Effect of Awake Prone Positioning on Endotracheal Intubation in Patients With COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial | Critical Care Medicine | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Effect of Awake Prone Positioning on Endotracheal Intubation in Patients With COVID-19 and Acute Respiratory FailureA Randomized Clinical Trial

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Does prone positioning reduce endotracheal intubation in adults who were awake and not intubated and who had hypoxemic respiratory failure from COVID-19?

Findings  In this randomized clinical trial that included 400 adults with acute hypoxemic respiratory failure from COVID-19, awake prone positioning compared with usual care resulted in endotracheal intubation at 30 days in 34.1% vs 40.5% of participants, respectively. Although the hazard ratio was 0.81, the result was not statistically significant.

Meaning  Although the findings do not support prone positioning in this setting, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit.

Abstract

Importance  The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19.

Objective  To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19.

Design, Setting, and Participants  Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021.

Intervention  Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195).

Main Outcomes and Measures  The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events.

Results  Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, −6.37% [95% CI, −15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, −1.15% [95% CI, −9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group.

Conclusions and Relevance  In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit.

Trial Registration  ClinicalTrials.gov Identifier: NCT04350723

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Waleed Alhazzani, MD, MSc, Department of Medicine and Department of Health Research Methods, Evidence, and Impact, McMaster University, 1200 Main St W, Hamilton, ON L8N 3Z5, Canada (waleed.al-hazzani@medportal.ca).

Accepted for Publication: April 26, 2022.

Published Online: May 15, 2022. doi:10.1001/jama.2022.7993

Author Contributions: Drs Alhazzani and Arabi had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Parhar, Weatherald, Al Duhailib, Fan, Lauzier, Rochwerg, Culgin, Nelson, Fiest, Stelfox, Solverson, Niven, Møller, Belley-Cote, Thabane, Cook, Arabi.

Acquisition, analysis, or interpretation of data: Alhazzani, Parhar, Weatherald, Al Duhailib, Alshahrani, Al-Fares, Buabbas, Cherian, Munshi, Fan, Al Hameed, Chalabi, Rahmatullah, Duan, Tsang, Lewis, Lauzier, Centofanti, Culgin, Nelson, Abdukahil, Fiest, Stelfox, Tlayjeh, Meade, Perri, Solverson, Lim, Møller, Belley-Cote, Thabane, Tamim, Cook.

Drafting of the manuscript: Alhazzani, Parhar, Weatherald, Al Duhailib, Chalabi, Lewis, Centofanti, Culgin, Nelson, Møller, Tamim, Arabi.

Critical revision of the manuscript for important intellectual content: Alhazzani, Parhar, Weatherald, Al Duhailib, Alshahrani, Al-Fares, Buabbas, Cherian, Munshi, Fan, Al Hameed, Rahmatullah, Duan, Tsang, Lewis, Lauzier, Centofanti, Rochwerg, Culgin, Nelson, Abdukahil, Fiest, Stelfox, Tlayjeh, Meade, Perri, Solverson, Niven, Lim, Møller, Belley-Cote, Thabane, Cook, Arabi.

Statistical analysis: Alhazzani, Al Duhailib, Møller, Thabane, Tamim, Arabi.

Obtained funding: Alhazzani, Parhar, Weatherald, Al Duhailib, Duan, Lauzier, Culgin, Fiest, Stelfox, Meade, Perri, Solverson, Niven, Belley-Cote, Cook, Arabi.

Administrative, technical, or material support: Alhazzani, Parhar, Weatherald, Alshahrani, Al-Fares, Buabbas, Cherian, Munshi, Rahmatullah, Duan, Tsang, Centofanti, Rochwerg, Culgin, Nelson, Abdukahil, Fiest, Tlayjeh, Perri, Solverson, Belley-Cote, Cook, Arabi.

Supervision: Alhazzani, Parhar, Weatherald, Alshahrani, Al-Fares, Al Hameed, Duan, Culgin, Nelson, Møller, Thabane, Cook, Arabi.

Conflict of Interest Disclosures: Dr Parhar reported receiving Rapid COVID-19 grants from the Cumming School of Medicine at the University of Calgary and Alberta Innovates. Dr Weatherald reported receiving Rapid COVID-19 grants from the Cumming School of Medicine at the University of Calgary; receiving grants, personal fees, and nonfinancial support from Janssen, Actelion, and Bayer; and receiving personal fees from Acceleron and Merck. Dr Alshahrani reported receiving grants from King Abdullah International Medical Research Center. Dr Fan reported receiving personal fees from ALung Technologies, Baxter, Aerogen, Inspira, GE Healthcare, and Vasomune. Dr Belley-Cote reported receiving grants from Bayer, Bristol Myers Squibb-Pfizer Alliance, and Roche Diagnostics. No other disclosures were reported.

