Breathing control training for functional seizures: A multi-site, open-label pilot study.

There are no well-validated treatments for functional seizures. While specialist psychotherapy is usually recommended, the evidence for its benefit is qualified, and it can be difficult to obtain. Given the association between hyperventilation and functional seizures we explored an alternative modality, breathing control training, in a multi-site open label pilot trial. Participants with functional seizures over the age of 16 received an hour of breathing training from a respiratory physiotherapist, with a half-hour booster session a month later. Seizure frequency and Nijmegen scores (a measure of hyperventilation) were reported at baseline and follow-up, 3-4 months later. Eighteen subjects were recruited, and 10 completed follow-up. Seven of these 10 had improved seizure frequency, and 3 did not (Wilcoxon signed rank test, p = 0.09), with seizure frequency correlating with Nijmegen score (Spearman's rank correlation = 0.75, p = 0.034). The intervention was well tolerated, with no adverse events reported. These preliminary results support a potentially new approach to treating functional seizures that should prove cost-effective and acceptable, though require confirmation by a randomised controlled trial.

Ultrasound-derived rates of muscle wasting in the intensive care unit and in the post-intensive care ward for patients with critical illness: Post hoc analysis of an international, multicentre randomised controlled trial of early rehabilitation.

BACKGROUND AND AIMS: Muscle wasting results in weakness for patients with critical illness. We aim to explore ultrasound-derived rates of change in skeletal muscle in the intensive care unit (ICU) and following discharge to the post-ICU ward. DESIGN: Post hoc analysis of a multicentre randomised controlled trial of functional-electrical stimulated cycling, recumbent cycling, and usual care delivered in intensive care. METHOD: Participants underwent ultrasound assessment of rectus femoris at ICU admission, weekly in the ICU, upon awakening, ICU discharge, and hospital discharge. The primary outcome was rate of change in rectus femoris cross-sectional area (ΔRFCSA) in mm2/day in the ICU (enrolment to ICU discharge) and in the post-ICU ward (ICU discharge to hospital discharge). Secondary outcomes included rate of change in echo intensity (ΔEI), standard deviation of echo intensity (ΔEISD), and the intervention effect on ultrasound measures. Echo intensity is a quantitative assessment of muscle quality. Elevated echo intensity may indicate fluid infiltration, adipose tissue, and reduced muscle quality. RESULTS: 154 participants were included (mean age: 58 ± 15 years, 34% female). Rectus femoris cross-sectional area declined in the ICU (-4 mm2/day [95% confidence interval {CI}: -9 to 1]) and declined further in the ward (-9 mm2/day [95% CI: -14 to -3]) with a mean difference between ICU and ward of -5 mm2/day ([95% CI: -2, to 11]; p = 0.1396). There was a nonsignificant difference in ΔEI between in-ICU and the post-ICU ward of 1.2 ([95% CI: -0.1 to 2.6]; p = 0.0755), a statistically significant difference in ΔEISD between in-ICU and in the post-ICU ward of 1.0 ([95% CI, 0.5 to 1.5]; p = 0.0003), and no difference in rate of change in rectus femoris cross-sectional area between groups in intensive care (p = 0.411) or at hospital discharge (p = 0.1309). CONCLUSIONS: Muscle wasting occurs in critical illness throughout the hospital admission. The average rate of loss in muscle cross-sectional area does not slow after ICU discharge, even with active rehabilitation.

Incidence and Risk Factors of Pneumonia in Individuals With Acute Spinal Cord Injury: A Multi-national, Multi-center, Prospective Cohort Study.

OBJECTIVE: To describe the occurrence of pneumonia in individuals with acute spinal cord injury (SCI) and identify its key predictors. DESIGN: Multi-centric, longitudinal cohort study. SETTING: 10 specialized SCI rehabilitation units in Europe and Australia. PARTICIPANTS: Eligible were 902 men and women with acute SCI, aged 18 years or older, with cervical or thoracic lesions and not dependent on 24-hour mechanical ventilation; 503 participated in the study (N=503). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We assessed demographics and lesion related parameters at study entry, and any pneumonia events throughout inpatient rehabilitation. Respiratory function, decubitus, and urinary tract infections were assessed at 1, 3, and 6 months post injury as well as at discharge from inpatient rehabilitation. Time to event (pneumonia) analyses were done using the Kaplan-Meier method, and potential predictors for pneumonia were analyzed with multivariable survival models. RESULTS: Five hundred three patients with SCI were included, with 70 experiencing at least 1 pneumonia event. 11 participants experienced 2 or more events during inpatient rehabilitation. Most events occurred very early after injury, with a median of 6 days. Pneumonia risk was associated with tetraplegia (hazard ratio [HR]=1.78; 95% confidence interval [CI] 1.00-3.17) and traumatic etiology (HR=3.75; 95% CI 1.30-10.8) American Spinal Injury Impairment Scale (AIS) A (HR=5.30; 95% CI 2.28-12.31), B (HR=4.38; 95% CI 1.77-10.83), or C (HR=4.09; 95% CI 1.71-9.81) lesions. For every 10 cmH2O increase in inspiratory muscle strength, pneumonia risk was reduced by 13% (HR=0.87; 95% CI 0.78-0.97). CONCLUSION: Pneumonia is a major complication after SCI with the highest incidence very early after injury. Individuals with traumatic or AIS A, B, or C tetraplegia are at highest risk for pneumonia.

