Respiratory follow-up of patients with COVID-19 pneumonia.

The COVID-19 pandemic has led to an unprecedented surge in hospitalised patients with viral pneumonia. The most severely affected patients are older men, individuals of black and Asian minority ethnicity and those with comorbidities. COVID-19 is also associated with an increased risk of hypercoagulability and venous thromboembolism. The overwhelming majority of patients admitted to hospital have respiratory failure and while most are managed on general wards, a sizeable proportion require intensive care support. The long-term complications of COVID-19 pneumonia are starting to emerge but data from previous coronavirus outbreaks such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) suggest that some patients will experience long-term respiratory complications of the infection. With the pattern of thoracic imaging abnormalities and growing clinical experience, it is envisaged that interstitial lung disease and pulmonary vascular disease are likely to be the most important respiratory complications. There is a need for a unified pathway for the respiratory follow-up of patients with COVID-19 balancing the delivery of high-quality clinical care with stretched National Health Service (NHS) resources. In this guidance document, we provide a suggested structure for the respiratory follow-up of patients with clinicoradiological confirmation of COVID-19 pneumonia. We define two separate algorithms integrating disease severity, likelihood of long-term respiratory complications and functional capacity on discharge. To mitigate NHS pressures, virtual solutions have been embedded within the pathway as has safety netting of patients whose clinical trajectory deviates from the pathway. For all patients, we suggest a holistic package of care to address breathlessness, anxiety, oxygen requirement, palliative care and rehabilitation.

Protocolised non-invasive compared with invasive weaning from mechanical ventilation for adults in intensive care: the Breathe RCT.

BACKGROUND: Invasive mechanical ventilation (IMV) is a life-saving intervention. Following resolution of the condition that necessitated IMV, a spontaneous breathing trial (SBT) is used to determine patient readiness for IMV discontinuation. In patients who fail one or more SBTs, there is uncertainty as to the optimum management strategy. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of using non-invasive ventilation (NIV) as an intermediate step in the protocolised weaning of patients from IMV. DESIGN: Pragmatic, open-label, parallel-group randomised controlled trial, with cost-effectiveness analysis. SETTING: A total of 51 critical care units across the UK. PARTICIPANTS: Adult intensive care patients who had received IMV for at least 48 hours, who were categorised as ready to wean from ventilation, and who failed a SBT. INTERVENTIONS: Control group (invasive weaning): patients continued to receive IMV with daily SBTs. A weaning protocol was used to wean pressure support based on the patient's condition. Intervention group (non-invasive weaning): patients were extubated to NIV. A weaning protocol was used to wean inspiratory positive airway pressure, based on the patient's condition. MAIN OUTCOME MEASURES: The primary outcome measure was time to liberation from ventilation. Secondary outcome measures included mortality, duration of IMV, proportion of patients receiving antibiotics for a presumed respiratory infection and health-related quality of life. RESULTS: A total of 364 patients (invasive weaning, n = 182; non-invasive weaning, n = 182) were randomised. Groups were well matched at baseline. There was no difference between the invasive weaning and non-invasive weaning groups in median time to liberation from ventilation {invasive weaning 108 hours [interquartile range (IQR) 57-351 hours] vs. non-invasive weaning 104.3 hours [IQR 34.5-297 hours]; hazard ratio 1.1, 95% confidence interval [CI] 0.89 to 1.39; p = 0.352}. There was also no difference in mortality between groups at any time point. Patients in the non-invasive weaning group had fewer IMV days [invasive weaning 4 days (IQR 2-11 days) vs. non-invasive weaning 1 day (IQR 0-7 days); adjusted mean difference -3.1 days, 95% CI -5.75 to -0.51 days]. In addition, fewer non-invasive weaning patients required antibiotics for a respiratory infection [odds ratio (OR) 0.60, 95% CI 0.41 to 1.00; p = 0.048]. A higher proportion of non-invasive weaning patients required reintubation than those in the invasive weaning group (OR 2.00, 95% CI 1.27 to 3.24). The within-trial economic evaluation showed that NIV was associated with a lower net cost and a higher net effect, and was dominant in health economic terms. The probability that NIV was cost-effective was estimated at 0.58 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. CONCLUSIONS: A protocolised non-invasive weaning strategy did not reduce time to liberation from ventilation. However, patients who underwent non-invasive weaning had fewer days requiring IMV and required fewer antibiotics for respiratory infections. FUTURE WORK: In patients who fail a SBT, which factors predict an adverse outcome (reintubation, tracheostomy, death) if extubated and weaned using NIV? TRIAL REGISTRATION: Current Controlled Trials ISRCTN15635197. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 48. See the NIHR Journals Library website for further project information.

