Pressure–Time Curve Predicts Minimally Injurious Ventilatory Strategy in an Isolated Rat Lung Model

TLDR

The study tested whether the pressure‑time (P‑t) curve during constant‑flow ventilation can identify a non‑injurious ventilatory strategy. Using an isolated, non‑perfused, lavaged rat lung model of acute injury, the authors set tidal volume and PEEP to produce straight, concave‑down, or concave‑up P‑t curves, fitted each curve to P = a t^b + c, and after 3 h assessed histology and inflammatory mediators to determine injury. The coefficient b, with a threshold of 0.90–1.10, predicted non‑injurious ventilation with 100 % sensitivity and correlated strongly (P < 0.001) with injury score, IL‑6, and MIP‑2, demonstrating high predictive power.

Abstract

Background We tested the hypothesis that the pressure-time (P-t) curve during constant flow ventilation can be used to set a noninjurious ventilatory strategy. Methods In an isolated, nonperfused, lavaged model of acute lung injury, tidal volume and positive end-expiratory pressure were set to obtain: (1) a straight P-t curve (constant compliance, minimal stress); (2) a downward concavity in the P-t curve (increasing compliance, low volume stress); and (3) an upward concavity in the P-t curve (decreasing compliance, high volume stress). The P-t curve was fitted to: P = a. tb +c, where b describes the shape of the curve, b = 1 describes a straight P-t curve, b &amp;lt; 1 describes a downward concavity, and b &amp;gt; 1 describes an upward concavity. After 3 h, lungs were analyzed for histologic evidence of pulmonary damage and lavage concentration of inflammatory mediators. Ventilator-induced lung injury occurred when injury score and cytokine concentrations in the ventilated lungs were higher than those in 10 isolated lavaged rats kept statically inflated for 3 h with an airway pressure of 4 cm H2O. Results The threshold value for coefficient b that discriminated best between lungs with and without histologic and inflammatory evidence of ventilator-induced lung injury (receiver-operating characteristic curve) ranged between 0.90-1.10. For such threshold values, the sensitivity of coefficient b to identify noninjurious ventilatory strategy was 1.00. A significant relation (P &amp;lt; 0.001) between values of coefficient b and injury score, interleukin-6, and macrophage inflammatory protein-2 was found. Conclusions The predictive power of coefficient b to predict noninjurious ventilatory strategy in a model of acute lung injury is high.