A review of supine position related obstructive sleep apnea: Classification, epidemiology, pathogenesis and treatment.

Supine related obstructive sleep apnea (OSA) is the most common clinical and physiological phenotype of OSA. This condition is recognizable by patients, their families and through polysomnographic recordings. Commonly used definitions distinguish the presence of supine related OSA when respiratory events occur at twice the frequency when the patient lies in the supine compared to non-supine sleeping positions. Recent physiology studies have demonstrated that airway obstruction arises more commonly in the supine position particularly at the level of the soft palate and epiglottis. Increased airway collapsibility is reliability observed supine relative to lateral position. To a lesser extent, changes in control of breathing favour less stable ventilation when the supine sleeping posture is adopted. Many treatments have been developed and trialled to help patients avoid sleeping on their back. The last 10 years has seen the emergence of vibrotactile warning devices that are worn on the patients' neck or chest. High quality randomized controlled trial data is accumulating on the efficacy and common pitfalls of the application of these treatments.

A single dose of noradrenergic/serotonergic reuptake inhibitors combined with an antimuscarinic does not improve obstructive sleep apnoea severity.

Previous trials have demonstrated that the combination of noradrenergic reuptake inhibitors with an antimuscarinic can substantially reduce the apnoea-hypopnoea index (AHI) and improve airway collapsibility in patients with obstructive sleep apnoea (OSA). However, some studies have shown that when administered individually, neither noradrenergic or serotonergic agents have been effective at alleviating OSA. This raises the possibility that serotonergic agents (like noradrenergic agents) may also need to be delivered in combination to be efficacious. Therefore, we investigated the effect of an antimuscarinic (oxybutynin) on OSA severity when administered with either duloxetine or milnacipran, two dual noradrenergic/serotonergic reuptake inhibiters. A randomized, double-blind, 4 way cross-over, placebo-controlled trial in ten OSA patients was performed. Patients received each drug condition separately across four overnight in-lab polysomnography (PSG) studies ~1-week apart. The primary outcome measure was the AHI. In addition, the four key OSA endotypes (collapsibility, muscle compensation, arousal threshold, loop gain) were measured non-invasively from the PSGs using validated techniques. There was no significant effect of either drug combinations on reducing the total AHI or improving any of the key OSA endotypes. However, duloxetine+oxybutynin did significantly increase the fraction of hypopnoeas to apnoeas (FHypopnoea ) compared to placebo (p = 0.02; d = 0.54). In addition, duloxetine+oxybutynin reduced time in REM sleep (p = 0.009; d = 1.03) which was positively associated with a reduction in the total AHI (R2  = 0.62; p = 0.02). Neither drug combination significantly improved OSA severity or modified the key OSA endotypes when administered as a single dose to unselected OSA patients.

Examining the impact of multilevel upper airway surgery on the obstructive sleep apnoea endotypes and their utility in predicting surgical outcomes.

BACKGROUND AND OBJECTIVE: Upper airway surgery for obstructive sleep apnoea (OSA) is an alternative treatment for patients who are intolerant of continuous positive airway pressure (CPAP). However, upper airway surgery has variable treatment efficacy with no reliable predictors of response. While we now know that there are several endotypes contributing to OSA (i.e., upper airway collapsibility, airway muscle response/compensation, respiratory arousal threshold and loop gain), no study to date has examined: (i) how upper airway surgery affects all four OSA endotypes, (ii) whether knowledge of baseline OSA endotypes predicts response to surgery and (iii) whether there are any differences when OSA endotypes are measured using the CPAP dial-down or clinical polysomnographic (PSG) methods. METHODS: We prospectively studied 23 OSA patients before and ≥3 months after multilevel upper airway surgery. Participants underwent clinical and research PSG to measure OSA severity (apnoea-hypopnoea index [AHI]) and endotypes (measured in supine non-rapid eye movement [NREM]). Values are presented as mean ± SD or median (interquartile range). RESULTS: Surgery reduced the AHITotal (38.7 [23.4 to 79.2] vs. 22.0 [13.3 to 53.5] events/h; p = 0.009). There were no significant changes in OSA endotypes, however, large but variable improvements in collapsibility were observed (CPAP dial-down method: ∆1.9 ± 4.9 L/min, p = 0.09, n = 21; PSG method: ∆3.4 [-2.8 to 49.0]%Veupnoea , p = 0.06, n = 20). Improvement in collapsibility strongly correlated with improvement in AHI (%∆AHISupineNREM vs. ∆collapsibility: p < 0.005; R2  = 0.46-0.48). None of the baseline OSA endotypes predicted response to surgery. CONCLUSION: Surgery unpredictably alters upper airway collapsibility but does not alter the non-anatomical endotypes. There are no baseline predictors of response to surgery.