Patients who become very unwell may require help from a breathing machine. This requires the patient to be given drugs to put them to sleep (sedation) and have a tube placed through their mouth directly into the windpipe (tube ventilation). This can be life-saving, but may cause harm if used for long periods of time. Non-invasive ventilation (mask ventilation) provides breathing support through a mask that covers the face. Mask ventilation has several advantages over tube ventilation, such as less need for sedation, and it enables the patient to cough and communicate. In previous studies, switching patients from tube to mask ventilation when they start to get better seemed to improve survival rates and reduce complications. The Breathe trial tested if using a protocol to remove tube ventilation and replace it with mask ventilation is better than continuing with tube ventilation until the patient no longer needs breathing machine support. The trial recruited 364 patients. Half of these patients were randomly selected to have the tube removed and replaced with mask ventilation and half were randomly selected to continue with tube ventilation until they no longer needed breathing machine support. The mask group spent 3 fewer days receiving tube ventilation, although the overall time needing breathing machine help (mask and tube) did not change. Fewer patients in the mask group needed antibiotics for chest infections. After removing the tube, twice as many patients needed the tube again in the mask group as in the tube group. There were no differences between the groups in the number of adverse (harm) events or the number of patients who survived to leave hospital. Mask ventilation was no more expensive than tube ventilation. In conclusion, mask ventilation may be an effective alternative to continued tube ventilation when patients start to get better in intensive care.

ß-Hydroxy-ß-methylbutyrate and its impact on skeletal muscle mass and physical function in clinical practice: a systematic review and meta-analysis.

BACKGROUND: Loss of skeletal muscle mass and muscle weakness are common in a variety of clinical conditions with both wasting and weakness associated with an impairment of physical function. ß-Hydroxy-ß-methylbutyrate (HMB) is a nutrition supplement that has been shown to favorably influence muscle protein turnover and thus potentially plays a role in ameliorating skeletal muscle wasting and weakness. OBJECTIVES: The aim of this study was to investigate the efficacy of HMB alone, or supplements containing HMB, on skeletal muscle mass and physical function in a variety of clinical conditions characterized by loss of skeletal muscle mass and weakness. METHODS: A systematic review and meta-analysis of randomized controlled trials reporting outcomes of muscle mass, strength, and physical function was performed. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment. Outcome data were synthesized through meta-analysis with the use of a random-effects model and data presented as standardized mean differences (SMDs). RESULTS: Fifteen randomized controlled trials were included, involving 2137 patients. Meta-analysis revealed some evidence to support the effect of HMB alone, or supplements containing HMB, on increasing skeletal muscle mass (SMD = 0.25; 95% CI: -0.00, 0.50; z = 1.93; P = 0.05; I2 = 58%) and strong evidence to support improving muscle strength (SMD = 0.31; 95% CI: 0.12, 0.50; z = 3.25; P = 0.001; I2 = 0%). Effect sizes were small. No effect on bodyweight (SMD = 0.16; 95% CI: -0.08, 0.41; z = 1.34; P = 0.18; I2 = 67%) or any other outcome was found. No study was considered to have low risk of bias in all categories. CONCLUSION: HMB, and supplements containing HMB, increased muscle mass and strength in a variety of clinical conditions, although the effect size was small. Given the bias associated with many of the included studies, further high-quality studies should be undertaken to enable interpretation and translation into clinical practice. The trial was registered on PROSPERO as CRD42017058517.

Pulmonary rehabilitation, physical activity, respiratory failure and palliative respiratory care.

The CIRO Academy in Horn (the Netherlands) organised a 2-day meeting to present and discuss the studies published in 2017 pertaining to key priority areas of respiratory and critical care medicine. This review summarises studies focussing on pulmonary rehabilitation and exercise training, physical activity, chronic respiratory failure and palliative respiratory care published in 2017.

Nutrition and Exercise Rehabilitation in Obesity hypoventilation syndrome (NERO): a pilot randomised controlled trial.

