Mechanical Power in ARDS: Hand in Hand With Gattinoni

High levels of mechanical power are associated with a higher incidence of lung damage and worse outcomes in patients with Acute Respiratory Distress Syndrome. This article explores the fundamentals of mechanical power, proper regulation of ventilatory support and the prevention of lung damage associated with mechanical ventilation.

Introduction

Acute respiratory distress syndrome (ARDS) is a condition characterised by an exacerbated pulmonary inflammatory response, resulting in severe hypoxaemia and decreased lung compliance (Bellani et al. 2016). In this context, mechanical ventilation becomes an essential tool for oxygenation and respiratory support; however, it may also contribute to ventilator-induced lung injury (VILI) (Fan et al. 2018). One of the emerging concepts in the pathophysiology of VILI is mechanical power, which integrates pressure, tidal volume, respiratory rate and inspiratory flow into a single variable to estimate the energy transferred to the lung during mechanical ventilation (Gattinoni et al. 2016). Some studies have suggested that high levels of mechanical power are associated with a higher incidence of lung damage and worse outcomes in patients with ARDS (Cressoni et al. 2016). However, debate persists as to whether mechanical power acts as a trigger for VILI or instead represents an epiphenomenon of pre-existing lung dysfunction (Silva et al. 2021).

Transcendence of Mechanical Power

Ventilatory support is an essential tool for the maintenance of respiratory function in various clinical scenarios. However, its use requires rigorous assessment to prevent ventilator-induced lung damage (Silva et al. 2019). The energy required to mobilise the lung from functional residual capacity to a level determined by the pressure-volume curve depends on both the muscle pressure generated in spontaneous breathing and the support provided by the mechanical ventilator. The latter can partially or fully assume this function, leading to an increase in airway pressure to overcome the elastic and resistive forces of the respiratory system (Gattinoni et al. 2016).

The concept of mechanical power emerges as an integrated variable that allows estimation of the energy transferred to the lung during mechanical ventilation, based on the equation of motion plus the energy equation:

P=ELrs∙∆V+Raw⋅F+PEEP

W= ∆P∙∆V

The term ELrs⋅V represents the elastic component of the energy expenditure during mechanical ventilation, while Raw⋅F corresponds to the resistive component, both of which contribute to the overall mechanical power delivered to the lungs (Gattinoni et al. 2016). Recognising the relevance of these forces, Gattinoni et al. (2016) developed a specific equation to quantify mechanical power, integrating the main determinants of ventilator-induced lung injury (pressure, volume, flow, and respiratory rate) into a single comprehensive variable.

Mechanical power=0.098∙RR∙Vt(Ppeak- ((Pplat-PEEP))/2)

These studies found that a value higher than 12 J/min is associated with an increased risk of mechanical ventilation-induced lung injury in healthy individuals and with clinical deterioration in patients with ARDS (Gattinoni et al. 2023). In addition, high mechanical power values have been associated with increased mortality and fewer ventilator-free days in critically ill patients (Table 1) (Rosas Sánchez et al. 2017).

Advantages and Disadvantages of Mechanical Power

The application of a gas volume in the respiratory system generates a complex interaction of pressures and flows, whose dynamics depend on multiple factors, including the presence or absence of active ventilation, the characteristics of the airways, the properties of the lung parenchyma and chest wall, as well as the activation of the respiratory musculature (Amado-Rodríguez et al. 2017). In this context, the monitoring of patients undergoing mechanical ventilation (MV) results from the interaction of these elements, allowing the pulmonary response to be assessed and the ventilatory strategy to be adjusted in an individualised manner (Cruz et al. 2018).

From a causal approach, the interaction of different components of lung protection is conceptualised as a mechanism that seeks to minimise mechanical stresses on the lung, reducing the risk of VILI (Cruz et al. 2018). However, the programming of invasive ventilatory support represents a clinical challenge, as the modification of one parameter may generate adverse effects on others, making it difficult to implement optimal strategies and compromising patient stability (Das et al. 2019).

Critically ill patients requiring mechanical ventilation constitute a high-risk population for the development of VILI, which has motivated the design of strategies aimed at reducing the impact of ventilation on lung tissue and preventing systemic complications (Amado-Rodríguez et al. 2017). Optimisation of mechanical ventilation in these patients can be conceptualised as an interdependent system in which airway resistance and lung compliance act as key players in shaping effective treatment (Das et al. 2019).

