When hope meets reality: the challenges of awake proning in unmonitored settings
Editorial Commentary

When hope meets reality: the challenges of awake proning in unmonitored settings

Manel Luján1,2, Javier Sayas3

1Servei de Pneumologia, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain; 2Centro de Investigacion Biomédica en Red (CIBERES), Madrid, Spain; 3Pulmonology Service, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain

Correspondence to: Manel Luján, MD. Servei de Pneumologia, Parc Taulí Hospital Universitari, 08208 Sabadell, Spain; Centro de Investigacion Biomédica en Red (CIBERES), Madrid, Spain. Email: mlujan@tauli.cat.

Comment on: Nay MA, Hindre R, Perrin C, et al. Prone position versus usual care in hypoxemic COVID-19 patients in medical wards: a randomised controlled trial. Crit Care 2023;27:240.

Keywords: Acute respiratory failure (ARF); coronavirus disease 2019 (COVID-19); non-invasive respiratory support

Submitted Oct 13, 2023. Accepted for publication Nov 24, 2023. Published online Dec 11, 2023.

doi: 10.21037/jtd-23-1588

The prone position has been used in the management of severe acute respiratory failure (ARF) since the 1970s (1). In one of the first reports, Mellins et al. observed that patients with advanced cystic fibrosis spontaneously adopted the prone position to improve ventilation (2). From these early experiences, the beneficial effects of the prone position began to be documented.

In the supine position, the dorsal areas of the lung are compressed by the weight of the mediastinal structures, the pleural pressure gradient, and the rest of the lung itself. In contrast, in the prone position, these areas are relieved of this pressure, with an increase in functional residual capacity, resulting in improved ventilation/perfusion ratio, cardiac output, and diaphragm function (3).

Prone positioning in intubated and mechanically ventilated patients has been shown to improve pulmonary gas exchange and lung mechanics in patients with severe hypoxemic respiratory failure. In fact, it is part of most intensive care unit protocols. There are current guidelines (4) that support this intervention in intubated patients with acute respiratory distress syndrome (ARDS), specifying that patients must be in the prone position for at least 16 hours per day to be effective.

During the coronavirus disease (COVID) pandemic, different strategies have been tried in the management of patients with COVID and moderate hypoxaemia to prevent worsening of the disease. Perhaps the most studied has been the early administration of therapy with high flow nasal cannula (HFNC). Crimi et al. found no significant difference in disease progression in a cohort of patients with an arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio between 200 and 300 after randomisation to high flow or conventional oxygen therapy (5). In contrast, differences in intubation rates have been demonstrated in patients with PaO2/FiO2 below 200 (6,7).

Awake proning position (APP) has been also used as a strategy, suggesting that it could improve the prognosis of non-intubated patients with moderate or severe respiratory failure. The aim of APP would be to prevent the progression of ARF, thereby reducing the need for orotracheal intubation and ultimately improving survival. Some early studies demonstrated a lower rate of intubation in patients under APP (8). However, the results of the studies are conflicting and merit careful consideration (9). Although considered a non-invasive treatment, tolerance to APP is highly variable, with most patients not tolerating it for long periods of time. For example, in the meta-trial published by Ehrmann et al., which included 6 RCTs, the number of hours of pronation per day ranged from 1.6 to 8 hours (10). Some other studies achieved a mean duration of 12 hours in the first day of admission to intensive care unit (ICU) (11). Although no ideal number of hours of compliance has been defined for awake patients, in the aforementioned meta-trial, the rate of APP failure and progression of lung disease was significantly lower in patients with longer hours of compliance. Table 1 shows the most relevant studies on APP.

