Initial correspondence from Drs. Allardet-Servent, Castanier, Signouret and Seghboyan

Dear Editor,

We read with interest the article recently published in Intensive Care Medicine by Morelli et al. [1]. We would like to introduce another potential field of interest for the use of extracorporeal carbon dioxide removal (ECCO2R) in patients presenting with both acute respiratory distress syndrome (ARDS) and acute kidney injury, namely the combination of renal and pulmonary support in a unique device. We, and others, have described the feasibility of combining ECCO2R and continuous renal replacement therapy (RRT) through the integration of a membrane oxygenator within a RRT circuit [2,3,4]. In the Pulmonary and Renal Support during ARDS (PARSA) study [4], we investigated the efficacy of combined therapy using continuous venovenous hemofiltration in 11 ARDS patients and reported an average reduction of PaCO2 of 21% at constant tidal volume (6 ml kg−1 predicted body weight). We then prolonged the combined therapy for 72 h, successfully in two-thirds of patients, in addition to a reduction of tidal volume at 4 ml kg−1. The efficient and sustain CO2 removal rate observed (83 ml min−1 with a blood flow of 410 ml min−1) prevents tidal volume reduction-associated hypercapnia. Of note, a higher CO2 removal rate was obtained when the membrane oxygenator was placed upstream of the hemofilter (Supplementary Fig. 1a), as compared to the downstream position where the blood flow decreased in proportion to the effluent rate (Supplementary Fig. 1b). Therefore, such a combination of therapies (ECCO2R + RRT) may both provide appropriate blood purification and enhance lung protective ventilation.

Although there is a strong rationale, coming mainly from experimental evidence, to conceive that ventilation with very low tidal volume (≤4 ml kg−1) would further reduce ventilator-induced lung injury, there has only been one study in ten ARDS patients, presenting an elevated plateau pressure (28–30 cmH2O) at a tidal volume of 6 ml kg−1, which reported a reduction of the pulmonary inflammatory response using such a “limited stretch” strategy [5]. Recently, driving pressure (the difference between end-inspiratory and end-expiratory pressure) has been identified as the main respiratory determinant of the in-hospital mortality of ARDS patients, in contrast with plateau pressure. Whether a strategy aiming at lowering the driving pressure (≤14 cmH2O), through the reduction of tidal volume, is further lung-protective remains to be demonstrated and will be investigated in the Enhanced Lung Protective Ventilation for ARDS Patients With PrismaLung (PROVAP) study (ClinicalTrials.gov NCT03004885).

Reply from Dr. Morelli

We thank Allardet-Servent and colleagues for their comments. In critically ill patients, lungs and kidneys very often become dysfunctional, leading to the onset of multiple organ failure which in turn contributes to poor outcome. In addition to the common causes that negatively affect organ function, such as sepsis, shock states and trauma, a specific detrimental interaction and cross-talk between ventilated lungs and kidneys play a pivotal role. Nowadays, it is clearer that mechanical ventilation may contribute to worsening of not only kidney function but also other distal organ function. Implementing extracorporeal carbon dioxide removal (ECCO2R) with continuous renal replacement therapy (CRRT) might therefore represent an effective supportive strategy that allows the reduction of tidal volume together with an adequate blood purification—a rational therapeutic option in patients suffering from combined respiratory and renal failure. In their letter, the authors nicely reviewed some preliminary findings regarding the feasibility of combining ECCO2R and CRRT. Although the rationale for this strategy in specific patient populations is compelling, such a therapeutic strategy should be considered an experimental therapy at this point in time. Due to the preliminary nature of available findings on such a technique, we decided not to discuss combinational supportive organ strategies in our review [1]. Nevertheless, we concur with Allardet-Servent and colleagues that additional, larger, and controlled studies are urgently needed to assess the impact of combined ECCO2R–CRRT systems in critically ill patients. Likewise, we agree that the assumption of lowering driving pressure through the reduction of tidal volume to further protect the lung needs to be addressed in future studies.