol Limitations –Inability to achieve adequate statistical power because of low enrollment (94% of screened patients refused participation) –Although APAP improved OSA, it did not lead to a full resolution of sleep-disordered breathing –Unfortunately, the APAP units were not equipped with forced oscillation technology to distinguish between obstructive and central apneas –Patients randomized to APAP therapy were not fully adherent to therapy (median usage of 185 min per night) –APAP may have adversely impacted sleep duration and consolidation in these CPAP-naive patients, which in turn may have negatively impacted their postoperative recovery

21. Many important and clinically relevant questions remain unanswered –How should OSA be diagnosed in high-risk presurgical patients? –Which subgroups of patients with sleep-disordered breathing are more likely to benefit from PAP therapy? –When is the most appropriate time to implement PAP therapy? –Can PAP adherence be improved during the perioperative period? –What are the obstacles to implementing a postoperative APAP protocol? –Would the benefits of empirical APAP therapy differ between highly staffed academic tertiary care centers and nonacademic settings? –What therapeutic options should be explored in PAP-intolerant patients? Perioperative PAP therapy should be strongly considered in patients with an established diagnosis of clinically significant OSA as well as in patients suspected of having severe forms of sleep-disordered breathing based on validated screening tools Given the large volume of elective surgeries performed globally, implementation of systematic screening and empirical APAP therapy in those patients at risk for OSA would impose a significant cost burden, underlying the urgency for further clinical research to determine whether PAP therapy is helpful or harmful in the immediate postoperative period