Awake prone positioning in acute hypoxaemic respiratory failure.

Awake prone positioning (APP) of patients with acute hypoxaemic respiratory failure gained considerable attention during the early phases of the coronavirus disease 2019 (COVID-19) pandemic. Prior to the pandemic, reports of APP were limited to case series in patients with influenza and in immunocompromised patients, with encouraging results in terms of tolerance and oxygenation improvement. Prone positioning of awake patients with acute hypoxaemic respiratory failure appears to result in many of the same physiological changes improving oxygenation seen in invasively ventilated patients with moderate-severe acute respiratory distress syndrome. A number of randomised controlled studies published on patients with varying severity of COVID-19 have reported apparently contrasting outcomes. However, there is consistent evidence that more hypoxaemic patients requiring advanced respiratory support, who are managed in higher care environments and who can be prone for several hours, benefit most from APP use. We review the physiological basis by which prone positioning results in changes in lung mechanics and gas exchange and summarise the latest evidence base for APP primarily in COVID-19. We examine the key factors that influence the success of APP, the optimal target populations for APP and the key unknowns that will shape future research.

Objective and subjective cognition in survivors of COVID-19 one year after ICU discharge: the role of demographic, clinical, and emotional factors.

BACKGROUND: Intensive Care Unit (ICU) COVID-19 survivors may present long-term cognitive and emotional difficulties after hospital discharge. This study aims to characterize the neuropsychological dysfunction of COVID-19 survivors 12 months after ICU discharge, and to study whether the use of a measure of perceived cognitive deficit allows the detection of objective cognitive impairment. We also explore the relationship between demographic, clinical and emotional factors, and both objective and subjective cognitive deficits. METHODS: Critically ill COVID-19 survivors from two medical ICUs underwent cognitive and emotional assessment one year after discharge. The perception of cognitive deficit and emotional state was screened through self-rated questionnaires (Perceived Deficits Questionnaire, Hospital Anxiety and Depression Scale and Davidson Trauma Scale), and a comprehensive neuropsychological evaluation was carried out. Demographic and clinical data from ICU admission were collected retrospectively. RESULTS: Out of eighty participants included in the final analysis, 31.3% were women, 61.3% received mechanical ventilation and the median age of patients was 60.73 years. Objective cognitive impairment was observed in 30% of COVID-19 survivors. The worst performance was detected in executive functions, processing speed and recognition memory. Almost one in three patients manifested cognitive complaints, and 22.5%, 26.3% and 27.5% reported anxiety, depression and post-traumatic stress disorder (PTSD) symptoms, respectively. No significant differences were found in the perception of cognitive deficit between patients with and without objective cognitive impairment. Gender and PTSD symptomatology were significantly associated with perceived cognitive deficit, and cognitive reserve with objective cognitive impairment. CONCLUSIONS: One-third of COVID-19 survivors suffered objective cognitive impairment with a frontal-subcortical dysfunction 12 months after ICU discharge. Emotional disturbances and perceived cognitive deficits were common. Female gender and PTSD symptoms emerged as predictive factors for perceiving worse cognitive performance. Cognitive reserve emerged as a protective factor for objective cognitive functioning. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04422444; June 9, 2021.

Awake Prone Positioning in Non-Intubated Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19.

BACKGROUND: Awake prone positioning (APP) has been advocated to improve oxygenation and prevent intubation of patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). This paper aims to synthesize the available evidence on the efficacy of APP. METHODS: We performed a systematic review of proportional outcomes from observational studies to compare intubation rate in patients treated with APP or with standard care. RESULTS: A total of 46 published and 4 unpublished observational studies that included 2,994 subjects were included, of which 921 were managed with APP and 870 were managed with usual care. APP was associated with significant improvement of oxygenation parameters in 381 cases of 19 studies that reported this outcome. Among the 41 studies assessing intubation rates (870 subjects treated with APP and 852 subjects treated with usual care), the intubation rate was 27% (95% CI 19-37%) as compared to 30% (95% CI 20-42%) (P = .71), even when duration of application, use of adjunctive respiratory assist device (high-flow nasal cannula or noninvasive ventilation), and severity of oxygenation deficit were taken into account. There appeared to be a trend toward improved mortality when APP was compared with usual care (11% vs 22%), which was not statistically significant. CONCLUSIONS: APP was associated with improvement of oxygenation but did not reduce the intubation rate in subjects with acute respiratory failure due to COVID-19. This finding is limited by the high heterogeneity and the observational nature of included studies. Randomized controlled clinical studies are needed to definitively assess whether APP could improve key outcome such as intubation rate and mortality in these patients.

