Use of a novel "Split" ventilation system in bench and porcine modeling of acute respiratory distress syndrome

Abstract

Split ventilation (using a single ventilator to ventilate multiple patients) is technically feasible. However, connecting two patients with acute respiratory distress syndrome (ARDS) and differing lung mechanics to a single ventilator is concerning. This study aimed to: (1) determine functionality of a split ventilation system in benchtop tests, (2) determine whether standard ventilation would be superior to split ventilation in a porcine model of ARDS and (3) assess usability of a split ventilation system with minimal specific training. The functionality of a split ventilation system was assessed using test lungs. The usability of the system was assessed in simulated clinical scenarios. The feasibility of the system to provide modified lung protective ventilation was assessed in a porcine model of ARDS (n = 30). In bench testing a split ventilation system independently ventilated two test lungs under conditions of varying compliance and resistance. In usability tests, a high proportion of naïve operators could assemble and use the system. In the porcine model, modified lung protective ventilation was feasible with split ventilation and produced similar respiratory mechanics, gas exchange and biomarkers of lung injury when compared to standard ventilation. Split ventilation can provide some elements of lung protective ventilation and is feasible in bench testing and an in vivo model of ARDS.

Keywords: acute lung injury; acute respiratory distress syndrome; lung protective ventilation; split ventilation.

FIGURE 1

Design of the Combi‐Ventilate “Split” ventilation system (a) Schematic of Combi‐Ventilate circuit setup. (b) Circuit diagram of Combi‐Ventilate system. (c) Photograph of Combi‐Ventilate system connected to a Servo‐I ventilator (Maquet, Germany) and two test lungs.

FIGURE 2

Volume and pressure waveforms of two test lungs undergoing “Split” ventilation. (a) The effect of a decrease in compliance in test lung B on gas flow and respiratory mechanics in test lungs A and B. Marker A1 represents the point that compliance decreased in test lung B. As expected, tidal volumes decrease in test lung B but no significant change in tidal volumes is seen in test lung A. Marker A2 is the point at which the tidal volume retargeting algorithm is initialized by the user. Marker A3 is the point at which original tidal volume is restored. (b) The effect of an increase in compliance in test lung B on gas flow and respiratory mechanics in both test lungs. Marker B1 represents the point at which compliance increases in test lung B, with a corresponding reduction in airway pressure and increase in tidal volumes in test lung B. Test lung A is not significantly affected by this. Marker B2 is the point at which the tidal volume retargeting algorithm is initialized by the user. Marker B3 is the point that the original volume is restored to test lung B. (c) The effect of an increase in resistance in test lung B on gas flow and respiratory mechanics in both test lungs. Resistance in test lung B increases at marker C1, with corresponding increased airway pressure and decreased tidal volume in that test lung but without any significant changes in test lung A. Marker C2 is the point at which the tidal volume retargeting algorithm is initialized by the user. Marker C3 is the point that the original tidal volume is restored. (d) The effect of a disconnection in test lung B. Test lung B is disconnected at the time point represented by marker D1. There is no significant change in gas flow or respiratory mechanics in test lung A and original conditions are restored upon reconnection of test lung B (Marker D2).

FIGURE 3

Respiratory mechanics of injured and uninjured animals undergoing “Split”(Combi‐Ventilate) or “Standard” ventilation. Panel (a) shows tidal volume (ml/kg) over time. There were no significant differences between groups receiving “split” compared to standard ventilation (p = 0.289). Panel (b) displays compliance measurements over time in all groups. Post‐injury, injured animals had reduced levels of compliance compared to uninjured animals (p < 0.001). Panel (c) shows driving pressure over time. Post‐injury, driving pressures were higher in injured vs uninjured animals (p < 0.001). Panel (d) shows plateau pressures measured over time. Plateau pressures were higher in injured animals versus uninjured (p < 0.001). Panel (e) demonstrates positive end‐expiratory pressure (PEEP) in all groups over time. PEEP was higher in shared ventilated animals in both uninjured and injured groups compared to those undergoing standard ventilation (p = 0.012). For panels (a–c), there was no significant difference between animals who received “split” ventilation compared to standard ventilation. For panel (d), there were no significant differences between standard and split ventilated animals after 30 min. For panel (e) only, there were significant differences between shared and standard ventilation in uninjured animals at every time point (all adjusted p < 0.05). Data are presented as box and whisker plots. The box indicates the interquartile range and contains a line at the median value. The whiskers denote the range. Differences in treatments were determined using a two‐way repeated measures ANOVA. Pairwise comparisons between ventilation types were performed using a t‐test and p‐values were adjusted using the Benjamini–Hochberg method. SVU = Single (“Standard”) Ventilator Uninjured (n = 5); SVI = single (“Standard”) ventilator injured (n = 5); CVU = combi‐ventilate(“Split”) uninjured (n = 10); CVI = combi‐ventilate (“Split”) injured (n = 10).

