Positive role of continuous positive airway pressure for intensive care unit patients with severe hypoxaemic respiratory failure due to COVID-19 pneumonia: A single centre experience.

OBJECTIVES: Continuous positive airway pressure (CPAP) may be a useful treatment strategy for patients with severe COVID-19 pneumonia but its effectiveness in preventing mechanical ventilation is unknown. We aimed to evaluate the outcomes of COVID-19 patients treated with CPAP and determine predictors of CPAP response. DESIGN: This was a retrospective observational cohort study. SETTING: The study took place in the intensive care unit (ICU) at Royal Papworth Hospital (RPH) in Cambridge, UK. PATIENTS: We included all consecutive patients with confirmed COVID-19 pneumonia who were transferred from neighbouring hospitals between 14th March and 6th May, 2020 for consideration of ventilatory support. INTERVENTION: We instituted the use of CPAP for all patients who arrived in RPH not intubated and were not making satisfactory progress on supplemental oxygen alone. MEASUREMENTS AND MAIN RESULTS: Of 33 self-ventilating patients included in this study, 22 (66.7%) were male and the mean age was 54 ± 13.23 patients received CPAP. They were more hypoxaemic than those treated with oxygen alone (PaO2/FiO2 ratio; 84.3 ± 19.0 vs 170.0 ± 46.0 mmHg, p = 0.001). There was a significant improvement in PaO2/FiO2 ratio 1-2 hours after CPAP initiation (167.4 ± 49.0 from 84.3 ± 19.0 mmHg, p = 0.001). 14 (61%) patients responded to CPAP and 9 required intubation. There was no difference between these two groups in terms of the severity of baseline hypoxaemia (PaO2/FiO2 ratio; 84.5 ± 16.0 vs 83.9 ± 23.0 mmHg, p = 0.94) but CPAP responders had significantly lower C-reactive protein (CRP) (176 ± 83 vs 274 ± 63 mg/L, p = 0.007), interleukin-6 (IL-6) (30 ± 47 vs 139 ± 148 pg/mL, p = 0.037), and D-dimer (321 ± 267 vs 941 + 1990 ng/mL, p = 0.003). CT pulmonary angiogram was performed in 6 out of 9 intubated patients and demonstrated pulmonary emboli in 5 of them. All patients were discharged from ICU and there were no fatalities. CONCLUSIONS: In this cohort, CPAP was an effective treatment modality to improve hypoxaemia and prevent invasive ventilation in a substantial proportion of patients with severe respiratory failure. Accepting the small sample size, we also found raised biomarkers of inflammation (CRP and IL-6) and coagulopathy (D-Dimer) to be more useful predictors of CPAP responsiveness than the severity of hypoxaemia, and could help to guide intubation decisions in this clinical setting.

Educational, supportive and behavioural interventions to improve usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea.