Lung Recruitment Assessed by Electrical Impedance Tomography (RECRUIT): A Multicenter Study of COVID-19 Acute Respiratory Distress Syndrome.

Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. Methods: This is the analysis of patients with coronavirus disease (COVID-19) from an ongoing multicenter prospective physiological study including patients with moderate-severe acute respiratory distress syndrome of different causes. EIT, ventilator data, hemodynamics, and arterial blood gases were obtained during PEEP titration maneuvers. EIT-based optimal PEEP was defined as the crossing point of the overdistension and collapse curves during a decremental PEEP trial. Recruitability was defined as the amount of modifiable collapse when increasing PEEP from 6 to 24 cm H2O (ΔCollapse24-6). Patients were classified as low, medium, or high recruiters on the basis of tertiles of ΔCollapse24-6. Measurements and Main Results: In 108 patients with COVID-19, recruitability varied from 0.3% to 66.9% and was unrelated to acute respiratory distress syndrome severity. Median EIT-based PEEP differed between groups: 10 versus 13.5 versus 15.5 cm H2O for low versus medium versus high recruitability (P < 0.05). This approach assigned a different PEEP level from the highest compliance approach in 81% of patients. The protocol was well tolerated; in four patients, the PEEP level did not reach 24 cm H2O because of hemodynamic instability. Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension. Clinical trial registered with www.clinicaltrials.gov (NCT04460859).

Biomarker Profiles Associated with COVID-19 Severity and Mortality.

INTRODUCTION: The aim of this study was to analyze biomarkers that might predict the severity and progression of the SARS-CoV-2 infection, both in the acute phase and after recovery. METHODS: Unvaccinated patients infected with the original strain of COVID-19 requiring ward (Group 1, n = 48) or ICU (Group 2, n = 41) admission were included. At the time of admission (visit 1), a clinical history was acquired, and blood samples were obtained. One and six months after discharge from the hospital (visits 2 and 3, respectively), a clinical history, lung function tests, and blood samples were carried out. At visit 2, patients also underwent a chest CT scan. Different cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, G-CSF, GM-CSF, IFN-É£, MCP-1, MIP-1ß, and TNF-α) and lung fibrosis biomarkers (YKL-40 and KL-6) were measured in blood samples obtained at visits 1, 2, and 3. RESULTS: At visit 1, IL-4, IL-5, and IL-6 levels were higher in Group 2 (p = 0.039, 0.011, and 0.045, respectively), and IL-17 and IL-8 levels were higher in Group 1 (p = 0.026 and 0.001, respectively). The number of patients in Groups 1 and 2 who died during hospitalization was 8 and 11, respectively. YKL-40 and KL-6 levels were higher in patients who died. Serum YKL-40 and KL-6 levels determined at visit 2 correlated negatively with FVC (p = 0.022 and p = 0.024, respectively) and FEV1 (p = 0.012 and p = 0.032, respectively) measured at visit 3. KL-6 levels also correlated negatively with the diffusing capacity of the lungs for carbon monoxide (DLCO, p = 0.001). CONCLUSIONS: Patients who required ICU admission had higher levels of Th2 cytokines, while patients admitted to the ward showed an innate immune response activation, with IL-8 release and Th1/Th17 lymphocyte contribution. Increased levels of YKL-40 and KL-6 were associated with mortality in COVID-19 patients.

Oxygen Consumption with High-Flow Nasal Oxygen versus Mechanical Ventilation- An International Multicenter Observational Study in COVID-19 Patients (PROXY-COVID).