Table 1

Summary of the most relevant studies (including >15 patients in each arm) on APP in COVID-19

Reference Study type/setting N (prone/control) Groups comparators % of patients under NIRS Time on prone position planned/reported Main outcome
Gad (12) Single center RCT/ICU 15/15 Face mask oxygen + APP vs. NIV 50% (control group) 1–2 h shifts between 3 h rest/not reported No difference in mortality or intubation
Johnson et al. (13) Single center RCT/ward 15/15 APP/usual care (nasal cannula) 0% 1–2 h every 4 h/not reported No differences in oxygenation
Taylor et al. (14) Single center/RCT/ward 27/13 APP/usual care 1% 12–16 h/10–120 min per day No improvements in oxygenation. Low adherence and low tolerance to APP
Rosén et al. (15) Multicenter RCT ICU 36/39 Required NIV/HFNC 100% >16 h a day/14% patients were able to perform >16 h a day Safe, but no differences in intubation
Jayakumar et al. (16) Multicenter RCT/ICU 30/30 Usual care vs. APP Baseline 10% on NIRS >6 h per day/43% tolerate >6 h per day No differences in outcomes
Gopalakrishnan et al. (17) Single center/ward 257/245 Usual care vs. APP 0% baseline 6–8 h/23 % did not tolerate >2 h/day No differences in outcomes
Ehrmann et al. (10) Multicenter RCT ICU (60%), intermediate care unit (35%) 554/567 Usual care vs. APP HFNC (not available) As long as possible/5 h per day Positive effects of APP in intubation and mortality
Hashemian et al. (18) Single center RCT/ICU 30/45 NIV vs. NIV + APP 100% on NIV Not available Improve in oxygenation in the most severe group, favouring the APP + NIV group. Lower need for intubation (22% vs. 40%, P=0.082) and mortality (20% vs. 33%, P=0.152) in NIV + APP
Alhazzani et al. (19) Multicenter RCT/ICU 205/195 Usual care vs. APP – 8–10 h a day/5 h a day No reduction in intubation
Rampon et al. (20) Single center RCT/ward 159/134 Usual care vs. APP 1% on HFNC 4 times/day for 1–2 h + 12 h night/only 2% achieved >12 h Smartphone-guided self-prone positioning. No improvement in APP adherence
Fralick et al. (21) Multicenter RCT/ward 126/122 Usual care vs. APP 2–4% on HFNC 2 h 4 times a day/6 h a day No differences in death or mechanical ventilation

APP, awake prone position; COVID-19, coronavirus disease 2019; RCT, randomized control trial; ICU, intensive care unit; NIV, non-invasive ventilation; HFNC, high flow nasal cannula; NIRS, noninvasive ventilator support.

But the question did not stop at critical care. In a randomised controlled trial, Nay et al. recruited 265 patients on inpatient wards in 15 hospitals. Patients were randomised to awake proning plus usual care in the intervention arm and usual care in the control arm. The target time interval for patients to be in the prone position was 270 min/day. The results of the study showed no significant differences in the primary composite endpoint [non-invasive ventilation (NIV) or intubation or death] but did show differences in intubation and death (secondary endpoints). Interestingly and counter-intuitively, patients with milder ARF, defined by oxygen saturation (SpO2) >95% on admission, showed a greater benefit than patients with more severe ARF (SpO2 <95%) (22). Due to the important limitations, the results of the study are highly controversial and deserve further analysis. Four important questions arise from the results of the study: what would be the minimum monitoring requirements to implement APP? Could APP prevent deterioration in patients with mild ARF? Is it a worthwhile intervention? Does APP work the same in patients on conventional oxygen as it does in patients on NIV?

Regarding the first question, the study was conducted in a completely different setting (conventional ward) than where most studies have shown benefits of prone positioning (monitored/intermediate care units or intensive care units). Therefore, there is no way of knowing whether the patients had any kind of continuous monitoring. Even more, as shown in the supplemental data, there can be huge differences in ward management, with different thresholds to start NIV or to move to ICU, similar to the absence of pre-established intubation criteria in ICU studies. Finally, the use of monitoring could have identified those patients with oximetry improvement or deterioration after APP. On the other hand, it is understandable that in the early stages of the pandemic, monitoring facilities in wards were scarce. In a very similar study, Gopalakrishnan et al. found no significant difference in mortality or need for intubation in a cohort of 502 patients with mild ARF randomised to APP versus usual care (17) in an unmonitored environment. These results suggest the need for monitoring, that should include cardiorespiratory parameters [electrocardiogram (ECG) and oximeter]. As shown in Table 1, trials conducted in non-monitored wards showed no differences between groups and, on the other hand, reported significant problems with adherence and tolerability.

