This is a unique study from our region to evaluate the clinical characteristics, complications and mortality in patients with post-trauma ARDS managed with ECMO support versus conventional mechanical ventilation. During the study period, the rate of ARDS in trauma patients was 0.9%, of which one quarter of cases underwent ECMO therapy. Almost, one third of the ECMO group died with severe head injury whereas two thirds of non-ECMO died with head injury. The overall mean SOFA score (9.3±3.4) and on-admission shock index (1.05±0.47) were high which indicates the potential unfavorable outcome. MLI scoring was significantly higher in the ECMO group. The MLI scoring showed that ECMO use was associated with significantly higher survival in patients with severe lung injury than non-ECMO severe MLI group.
The selection of candidates for ECMO is challenging for intensivists due to heterogeneous patient population and the availability of expert team. Moreover, early identiﬁcation of risk factors of mortality and analysis of long-term outcomes of survivors are necessary to predict the prognosis [20,22]. In our cohort, the overall rate of mortality was 41% and the presence of brain edema and AKI were found to be the independent predictors of mortality. The 30-day survival rate was relatively better in the ECMO group and the long-term survival was better in the non-ECMO group, however these differences in survival were statistically not significant. Our findings indicate that early ECMO (≤2 days) was associated with better survival in comparison to delayed ECMO. The literature suggested an overall survival rate after VV ECMO in trauma patients ranges from 50% to 79%  which agrees with our findings (64%). Also, Guirand et al  showed that ECMO was independently associated with improved survival as compared to the conventional ventilation matched group (age and ISS), however, acute intracranial hemorrhage patients were excluded from this study. An earlier study by Bosarge et al  reported significant reduction in mortality among the ECMO group (13.3%) compared to the conventional (64.3%) which were matched for age, ISS, TBI, SOFA and MLI scores. Similarly, an observational study reported significantly higher ICU and hospital survival rates in the traumatic extracorporeal life-support (ECLS) cohort as opposed to the non-traumatic ECLS group . In contrast with our findings the EOLIA trial , showed that patients with severe ARDS had no significant reduction in 60-day mortality from early ECMO, as compared to conventional mechanical ventilation.
In our cohort, the duration of mechanical ventilation, ICU and hospital length of stay tends to be prolonged in the ECMO group. Contrarily, Bosarge et al  showed shorter mean ventilatory days were (7.5 ± 8.4 days) and patients were transitioned to ECMO in a relatively shorter period. Over 59% of our patients had ECMO started within 48 hours of admission. On the contrary, in a study of 7 trauma patients by Strumwasser et al , the survivors had ECMO initiated later than non-survivors (15 vs 7.8 days).The ELSO registry study , demonstrated the mean duration of extracorporeal life support was 8.8±9.5 days which is slightly higher [median 9.5 (1-29) days] in our cohort.
A recent study by Chen et al  showed higher rate of all-cause mortality in patients with D-AKI (52.3%) as compared to those without D-AKI (33.3%). Also, the long-term mortality in patients survived >90 days after hospital discharge was significantly lower in patients without D-AKI (22.0%) than those required long-term dialysis (50.0%). In our cohort, AKI was reported in 38.8% of cases (n=33), of them 13 cases had ECMO. AKI was associated with higher mortality in patients with (54%) and without ECMO therapy (80%). The ECMO group with AKI had higher mortality in comparison to those without AKI (11%).
Several studies have shown that the RESP score is a useful tool for prediction and discrimination of survival probabilities in ARDS patients treated with ECMO [20,22,29]. In the present study, over 81% of patients in the ECMO group had risk Class IV-V.
Comparison of the long-term outcomes of ARDS patients treated with ECMO and conventional ventilation strategies showed no significant difference in the 1-year survival but the non-ECMO group had greater impairment of health-related quality of life . It has been suggested that the long-term functional limitation in ARDS survivors is not related to the degree of pulmonary dysfunction at admission, but rather to the consequences of invasive treatment at ICU and severity of illness [22,31]. In our study, 18% of ECMO and 25% of non-ECMO group were discharged home, while higher proportion of patients from ECMO group (50%) were transferred to long-term facility with variable degree of disability as opposed to non-ECMO group (25.4%). Swol et al  reported ECLS survivors, 23% were discharged home, 19% were transferred back to the referring hospital, and 58% were discharged to another facility.
In our cohort, VAP, sepsis, GI bleeding and thromboembolic events such as PE and DVT were the frequent in-hospital complications. Our findings are consistent with the previous studies reported bleeding, nosocomial infection and thromboembolic events as ECMO-related complications. Bleeding occurs in about 20-40% of patients on ECMO with various degrees of severity [12,24,32,33]. Also, nosocomial infections are common in ECMO patients which ranges from 11.7-64% [34,35]. Occurrence of limb ischemia is an uncommon event in trauma patients  which is also evident from our findings (1.2%). Luyt et al  reported cerebral bleeding (7.5%) and ischemic stroke (2%) as the neurological events in brain injury patients on VV-ECMO. However, in the present study, overall stroke was reported in 4 patients (4.7%), with only one patient in the ECMO group (4.5%).
In our study, the presence of brain edema and AKI were found to be the independent predictors of mortality. While others suggested ISS > 35 and a refractory post-traumatic shock/cardiac arrest were the independent predictors of hospital mortality . Similarly, Parker et al  found that only the presence of hemorrhagic shock at admission was significantly associated with mortality in patients requiring ECMO, and not the age or TBI. However, ISS and admission shock index were not found to be independently associated with mortality in our study. The number of pre-ECMO organ dysfunctions has been used as an important prognostic factor. In previous studies, SOFA score was used as a surrogate for organ failure and pre-ECMO central nervous system dysfunction was associated with poor outcome in the RESP score [20,37,38]. Cheng et al , demonstrated that in adult VV-ECMO patients, pre-ECMO SOFA score >9, ventilatory day > 4 and immunocompromised status were independent predictors of mortality. However, the mean SOFA score was comparable in patients with and without ECMO in our study.
The use of ECMO in patients with TBI remains controversial. Wu et al , studied TBI patients before ECMO. TBI was significant in 19 patients, and a heparin-free ECMO was provided to most patients. No TBI re-bleeding occurs, and only one in-hospital death was reported. In our study, 68% of ECMO group and 51% of non-ECMO group had TBI; no cerebral bleeding was observed but three patients with TBI died in ECMO group. According to the above-mentioned findings, ECMO with a heparin-free strategy seems to be safe in patients with minor or drained TBI .
This study has certain limitations that need to be addressed. It is a single center study with a retrospective nature and relatively small sample size. However, it is representative of the country as our trauma center is the only tertiary level 1 trauma center in the country that manages moderate to severe trauma cases including ECMO support. The two study groups were matched for age, ISS, and AIS but not for MLI scoring, however, multivariable analysis and sub-analysis were performed to mitigate selection bias and to assess the impact of MLI on the outcome. Of note, ECMO was started in 3 cases with mild-moderate MLI because of difficulty of prone positioning in 1 abdominal injury case and difficulty in optimizing ventilatory setting in 2 cases with significant head injury. In addition, due to lack of standard treatment algorithm, some patients in both groups have received various treatment at the discretion of the attending physician. In the non-ECMO group, we found that only 5 cases had official referral/consultation to the ECMO team which declined the ECMO support because of poor prognosis. Also, health-related quality of life post-discharge was not addressed.