Obstructive sleep apnea (OSA) is characterized by periodic, partial or complete obstruction of the upper airway during sleep. The underlying pathophysiology of OSA is complex. However, it is generally accepted that the stability and patency of the upper airway is dependent upon the action of oropharyngeal dilator muscles, which are normally activated during each inspiration. These muscles can increase their activity to overcome obstruction during wakefulness, but the normal decrease in activity that occurs with sleep can allow the susceptible airway to collapse. Return of airway muscle activity appears to require either arousal, or a change of brain state to a lighter stage of sleep. Given the choice between sleeping and breathing, the un-medicated brain will choose breathing. The repetitive asphyxia causes repetitive arousals, resulting in fragmented sleep and daytime somnolence. Airway obstruction also causes sleep-associated oxygen desaturation (Chronic Intermittent Hypoxia, or CIH), episodic hypercarbia, and cardiovascular dysfunction.
The prevalence of OSA in adults in Western countries is estimated to be 5%. See Young, T., P. E. Peppard, and D. J. Gottlieb in their article entitled “Epidemiology of obstructive sleep apnea: a population health perspective”, published in American Journal of Respiratory and Critical Care Medicine, 2002, 165(9): p. 1217-39. This number is likely to increase as the population becomes older and more obese. The prevalence of obstructive sleep apnea in surgical patients has been estimated to be 1-9%, and may be even more common in certain populations. See Kaw, R., F. Michota, A. Jaffer, S. Ghamande, D. Auckley, and J. Golish in their article entitled “Unrecognized sleep apnea in the surgical patient: implications for the perioperative setting,” published in Chest, 2006. 129(1): p. 198-205. A recently completed study at Washington University found that the prevalence of OSA (defined as AHI≧5) in surgical patients was more than 19%. See Finkel, K., L. Saager, E. Safarzadeh, M. Bottros, and M. Avidan in their article entitled “Obstructive Sleep Apnea: The Silent Pandemic,” presented in the ASA Annual Meeting, 2006, Chicago, Ill.
Patients with OSA, even if asymptomatic, present special perioperative challenges. During the first three postoperative days, the risk of life-threatening apnea is increased in OSA patients due to the high levels of pain that mandate administration of analgesics (especially opioids). In the subsequent three postoperative days, REM sleep and deep slow-wave NREM rebounds, which again increases the risk of prolonged apneas during sleep. Therefore, patients who suffer from OSA appear to have two separate, sequential reasons for increased apnea during the week following surgery. See Rosenberg, J., G. Wildschiodtz, M. H. Pedersen, F. von Jessen, and H. Kehlet, in the article entitled “Late postoperative nocturnal episodic hypoxaemia and associated sleep pattern” published in the British Journal of Anaesthesia, 1994. 72(2): p. 145-50, Reeder, M. K., M. D. Goldman, L. Loh, A. D. Muir, K. R. Casey, and J. R. Lehane, in the article entitled “Late postoperative nocturnal dips in oxygen saturation in patients undergoing major abdominal vascular surgery. Predictive value of pre-operative overnight pulse oximetry” published in the British Journal of Anaesthesia, 1992. 7(2): p. 110-5, Reeder, M. K., M. D. Goldman, L. Loh, A. D. Muir, K. R. Casey, and D. A. Gitlin, in the article entitled “Postoperative obstructive sleep apnea. Haemodynamic effects of treatment with nasal CPAP” published in the British Journal of Anaesthesia, 1991. 46(10): p. 849-53, Reeder, M. K., M. D. Goldman, L. Loh, A. D. Muir, P. Foex, K. R. Casey, and P. J. McKenzie, in the article entitled “Postoperative hypoxaemia after major abdominal vascular surgery” published in the British Journal of Anaesthesia, 1992. 68(1): p. 23-6 and Rosenberg, J. and H. Kehlet, in the article entitled “Postoperative episodic oxygen desaturation in the sleep apnoea syndrome” published in Acta Anaesthesiol Scand, 1991. 35(4): p. 368-9.