Concerning second question, the prone position had shown benefits mainly in non-intubated patients when used in conjunction with high nasal flow or continuous positive airway pressure (CPAP), and Nay and coworkers reported better results in the subgroup with mild hypoxaemia. They argue that APP would have had a protective effect in these patients by reducing stress and strain. However, the definition of moderate hypoxaemia using a not-so-accurate SpO2 threshold of 95% under nasal prongs with a 5 L/min oxygen flow may pose a potential source of relevant variability of disease severity. Inspired oxygen fraction under nasal prongs may vary widely according to different respiratory rates and tidal volume. In addition, it may not account for other physiological variables as respiratory effort. Some authors have suggested the need to look also to arterial blood carbon dioxide tension (PaCO2) as a relevant disease severity marker and highlighted the limitations of SpO2/FiO2 ratio (23).

Thirdly, it should be noted that a high level of willingness and effort on the part of the patient is required to acquire sufficient time in the prone position. Furthermore, there may be individual differences in tolerance, which could confound the results. In the same way that one patient in the control group decided to prone himself despite being advised not to, patients assigned to the self-proning arm may not have been adherent enough, as stated in the limitations. It is also an intervention that can be very staff-intensive in lower-resource settings such as conventional wards. The lack of continuous monitoring may have reduced the ability to identify those who could be considered responders and those who worsened with APP. In a very small study, Solverson showed that half of the patients in the prone position experienced pain and discomfort (24). Even more, in a very recent study (25), a review on the trends of prone position use in ICU showed a steady decrease of its use between 2020 and 2022 in COVID-19 related ARDS patients. Significantly, that decrease took place in intubated, ICU patients, where a better nurse-to-patient ratio is assumed. If in a high resource area, such as an ICU, is a decrease in its use despite being considered an evidence-based intervention, the explanation could be related to the high significant resources needed to prone an ICU patient, and to lower patient tolerance. To improve tolerance some authors combined prone and lateral decubitus (with non-invasive respiratory support), without significant results, but expanding the definition of therapeutic intervention (26). All these limitations and biases were addressed by the authors.

Finally, only about 5% of the patients in the study received NIV. A full understanding of the different physiological mechanisms that may influence the effects of prone positioning in spontaneously breathing patients, intubated patients or patients receiving NIV (HFNC or NIV) is essential. In a recent letter, Shao and Shao (27) discussed the physiological differences in the effects of the prone position in patients receiving non-invasive respiratory support compared to those receiving conventional oxygen support. It appears that the recruitment effect associated with NIV and HFNC, which increases end-expiratory lung volume, may have a synergistic effect with APP, resulting in improved compliance, reduced strain and stress forces and more homogeneous lung inflation. Whether the presence of “advanced non-invasive respiratory support” can facilitate prolonged periods of prone positioning remains to be demonstrated.

We believe that the concept of APP responder is key to defining future strategies, especially because it is of questionable benefit to maintain the prone position in non-responders after the first therapy sessions. If we analyse the premises under which the benefit in intubated patients was established, one of them may have important implications for the application in the awake, non-intubated patient, such as the distribution or pattern of pulmonary involvement. None of the studies published to date provide information on the topographical distribution of lung involvement. However, there are tools that, because of their simplicity, such as bedside (point-of-care) ultrasound, could help to select those patients most likely to respond. In intubated patients, Prat et al. demonstrated that the presence of a normal lung ultrasound (LUS) score in the anterior fields was predictive of a favourable response to prone positioning in patients with ARDS (28). However, this was not confirmed in a later study, although it was possible to monitor changes in ventilation with APP using ultrasound (29). Another potentially useful tool for indicating and monitoring the response to APP may be electrical impedance plethysmography, although its complexity and high cost clearly limit its widespread use (30,31). Future trends may make this technique more affordable and accessible, even in intermediate care units or wards, in a similar way to chest radiography (32).

