Within the past several decades, epidemiological studies have reported that the incidence of ARDS is higher in the elderly population and is associated with higher mortality. Even the outcomes of patients with ARDS have been improved over time, but the mortality rate for ARDS in elderly population still remains a high mortality rate. Mechanical ventilation plays critical role in the management for ARDS, however, elderly population showed increased susceptibility to multiple organ dysfunction, systemic inflammation and death induced by VILI[7, 10, 15]. For reducing the VILI, ECMO was applied to ensure adequate gas exchange for severe ARDS patients. But the effects of ventilation combined with ECMO therapy are unclear. The clinical studies of ARDS rarely include substantial numbers of elderly patients. Given the difficulties in randomized clinical studies, aged Beagle dogs of severe ARDS model were used in our study to explore the optimal MV settings in elderly population of ARDS.
We designed an experimental study to compare the ultra protective ventilation strategy versus protective ventilation strategies in its ability to modulate lung injury and inflammatory response. The conventional ventilation strategy and none -ARDS animals group were used as positive and negative control to confirm the results. We demonstrated that even protective ventilation strategy still induced severe lung injury and inflammatory response, which can be ameliorated by applying ultra protective ventilation.
It is reported that near-apneic ventilation can decrease lung injury in an adult pig ARDS model with ECMO. But near-apneic ventilation strategies require higher FiO2 to improve oxygenation, and patients should be sedated without spontaneous breathing, which can lead to atelectasis and inflammation. Thus, in our study, we designed a ultra protective ventilation instead of near-apneic ventilation strategy to reduce VILI of ARDS.
Pplat, ELWI, lung compliance and lung injury scores were collected in this study to evaluate the efficacy of MV strategies in ARDS model undergoing V-V ECMO. High Pplat is an independent risk factor of mortality in ARDS patients, especially those with a Pplat over 30 cmH2O means a poor prognosis. Clinical studies and animals experiments showed that ARDS mortality reduces when Pplat is decreased and this relationship appears to be linear. Current recommendation by the ARDS net for ARDS suggested a protective ventilation strategy based on limitation of Pplat to 30 cmH2O. However, recent studies have shown that, even Pplat was lower than 30 cmH2O, patients with ARDS may still be at risk of VILI and hyperinflation station. Our study showed that conventional ventilation strategy leads to a Pplat around 35 cmH2O, and even in protective ventilation strategy group, the Pplat was still very high over 25 cmH2O. We demonstrated that Pplat- only around 18 cmH2O in ultra protective ventilation group, which was significantly lower than in protective ventilation strategy group. ELWI is a parameter representing edema of lung which indicates the severity of ARDS. In this study, ELWI of the three injured groups reached climax early after 5 minutes ECMO circulation, and then reduced gradually. We demonstrated that an obvious decreasing were found in UPV groups than the other two injured groups after 12 hours of connecting to MV. In our study, lung compliance declined about 50% in response to ARDS induction in three injured groups. Even after connected to V-V ECMO and MV, lung compliance was further reduced in CV group, which indicating that the conventional ventilation strategy may cause secondary damage to lung. We discovered that lung compliance of UPV group was increased and maintained steady in the study period, which was the same as pathological results of mildest changes. It showed that in UPV group, the injury scores were significantly lower than in the other two injured groups.
In spite of different etiologies, inflammatory response is the common mechanism of ARDS, which leads to high permeability of pulmonary capillaries, alveolar/interstitial edema and effusion, inflammatory cells infiltration and hyaline membrane formation[20–22]. Plenty of studies demonstrated the relation between elevated cytokines concentrations and mortality in ARDS. It has proven that cytokine storm induces in ARDS elderly patients was more common than in young patients. The inflammatory cytokines including IL-6, IL-8 and TNF-α were analyzed in our study. We showed that UPV strategy, with lower VT, FiO2 and RR, demonstrated a significant decrease in IL-6, IL-8 and TNF-α production, which indicating that ultra-protective ventilation strategy can give full lung protection against the damage induced by mechanical ventilation and ARDS.
There are still some limitations of this study. First, the sample capacity was small, we have got only 6 individuals in different ventilation strategy groups. Second, the treatment lasted for only 24 hours due to the difficulty on transfusion of blood and colloid, anti-infection. Compared with clinical ARDS treatment for over one week, this weakened the significance of the results. Finally, more molecular biological markers could be measured to help to discover the mechanism of treatment more clearly. All these should be under the considerations of future studies.