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Three Part Question

In [awake adult patients with hypoxaemic respiratory failure] does the use of [regular prone positioning] lead to reduction in [morbidity or mortality].

Clinical Scenario

A 55 year old with a background of hypertension is brought to the emergency department with a 7 day history of fever, cough, and shortness of breath. His oxygen saturations are 93% on 6 litres of oxygen via facemask and arterial blood gas results suggest type 1 respiratory failure. You suspect COVID-19 and refer to the medical team for conservative management and inpatient care. Having made the referral, you remember listening to a podcast about prone positioning and wonder if this would improve his oxygenation or reduce the likelihood of clinical deterioration?

Search Strategy

Medline database searched from 1900 until 28/4/2020 via the Pubmed interface.
Search criteria: (respiratory failure OR ARDS) AND (awake OR conscious OR non-intubated OR nasal high flow OR CPAP OR non-invasive ventilation) AND (prone position* OR proning).
The search was limited to human studies.

51 search results were returned of which all abstracts were screened

Search Outcome

29 articles were excluded as they related to prone positioning in the context of mechanical ventilation. 16 articles were excluded as they were not reporting on the population of relevance (paediatric and bypass studies). A further article was excluded as a commentary and another as a case series of <5 patients.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Ding et al 2020 China	Patients with moderate (n=10) to severe (n=10) ARDS secondary to viral or bacterial pneumonitis. Patients were escalated through HFNC, HFNC with prone position, NIV, and NIV with prone position according to their O2 saturations.	Level 4 – Non-controlled prospective cohort study.	Rate of intubation.	9 out of 20 patients were intubated (45% failure rate)	Small convenience sample. No control group so inappropriate study design to determine whether prone positioning improves rates of intubation. Heterogenous cohort with multifaceted interventions.
Caputo et al 2020 USA	A pilot study of 50 patients attending the Emergency Department (ED) with hypoxia, in the context of suspected COVID-19.	Level 4 – Non-controlled prospective cohort study	Median SpO2 Increase	Median increase of 10% in saturation levels following prone position for 5 minutes.	Single centre convenience sample with no controlled aspects of care or intervention. Patients receiving any form of NIV were excluded from the study. Surrogate endpoint. Short term primary outcome, subjective secondary outcome.
			Rate of intubation within 24h of presentation.	13 (24%) of subjects required intubation for respiratory failure within 24h of presentation. 7 of these were intubated within 60 minutes of attempted prone positioning. 5 patients were subsequently intubated as inpatients.
Scaravilli et al 2015 Italy	Analysis of 43 proning procedures in 15 non-intubated patients (14 adults and 1 child) with hypoxaemic acute respiratory failure (PaO2/FiO2 <300mmHg). A range of O2 devices were used while proning including O2 via facemask (n=24), HFNC (n=1), helmet CPAP (n=11), and mask NIV (n=7).	Level 4 – Non-controlled retrospective observational study.	Change in PaO2/FiO2 ratio.	PaO2/FiO2 ratio 124 ± 50mmHg, 187 ± 72 mmHg, 140 ± 61 mmHg, during pre, prone, and post steps respectively, p< 0.001). P/F ratio deemed to be significantly higher during prone positioning compared to pre- and post.	Small patient cohort and convenience sample No consistency in proning duration and frequency. No controlled aspects of care: respiratory device, PEEP and/or FiO2 were altered during 25 of the 43 proning procedures. No control group. Surrogate outcome reported.
Perez-Nieto et al., 2020 Mexico	6 patients with severe non-infectious ARDS.	Level 4 – Case series.	Oxygenation.	In each individual patient the PaO2/FiO2 and SO2/FiO2 ratio was generally higher after being placed in the prone position.	Small case series, therefore no control over intervention and no comparison group

Comment(s)

Recent evidence supports the use of prone positioning in patients with moderate to severe Adult Respiratory Distress Syndrome (ARDS), receiving mechanical ventilation. This intervention features in contemporary guidelines and has been widely applied to critically ill patients meeting the Berlin definition of ARDS during the COVID-19 pandemic. Prone positioning aims to provide net clinical benefit through a variety of actions: recruitment of posterior lung segments, secretion clearance and improved VQ matching through maximal blood supply to better aerated lung units. In ventilated patients, prone positioning is recommended for >16h at a time in attempt to facilitate further beneficial interventions, such as oxygen weaning and reduced barotrauma from ventilation at high plateau pressures. Previous researchers have proposed that the same physiological benefits may apply to ARDS patients not receiving mechanical ventilation. In the context of limited resources and effective treatment options for COVID-19, prone positioning has recently received a high level of attention. National groups have argued for the simplicity and low cost of the intervention, proposing trial attempts on all suitable ward patients. However, it is unclear as to whether this intervention leads to improvement in any clinically relevant outcomes, what protocol should be used, whether there are risks involved and what contraindications should be noted. In addition, many of the proposed physiological benefits to prone positioning of awake patients can be met with the simple intervention of sitting patients out in a chair. Human beings have evolved to be upright, not face down. Prone positioning is used for mechanically ventilated patients on intensive care, purely because these patients cannot be safely managed erect. As such, any proposed benefit to prone position in the awake patient requires comparison against patients who are mobilised into sitting or standing positions, at regular intervals. The studies to date on this topic are case series, inconsistent in protocol, and subject to multiple sources of confounding. All lack standardised care or control arms. Several suggest a transient benefit to oxygenation during time in the prone position, but none provide evidence that this benefit is sustained or impacts on any clinically relevant outcomes, such as rate of intubation, length of stay or mortality. As such, there is no evidence to support routine use of prone positioning in awake patients.

Clinical Bottom Line

There is no evidence that regular prone positioning in the awake patient with hypoxaemic respiratory failure impacts on clinically relevant outcomes. Controlled trials are needed to determine if this intervention is well tolerated, safe and clinically effective compared to routine supported mobilisation, prior to widespread adoption.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. 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(1): 28.
2. 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;10.1111acem.13994
3. 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(6): 1390-4.
4. Perez-Nieto OR, Guerrero-Gutierrez MA, Deloya-Tomas E, Namendys-Silva SA. Prone positioning combined with high-flow nasal cannula in severe noninfectious ARDS. Crit Care 2020; 24(1): 114.