Considering the Role of Adherence in New and Emerging Sleep Treatments.

There are several novel and emerging treatments for obstructive sleep apnea (OSA), including new devices and pharmacotherapies. Long-term efficacy and adherence data for these interventions in the sleep context are lacking. Future studies exploring the long-term adherence and efficacy in novel and emerging treatments of OSA are required to fully understand the place of these treatments in treatment hierarchies. Such research also should aim to evaluate the use of these novel therapies in real-world clinical settings, because many of the studies performed to date have been done under closely monitored research populations and relatively small sample sizes.

Assessing the Physiologic Endotypes Responsible for REM- and NREM-Based OSA.

BACKGROUND: Patients with OSA can have the majority of their respiratory events in rapid eye movement (REM) sleep or in non-rapid eye movement (NREM) sleep. No previous studies have linked the different physiologic conditions in REM and NREM sleep to the common polysomnographic patterns seen in everyday clinical practice, namely REM predominant OSA (REMOSA) and NREM predominant OSA (NREMOSA). RESEARCH QUESTION: (1) How does OSA physiologic condition change with sleep stage in patients with NREMOSA and REMOSA? (2) Do patients with NREMOSA and REMOSA have different underlying OSA pathophysiologic conditions? STUDY DESIGN AND METHODS: We recruited patients with three polysomnographic patterns. (1) REMOSA: twice as many respiratory events in REM sleep, (2) NREMOSA: twice as many events in NREM sleep, and (3) uniform OSA: equal number of events in NREM/REM sleep. We deployed a noninvasive phenotyping method to determine OSA endotype traits (Vpassive, Vactive, loop gain, arousal threshold) in NREM sleep, REM sleep, and total night sleep in each group of patients (NREMOSA, REMOSA, uniform OSA). RESULTS: Patients with NREMOSA have significantly worse ventilatory control stability in NREM sleep compared with REM sleep (loop gain, 0.546 [0.456,0.717] in NREM vs 0.365 [0.238,0.459] in REM sleep; P = .0026). Patients with REMOSA displayed a significantly more collapsible airway (ie, lower Vpassive) in REM compared with NREM sleep (98.4 [97.3,99.2] %Veupnea in NREM vs 95.9 [86.4,98.9] %Veupnea in REM sleep; P < .0001). The major between-group difference across the whole night was a significantly higher loop gain in the NREMOSA group (0.561 [0.429,0.675]) compared with the REMOSA group (0.459 [0.388,0.539]; P = .0033). INTERPRETATION: This study is the first to link long-recognized polysomnographic patterns of OSA to underlying physiologic differences. Patients with NREMOSA have a higher loop gain in NREM sleep; patients with REMOSA have a worsening of Vpassive in REM sleep.

A randomized controlled trial of oxygen therapy for patients who do not respond to upper airway surgery for obstructive sleep apnea.

STUDY OBJECTIVES: We aimed to determine whether patients diagnosed with obstructive sleep apnea (OSA) who fail to respond to upper airway surgery may be successfully treated with supplemental oxygen and whether we could identify baseline physiologic endotypes (ie, collapsibility, loop gain, arousal threshold, and muscle compensation) that predict response to oxygen therapy. METHODS: We conducted a single night, randomized double-blinded cross over trial in which patients with OSA who failed to respond to upper airway surgery were treated on separate nights with oxygen therapy (4 L/min) or placebo (medical air). Effect of oxygen/air on OSA on key polysomnography outcomes were assessed: apnea-hypopnea index (AHI), AHI without desaturation (ie, flow-based AHI), arousal index, and morning blood pressure. OSA endotypes were estimated from the polysomnography signals to determine whether baseline OSA physiology could be used to predict response to oxygen therapy. RESULTS: There was a statistically significant reduction in AHI and flow-based AHI on oxygen vs placebo (flow-based AHI: 42.4 ± 21.5 vs 30.5 ± 17.1 events/h, P = .008). Arousal index was also reduced on oxygen vs placebo (41.1 ± 19.5 vs 33.0 ± 15.3 events/h, P = .006). There was no significant difference in morning blood pressure between oxygen and placebo. Although 7 of 20 individuals experienced a 50% reduction or greater in flow-based AHI on oxygen (responders), there was no difference in the baseline OSA endotypes (or clinical characteristics) between responders and nonresponders. CONCLUSIONS: Our findings demonstrate that a proportion of patients who fail to respond to upper airway surgery for OSA respond acutely to treatment with supplemental oxygen. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Oxygen therapy for treating patients with residual obstructive sleep apnea following upper airway surgery; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373566; Identifier: ACTRN12617001361392.