In conclusion, the efficacy of prone positioning in non-intubated patients remains controversial. For the future, it seems to be of paramount importance to define the implementation scenarios, considering the control and monitoring needs of APP patients. Based on current data, it seems advisable to restrict APP to monitored environments with trained personnel. In addition, the strategy of demonstrating benefit in the short or medium term would require the inclusion of patients with the highest a priori probability of response. A better characterisation of the patterns of respiratory failure and the severity of ARDS is needed to avoid that false hopes are met with harsh reality.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease. The article has undergone external peer review.

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1588/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1588/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

  1. Piehl MA, Brown RS. Use of extreme position changes in acute respiratory failure. Crit Care Med 1976;4:13-4. [Crossref] [PubMed]
  2. Mellins RB. Pulmonary physiotherapy in the pediatric age group. Am Rev Respir Dis 1974;110:137-42. [Crossref] [PubMed]
  3. McNicholas BA, Ibarra-Estrada M, Perez Y, et al. Awake prone positioning in acute hypoxaemic respiratory failure. Eur Respir Rev 2023;32:220245. [Crossref] [PubMed]
  4. Papazian L, Aubron C, Brochard L, et al. Formal guidelines: management of acute respiratory distress syndrome. Ann Intensive Care 2019;9:69. [Crossref] [PubMed]
  5. Crimi C, Noto A, Madotto F, et al. High-flow nasal oxygen versus conventional oxygen therapy in patients with COVID-19 pneumonia and mild hypoxaemia: a randomised controlled trial. Thorax 2023;78:354-61. [Crossref] [PubMed]
  6. Panadero C, Abad-Fernández A, Rio-Ramirez MT, et al. High-flow nasal cannula for Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Multidiscip Respir Med 2020;15:693. [Crossref] [PubMed]
  7. Teran-Tinedo JR, Gonzalez-Rubio J, Najera A, et al. Clinical characteristics and respiratory care in hospitalized vaccinated SARS-CoV-2 patients. EClinicalMedicine 2022;48:101453. [Crossref] [PubMed]
  8. Jagan N, Morrow LE, Walters RW, et al. The POSITIONED Study: Prone Positioning in Nonventilated Coronavirus Disease 2019 Patients-A Retrospective Analysis. Crit Care Explor 2020;2:e0229. [Crossref] [PubMed]
  9. Padrão EMH, Valente FS, Besen BAMP, et al. Awake Prone Positioning in COVID-19 Hypoxemic Respiratory Failure: Exploratory Findings in a Single-center Retrospective Cohort Study. Acad Emerg Med 2020;27:1249-59. [Crossref] [PubMed]
  10. 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;9:1387-95. [Crossref] [PubMed]
  11. Perez-Nieto OR, Escarraman-Martinez D, Guerrero-Gutierrez MA, et al. Awake prone positioning and oxygen therapy in patients with COVID-19: the APRONOX study. Eur Respir J 2022;59:2100265.
  12. Gad GS. Awake prone positioning versus non invasive ventilation for COVID-19 patients with acute hypoxemic respiratory failure. Egyptian Journal of Anaesthesia. 2021;37:85-90.
  13. 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;18:1424-6. [Crossref] [PubMed]
  14. Taylor SP, Bundy H, Smith WM, et al. Awake Prone Positioning Strategy for Nonintubated Hypoxic Patients with COVID-19: A Pilot Trial with Embedded Implementation Evaluation. Ann Am Thorac Soc 2021;18:1360-8. [Crossref] [PubMed]
  15. Rosén J, von Oelreich E, Fors D, et al. Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial. Crit Care 2021;25:209. [Crossref] [PubMed]