The COVID-19 pandemic led to local oxygen shortages worldwide. To gain a better understanding of oxygen consumption with different respiratory supportive therapies, we conducted an international multicenter observational study to determine the precise amount of oxygen consumption with high-flow nasal oxygen (HFNO) and with mechanical ventilation. A retrospective observational study was conducted in three intensive care units (ICUs) in the Netherlands and Spain. Patients were classified as HFNO patients or ventilated patients, according to the mode of oxygen supplementation with which a patient started. The primary endpoint was actual oxygen consumption; secondary endpoints were hourly and total oxygen consumption during the first two full calendar days. Of 275 patients, 147 started with HFNO and 128 with mechanical ventilation. Actual oxygen use was 4.9-fold higher in patients who started with HFNO than in patients who started with ventilation (median 14.2 [8.4-18.4] versus 2.9 [1.8-4.1] L/minute; mean difference = 11.3 [95% CI 11.0-11.6] L/minute; P < 0.01). Hourly and total oxygen consumption were 4.8-fold (P < 0.01) and 4.8-fold (P < 0.01) higher. Actual oxygen consumption, hourly oxygen consumption, and total oxygen consumption are substantially higher in patients that start with HFNO compared with patients that start with mechanical ventilation. This information may help hospitals and ICUs predicting oxygen needs during high-demand periods and could guide decisions regarding the source of distribution of medical oxygen.

Effect of postextubation noninvasive ventilation with active humidification vs high-flow nasal cannula on reintubation in patients at very high risk for extubation failure: a randomized trial.

PURPOSE: High-flow nasal cannula (HFNC) oxygen therapy was noninferior to noninvasive ventilation (NIV) for preventing reintubation in a heterogeneous population at high-risk for extubation failure. However, outcomes might differ in certain subgroups of patients. Thus, we aimed to determine whether NIV with active humidification is superior to HFNC in preventing reintubation in patients with ≥ 4 risk factors (very high risk for extubation failure). METHODS: Randomized controlled trial in two intensive care units in Spain (June 2020‒June 2021). Patients ready for planned extubation with ≥ 4 of the following risk factors for reintubation were included: age > 65 years, Acute Physiology and Chronic Health Evaluation II score > 12 on extubation day, body mass index > 30, inadequate secretions management, difficult or prolonged weaning, ≥ 2 comorbidities, acute heart failure indicating mechanical ventilation, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, prolonged mechanical ventilation, or hypercapnia on finishing the spontaneous breathing trial. Patients were randomized to undergo NIV with active humidification or HFNC for 48 h after extubation. The primary outcome was reintubation rate within 7 days after extubation. Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis, multiorgan failure, length of stay, mortality, adverse events, and time to reintubation. RESULTS: Of 182 patients (mean age, 60 [standard deviation (SD), 15] years; 117 [64%] men), 92 received NIV and 90 HFNC. Reintubation was required in 21 (23.3%) patients receiving NIV vs 35 (38.8%) of those receiving HFNC (difference -15.5%; 95% confidence interval (CI) -28.3 to -1%). Hospital length of stay was lower in those patients treated with NIV (20 [12‒36.7] days vs 26.5 [15‒45] days, difference 6.5 [95%CI 0.5-21.1]). No additional differences in the other secondary outcomes were observed. CONCLUSIONS: Among adult critically ill patients at very high-risk for extubation failure, NIV with active humidification was superior to HFNC for preventing reintubation.

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic: a matched analysis.

BACKGROUND: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. METHODS: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. RESULTS: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. CONCLUSIONS: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannula.

Prone positioning of nonintubated patients with acute hypoxemic respiratory failure.

PURPOSE OF REVIEW: Since the early pandemic, prone positioning has been broadly utilized for nonintubated patients (so-called 'awake prone positioning, APP') with coronavirus disease 2019 (COVID-19) induced acute hypoxemic respiratory failure (AHRF). RECENT FINDINGS: Numerous clinical studies have been conducted to investigate the effects of APP on oxygenation, intubation, and mortality. However, several questions remain unclear, such as the patient populations who benefit most from APP, the best length of daily duration on APP, how to improve adherence to APP, and the mechanisms of APP efficacy. SUMMARY: APP has been shown to improve oxygenation for patients with COVID-19 induced AHRF and is a safe treatment. However, the benefits of reducing intubation rates are only seen in moderate-to-severe patients who are undergoing HFNC treatment. In these patients, APP should be initiated early and with a target of at least 8 h/day of APP. Pillows under the body and patients-healthcare team collaboration to find the optimal position is essential to enhance patients' adherence. Oxygenation improvement and changes in the lung ultrasound findings may help to identify those patients who are more likely to avoid the need for intubation.

