Discussion
To our knowledge, we report the largest study focusing on outcomes of VA-ECMO treatment considering blood pH at VA-ECMO initiation. Our findings suggest: 1) the survival at one year of patients with a blood pH at cannulation <7 is low but does exist. However, patients were younger and treated mainly for refractory cardiac arrest, but after adjustment blood pH remains associated with mortality. 2) The lactate level is highly correlated with the pH level.
The use of ECMO has been used exponentially since the early 2000s in western countries, allowing to treat even patients in refractory out-of-hospital cardiopulmonary arrest with better results than standard resuscitation (43% vs 7% at discharge and 43% vs 0% at 3 months)(7). VA-ECMO might become in a near future the standard treatment for refractory cardiorespiratory arrest, however clinical results remain questionable in many centers. Mørk and al. recently reported a thirty day survival rate of 26% after ECMO initiation for out of hospital refractory cardiac arrest(8). Predicted scores have been proposed but the optimal tool remains an unmet need (9). We believe pH and lactates may represent interesting parameters to consider to
help in this goal research.
The survival rate in group 1 (lowest pH) was significantly lower than in the other 2 groups (p<0.001). In our experience, having a pH lower than 7 at implantation multiplies the risk of death by four (Table 3). In the literature, survival in the adult population treated with VA-ECMO for cardiogenic shock is similar than in our study(10). However, we do report here our real-life daily practice without excluding patients with high acidity, even those who were supported for a few hours. Interestingly, Mørk et al. reported good outcomes on a population similar to our group 1(8). In our study, the survival rate, in group 1 although very low, is not negligible. Indeed, in this group one patient out of 6 has been discharged alive from the hospital despite the extreme acidity at cannulation.
It is important to note that the high mortality rate occurs within the first 30 days post-cannulation and that the median survival is respectively 1, 14 and 33 days for groups 1, 2 and 3. These results indicate that financial and human resources require to manage such patients, although important, might not last for a long time of mechanical support, especially for group 1 patients. The most critically-ill ones die promptly, mainly within the first days. An ongoing study (ECMONOMY) at the Rennes’s University Hospital, aims to accurately study the cost of a hospital stay for a patient treated with VA ECMO (NCT03686540 ). This study will eventually help to explore the financial ratio in order to avoid unnecessary expenses.
Patients in group 1 had fewer complications, whether thrombotic or infectious, than the others groups. One may consider it is because these patients die more quickly and did not have time to develop such complications.
As in daily life practice we demonstrated a strong correlation between the blood pH level and the lactate level (-0.66). This strong correlation is interesting as one or both parameters might be part of a new decision-making algorithm at cannulation. There are already scores such as the SAVE score which predicts the survival rate in patients with refractory cardiogenic shock requiring ECMO(3). This score requires a blood sample to get serum creatinine or bicarbonate levels, excluding its easy use out of hospital and requiring a minimal delay. We believe pH and lactates dosage can be obtained almost instantaneously, even outside hospital with small ambulatory biological samples devices. Such strategy may allow to help in the difficult decision-making process, especially in high emergent cases, out of hospital or in the emergency room. Indeed, our study showed that when blood pH level is low (<7) and blood lactate level is high (>7) the survival prognosis is low (<7%). This simple algorithm with “the three seven rule” may be very helpful for emergent real-life clinical.
Moreover Mungan et al. indicate that in addition to the lactate level at ECMO initiation, the evolution of lactate clearance is also important as these 2 factors allow to estimate a reliable prognosis of the patient’s outcome(11). To be more precise, Li et al. indicate from their univariate and multivariate analyses that the important factors are the mean lactate concentration and lactate clearance at 6 and 12 hours after the initiation of ECMO(12). This approach integrating pH and lactates levels at ECMO initiation seems logical as the elevation of lactate levels is related to tissue damage and that lactate clearance therefore indicates a restoration of tissue oxygenation and hemodynamic circulation. In our study low pH and high lactate rates are mortality’s predicting factors as demonstrated by Seeger and al(6).
We believe our study pleads strongly for further investigations to precise utility or futility of ECMO treatment using pH and lactates level. These additional investigations seem to be essential because new indications of short-term assistance (ECMO or Impella®) may develop such as High Risk Percutaneous Coronary Indication (HR PCI), Transcatheter Aortic Valve Implantation (TAVI) or Mitraclip®. Moral and ethical obligations will require careful evaluation of these possible new indications to avoid futile results. Heart team approach will be even more essential to define possible new indications in a very severe population.
Our study has some limitations, including its retrospective nature and the heterogeneity of its cohort. The retrospective character is somewhat mitigated by the fact that the data in the database are entered prospectively by nurses dedicated to the database. Moreover, our study compares survival outcomes between different subgroups of patients in a tertiary high-volume ECMO center. Our database does not contain the data of all the requests for ECMO procedure but only the patients implanted; it is therefore possible that a selection was made at the discretion of the surgical team when managing the call for ECMO patient, especially given the patient’s age and comorbidities.