SCCM Resource Library-Mechanical Power Is Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome

Video Transcription

My name is Andrew Percy. I'm a Pediatric Critical Care Fellow at the Children's Hospital of Philadelphia. In this presentation, I'm going to talk about  mechanical power in pediatric ARDS, and specifically a project that I've been working on with my research mentor, Nader Yeya. One of the main reasons I pursued  fellowship training at CHOP was for the chance to work with Nader, and it has been such a pleasure to learn more about this topic and about study design with him.  When we talk about lung injury, we use words like barotrauma or volutrauma. And these are all attempts to describe mechanical concepts of stress and strain  that are imposed on the lung and cause injury. But stress and strain aren't easily measurable. So the goal then is to identify accurate surrogates  of stress and strain that allow us to quantify ventilator-induced lung injury risk. Surrogates that have been previously described include low tidal volume strategies  popularized by ARDSnet, driving pressure described by Amato in 2015, and now mechanical power. While adult data have demonstrated mortality benefits  of low tidal volume and driving pressure, retrospective pediatric studies have failed to demonstrate similar outcome data. Our study that I will present includes  the largest reported cohort of children that has been associated with mechanical power outcomes.  We talk a lot about ventilator-induced lung injury in the pediatric ICU, but almost all of it is extrapolated from adult data. There are very little data in children,  certainly no pediatric RCTs equivalent to ARDSnet. And this extrapolation may be problematic for all sorts of reasons, not least of which is because the most common modes  of invasive ventilation are different in adults and children, specifically differences in volume versus pressure-controlled flow patterns that likely affect the mechanical static,  dynamic, and resistive strain imposed on the lung. So even though lung protection is something we all think about, talk about, teach about,  and manage every day in our patients in the ICU, optimal event settings in pediatrics remains an active subject of debate. In fact, there are published data showing  a wide variety of ventilator management  across different pediatric institutions, which underscores the importance of more pediatric-specific research into lung protective ventilation strategies.  Mechanical power was first described in 2016 and really ties together all the possible causes of ventilator-induced lung injury into a single explanatory variable,  tidal volume, driving pressure, flow, respiratory rate, and PEEP. The idea is that all of this imparts energy on the very inflamed and injured lung  that the lung then has to dissipate.  So if we could find ways to limit mechanical power to the lung, that might be important. And if we could figure out what the main determinants are of mechanical power and energy  that are delivered to the lung, that might also be important.  We know from physics that work equals force required to move a distance. And with further derivation of force and distance, we see that work, or energy,  is equal to pressure times volume. Therefore, mathematically, mechanical energy is the integral of the area under the airway pressure volume curve.  And when multiplied by the respiratory rate, or the energy delivered per minute, we get mechanical power in work per unit time, or joules per minute.  So we see this pressure-volume curve illustrating the computation of power in its components. We see an area of energy attributed to a static component,  or the energy required to maintain volume, which is defined by PEEP. We see another area of energy representing a dynamic energy required to move gas into the lungs,  which is defined by driving pressure. And we see an area of energy required to overcome tissue resistance, which is defined by the PEEP pressure.  And these individual areas can be computed by simple geometry, because the PEEP-related static work is a rectangle, the driving pressure-related dynamic work is a triangle,  and the resistive work is approximated by a parallelogram. So using basic geometry, the area of a rectangle and parallelogram equals base times height, and the area of a triangle  equals one-half base times height.  We can start to see how the scary-looking equation is derived that shows the static PEEP-related work in pink, resistive work in blue, and dynamic work in red,  times the respiratory rate,  times a conversion factor.  There have been several validated simplified power equations that are more easily computable at the bedside and more applicable to pediatric patients  who receive decelerating flow of ventilation rather than constant square flow that the original power calculation assumed. So for a healthy adult subject,  you'd expect a normal mechanical power value of around 3.7 joules per minute.  It's beyond the scope of this talk to discuss all the data from adult studies, but numerous reports from the adult population have documented a clear association  with mechanical power and worse outcomes, including higher mortality and fewer ventilator-free days.  