Osteonecrosis and Osteomyelitis of the Proximal Third of Tibia as a Late Sequela of COVID-19: A Case Report.

Coronavirus disease was first described as an identified syndrome in December 2019 (COVID-19). Since then, a global pandemic has taken place and the disease has repeatedly been associated with thromboembolic complications, most of which are venous, but may also occur at the arterial level, even in patients receiving thromboprophylaxis. To date, only medium- and large-caliber vessels have been affected by arterial thrombosis secondary to COVID-19. This article describes the case of a 60-year-old woman with a prior severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection who developed multiple bone infarcts, complicated by secondary osteomyelitis. The patient underwent multiple surgical debridements and received a variety of antibiotics before the correct diagnosis was made and a multidisciplinary surgery was planned that provided coverage with a medial gastrocnemius flap. At 5-months follow-up, the patient had recovered well without any clinical evidence of infection or other complications. To the best of our knowledge, this is the first known case of a bone infarct complicated with a secondary osteomyelitis occurring in a patient having suffered a previous SARS-CoV-2 infection. We postulate as our main hypothesis that the prothrombogenic state secondary to SARS-CoV-2 infection may have contributed to thrombosis of small-caliber vessels, in our patient the arteria nutricia tibialis, triggering bone infarcts and a secondary infection with Staphylococcus aureus .

Lung ultrasound response to awake prone positioning predicts the need for intubation in patients with COVID-19 induced acute hypoxemic respiratory failure: an observational study.

BACKGROUND: Awake prone positioning (APP) reduces the intubation rate in COVID-19 patients treated by high-flow nasal cannula (HFNC). However, the lung aeration response to APP has not been addressed. We aimed to explore the lung aeration response to APP by lung ultrasound (LUS). METHODS: This two-center, prospective, observational study enrolled patients with COVID-19-induced acute hypoxemic respiratory failure treated by HFNC and APP. LUS score was recorded 5-10 min before, 1 h after APP, and 5-10 min after supine in the first APP session within the first three days. The primary outcome was LUS score changes in the first three days. Secondary outcomes included changes in SpO2/FiO2 ratio, respiratory rate and ROX index (SpO2/FiO2/respiratory rate) related to APP, and the rate of treatment success (patients who avoided intubation). RESULTS: Seventy-one patients were enrolled. LUS score decreased from 20 (interquartile range [IQR] 19-24) to 19 (18-21) (p < 0.001) after the first APP session, and to 19 (18-21) (p < 0.001) after three days. Compared to patients with treatment failure (n = 20, 28%), LUS score reduction after the first three days in patients with treatment success (n = 51) was greater (- 2.6 [95% confidence intervals - 3.1 to - 2.0] vs 0 [- 1.2 to 1.2], p = 0.001). A decrease in dorsal LUS score > 1 after the first APP session was associated with decreased risk for intubation (Relative risk 0.25 [0.09-0.69]). APP daily duration was correlated with LUS score reduction in patients with treatment success, especially in dorsal lung zones (r = - 0.76; p < 0.001). CONCLUSIONS: In patients with acute hypoxemic respiratory failure due to COVID-19 and treated by HFNC, APP reduced LUS score. The reduction in dorsal LUS scores after APP was associated with treatment success. The longer duration on APP was correlated with greater lung aeration. Trial registration This study was prospectively registered on clinicaltrials.gov on April 22, 2021. Identification number NCT04855162 .

Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study).