BACKGROUND: Although highly effective in the treatment of obstructive sleep apnoea (OSA), continuous positive airway pressure (CPAP) is not universally accepted by users. Educational, supportive and behavioural interventions may help people with OSA initiate and maintain regular and continued use of CPAP. OBJECTIVES: To assess the effectiveness of educational, supportive, behavioural, or mixed (combination of two or more intervention types) strategies that aim to encourage adults who have been prescribed CPAP to use their devices. SEARCH METHODS: Searches were conducted on the Cochrane Airways Group Specialised Register of trials. Searches are current to 29 April 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed intervention(s) designed to inform participants about CPAP/OSA, to support them in using CPAP, or to modify their behaviour to increase use of CPAP devices. DATA COLLECTION AND ANALYSIS: We assessed studies to determine their suitability for inclusion in the review. Data were extracted independently and were entered into RevMan for analysis. 'Risk of bias' assessments were performed, using the updated 'Risk of bias 2' tool, for the primary outcome, CPAP usage. Study-level 'Risk of bias' assessments were performed using the original 'Risk of bias' tool. GRADE assessment was performed using GRADEpro. MAIN RESULTS: Forty-one studies (9005 participants) are included in this review; 16 of these studies are newly identified with updated searches. Baseline Epworth Sleepiness Scale (ESS) scores indicate that most participants suffered from excessive daytime sleepiness. The majority of recruited participants had not used CPAP previously. When examining risk of bias for the primary outcome of hourly machine usage/night, 58.3% studies have high overall risk (24/41 studies), 39.0% have some concerns (16/41 studies), and 2.4% have low overall risk (1/41 studies). We are uncertain whether educational interventions improve device usage, as the certainty of evidence was assessed as very low. We were unable to perform meta-analyses for number of withdrawals and symptom scores due to high study heterogeneity. Supportive interventions probably increase device usage by 0.70 hours/night (95% confidence interval (CI) 0.36 to 1.05, N = 1426, 13 studies, moderate-certainty evidence), and low-certainty evidence indicates that the number of participants who used their devices ≥ 4 hours/night may increase from 601 to 717 per 1000 (odds ratio (OR), 1.68, 95% CI 1.08 to 2.60, N = 376, 2 studies). However, the number of withdrawals may also increase from 136 to 167 per 1000 (OR 1.27, 95% CI 0.97 to 1.66, N = 1702, 11 studies, low-certainty evidence). Participants may experience small improvements in symptoms (ESS score -0.32 points, 95% CI -1.19 to 0.56, N = 470, 5 studies, low-certainty evidence), and we are uncertain whether quality of life improves with supportive interventions, as the certainty of evidence was assessed as very low. When compared with usual care, behavioural interventions produce a clinically-meaningful increase in device usage by 1.31 hours/night (95% CI 0.95 to 1.66, N = 578, 8 studies, high-certainty evidence), probably increase the number of participants who used their machines ≥ 4 hours/night from 371 to 501 per 1000 (OR 1.70, 95% CI 1.20 to 2.41, N = 549, 6 studies, high-certainty evidence), and reduce the number of study withdrawals from 146 to 101 per 1000 (OR 0.66, 95% CI 0.44 to 0.98, N = 939, 10 studies, high-certainty evidence). Behavioural interventions may reduce symptoms (ESS score -2.42 points, 95% CI -4.27 to -0.57, N = 272, 5 studies, low-certainty evidence), but probably have no effect on quality of life (Functional Outcomes of Sleep Questionnaire (FOSQ), standardised mean difference (SMD) 0.00, 0.95% CI -0.26 to 0.26, N = 228, 3 studies, moderate-certainty evidence). We are uncertain whether behavioural interventions improve apnoea hypopnoea index (AHI), as the certainty of evidence was assessed as very low. We are uncertain if mixed interventions improve device usage, increase the number of participants using their machines ≥ 4 hours/night, reduce study withdrawals, improve quality of life, or reduce anxiety symptoms, as the certainty of evidence for these outcomes was assessed to be very low. Symptom scores via the ESS could not be measured due to considerable heterogeneity between studies. AUTHORS' CONCLUSIONS: In CPAP-naïve people with OSA, high-certainty evidence indicates that behavioural interventions yield a clinically-significant increase in hourly device usage when compared with usual care. Moderate certainty evidence shows that supportive interventions increase usage modestly. Very low-certainty evidence shows that educational and mixed interventions may modestly increase CPAP usage. The impact of improved CPAP usage on daytime sleepiness, quality of life, and mood and anxiety scores remains unclear since these outcomes were not assessed in the majority of included studies. Studies addressing the choice of interventions that best match individual patient needs and therefore result in the most successful and cost-effective therapy are needed.

Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is the repetitive closure of the upper airway during sleep. This results in disturbed sleep and excessive daytime sleepiness. It is a risk factor for long-term cardiovascular morbidity. Continuous positive airway pressure (CPAP) machines can be applied during sleep. They deliver air pressure by a nasal or oronasal mask to prevent the airway from closing, reducing sleep disturbance and improving sleep quality. Some people find them difficult to tolerate because of high pressure levels and other symptoms such as a dry mouth. Switching to machines that vary the level of air pressure required to reduce sleep disturbance could increase comfort and promote more regular use. Humidification devices humidify the air that is delivered to the upper airway through the CPAP circuit. Humidification may reduce dryness of the throat and mouth and thus improve CPAP tolerability. This updated Cochrane Review looks at modifying the delivery of positive pressure and humidification on machine usage and other clinical outcomes in OSA. OBJECTIVES: To determine the effects of positive pressure modification or humidification on increasing CPAP machine usage in adults with OSA. SEARCH METHODS: We searched Cochrane Airways Specialised Register and clinical trials registries on 15 October 2018. SELECTION CRITERIA: Randomised parallel group or cross-over trials in adults with OSA. We included studies that compared automatically adjusting CPAP (auto-CPAP), bilevel positive airway pressure (bi-PAP), CPAP with expiratory pressure relief (CPAPexp), heated humidification plus fixed CPAP, automatically adjusting CPAP with expiratory pressure relief, Bi-PAP with expiratory pressure relief, auto bi-PAP and CPAPexp with wakefulness detection with fixed pressure setting. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. We assessed the certainty of evidence using GRADE for the outcomes of machine usage, symptoms (measured by the Epworth Sleepiness Scale (ESS)), Apnoea Hypopnoea Index (AHI), quality of life measured by Functional Outcomes of Sleep Questionnaire (FOSQ), blood pressure, withdrawals and adverse events (e.g. nasal blockage or mask intolerance). The main comparison of interest in the review is auto-CPAP versus fixed CPAP. MAIN RESULTS: We included 64 studies (3922 participants, 75% male). The main comparison of auto-CPAP with fixed CPAP is based on 36 studies with 2135 participants from Europe, USA, Hong Kong and Australia. The majority of studies recruited participants who were recently diagnosed with OSA and had not used CPAP previously. They had excessive sleepiness (ESS: 13), severe sleep disturbance (AHI ranged from 22 to 59), and average body mass index (BMI) of 35 kg/m2. Interventions were delivered at home and the duration of most studies was 12 weeks or less. We judged that studies at high or unclear risk of bias likely influenced the effect of auto-CPAP on machine usage, symptoms, quality of life and tolerability, but not for other outcomes. Primary outcome Compared with average usage of about five hours per night with fixed CPAP, people probably use auto-CPAP for 13 minutes longer per night at about six weeks (mean difference (MD) 0.21 hours/night, 95% confidence interval (CI) 0.11 to 0.31; 31 studies, 1452 participants; moderate-certainty evidence). We do not have enough data to determine whether auto-CPAP increases the number of people who use machines for more than four hours per night compared with fixed CPAP (odds ratio (OR) 1.16, 95% CI 0.75 to 1.81; 2 studies, 346 participants; low-certainty evidence). Secondary outcomes Auto-CPAP probably reduces daytime sleepiness compared with fixed CPAP at about six weeks by a small amount (MD -0.44 ESS units, 95% CI -0.72 to -0.16; 25 studies, 1285 participants; moderate-certainty evidence). AHI is slightly higher with auto-CPAP than with fixed CPAP (MD 0.48 events per hour, 95% CI 0.16 to 0.80; 26 studies, 1256 participants; high-certainty evidence), although it fell with both machine types from baseline values in the studies. Ten per cent of people in auto-CPAP and 11% in the fixed CPAP arms withdrew from the studies (OR 0.90, 95% CI 0.64 to 1.27; moderate-certainty evidence). Auto-CPAP and fixed CPAP may have similar effects on quality of life, as measured by the FOSQ but more evidence is needed to be confident in this result (MD 0.12, 95% CI -0.21 to 0.46; 3 studies, 352 participants; low-certainty evidence). Two studies (353 participants) provided data on clinic-measured blood pressure. Auto-CPAP may be slightly less effective at reducing diastolic blood pressure compared to fixed CPAP (MD 2.92 mmHg, 95% CI 1.06 to 4.77 mmHg; low-certainty evidence). The two modalities of CPAP probably do not differ in their effects on systolic blood pressure (MD 1.87 mmHg, 95% CI -1.08 to 4.82; moderate-certainty evidence). Nine studies (574 participants) provided information on adverse events such as nasal blockage, dry mouth, tolerance of treatment pressure and mask leak. They used different scales to capture these outcomes and due to variation in the direction and size of effect between the studies, the comparative effects on tolerability outcomes are uncertain (very low-certainty evidence).  The evidence base for other interventions is smaller, and does not provide sufficient information to determine whether there are important differences between pressure modification strategies and fixed CPAP on machine usage outcomes, symptoms and quality of life. As with the evidence for the auto-CPAP, adverse events are measured disparately. AUTHORS' CONCLUSIONS: In adults with moderate to severe sleep apnoea starting positive airway pressure therapy, auto-CPAP probably increases machine usage by about 13 minutes per night. The effects on daytime sleepiness scores with auto-CPAP are not clinically meaningful. AHI values are slightly lower with fixed CPAP. Use of validated quality of life instruments in the studies to date has been limited, although where they have been used the effect sizes have not exceeded proposed clinically important differences. The adoption of a standardised approach to measuring tolerability would help decision-makers to balance benefits with harms from the different treatment options available. The evidence available for other pressure modification strategies does not provide a reliable basis on which to draw firm conclusions. Future studies should look at the effects of pressure modification devices and humidification in people who have already used CPAP but are unable to persist with treatment.

Unmet needs of patients with narcolepsy: perspectives on emerging treatment options.

The treatment options currently available for narcolepsy are often unsatisfactory due to suboptimal efficacy, troublesome side effects, development of drug tolerance, and inconvenience. Our understanding of the neurobiology of narcolepsy has greatly improved over the last decade. This knowledge has not yet translated into additional therapeutic options for patients, but progress is being made. Some compounds, such as histaminergic H3 receptor antagonists, may prove useful in symptom control of narcolepsy. The prospect of finding a cure still seems distant, but hypocretin replacement therapy offers some promise. In this narrative review, we describe these developments and others which may yield more effective narcolepsy treatments in the future.

Educational, supportive and behavioural interventions to improve usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea.

