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Fragmented Sleep Enhances Postoperative Neuroinflammation but Not Cognitive Dysfunction

Sleep is integral to biologic function, and sleep disruption can result in both physiological and psychologic dysfunction including cognitive decline. The brain’s capacity to successfully respond to cognitive challenges through compensatory recruitment becomes overwhelmed if the patient is not presented with appropriate and continual sleep. Surgery activates the innate immune system, inducing neuroinflammatory changes that interfere with cognition. Because surgical patients with sleep disorders have an increased likelihood of exhibiting postoperative delirium, an acute form of cognitive decline, the authors investigated the contribution of perioperative sleep fragmentation to the neuroinflammatory and cognitive responses of surgery.

The authors show that sleep fragmentation and surgery can independently produce significant memory impairment, but perioperative SF significantly increased hippocampal inflammation without further cognitive impairment. It may be possible that by day 3 the rebound REM and NREM sleep is enough to restore the brain to a state that is capable of appropriately processing sensory input.


Society of Anesthesia and Sleep Medicine Guideline on Preoperative Screening and Assessment of Patients with Obstructive Sleep Apnea

The management of patients with known or suspected OSA is an evolving field. Practice guidelines have been published though most are consensus-based and limited by issues such as failing to objectively establish OSA as a perioperative risk factor, not addressing how to identify OSA patients preoperatively, and making recommendations that may be difficult to implement and cost prohibitive for clinical practice. As such, SASM formed a task force to develop a more evidence-based and cost effective approach to preoperative work up of patient with known or suspected OSA.  The task force was comprised of 28 members of SASM, including 12 anesthesiologists, 9 sleep medicine specialists, 2 hospitalists, 1 otolaryngologist, 2 research assistants, a research librarian and a clinical epidemiologist. Members represented both academic and non-academic settings in various parts of the United States, Canada, Europe, Australia and South America. The task force performed a literature review from 1946 through June of 2014, analyzed the relevant literature, and developed recommendations with the goal of finding a practical balance between minimizing postoperative complications and the efficient use of healthcare resources.

A summary of the recommendations is as follows:

  1. OSA patients undergoing procedures under anesthesia are at increased risk for perioperative complications compared to patients without the disease diagnosis. Identifying patients at high risk for OSA prior to surgery for targeted perioperative precautions and interventions may help to reduce perioperative patient complications.
  2. Screening tools may help to risk stratify patients with suspected OSA with reasonable accuracy. Practice groups should consider making OSA screening part of standard pre-anesthetic evaluation.
  3. There is insufficient evidence in the current literature to support canceling or delaying surgery for a formal diagnosis (laboratory or home polysomnography) in patients with suspected OSA, unless there is evidence of uncontrolled systemic disease.
  4. The patient and the health care team should be aware that known, treated, partially treated and untreated OSA as well as suspected OSA may be associated with increased postoperative morbidity.
  5. Consideration should be given to obtaining the results of the sleep study and the recommended Positive Airway Pressure (PAP) setting before surgery.
  6. If resources allow, facilities should consider having PAP equipment for perioperative use, or have patients bring their own PAP equipment with them to the surgical facility.
  7. Additional evaluation for preoperative cardiopulmonary optimization should be considered in patients with known, partially treated/untreated and suspected OSA who have uncontrolled systemic conditions e.g. i) hypoventilation syndromes, ii) severe pulmonary hypertension, and iii) resting hypoxemia in the absence of other cardiopulmonary disease.
  8. Patients with known OSA, partially treated/untreated and suspected OSA with optimized co-morbid conditions may proceed to surgery provided strategies for mitigation of postoperative complications are implemented.
  9. The risks and benefits of the decision should include consultation and discussion with the surgeon and the patient.
  • The use of PAP therapy in previously undiagnosed but suspected OSA patients should be considered case by case. Due to the lack of evidence from randomized controlled trials, we cannot recommend its routine use.
  • Continued use of PAP therapy at previously prescribed settings is recommended during periods of sleep while hospitalized, both preoperatively and postoperatively. Adjustments may need to be made to the settings to account for perioperative changes such as facial swelling, fluid shifts, recent pharmacotherapy, and pulmonary function.

The primary goal of this SASM guideline is to ensure optimal pre-operative evaluation of patients with known or suspected OSA in order to improve patient safety.  It is hoped that the recommendations from this guideline will influence clinical practice as well as stimulate additional research to address the questions for which there is currently insufficient evidence to support recommendations.