So why does this matter for us? As we all know, children are not little adults. They are fundamentally a different patient population  with less chest wall resistance to have to overcome, less baseline inflammation, and potentially less susceptibility to ventilator-induced injury at microscopic levels  that have been demonstrated in the lab. It is entirely possible for these reasons that mechanical power, just like higher tidal volume or higher driving pressure,  doesn't have an association with bad outcomes in pediatric patients.  This study published in January from the CHLA group is the largest published study evaluating mechanical power in children, 300 children from 55 PICUs.  They found an association with ventilator-free days, and they did find effect modification by age in that ventilator-free day analysis associated with children under two years old  appearing to drive this association. They did not find an association between mechanical power and mortality.  They used mediation analysis to identify any individual ventilator settings further driving this association, and were unable to find any.  I hope I've convinced you that while we all do our best to minimize ventilator-induced injury, it is actually exceedingly difficult  to use a pediatric evidence base to inform our practices.  We have various trials from adult literature, but none in pediatrics. And yet the patient population and disease itself is fundamentally different in adults versus in children.  Therefore, we should be doing a trial to find the limits of damaging ventilation in children. But we need to know what that trial is aimed at.  Tidal volume, PEEP, driving pressure, mechanical power.  Our study was a retrospective cohort, single center study that included 546 children with Berlin-defined ARDS between January, 2013 and November, 2019.  This represents the largest pediatric study to evaluate mechanical power by almost double. All patients received conventional mechanical ventilation,  and our primary outcome was mortality at 28 days. Our hypothesis was that high mechanical power is associated with higher mortality.  Our secondary outcomes included ventilator-free days at 28 days, and the association of individual components of mechanical power with mortality and ventilator-free days.  This study was IRB approved and informed consent was waived.  To be included in the study, patients needed to be admitted to the PICU, have Berlin-defined criteria for ARDS, be older than one month and less than 18 years old  at the time of intubation, and patients had to receive conventional invasive positive pressure ventilation via endotracheal tube within the first 24 hours of ARDS.  Exclusion criteria included cyanotic congenital heart disease or pulmonary vascular disease, chronic mechanical ventilation at home, or respiratory failure from heart failure  or volume overload. For every patient, we obtained age, gender, their cause of ARDS, comorbidities, severity of illness,  initial ventilator settings at ARDS onset, whether they received additional support therapies like nitric, steroids, prone positioning,  vasopressors, sedatives, or neuromuscular blockade. We also identified cause of death, generally categorized into three buckets of primarily hypoxemia,  multi-system organ failure, or neurologic failure.  All analyses were performed using Stata software. Baseline and demographic characteristics were characterized with standard descriptive summaries.  For univariate comparison between survivors and non-survivors, Wilcoxon rank sum was performed for continuous variables like age and mechanical power,  and Fisher's exact test was used for categorical variables like gender or immunocompromised status. For our main mortality model, we used Cox proportional hazards regression  and competing risk regression for ventilator-free days, controlling for the competing risk of death.  Our regression model was adjusted for confounders known to be associated with ARDS outcomes, including age, PF ratio, vaso score, organ failure, and immunocompromised status.  This is our table one, stratified by survival status. Survivors had lower vasopressor scores and were more likely to be immunocompromised or stem cell transplant recipients.  There were no differences in comorbidities between survivors and non-survivors. Survivors were more likely to have pneumonia as a cause of ARDS,  while non-survivors were more likely to have sepsis as a cause of ARDS, which certainly invites whether these patients died with their ARDS and not because of their ARDS  in potentially injurious ventilator settings. Non-survivors had higher mechanical power in univariate analysis.  For our primary outcome of mortality, we found that the hazard ratio was 1.34 and that it was significant in both adjusted and unadjusted models with wider confidence intervals  in the adjusted model.  For our secondary outcome of ventilator-free days, in the adjusted univariate model, per one sample, we found that the hazard ratio was 1.34 and in the adjusted univariate model,  per one standard deviation increase in power, we found a lower probability of extubation, an 18% lower probability of extubation, but it was attenuated to only 9%  and not significant in multivariate adjusted analysis.  We then ran a couple of sensitivity analyses. The first sensitivity analysis was to remove patients who died for neurologic reasons, the assumption being that these patients  almost certainly died because of their neurologic status rather than their lung disease and ventilator settings. And we still found a mortality effect.  