Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males.

Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO2 levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO2 and 3.0 ± 0.2% O2) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO2, O2 saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea.NEW & NOTEWORTHY Both arousal state and concomitant CO2 levels are known modulators of the effects of intermittent hypoxia on ventilatory neuroplasticity. This is the first study to investigate the effects of combined intermittent hypercapnic hypoxia during sleep in humans. The lack of neuroplastic effects suggests a need for further studies more closely replicating obstructive sleep apnea to determine the pathophysiological relevance of intermittent hypoxia-induced ventilatory neuroplasticity.

Treatment of Obstructive Sleep Apnea. Prospects for Personalized Combined Modality Therapy.

Obstructive sleep apnea (OSA) is a common sleep disorder with serious associated morbidities. Although several treatment options are currently available, variable efficacy and adherence result in many patients either not being treated or receiving inadequate treatment long term. Personalized treatment based on relevant patient characteristics may improve adherence to treatment and long-term clinical outcomes. Four key traits of upper airway anatomy and neuromuscular control interact to varying degrees within individuals to cause OSA. These are: (1) the pharyngeal critical closing pressure, (2) the stability of ventilator chemoreflex feedback control (loop gain), (3) the negative intraesophageal pressure that triggers arousal (arousal threshold), and (4) the level of stimulus required to activated upper airway dilator muscles (upper airway recruitment threshold). Simplified diagnostic methods are being developed to assess these pathophysiological traits, potentially allowing prediction of which treatment would best suit each patient. In contrast to current practice of using various treatment modes alone, model predictions and pilot clinical trials show improved outcomes by combining several treatments targeted to each patient's pathophysiology profile. These developments could theoretically improve efficacy and adherence to treatment and in turn reduce the social and economic health burden of OSA and the associated life-threatening morbidities. This article reviews OSA pathophysiology and identifies currently available and investigational treatments that may be combined in the future to optimize therapy based on individual profiles of key patient pathophysiological traits.

Frequency and survival pattern of in-hospital cardiac arrests: The impacts of etiology and timing.

OBJECTIVE: Define the frequency and survival pattern of cardiac arrests in relation to the hospital day of event and etiology of arrest. SUBJECT AND METHODS: Retrospective cohort study of adult in-hospital cardiac arrests between July 1, 2005, and June 30, 2013, that were classified by etiology of deterioration. Arrests were divided based on hospital day (HD) of event (HD1, HD2-7, HD>7 days), and analysis of frequency was performed. The primary outcome of survival to discharge and secondary outcomes of return of spontaneous circulation (ROSC) and favorable neurological outcomes were compared using multivariable logistic regression analysis. RESULTS: A total of 627 cases were included, 193 (30.8%) cases in group HD1, 206 (32.9%) in HD2-7, and 228 (36.4%) in HD>7. Etiology of arrest demonstrated variability across the groups (p<0.001). Arrests due to ventilation issues increased in frequency with longer hospitalization (p<0.001) while arrests due to dysrhythmia had the opposite trend (p=0.014). Rates of survival to discharge (p=0.038) and favorable neurological outcomes (p=0.002) were lower with increasing hospital days while ROSC was not different among the groups (p=0.183). Survival was highest for HD1 (HD1: 38.9% [95% CI, 32.0-45.7%], p=0.002 vs HD2-7: 34.0% [95% CI, 27.5-40.4%], p<0.001 vs HD>7: 27.2% [95% CI, 21.4-33.0%], p<0.001). CONCLUSIONS: The etiology of cardiac arrests varies in frequency as length of hospitalization increases. Survival rates and favorable neurological outcomes are lower for in-hospital arrests occurring later in the hospitalization, even when adjusted for age, sex, and location of event. Understanding these issues may help with focusing therapies and accurate prognostication.

The role of high loop gain induced by intermittent hypoxia in the pathophysiology of obstructive sleep apnoea.

Intermittent hypoxia and unstable breathing are key features of obstructive sleep apnoea (OSA), the most common pathological problem of breathing in sleep. Unstable ventilatory control is characterised by high loop gain (LG), and likely contributes to cyclical airway obstruction by promoting airway collapse during periods of low ventilatory drive. Potential new strategies to treat OSA include manipulations designed to lower LG. However, the contribution of inherent versus induced LG abnormalities in OSA remains unclear. Hence, a better understanding of the mechanisms causing high LG in OSA is needed to guide the design of LG based treatments. OSA patients exhibit abnormal chemoreflex control which contributes to increased LG. These abnormalities have been shown to normalise after continuous positive airway pressure treatment, suggesting induced rather than inherent trait abnormalities. Experimental intermittent hypoxia, mimicking OSA, increases hypoxic chemosensitivity and induces long term facilitation; a sustained increase in ventilatory neural output which outlasts the original stimulus. These neuroplastic changes induce the same abnormalities in chemoreflex control as seen in OSA patients. This review outlines the evidence to support that a key component of high LG in OSA is induced by intermittent hypoxia, and is reversed by simply preventing this inducing stimulus.

Functional capacity evaluation reports for clients with personal injury claims: A content analysis.

Functional capacity evaluations (FCEs) for personal injury claimants are rigorously scrutinized by the stakeholders because of their financial implications. This study examined 51 medico-legal FCE reports for clients all of whom suffered with spinal pain attributed to a motor vehicle accident. The FCEs were completed by 14 occupational therapists. Content analysis of the FCE reports identified categories and sub-categories of objective and subjective information on which occupational therapists reported. They included employment, activities of daily living, pain, functional physical capacities and job demands. Recommendations included the suitability of current and future jobs. However, the reasoning behind occupational therapists' recommendations in the FCE reports was frequently not stated. This content analysis demonstrated that these detailed FCE reports had a consistent focus on work capacity; further, the researchers suggest refinements to FCE reporting practices so that findings, recommendations and predictions about work outcomes for clients are interpreted clearly and realistically.