Proning in COVID-19 Patients

COVID IN FOCUS: PERSPECTIVES ON THE LITERATURE

This CHEST series highlights specific studies in the COVID-19 literature that may warrant discourse or reading for members of the chest medicine community. Articles are written by members of CHEST Networks. You can read additional articles in this series.

NOTE: The perspectives shared in this article are those of the author(s) and not those of CHEST.

Proning in COVID-19 Patients

By: Mary Jo S. Farmer, MD, PhD, FCCP; Claudia Onofrei, MD, MSc; and Salim Surani, MD, MPH, MSHM, FCCP
Clinical Pulmonary Medicine Network

Published: May 17, 2021

Prone positioning with or without mechanical ventilation has been widely adopted in treating patients with respiratory failure due to COVID-19. Previous experience in patients with moderate to severe acute respiratory distress syndrome (ARDS) demonstrated a survival benefit associated with early application of prone positioning.1,2

In the landmark PROSEVA trial, Guerin et al found that early application of prone positioning sessions of at least 16 hours in patients with severe ARDS significantly decreased 28-day mortality (16% proned vs 33% non-proned) and 90-day mortality (24% proned vs 41% non-proned). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150 mm Hg with an FIO2 of at least 0.6, a positive end-expiratory pressure of at least 5 cm of water, and a tidal volume close to 6 cc per kilogram of predicted body weight.

How Does Proning Work?

Prone positioning improves ventilation by re-expansion of collapsed lung parenchyma in dorsal lung regions and reduction in aeration of ventral lung regions, resulting in lung recruitment and more homogenous lung aeration. Lung perfusion is thought to be less dependent on gravity; however, the net effect yields improvement in ventilation and perfusion (V/Q) matching, facilitating gas exchange. In addition, more homogenous distribution of ventilation should reduce ventilator-induced lung injury.3 Proning also helps with secretion clearance and with decreasing the weight of the mediastinum on the lungs.

Use of Awake Proning

Proning—in particular, awake or self-proning—has been incorporated in treatment protocols for patients with COVID-19 disease. A sentinel case analysis4 coined the term “awake prone position.” Patients who met criteria—respiratory rate >30/minute, oxygen saturation (SpO2) <93% on room air, or heart rate >120 beats/minute—were managed with high-flow nasal cannula or noninvasive ventilation, fluid restriction, and awake prone positioning. This management was thought to contribute to low mortality and high discharge rates, although the data was not analyzed for statistical significance.

Averting the need for intubation and ICU care are among the objectives for awake proning of patients with mild to moderate COVID-19 disease. In addition, avoiding intubation may provide a benefit to health care workers since intubation is a procedure associated with higher risk of infection transmission.5 A number of reports—including case series and retrospective analyses from the US, China, France, and Italy—support the use of monitored awake proning as a remedy for COVID-associated ARDS while avoiding or forestalling intubation and mechanical ventilation.6,7

Intubation was avoided in 64% of patients who were hospitalized and COVID-positive when awake proning was applied in a consecutive series of patients in a New York City emergency department.5 In this observational study, 50 patients with confirmed COVID-19 and hypoxia (SpO2 <90%), unresolved (SpO2 >93%) despite supplemental oxygen, self-proned. The change in oxygen saturation was measured 5 minutes after self-proning. Median oxygen saturation was 80% on arrival and increased to 84% after patients were placed on supplemental oxygen. After 5 minutes of proning, median oxygen saturation increased to 94%. The duration of this effect is unclear. Interestingly, 36% of patients were intubated within 72 hours, and of these, 38% (n = 7) were intubated within the first hour.

Indications for Awake Proning

Indications for awake proning include vital sign and hemodynamic stability, oxygen saturation <92% on supplemental oxygen, and a conscious and responsive patient who is able to turn in and out of the prone position either on the stomach or side with minimal or no assistance. Patients are in a negative pressure room closely monitored with telemetry and appropriate nursing ratios. Close monitoring and frequent re-evaluation are recommended during the hospital course since these patients can abruptly worsen. Padding over pressure points should be provided to prevent skin breakdown and injury. If the patient cannot tolerate the prone position or has worsening hypoxia, work of breathing, or tachycardia, the patient is returned to supine position with the head of the bed elevated. Intubation and mechanical ventilation are considered.

A summary of recent papers about awake proning in COVID-19 is provided in the table. Overall, success has been variable and is based on case reports; small, nonrandomized control trials; and recently, a randomized control trial. There is evidence that awake proning is feasible and safe. There is little downside to attempting awake proning, as it is inexpensive and easy. Whether this intervention affects patient outcomes would be clearer if study population definitions regarding disease severity, length of proning, and follow-up times were standardized. Simultaneous use of high-flow supplemental oxygen and/or noninvasive ventilation and effect on mortality should be studied.