To understand the fundamentals of mechanical power in mechanical ventilation, it is essential to analyse the respiratory motion equation, which describes the relationship between the pressure within the system and the volume, flow and acceleration values of the delivered gas. This equation establishes that the pressure in the respiratory system at a given moment is composed of three elements: an elastic component, related to the distension of the lung parenchyma; a resistive component, which allows overcoming airway resistance and facilitates the advancement of airflow; and an interstitial component, linked to changes in lung structure due to tidal volume acceleration (Ruiz et al. 2021; Grieco et al. 2019). These principles are fundamental to the proper regulation of ventilatory support, and the prevention of lung damage associated with mechanical ventilation.

Condition for the Estimation of Mechanical Power

In volume-controlled ventilation mode, the pressure-time curve shows a pressure drop immediately after inspiratory valve closure. During the inspiratory pause, before the expiratory valve opens, the flow stops, allowing the delivered volume to be distributed homogeneously within the lung. This phenomenon occurs due to the equilibrium reached by the elastic forces of the respiratory system. The pressure reached under these static conditions is defined as plateau pressure or plateau pressure (Pplat) and reflects the elastic retraction pressure of the respiratory system (Tonetti et al. 2017). In situations where equilibrium between the patient's airway pressures has been achieved, Pplat can be used as an indirect approximation of alveolar pressure (Vasques et al. 2018).

The distensibility of the respiratory system is expressed as the ratio between the change in lung volume (ΔV) and the change in pressure (ΔP), usually in millilitres per centimetre of water (mL/cmH2O), and is estimated with the following formula:

Crs est=Vt/(Pplat-PEEP)

Crs din=Vt/(Ppeak-PEEP)

Elastance is defined as the inverse of distensibility, the ratio between the change in lung pressure (ΔP) and the change in volume (ΔV), is estimated with the following formula:

e=(Pplat-PEEP)/Vt

The distensibility changes as the conditions of both the lung parenchyma (Crs est) and the rib cage (Crs din) change. However, the calculation of distensibility according to this formula is limited to a specific state of the respiratory system.

Total positive end-expiratory pressure (PEEP) is also performed at 0 flow conditions, the end of expiration with a pause before the next cycle, so that no respiratory effort is required to avoid generating an intrinsic pressure in addition to the programmed value. Another variable that can be monitored is the resistance that opposes the flow, which is calculated as the quotient between the initial and final pressure difference of the circuit and the circulating air flow, generally in millilitres per centimetre of water (cmH₂O/L/sec), and is estimated with the following formula:

Raw=(Ppeak-Pplat)/(inspiratory flow)

Airway resistance is closely related to lung volume, as it tends to decrease as the lung is inflated and the airways expand. Under laminar flow conditions and at low velocities, airway resistance varies directly proportional to gas viscosity and airway length, while it is inversely proportional to the fourth power of airway radius (Parker et al. 1993). This principle explains why small reductions in airway calibre, such as those observed in pathological conditions (e.g. bronchospasm or mucosal oedema), can generate significant increases in airflow resistance (McGuiness et al. 2020; Curley et al. 2016).

Mechanical Ventilation-Induced Lung Injury

Lung injuries associated with mechanical ventilation fall under the term VILI. In 1993, four main mechanisms of lung injury were postulated: barotrauma, volutrauma, atelectrauma and biotrauma (Serpa-Neto et al. 2016; Marini and Gattitoni 2016; Cressoni et al. 2016).

Mechanisms of lung injury induced by mechanical ventilation

Barotrauma: refers to lung injury caused by stress high enough to rupture the lung parenchymal structure. This occurs due to excessive airway pressure, generating macroscopic injuries secondary to lung rupture (Gattinoni et al. 2016; Gattinoni et al. 2017; Gattinoni et al. 2012).

Volutrauma: This is related to the administration of low end-expiratory volumes, resulting in lung damage due to repetitive cycles of opening and closing of the distal airways and alveolar units (Gattinoni et al. 2012).