Funding/Support: The trial was supported by peer-review grants from the Canadian Institute of Health Research and King Abdullah International Medical Research Center in Saudi Arabia and a McMaster University COVID-19 research grant.

Role of the Funder/Sponsor: The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The COVI-PRONE Trial Investigators and the Saudi Critical Care Trials Group members are listed in Supplement 4.

Meeting Presentation: This was presented at the American Thoracic Society International Conference; May 15, 2022; San Francisco, California.

Data Sharing Statement: See Supplement 5.

Additional Contributions: We thank the patients and families participating in this trial. We also thank the collaborating research coordinators and investigators and the bedside clinicians who supported this work. We specifically thank Kelly Hassall, RRT (St Joseph’s Healthcare Hamilton; did not receive financial compensation), and France Clarke, RRT (McMaster University; did not receive financial compensation), who were instrumental in championing the trial with their respiratory therapy colleagues and respective societies, Joshua Piticaru, MD (McMaster University; did not receive financial compensation), for producing prone positioning educational material, and Tom Piraino, RRT (University of Toronto; did not receive financial compensation), for his contributions to the trial design. We thank Melanie Columbus, PhD (University of Calgary; received financial compensation), Olesya Dmitrieva, BHSc (University of Calgary; received financial compensation), and Cassidy Codan, BSc (University of Calgary; received financial compensation), for serving as research coordinators. We also thank Kelly Nelson, RN (St Joseph’s Healthcare Hamilton; received financial compensation), for her role in the methods center with data cleaning and Will Cullimore (St Joseph’s Healthcare Hamilton; received financial compensation) for creating the trial’s website and social media platforms. We are grateful to the Canadian Society of Respiratory Therapists, the Canadian Critical Care Society, and the Alberta Health Services Critical Care Strategic Clinical Network for endorsing and supporting the trial grant application.

Additional Information: Dr Alhazzani holds a McMaster University Department of Medicine Mid-Career Research Award. Dr Cook holds a Canada Research Chair.