Study Sample size & study design Percentage of patients proned Improvement in or maintained oxygenation among proned (percentage of patients)
Caputo et al5 50
Observational
100% 76% improved or maintained oxygenation
Elharrar et al6 24
Single-center prospective
100% proned; only 63% proned for at least 3 hours 6 responders with PaO2 increased =>20% before and during prone positioning; 24% (6/24), 40% (6/15)
Sartini et al7 15
Retrospective cross-sectional review
100% 100% improved SpO2 and P/F ratio during pronation; 80% improved SpO2 and P/F ratio after pronation; 13.3% same value
Xu Q et al8 10
Retrospective, observational multicenter
100% 100%
Coppo et al9 56
Prospective feasibility
84% proned for at least 3 hours 100% significant change in P/F ratio from supine to prone; after resupination, 49% (23/47) maintained improved oxygenation, but this was not significant
Damarla et al10 10
Retrospective review
100% 80% (8/10) did not require intubation; all experienced significant improvement in respiratory status
Kharat et al11 10 prone group;
17 usual care group
Single-center cluster randomized controlled trial
90% (9/10) Overall, clinically meaningful reduction of oxygen flow not statistically significant; trial stopped due to lack of available subjects and effective COVID-19 containment measures

Proning Intubated and Mechanically Ventilated Patients

Contrary to awake proning, proning the intubated and mechanically ventilated patient with COVID-19 disease is more labor intensive, requiring dedicated and experienced personnel, and it is associated with increased risk of device displacement (such as central lines and endotracheal tubes) and development of pressure ulcers. Incremental dosing of sedatives and paralytics may result in hemodynamic instability. Prone positioning teams can provide consultation regarding patient eligibility for proning, as well as expertise and staffing for safe implementation.

Langer et al published a large, multicenter, retrospective study including more than 1,000 patients in 24 Italian intensive care units, investigating the use and effect of prone positioning in intubated, mechanically ventilated patients with COVID-19.3 Respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as oxygen responders if the P/F ratio increased ≥20 mm Hg during prone position and as carbon dioxide responders if the ventilatory ratio was reduced during prone position.

One thousand fifty-seven patients with mild (15%), moderate (50%), and severe (35%) ARDS had a mortality of 25%, 33%, and 41%, respectively. Prone position was applied in 61%. Overall, proned patients experienced more severe disease and more significant deaths (45% vs 33%, P < .001). P/F ratio increased significantly with prone position, without change in respiratory system compliance or ventilatory ratio. Of the subset, 78% were oxygen responders. Nonresponders experienced more severe respiratory failure and died more often. Carbon dioxide responders were 47% of the subset; however, no difference in ICU mortality was observed.

Limitations of the study included its retrospective nature, criteria to prone was not standardized among participating hospitals, information on complications of prone positioning was not collected, and efficacy of pronation in terms of outcome was not provided. The fact that respiratory system compliance did not change over three timepoints suggests that lung recruitment did not play a significant role during first pronation; however, the number of patients included in this subset was small.

Mathews and colleagues looked at ICU survival with prone positioning in mechanically ventilated patients with COVID-19 at 68 US sites.12 Of the 2,338 patients with a P/F ratio of <200, 30% were proned in the first 2 days of ICU admission; 43.5% of patients survived and were discharged; 47.1% died; and 9.4% remained hospitalized at last follow-up. Patients who were proned in the first 2 days of ICU had a lower adjusted risk of death (HR: 0.84; 95% CI, 0.73-0.97).

Further studies will clarify the role of proning in the treatment of COVID-19 disease.




References

  1. Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. NEJM. 2013;368:2159-2168.
  2. Gattinoni L, Taccone P, Carlesso E, et al. Prone position in acute respiratory distress syndrome. Rationale, indications, and limits. Am J Resp Crit Care Med. 2013;188(11):1286-1293.
  3. Langer T, Brioni M, Guzzardella A, et al. Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients. Critical Care. 2021;25(1):128.
  4. Sun Q, Qiu H, Huang M, et al. Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province. Ann Intensive Care. 2020;10(1):33.
  5. Caputo ND, Strayer RJ, Levitan R. Early self‐proning in awake, non‐intubated patients in the emergency department: a single ED’s experience during the COVID‐19 pandemic. Acad Emerg Med. 2020;27(5):375-378.
  6. Elharrar X, Trigui Y, Dols AM, et al. Use of prone positioning in nonintubated patients with COVID-19 and hypoxemic acute respiratory failure. JAMA. 2020;323(22):2336-2338.
  7. Sartini C, Tresoldi M, Scarpellini P, et al. Respiratory parameters in patients with COVID-19 after using noninvasive ventilation in the prone position outside the intensive care unit. JAMA. 2020;323(22):2338-2340.
  8. Xu Q, Wang T, Qin X, et al. Early awake prone position combined with high-flow nasal oxygen therapy in severe COVID-19: a case series. Crit Care. 2020;24(1):250.
  9. Coppo A, Bellani G, Winterton D, et al. Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study. Lancet Respir Med. 2020;8(8):765-774.
  10. Damarla M, Zaeh S, Niedermeyer S, et al. Prone positioning of nonintubated patients with COVID-19. Am J Resp Crit Care Med. 2020;202(4):604-606.
  11. Kharat A, Dupius-Lozeron E, Cantero C, et al. Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial. ERJ Open Resp. 2021;7(1):00692-2020.
  12. Mathews KS, Soh H, Shaefi S, et al. Prone positioning and survival in mechanically ventilated patients with coronavirus disease 2019-related respiratory failure. Preprint. Posted online February 17, 2021. Crit Care Med.



 Mary Jo S. Farmer, MD, PhD, FCCP

Mary Jo S. Farmer, MD, PhD, FCCP

  • Director, Pulmonary Hypertension Services at Baystate Health
  • Assistant Professor of Medicine, University of Massachusetts Medical School, Baystate
Claudia Onofrei, MD, MSc

Claudia Onofrei, MD, MSc

  • Pulmonologist and Assistant Professor, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health
Salim Surani, MD, MPH, MSHM, FCCP

Salim Surani, MD, MPH, MSHM, FCCP

  • Adjunct Clinical Professor of Medicine and Program Director, Pulmonary Fellowship, Texas A&M University



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COVID-19 and Pregnancy

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