Intrathoracic Pressure Regulator Performance in the Setting of Hemorrhage and Acute Lung Injury
Authors: Morris Mackenzie C , Niziolek Grace M , Blakeman Thomas C , Stevens-Topie Sabre , Veile Rosalie , Heh Victor , Zingarelli Basilia , Rodriquez Dario , Branson Richard D , Goodman Michael D 
Published: April 2020

Abstract
Introduction: Intrathoracic pressure regulation (ITPR) can be utilized to enhance venous return and cardiac preload by inducing negative end expiratory pressure in mechanically ventilated patients. Previous preclinical studies have shown increased mean arterial pressure (MAP) and decreased intracranial pressure (ICP) with use of an ITPR device. The aim of this study was to evaluate the hemodynamic and respiratory effects of ITPR in a porcine polytrauma model of hemorrhagic shock and acute lung injury (ALI). Methods: Swine were anesthetized and underwent a combination of sham, hemorrhage, and/or lung injury. The experimental groups included: no injury with and without ITPR (ITPR, Sham), hemorrhage with and without ITPR (ITPR/Hem, Hem), and hemorrhage and ALI with and without ITPR (ITPR/Hem/ALI, Hem/ALI). The ITPR device was initiated at a setting of −3 cmH2O and incrementally decreased by 3 cmH2O after 30 minutes on each setting, with 15 minutes allowed for recovery between settings, to a nadir of −12 cmH2O. Histopathological analysis of the lungs was scored by blinded, independent reviewers. Of note, all animals were chemically paralyzed for the experiments to suppress gasping at ITPR pressures below −6 cmH2O. Results: Adequate shock was induced in the hemorrhage model, with the MAP being decreased in the Hem and ITPR/Hem group compared with Sham and ITPR/Sham, respectively, at all time points (Hem 54.2 ± 6.5 mmHg vs. 88.0 ± 13.9 mmHg, p &lt; 0.01, −12 cmH2O; ITPR/Hem 59.5 ± 14.4 mmHg vs. 86.7 ± 12.1 mmHg, p &lt; 0.01, −12 cmH2O). In addition, the PaO2/FIO2 ratio was appropriately decreased in Hem/ALI compared with Sham and Hem groups (231.6 ± 152.5 vs. 502.0 ± 24.6 (Sham) p &lt; 0.05 vs. 463.6 ± 10.2, (Hem) p &lt; 0.01, −12 cmH2O). Heart rate was consistently higher in the ITPR/Hem/ALI group compared with the Hem/ALI group (255 ± 26 bpm vs. 150.6 ± 62.3 bpm, −12 cmH2O) and higher in the ITPR/Hem group compared with Hem. Respiratory rate (adjusted to maintain pH) was also higher in the ITPR/Hem/ALI group compared with Hem/ALI at −9 and − 12 cmH2O (32.8 ± 3.0 breaths per minute (bpm) vs. 26.8 ± 3.6 bpm, −12 cmH2O) and higher in the ITPR/Hem group compared with Hem at −6, −9, and − 12 cmH2O. Lung compliance and end expiratory lung volume (EELV) were both consistently decreased in all three ITPR groups compared with their controls. Histopathologic severity of lung injury was worse in the ITPR and ALI groups compared with their respective injured controls or Sham. Conclusion: In this swine polytrauma model, we demonstrated successful establishment of hemorrhage and combined hemorrhage/ALI models. While ITPR did not demonstrate a benefit for MAP or ICP, our data demonstrate that the ITPR device induced tachycardia with associated increase in cardiac output, as well as tachypnea with decreased lung compliance, EELV, PaO2/FIO2 ratio, and worse histopathologic lung injury. Therefore, implementation of the ITPR device in the setting of polytrauma may compromise pulmonary function without significant hemodynamic improvement.