BACKGROUND: Respiratory management of obesity hypoventilation syndrome (OHS) focusses on the control of sleep-disordered breathing rather than the treatment of obesity. Currently, there are no data from randomised trials of weight loss targeted rehabilitation programmes for patients with OHS. INTERVENTION: A 3-month multimodal hybrid inpatient-outpatient motivation, exercise and nutrition rehabilitation programme, in addition to non invasive ventilation (NIV), would result in greater per cent weight loss compared with standard care. METHODS: A single-centre pilot randomised controlled trial allocated patients to either standard care or standard care plus rehabilitation. Primary outcome was per cent weight loss at 12 months with secondary exploratory outcomes of weight loss, exercise capacity and health-related quality of life (HRQOL) at the end of the rehabilitation programme to assess the intervention effect. RESULTS: Thirty-seven patients (11 male, 59.8±12.7 years) with a body mass index of 51.1±7.7 kg/m2 were randomised. At 12 months, there was no between-group difference in per cent weight loss (mean difference -5.9% (95% CI -14.4% to 2.7%; p=0.17)). At 3 months, there was a greater per cent weight loss (mean difference -5% (95% CI -8.3% to -1.4%; p=0.007)), increased exercise capacity (6 min walk test 60 m (95% CI 29.5 to 214.5) vs 20 m (95% CI 11.5 to 81.3); p=0.036) and HRQL (mean difference SF-36 general health score (10 (95% CI 5 to 21.3) vs 0 (95% CI -5 to 10); p=0.02)) in the rehabilitation group. CONCLUSION: In patients with OHS, a 3-month comprehensive rehabilitation programme, in addition to NIV, resulted in improved weight loss, exercise capacity and QOL at the end of the rehabilitation period, but these effects were not demonstrated at 12 months, in part, due to the limited retention of patients at 12 months. TRIAL REGISTRATION NUMBER: Pre-results; NCT01483716.

Randomised sham-controlled trial of transcutaneous electrical stimulation in obstructive sleep apnoea.

INTRODUCTION: Obstructive sleep apnoea (OSA) is characterised by a loss of neuromuscular tone of the upper airway dilator muscles while asleep. This study investigated the effectiveness of transcutaneous electrical stimulation in patients with OSA. PATIENTS AND METHODS: This was a randomised, sham-controlled crossover trial using transcutaneous electrical stimulation of the upper airway dilator muscles in patients with confirmed OSA. Patients were randomly assigned to one night of sham stimulation and one night of active treatment. The primary outcome was the 4% oxygen desaturation index, responders were defined as patients with a reduction >25% in the oxygen desaturation index when compared with sham stimulation and/or with an index <5/hour in the active treatment night. RESULTS: In 36 patients (age mean 50.8 (SD 11.2) years, male/female 30/6, body mass index median 29.6 (IQR 26.9-34.9) kg/m(2), Epworth Sleepiness Scale 10.5 (4.6) points, oxygen desaturation index median 25.7 (16.0-49.1)/hour, apnoea-hypopnoea index median 28.1 (19.0-57.0)/hour) the primary outcome measure improved when comparing sham stimulation (median 26.9 (17.5-39.5)/hour) with active treatment (median 19.5 (11.6-40.0)/hour; p=0.026), a modest reduction of the mean by 4.1 (95% CI -0.6 to 8.9)/hour. Secondary outcome parameters of patients' perception indicated that stimulation was well tolerated. Responders (47.2%) were predominantly from the mild-to-moderate OSA category. In this subgroup, the oxygen desaturation index was reduced by 10.0 (95% CI 3.9 to 16.0)/hour (p<0.001) and the apnoea-hypopnoea index was reduced by 9.1 (95% CI 2.0 to 16.2)/hour (p=0.004). CONCLUSION: Transcutaneous electrical stimulation of the pharyngeal dilators during a single night in patients with OSA improves upper airway obstruction and is well tolerated. TRIAL REGISTRATION NUMBER: NCT01661712.

Neuromuscular electrical stimulation to improve exercise capacity in patients with severe COPD: a randomised double-blind, placebo-controlled trial.