  16. Jayakumar D, Ramachandran Dnb P, Rabindrarajan Dnb E, et al. 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;36:918-24. [Crossref] [PubMed]
  17. Gopalakrishnan M, Khichar S, Saurabh S, et al. Effectiveness of early awake self proning strategy in non-intubated patients with COVID-19 hypoxemia: an open-labelled randomized clinical trial from Jodhpur, India. Monaldi Arch Chest Dis 2022;93: [Crossref] [PubMed]
  18. Hashemian SM, Jamaati H, Malekmohammad M, et al. Efficacy of Early Prone Positioning Combined with Noninvasive Ventilation in COVID-19. Tanaffos 2021;20:82-5.
  19. Alhazzani W, Parhar KKS, Weatherald J, et al. Effect of Awake Prone Positioning on Endotracheal Intubation in Patients With COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial. JAMA 2022;327:2104-13. [Crossref] [PubMed]
  20. Rampon G, Jia S, Agrawal R, et al. Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial. Chest 2022;162:782-91. [Crossref] [PubMed]
  21. Fralick M, Colacci M, Munshi L, et al. Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE). BMJ 2022;376:e068585. [Crossref] [PubMed]
  22. Nay MA, Hindre R, Perrin C, et al. Prone position versus usual care in hypoxemic COVID-19 patients in medical wards: a randomised controlled trial. Crit Care 2023;27:240. [Crossref] [PubMed]
  23. Winck JC, Scala R. Non-invasive respiratory support paths in hospitalized patients with COVID-19: proposal of an algorithm. Pulmonology 2021;27:305-12. [Crossref] [PubMed]
  24. 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;68:64-70. [Crossref] [PubMed]
  25. Hochberg CH, Psoter KJ, Eakin MN, et al. Declining Use of Prone Positioning After High Initial Uptake in COVID-19 Adult Respiratory Distress Syndrome. Crit Care Med 2023;51:1547-51. [Crossref] [PubMed]
  26. Retucci M, Aliberti S, Ceruti C, et al. Prone and Lateral Positioning in Spontaneously Breathing Patients With COVID-19 Pneumonia Undergoing Noninvasive Helmet CPAP Treatment. Chest 2020;158:2431-5. [Crossref] [PubMed]
  27. Shao X, Shao J. Lung physiological changes during awake prone positioning in non-intubated hypoxemia patients. Crit Care 2023;27:393. [Crossref] [PubMed]
  28. Prat G, Guinard S, Bizien N, et al. Can lung ultrasonography predict prone positioning response in acute respiratory distress syndrome patients? J Crit Care 2016;32:36-41. [Crossref] [PubMed]
  29. Haddam M, Zieleskiewicz L, Perbet S, et al. Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS. Intensive Care Med 2016;42:1546-56. [Crossref] [PubMed]
  30. Zarantonello F, Andreatta G, Sella N, et al. Prone Position and Lung Ventilation and Perfusion Matching in Acute Respiratory Failure due to COVID-19. Am J Respir Crit Care Med 2020;202:278-9. [Crossref] [PubMed]
  31. Pulletz S, Krukewitt L, Gonzales-Rios P, et al. Dynamic relative regional strain visualized by electrical impedance tomography in patients suffering from COVID-19. J Clin Monit Comput 2022;36:975-85. [Crossref] [PubMed]
  32. Rauseo M, Mirabella L, Laforgia D, et al. A Pilot Study on Electrical Impedance Tomography During CPAP Trial in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: The Bright Side of Non-invasive Ventilation. Front Physiol 2021;12:728243. [Crossref] [PubMed]
Cite this article as: Luján M, Sayas J. When hope meets reality: the challenges of awake proning in unmonitored settings. J Thorac Dis 2024;16(1):810-815. doi: 10.21037/jtd-23-1588

Article Options

Download Citation

Share