Routine lung volume recruitment in boys with Duchenne muscular dystrophy: a randomised clinical trial.

BACKGROUND: Impaired cough results in airway secretion retention, atelectasis and pneumonia in individuals with Duchenne muscular dystrophy (DMD). Lung volume recruitment (LVR) stacks breaths to inflate the lungs to greater volumes than spontaneous effort. LVR is recommended in DMD clinical care guidelines but is not well studied. We aimed to determine whether twice-daily LVR, compared with standard of care alone, attenuates the decline in FVC at 2 years in boys with DMD. METHODS: In this multicentre, assessor-blinded, randomised controlled trial, boys with DMD, aged 6-16 years with FVC >30% predicted, were randomised to receive conventional treatment or conventional treatment plus manual LVR twice daily for 2 years. The primary outcome was FVC % predicted at 2 years, adjusted for baseline FVC % predicted, age and ambulatory status. Secondary outcomes included change in chest wall distensibility (maximal insufflation capacity minus FVC) and peak cough flow. RESULTS: Sixty-six boys (36 in LVR group, 30 in control) were evaluated (median age (IQR): 11.5 years (9.5-13.5), median baseline FVC (IQR): 85% predicted (73-96)). Adjusted mean difference in FVC between groups at 2 years was 1.9% predicted (95% CI -6.9% to 10.7%; p=0.68) in the direction of treatment benefit. We found no differences in secondary outcomes. CONCLUSION: There was no difference in decline in FVC % predicted with use of twice-daily LVR for boys with DMD and relatively normal lung function. The burden associated with routine LVR may outweigh the benefit. Benefits of LVR to maintain lung health in boys with worse baseline lung function still need to be clarified. TRIAL REGISTRATION NUMBER: NCT01999075.

Physical activity of patients with critical illness undergoing rehabilitation in intensive care and on the acute ward: An observational cohort study.

BACKGROUND: There are limited published data on physical activity of survivors of critical illness engaged in rehabilitation in hospital, despite it plausibly influencing outcome. OBJECTIVE: The aims of this study were to measure physical activity of patients with critical illness engaged in rehabilitation in the intensive care unit (ICU) and on the acute ward and report discharge destination, muscle strength, and functional outcomes. METHODS: This was a single-centre, prospective observational study. Adults with critical illness, who received ≥48 h of invasive mechanical ventilation, and who were awake and able to participate in rehabilitation were eligible. To record physical activity, participants wore BodyMedia SenseWear Armbands (BodyMedia Incorporated, USA), during daylight hours, from enrolment until hospital discharge or day 14 of ward stay (whichever occurred first). The primary outcome was time (minutes) spent performing physical activity at an intensity of greater than 1.5 Metabolic Equivalent Tasks. Secondary outcomes included discharge destination, muscle strength, and physical function. RESULTS: We collected 807 days of physical activity data (363 days ICU, 424 days ward) from 59 participants. Mean (standard deviation) duration of daily physical activity increased from the ICU, 17.8 (22.8) minutes, to the ward, 52.8 (51.2) minutes (mean difference [95% confidence interval] = 35 [23.8-46.1] minutes, P < .001). High levels of activity in the ICU were associated with higher levels of activity on the ward (r = .728), n = 48, P < .001. CONCLUSIONS: Patients recovering from critical illness spend less than 5% of the day being physically active throughout hospital admission, even when receiving rehabilitation. Physical activity increased after discharge from intensive care, but had no relationship with discharge destination. Only the absence of ICU-acquired weakness on awakening was associated with discharge directly home from the acute hospital. Future studies could target early identification of ICU-acquired weakness and the preservation of muscle strength to improve discharge outcomes.

Prevalence of sleep-disordered breathing in people with tetraplegia-a systematic review and meta-analysis.

STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVES: To determine the prevalence of sleep-disordered breathing (SDB) in people with tetraplegia and to identify the characteristics associated with SDB. METHODS: A systematic literature search using Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and grey literature sources was conducted using a combination of spinal cord injury (SCI) and SDB related terms. Articles were restricted to publication dates between 1/1/2000 and 4/9/2020 and with objectively measured SDB with an overnight sleep study. The frequency of SDB stratified by the apnoea hypopnea index (AHI) was extracted and weighted averages, using a random effects model, were calculated with 95% confidence intervals. Sub-group analyses were performed where possible. RESULTS: Twelve articles were included in the review; of these nine were included in meta-analysis (combined sample = 630). Sample sizes and case detection methods varied. Reported SDB prevalence rates ranged from 46 to 97%. The prevalence of at least mild (AHI ≥ 5), moderate (AHI ≥ 15) and severe (AHI ≥ 30) SDB were 83% (95% CI = 73-91), 59% (46-71) and 36% (26-46), respectively. Sub-group analyses found that prevalence increased with age (p < 0.001). There were no statistically significant differences in SDB prevalence by sex (p = 0.06), complete/incomplete SCI (p = 0.06), body mass index (p = 0.07), acute/chronic SCI (p = 0.73) or high/low level of cervical SCI (p = 0.90). CONCLUSION: Our results confirm that SDB is highly prevalent in people with tetraplegia, and prevalence increases with age. The high prevalence suggests that routine screening and subsequent treatment should be considered in both acute and community care.

Positive airway pressure for sleep-disordered breathing in acute quadriplegia: a randomised controlled trial.

RATIONALE: Highly prevalent and severe sleep-disordered breathing caused by acute cervical spinal cord injury (quadriplegia) is associated with neurocognitive dysfunction and sleepiness and is likely to impair rehabilitation. OBJECTIVE: To determine whether 3 months of autotitrating CPAP would improve neurocognitive function, sleepiness, quality of life, anxiety and depression more than usual care in acute quadriplegia. METHODS AND MEASUREMENTS: Multinational, randomised controlled trial (11 centres) from July 2009 to October 2015. The primary outcome was neurocognitive (attention and information processing as measure with the Paced Auditory Serial Addition Task). Daytime sleepiness (Karolinska Sleepiness Scale) was a priori identified as the most important secondary outcome. MAIN RESULTS: 1810 incident cases were screened. 332 underwent full, portable polysomnography, 273 of whom had an apnoea hypopnoea index greater than 10. 160 tolerated at least 4 hours of CPAP during a 3-day run-in and were randomised. 149 participants (134 men, age 46±34 years, 81±57 days postinjury) completed the trial. CPAP use averaged 2.9±2.3 hours per night with 21% fully 'adherent' (at least 4 hours use on 5 days per week). Intention-to-treat analyses revealed no significant differences between groups in the Paced Auditory Serial Addition Task (mean improvement of 2.28, 95% CI -7.09 to 11.6; p=0.63). Controlling for premorbid intelligence, age and obstructive sleep apnoea severity (group effect -1.15, 95% CI -10 to 7.7) did not alter this finding. Sleepiness was significantly improved by CPAP on intention-to-treat analysis (mean difference -1.26, 95% CI -2.2 to -0.32; p=0.01). CONCLUSION: CPAP did not improve Paced Auditory Serial Addition Task scores but significantly reduced sleepiness after acute quadriplegia. TRIAL REGISTRATION NUMBER: ACTRN12605000799651.

Randomised controlled trial of polysomnographic titration of noninvasive ventilation.

Noninvasive ventilation (NIV) settings determined during wakefulness may produce patient-ventilator asynchrony (PVA) during sleep, causing sleep disruption and limiting tolerance. This study investigated whether NIV titrated with polysomnography (PSG) is associated with less PVA and sleep disruption than therapy titrated during daytime alone.Treatment-naive individuals referred for NIV were randomised to control (daytime titration followed by sham polysomnographic titration) or PSG (daytime titration followed by polysomnographic titration) groups. Primary outcomes were PVA and arousal indices on PSG at 10 weeks. Secondary outcomes included adherence, gas exchange, symptoms and health-related quality of life (HRQoL).In total, 60 participants were randomised. Most (88.3%) had a neuromuscular disorder and respiratory muscle weakness but minor derangements in daytime arterial blood gases. PVA events were less frequent in those undergoing polysomnographic titration (median (interquartile range (IQR)): PSG 25.7 (12-68) events·h-1 versus control 41.0 (28-182) events·h-1; p=0.046), but arousals were not significantly different (median (IQR): PSG 11.4 (9-19) arousals·h-1 versus control 14.6 (11-19) arousals·h-1; p=0.258). Overall adherence was not different except in those with poor early adherence (<4 h·day-1) who increased their use after polysomnographic titration (mean difference: PSG 95 (95% CI 29-161) min·day-1 versus control -23 (95% CI -86-39) min·day-1; p=0.01). Arterial carbon dioxide tension, somnolence and sleep quality improved in both groups. There were no differences in nocturnal gas exchange or overall measures of HRQoL.NIV titrated with PSG is associated with less PVA but not less sleep disruption when compared with therapy titrated during daytime alone.