BACKGROUND: Skeletal muscle dysfunction and exercise intolerance are common in severe chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of neuromuscular electrical stimulation (NMES) as a home-based exercise therapy. METHODS: In this double-blind, placebo-controlled trial, undertaken across three UK National Health Service sites, we randomly assigned (1:1) adults with COPD, a forced expiratory volume in 1 s (FEV1) less than 50% predicted, and incapacitating breathlessness (Medical Research Council dyspnoea scale ≥4) to receive active or placebo NMES, daily over a 6-week period. Randomisation was by an independent system using minimisation to balance age, GOLD stage, and quadriceps strength. Participants and outcome assessors were masked to group allocation. The primary endpoint was change in 6-min walk test (6MWT) distance at 6 weeks. Analysis was by intention to treat. The trial was registered as ISRCTN15985261 and is now closed. FINDINGS: Between June 29, 2012, and July 4, 2014, we enrolled 73 participants, of whom 52 participants were randomly assigned; 25 to receive active NMES and 27 to placebo NMES. Change in 6MWT distance was greater in the active NMES group (mean 29·9 [95% CI 8·9 to 51·0]) compared with in the placebo group (-5·7 [-19·9 to 8·4]; mean difference at 6 weeks 35·7 m [95% CI 10·5 to 60·9]; p=0·005). Sensitivity analyses for complete-cases and adjustment for baseline values showed similar results. 6 weeks after stopping the intervention the effect waned (7·3 m [95% CI -32·5 to 47·0]; p=0·50). The proportion of participants who had adverse events was similar between groups (five [20%] in the active NMES group and nine [33%] in the placebo group). Two participants, one from each group, reported persistent erythema, which was considered to be possibly related to NMES and the use of adhesive electrodes. INTERPRETATION: NMES improves functional exercise capacity in patients with severe COPD by enhancing quadriceps muscle mass and function. These data support the use of NMES in the management of patients unable to engage with conventional pulmonary rehabilitation. More work is needed to study how to maintain the effect. FUNDING: National Institute for Health Research.

Functional electrical stimulation with cycling in the critically ill: a pilot case-matched control study.

PURPOSE: The purpose was to determine (a) safety and feasibility of functional electrical stimulation (FES)-cycling and (b) compare FES-cycling to case-matched controls in terms of functional recovery and delirium outcomes. MATERIALS AND METHODS: Sixteen adult intensive care unit patients with sepsis ventilated for more than 48 hours and in the intensive care unit for at least 4 days were included. Eight subjects underwent FES-cycling in addition to usual care and were compared to 8 case-matched control individuals. Primary outcomes were safety and feasibility of FES-cycling. Secondary outcomes were Physical Function in Intensive Care Test scored on awakening, time to reach functional milestones, and incidence and duration of delirium. RESULTS: One minor adverse event was recorded. Sixty-nine out of total possible 95 FES sessions (73%) were completed. A visible or palpable contraction was present 80% of the time. There was an improvement in Physical Function in Intensive Care Test score of 3.9/10 points in the intervention cohort with faster recovery of functional milestones. There was also a shorter duration of delirium in the intervention cohort. CONCLUSIONS: The delivery of FES-cycling is both safe and feasible. The preliminary findings suggest that FES-cycling may improve function and reduce delirium. Further research is required to confirm the findings of this study and evaluate the efficacy of FES-cycling.

High pressure versus high intensity noninvasive ventilation in stable hypercapnic chronic obstructive pulmonary disease: a randomized crossover trial.

BACKGROUND: High-intensity (high-pressure and high backup rate) noninvasive ventilation has recently been advocated for the management of stable hypercapnic chronic obstructive pulmonary disease (COPD). However, the relative contributions of high inspiratory pressure and high backup rate to ventilator adherence and physiological outcome have not been investigated. METHODS: Patients with stable hypercapnic COPD (daytime PaCO(2) > 6 kPa) and nocturnal hypoventilation were enrolled. Patients were randomly allocated to high-pressure and high backup rate (high-intensity) and high-pressure and low backup rate (high-pressure) for a 6-week period. At the end of the first treatment period, patients were switched to the alternative treatment. The primary outcome measure was mean nightly ventilator usage. RESULTS: Twelve patients were recruited, with seven completing the 12-week trial protocol. The mean patient age was 71 ± 8 years, with a forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) of 50% ± 13% and FEV(1) of 32% ± 12%. The baseline PaCO(2) and PaO(2) were 8.6 ± 1.7 kPa and 7.3 ± 1.4 kPa, respectively. There was no significant difference demonstrated in mean nightly ventilator usage between the high-intensity and high-pressure groups (difference of 4 minutes; 95% confidence interval -45 to 53; P = 0.9). Furthermore, there were no differences in any of the secondary endpoints, with the exception of the respiratory domain of the Severe Respiratory Insufficiency questionnaire, which was lower in the high-intensity arm than in the high-pressure arm (57 ± 11 versus 69 ± 16; P < 0.05). CONCLUSION: There was no additional benefit, in terms of night-time ventilator adherence or any of the other measured parameters, demonstrated by addition of a high backup rate to high-pressure noninvasive ventilation. These data suggest that it is the high-pressure component of the high-intensity noninvasive ventilation approach that plays the important therapeutic role in the management of hypercapnic respiratory failure in COPD patients.