The majority of the postoperative concerns in OSA patients are possible respiratory depression and hypoxemia following surgery. This may be potentiated by administration of systemic opioids for analgesia. Narcotics and sedatives suppress the brain's afferent output to pump muscles, such as the diaphragm and chest wall, resulting in inadequate tidal volume and associated fall in minute ventilation and a progressive rise in carbon dioxide levels. The rise in carbon dioxide levels causes further suppression of the arousal response. therefore, potentially causing respiratory arrest. Narcotics and sedatives also depress the brains afferent output to upper airway dilator muscles causing a reduction in upper airway tone.
In the early postoperative period, high pain scores, opioid consumption, and surgery itself may all contribute to a disruption of the normal sleep architecture. See Rosenberg-Adamsen, S., H. Kehlet, C. Dodds, and J. Rosenberg in their article entitled “Postoperative sleep disturbances: mechanisms and clinical implications” published in the British Journal of Anaesthesia, 1996. 76(4): p. 552-9, Cronin, A., J. C. Keifer, H. A. Baghdoyan, and R. Lydic, Opioid in their article “inhibition of rapid eye movement sleep by a specific mu receptor agonist” published in the British Journal of Anaesthesia, 1995. 74(2): p. 188-92, Keifer, J. C., H. A. Baghdoyan, and R. Lydic, in their article entitled “Sleep disruption and increased apneas after pontine microinjection of morphine” published in Anesthesiology, 1992. 77(5): p. 973-82 and Knill, R. L., C. A. Moote, M. I. Skinner, and E. A. Rose, in the article entitled “Anesthesia with abdominal surgery leads to intense REM sleep during the first postoperative week” published in Anesthesiology, 1990. 73(1): p. 52-61. The observed changes are sleep deprivation and fragmentation in the early days after surgery, REM sleep is usually absent on the first postoperative night, and sometimes even on the second and third postoperative nights. See Knill, R. L., C. A. Moote, M. I. Skinner, and E. A. Rose, in the article entitled “Anesthesia with abdominal surgery leads to intense REM sleep during the first postoperative week” published in Anesthesiology, 1990. 73(1): p. 52-61. Slow-wave sleep is also suppressed. Obstructive breathing is exacerbated in the late post-operative period as a result of a raised arousal threshold during deep non-REM sleep and the inherent breathing instability during REM sleep. In most patients, REM sleep subsequently reappears (rebound REM sleep) with increased intensity and duration, and REM-associated hypoxemic episodes increase about three-fold on the second and third postoperative nights compared with the night before surgery. See Knill, R. L., C. A. Moote, M. I. Skinner, and E. A. Rose, in the article entitled “Anesthesia with abdominal surgery leads to intense REM sleep during the first postoperative week” published in Anesthesiology, 1990. 73(1): p. 52-61 and Rosenberg, J., G. Wildschiodtz, M. H. Pedersen, F. von Jessen, and H. Kehlet, in their article entitled “Late postoperative nocturnal episodic hypoxaemia and associated sleep pattern” published in the British Journal of Anaesthesia, 1994. 72(2): p. 145-50. Sleep studies [8, 10-12], performed in patients undergoing major abdominal surgery and open heart surgery have shown that postoperative sleep patterns are disturbed severely by early depression of REM and slow wave sleep (SWS) in the early postoperative period, and by rebound of REM sleep and SWS in the late postoperative period. See Knill, R. L., C. A. Moote, M. I. Skinner, and E. A. Rose, in the article entitled “Anesthesia with abdominal surgery leads to intense REM sleep during the first postoperative week” published in Anesthesiology, 1990. 