Respiratory adjuncts to NIV in neuromuscular disease.

Muscle weakness is an intrinsic feature of neuromuscular diseases (NMD). When the respiratory muscles are involved, the ability to take a deep breath is compromised, leading to reduced lung volumes and a restrictive ventilatory impairment. Inspiratory, expiratory and bulbar muscle weakness can also impair cough, which may impede secretion clearance. Non-invasive ventilation (NIV) is an established and indispensable therapy to manage hypoventilation and respiratory failure. The role of other therapies that support respiratory health is less clearly defined, and the evidence of efficacy is also harder to summarize as the underlying data are of a lesser quality. This narrative review appraises the evidence for respiratory therapies in adults with NMD and respiratory system involvement. Techniques that assist lung inflation and augment cough, such as lung volume recruitment (LVR) and mechanical insufflation-exsufflation (MI-E), are a particular focus of this review. The evidence suggests that LVR, MI-E and various combinations thereof have clinical utility generally, but important methodological limitations limit the strength of clinical recommendations and hamper the integration of evidence into practice. Future trials should prospectively assess the long-term impact of LVR and cough augmentation on clinical outcomes and burden of care in addition to lung mechanics, as well as determine clear predictors of benefit from these techniques.

Continuous Positive Airway Pressure Use for Obstructive Sleep Apnea in Acute, Traumatic Tetraplegia.

OBJECTIVE: To describe continuous positive airway pressure (CPAP) use for treatment of obstructive sleep apnea (OSA) in acute tetraplegia, including adherence rates and associated factors. DESIGN: Secondary analysis of CPAP data from a multinational randomized controlled trial. SETTING: Inpatient rehabilitation units of 11 spinal cord injury centers. PARTICIPANTS: People with acute, traumatic tetraplegia and OSA (N=79). INTERVENTIONS: Autotitrating CPAP for OSA for 3 months. MAIN OUTCOME MEASURES: Adherence measured as mean daily hours of use. Adherent (yes/no) was defined as an average of at least 4 hours a night throughout the study. Regression analyses determined associations between baseline factors and adherence. CPAP device pressure and leak data were analyzed descriptively. RESULTS: A total of 79 participants from 10 spinal units (91% men; mean age ± SD, 46±16; 78±64d postinjury) completed the study in the treatment arm and 33% were adherent. Mean daily CPAP use ± SD was 2.9±2.3 hours. Better adherence was associated with more severe OSA (P=.04) and greater CPAP use in the first week (P<.01). Average 95th percentile pressure was low (9.3±1.7 cmH2O) and 95th percentile leak was high (27.1±13.4 L/min). CONCLUSION: Adherence to CPAP after acute, traumatic tetraplegia is low. Early acceptance of therapy and more severe OSA predict CPAP use over 3 months. People with acute tetraplegia require less pressure to treat their OSA than the nondisabled; however, air leak is high. These findings highlight the need for further investigation of OSA treatment in acute tetraplegia.

Understanding the clinical management of obstructive sleep apnoea in tetraplegia: a qualitative study using the theoretical domains framework.

