Awake proning in non-intubated patients

The physiological benefits and improvement in clinical outcomes with prone ventilation are well established in patients who are intubated and mechanically ventilated (1). Would the favorable physiological effects of the prone position benefit non-intubated, spontaneously breathing patients with acute hypoxemic respiratory failure? In light of an increasing number of patients with COVID-19 pneumonia and constrained healthcare resources worldwide, awake proning is being explored as a possible intervention to avoid invasive mechanical ventilation. There were early reports of the prone positioning in non-intubated, spontaneously breathing patients in lung transplant recipients (2), and in acute hypoxemic respiratory failure in patients with acute respiratory distress syndrome (ARDS) (3).  

Lung injury and the supine position 

The force of diaphragmatic contractility is greater in the dependent areas of the lung. This results in a more negative pleural pressure being exerted in the dependent areas compared to non-dependent areas during spontaneous breathing in patients with lung injury. As a result, airflow occurs across a gradient from the non-dependent to dependent alveoli; this leads to hyperinflation injury to the dependent lung. Injury may occur even with normal spontaneously generated tidal volumes. This pendelluft movement of air from the non-dependent to the dependent areas of the lung may provoke self-inflicted lung injury in patients who have vigorous spontaneous respiratory efforts (4). In the prone position, when the diseased lung becomes non-dependent, the diaphragmatic contraction may distribute lung stress more uniformly, with a relatively less likelihood of propagation of lung injury. 

The posterior lung mass is greater compared to the anterior parts of the lung. In the supine position, the dependent lung bears the weight of the anterior, non-dependent lung, and the mediastinal structures, including the heart. This leads to compression collapse of dependent areas of the lung in the supine position. The other important consideration is the greater perfusion of the dependent lung, which is unrelated to gravitational changes. Thus, in ARDS, the dorsal areas of the lung, which are involved to a greater extent, receive disproportionately higher perfusion, leading to a significant increase in the shunt fraction across the lung. This is one of the important reasons for arterial hypoxemia in patients with ARDS. 

Physiology of prone positioning

When patients with ARDS assume the prone position, two important changes occur. First, the dorsal areas of the lung, which were collapsed or de-recruited, become non-dependent. The dorsal lung is freed from the mechanical effects of gravity, leading to significant alveolar recruitment. The sternum supports the mediastinum anteriorly. Second, due to the gravitational effect, perfusion improves to the anterior regions of the lung, which are already better ventilated compared to the posterior regions. This change of predilection of perfusion to better-ventilated areas improves overall ventilation-perfusion matching, thus improving gas exchange. Furthermore, change from the supine to the prone position results in improved mobilization of secretions from the dorsal areas of the lung. 

The improved recruitment that occurs in the prone position results in better ventilation and oxygenation, mitigating the impact of hypoxic pulmonary vasoconstriction. Consequently, blood flow improves across the lungs, thus reducing the afterload to the right ventricle, leading to improved function.

Prone position in non-intubated patients with lung injury: the evidence

The prone position is well-established to improve clinical outcomes, including mortality, among patients who are intubated and mechanically ventilated (1). Recently, there has been increasing interest in using the prone position in non-intubated patients with acute hypoxemic respiratory failure. The outbreak of COVID-19 pneumonia across the world resulted in a surge of hypoxic patients in resource-constrained health care settings. “Awake proning” in non-intubated patients has emerged as a possible intervention to improve respiratory parameters. 

In a retrospective study, Scaravilli et al. evaluated the effect of the prone position in spontaneously breathing, non-intubated patients with acute hypoxemic respiratory failure. In this study of 15 patients, different modalities of respiratory support were used, including oxygen mask, high-flow nasal cannula (HFNC), helmet CPAP, or non-invasive ventilation (NIV). The type of respiratory support and FiO2 were unaltered on assuming the prone position. Prone positioning resulted in a significant increase in the PaO₂/FiO₂ ratios; however, the effect dissipated when patients were turned back to the supine position. No changes were observed in the respiratory rate, hemodynamic status, the PaCO₂, and pH levels (5).  

In an observational cohort study, 20 patients with ARDS of variable etiology were placed in the prone position in combination with HFNC or NIV. Improvement in oxygenation was assessed in four groups: those who had HFNC or NIV alone, and those who had either HFNC or NIV combined with prone positioning. The primary endpoint, the requirement for endotracheal intubation, occurred in 9 of 20 patients. The PaO₂/FiO₂ ratio among patients who received the HFNC-prone combination was significantly higher in those who did not require intubation. The authors concluded that prone positioning combined with HFNC, if applied early, may help avoid intubation in patients with moderate ARDS (6). 

One of the initial experiences with prone positioning in non-intubated, spontaneously breathing patients with COVID-19 infection was reported from the Jiangsu province in China. Among patients with moderate to severe ARDS due to COVID-19 pneumonia, Sun et al. observed improved oxygenation in awake, non-intubated patients with prone positioning. They attributed improved outcomes among their patients and a reduced requirement for intubation to a combination of awake proning, restrictive fluid therapy, and the use of NIV (7).  

In an observational cohort study, 50 patients with confirmed COVID-19 infection by RT-PCR were enrolled from an academic emergency department in New York City. The median SaO₂ with supplemental oxygen was 84% (IQR: 75–90). Patients assumed the prone position on their own. At 5 minutes after proning, the SaO₂ increased significantly, to a median value of 94% (IQR: 90–95%) (p = 0.001). Thirteen patients required endotracheal intubation and mechanical ventilation within 24 hours of presenting to the emergency department. Among the remaining 37 patients, five were intubated subsequently. This study revealed improved SaO₂ on assuming the prone position among awake, non-intubated, spontaneously breathing patients (8).   

