Influence of respiratory rate and end-expiratory pressure variation on cyclic alveolar recruitment in an experimental lung injury model

Abstract

Introduction: Cyclic alveolar recruitment/derecruitment (R/D) is an important mechanism of ventilator-associated lung injury. In experimental models this process can be measured with high temporal resolution by detection of respiratory-dependent oscillations of the paO2 (ΔpaO2). A previous study showed that end-expiratory collapse can be prevented by an increased respiratory rate in saline-lavaged rabbits. The current study compares the effects of increased positive end-expiratory pressure (PEEP) versus an individually titrated respiratory rate (RRind) on intra-tidal amplitude of Δ paO2 and on average paO2 in saline-lavaged pigs.

Methods: Acute lung injury was induced by bronchoalveolar lavage in 16 anaesthetized pigs. R/D was induced and measured by a fast-responding intra-aortic probe measuring paO2. Ventilatory interventions (RRind (n=8) versus extrinsic PEEP (n=8)) were applied for 30 minutes to reduce Δ paO2. Haemodynamics, spirometry and Δ paO2 were monitored and the Ventilation/Perfusion distributions were assessed by multiple inert gas elimination. The main endpoints average and Δ paO2 following the interventions were analysed by Mann-Whitney-U-Test and Bonferroni's correction. The secondary parameters were tested in an explorative manner.

Results: Both interventions reduced Δ paO2. In the RRind group, ΔpaO2 was significantly smaller (P<0.001). The average paO2 continuously decreased following RRind and was significantly higher in the PEEP group (P<0.001). A sustained difference of the ventilation/perfusion distribution and shunt fractions confirms these findings. The RRind application required less vasopressor administration.

Conclusions: Different recruitment kinetics were found compared to previous small animal models and these differences were primarily determined by kinetics of end-expiratory collapse. In this porcine model, respiratory rate and increased PEEP were both effective in reducing the amplitude of paO2 oscillations. In contrast to a recent study in a small animal model, however, increased respiratory rate did not maintain end-expiratory recruitment and ultimately resulted in reduced average paO2 and increased shunt fraction.

Figure 1

Real-time recording of paO₂ oscillations before and after intervention. Exemplary real-time data (time resolution: 10 Hz) of RR_ind (upper graphs) and PEEP (lower graphs) intervention following amplitude-stable paO₂ oscillations representing cyclic R/D. A steady-state between recruitment and derecruitment is hardly achieved before the interventions. Correlation to airway pressure (p_aw) and airflow demonstrates the respiratory-dependent character of Δ paO₂.

Figure 2

Time chart of the Δ paO₂. Δ paO₂ (mmHg) after induction (R/D I), within 30 minutes of intervention and after re-induction (R/D II): no respiratory-dependent Δ paO₂ was founded before provocation. A significantly higher Δ paO₂ persists following PEEP intervention (p_adjusted < 0.001 after Bonferroni correction). In four animals of the RR_ind group no Δ paO₂ with an amplitude ≥ 50 mmHg was inducible in R/D II due to fixed atelectasis.

Figure 3

Time chart of the average paO₂. Average paO₂ (mmHg) after induction (R/D I), within 30 minutes of intervention and after re-induction (R/D II): a significantly decreased oxygenation develops following RR_ind intervention while PEEP induces a stable lung recruitment (p_adjusted < 0.001 after Bonferroni correction).

Figure 4

Ventilation/Perfusion distribution after PEEP or RR_ind intervention. MMIMS-MIGET derived $\stackrel{\cdot }{\mathsf{\text{V}}}/\stackrel{\cdot }{\mathsf{\text{Q}}}$ after 30 minutes of intervention: maintained lung recruitment in the PEEP group and impaired pulmonary function in the RR_ind group. Intergroup differences: shunt, low and normal $\stackrel{\cdot }{\mathsf{\text{V}}}/\stackrel{\cdot }{\mathsf{\text{Q}}}$ each P ≤ 0.001, high $\stackrel{\cdot }{\mathsf{\text{V}}}/\stackrel{\cdot }{\mathsf{\text{Q}}}$P = 0.012 (Mann-Whitney-U-Tests).