Conscious prone positioning in nonintubated COVID-19 patients with acute respiratory distress syndrome: systematic review and meta-analysis

Vásquez-Tirado, Gustavo Adolfo; Meregildo-Rodríguez, Edinson Dante; Asmat-Rubio, Martha Genara; Salazar-Castillo, María José; Quispe-Castañeda, Claudia Vanessa; Cuadra-Campos, María del Carmen

doi:10.62675/2965-2774.20240176-en

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Original Article • Crit. Care Sci. 36 • 2024 • https://doi.org/10.62675/2965-2774.20240176-en linkcopy

Conscious prone positioning in nonintubated COVID-19 patients with acute respiratory distress syndrome: systematic review and meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Objective: To systematically review the effect of the prone position on endotracheal intubation and mortality in nonintubated COVID-19 patients with acute respiratory distress syndrome.

Methods: We registered the protocol (CRD42021286711) and searched for four databases and gray literature from inception to December 31, 2022. We included observational studies and clinical trials. There was no limit by date or the language of publication. We excluded case reports, case series, studies not available in full text, and those studies that included children < 18-years-old.

Results: We included ten observational studies, eight clinical trials, 3,969 patients, 1,120 endotracheal intubation events, and 843 deaths. All of the studies had a low risk of bias (Newcastle-Ottawa Scale and Risk of Bias 2 tools). We found that the conscious prone position decreased the odds of endotracheal intubation by 44% (OR 0.56; 95%CI 0.40 - 0.78) and mortality by 43% (OR 0.57; 95%CI 0.39 - 0.84) in nonintubated COVID-19 patients with acute respiratory distress syndrome. This protective effect on endotracheal intubation and mortality was more robust in those who spent > 8 hours/day in the conscious prone position (OR 0.43; 95%CI 0.26 - 0.72 and OR 0.38; 95%CI 0.24 - 0.60, respectively). The certainty of the evidence according to the GRADE criteria was moderate.

Conclusion: The conscious prone position decreased the odds of endotracheal intubation and mortality, especially when patients spent over 8 hours/day in the conscious prone position and treatment in the intensive care unit. However, our results should be cautiously interpreted due to limitations in evaluating randomized clinical trials, nonrandomized clinical trials and observational studies. However, despite systematic reviews with meta-analyses of randomized clinical trials, we must keep in mind that these studies remain heterogeneous from a clinical and methodological point of view.

Keywords:
COVID-19; Coronavirus infections; Prone position; Patient positioning; Hospital mortality; Mortality

