Dataset Information

Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.

ABSTRACT:

Background

The effect of awake prone positioning on intubation rates is not established. The aim of this trial was to investigate if a protocol for awake prone positioning reduces the rate of endotracheal intubation compared with standard care among patients with moderate to severe hypoxemic respiratory failure due to COVID-19.

Methods

We conducted a multicenter randomized clinical trial. Adult patients with confirmed COVID-19, high-flow nasal oxygen or noninvasive ventilation for respiratory support and a PaO₂/FiO₂ ratio ≤ 20 kPa were randomly assigned to a protocol targeting 16 h prone positioning per day or standard care. The primary endpoint was intubation within 30 days. Secondary endpoints included duration of awake prone positioning, 30-day mortality, ventilator-free days, hospital and intensive care unit length of stay, use of noninvasive ventilation, organ support and adverse events. The trial was terminated early due to futility.

Results

Of 141 patients assessed for eligibility, 75 were randomized of whom 39 were allocated to the control group and 36 to the prone group. Within 30 days after enrollment, 13 patients (33%) were intubated in the control group versus 12 patients (33%) in the prone group (HR 1.01 (95% CI 0.46-2.21), P = 0.99). Median prone duration was 3.4 h [IQR 1.8-8.4] in the control group compared with 9.0 h per day [IQR 4.4-10.6] in the prone group (P = 0.014). Nine patients (23%) in the control group had pressure sores compared with two patients (6%) in the prone group (difference - 18% (95% CI - 2 to - 33%); P = 0.032). There were no other differences in secondary outcomes between groups.

Conclusions

The implemented protocol for awake prone positioning increased duration of prone positioning, but did not reduce the rate of intubation in patients with hypoxemic respiratory failure due to COVID-19 compared to standard care.

Trial registration

ISRCTN54917435. Registered 15 June 2020 ( https://doi.org/10.1186/ISRCTN54917435 ).

SUBMITTER: Rosen J

PROVIDER: S-EPMC8200797 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Infection with SARS-CoV-2 can result in Coronavirus Disease–19 (COVID-19) [1, 2]. While the majority of patients are asymptomatic or have mild disease [3], approximately 14% develop more severe disease including hypoxemic respiratory failure and/or Acute Respiratory Distress Syndrome (ARDS) [3]. Prone positioning is a life-saving intervention for mechanically ventilated patients with moderate-severe ARDS [4]. Based on this, the World Health Organization (WHO) guidelines recommend these patients be considered for a trial of prone positioning [5]. Recently the use of prone positioning in awake non-intubated COVID-19 patients has been recommended by several notable organizations with the goal of preventing intubation and potentially improving patient-oriented outcomes [6, 7]. In contrast to prone positioning for intubated mechanically ventilated patients with ARDS, there have been no randomized control trials examining the role of awake prone positioning for non-intubated patients with hypoxemic respiratory failure. To further explore this question we used rapid review methodology (Tricco et al., 2015 [8]) to quickly identify and synthesize studies examining the effect of awake prone positioning on patients with hypoxemic respiratory failure (including those with ARDS and/or COVID-19). Methods We have elected to use “rapid review” methodology rather than “systematic review” methodology primarily due to the speed and efficiency through which we are able to conduct this review, as previously described [8]. In the absence of an EQUATOR guidance document, we used PRISMA guidelines where applicable [9]. Studies were included if they met the following criteria 1) population – non-intubated patients with hypoxemic respiratory failure, 2) intervention – prone positioning, 3) comparator – usual management, 4) outcomes – intubation, survival, change in respiratory parameters, adverse events, 5) setting – hospitalized patients 6) study design – observational or randomized control trial. Studies were not limited to ARDS or COVID-19 patients. The search strategy was developed by a critical care physician (KP), a critical care epidemiologist (KF) and a medical librarian (NL) (See search details in Online Supplement). Briefly, the search strategy involved combinations of keywords and subject headings relating to the concepts of, 1) SARS-Cov-2 or COVID-19 or coronavirus, 2) awake prone positioning, and 3) hypoxemic respiratory failure, including but not limited to ARDS and other potentially relevant conditions. The search was conducted on May 19, 2020 and was updated on August 7, 2020 with no restrictions on publication language or date. Databases and grey literature sources searched included: MEDLINE (Ovid), PubMed, Trip PRO, Cochrane Library, LitCOVID, WHO COVID-19 Research Database, Centre for Evidence-Based Medicine (CEBM), National Institute for Health and Care Excellence (NICE), medRxiv, BMJ Best Practice, Cambridge Coronavirus Free Access Collection, and Google Scholar. Titles and abstracts were reviewed independently and in duplicate (KP and JW) for selection for full text review. Disagreements were resolved through discussion or with a third reviewer (KS). Full text review and data abstraction was conducted independently and in duplicate (KP, KS, JW). Data abstracted included study characteristics, participant demographics, and outcomes.

