With this retrospective study we could demonstrate that RESP and Preserve score are correlating with the mortality of ARDS patients with pECLA. For the first time two specific risk scores were validated for an ECCO2R device and were superior to a general organ dysfunction score, the SOFA score. In the past RESP and PRESERVE score were developed and multiple validated for veno-venous ECMO in hypoxemic ARDS.
In the ELSO registry, used for the RESP score definition, only 21% of the subjects had a bacterial pneumonia, and major diagnostic groups were other acute respiratory diagnosis with 28% as well as unspecified with 30%. This origin of ARDS also contributes to the calculated RESP score (1). Nevertheless in the recently published EOLIA ECMO trial 45% of ARDS subjects suffered from a bacterial pneumonia and 18% from viral pneumonia (19). In our study, bacterial pneumonia was also the most frequent origin of ARDS with 40% and viral pneumonia was observed in 14%, demonstrating a typical collective of ARDS patients. RESP and PRESERVE score development and validation showed, that age, immunocompromised status, duration of mechanical ventilation, and SOFA score are relevant risk factors for outcome of ECMO (1, 2). We observed also a significantly younger age, less immunocompromised status, shorter pre-pECLA duration of mechanical ventilation and lower SOFA score in the survivor group (table 1). There was no direct impact of ARDS etiology to survival rate. Pre- and post-pECLA salvage therapy was not different between survivors and non-survivors. The multivariate analysis of our data revealed also age, SOFA score, immunocompromised status and PaCO2 before pECLA as relevant factors for mortality (table 3). As in former pECLA studies extracorporeal CO2 removal allowed an enhanced lung protective ventilation.
The PRESERVE score used a database of 140 ARDS subjects with ECMO to identify risk factors and to generate this score (2). Subjects presented with a median PaO2/FIO2 of 53 mmHg (interquartile range 43 – 60 mmHg), a median PaCO2 of 63 mmHg (51 – 77 mmHg) and a median pH of 7.22 (7.15 – 7.32) before ECMO. Based on pre-ECMO assessment data of the Extracorporeal Life Support Organization Registry (ELSO) the RESP score was published 2014 using 2,355 ECMO cases from 2000 to 2012 (1). Blood gas analysis revealed similar values before ECMO initiation with a median PaO2/FIO2 of 59 mmHg (interquartile range 48 – 75 mmHg), median PaCO2 of 56 mmHg (44 – 73 mmHg) and a median pH of 7.25 (7.15 – 7.35). In our study, subjects presented with a better oxygenation, indicated by a Horowitz index of 126 ± 59 mmHg, but with a severe respiratory acidosis (PaCO2 79.4 ± 30.6 mmHg and pH 7.23 ± 0.14). Patients with a severe disturbed oxygenation comparable to the PRESERE and RESP validation studies were not suitable for pECLA due to the limited oxygen uptake. These patients were primary connected to veno-venous ECMO. Nine pECLA patients were switched to veno-venous ECMO after further deteriorating oxygenation. Nevertheless, oxygenation and acid base status were more compromised than in the prospective randomized controlled Xtravent study, which evaluated pECLA in combination with an ultraprotektive ventilation strategy compared to lung protective ventilation in severe ARDS (20).
ECCO2R therapy as arterio-venous pECLA or low-flow veno-venous device seems a promising option to ensure optimized lung protection avoiding further ventilator induced lung injury (VILI) (21) and clinical trials are ongoing (22). Although there was no leading severe hypoxemia, hospital mortality was 49% in our study compared to 43% in the RESP score study by Schmid et al. (1). Therefore, in case of extracorporeal carbon dioxide removal a specific risk score seems also useful to identify high-risk patients.
In the PRESERVE and RESP score validation study most of the included patients suffered from severe hypoxemic ARDS (1, 2), whereas only 33% of our subjects had a severe ARDS before pECLA start. In the Berlin definition of ARDS, severity of disturbed oxygenation defines the grade and correlates with mortality (9, 17). On the other hand severe hypercapnia is independently associated with mortality of ARDS (23). Therefore, a direct transfer of the RESP and PRESERVE score from ECMO to ECCO2R seems not suitable, because patients have different ARDS characteristics with leading hypercapnia and concomitant acidosis but without life-threatening hypoxemia. After positive validation for ARDS patients with leading hypercapnia and ECCO2R therapy the established RESP and PRESERVE scores could be used for hypoxic as well as hypercapnic ARDS patients intended for extracorporeal lung support.
Validation of pECLA in our study demonstrated comparable results to other studies analyzing PRESERVE and RESP score for veno-venous ECMO (table 5). We additionally tested, if a non-specific SOFA score could be an alternative tool to assess the risk profile, but AUC as indicator for accuracy was lower. Nevertheless a SOFA score > 12 represents a risk factor in the PRESERVE score but not in the RESP score. Overall, only the specific scores demonstrated a good diagnostic accuracy for pECLA. Comparing both scores, the PRESERVE score requires less items and as a result seems easier to handle than the RESP score. In conclusion both scores seem suitable for pECLA as ECCO2R device.
As mentioned above several studies evaluated RESP and PRESERVE scores for other ECMO populations with differing accuracy and without superiority of one score (table 4). Survival in the different predefined risk classes demonstrated some inconsistent results but with a generally increasing mortality for a higher risk score (table 5). Compared to these studies the performance of PRESERVE and RESP was non-inferior for pECLA in our study. Limitations of our study are the retrospective small validation cohort from one ARDS center without additional data from other centers to verify our results, the missing long-term survival data and the restriction to one specific low-flow device for ECCO2R. A prospective registry of ECCO2R could be able to generate more detailed as well as long-term data. With our retrospective study, PRESERVE and RESP score could be sufficiently validated to identify a high-risk profile before starting an extracorporeal carbon dioxide elimination. Nevertheless, ARDS therapy and especially time of initiation and decision for conventional therapy versus ECCO2R or ECMO require clinical assessment and could not be replaced by a simple scoring.
In our study we focused on pumpless ECLA as ECCO2R device, but other veno-venous low-flow ECLA systems are also used for hypercapnic ARDS. For veno-venous devices, there is an ongoing transition from leading decarboxylation to decarboxylation plus oxygenation with increasing blood flow. As RESP and PRESERVE were primary validated for classical high-flow ECMO and now were additionally validated for pECLA as decarboxylation device by our study, we hypothesize that these scoring systems are also suitable for other low-flow ECLA systems. Further investigations of low-flow veno-venous ECCO2R could be used to confirm this assumption.