FIGURE 4

Measurements of gas exchange in “Split”(Combi‐Ventilate) and “Standard” ventilation groups of injured and uninjured animals. Panel (a) demonstrates PaO₂/FiO₂ (P:F) ratio measurements in all groups over time. Post‐injury, animals in both the “split” and standard ventilation injured groups had lower P:F ratios compared to uninjured animals (p < 0.001). Panel (b) displays PaCO₂ levels in all groups over time. Higher PaCO₂ levels were recorded in injured animals compared to uninjured animals (p = 0.014). Panel (c) demonstrates pH measurements in all groups over time. Uninjured animals had a higher pH compared to injured animals (p = 0.005) and there was no significant difference between “split” or standard ventilation animals. For panels (a–c), there was no significant difference between animals who received “split” ventilation compared to standard ventilation. Data are presented as box and whisker plots. The box indicates the interquartile range and contains a line at the median value. The whiskers denote the range. Differences in treatments were determined using a two‐way repeated measures ANOVA. Pairwise comparisons between ventilation types were performed using a t‐test and p‐values were adjusted using the Benjamini‐Hochberg method. SVU = Single (“Standard”) Ventilator Uninjured (n = 5). SVI = Single (“Standard”) Ventilator Injured (n = 5); CVU = Combi‐Ventilate (“Split”) Uninjured (n = 10); CVI = Combi‐Ventilate (“Split”) Injured (n = 10).

FIGURE 5

Immunological markers of lung injury. Panel (a) demonstrates BALF protein concentrations in both “split” ventilation and standard ventilation groups of injured and uninjured animals. BALF protein levels were low in all groups at T0 (pre‐injury). Significant increases in BALF protein from baseline were observed in both “split” and standard ventilation groups of injured animals at T1 and T2 (p = 0.001). There was no significant difference between “split” and standard ventilation groups. Panel (b) displays bronchoalveolar lavage fluid (BALF) levels of interleukin 6 (IL‐6) in both “split” ventilated and conventionally ventilated injured and uninjured animals. IL‐6 values were low in all groups at T0 (pre‐injury). Levels remain low immediately after injury at T1 in all groups. At T2, following 6 h of ventilation, significant increases in IL‐6 levels were noted in both “split” ventilated injured animals and the standard ventilation group of injured animals compared to uninjured control groups (p = 0.006). There was no significant difference between animals who received “split” ventilation and standard ventilation in both the uninjured and injured groups at T2. Panel (c) displays bronchoalveolar lavage fluid (BALF) levels of tumor necrosis factor‐alpha (TNFα) in both the “split” ventilated and standard ventilation groups of injured and uninjured animals. There was no significant difference in BALF TNFα levels between animals who received “split” and standard ventilation in both the uninjured and injured groups at any timepoint. Panel (d) displays bronchoalveolar lavage fluid (BALF) levels of interleukin 10 (IL‐10) in both “split” and standard ventilation groups of injured and uninjured animals. There was no significant difference in BALF IL‐10 levels between animals who received “split” and standard ventilation in both the uninjured and injured groups at any timepoint. SVU = Single (“Standard”) Ventilator Uninjured (n = 5); SVI = Single (“Standard”) Ventilator Injured (n = 5); CVU = Combi‐Ventilate (“Split”) Uninjured (n = 10); CVI = Combi‐Ventilate (“Split”) Injured (n = 10).