BACKGROUND: Clinical practice guidelines recommend further testing for people with tetraplegia and signs and symptoms of obstructive sleep apnoea (OSA), followed by treatment with positive airway pressure therapy. Little is known about how clinicians manage OSA in tetraplegia. The theoretical domains framework (TDF) is commonly used to identify determinants of clinical behaviours. This study aimed to describe OSA management practices in tetraplegia, and to explore factors influencing clinical practice. METHODS: Semi-structured interviews were conducted with 20 specialist doctors managing people with tetraplegia from spinal units in Europe, UK, Canada, USA, Australia and New Zealand. Interviews were audiotaped for verbatim transcription. OSA management was divided into screening, diagnosis and treatment components for inpatient and outpatient services, allowing common practices to be categorised. Data were thematically coded to the 12 constructs of the TDF. Common beliefs were identified and comparisons were made between participants reporting different practices. RESULTS: Routine screening for OSA signs and symptoms was reported by 10 (50%) doctors in inpatient settings and eight (40%) in outpatient clinics. Doctors commonly referred to sleep specialists for OSA diagnosis (9/20 in inpatients; 16/20 in outpatients), and treatment (12/20, 17/20). Three doctors reported their three spinal units were managing non-complicated OSA internally, without referral to sleep specialists. Ten belief statements representing six domains of the TDF were generated about screening. Lack of time and support staff (Environmental context and resources) and no prompts to screen for OSA (Memory, attention and decision processes) were commonly identified barriers to routine screening. Ten belief statements representing six TDF domains were generated for diagnosis and treatment behaviours. Common barriers to independent management practices were lack of skills (Skills), low confidence (Beliefs about capabilities), and the belief that OSA management was outside their scope of practice (Social/Professional role and identity). The three units independently managing OSA were well resourced with multidisciplinary involvement (Environmental context and resources), had 'clinical champions' to lead the program (Social influences). CONCLUSION: Clinical management of OSA in tetraplegia is highly varied. Several influences on OSA management within spinal units have been identified, facilitating the development of future interventions aiming to improve clinical practice.

Apnoea and hypopnoea scoring for people with spinal cord injury: new thresholds for sleep disordered breathing diagnosis and severity classification.

STUDY DESIGN: Descriptive study. OBJECTIVES: To determine the effect of respiratory event rule-set changes on the apnoea hypopnoea index, and diagnostic and severity thresholds in people with acute and chronic spinal cord injury. SETTING: Eleven acute spinal cord injury inpatient hospitals across Australia, New Zealand, Canada and England; community dwelling chronic spinal cord injury patients in their own homes. METHODS: Polysomnography of people with acute (n = 24) and chronic (n = 78) tetraplegia were reanalysed from 1999 American Academy of Sleep Medicine (AASM) respiratory scoring, to 2007 AASM 'alternative' and 2012 AASM respectively. Equivalent cut points for published 1999 AASM sleep disordered breathing severity ranges were calculated using receiver operator curves, and results presented alongside analyses from the able-bodied. RESULTS: In people with tetraplegia, shift from 1999 AASM to 2007 AASM 'alternative' resulted in a 22% lower apnoea hypopnoea index, and to 2012 AASM a 17% lower index. In people with tetraplegia, equivalent cut-points for 1999 AASM severities of 5,15 and 30 were calculated at 2.4, 8.1 and 16.3 for 2007 AASM 'alternative' and 3.2, 10.0 and 21.2 for 2012 AASM. CONCLUSION: Interpreting research, prevalence and clinical polysomnography results conducted over different periods requires knowledge of the relationship between different rule-sets, and appropriate thresholds for diagnosis of disease. SPONSORSHIP: This project was proudly supported by the Traffic Accident Commission (Program grant) and the National Health and Medical Research Council (PhD stipend 616605).

Worth the effort? Weighing up the benefit and burden of continuous positive airway pressure therapy for the treatment of obstructive sleep apnoea in chronic tetraplegia.

STUDY DESIGN: Mixed methods OBJECTIVES: Continuous positive airway pressure (CPAP) therapy is the recommended treatment for obstructive sleep apnoea (OSA). The aim of this study was to estimate CPAP adherence in people with tetraplegia and OSA, and to explore the barriers and facilitators to CPAP use. SETTING: Hospital outpatient department in Melbourne, Australia METHODS: People with chronic tetraplegia and OSA were commenced with auto-titrating CPAP and supported for 1 month. Semi-structured interviews were conducted with participants at one month and analysed thematically. CPAP usage was measured at 1, 6 and 12 months, with "adherent" defined as achieving more than 4 h average per night. RESULTS: Sixteen participants completed the study (80% male; mean age 56 (SD = 15)). Mean nightly CPAP use at one month was 3.1 h (SD = 2.5; 38% adherent), and at 6 months and 12 months were 2.6 h (SD = 2.8; 25% adherent) and 2.1 h (SD = 3.2; 25% adherent). The perceived benefit/burden balance strongly influenced ongoing use. Burden attributed to CPAP use was common, and included mask discomfort, and physical and emotional problems. Adherent participants were motivated by the immediate daytime benefits to mood, alertness and sleepiness. There was a tendency to not recognise symptoms of OSA until after they were treated. CONCLUSION: CPAP use is challenging for people with tetraplegia, who experience substantial burden from using the device. When tolerated, the proximate benefits are substantial. People with tetraplegia need more intensive support for longer to help them overcome the burdens of CPAP and benefit from the treatment.

Development and validation of models to predict respiratory function in persons with long-term spinal cord injury.