Modeling Respiratory Depression Induced by Remifentanil and Propofol During Sedation and Analgesia Using a Continuous Noninvasive Measurement of pCO2

Adequate control of respiratory function under sedation-analgesia remains a challenge for the anesthesiologist because neither respiratory rate, tidal volume, pulse oximetry nor capnography are sensitive and specific enough measures. The present study uses a continuous transcutaneous noninvasive measure of CO2 which directly reflect the efficiency of ventilatory function as a pharmacodynamic endpoint of respiratory depression in response to propofol and remifentanil predicted concentrations to construct a mathematical model based on the data collected from 136 patients. The proposed pharmacodynamic model of respiratory depression integrates respiratory physiology principles and allows the clinician to estimate the level of CO2 as a function of propofol and remifentanil in patients sedated although breathing spontaneously. Such a model opens many possibilities to study in deeper detail respiratory response to anesthetic drugs or to be used as a learning tool to train anesthesiologist to perform safer sedation or to be used as an alert system while performing sedation-analgesia in real patients.


CPAP in the Perioperative Setting: Evidence of Support

The prevalence of OSA in surgical patients may be as high as 70%. These patients pose a significant clinical challenge to health-care professionals, and the lack of evidence behind the current guidelines recommendations and significant costs of guideline implementation have created a dilemma between potentially improved postoperative adverse events and increased health-care resource utilizations. This review examines the evidence regarding the use of CPAP in the perioperative period.

For surgical patients with OSA it is clear that those who are treated and adherent to CPAP should continue their CPAP in the postoperative period. Those patients with diagnosed OSA who are not adherent to therapy or undiagnosed OSA pose a more significant clinical challenge. CPAP has been shown to have beneficial effects on postoperative adverse events.

There are several barriers to effective diagnosis and treatment of OSA in the perioperative setting. In both clinical and research settings, a significant proportion of patients who may have suspected OSA refuse to undergo additional testing for establishing an OS diagnosis. Also, for those patients that actually are on home CPAP therapy only one third used their CPAP during the postoperative stay in the hospital.

Individual evaluation is important to determine the best course of action. Referral to sleep medicine for CPAP therapy may have to be taken in the absence of overwhelming evidence from RCTs in certain groups of patients. Patients with severe OSA, COPD or overlap syndrome, obesity hypoventilation syndrome, or pulmonary hypertension would definitely benefit from further evaluation and workup. Patients who have preoperative resting hypoxemia on room air with no known cardiopulmonary cause are potential candidates for further preoperative evaluation. Patients with decreased respiratory responses to hypoxia/hypercapnia stimuli and a high arousal threshold presenting with recurrent severe hypoxemia may benefit from preoperative CPAP.


Postoperative Complications in Obesity Hypoventilation Syndrome and Hypercapnic OSA: CO2 Levels Matter!

The investigators looked at a total of 1800 patients with BMI > 30 who underwent polysomnography and non-cardiac surgery and had arterial blood gases drawn on more than one occasion at a major tertiary care center. 194 patients met criteria for possible or definite Obesity hypoventilation syndrome and these were compared to patients only known to have OSA (AHI >5). They found that patients with hypercapnia from definite or possible OHS, and overlap syndrome were more likely to develop postoperative respiratory failure [OR: 10.9 (95% CI 3.7-32.3), p<0.0001], postoperative heart failure (p<0.0001), prolonged intubation [OR: 5.4 (95% CI 1.9-15.7), p=0.002), postoperative ICU transfer (OR: 3.8 (95% CI 1.7-8.6), p=0.002]; longer ICU (beta coefficient: 0.86; SE: 0.32, p=0.009) and hospital length of stay (beta coefficient: 2.94; SE: 0.87, p=0.0008) Among the clinical determinants of OHS, neither BMI not AHI showed associations with any postoperative outcomes with univariable or multivariable regression analyses.

These results suggest that emphasis be placed on better preoperative recognition of hypercapnia among patients with OSA or overlap syndrome undergoing elective non-cardiac surgery. This is not standard of care at present. The investigators propose a scheme for preoperative recognition and risk stratification of patients with hypercapnic OSA.


Postoperative Complications in Patients with Unrecognized Obesity Hypoventilation Syndrome Undergoing Elective Non-Cardiac Surgery

Among patients with OSA, a higher number of medical morbidities are known to be associated with those who have obesity hypoventilation syndrome (OHS) compared with OSA alone. OHS can pose a higher risk of postoperative complications after elective noncardiac surgery (NCS) and often is unrecognized at the time of surgery. The objective of this study was to retrospectively identify patients with OHS and compare their postoperative outcomes with those of patients with OSA alone.