73(1): p. 52-61, Aurell, J. and D. Elmqvist, in the article entitled “Sleep in the surgical intensive care unit: continuous polygraphic recording of sleep in nine patients receiving postoperative care” published in the British Medical Journal (Clin Res Ed), 1985. 290(6474): p. 1029-32, Ellis, B. W. and H. A. Dudley, in the article entitled “Some aspects of sleep research in surgical stress” published in the J Psychosom Res, 1976. 20(4): p. 303-8 and Orr, W. C. and M. L. Stahl, in the article entitled “Sleep disturbances after open heart surgery” published in the American Journal of Cardiology, 1977. 39(2): p. 196-201. The rebound of REM sleep may contribute to the development of sleep-disordered breathing and nocturnal episodic hypoxemia. See Catley, D. M., C. Thornton, C. Jordan, J. R. Lehane, D. Royston, and J. G. Jones, in the article entitled “Pronounced, episodic oxygen desaturation in the postoperative period: its association with ventilatory pattern and analgesic regimen” published in Anesthesiology, 1985. 63(1): p. 20-8, Gentil, B., A. Lienhart, and B. Fleury, in the article entitled “Enhancement of postoperative desaturation in heavy snorers” published in Anesthesia Analgesia, 1995. 81(2): p. 389-92 and Reeder, M. K., M. D. Goldman, L. Loh, A. D. Muir, K. R. Casey, and J. R. Lehane, in the article entitled “Late postoperative nocturnal dips in oxygen saturation in patients undergoing major abdominal vascular surgery. Predictive value of pre-operative overnight pulse oximetry” published in Anaesthesia, 1992. 47(2): p. 110-5. Also REM rebound in the late postoperative period (at a time when oxygen therapy is likely to be discontinued and the patient discharged) may explain the finding that the highest perioperative mortality risk is not the day of surgery, or even the second day; it is on the third or fourth postoperative day. See Rosenberg, J., M. H. Pedersen, T. Ramsing, and H. Kehlet, in the article entitled “Circadian variation in unexpected postoperative death” published in the British Journal of Surgery, 1992. 79(12): p. 1300-2, which is herein incorporated by reference. The rebound of SWS can raise the arousal threshold, prolonging the time to arousal and allowing longer episodes of obstruction with deeper oxyhemoglobin desaturations.
The impact of OSA on patient safety is beginning to be recognized. See Deutscher, R., D. Bell, and S. Sharma, in the article entitled “OSA protocol promotes safer care” published in the Anesthesia Patient Safety Foundation Newsletter 2002-2003: p. 58. When compared to matched controls, orthopedic patients with OSA had more adverse outcomes. See Gupta, R., J. Parvizi, A. Hanssen, and P. Gay, in the article entitled “Postoperative complications in patients with obstructive sleep apnea syndrome undergoing hip or knee replacement: a case-control study” published in the Mayo Clinic Proceedings, 2001. 76: p. 897-905. Up to one-third of these patients developed substantial respiratory or cardiac complications, including arrhythmias, myocardial ischemia, unplanned ICU transfers and/or reintubation. The length of hospitalization was significantly longer for patients with OSA compared to the control subjects. For these orthopedic patients the majority of the cardiorespiratory or neuropsychiatric postoperative complications occurred within the first 72 hours after the joint replacement. The authors theorized that this might have been due to the combination of anesthetic agents, sedatives, and narcotics in conjunction with supine positioning during sleep postoperatively. Conversely, Sabers et al. found that OSA was not an independent risk factor for unanticipated hospital admission or for other adverse perioperative events in patients scheduled for outpatient surgery. These conflicting findings suggest that the type/invasiveness of surgery, which in turn may extend length of hospitalization, may contribute to the interaction between OSA and post-surgical complications.