We then wondered why we were seemingly powered enough to detect a mortality difference, but were unable to find the association between mechanical power and vent-free days  that other groups have found. One reason may be because we did not define power as tidal volume normalized to ideal body weight.  So it was possible that we didn't find an association between power and ventilator-free days because we had exposure misclassification  and we mismeasured mechanical power because we didn't use ideal body weight. Our group from CHOP has previously shown that normalizing tidal volume to ideal body weight  usually increases the tidal volume by one to two mLs per kilogram.  We did find in our table one that tidal volume normalized to ideal body weight increased from 7.3 mLs per kilo to 8.1 mLs per kilo. So we did a sensitivity analysis  where we redefined the tidal volume term in mechanical power equation to be normalized to ideal body weight. And we found that it slightly attenuated  our adjusted mortality hazard ratio, but it was still significant. And importantly, it now made our secondary outcome of ventilator-free days significant. So this is interesting  because from a mechanical power point of view, both versions of mechanical power, tidal volume and tidal volume normalized to ideal body weight seem associated with mortality.  But only one version of mechanical power where tidal volume is normalized to ideal body weight also seems statistically significantly to be picking up ventilator-free days,  another outcome that we care about. So maybe in pediatrics, we should be paying more attention to ideal body weight rather than to actual body weight.  We then tried to determine if the association between mechanical power mortality and ventilator-free days differed by subgroup effect modification  by age, immunocompromised status or hypoxemia severity, which are known effect modifiers in other ARDS studies. We did not find any based on non-significant interaction p-values.  We then tried to look at which ventilator components included in mechanical power were most associated with mortality and ventilator-free days in children.  And these are all adjusted models. Among the ventilator variables used in the computation of mechanical power, only PEEP was independently associated with survival  and high respiratory rate was associated with decreased ventilator-free days.  We did a final analysis to try to get at what is driving the significance of the association between mechanical power and mortality. We already said that mechanical power  is composed of static, dynamic, and resistive forces generating tissue strain, and it is unclear whether each of these forces  contributes to lung injury during mechanical ventilation. If you change the power equation and take away different parts of it, how much does your hazard ratio change?  Maybe that gets at what is driving our outcomes. Static power takes away delta P and focuses on PEEP.  Dynamic power takes away PEEP and focuses on driving pressure. And mechanical energy removes the age-dependent variable of respiratory rate. And again, these are all adjusted models  that consider confounders. And we found that all of these terms were still associated with mortality, although static strain with primarily a PEEP component  had the highest magnitude of hazard ratio and most significant P value.  In conclusion, mechanical power describes the degree to which lung damage in ventilator-induced lung injury is caused by energy transferred from the ventilator  to the respiratory system within a given timeframe. There are several ways to calculate mechanical power, assuming either constant or decelerating flow patterns.  Ours is the largest study evaluating mechanical power in pediatrics by almost double.  Higher mechanical power is associated with worse outcomes in children with ARDS, including higher mortality in adjusted models and fewer ventilator-free days in unadjusted model.  PEEP appears to be the modifiable ventilator setting most implicated with these associations. And finally, it may be worth scaling tidal volume  to ideal body weight more frequently in pediatrics.  Calculating mechanical power may be an important step towards better care of patients with pediatric ARDS in the PICU.  And finally, is mechanical power ultimately just a marker of severity of illness or is it a manipulatable marker? We acknowledge that the PEEP signal we found  could just be confounding by higher levels of PEEP being used in sicker patients. But because this is an observational study that can't prove causation,  this supports conducting a trial that evaluates different levels of PEEP.  Limitations to the study include the retrospective observational single center nature of it. Again, we cannot imply causality that lowering mechanical power will result  in better outcomes for children with ARDS.  Ventilator data was captured at only a single point in time.  Confounders were chosen based on plausibility and analysis was performed in a causal framework. Randomization will be important to break the co-linearity  between PEEP and underlying disease severity.  Even adjusting for potential confounders, it is possible that there was residual confounding.  Finally, our primary exposures were continuous, precluding the use of alternative analyses of causal inference. For example, propensity matching by power quartiles.  Ultimately, our sensitivity analyses did not change our conclusions.  This is a list of the references used in preparation for this study and presentation.  Thank you all very much for listening to this presentation.