Project description:ObjectiveTo determine the efficacy and safety of awake prone positioning versus usual care in non-intubated adults with hypoxemic respiratory failure due to covid-19.DesignSystematic review with frequentist and bayesian meta-analyses.Study eligibilityRandomized trials comparing awake prone positioning versus usual care in adults with covid-19 related hypoxemic respiratory failure. Information sources were Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to 4 March 2022.Data extraction and synthesisTwo reviewers independently extracted data and assessed risk of bias. Random effects meta-analyses were performed for the primary and secondary outcomes. Bayesian meta-analyses were performed for endotracheal intubation and mortality outcomes. GRADE certainty of evidence was assessed for outcomes.Main outcome measuresThe primary outcome was endotracheal intubation. Secondary outcomes were mortality, ventilator-free days, intensive care unit (ICU) and hospital length of stay, escalation of oxygen modality, change in oxygenation and respiratory rate, and adverse events.Results17 trials (2931 patients) met the eligibility criteria. 12 trials were at low risk of bias, three had some concerns, and two were at high risk. Awake prone positioning reduced the risk of endotracheal intubation compared with usual care (crude average 24.2% v 29.8%, relative risk 0.83, 95% confidence interval 0.73 to 0.94; high certainty). This translates to 55 fewer intubations per 1000 patients (95% confidence interval 87 to 19 fewer intubations). Awake prone positioning did not significantly affect secondary outcomes, including mortality (15.6% v 17.2%, relative risk 0.90, 0.76 to 1.07; high certainty), ventilator-free days (mean difference 0.97 days, 95% confidence interval -0.5 to 3.4; low certainty), ICU length of stay (-2.1 days, -4.5 to 0.4; low certainty), hospital length of stay (-0.09 days, -0.69 to 0.51; moderate certainty), and escalation of oxygen modality (21.4% v 23.0%, relative risk 1.04, 0.74 to 1.44; low certainty). Adverse events related to awake prone positioning were uncommon. Bayesian meta-analysis showed a high probability of benefit with awake prone positioning for endotracheal intubation (non-informative prior, mean relative risk 0.83, 95% credible interval 0.70 to 0.97; posterior probability for relative risk <0.95=96%) but lower probability for mortality (0.90, 0.73 to 1.13; <0.95=68%).ConclusionsAwake prone positioning compared with usual care reduces the risk of endotracheal intubation in adults with hypoxemic respiratory failure due to covid-19 but probably has little to no effect on mortality or other outcomes.Systematic review registrationPROSPERO CRD42022314856.

Project description:BackgroundIt is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation-related complications.Design and methodsThe PRONELIFE study is an investigator-initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all-cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning.DiscussionThe PRONELIFE study is among the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation-patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible-however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study have the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure.Trial registrationISRCTN ISRCTN11536318 . Registered on 17 September 2021. The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).

Project description:BackgroundAwake 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).MethodsThis 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).ResultsSeventy-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).ConclusionsIn 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 .