Atelectrauma: Occurs as a consequence of repetitive alveolar collapse and reopening during mechanical ventilation. This phenomenon generates stress on the extracellular matrix, as well as on epithelial and endothelial cells (Gattinoni et al. 2012; Costa et al. 2021).

Biotrauma: Biotrauma is defined as the process in which biophysical forces alter lung cell physiology, increasing levels of inflammatory mediators and promoting tissue repair and remodelling processes (Costa et al. 2021).

During mechanical ventilation in patients with severe lung injury, alveolar collapse induces deformities in adjacent alveoli across the interalveolar septum, resulting in non-uniform insufflation and lung heterogeneity. To mitigate this effect, it has been suggested to reduce lung stress by using high PEEP and limiting low tidal volumes, which improves transpulmonary pressure (Costa et al. 2021). Monitoring transpulmonary pressure presents difficulties, so the use of lung distending pressure (ΔP) as a surrogate parameter has been proposed. However, although this factor is key in predicting mortality, it has limitations in certain patients (Figure 1) (Huhle et al. 2018).

Mechanical Power: Cause or Consequence?

The concept of protective ventilation has evolved, with Gattinoni et al. (2016) arguing that VILI is nothing more than excess mechanical power applied to a heterogeneous lung surface. This phenomenon has been termed ergotrauma, which has been quantified using various algebraic and arithmetic formulae (Romitti et al. 2022; Gómez et al. 2018).

Recent studies have incorporated additional variables into the analysis of mechanical power without significant impact on mortality reduction. These findings support the hypothesis that cyclic loading imposed on the lungs, due to oscillating mechanical stresses, is more detrimental than static loading. This phenomenon is reflected in the association between distending pressure and respiratory rate, both of which have been associated with an increased risk of adverse outcomes (Vasques et al. 2018).

The concept of mechanical power was formalised with the following objectives (Costa et al. 2021):

1. To quantify the contribution of respiratory rate and PEEP to the total energy delivered by the ventilator.
2. To integrate these variables into a single physical measure, allowing a relationship to be established between their value and the risk of VILI.

The study by Serpa-Neto et al. (2016) identified an association between mechanical power and mortality. In prognostic terms, this relationship has been compared with individual variables and, more recently, with a combination of distension pressure and respiratory rate, expressed as 4 x ΔP + FR, which reflects the relative impact of these variables on the probability of death (Vasques et al. 2018).

A mechanical power level within a standardised range allows adequate oxygenation and carbon dioxide removal to be maintained within safe limits. In experimental studies with animal models, an upper safety limit of 12 J/min and a lower limit of 4-7 J/min have been established (Cressoni et al. 2014). However, these values are averages and, in practice, the distribution of mechanical power throughout the respiratory cycle could play an equally important role.

Furthermore, not all components of mechanical power have the same impact. For example, doubling tidal volume quadruples mechanical power; doubling respiratory rate increases it by 1.4 times; and doubling PEEP doubles it (Serpa-Neto et al. 2016). However, the question remains as to the optimal way to match mechanical power to lung size. In this context, the normalisation of mechanical power through its relation to carbon dioxide consumption (VCO₂) is investigated, with the aim of developing a more personalised strategy for critically ill patients (Cressoni et al. 2014).

Methodology

A systematic search of publications in electronic databases such as PubMed, ScienceDirect, Scopus and Google Scholar was carried out, prioritising articles published in the last five years. However, studies from previous years were also included as long as they were statistically significant. Clinical trials with protocols registered in recognised platforms such as ClinicalTrials.gov and Controlled-Trials.com, as well as references from previously identified articles, were selected at the discretion of the researchers.

Data-Driven Clinical Outcomes

In patients undergoing prolonged invasive mechanical ventilation (7 days), a mechanical power equal to or greater than 22.4 J/min has been associated with a significantly increased risk of mortality, with an RR of 5.89. Furthermore, a logistic regression analysis determined that mechanical power at day 3 of ventilation has a discriminative ability to predict mortality, with an area under the curve (AUC) of 0.66 (Azevedo et al. 2014; Serpa Neto et al. 2012). Similarly, Marini and Gattinoni (2016) evaluated an alternative equation without including peak pressure, also demonstrating a predictive ability for mortality with an RR of 1.65 (Table 2) (Figure 2) (Gattinoni et al. 2016; Marini et al 2016; Amato et al. 2015).