How bad can life be? A case of concurrent cardiac tamponade and pulmonary embolus.

We present a rare case of a patient presenting with submassive pulmonary embolism (PE) further complicated by cardiac tamponade with the clinical dilemma on whether to perform thrombolysis or emergency pericardiocentesis to save her life. The aetiology of her pericardial effusion remains unclear but may possibly relate to post-PE pericarditis, a condition that resembles Dressler's syndrome. The pathophysiological processes of concurrent PE and cardiac tamponade combined to result in an unusual right ventricular shape on transthoracic echocardiography, and our findings raise the possibility of a fourth mechanism for the explanation of McConnell's sign - restricted free wall dilation via the moderator band.

Obstructive sleep apnoea predicted by the STOP-BANG questionnaire is not associated with higher rates of post-operative complications among a high-risk surgical cohort.

PURPOSE: The purpose of this study is to establish if obstructive sleep apnoea (OSA) predicted by the STOP-BANG questionnaire would be associated with higher rates of post-operative cardiac, respiratory or neurological complications among a selected high-risk population with established major comorbidities undergoing major surgery. We hypothesise that a cohort selected for major comorbidities will show a higher post-operative complication rate that may power any potential association with co-existent OSA and identify an important target group for OSA screening and treatment pathways in preparation for major surgery. METHODS: Patients attending a high-risk preadmission clinic prior to major surgery from May 2015 to November 2015 were prospectively screened for OSA using the STOP-BANG questionnaire. Patients with treated OSA were excluded. Patient data and complications were attained from the pre-admission clinic and subsequent inpatient medical record at discharge. RESULTS: Three-hundred-and-ten patients were included in the study (age 68.6 ± 13.1 years, body mass index [BMI] 30.6 ± 7.4 kg/m2; 52.9% female). Sixty-four patients (20.6%) experienced 82 post-operative complications. Seventy-five percent of the cohort had a STOP-BANG ≥ 3. There was no association between the STOP-BANG score (unadjusted and adjusted for comorbidity) with the development of post-operative complications. CONCLUSIONS: OSA predicted by the STOP-BANG score was not associated with higher rates of post-operative complications in patients with major comorbidities undergoing high-risk surgery. As the findings from this cohort contrast with other observational studies, more definitive studies are required to establish a causative link between OSA and post-operative complications and determine whether treating OSA reduces this complication rate.

Effect of Hypopnea Scoring Criteria on Noninvasive Assessment of Loop Gain and Surgical Outcome Prediction.

Rationale: Unstable ventilatory control (high loop gain) is a causal factor in the development of obstructive sleep apnea. Methods for quantifying loop gain using polysomnography have been developed that predict favorable responses to upper airway surgery. However, this method is reliant on respiratory event scoring and hence may be affected by hypopnea scoring criteria.Objectives: To determine to what extent differences in hypopnea scoring influence loop gain measurement.Methods: We performed a retrospective analysis of 46 polysomnograms before and after upper airway surgery. Polysomnograms were rescored according to three different American Academy of Sleep Medicine hypopnea definitions (2007Alternative, 2012Recommended, and 2012Acceptable criteria). Loop gain and apnea-hypopnea indexes (AHIs) were compared between criteria using linear regression and Bland-Altman limits of agreement (LOA). Responders to surgery were classified by a 50% or greater reduction in AHI and AHIpostsurgery less than 10 events per hour. Responders were determined separately for each American Academy of Sleep Medicine criterion. Receiver operating characteristic curve analysis predicting surgical outcome was performed for each loop gain measurement derived from each criterion.Results: A near-perfect agreement was found between loop gains derived using the 2007Alternative and 2012Recommended criteria (r2 = 0.99; bias = -0.003; LOA, -0.016 to 0.010). Greater variability was found for 2012Acceptable compared to the 2007Alternative (r2 = 0.70; bias = -0.015; LOA, -0.099 to 0.070) and 2012Recommended (r2 = 0.69; bias = +0.018; LOA, -0.068 to 0.104) criteria. Both 2007Alternative and 2012Recommended loop gains significantly predicted surgical response with similar areas under the curve (AUCs; 2007Alternative AUC = 0.86 [95% confidence interval (CI), 0.75-0.97]; 2012Recommended AUC = 0.84 [95% CI, 0.71-0.97]). 2012Acceptable loop gains were a poor predictor of surgical response (AUC = 0.62 [95% CI, 0.43-0.80]).Conclusions: Loop gain measured noninvasively by polysomnography can be influenced by respiratory event scoring. We recommend caution when using the 2012Acceptable criteria with this method, because such findings may not be directly generalizable to other loop gain values derived from other scoring criteria.