BACKGROUND: Although effective in the treatment of obstructive sleep apnoea (OSA), continuous positive airway pressure (CPAP) is not universally accepted by users. Educational, supportive and behavioural interventions may help people with OSA recognise the need for regular and continued use of CPAP. OBJECTIVES: To assess the effectiveness of strategies that are educational, supportive or behavioural in encouraging people who have been prescribed CPAP to use their machines. SEARCH METHODS: Searches were conducted on the Cochrane Airways Group Specialised Register of trials. Searches are current to 17 January 2013. SELECTION CRITERIA: We included randomised parallel controlled trials that assessed an intervention designed to inform participants about CPAP or OSA, to support them in using CPAP or to modify their behaviour in increasing their use of CPAP machines. Studies of any duration were considered. DATA COLLECTION AND ANALYSIS: Two review authors assessed studies to determine their suitability for inclusion in the review. Data were extracted independently and were entered into Review Manager software for analysis. MAIN RESULTS: Thirty studies (2047 participants) were included. We categorised studies by intervention type: supportive interventions during follow-up, educational interventions and behavioural therapy. Across all three intervention classes, most studies incorporated elements of more than one intervention. For the purposes of this systematic review, we categorised them by the prevailing type of intervention, which we expected would have the greatest impact on the study outcome.Baseline Epworth Sleepiness Scale (ESS) scores indicated that most participants experienced daytime sleepiness, and CPAP was indicated on the basis of sleep disturbance indices. A vast majority of recruited participants had not used CPAP previously. Most of the studies were at an unclear risk of bias overall, although because of the nature of the intervention, blinding of both study personnel and participants was not feasible, and this affected a number of key outcomes. Adverse events were not reported in these studies.Low- to moderate-quality evidence showed that all three types of interventions led to increased machine usage in CPAP-naive participants with moderate to severe OSA syndrome. Compared with usual care, supportive ongoing interventions increased machine usage by about 50 minutes per night (0.82 hours, 95% confidence interval (CI) 0.36 to 1.27, N = 803, 13 studies; low-quality evidence), increased the number of participants who used their machines for longer than four hours per night from 59 to 75 per 100 (odds ratio (OR) 2.06, 95% CI 1.22 to 3.47, N = 268, four studies; low-quality evidence) and reduced the likelihood of study withdrawal (OR 0.65, 95% CI 0.44 to 0.97, N = 903, 12 studies; moderate-quality evidence). With the exception of study withdrawal, considerable variation was evident between the results of individual studies across these outcomes. Evidence of an effect on symptoms and quality of life was statistically imprecise (ESS score -0.60 points, 95% CI -1.81 to 0.62, N = 501, eight studies; very low-quality evidence; Functional Outcomes of Sleep Questionnaire 0.98 units, 95% CI -0.84 to 2.79, N = 70, two studies; low-quality evidence, respectively).Educational interventions increased machine usage by about 35 minutes per night (0.60 hours, 95% CI 0.27 to 0.93, N = 508, seven studies; moderate-quality evidence), increased the number of participants who used their machines for longer than four hours per night from 57 to 70 per 100 (OR 1.80, 95% CI 1.09 to 2.95, N = 285, three studies; low-quality evidence) and reduced the likelihood of withdrawal from the study (OR 0.67, 95% CI 0.45 to 0.98, N = 683, eight studies; low-quality evidence). Participants experienced a small improvement in symptoms, the size of which may not be clinically significant (ESS score -1.17 points, 95% CI -2.07 to -0.26, N = 336, five studies).Behavioural therapy led to substantial improvement in average machine usage of 1.44 hours per night (95% CI 0.43 to 2.45, N = 584, six studies; low-quality evidence) and increased the number of participants who used their machines for longer than four hours per night from 28 to 47 per 100 (OR 2.23, 95% CI 1.45 to 3.45, N = 358, three studies; low-quality evidence) but with high levels of statistical heterogeneity. The estimated lower rate of withdrawal with behavioural interventions was imprecise and did not reach statistical significance (OR 0.85, 95% CI 0.57 to 1.25, N = 609, five studies, very low-quality evidence). AUTHORS' CONCLUSIONS: In CPAP-naive people with severe sleep apnoea, low-quality evidence indicates that supportive interventions that encourage people to continue to use their CPAP machines increase usage compared with usual care. Moderate-quality evidence shows that a short-term educational intervention results in a modest increase in CPAP usage. Low-quality evidence indicates that behavioural therapy leads to a large increase in CPAP machine usage. The impact of improved CPAP usage on daytime sleepiness, quality of life and long-term cardiovascular risks remains unclear. For outcomes reflecting machine usage, we downgraded for risk of bias and inconsistency. An additional limitation for daytime sleepiness and quality of life measures was imprecision. Trials in people who have struggled to persist with treatment are needed, as currently little evidence is available for this population. Optimal timing and duration and long-term effectiveness of interventions remain uncertain. The relationship between improved machine usage and effect on symptoms and quality of life requires further assessment. Studies addressing the choice of interventions that best match individual patient needs and therefore result in the most successful and cost-effective therapy are needed.