Preoperative Sleep Disruption and Postoperative Delirium

Delirium and sleep disruption are both common in the older patients who are hospitalized. Sleep disruption, including changes in sleep patterns and architecture, and decreased quality of sleep are commonly observed in older subjects. In a preliminary study, we monitored sleep in 50 patients (mean age 66 ± 11 years) with wrist actigraphy for 3 days before and 3 days after surgery. Postoperative delirium was measured using the Confusion Assessment Method. By actigraphy, the preoperative sleep for patients who ultimately developed postoperative delirium showed disruption beginning 2 days before surgery. The incidence of postoperative delirium observed during any of the 3 postoperative days was 14%. For the 7 patients with postoperative delirium, wake after sleep onset (WASO) as a percentage of total sleep time was significantly higher (44% ± 22%) during the night before surgery compared to the patients without delirium (21% ± 20%, p = 0.012). Patients with WASO < 10% did not experience postoperative delirium. We concluded in this pilot study that sleep disruption was more severe in the days just before surgery in the patients who experienced postoperative delirium. Our novel finding of sleep disruption beginning before surgery provides important guidance for clinical assessment and interventions to improve sleep before surgery. Specifically, future work should target the etiology of nocturnal wake time in the period immediately before the planned surgery.


Neck Circumference Percentile: A Screening Tool for Pediatric Obstructive Sleep Apnea

Adults with large neck circumference (NC) are more likely to develop obstructive sleep apnea (OSA), especially in males. As NC changes with age and sex, no reference ranges for NC existed, until now. Investigators at the Children’s Hospital of Eastern Ontario have developed reference ranges – a new pediatric growth curve – to measure and track NC for children between the ages 6–17 years old. Their new study, published in Pediatric Pulmonology, reports NC data on 245 children aged 6–17 years presenting for polysomnography, in whom NC reference ranges were applied, to test the association between NC > 95th percentile and OSA.

The study found that in children, NC measuring > 95th percentile for age and sex is associated with increased risk of OSA. When examined by sex, the association was significant in males aged 12 or older, but not in females. Body Mass Index (BMI), did not did not predict OSA in this group.

In older males, as in adults, neck size is a predictor of OSA. This suggests that as in adults, it is not just overall obesity, but body fat distribution centrally (in the trunk and neck) that predicts risk of OSA.


Association of Adenotonsillectomy With Asthma Outcomes in Children: A Longitudinal Database Analysis

Bhattacharjee and Mokhlesi examined the 2003–2010 MarketScan database. MarketScan database provides access to a large database of over 25 million children capturing reimbursements from the health private insurance plans and payments accrued by patients including inpatient and outpatient settings as well as pharmacy expenses. Children were identified for a study period between January 1, 2003, and December 31, 2010. A total of 13,506 children with asthma in the United States who underwent adenotonsillectomy (AT). Asthma outcomes during 1 y preceding AT were compared to those during 1 y following AT. In addition, 27,012 age-, sex-, and geographically matched children with asthma without AT were included to examine asthma outcomes among children without known adenotonsillar tissue morbidity. AT was associated with significant improvements in several asthma outcomes such as asthma exacerbation, ER visits, hospitalizations, reduction in prescription refills for bronchodilators, inhaled corticosteroids and systemic corticosteroids. In contrast, there were no significant reductions in these outcomes in children with asthma who did not undergo AT over an overlapping follow-up period.


Obstructive Sleep Apnea During REM Sleep and Hypertension. Results of the Wisconsin Sleep Cohort

In another study, Mokhlesi and colleagues examined the Wisconsin Sleep Cohort to quantify the independent association between prevalent hypertension (cross-sectional analysis) and incident hypertension (longitudinal analysis). The analysis included 4,385 sleep studies on 1,451 individuals as well as a subset with ambulatory blood pressure data (n = 1,085 sleep studies on 742 individuals). Given the large sample size, they were also able to perform the analyses in a subset of subjects who had no disease in non-REM sleep (i.e. non-REM AHI < 5 events per hour). In individuals with non-REM AHI less than or equal to 5, a twofold increase in REM AHI was associated with 24% higher odds of hypertension (odds ratio, 1.24; 95% confidence interval, 1.08–1.41). Longitudinal analysis revealed a significant association between REM AHI categories and the development of hypertension (P trend = 0.017). Non-REM AHI was not a significant predictor of hypertension in any of the models. The authors concluded that REM OSA is cross-sectionally and longitudinally associated with hypertension. This is clinically relevant because treatment of OSA is often limited to the first half of the sleep period leaving most of REM sleep untreated.