Among the proliferation of research prompted by the coronavirus disease 2019 (COVID-19) pandemic, a growing number of studies involve the role of prone positioning to improve ventilation in patients with acute respiratory distress syndrome (ARDS) related to the virus. In addition to its effectiveness in patients on mechanical ventilation, emerging results suggest that the practice may help to prevent intubation and associated complications in some patients.

The value of prone positioning in improving oxygenation and reducing mortality had been previously established in studies of patients with non-COVID-19-related moderate to severe ARDS, including those requiring venovenous extracorporeal oxygenation (ECMO). In a multicenter retrospective cohort study published in September 2020 in the Annals of the American Thoracic Society, researchers compared outcomes between ARDS patients managed with prone vs supine positioning during ECMO.1

Compared to the supine group (n=133), the prone group (n=107) showed significant improvements in the intrapulmonary shunt fraction and PaO2/FiO2 ratio, as well as reduced hospital mortality after adjustment for covariates (odds ratio [OR], 0.50; 95% CI, 0.29-0.87). Minor reversible complications occurred in 6% of prone positioning cases. These findings align with those of a retrospective single-center study (n=158) published Critical Care in July 2020, which demonstrated reduced hospital mortality with prone positioning — but only with early initiation — compared with late or no prone positioning in severe ARDS patients on ECMO (81.8% vs 33.3%; P =.02).2


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Additionally, results of a multicenter prospective cohort study (n=20) reported in Critical Care in January 2020 suggest that early initiation of prone positioning combined with high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV) may obviate the need for intubation in up to one-half of patients with moderate ARDS and baseline SpO2 > 95%. “[W]hen [prone positioning] was added, PaO2/FiO2 increased by 25 to 35 mm Hg compared with the prior HFNC or NIV; and [prone positioning] was safely performed and well tolerated by the moderate ARDS patients,” wrote the authors.3 However, patients with severe ARDS “were not appropriate candidates for NFNC/NIV+[prone positioning], and the risk of complications with delayed intubation may be increased.” 

Prone Positioning in COVID-19-Related ARDS

In patients with ARDS as a result of COVID-19, emerging research exploring the effects of prone positioning has produced favorable results overall. Results from a July 2020 study of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced ARDS on ECMO found that prone positioning improved oxygenation (median PaO2/FiO2 ratio improvement=28%). However, the prone group showed a significantly higher mortality rate than the supine group, which “may be explained by the greater illness severity and the lack of an immunomodulatory therapy such as corticosteroids,” according to the paper.4 

A prospective cohort study published in August 2020 in the Lancet Respiratory Medicine examined the use of prone positioning in non-intubated patients with ARDS related to COVID-19 who were receiving supplemental oxygen or noninvasive continuous positive airway pressure.5 They determined that the technique was feasible in 47 of 56 enrolled patients, and substantial improvements were observed when patients were changed from supine to prone positioning (PaO2/FiO2 ratio of 180.5 mm Hg [SD 76.6] vs 285.5 mm Hg [112.9]; P <.0001). 

Various other studies and case reports have found similar results in patients with COVID-19, including results from a New York City emergency department showing that SpO2 increased from 84% to 94% (P =.001) after 5 minutes of early self-proning in awake patients, and results from a Spanish study demonstrating improved oxygenation following prone positioning (PaO2/FiO2 increased from 196±68 to 242±107; P =.0072) in non-ICU patients with COVID-19 and mild to moderate ARDS who required oxygen therapy.6,7 

While findings thus far indicate the likely important role of awake prone positioning in the treatment of certain patients with COVID-19-induced ARDS, some experts have cautioned against its rapid, widespread adoption, noting the need for high-quality data from clinical trials before the benefits and best practices of the technique can be confirmed in this population.8,9

For an in-depth discussion regarding the benefits of prone position ventilation in general, we interviewed Abhijit Duggal, MD, pulmonologist and director of critical care research at Cleveland Clinic in Ohio. 

What does the evidence suggest about the pros and cons of prone positioning for patients with ARDS — both in general and in the context of COVID-19?

Prone position ventilation is perhaps one of the most effective interventions that we can use in patients with moderate to severe ARDS. First, a bit of historical context: Prone position ventilation has been around since the mid-1980s when the original physiologic studies were done in this area.10 Over the last 2 decades, multiple randomized trials have examined this. What we realized is that prone position ventilation is not needed for all patients with ARDS, but its effectiveness is most pronounced in patients who have severe ARDS.

A large randomized controlled trial found that utilizing prone position ventilation dropped the mortality associated with moderate to severe ARDS from about 33% in the control arm down to 16% in the intervention arm.10 Basically, the researchers were able to halve the risk of death by using prone positioning in patients with moderate to severe ARDS. Based on these results, prone position ventilation is strongly recommended by international societies.

In patients with COVID-19-associated ARDS, the same rules apply. It has been utilized extensively in these patients, and preliminary reports across the world have shown that this is an effective intervention. We have had positive outcomes in COVID-19-associated ARDS, just as we would have expected because of the extensive literature supporting this in other ARDS.

When would this be contraindicated, and what are other relevant caveats or recommendations regarding this practice?