Discussion

Over the past 50 years, significant progress has been made in understanding the pathophysiology of ARDS and its complex interaction with mechanical ventilation. This progress has clarified the complications associated with this therapeutic strategy, which have been grouped under the term VILI, a concept introduced in 1993 (Vasques et al. 2018).

Despite decades of research, the exact pathogenic pathways of VILI have not been fully elucidated. Furthermore, optimal strategies to prevent this damage in patients with moderate to severe ARDS have not been definitively established (Amato et al. 2015; Gattinoni et al. 2016; Slutsky and Ranieri 2013). Currently, the term VILI is used to describe two similar but distinct concepts: ventilator-induced lung injury, which includes damage occurring even during spontaneous ventilation under certain conditions (e.g. in ARDS), and ventilator-induced lung injury, which emphasises the importance of ventilatory parameters in preventing damage (Pelosi et al. 2018). Despite the application of optimised ventilatory strategies, VILI still occurs in patients with ARDS. However, in clinical practice, quantifying mortality directly attributable to mechanical ventilation is challenging, given that this treatment is used in already injured lungs (Bellani et al. 2016).

ARDS and VILI are intrinsically related to mechanical ventilation. Once established, both phenomena converge into a complex and unique form of lung damage, in which their relative contribution is no longer distinguishable (Vasques et al. 2018). Since it is not possible to differentiate with certainty the mortality attributable to each entity, the most reasonable strategy is to minimise the risks associated with mechanical ventilation. Furthermore, the concept of VILI may be limited as it does not consider other adverse effects of ventilation, such as haemodynamic alterations induced by high volumes and intrathoracic pressures, which may compromise survival regardless of pulmonary status (Marini and Gattinoni 2016).

Mechanical ventilation is a complex system composed of several clinician-adjustable parameters to optimise gas exchange while minimising the risk of lung damage. However, given its complexity, it is unlikely that a single parameter can accurately predict ventilatory safety in clinical practice. In this context, the integration of different ventilatory determinants, such as PEEP, plateau pressure, distending pressure, tidal volume and respiratory rate, has been proposed in order to optimise the ventilatory strategy in each patient. However, attempts to identify a magic number that accurately delineates safe from harmful ventilation have been unsuccessful (Beitler et al. 2019).

From a conceptual perspective, Vasques et al. (2018) represented mechanical ventilation using an irregular geometric model with six main components: tidal volume, respiratory rate, PEEP, distending pressure, resistance, and flow. In this model, each component has a different relative weight in determining lung damage. Although each parameter is essential to define the structure, none is sufficient on its own to describe the entire phenomenon. In this sense, combining the different components into a comprehensive variable could provide a more comprehensive view of the impact of mechanical ventilation on lung injury, reinforcing the concept of mechanical power as a key determinant in ventilatory risk stratification (Figure 3) (Gattinoni et al. 2020).

In the context of extracorporeal membrane oxygenation (ECMO) support, Umer et al. (2019) analysed 13,939 patients and suggested that higher ventilatory intensity, as reflected by driving pressure and mechanical power, is associated with worse clinical outcomes, even in short periods. These findings support the hypothesis that early implementation of extracorporeal support, such as ECMO or ECCO₂R, could improve the prognosis in patients with severe ARDS. However, further studies are still needed to determine the relative benefit compared to patients without ECMO, given that current strategies are based on values ​​documented in various population-based cohorts (Combes et al. 2018).

Conclusion

Mechanical power is emerging as the final word in understanding VILI, as it offers a more comprehensive view of the complex interaction between the lung and mechanical ventilation. Its use should be encouraged as a key tool for lung protection. Available evidence indicates an increased risk of mortality in patients with mechanical power above 12 J/min; however, a clearly tolerable threshold has not yet been determined. Further research in different populations undergoing invasive ventilatory support is essential to refine its clinical application and improve outcomes in critically ill patients.

Acknowledgements

We are deeply grateful to Dr Luciano Gattinoni, whose brilliance and dedication transformed the understanding of mechanical ventilation and pulmonary pathophysiology in intensive care. His efforts transcend generations for all of us who had the privilege of learning from his work. His legacy will live on in every protected breath.

Conflict of Interest

None.