By J. Brady Scott, PhD, RRT, RRT-ACCS, AE-C, FAARC, FCCP
Associate Professor, Department of Cardiopulmonary Sciences, Division of Respiratory Care, College of Health Sciences, Rush University, Chicago
During the coronavirus disease (COVID-19) pandemic, awake prone positioning (APP) has been to improve oxygenation and reduce the need for endotracheal intubation and unnecessary invasive mechanical ventilation.1 The concept of placing non-intubated patients in the prone position was described before the pandemic, but its use increased significantly as the pandemic evolved.1-8 As the use of APP increased dramatically, so did clinical trials evaluating its effectiveness on various important patient outcomes. This special feature summarizes the literature associated with APP, describes known factors related to successful APP, and highlights current recommendations regarding APP in the setting of COVID-19.
Outcomes of Awake Prone Positioning
In 2003, Valter et al reported results of using APP for four patients with hypoxemic respiratory failure.3 The authors noted that oxygenation increased in patients placed in the prone position while awake, and patients could indeed tolerate the position. Six years later, Feltracco et al reported an improvement in oxygenation in two cases in which APP was used in addition to noninvasive ventilation (NIV) for refractory hypoxemia after lung transplantation.4 In 2012, Feltracco et al described results from three post-lung transplant patients who were in the prone position while receiving noninvasive high-frequency percussive ventilation (HFPV) for ventilatory assistance and secretion mobilization.5 They suggested that APP (in addition to HFPV) could be a supportive intervention to decrease respiratory distress in that patient population with impending ventilatory failure. In 2015, a larger retrospective observational study that included 15 patients was published that demonstrated significant improvement in oxygenation for non-intubated patients in acute respiratory failure placed in the prone position. While limited to small case studies and retrospective data, the study suggested that APP was feasible, safe, and could improve oxygenation. The impact of APP on other clinically relevant outcomes such as intubation rate, need for intensive care, hospital length of stay, and mortality remained unknown.
Since the beginning of the COVID-19 pandemic, several papers have been published on the impact of APP, 13 of which are systematic reviews and/or meta-analyses reporting pooled outcome data.9 Early analyses of pooled data were limited to case series, cohort, prospective observational, before and after, and retrospective studies.10-15 In those early studies evaluating oxygenation as an outcome, the benefit of improved oxygenation was noted consistently.10,11,13-15 As more robust clinical trials were published, researchers could better evaluate the effect of APP on other clinical outcomes.2,16-18
A recently published systematic review and meta-analysis published by Li et al included 29 studies.18 Ten of the studies included in the analysis were randomized controlled trials (RCTs), and 19 were observational studies. The systematic review and meta-analysis included papers published from January 2020 to November 2021 and included aggregate data from three unpublished studies. In total, the analysis included 4,654 patients between the supine position and APP groups. In a primary analysis of the data, the authors found that APP compared to supine position reduced the need for intubation (risk ratio [RR] = 0.84; 95% confidence interval [CI]: 0.72-0.97), particularly in those who received advanced respiratory support (i.e., NIV or high-flow nasal cannula [HFNC] oxygen therapy) or were treated in the intensive care unit (ICU) when enrolled (RR = 0.83; 95% CI: 0.71-0.97). Interestingly, the study authors found no significant differences in mortality between the APP and supine groups. They attributed this finding to a study power issue, since mortality was investigated as a secondary outcome in the available RCTs included in their analysis. Additional significant findings were that APP did not reduce ICU admission, ICU length of stay, hospital length of stay, or escalation of respiratory support in patients with COVID-19-related acute hypoxemic respiratory failure (AHRF). No serious adverse events were associated with APP.
Based on the available evidence, mainly published during the COVID-19 pandemic, APP appears safe and practical, and can improve oxygenation. In patients with COVID-19-related AHRF requiring HFNC or NIV, it also may reduce the need for intubation. While it is helpful for some patients, many questions remain regarding APP. In the accompanying editorial for the systematic review and meta-analysis by Li et al, Shekar and Ling consider if APP should be used in all patients with AHRF from COVID-19, and if APP should be used only in the ICU setting, citing resource allocation (e.g., ICU bed/staff availability) as an issue.18,19 Additionally, it is not entirely clear when APP should be used. In a post hoc analysis of an RCT evaluating APP for patients with COVID-19-related AHRF, Kaur et al found a 28-day survival benefit associated with the early (< 24 hours of HFNC use) initiation of APP.20,21 However, these findings should be interpreted with caution, given that the study design (post hoc analysis) lacks randomization and possibly inflated statistical significance.21
Factors Associated with Successful APP
Ibarra-Estrada et al sought to identify factors associated with APP success in patients with COVID-19-related AHRF using data from their RCT published in 2021.20,22 They found that APP success was associated with an APP duration of > 8 hours/day, respiratory rate at enrollment of ≤ 25 breaths/minute, and positive responses to APP (e.g., improvement in ROX index and lung ultrasound score after APP). Results from the study suggest that close monitoring of patient response to APP, particularly within the first three days, may aid in identifying patients who are less likely to improve with APP and ultimately require intubation and mechanical ventilation. This close monitoring may help avoid unnecessary delays in intubation. The authors concluded that APP should be considered early in patients with COVID-19-related AHRF and applied for as long as possible, preferably for at least eight hours/day.22
Current Recommendations
The National Institutes of Health currently recommends APP for adult patients with COVID-19 and persistent hypoxemia who require HFNC oxygen therapy and are not in immediate need of endotracheal intubation. APP is not recommended as rescue therapy for refractory hypoxemia in patients in whom endotracheal intubation and mechanical ventilation are indicated.23 Additionally, they note that APP is feasible for pregnant patients and can be performed in the fully prone or lateral decubitus positions. APP may not be possible or practical in patients with facial or pelvic fractures, spinal instability, or an open chest/unstable chest wall.23 They caution the use of APP in patients who are hemodynamically unstable, confused, delirious, have nausea or vomiting, have had recent abdominal surgery, and are unable to change positions independently.
