Overpowered or Underexplored

FOR RELATED ARTICLE, SEE PAGE 901

The concept of mechanical power was first introduced in 2016,¹ postulating that ventilator-induced lung injury (VILI) is mediated by the total energy transmitted to the respiratory system during each breathing cycle, rather than by individual ventilator parameters such as tidal volume or driving pressure. A summative variable combining volume, pressure, flow, and respiratory rate, mechanical power is thought to represent the structural impact on the lung parenchyma at cellular and tissue levels via potential, kinetic, and heat energy.²

Over the past decade, multiple studies have shown associations between mechanical power and higher mortality rates in ARDS populations,^3,4 post-cardiac arrest⁵ and other acute brain injury cohorts,⁶ and in patients with pneumonia,⁷ pediatric populations,⁸ and the perioperative setting.⁹

In this issue of CHEST, von Düring et al¹⁰ report associations between high mechanical power (defined as > 17 J/min) within the first 24 hours of invasive mechanical ventilation (IMV) and mortality rates during the ICU stay in patients with acute hypoxemic respiratory failure. Mechanical power was calculated using dynamic driving pressure (ΔP_dyn), defined as peak pressure-positive end-expiratory pressure. The authors’ rationale behind this choice was that ΔP_dyn is more easily measurable than static driving pressure and is thought to be applicable to different ventilation modes. Using a combination of eloquent statistical methods, the authors were not able to identify 1 consistent “safe” mechanical power threshold; therefore, they posit whether the potentially injurious effects of mechanical power exist on a continuum.

As the authors thoughtfully acknowledge, several important limitations preclude the ability to draw firm conclusions from this study—but also underscore unanswered questions about how mechanical power might be measured, interpreted, and utilized in real-life practice.¹⁰

One main challenge is how to quantify mechanical power reliably, because measurement errors may be propagated through the calculation of this summative variable. While ΔP_dyn is easily obtainable, mechanical power values can be confounded by high airway resistance, and changes in pressure delivered to the lung parenchyma are less accounted for within the simplified formula. Prior research has suggested that associations between mechanical power and mortality rates are driven by its elastic-dynamic components,⁴ and the mathematical modelling to integrate the role of positive end-expiratory pressure remains a topic of debate.¹¹

The use of 1 formula across multiple ventilator modes in a heterogeneous patient population represents a pragmatic approach; however, this generalization could lead to miscalculations and miscategorizations. Distinct mechanical power formulas have been described to account for differences in flow delivery and distribution of mechanical power during the inspiratory cycle.^1,12 Of note, 31% of patients in this study received pressure-support ventilation.¹⁰ While the associations were robust in a sensitivity analysis that excluded those patients on pressure-support ventilation, the mechanisms of how spontaneous breathing may contribute to VILI remain elusive. Therefore, a critical question in integrating mechanical power into the real world is how to account for a patient’s own breathing efforts in both spontaneous and controlled ventilator modes.

The study defined “mechanical power within 24 hours” as the first available measure during IMV.¹⁰ While an early measurement may be valuable in the detection of VILI risk, the initial phase of IMV is often very dynamic as a patient’s condition evolves, and ventilator adjustments may occur frequently over short time periods. Furthermore, a single value does not account for the cumulative mechanical power exposure or varying mechanical power trajectories over time, which are common limitations in most studies that investigate mechanical power.

If a precise cutoff of an injurious mechanical power level exists, the value of > 17 J/min, previously described in an ARDS population, may not be appropriate for all patients with acute hypoxemic respiratory failure. Prior experimental and clinical studies have suggested varying thresholds that range from 12 J/min to 22 J/min.^2,4,13,14 Data from 8 ARDSnet randomized controlled trials (RCTs) suggest that mechanical power normalized to predicted body weight or compliance was more predictive than absolute mechanical power in the subgroup with moderate-to-severe ARDS.¹⁵ Accordingly, an important question is how to determine individualized thresholds, which may be guided by disease processes and patient-specific factors. This will require better outcome measures to represent VILI than pneumothorax, which likely underrepresents the spectrum of clinically evident and occult VILI.

While the heterogeneity of the cohort may strengthen generalizability, the dearth of granularity may dilute or even skew the findings and limit their applicability in specific subpopulations, especially when investigating “safe” thresholds. For example, one-third of patients in this cohort required IMV for “altered level of consciousness,” which can encompass a wide range of metabolic and structural pathologies. Brain-lung crosstalk mediated by neuroinflammation, intracranial hypertension, excessive sympathetic drive, and central hormonal dysregulation has been shown to mediate or further exacerbate lung injury¹⁶ and therefore may render the lungs more prone to VILI.

Overall, this study¹⁰ complements a growing body of literature that suggests a relationship between mechanical power and outcomes. However, a main limitation across studies is the potential for residual confounding. Most studies to date investigated associations in observational cohorts or performed post hoc analyses of RCTs. Further, causes of death are often not specified, and withdrawal of life-sustaining treatment due to anticipated poor prognosis, which is potentially influenced by concerning ventilator parameters and disease severity, can result in a self-fulfilling prophecy. In fact, the association of mechanical power with nonpulmonary Sequential Organ Failure Assessment score, limitations in the measurement of VILI, and lacking data on cause of death in this cohort obfuscate whether high mechanical power indicates physiologic need, severity of illness, risk of VILI because of exposure to potentially injurious levels of IMV, or a combination of these elements.

Ultimately, RCTs that compare mechanical power-guided protocols to established lung-protective strategies are needed to establish causality and clinical relevance. In addition to determining feasible ways to measure mechanical power accurately and identifying mechanical power targets to guide trial design, fundamental questions about the bedside application of mechanical power remain. How can mechanical power be lowered in patients with severe lung injury while ensuring adequate gas exchange? Which components should be prioritized? How should one balance risks of sedation and neuromuscular blockade to achieve the “ideal” mechanical power? Although the concept of 1 unified mechanism for VILI is enticing and the physiologic rationale is plausible, many nuances and complexities warrant further clarification to inform implementation in clinical practice.

Funding/Support

S. W. receives funding from the National Institutes of Health (NIH NINDS U01NS124613, AWD 14238).

Financial/Nonfinancial Disclosures

None declared.