Improving physical function of patients following intensive care unit admission (EMPRESS): protocol of a randomised controlled feasibility trial.

INTRODUCTION: Physical rehabilitation delivered early following admission to the intensive care unit (ICU) has the potential to improve short-term and long-term outcomes. The use of supine cycling together with other rehabilitation techniques has potential as a method of introducing rehabilitation earlier in the patient journey. The aim of the study is to determine the feasibility of delivering the designed protocol of a randomised clinical trial comparing a protocolised early rehabilitation programme including cycling with usual care. This feasibility study will inform a larger multicentre study. METHODS AND ANALYSIS: 90 acute care medical patients from two mixed medical-surgical ICUs will be recruited. We will include ventilated patients within 72 hours of initiation of mechanical ventilation and expected to be ventilated a further 48 hours or more. Patients will receive usual care or usual care plus two 30 min rehabilitation sessions 5 days/week.Feasibility outcomes are (1) recruitment of one to two patients per month per site; (2) protocol fidelity with >75% of patients commencing interventions within 72 hours of mechanical ventilation, with >70% interventions delivered; and (3) blinded outcome measures recorded at three time points in >80% of patients. Secondary outcomes are (1) strength and function, the Physical Function ICU Test-scored measured on ICU discharge; (2) hospital length of stay; and (3) mental health and physical ability at 3 months using the WHO Disability Assessment Schedule 2. An economic analysis using hospital health services data reported with an embedded health economic study will collect and assess economic and quality of life data including the Hospital Anxiety and Depression Scales core, the Euroqol-5 Dimension-5 Level and the Impact of Event Score. ETHICS AND DISSEMINATION: The study has ethical approval from the South Central Hampshire A Research Ethics Committee (19/SC/0016). All amendments will be approved by this committee. An independent trial monitoring committee is overseeing the study. Results will be made available to critical care survivors, their caregivers, the critical care societies and other researchers. TRIAL REGISTRATION NUMBER: NCT03771014.

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration: isrctn.org Identifier: ISRCTN16912075.

Severe Acute Respiratory Syndrome Coronavirus 2

COVID-19, caused by SARS-CoV-2, is an emerging viral respiratory pathogen. The disease was first described in China in 2019, likely emerging as a zoonosis, before spreading worldwide to cause a severe global pandemic in 2020. COVID-19 is transmitted person to person, predominantly by droplet spread. COVID-19 causes a wide spectrum of clinical illness ranging from asymptomatic infection, to a mild self-limiting illness. A small proportion of individuals will go on to develop a more severe respiratory illness which may be complicated by acute respiratory distress syndrome. The majority of individuals will make a full recovery but a minority of patients will have a more severe outcome. Age is the strongest predictor of outcomes with mortality increasing to 15% or higher among those aged 80years or older. Treatment options for COVID-19 continue to evolve. The strongest current evidence is the use of systemic corticosteroids which reduce mortality in patients with moderate to severe COVID-19. Given the epidemic nature of COVID-19 early surge planning and expansion of both staff and bed base capacity are critical. At the time of writing a number of promising COVID-19 vaccines have been developed but the long term impact of these vaccines on the pandemic is uncertain.

High-flow therapy: physiological effects and clinical applications.

Humidified high-flow therapy (HFT) is a noninvasive respiratory therapy, typically delivered through a nasal cannula interface, which delivers a stable fraction of inspired oxygen (F IO2 ) at flow rates of up to 60 L·min-1. It is well-tolerated, simple to set up and ideally applied at 37°C to permit optimal humidification of inspired gas. Flow rate and F IO2 should be selected based on patients' inspiratory effort and severity of hypoxaemia. HFT yields beneficial physiological effects, including improved mucociliary clearance, enhanced dead space washout and optimisation of pulmonary mechanics. Robust evidence supports its application in the critical care setting (treatment of acute hypoxaemic respiratory failure and prevention of post-extubation respiratory failure) and emerging data supports HFT use during bronchoscopy, intubation and breaks from noninvasive ventilation or continuous positive airway pressure. There are limited data on HFT use in patients with hypercapnic respiratory failure, as an adjunct to pulmonary rehabilitation and in the palliative care setting, and further research is needed to validate the findings of small studies. The COVID-19 pandemic raises questions regarding HFT efficacy in COVID-19-related hypoxaemic respiratory failure and concerns regarding aerosolisation of respiratory droplets. Clinical trials are ongoing and healthcare professionals should implement strict precautions to mitigate the risk of nosocomial transmission. EDUCATIONAL AIMS: Provide a practical guide to HFT setup and delivery.Outline the physiological effects of HFT on the respiratory system.Describe clinical applications of HFT in adult respiratory and critical care medicine and evaluate the supporting evidence.Discuss application of HFT in COVID-19 and aerosolisation of respiratory droplets.