Summary
For patients with AHRF from COVID-19 who require advanced respiratory support with HFNC or NIV, current literature suggests that APP may help reduce the need for intubation and invasive mechanical ventilation. Longer durations of APP (> 8 hours/day) seem beneficial for patients, but it must be acknowledged that not all patients can tolerate long periods in the prone position. Attempts to maximize patient comfort, close monitoring, and consistent encouragement by clinicians may improve APP duration. More research is needed to find ways to maximize patient comfort while awake and in the prone position. It is currently unknown if APP is beneficial for non-COVID-19 causes of AHRF. Only time and results of well-designed clinical trials will tell if APP fades away along with memories of the pandemic or becomes a standard way to treat non-intubated patients with AHRF in the future.
REFERENCES
- Chua EX, Zahir SMISM, Ng KT, et al. Effect of prone versus supine position in COVID-19 patients: A systematic review and meta-analysis. J Clin Anesth 2021;74:110406.
- Kharat A, Simon M, Guérin C. Prone position in COVID 19-associated acute respiratory failure. Curr Opin Crit Care 2022;28:57-65.
- Valter C, Christensen AM, Tollund C, Schønemann NK. Response to the prone position in spontaneously breathing patients with hypoxemic respiratory failure. Acta Anaesthesiol Scand 2003;47:416-418.
- Feltracco P, Serra E, Barbieri S, et al. Noninvasive ventilation in prone position for refractory hypoxemia after bilateral lung transplantation. Clin Transplant 2009;23:748-750.
- Feltracco P, Serra E, Barbieri S, et al. Noninvasive high-frequency percussive ventilation in the prone position after lung transplantation. Transplant Proc 2012;44:2016-2021.
- Scaravilli V, Grasselli G, Castagna L, et al. Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: A retrospective study. J Crit Care 2015;30:1390-1394.
- Bellone A, Basile A. Prone positioning in severe acute hypoxemic respiratory failure in the emergency ward. Emerg Care J 2018;14:22-23.
- Ding L, Wang L, Ma W, He H. Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: A multi-center prospective cohort study. Crit Care 2020;24:28.
- Scott JB, Weiss TT, Li J. COVID-19 lessons learned: Prone positioning with and without invasive mechanical ventilation. Respir Care (In Press)
- Tan W, Xu DY, Xu MJ, et al. The efficacy and tolerance of prone positioning in non-intubation patients with acute hypoxemic respiratory failure and ARDS: A meta-analysis. Ther Adv Respir Dis 2021;15:17534666211009407.
- Pb S, Mittal S, Madan K, et al. Awake prone positioning in non-intubated patients for the management of hypoxemia in COVID-19: A systematic review and meta-analysis. Monaldi Arch Chest Dis 2021;91:10.4081/monaldi.2021.1623.
- Cardona S, Downing J, Alfalasi R, et al. Intubation rate of patients with hypoxia due to COVID-19 treated with awake proning: A meta-analysis. Am J Emerg Med 2021;43:88-96.
- Pavlov I, He H, McNicholas B, et al. Awake prone positioning in non-intubated patients with acute hypoxemic respiratory failure due to COVID-19. Respir Care 2021; Jul 7. doi:10.4187/respcare.09191. [Online ahead of print].
- Parashar S, Karthik AR, Gupta R, Malviya D. Awake proning for nonintubated adult hypoxic patients with COVID-19: A systematic review of the published evidence. Indian J Crit Care Med 2021;25:906-916.
- Ponnapa Reddy M, Subramaniam A, Afroz A, et al. Prone positioning of nonintubated patients with coronavirus disease 2019-A systematic review and meta-analysis. Crit Care Med 2021;49:e1001-e1014.
- Schmid B, Griesel M, Fischer AL, et al. Awake prone positioning, high-flow nasal oxygen and noninvasive ventilation as noninvasive respiratory strategies in COVID-19 acute respiratory failure: A systematic review and meta-analysis. J Clin Med 2022;11:391.
- 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;128:352-362.
- Li J, Luo J, Pavlov I, et al. Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: A systematic review and meta-analysis. Lancet Respir Med 2022;S2213-2600(22)00043-1. [Online ahead of print].
- Shekar K, Ling RR. The pandemic and the great awakening in the management of acute hypoxaemic respiratory failure. Lancet Respir Med 2022;S2213-2600(22)00051-0. [Online ahead of print].
- Ehrmann S, Li J, Ibarra-Estrada M, et al. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: A randomised, controlled, multinational, open-label meta-trial. Lancet Respir Med 2021;9:1387-1395.
- Kaur R, Vines DL, Mirza S, et al. Early versus late awake prone positioning in non-intubated patients with COVID-19. Crit Care 2021;25:340.
- Ibarra-Estrada M, Li J, Pavlov I, et al. Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: Analysis of a randomized controlled trial. Crit Care 2022;26:84.
- National Institutes of Health. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. https://www.covid19treatmentguidelines.nih.gov/
This special feature summarizes the literature associated with awake prone positioning (APP), describes known factors related to successful APP, and highlights current recommendations regarding APP in the setting of COVID-19.
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