Proning- keeping up to date.

 April 19

by Jonathan Downham

Having covered the PROSEVA trial I have been looking at further research covered since that.

The first is “The efficacy and safety of prone positioning in adult patients with acute respiratory distress syndrome: a meta analysis of randomised controlled trials”

This was a study to evaluate the effects of prone positioning on mortality rates with a particular focus on the duration and concurrent use of protective lung strategies.

In order to be included in the study prone ventilation must have been applied intermittently or continuously and they were excluded is they did not report mortality rates or evaluated only the effects of proning on heamodynamics or respiratory mechanics. 

From this they extracted eight trials meeting this criteria with high methodological quality. However they do go on to remark on the lack of blinding in all the trials as being one of the first weaknesses.

The mortality rates of the included studies from prone and supine are 41% and 47% respectively and this was statistically significant with a relative risk of  0.90.

However there was statistical heterogeneity. Heterogeneity in statistics means that your populations, samples or results are differentThis is a common problem when undertaking this kind of study and can impact upon the results.

In sub group analysis (Subgroup analysis is one way of finding out. It's a type of analysis done by breaking down study samples into subsets of participants based on a shared characteristic. The goal is to explore differences in how people respond to an intervention.) All cause mortality rates in the three trials not including those utilising lung protective ventilation i.e. where lower tidal volumes are used, did not differ.

However when proning was carried out for more than 12 hours mortality was further reduced with a relative risk of 0.75.

The significance of the heterogeneity within the studies means overall that the effects were not statistically significant however.

Guerins' trial was the only one without such a degree of heterogeneity and is the most recent in this analysis and in this study those recruited were defined as having severe ARDS rather than moderate to severe. Indeed some of them may have included mild ARDS.

Duration of proning across the trials was also very varied and they all used a low PEEP strategy.

The authors of the paper then also go on to to acknowledge the diversity of the included trials and lack of availability of raw data for sub group analysis well as the small number of studies actually included in the analysis. 

They conclude:

Prone positioning tends to reduce the mortality rates in ARDS patients, especially when used in conjunction with a lung protective strategy and longer prone position durations. Prone positioning for ARDS patients should be prioritized over other invasive procedures because related life-threatening complications are rare.

The next trial I looked at was "Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: A Cohort Study and Analysis of Physiology" a study published in 2021. 

This was obviously a study aimed at those presenting with COVID-19, the primary outcome being in hospital death and the secondary outcomes being changes in physiologic conditions.

This was a study carried out in the South Bronx constituting almost entirely Hispanic or Black patients. Clearly then its generalisability is not strong, something the authors acknowledge. They also go on to say that the demographics of the two groups are similar, those proned and not proned, but looking at the table below I am not convinced by this assertion.

There seemed to be a large number not proned even though they fulfilled the criteria and this is not explained. The final decision to prone was left to the primary care team and this might imply that there was a lot of resistance to proning amongst them leading to a degree of bias. 

I think you can also see from above that in the proning cohort there was a higher proportion amongst the 41-60 age group whilst the opposite is true in the >80yrs age group. Also notice that across both groups these were very obese patients.

Using their statistical tool they found an improvement in in-hospital mortality between the two groups and well as some improved physiological markers.

In their conclusion they go on to mention three key findings-

  • Mortality benefit of prone positioning with a Number Needed to Treat of 8 (The Number Needed to Treat (NNT) is the number of patients you need to treat to prevent one additional bad outcome).
  • Benefit of more days of proning- more seems to be better.
  • The improvement in the physiological parameters may support the hypothesis of improved V/Q matching with proning.

They conclude:

Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every 8 patients treated.

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