A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury

Abstract

Background: Biologically variable ventilation (return of physiological variability in rate and tidal volume using a computer-controller) was compared to control mode ventilation with and without a recruitment manoeuvre - 40 cm H2O for 40 sec performed hourly; in a porcine oleic acid acute lung injury model.

Methods: We compared gas exchange, respiratory mechanics, and measured bronchoalveolar fluid for inflammatory cytokines, cell counts and surfactant function. Lung injury was scored by light microscopy. Pigs received mechanical ventilation (FIO2 = 0.3; PEEP 5 cm H2O) in control mode until PaO2 decreased to 60 mm Hg with oleic acid infusion (PaO2/FIO2 <200 mm Hg). Additional PEEP to 10 cm H2O was added after injury. Animals were randomized to one of the 3 modes of ventilation and followed for 5 hr after injury.

Results: PaO2 and respiratory system compliance was significantly greater with biologically variable ventilation compared to the other 2 groups. Mean and mean peak airway pressures were also lower. There were no differences in cell counts in bronchoalveolar fluid by flow cytometry, or interleukin-8 and -10 levels between groups. Lung injury scoring revealed no difference between groups in the regions examined. No differences in surfactant function were seen between groups by capillary surfactometry.

Conclusions: In this porcine model of acute lung injury, various indices to measure injury or inflammation did not differ between the 3 approaches to ventilation. However, when using a low tidal volume strategy with moderate levels of PEEP, sustained improvements in arterial oxygen tension and respiratory system compliance were only seen with BVV when compared to CMV or CMV with a recruitment manoeuvre.

Figure 1

1a and b – Arterial Oxygenation and Respiratory System Compliance. Arterial oxygen tension (PaO₂) over time for the 3 groups (BVV in red; CMV in blue and CMV-RM in green) (a). The group × time interaction is p = 0.0001. No difference is seen between groups at baseline and following oleic acid infusion. By 2 hr the PaO₂ is greater with BVV (+). There is no difference between CMV and CMV-RM. Respiratory system compliance over time for the 3 groups (b). The group × time interaction is p = 0.089. Least squares means tests revealed BVV had significantly greater compliance after 2 hr (+). There was no difference between CMV and CMV-RM.

Figure 2

Capillary Surfactometry. Box and whisker plots for capillary surfactometry results from both raw (blue) and chloroform/methanol extracted (red) BAL fluid and patency time (%) over 2 min – log scale. In most circumstances the raw BAL fluid has minimal surface activity – low capillary patency. The one animal with a high raw value was from the BVV group. This patency markedly improved with extraction suggesting reactivation of surfactant with removal of BAL oedema fluid, proteins, including cytokines and cellular debris. In 4 animals there was essentially no change in function with extraction. There were 2 animals in the CMV group, and one each in the BVV and CMV-RM in this population. No statistically different behaviour in surfactant function was seen between groups, either for raw or extracted surfactant function.

Figure 3

Human Respiratory Rate Variability File. Human breathing variability file used for the study. This is the raw data from a spontaneously breathing healthy female volunteer. The mean rate was 13.4 ± 2.0 breaths/min (shown as the red line). There are 1587 breaths in this file. With BVV, the ventilator is configured as a volume divider at a fixed minute ventilation so that respiratory rate × tidal volume product is constant. Thus the breath-by-breath volume related to instantaneous respiratory rate obtained from sequentially reading the above file in any given experiment is obtained from the minute ventilation/[(instantaneous breath rate/13.4) × chosen mean rate]. Analysis reveals that these data have fractal characteristics.