Unstable Inflation Causing Injury. Insight from Prone Position and Paired Computed Tomography Scans

Abstract

Rationale: It remains unclear how prone positioning improves survival in acute respiratory distress syndrome. Using serial computed tomography (CT), we previously reported that "unstable" inflation (i.e., partial aeration with large tidal density swings, indicating increased local strain) is associated with injury progression.

Objectives: We prospectively tested whether prone position contains the early propagation of experimental lung injury by stabilizing inflation.

Methods: Injury was induced by tracheal hydrochloric acid in rats; after randomization to supine or prone position, injurious ventilation was commenced using high tidal volume and low positive end-expiratory pressure. Paired end-inspiratory (EI) and end-expiratory (EE) CT scans were acquired at baseline and hourly up to 3 hours. Each sequential pair (EI, EE) of CT images was superimposed in parametric response maps to analyze inflation. Unstable inflation was then measured in each voxel in both dependent and nondependent lung. In addition, five pigs were imaged (EI and EE) prone versus supine, before and (1 hour) after hydrochloric acid aspiration.

Measurements and main results: In rats, prone position limited lung injury propagation and increased survival (11/12 vs. 7/12 supine; P = 0.01). EI-EE densities, respiratory mechanics, and blood gases deteriorated more in supine versus prone rats. At baseline, more voxels with unstable inflation occurred in dependent versus nondependent regions when supine (41 ± 6% vs. 18 ± 7%; P < 0.01) but not when prone. In supine pigs, unstable inflation predominated in dorsal regions and was attenuated by prone positioning.

Conclusions: Prone position limits the radiologic progression of early lung injury. Minimizing unstable inflation in this setting may alleviate the burden of acute respiratory distress syndrome.

Keywords: acute respiratory distress syndrome; computed tomography; parametric response mapping; prone position ventilation; ventilator-associated lung injury.

Figure 1.

Experimental timeline in rats ventilated in supine versus prone position after hydrochloric acid aspiration. Identical ventilator settings were used in both groups. In the prone group, additional inspiratory and expiratory computed tomography scans were acquired at baseline (after hydrochloric acid) in the supine position to assess the acute effects of prone ventilation on inflation distribution and to compare injury distribution with supine ventilation group. CT = computed tomography; EE = end-expiration; EI = end-inspiration; HCl = hydrochloric acid; PEEP = positive end-expiratory pressure; TV = tidal volume.

Figure 2.

Group statistics (mean and SD) of (A) respiratory system compliance, (B) total lung volumes, and (C) lung mass normalized to baseline. All measurements were obtained at baseline (after hydrochloric acid) and after 1 and 2 hours of ventilation. ^†P < 0.05 between cohorts; ^§P < 0.05 versus baseline in the same group. EE = end-expiration; EI = end-inspiration.

Figure 3.

Radiologic injury propagation in four representative rats ventilated in prone versus supine position (two rats in each group) and imaged at end-inspiration. Baseline (after hydrochloric acid) supine images are also shown for the two prone rats (#3 and #4). In all rats, primary injury was initially localized in the dorsal lung regions. In the rats ventilated supine (#1 and #2), injury rapidly spread over the entire lung. In the prone rats, position change improved aeration in the dorsal lung regions (black arrows) and subsequent injury propagation was more contained. The blue triangles indicate body position (up-pointing, supine; down-pointing, prone).

Figure 4.

Whole-lung parametric response maps obtained at baseline after hydrochloric acid aspiration and hourly until the end of the experiment in the two experimental cohorts. Each map shows a cumulative voxel distribution for each condition, obtained by incorporating all rats in each group and averaging the distributions. The blue triangles indicate body position (up-pointing, supine; down-pointing, prone). In the supine rats, maps evolved with increased representation of voxels with nonreversible high-density (square), indicating edema and/or nonreversible atelectasis (severe injury). In this group, voxels with complete expiratory loss of gas content and inspiratory reaeration (indicating reversible atelectasis) appeared only after 1 and 2 hours of ventilation (arrow). In the prone rats, the voxel distributions were more stable over time. HU = Hounsfield units.

Figure 5.

Cumulative parametric response maps of end-inspiration/end-expiration voxels partitioned in nondependent, mid-level, and dependent regions of the lungs (indicated by the solid blue color in the triangle) in the prone and supine position (indicated by the tip of the triangle). In the supine position at baseline, the centroid of the voxel distribution shifted toward higher density following the gravitational gradient. Over time, changes in the voxel distributions were more evident in the dependent lung regions than in the nondependent ones. In the prone position, the centroid and the voxel distribution changed minimally in the three regions at baseline (minimal deviation from white vertical reference line); evolution in the dorsal lung regions was less than in the supine rats. The area including voxels with unstable inflation is highlighted (green border) in the dorsal maps. HU = Hounsfield units.

Figure 6.

(A) Unstable inflation and severely injured voxels are shown (as a percent of total) in the nondependent, mid-level, and dependent lung regions of the baseline images obtained in supine and prone rats. (B) Correlation between change in compliance (between baseline and the end of the experiment) and baseline percent fraction of unstable inflation voxels in the dependent lung regions. Solid triangles indicate rats that died before 2 hours of ventilation. ^†P < 0.05 between cohorts.

Figure 7.

Cumulative parametric response maps in five pigs imaged before and 1 hour after HCl aspiration. Pigs were ventilated in the prone versus supine position with tidal volume 8 ml/kg and PEEP 5 and 10 cm H₂O. Similar to the rats, we observed a gravitational gradient of inflation distribution when the animals were supine, with more representation of unstable inflation voxels in dependent lung after injury. This maldistribution improved at higher PEEP, but it persisted in the supine position. Prone positioning caused a more homogeneous voxel distribution at both PEEP levels. The triangles follow the same format as in Figure 5. HCl = hydrochloric acid; HU = Hounsfield units; PEEP = positive end-expiratory pressure.