Author	Country/Study	Participants	Outcomes
Coppo et al.(⁶)	Italy UC, PCS	n = 46 patients. Both sexes	ETI in 18 patients, five deaths unrelated to the procedure
Rosén et al.(¹⁰)	Sweden MC, RCT	n = 75 were randomized, 39 in the SC Group and 36 in the CPP Group. Both sexes	13 patients needed ETI in the SC Group versus 12 patients in the CPP Group (HR 1.01; 95%CI 0.46 - 2.21)
Tonelli et al.(¹³)	Italy MC, RCS	n = 114 patients, 76 in the SC and 38 in the CPP Group. Both sexes	22 patients died (17 in SC Group and 5 in CPP Group); 37 patients needed ETI (7 in CPP Group and 30 in SC Group)
Sryma et al.(¹⁴)	India UC, non-RCT	n = 45 subjects (30 cases and 15 controls). Both sexes.	The need for IMV was higher in the Control Group (33.3%) versus Prone Group (6.7%).
Ferrando et al.(³³)	Spain and Andorra MC, PCS	n = 199 patients on HFNC therapy. Both sexes	82 patients needed ETI (HFNC Group 60, HFNC + CPP Group 22); 17 died in the HFNC Group, and eight in the HFNC + CPP Group
Dubosh et al.(³⁴)	USA UC, PCS	n = 22 patients. Both sexes.	7 patients needed ETI (5 patients in the first 48 hours, 2 after the next 48 hours), 2 patients died
Kaur et al.(³⁵)	USA UC, RCT	n = 125 patients. Of them, 92 received early CPP, and 33 received late CPP. Both sexes	The early CPP Group had lower mortality than the late CPP Group (26% versus. 45%, p = 0.039), without a difference in ETI rate. However, advanced age, ETI, longer time to initiate CPP and hydrocortisone use were associated with increased mortality
Ehrmann et al.(³⁶)	Europe, North America and South America MC, RCT	n = 1,126 patients, CPP 567, SC 559. Included in the ITT analysis 1,121 patients. Both sexes	Treatment failure in 40% of patients in the CPP Group and 46% of patients in the SC Group (RR 0.86; 95%CI 0.75 - 0.98). HR for ETI 0.75 (95%CI 0.62 - 0.91), HR for mortality 0.87 (95%CI 0.68 - 1.11) with CPP compared with SC at 28 days of enrollment
Perez-Nieto et al.(³⁷)	México, and Ecuador. MC, RCS	n= 827 nonintubated patients in the CPP (n = 505) and SC (n = 322) Groups. Both sexes	Fewer patients in the CPP Group needed ETI (23.6% versus. 40.4%) or died (19.8% versus. 37.3%)
Dueñas-Castell et al.(³⁸)	Colombia UC, RCS	n = 212 patients with SC and CPP. Both sexes.	Overall mortality 34% (73/212)
Vianello et al.(³⁹)	Italy UC, PCS	n = 93 patients were included in the study. Both sexes	CPP was feasible and safe in 50 patients. Sixteen patients received ETI, and 27 escalated respiratory support. The mortality rate was 9/93. In 41/50 of subjects who passed the trial and underwent CPP, there was clinical benefit and survival without escalation of therapy
Altinay et al.(⁴⁰)	Turkey UC, RCS	n = 72. CPP Group (n = 49), analyzed (n = 25). SC Group (n = 23), analyzed (n = 23). Both sexes	CPP Group: 9 patients died, and eight needed ETI (p = 0.020). SC Group: 16 patients died, and 19 needed ETI (p = 0.001)
Jayakumar et al.(⁴¹)	India MC, RCT	n= 60 patients. CPP 30, SC: 30. Both sexes	CPP Group: 3 patients died, and four needed ETI. SC Group: 2 patients died, and 4 needed ETI
Solverson et al.(⁴²)	Canada MC, RCS	n = 17 patients. Both sexes. ICU 12, hospital ward 5	7 patients needed ETI and IMV; 2 patients died in the ICU after a course of IMV
Gad et al.(⁴³)	Egypt MC, RCS	n = 30 patients; CPP 15; NIV 15	6 patients needed IMV (3 in the CPP Group and 3 in the NIV Group); these same six patients died
Burton-Papp et al.(⁴⁴)	USA UC, RCS	n = 81 patients. A total of 20 patients received CPP in conjunction with NIV	7 patients were intubated; no patient died
Tatlow et al.(⁴⁵)	Australia UC, RCS	n = 13 patients. Both sexes	7 patients died
Bahloul et al.(⁴⁶)	Túnez UC, PCS	n = 21 patients. Both sexes. CPP Group 21, SC Group 17	7 patients died in the CPP Group and 5 in the SC Group; 9 needed IMV. CPP was not associated with a reduction in mortality or IMV rate (p > 0.05 for both)
Pierucci et al.(⁴⁷)	Italy UC, PCS	n = 32 patients, CPP 16, NIV 16. Both sexes	5 patients were intubated (3 in the SC Group and 2 in the CPP), and 3 in the SC Group died (the same ones needed ETI)
Winearls et al.(⁴⁸)	UK UC, RCS	n = 24 patients with CPAP. Both sexes	1 patient had invasive ventilation and 4 patients died
Musso et al.(⁴⁹)	Italy UC, Non-RCT	n = 243 patients; CPP Group 81, SC Group 162. Both sexes	69 patients died, 59 in the SC Group and 10 in the CPP Group; 52 patients needed ETI, 44 in the control Group, and 8 in the CPP Group
Aisa et al.(⁵⁰)	Ireland UC, PCS	n = 50 patients	7 patients were intubated (14%). CPP was feasible in 41 (82%) patients, and 38 (76%) patients reported good tolerance
Althunayyan et al.(⁵¹)	Saudi Arabia UC, PCS	n = 49 patients. Both sexes	6 patients were intubated (12.2%) and 7 patients died (14.3%)
Qian et al.(⁵²)	USA MC, Non-RCT	n = 501 patients assigned 1:1 to either CPP Group or SC Group. Both sexes	CPP Group: 31 patients were intubated and 56 patients died. SC Group: 30 were intubated, 47 died.
Fralick et al.(⁵³)	Canada, USA MC, RCT	n = 248 patients; CPP Group 126, SC Group 122. Both sexes	2 patients died, one from CPP and one from the SC Group
Barker et al.(⁵⁴)	UK UC, RCCS	n = 20 patients; CPP Group 10 patients, SC Group 10 patients. Both sexes	6 (60%) patients needed IMV in the CPP Group and 5 (50%) in the SC Group; 1 (10%) died in the CPP Group and 4 (40%) in the SC Group.
Esperatti et al.(⁵⁵)	Argentina MC, PCS	n = 335 patients; CPP Group 187, SC Group 148. Both sexes	44 patients in the CPP Group (23%) and 79 (53%) in the SC Group were intubated; 2 patients died, one from each group.
Kumar et al.(⁵⁶)	India UC, PCS	n = 67 patients	NR