Outcomes of critically ill COVID-19 patients managed in a high-volume severe respiratory failure and ECMO centre in the United Kingdom.

During the Coronavirus Disease 2019 (COVID-19) pandemic institutions have needed to develop pragmatic clinical pathways to balance the excess critical care demand and local resources. In this single-centre retrospective cohort study we describe the outcomes of COVID-19 patients admitted to Guy's and St. Thomas' NHS Foundation Trust (GSTT) critical care service. Patients were managed according to a local respiratory failure management pathway that was predicated on timely invasive ventilation when indicated and tailored ventilatory strategies according to pulmonary mechanics. Between 2 March and 25 May 2020 GSTT critical care service admitted 316 patients with confirmed COVID-19. Of the 201 patients admitted directly through the Emergency Department (ED) with a completed critical care outcome, 71.1% survived to critical care discharge. These favourable outcomes may serve to inform the wider debate on optimal organ support in COVID-19.

Timing of Tracheostomy for Prolonged Respiratory Wean in Critically Ill Coronavirus Disease 2019 Patients: A Machine Learning Approach.

OBJECTIVES: To propose the optimal timing to consider tracheostomy insertion for weaning of mechanically ventilated patients recovering from coronavirus disease 2019 pneumonia. We investigated the relationship between duration of mechanical ventilation prior to tracheostomy insertion and in-hospital mortality. In addition, we present a machine learning approach to facilitate decision-making. DESIGN: Prospective cohort study. SETTING: Guy's & St Thomas' Hospital, London, United Kingdom. PATIENTS: Consecutive patients admitted with acute respiratory failure secondary to coronavirus disease 2019 requiring mechanical ventilation between March 3, 2020, and May 5, 2020. INTERVENTIONS: Baseline characteristics and temporal trends in markers of disease severity were prospectively recorded. Tracheostomy was performed for anticipated prolonged ventilatory wean when levels of respiratory support were favorable. Decision tree was constructed using C4.5 algorithm, and its classification performance has been evaluated by a leave-one-out cross-validation technique. MEASUREMENTS AND MAIN RESULTS: One-hundred seventy-six patients required mechanical ventilation for acute respiratory failure, of which 87 patients (49.4%) underwent tracheostomy. We identified that optimal timing for tracheostomy insertion is between day 13 and day 17. Presence of fibrosis on CT scan (odds ratio, 13.26; 95% CI [3.61-48.91]; p ≤ 0.0001) and Pao2:Fio2 ratio (odds ratio, 0.98; 95% CI [0.95-0.99]; p = 0.008) were independently associated with tracheostomy insertion. Cox multiple regression analysis showed that chronic obstructive pulmonary disease (hazard ratio, 6.56; 95% CI [1.04-41.59]; p = 0.046), ischemic heart disease (hazard ratio, 4.62; 95% CI [1.19-17.87]; p = 0.027), positive end-expiratory pressure (hazard ratio, 1.26; 95% CI [1.02-1.57]; p = 0.034), Pao2:Fio2 ratio (hazard ratio, 0.98; 95% CI [0.97-0.99]; p = 0.003), and C-reactive protein (hazard ratio, 1.01; 95% CI [1-1.01]; p = 0.005) were independent late predictors of in-hospital mortality. CONCLUSIONS: We propose that the optimal window for consideration of tracheostomy for ventilatory weaning is between day 13 and 17. Late predictors of mortality may serve as adverse factors when considering tracheostomy, and our decision tree provides a degree of decision support for clinicians.

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.