Video Summary

In this presentation, Andrew Percy, a Pediatric Critical Care Fellow at the Children's Hospital of Philadelphia, discusses the concept of mechanical power in pediatric acute respiratory distress syndrome (ARDS). He explains that mechanical power is used as a surrogate measure of stress and strain imposed on the lung during mechanical ventilation, which can cause injury. While there have been studies on lung injury in adults, there is a lack of evidence in pediatric patients. Percy's study aimed to evaluate the association between mechanical power and outcomes in children with ARDS. The study found that higher mechanical power was associated with worse outcomes, including higher mortality and fewer ventilator-free days. The study also identified positive end-expiratory pressure (PEEP) as the ventilator setting most implicated in these associations. Percy concludes that calculating mechanical power may be an important step towards improving the care of pediatric ARDS patients.

Asset Subtitle

Pulmonary, Pediatrics, Procedures, 2022

Asset Caption

INTRODUCTION: Mechanical power (MP) transferred from the ventilator to the lungs has been proposed as a summary variable that may impact mortality in patients with acute respiratory distress syndrome (ARDS). We investigated the association between high MP and 28-day mortality, as well as the individual components that may drive this association. METHODS: We performed a secondary analysis of a prospectively enrolled cohort of pediatric ARDS (Berlin and PALICC criteria) admitted between January 2013 and December 2019, excluding subjects on non-conventional ventilation. All patients received conventional ventilation with decelerating flow. MP was calculated from variables at ARDS onset, and multivariable Cox regression was used to test for association between individual variables comprising MP, as well as MP itself, with 28-day mortality. We adjusted for age, PaCO2, initial PaO2/FIO2, vasopressor score, organ failures, and immunocompromised status. Finally, we tested whether there remained an association when specific terms were removed from the MP equation by calculating static strain (remove delta P [PIP minus PEEP]), dynamic strain (remove PEEP), and mechanical energy (remove respiratory rate). RESULTS: Five hundred forty-six children were eligible, with a median PaO2/FIO2 of 162 (IQR 110, 225) and age 5.7 years (IQR 1.8, 12.9). Higher MP was associated with increased mortality (HR 1.34 per 1 SD increase, 95% CI 1.08 to 1.65, p=0.007). When assessing the contribution of individual components, only PEEP was associated with mortality (HR 1.32, p=0.007), while tidal volume, respiratory rate, and delta P were not. Static strain (HR 1.44, p < 0.001), dynamic strain (HR 1.25, p=0.042), and mechanical energy (HR 1.29, p=0.009) were all associated with mortality. CONCLUSIONS: This is the largest reported cohort in which MP has been evaluated in pediatric ARDS. We found that higher MP is associated with mortality, and that PEEP appears to be the component most consistently driving this association. As higher PEEP is used in sicker patients, the association between MP and mortality may simply reflect a marker of illness severity rather than MP itself being causal for mortality. However, our results also support future trials conducting different levels of PEEP in children with ARDS.

Meta Tag

Content Type Presentation

Knowledge Area Pulmonary

Knowledge Area Pediatrics

Knowledge Area Procedures

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Acute Respiratory Distress Syndrome ARDS

Tag Pediatrics

Tag Mechanical Ventilation

Tag Respiratory Failure

Year 2022

Keywords

mechanical power

pediatric acute respiratory distress syndrome

lung injury

ventilator settings

pediatric ARDS patients

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