Study	Type study	Site of attendance	Tool	Conclusion
Rosén et al.(¹⁰)	RCT	ICU and medical ward	ROB 2	Low risk
Tonelli et al.(¹³)	Retrospective cohort study	ICU	NOS	Low risk
Sryma et al.(¹⁴)	Non-RCT	No data	ROBINS-I	Low risk
Ferrando et al.(³³)	Prospective cohort study	ICU	NOS	Low risk
Ehrmann et al.(³⁶)	RCT	ICU and medical ward	ROB 2	Low risk
Perez-Nieto et al.(³⁷)	Retrospective cohort study	ICU and medical ward	NOS	Low risk
Altinay et al.(⁴⁰)	Retrospective cohort study	ICU	NOS	Low risk
Jayakumar et al.(⁴¹)	RCT	ICU	ROB 2	Low risk
Gad et al.(⁴³)	Retrospective cohort study	ICU	NOS	Low risk
Burton-Papp et al.(⁴⁴)	Retrospective cohort study	ICU	NOS	Low risk
Bahloul et al.(⁴⁶)	Prospective cohort study	ICU	NOS	Low risk
Pierucci et al.(⁴⁷)	Prospective cohort study	Medical ward	NOS	Low risk
Musso et al.(⁴⁹)	Non-RCT	ICU	ROBINS-I	Low risk
Qian et al.(⁵²)	Non-RCT	ICU and medical ward	ROBINS-I	Low risk
Fralick et al.(⁵³)	RCT/MW	Medical ward	ROB 2	Low risk
Barker et al.(⁵⁴)	Retrospective case control	ICU	NOS	Low risk
Esperatti et al.(⁵⁵)	Prospective cohort study	ICU	NOS	Low risk

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[TFN1] UC - unicenter, PCS - prospective cohort study; ETI - endotracheal intubation; MC - multicenter; RCT - randomized controlled trial; SC - standard care; CPP - conscious prone position; HR - hazard ratio; 95%CI - 95% confidence interval; RCS - retrospective cohort study; IMV - invasive mechanical ventilation; HFNC - high-flow nasal cannula; ITT – intent-to-treat; ICU - intensive care unit; NIV - noninvasive mechanical ventilation; RCCS - retrospective case-control study; NR - not reported.