A prospective study was conducted among consecutive, spontaneously breathing, non-intubated patients with COVID-19 pneumonia and acute hypoxemic acute respiratory failure in a single center in France. Among 24 patients who were enrolled, 15 tolerated the prone position for more than 3 hours. Six patients experienced a 20% improvement in the PaO₂/FiO₂ ratio after assuming the prone position. Among these, three patients sustained the improvement in PaO₂/FiO₂ ratios after reassuming the supine position. There was no significant difference noted in the PaO₂ levels before assuming the prone position and after re-supination. No major complications were noted with prone positioning (9). 

NIV in the prone position

Is prone positioning a feasible option among patients who are on NIV? Sixty-two patients with COVID-19 infection and mild to moderate ARDS were studied in Milan, Italy. These patients were treated in the general wards and received mask CPAP support of 10 cm of H2O with an FiO2 of 0.6. In case of a poor response to CPAP, patients were turned to the prone position. Fifteen patients were turned prone; all the patients experienced a reduction in the respiratory rate in the prone position that was sustained after re-supination. The SaO₂ and PaO₂/FiO₂ ratios improved in all 15 patients when they were in the prone position; this improvement was sustained after re-supination in 12 patients. Eleven patients experienced an improved level of comfort when they were prone. On follow-up at 14 days, one patient required intubation and required ICU transfer, while one patient died. Nine patients were discharged home, one patient did not require proning any more, while three patients continued to require intermittent pronation (10).  

A practical approach to awake proning

As a first step, the ability of the patient to assume the prone position and re-supine independently or with minimal assistance needs to be assessed. Patients must be hemodynamically stable and able to communicate. Document the FiO₂, the oxygen support device, and the SaO₂ at baseline. If the PaO₂/FiO₂ ratio is less than 150 mm Hg, awake proning may not be appropriate. Patients are placed in the prone position supported by their arms, using a pillow to allow unobstructed passage of the oxygen tubing. Additional pillows may be placed under the hips or legs, to enable patient comfort. The initial duration of the prone position may be 1 hour, after which the patient may be allowed to re-supine. The change in respiratory rate and SaO₂ levels must be diligently monitored when the patient is in the prone position. If improvement is noted, allow proning for longer periods, for up to 3 hours at a time or as long as the patient remains comfortable. Pronation may be continued for 2–4 hours per session, about 2–4 times per day as tolerated (11). 

Summary 

• The physiological advantages of the prone position in acute hypoxemic respiratory failure include improved recruitment of the dorsal lung and more favorable ventilation-perfusion matching.

• Previous case series have revealed improved oxygenation with awake proning.

• Early experience suggests that improved PaO₂/FiO₂ ratios and reduced respiratory rates may ensue from awake proning in patients with COVID-19 infection.
• Awake proning may be combined with conventional modalities of respiratory support in spontaneously breathing patients, including nasal cannulae, oxygen masks, HFNC, and NIV.

• Sustained improvement in oxygenation may not occur once re-supination occurs; hence, longer periods of proning, several times a day, may be required. 

• Awake proning may also be a viable option for patients in whom invasive ventilation may be considered futile. 

• Future studies are required to investigate if early awake proning may reduce the requirement for invasive ventilation.

References

1.         Guérin C, Reignier J, Richard J-C, Beuret P, Gacouin A, Boulain T, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013 Jun 6;368(23):2159–68. 

2.         Feltracco P, Serra E, Barbieri S, Milevoj M, Michieletto E, Carollo C, et al. Noninvasive high-frequency percussive ventilation in the prone position after lung transplantation. Transplant Proc. 2012 Sep;44(7):2016–21. 

3.         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 Apr;47(4):416–8. 

4.         Yoshida T, Torsani V, Gomes S, De Santis RR, Beraldo MA, Costa ELV, et al. Spontaneous Effort Causes Occult Pendelluft during Mechanical Ventilation. Am J Respir Crit Care Med. 2013 Nov 7;188(12):1420–7. 

5.         Scaravilli V, Grasselli G, Castagna L, Zanella A, Isgrò S, Lucchini A, et al. Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: A retrospective study. J Crit Care. 2015 Dec;30(6):1390–4.

6.         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 [Internet]. 2020 Jan 30 [cited 2020 May 19];24. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993481/

7.         Sun Q, Qiu H, Huang M, Yang Y. Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province. Ann Intensive Care. 2020 Mar 18;10(1):33. 

8.         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. Kline J, editor. Acad Emerg Med. 2020 May;27(5):375–8. 

9.         Elharrar X, Trigui Y, Dols A-M, Touchon F, Martinez S, Prud’homme E, et al. Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure. JAMA [Internet]. 2020 May 15 [cited 2020 May 19]; Available from: https://jamanetwork.com/journals/jama/fullarticle/2766292

10.       Sartini C, Tresoldi M, Scarpellini P, Tettamanti A, Carcò F, Landoni G, et al. Respiratory Parameters in Patients With COVID-19 After Using Noninvasive Ventilation in the Prone Position Outside the Intensive Care Unit. JAMA [Internet]. 2020 May 15 [cited 2020 May 19]; Available from: https://jamanetwork.com/journals/jama/fullarticle/2766291

11.       “Massachusetts General Hospital Prone Positioning for Non-Intubated Patients Guideline.” https://www.massgeneral.org/Assets/MGH/Pdf/News/Coronavirus/Prone-Positioning-Protocol-for-Non-Intubated-Patients.pdf.