STUDY DESIGN: Multicenter, cross-sectional study. OBJECTIVES: To validate previously developed respiratory function prediction models for persons with long-term spinal cord injury (SCI) and if necessary develop and validate new models. SETTING: Ten SCI rehabilitation centers. METHODS: Five respiratory function parameters were measured in adults with chronic, traumatic, motor complete SCI (C4-T12). First, the models published in 2012 were validated using Bland-Altman plots. Then, new models were calculated using 80% of the dataset by multiple regression analysis with the candidate predictors gender, age, height, weight, time post injury (TPI), lesion level, and smoking. In a third step, the new models were validated using the other 20% of the dataset by Bland-Altman plots. RESULTS: In total 613 participants were included. For persons with long-term SCI, the 2012 models were poorly predictive, especially for respiratory muscle strength (R2 = 0.4). Significant predictors for all respiratory function parameters in the new models (R2 = 0.7-0.8) were lesion level, gender and weight. Small effects on single outcome parameters were observed for TPI and age whereas smoking had no effect. For the new models the mean differences between measured and predicted values for respiratory muscle strength were 4.0 ± 36.0 cm H2O and for lung function parameters -0.5 ± 1.2 L (FVC), -0.3 ± 0.9 L (FEV1) and -0.5 ± 2.0 L/s (PEF). CONCLUSION: We did not find better models for lung function in long-term SCI but those for respiratory muscle strength showed better accuracy. SPONSORSHIP: The content of this publication was developed under grant from Wings for Life, grant number WFL-CH-017/14.

A randomised controlled trial of nasal decongestant to treat obstructive sleep apnoea in people with cervical spinal cord injury.

STUDY DESIGN: Prospective, double-blind, randomised, placebo-controlled, cross-over trial of nasal decongestion in tetraplegia. OBJECTIVES: Tetraplegia is complicated by severe, predominantly obstructive, sleep apnoea. First-line therapy for obstructive sleep apnoea is nasal continuous positive airway pressure, but this is poorly tolerated. High nasal resistance associated with unopposed parasympathetic activation of the upper airway contributes to poor adherence. This preliminary study tested whether reducing nasal decongestion improved sleep. SETTING: Participants' homes in Melbourne and Sydney, Australia. METHODS: Two sleep studies were performed in participants' homes separated by 1 week. Participants were given a nasal spray (0.5 mL of 5% phenylephrine or placebo) in random order and posterior nasal resistance measured immediately. Outcomes included sleep apnoea severity, perceived nasal congestion, sleep quality and oxygenation during sleep. RESULTS: Twelve middle-aged (average (SD) 52 (12) years) overweight (body mass index 25.3 (6.7) kg/m2) men (C4-6, AIS A and B) participated. Nasal resistance was reduced following administration of phenylephrine (p = 0.02; mean between treatment group difference -5.20: 95% confidence interval -9.09, -1.32 cmH2O/L/s). No differences were observed in the apnoea hypopnoea index (p = 0.15; -6.37: -33.3, 20.6 events/h), total sleep time (p = 0.49; -1.33: -51.8, 49.1 min), REM sleep% (p = 0.50; 2.37: -5.6, 10.3), arousal index (p = 0.76; 1.15: -17.45, 19.75), 4% oxygen desaturation index (p = 0.88; 0.63: -23.5, 24.7 events/h), or the percentage of mouth breathing events (p = 0.4; -8.07: -29.2, 13.0) between treatments. The apnoea hypopnoea index did differ between groups, however, all except one participant had proportionally more hypopnoeas than apnoeas during sleep after decongestion. CONCLUSIONS: These preliminary data found that phenylephrine acutely reduced nasal resistance but did not significantly change sleep-disordered breathing severity.

Genioglossus reflex responses to negative upper airway pressure are altered in people with tetraplegia and obstructive sleep apnoea.