RECOVERY- Respiratory Support: Respiratory Strategies for patients with suspected or proven COVID-19 respiratory failure; Continuous Positive Airway Pressure, High-flow Nasal Oxygen, and standard care: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVE: The trial objective is to determine if Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) is clinically effective compared to standard oxygen therapy in patients with confirmed or suspected COVID-19. TRIAL DESIGN: Adaptive (group-sequential), parallel group, pragmatic, superiority randomised controlled, open-label, multi-centre, effectiveness trial. PARTICIPANTS: The trial is being conducted across approximately 60 hospitals across England, Wales, Scotland, and Northern Ireland. Inpatients at participating hospitals are eligible to participate if they have respiratory failure with suspected or proven COVID-19, and meet all of the inclusion criteria and none of the exclusion criteria. INCLUSION CRITERIA: 1) Adults ≥ 18 years; 2) Admitted to hospital with suspected or proven COVID-19; 3) Receiving oxygen with fraction of inspired oxygen (FiO2) ≥0.4 and peripheral oxygen saturation (SpO2) ≤94%; and 4) Plan for escalation to tracheal intubation if needed. EXCLUSION CRITERIA: 1) Planned tracheal intubation and mechanical ventilation imminent within 1 hour; 2) Known or clinically apparent pregnancy; 3) Any absolute contraindication to CPAP or HFNO; 4) Decision not to intubate due to ceiling of treatment or withdrawal of treatment anticipated; and 5) Equipment for both CPAP and HFNO not available. INTERVENTION AND COMPARATOR: Intervention one: Continuous positive airway pressure delivered by any device. Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Intervention two: High-flow nasal oxygen delivered by any device. Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Comparator group: Standard care- oxygen delivered by face mask or nasal cannula (excluding the use of continuous positive airway pressure or high-flow nasal oxygen). Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Intervention delivery continues up to the point of death, tracheal intubation, or clinical determination that there is no ongoing need (palliation or improvement). MAIN OUTCOMES: The primary outcome is a composite outcome comprising tracheal intubation or mortality within 30 days following randomisation. Secondary outcomes include tracheal intubation rate, time to tracheal intubation, duration of invasive ventilation, mortality rate, time to mortality, length of hospital stay, and length of critical care stay. RANDOMISATION: Participants are randomised in a 1:1:1 ratio to receive either continuous positive airway pressure, high-flow nasal oxygen or standard care. Due to the challenging environment of study delivery, a specific intervention may not always be available at the hospital site. The study uses two integrated randomisation systems to allow, where required, the site to randomise between all three interventions, between CPAP and standard care, and between HFNO and standard care. System integration ensures maintenance of balance between interventions. Randomisation is performed using a telephone-based interactive voice response system to maintain allocation concealment. The randomisation sequence was computer-generated using the minimisation method. Participant randomisation is stratified by site, gender (M/F), and age (<50, >=50 years). BLINDING (MASKING): The nature of the trial interventions precludes blinding of the researcher, patient and clinical team. Primary and secondary outcomes are all objective outcomes, thereby minimising the risk of detection bias. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 4002 participants (1334 to be randomized to each of the three study arms) TRIAL STATUS: Current protocol: Version 4.0, 29th May 2020. Recruitment began on April 6, 2020 and is anticipated to be complete by April 5, 2021. The trial has been awarded Urgent Public Health status by the National Institute of Health Research on 13th April 2020. TRIAL REGISTRATION: ISRCTN, ISRCTN16912075. Registered 6th April 2020, http://www.isrctn.com/ISRCTN16912075 FULL PROTOCOL: The full protocol (version 4.0, 29th May 2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Recommendation of a practical guideline for safe tracheostomy during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic is placing unprecedented demand upon critical care services for invasive mechanical ventilation. There is current uncertainty regarding the role of tracheostomy for weaning ventilated patients with COVID-19 pneumonia. This is due to a number of factors including prognosis, optimal healthcare resource utilisation, and safety of healthcare workers when performing such a high-risk aerosol-generating procedure. METHODS: Literature review and proposed practical guideline based on the experience of a tertiary healthcare institution with 195 critical care admissions for COVID-19 up until 4th April 2020. RESULTS: A synthesis of the current international literature and reported experience is presented with respect to prognosis, viral load and staff safety, thus leading to a pragmatic recommendation that tracheostomy is not performed until at least 14 days after endotracheal intubation in COVID-19 patients. Practical steps to minimise aerosol generation in percutaneous tracheostomy are outlined and we describe the process and framework for setting up a dedicated tracheostomy team. CONCLUSION: In selected COVID-19 patients, there is a role for tracheostomy to aid in weaning and optimise healthcare resource utilisation. Both percutaneous and open techniques can be performed safely with careful modifications to technique and appropriate enhanced personal protective equipment. ORL-HNS surgeons can play a valuable role in forming tracheostomy teams to support critical care teams during this global pandemic.