BACKGROUND: We aimed to assess the efficacy of a closed-loop oxygen control in critically ill patients with moderate to severe acute hypoxemic respiratory failure (AHRF) treated with high flow nasal oxygen (HFNO). METHODS: In this single-centre, single-blinded, randomized crossover study, adult patients with moderate to severe AHRF who were treated with HFNO (flow rate ≥ 40 L/min with FiO2 ≥ 0.30) were randomly assigned to start with a 4-h period of closed-loop oxygen control or 4-h period of manual oxygen titration, after which each patient was switched to the alternate therapy. The primary outcome was the percentage of time spent in the individualized optimal SpO2 range. RESULTS: Forty-five patients were included. Patients spent more time in the optimal SpO2 range with closed-loop oxygen control compared with manual titrations of oxygen (96.5 [93.5 to 98.9] % vs. 89 [77.4 to 95.9] %; p < 0.0001) (difference estimate, 10.4 (95% confidence interval 5.2 to 17.2). Patients spent less time in the suboptimal range during closed-loop oxygen control, both above and below the cut-offs of the optimal SpO2 range, and less time above the suboptimal range. Fewer number of manual adjustments per hour were needed with closed-loop oxygen control. The number of events of SpO2 < 88% and < 85% were not significantly different between groups. CONCLUSIONS: Closed-loop oxygen control improves oxygen administration in patients with moderate-to-severe AHRF treated with HFNO, increasing the percentage of time in the optimal oxygenation range and decreasing the workload of healthcare personnel. These results are especially relevant in a context of limited oxygen supply and high medical demand, such as the COVID-19 pandemic. Trial registration The HILOOP study was registered at www. CLINICALTRIALS: gov under the identifier NCT04965844 .

Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: analysis of a randomized controlled trial.

BACKGROUND: Awake prone positioning (APP) improves oxygenation in coronavirus disease (COVID-19) patients and, when successful, may decrease the risk of intubation. However, factors associated with APP success remain unknown. In this secondary analysis, we aimed to assess whether APP can reduce intubation rate in patients with COVID-19 and to focus on the factors associated with success. METHODS: In this multicenter randomized controlled trial, conducted in three high-acuity units, we randomly assigned patients with COVID-19-induced acute hypoxemic respiratory failure (AHRF) requiring high-flow nasal cannula (HFNC) oxygen to APP or standard care. Primary outcome was intubation rate at 28 days. Multivariate analyses were performed to identify the predictors associated to treatment success (survival without intubation). RESULTS: Among 430 patients randomized, 216 were assigned to APP and 214 to standard care. The APP group had a lower intubation rate (30% vs 43%, relative risk [RR] 0.70; CI95 0.54-0.90, P = 0.006) and shorter hospital length of stay (11 interquartile range [IQR, 9-14] vs 13 [IQR, 10-17] days, P = 0.001). A respiratory rate ≤ 25 bpm at enrollment, an increase in ROX index > 1.25 after first APP session, APP duration > 8 h/day, and a decrease in lung ultrasound score ≥ 2 within the first 3 days were significantly associated with treatment success for APP. CONCLUSION: In patients with COVID-19-induced AHRF treated by HFNC, APP reduced intubation rate and improved treatment success. A longer APP duration is associated with APP success, while the increase in ROX index and decrease in lung ultrasound score after APP can also help identify patients most likely to benefit. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov at July 20, 2021. Identification number NCT04477655. https://clinicaltrials.gov/ct2/show/NCT04477655?term=PRO-CARF&draw=2&rank=1.

Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Awake prone positioning has been broadly utilised for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure, but the results from published randomised controlled trials (RCTs) in the past year are contradictory. We aimed to systematically synthesise the outcomes associated with awake prone positioning, and evaluate these outcomes in relevant subpopulations. METHODS: In this systematic review and meta-analysis, two independent groups of researchers searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, and ClinicalTrials.gov for RCTs and observational studies (with a control group) of awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure published in English from Jan 1, 2020, to Nov 8, 2021. We excluded trials that included patients intubated before or at enrolment, paediatric patients (ie, younger than 18 years), or trials that did not include the supine position in the control group. The same two independent groups screened studies, extracted the summary data from published reports, and assessed the risk of bias. We used a random-effects meta-analysis to pool individual studies. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty and quality of the evidence. The primary outcome was the reported cumulative intubation risk across RCTs, and effect estimates were calculated as risk ratios (RR;95% CI). The analysis was primarily conducted on RCTs, and observational studies were used for sensitivity analyses. No serious adverse events associated with awake prone positioning were reported. The study protocol was prospectively registered with PROSPERO, CRD42021271285. FINDINGS: A total of 1243 studies were identified, we assessed 138 full-text articles and received the aggregated results of three unpublished RCTs; therefore, after exclusions, 29 studies were included in the study. Ten were RCTs (1985 patients) and 19 were observational studies (2669 patients). In ten RCTs, awake prone positioning compared with the supine position significantly reduced the need for intubation in the overall population (RR 0·84 [95% CI 0·72-0·97]). A reduced need for intubation was shown among patients who received advanced respiratory support (ie, high-flow nasal cannula or non-invasive ventilation) at enrolment (RR 0·83 [0·71-0·97]) and in intensive care unit (ICU) settings (RR 0·83 [0·71-0·97]) but not in patients receiving conventional oxygen therapy (RR 0·87 [0·45-1·69]) or in non-ICU settings (RR 0·88 [0·44-1·76]). No obvious risk of bias and publication bias was found among the included RCTs for the primary outcome. INTERPRETATION: In patients with COVID-19-related acute hypoxaemic respiratory failure, awake prone positioning reduced the need for intubation, particularly among those requiring advanced respiratory support and those in ICU settings. Awake prone positioning should be used in patients who have acute hypoxaemic respiratory failure due to COVID-19 and require advanced respiratory support or are treated in the ICU. FUNDING: OpenAI, Rice Foundation, National Institute for Health Research, and Oxford Biomedical Research Centre.

Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.

BACKGROUND: Awake prone positioning has been reported to improve oxygenation for patients with COVID-19 in retrospective and observational studies, but whether it improves patient-centred outcomes is unknown. We aimed to evaluate the efficacy of awake prone positioning to prevent intubation or death in patients with severe COVID-19 in a large-scale randomised trial. METHODS: In this prospective, a priori set up and defined, collaborative meta-trial of six randomised controlled open-label superiority trials, adults who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure due to COVID-19 were randomly assigned to awake prone positioning or standard care. Hospitals from six countries were involved: Canada, France, Ireland, Mexico, USA, Spain. Patients or their care providers were not masked to allocated treatment. The primary composite outcome was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. The six trials are registered with ClinicalTrials.gov, NCT04325906, NCT04347941, NCT04358939, NCT04395144, NCT04391140, and NCT04477655. FINDINGS: Between April 2, 2020 and Jan 26, 2021, 1126 patients were enrolled and randomly assigned to awake prone positioning (n=567) or standard care (n=559). 1121 patients (excluding five who withdrew from the study) were included in the intention-to-treat analysis. Treatment failure occurred in 223 (40%) of 564 patients assigned to awake prone positioning and in 257 (46%) of 557 patients assigned to standard care (relative risk 0·86 [95% CI 0·75-0·98]). The hazard ratio (HR) for intubation was 0·75 (0·62-0·91), and the HR for mortality was 0·87 (0·68-1·11) with awake prone positioning compared with standard care within 28 days of enrolment. The incidence of prespecified adverse events was low and similar in both groups. INTERPRETATION: Awake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula. FUNDING: Open AI inc, Rice Foundation, Projet Hospitalier de Recherche Clinique Interrégional, Appel d'Offre 2020, Groupement Interrégional de Recherche Clinique et d'Innovation Grand Ouest, Association pour la Promotion à Tours de la Réanimation Médicale, Fond de dotation du CHRU de Tours, Fisher & Paykel Healthcare Ltd.

Global lessons learned from COVID-19 mass casualty incidents.

With healthcare systems rapidly becoming overwhelmed and occupied by patients during a pandemic, effective and safe care for patients is easily compromised. During the course of the current pandemic, numerous treatment guidelines have been developed and published that have improved care for patients with COVID-19. Certain lessons have only been learned during the course of the outbreak, from which we can learn for future pandemics. This editorial aims to raise awareness about the importance of timely stockpiling of sufficient amounts of personal protection equipment and medications, adequate oxygen supplies, uninterrupted electricity, and fair locally adapted triage strategies.