KEY POINTS: Protective reflexes in the throat area (upper airway) are crucial for breathing. Impairment of these reflexes can cause breathing problems during sleep such as obstructive sleep apnoea (OSA). OSA is very common in people with spinal cord injury for unknown reasons. This study shows major changes in protective reflexes that serve to keep the upper airway open in response to suction pressures in people with tetraplegia and OSA. These results help us understand why OSA is so common in people with tetraplegia and provide new insight into how protective upper airway reflexes work more broadly. ABSTRACT: More than 60% of people with tetraplegia have obstructive sleep apnoea (OSA). However, the specific causes are unknown. Genioglossus, the largest upper-airway dilator muscle, is important in maintaining upper-airway patency. Impaired genioglossus muscle function following spinal cord injury may contribute to OSA. This study aimed to determine if genioglossus reflex responses to negative upper-airway pressure are altered in people with OSA and tetraplegia compared to non-neurologically impaired able-bodied individuals with OSA. Genioglossus reflex responses measured via intramuscular electrodes to ∼60 brief (250 ms) pulses of negative upper-airway pressure (∼-15 cmH2 O at the mask) were compared between 13 participants (2 females) with tetraplegia plus OSA and 9 able-bodied controls (2 females) matched for age and OSA severity. The initial short-latency excitatory reflex response was absent in 6/13 people with tetraplegia and 1/9 controls. Genioglossus reflex inhibition in the absence of excitation was observed in three people with tetraplegia and none of the controls. When the excitatory response was present, it was significantly delayed in the tetraplegia group compared to able-bodied controls: excitation onset latency (mean ± SD) was 32 ± 16 vs. 18 ± 9 ms, P = 0.045; peak excitation latency was 48 ± 17 vs. 33 ± 8 ms, P = 0.038. However, when present, amplitude of the excitation response was not different between groups, 195 ± 26 vs. 219 ± 98% at baseline, P = 0.55. There are major differences in genioglossus reflex morphology and timing in response to rapid changes in airway pressure in people with tetraplegia and OSA. Altered genioglossus function may contribute to the increased risk of OSA in people with tetraplegia. The precise mechanisms mediating these differences are unknown.

Diagnostic accuracy of a two-stage model for detecting obstructive sleep apnoea in chronic tetraplegia.

BACKGROUND: Obstructive sleep apnoea (OSA) is highly prevalent in people with spinal cord injury (SCI). Polysomnography (PSG) is the gold-standard diagnostic test for OSA, however PSG is expensive and frequently inaccessible, especially in SCI. A two-stage model, incorporating a questionnaire followed by oximetry, has been found to accurately detect moderate to severe OSA (MS-OSA) in a non-disabled primary care population. This study investigated the accuracy of the two-stage model in chronic tetraplegia using both the original model and a modified version for tetraplegia. METHODS: An existing data set of 78 people with tetraplegia was used to modify the original two-stage model. Multivariable analysis identified significant risk factors for inclusion in a new tetraplegia-specific questionnaire. Receiver operating characteristic (ROC) curve analyses of the questionnaires and oximetry established thresholds for diagnosing MS-OSA. The accuracy of both models in diagnosing MS-OSA was prospectively evaluated in 100 participants with chronic tetraplegia across four international SCI units. RESULTS: Injury completeness, sleepiness, self-reported snoring and apnoeas were included in the modified questionnaire, which was highly predictive of MS-OSA (ROC area under the curve 0.87 (95% CI 0.79 to 0.95)). The 3% oxygen desaturation index was also highly predictive (0.93 (0.87-0.98)). The two-stage model with modified questionnaire had a sensitivity and specificity of 83% (66-93) and 88% (75-94) in the development group, and 77% (65-87) and 81% (68-90) in the validation group. Similar results were demonstrated with the original model. CONCLUSION: Implementation of this simple alternative to full PSG could substantially increase the detection of OSA in patients with tetraplegia and improve access to treatments. TRIAL REGISTRATION NUMBER: Results, ACTRN12615000896572 (The Australian and New Zealand Clinical Trials Registry) and pre-results, NCT02176928 (clinicaltrials.gov).

Magnetic resonance imaging of the upper airway in patients with quadriplegia and obstructive sleep apnea.

The aim of this study was to investigate upper airway anatomy in quadriplegics with obstructive sleep apnea. Fifty subjects were recruited from three hospitals in Australia: people with quadriplegia due to spinal cord injury and obstructive sleep apnea (n = 11), able-bodied people with obstructive sleep apnea (n = 18), and healthy, able-bodied controls (n = 19). All underwent 3-Tesla magnetic resonance imaging of their upper airway. A subgroup (n = 34) received a topical vasoconstrictor, phenylephrine and post-phenylephrine magnetic resonance imaging. Mixed-model analysis indicated no significant differences in total airway lumen volume between the three groups (P = 0.086). Spinal cord injury-obstructive sleep apnea subjects had a significantly larger volume of soft palate (P = 0.020) and retroglossal lateral pharyngeal walls (P = 0.043) than able-bodied controls. Able-bodied-obstructive sleep apnea subjects had a smaller mandible volume than spinal cord injury-obstructive sleep apnea subjects and able-bodied control subjects (P = 0.036). No differences were seen in airway length between groups when controlling for height (P = 0.055). There was a marginal increase in velopharyngeal volume across groups post-phenylephrine (P = 0.050), and post hoc testing indicated the difference was confined to the able-bodied-obstructive sleep apnea group (P < 0.001). No other upper airway structures showed significant changes with phenylephrine administration. In conclusion, people with obstructive sleep apnea and quadriplegia do not have a structurally smaller airway than able-bodied subjects. They did, however, have greater volumes of soft palate and lateral pharyngeal walls, possibly due to greater neck fat deposition. The acute response to upper airway topical vasoconstriction was not enhanced in those with obstructive sleep apnea and quadriplegia. Changes in upper airway anatomy likely contribute to the high incidence in obstructive sleep apnea in quadriplegic subjects.

