Effect of Different Measurements of End-inspiratory Airway Pressure on Driving Pressure and Mechanical Power in Mechanically Ventilated Patients: the P1-P2 Decay Study

Introduction

Mechanical ventilation is necessary to ensure survival in critically ill patients but may be associated with ventilator-induced lung injury (VILI). Several respiratory variables have been employed to estimate the risk of VILI:

• In patients with the acute respiratory distress syndrome (ARDS), the prevention of VILI by limiting ventilatory pressures and volumes (i.e., tidal volumes of 4-8 mL per kilogram of ideal body weight and plateau pressure [Pplat], i.e., the pressure measured in the respiratory system during an end-inspiration pause of 0.5 second in the absence of flow and correlated to the end-inspiratory alveolar damage, less than 30 cmH2O) has been shown to improve patient survival. These ventilation settings are surrogates, yet not ideal predictors, of the risk of volutrauma and barotrauma, respectively.
• More recently, an important role in the pathogenesis of VILI has been attributed to the difference between Pplat and total positive end-expiratory pressure (PEEP), the latter measured after an end-expiratory pause. This difference, known as driving pressure (ΔP), represents the change in pressure above PEEP required to obtain the tidal volume in a patient without spontaneous inspiratory efforts and aggregate information about volutrauma, barotrauma, and atelectrauma in a single variable that is easily measurable at the bedside. The increase in ΔP has been associated with worse outcomes in patients with and without ARDS. Some observational studies have identified the ΔP value of 15 cmH2O as the threshold beyond which the risk of mortality in patients with ARDS increases significantly, but others have shown that a safety threshold value for ΔP cannot be identified, thus suggesting that the lower the ΔP, the lower the risk of mortality.
• Some studies suggest that inspiratory flow and strain rate may contribute to VILI in experimental animals and patients with moderate-to-severe ARDS. Therefore, taking into account inspiratory flow may give more insight into the risk of VILI in mechanically ventilated patients. Mechanical power (MP) is the total energy transferred from the ventilator to the lungs during inspiration and includes variables such as inspiratory flow and respiratory rate. MP has been shown to predict mortality in patients with and without ARDS.
• During ventilation, the lung has a viscoelastic mechanical behavior, dissipating energy both during inspiration and during expiration. This dissipation of energy can contribute to VILI through two mechanisms: stress relaxation, i.e., the release of the parenchymal tension accumulated during inspiration, and pendelluft, i.e., the redistribution of the volume of ventilation to the alveoli with a longer time constant.

In patients with ARDS, the lung parenchyma is heterogeneous because of the coexistence of aerated alveolar units and other regions that are filled with edema or collapsed due to the superimposed pressure. Therefore, both the alveolar units with shorter time constants and those with longer time constants are at risk of VILI: the former are affected by higher transpulmonary pressures, while the latter are exposed to pendelluft. Even lungs of patients without ARDS may be heterogeneous and thus predisposed to VILI through these mechanisms, e.g., because of alveolar atelectasis or consolidation and bronchiolar obstruction. Some imaging techniques available for clinical use may help assessing the degree of lung parenchymal heterogeneity. Electrical impedance tomography (EIT) is a non-invasive bedside technique that allows assessing the distribution of lung ventilation and perfusion by recording the impedance variation to small electrical currents delivered by an electrode belt wrapped around the patient's chest. This method has been shown to visualize and measure pendelluft during controlled mechanical ventilation. The EIT variables used to assess lung heterogeneity include the center of ventilation, i.e., the variation in the distribution of ventilation according to a ventro-dorsal gradient, the global inhomogeneity index, an index that estimates the heterogeneity of ventilation, and the regional ventilation delay, indicating the delay in ventilation compared to global ventilation due to atelectrauma or differences in the time constant of different lung areas.

Stress relaxation and pendelluft can be estimated at the bedside by applying an end-inspiratory pause. During this maneuver, the airway pressure curve exhibits two subsequent phases of decrease. First, a rapid pressure drop occurs, ranging from peak airway pressure to the pressure corresponding to zero flow (called pressure P1), which reflects the dissipation of pressure in the conduction airways. Then, a slow decrease in airway pressure follows, which goes from P1 to the final pressure at the end of the pause (called plateau pressure P2). The difference between P1 and P2 (P1-P2 decay) depends on stress relaxation and pendelluft and can be used as index of the time constant inequalities and viscoelastic tissue properties of the respiratory system.