There are 2 parts to this: First, there is a reluctance in terms of how people apply prone position ventilation because this is not something that is usually done in clinical practice, and it needs to be done at sites where there are people trained to do it. Once the personnel are trained to do it, it is a very simple procedure and is not associated with a lot of complications. But for those not trained in doing this procedure, there is a lot of apprehension in terms of potential risk for patients. One of the biggest things people worry about is that they may dislodge their endotracheal tube or other lines. 

There is a lot of literature showing that once personnel are have been trained to do this, those risk factors become small and inconsequential. As an example, we have been using this modality extensively at Cleveland Clinic for the last 8 years since it came out, and we have not faced any contraindications or associated adverse events.

The only cases in which prone position ventilation should not be considered are in patients with head injuries and a risk for increased intracranial pressures, patients with intraabdominal hypertension, and those who are hemodynamically unstable (eg, on high doses of vasopressors). For all other cases, prone positioning can be considered.

Now there are 2 points I want to make here: First, many providers think that they can only prone patients using a specialized bed called a RotoProne® bed, and that is not the case. If you look at all the literature, if you look at everything that has been published, no automated beds were used. This was all done with manual proning where patients were just flipped onto their abdomen on a standard bed by the physicians and nursing staff. That is what we do at Cleveland Clinic — we do not use RotoProne beds here; we use manual proning. It is really easy to do and greatly improves outcomes. The other factor that we need to be mindful of in these patients is this fear of the harm this might cause the patient, even though it has not been shown.

Another common reason that people will not apply prone position ventilation early is because they feel like perhaps their patient is just going to turn the corner in the next day or 2, and they should wait until this becomes really bad ARDS. But what the literature shows is that if you apply it early (within the first 2 days of the development of severe ARDS), that is where the greatest benefit occurs, so you should not wait for patients to become really sick and unstable.2 You should do it early because that is when it will help patients. Prone position ventilation should not be used a rescue intervention for refractory hypoxemia; it should be used as an adjunctive therapy in patients with moderate to severe ARDS.

There is literature available and recommendations on how to utilize this more effectively, by the American College of Critical Care Nurses and the American Thoracic Society.

At Cleveland Clinic, we have an extensive program with a nursing protocol and a physician protocol that we use to help these patients and train our staff.  We offer training at our regional locations, and we also offer it to other institutions that ask for our help.

What are some of the major remaining barriers in this area?

The research findings support that this is a highly effective intervention if used in the right context. The problem is that it often is not used when it should be. There is extensive literature showing that, at a global level, only about 30% of patients who meet criteria for prone position ventilation are proned, and that is because of a lack of education or a lack of recognition in most cases.10

For prone position ventilation, the number needed to treat to save 1 life was 6 — you will save 1 life for every 6 patients who receive this intervention, and that is a huge thing for people to understand and utilize.11 One of the biggest barriers at this point is just implementation in clinical practice in a consistent manner, and that is something that many people are working on. We have been involved in a lot of research around this and have identified how to change that at the Cleveland Clinic.12

References

1. Giani M, Martucci G, Madotto F, et al. Prone positioning during venovenous extracorporeal membrane oxygenation in acute respiratory distress syndrome: a multicentre cohort study and propensity-matched analysis. Published online September 17, 2020. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.202006-625OC

2. Rilinger J, Zotzmann V, Bemtgen X, et al. Prone positioning in severe ARDS requiring extracorporeal membrane oxygenation. Crit Care. 2020;24(1):397. doi:10.1186/s13054-020-03110-2

3. 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. doi:10.1186/s13054-020-2738-5

4. Garcia B, Cousin N, Bourel C, et al. Prone positioning under VV-ECMO in SARS-CoV-2-induced acute respiratory distress syndrome. Crit Care. 2020;24(1):428. doi:10.1186/s13054-020-03162-4

5. 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. doi:10.1016/S2213-2600(20)30268-X

6. 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. doi:10.1111/acem.13994

7. Taboada M, Rodríguez N, Riveiro V, Baluja A, Atanassoff PG. Prone positioning in awake non-ICU patients with ARDS caused by COVID-19. Anaesth Crit Care Pain Med. 2020;39(5):581-583. doi:10.1016/j.accpm.2020.08.002

8. Koeckerling D, Barker J, Mudalige NL, et al. Awake prone positioning in COVID-19. Thorax. 2020;75(10):833-834. doi:10.1136/thoraxjnl-2020-215133

9. Munshi L, Fralick M, Fan E. Prone positioning in non-intubated patients with COVID-19: raising the bar. Lancet Respir Med. 2020;8(8):744-745. doi:10.1016/S2213-2600(20)30269-1

10. Li X, Scales DC, Kavanagh BP. Unproven and expensive before proven and cheap: extracorporeal membrane oxygenation versus prone position in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2018;197(8):991-993. doi:10.1164/rccm.201711-2216CP

11. Guérin C, Reignier J, Richard JC, et al; for the PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159-2168. doi:10.1056/NEJMoa1214103

12. Duggal A, Panitchote A, Siuba M, et al. Implementation of protocolized care in ARDS improves outcomes. Published online October 13, 2020. Respir Care. doi:10.4187/respcare.07999