Comparison of diurnal blood pressure and urine production between people with and without chronic spinal cord injury.

STUDY DESIGN: Observational study. OBJECTIVES: To quantify diurnal blood pressure (BP) patterns and nocturnal hypertension and to measure diurnal urine production in people with chronic spinal cord injury (SCI), compared with controls without SCI. SETTING: Chronic SCI population in the community in Victoria, Australia. METHODS: Participants were recruited by advertisement, and sustained SCI at least a year prior or were healthy able-bodied volunteers. Participants underwent ambulatory BP monitoring (ABPM), measurement of urine production, and completed questionnaires regarding orthostatic symptoms. Comparisons were made between participants with tetraplegia or paraplegia and able-bodied controls. Participants with night:day systolic BP < 90% were classified as dippers, 90-100% as nondippers, and >100% as reverse dippers. RESULTS: Groups with tetraplegia (n = 51) and paraplegia (n = 33) were older (42.1 ± 15 and 41.1 ± 15 vs. 32.4 ± 13 years, mean ± s.d.) and had a higher prevalence of males (88 and 85% vs. 60%) than controls (n = 52). The average BP was 110.8 ± 1.5/64.4 ± 1.2 mmHg, 119.4 ± 2.1/69.8 ± 1.5 mmHg, and 118.1 ± 1.4/69.8 ± 1.0 mmHg in tetraplegia, paraplegia, and controls, respectively. Of participants with tetraplegia, paraplegia and controls, reverse dipping was observed in 45, 13, and 2% (p < 0.001), while nocturnal hypertension was observed in 13, 23, and 18%, respectively (p = 0.48). A reduction in nocturnal urine flow rate compared with the day was observed in paraplegia and controls, but not tetraplegia. CONCLUSIONS: Similar to the effects of acute SCI, chronic SCI, specifically tetraplegia, also causes isolated nocturnal hypertension, reverse dipping, orthostatic intolerance, and nocturnal polyuria. Cardiovascular risk management and assessment of orthostatic symptoms should include ABPM.

A randomised controlled trial of CPAP versus non-invasive ventilation for initial treatment of obesity hypoventilation syndrome.

BACKGROUND: Obesity hypoventilation syndrome (OHS) is the most common indication for home ventilation, although the optimal therapy remains unclear, particularly for severe disease. We compared Bi-level and continuous positive airways pressure (Bi-level positive airway pressure (PAP); CPAP) for treatment of severe OHS. METHODS: We conducted a multicentre, parallel, double-blind trial for initial treatment of OHS, with participants randomised to nocturnal Bi-level PAP or CPAP for 3 months. The primary outcome was frequency of treatment failure (hospital admission, persistent ventilatory failure or non-adherence); secondary outcomes included health-related quality of life (HRQoL) and sleepiness. RESULTS: Sixty participants were randomised; 57 completed follow-up and were included in analysis (mean age 53 years, body mass index 55 kg/m2, PaCO2 60 mm Hg). There was no difference in treatment failure between groups (Bi-level PAP, 14.8% vs CPAP, 13.3%, p=0.87). Treatment adherence and wake PaCO2 were similar after 3 months (5.3 hours/night Bi-level PAP, 5.0 hours/night CPAP, p=0.62; PaCO2 44.2 and 45.9 mm Hg, respectively, p=0.60). Between-group differences in improvement in sleepiness (Epworth Sleepiness Scale 0.3 (95% CI -2.8, 3.4), p=0.86) and HRQoL (Short Form (SF)36-SF6d 0.025 (95% CI -0.039, 0.088), p=0.45) were not significant. Baseline severity of ventilatory failure (PaCO2) was the only significant predictor of persistent ventilatory failure at 3 months (OR 2.3, p=0.03). CONCLUSIONS: In newly diagnosed severe OHS, Bi-level PAP and CPAP resulted in similar improvements in ventilatory failure, HRQoL and adherence. Baseline PaCO2 predicted persistent ventilatory failure on treatment. Long-term studies are required to determine whether these treatments have different cost-effectiveness or impact on mortality. TRIAL REGISTRATION NUMBER: ACTRN12611000874910, results.