Recent articles suggest that, at the present time, disastrous respiratory outcomes during the perioperative management of patients with obstructive sleep apnea are a major problem for the anesthesia community. See Benumof, J. L., in the article entitled “Obesity, sleep apnea, the airway, and anesthesia” published in Current Opinion in Anaesthesiology, 2004. 17(1): p. 21-30. The American Society of Anesthesiologists recently published Practice Parameters for the perioperative management of patients with OSA. See A Report by the American Society of Anesthesiologists Task Force on Perioperative Management of Patients with Obstructive Sleep Apnea, Practice Guidelines for the Perioperative Management of Patients with Obstructive Sleep Apnea, published in Anesthesiology, 2006. 104(5): p. 1081-1093. The purpose of the guideline was to improve perioperative care and reduce the risk of adverse outcomes in patients with OSA who receive sedation, analgesia, or anesthesia for diagnostic or therapeutic procedures under the care of an anesthesiologist. Unfortunately, due to a lack of medical evidence to guide the ASA recommendations, the practice parameters were based solely on expert opinion and are heavily reliant on the judgment of the anesthesiologist. Although there is an understanding of the broad categories of what increases the likelihood of developing a post-surgical complication, little is known about how individual risk factors interact to cause these complications. See Rock, P. and A. Passannante, in the article entitled “Preoperative assessment: pulmonary” published in Anesthesiology Clinics of North America, 2004. 22(1): p. 77-91, which is herein incorporated by reference. While several observations have led to considerable speculation in the literature as to the implications of sleep disturbance and sleep disordered breathing on perioperative morbidity and mortality, evidence of a causal relationship is still slight. See Loadsman, J. and D. Hillman, in the article entitled “Anaesthesia and sleep apnoea” published in the British Journal of Anaesthesia, 2001. 86(2): p. 254-266. Although OSA and anesthetic agents both produce significant changes in the respiratory system, little information exists regarding their relative contribution to the subsequent development of post-surgical complications, or the synergy between these and/or other risk factors such as the positional influence of OSA, type of anesthesia, use of opioids or invasiveness of the surgery.
A number of methods have been proposed to reduce the risk for postoperative complications. For example, Redmond proposed administering a drug or agent, such as methylol to a patient in conjunction with CPB surgery to reduce the risk for complications. See U.S. Pat. No. 6,641,571, issued Nov. 4, 2003. Turcott proposed monitoring respiration patterns to identify the presence of periodic breathing or Cheyne-Stokes respiration (i.e., recognize hyperventilation and apnea or hypoventilation) in patients with congestive heart failure. See U.S. Pat. No. 6,600,949, issued Jul. 29, 2003. This information may be used to warn the patient or healthcare provider of changes in the patient's condition that might result in a perioperative complication. Lynn proposed to automatically diagnose obstructive sleep apnea in a centralized hospital critical care or cardiac ward environment. In a preferred embodiment, the system would automatically identify the presence and severity of obstructive sleep apnea and communicate with an intravenous infusion system to prevent the progression of said identified obstructive sleep apnea by limiting infusion of a narcotic. Bardy proposed a method for an automated multiple near-simultaneous health disorder diagnosis and analysis, and, in particular, to an automated collection and analysis patient care system and method for ordering and prioritizing multiple health disorders to identify an index disorder. See U.S. Pat. No. 7,117,028, issued Oct. 3, 2006. These methods propose reducing the risk of complications via a means for monitoring or intervening, or identifying a patient with the pathophysiology corresponding to a heath disorder diagnosis. These methods differ from this invention which provides a means to identify those patients with an increased risk of perioperative complications, and provide physicians a method to reduce risk as a result of an intervention (change in sedative or narcotic, place on CPAP prior to surgery, etc).
There is no doubt that an integrated approach to the identification of patients at risk for perioperative complications will influence the practice of medicine. Advanced identification of patients at greater risk for perioperative complications will influence who administers an analgesic or, how, when and what sedative is administered. Prior identification of high risk patients can be used to determine the appropriate type of facility to be used for a given procedure (i.e., outpatient facility vs. hospital). Physicians can interactively model difference scenarios with the patient to assess changes in risk, making it easier for the clinician and patient to select the surgical option (i.e., nerve block vs. general anesthesia) which maximizes patient comfort and safety.