References
1.
Grasselli  G , Pesenti  A , Cecconi  M .  Critical care utilization for the COVID-19 outbreak in Lombardy, Italy: early experience and forecast during an emergency response.   JAMA. 2020;323(16):1545-1546. doi:10.1001/jama.2020.4031PubMedGoogle ScholarCrossref
2.
Pal  R , Yadav  U .  COVID-19 pandemic in India: present scenario and a steep climb ahead.   J Prim Care Community Health. 2020;11:2150132720939402. doi:10.1177/2150132720939402PubMedGoogle ScholarCrossref
3.
Aziz  S , Arabi  YM , Alhazzani  W ,  et al.  Managing ICU surge during the COVID-19 crisis: rapid guidelines.   Intensive Care Med. 2020;46(7):1303-1325. doi:10.1007/s00134-020-06092-5PubMedGoogle ScholarCrossref
4.
Piehl  MA , Brown  RS .  Use of extreme position changes in acute respiratory failure.   Crit Care Med. 1976;4(1):13-14. doi:10.1097/00003246-197601000-00003PubMedGoogle ScholarCrossref
5.
Malbouisson  LM , Busch  CJ , Puybasset  L , Lu  Q , Cluzel  P , Rouby  JJ ; CT Scan ARDS Study Group.  Role of the heart in the loss of aeration characterizing lower lobes in acute respiratory distress syndrome.   Am J Respir Crit Care Med. 2000;161(6):2005-2012. doi:10.1164/ajrccm.161.6.9907067PubMedGoogle ScholarCrossref
6.
Mutoh  T , Guest  RJ , Lamm  WJ , Albert  RK .  Prone position alters the effect of volume overload on regional pleural pressures and improves hypoxemia in pigs in vivo.   Am Rev Respir Dis. 1992;146(2):300-306. doi:10.1164/ajrccm/146.2.300PubMedGoogle ScholarCrossref
7.
Gattinoni  L , Vagginelli  F , Chiumello  D , Taccone  P , Carlesso  E .  Physiologic rationale for ventilator setting in acute lung injury/acute respiratory distress syndrome patients.   Crit Care Med. 2003;31(4)(suppl):S300-S304. doi:10.1097/01.CCM.0000057907.46502.7BPubMedGoogle ScholarCrossref
8.
Guérin  C , Reignier  J , Richard  JC ,  et al; PROSEVA Study Group.  Prone positioning in severe acute respiratory distress syndrome.   N Engl J Med. 2013;368(23):2159-2168. doi:10.1056/NEJMoa1214103PubMedGoogle ScholarCrossref
9.
Munshi  L , Del Sorbo  L , Adhikari  NKJ ,  et al.  Prone position for acute respiratory distress syndrome: a systematic review and meta-analysis.   Ann Am Thorac Soc. 2017;14(suppl 4):S280-S288. doi:10.1513/AnnalsATS.201704-343OTPubMedGoogle ScholarCrossref
10.
Telias  I , Katira  BH , Brochard  L .  Is the prone position helpful during spontaneous breathing in patients with COVID-19?   JAMA. 2020;323(22):2265-2267. doi:10.1001/jama.2020.8539PubMedGoogle ScholarCrossref
11.
Fazzini  B , Page  A , Pearse  R , Puthucheary  Z .  Prone positioning for non-intubated spontaneously breathing patients with acute hypoxaemic respiratory failure: a systematic review and meta-analysis.   Br J Anaesth. 2022;128(2):352-362. doi:10.1016/j.bja.2021.09.031PubMedGoogle ScholarCrossref
12.
Ehrmann  S , Li  J , Ibarra-Estrada  M ,  et al; Awake Prone Positioning Meta-Trial Group.  Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.   Lancet Respir Med. 2021;9(12):1387-1395. doi:10.1016/S2213-2600(21)00356-8PubMedGoogle ScholarCrossref
13.
Alhazzani  W , Evans  L , Alshamsi  F ,  et al.  Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update.   Crit Care Med. 2021;49(3):e219-e234. doi:10.1097/CCM.0000000000004899PubMedGoogle ScholarCrossref
14.
Duhailib  ZA , Arabi  YM , Culgin  S ,  et al.  Awake prone position in hypoxemic patients with coronavirus disease 19 (COVI-PRONE): a study protocol and statistical analysis plan for randomized clinical trial.   medRxiv. Posted online August 8, 2021. doi:10.1101/2021.08.06.21261531Google Scholar
15.
Wolbers  M , Koller  MT , Stel  VS ,  et al.  Competing risks analyses: objectives and approaches.   Eur Heart J. 2014;35(42):2936-2941. doi:10.1093/eurheartj/ehu131PubMedGoogle ScholarCrossref
16.
Glickman  ME , Rao  SR , Schultz  MR .  False discovery rate control is a recommended alternative to Bonferroni-type adjustments in health studies.   J Clin Epidemiol. 2014;67(8):850-857. doi:10.1016/j.jclinepi.2014.03.012PubMedGoogle ScholarCrossref
17.
Solverson  K , Weatherald  J , Parhar  KKS .  Tolerability and safety of awake prone positioning COVID-19 patients with severe hypoxemic respiratory failure.   Can J Anaesth. 2021;68(1):64-70. doi:10.1007/s12630-020-01787-1Google ScholarCrossref
18.
Gad  GS .  Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure.   Egypt J Anesth. 2021;37(1):85-90. doi:10.1080/11101849.2021.1889944Google ScholarCrossref
19.
Jayakumar  D , Ramachandran  P , Rabindrarajan  E , Vijayaraghavan  BKT , Ramakrishnan  N , Venkataraman  R .  Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial.   J Intensive Care Med. 2021;36(8):918-924. doi:10.1177/08850666211014480PubMedGoogle ScholarCrossref
20.
Johnson  SA , Horton  DJ , Fuller  MJ ,  et al.  Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization (PAPR).   Ann Am Thorac Soc. 2021;18(8):1424-1426. doi:10.1513/AnnalsATS.202011-1466RLPubMedGoogle ScholarCrossref
21.
Kharat  A , Dupuis-Lozeron  E , Cantero  C ,  et al.  Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial.   ERJ Open Res. 2021;7(1):00692-2020. doi:10.1183/23120541.00692-2020PubMedGoogle ScholarCrossref
22.
Rosén  J , von Oelreich  E , Fors  D ,  et al; PROFLO Study Group.  Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.   Crit Care. 2021;25(1):209. doi:10.1186/s13054-021-03602-9PubMedGoogle ScholarCrossref
23.
Taylor  SP , Bundy  H , Smith  WM , Skavroneck  S , Taylor  B , Kowalkowski  MA .  Awake prone positioning strategy for nonintubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.   Ann Am Thorac Soc. 2021;18(8):1360-1368. doi:10.1513/AnnalsATS.202009-1164OCPubMedGoogle ScholarCrossref
24.
Sun  X , Briel  M , Walter  SD , Guyatt  GH .  Is a subgroup effect believable? updating criteria to evaluate the credibility of subgroup analyses.   BMJ. 2010;340:c117. doi:10.1136/bmj.c117PubMedGoogle ScholarCrossref
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close