Assessing the impact of diet, exercise and the combination of the two as a treatment for OSA: A systematic review and meta-analysis.

This study aimed to provide an updated systematic review and meta-analysis of randomized controlled trials (RCT) investigating the effectiveness of lifestyle interventions on weight loss and the impact on the severity of obstructive sleep apnoea (OSA). A systematic search of five databases between 1980 and May 2018 was used to identify all RCT which employed a lifestyle intervention (i.e. diet-only, exercise-only or combination of the two) aiming to reduce the severity of OSA (assessed using the apnoea-hypopnoea index (AHI)). Random-effects meta-analyses followed by meta-regression were conducted. Ten RCT involving 702 participants (Intervention group: n = 354; Control group: n = 348) were assessed in two meta-analyses. The weighted mean difference in AHI (-8.09 events/h, 95% CI: -11.94 to -4.25) and body mass index (BMI, -2.41 kg/m2 , 95% CI: -4.09 to -0.73) both significantly favoured lifestyle interventions over control arms. Subgroup analyses demonstrated that all interventions were associated with reductions in the AHI, but only the diet-only interventions were associated with a significant reduction in BMI. No association was found between the reduction in AHI or BMI and the length of the intervention, or with baseline AHI and BMI levels. All lifestyle interventions investigated appear effective for improving OSA severity and should be an essential component of treatment for OSA. Future research should be directed towards identifying subgroups likely to reap greater treatment benefits as well as other therapeutic benefits provided by these interventions.

The effect of surgical weight loss on obstructive sleep apnoea: A systematic review and meta-analysis.

This review aimed to examine the relationship between surgical weight loss and obstructive sleep apnoea (OSA) severity (i.e., apnoea-hypopnoea index [AHI]), and how this relationship is altered by the various respiratory events scoring (RES) criteria used to derive the AHI. A systematic search of the literature was performed up to December 2017. Before-and-after studies were considered due to a paucity of randomised controlled trials (RCTs) available to be reviewed in isolation. Primary outcomes included pre- and post-surgery AHI and body mass index (BMI). Secondary outcomes included sleep study type and RES criteria. Meta-analysis was undertaken where possible. Overall, surgical weight loss resulted in reduction of BMI and AHI, however, OSA persisted at follow-up in the majority of subjects. There was high between-study heterogeneity which was largely attributable to baseline AHI and duration of follow-up when analysed using meta-regression. There was insufficient data to evaluate the impact of different RES criteria on OSA severity. Therefore, more RCTs are needed to verify these findings given the high degree of heterogeneity and future studies are strongly encouraged to report the RES criteria used to enable fair and uniform comparisons of the impact of any intervention on OSA severity.

Ultrasound-assisted peripheral vascular access in a paediatric ED.

OBJECTIVES: To assess the implementation and utility of US for assisting peripheral venous access in a paediatric ED. METHODS: A prospective, observational study of a convenience sample comparing the landmark and US-guided technique for peripheral vascular access in children from July 2006 to February 2007. Clinicians involved under went 3 months of training in US physics and with practical models. Clinicians estimated the degree of difficulty of insertion (using a Likert scale) before each line placement. Data including time of procedure and success or failure were collected, using a standardized clinical record form, by an observing researcher. RESULTS: A total of 84 patients were enrolled. There were 61 line placement episodes in the landmark group (with 253 attempts), and 38 in the US group (with 90 attempts). US recorded slightly higher success per attempt overall (42% vs 38%, P=0.08), and performed better in the patients with difficult access (success 35% vs 18%, P=0.003). US attempts took longer than landmark attempts (2 min 15 s vs 4 min, P<0.001). CONCLUSION: The US guidance may improve the success rate of peripheral vascular access in children rated to have difficult or very difficult vascular access.