EuroELSO Journal Club

Interested in the latest scientific publications?

EuroELSO is dedicated to knowledge and education. Therefore, EuroELSO Steering Committee has launched the EuroELSO Journal Club. We are selecting on a quarterly basis recent interesting ECLS related manuscripts and provided summaries in a concise format. We hope this activity might turn to a useful tool for all physicians and specialists interested in ECLS/ECMO.

On behalf of EuroELSO Steering Committee
Jan Belohlavek, Justyna Swol, Matteo di Nardo and Simon Finney

03 / 2022

Left ventricular unloading during ECPR with VA-ECMO has shown promising results. The research team from the University Hospital of Cologne retrospectively investigated the performance of concomitant implantation of a transfemoral micro-axial blood pump Impella in 18 patients with OHCA or in-hospital cardiac arrest (IHCA). The control group comprised 90 subjects from the same registry, who were supported by VA-ECMO only. Adding Impella to the ECPR resulted in significantly decreased all-cause mortality (82% vs. 56%, P=0.01). ECMO decannulation was more frequently achieved in the Impella group (72% vs. 32%, P=0.01), in which the low-flow time was also shorter (60 min vs. 55 min, p=0.01). On the other hand, the time of circulatory support was reduced in the VA-ECMO only cohort (2.0 ± 1.73 vs. 4.76 ± 2.88, P=0.05), and patients who have had Impella implanted suffered more frequently of an acute kidney injury (AKI) with the need for dialysis (72% vs. 18%, P≤0.01).

 

The authors acknowledged that no universally recommended unloading strategy exists at the moment, and randomized clinical trials are urgently needed. Their study is limited not only by its retrospective design but also by the small sample size of the Impella group. They explain the more prevalent AKI in the Impella supported group by the simple fact that unloaded patients survived long enough to develop complications, although shear stress and subsequent hemolysis might also contribute.

Gaisendrees, C., Djordjevic, I., Sabashnikov, A., Adler, C., Eghbalzadeh, K., Ivanov, B., Walter, S., Schlachtenberger, G., Merkle‐Storms, J., Gerfer, S., Carstens, H., Deppe, A. C., Kuhn, E., & Wahlers, T. (2021). Impact of left ventricular unloading using a peripheral Impella®‐pump in ECPR patients. Artificial Organs. https://doi.org/10.1111/aor.14067

Achieving optimal anticoagulation during ECMO remains challenging. In a systematic review and meta-analysis primarily from Leiden in the Netherlands, the authors compared a time-based approach with an anticoagulation regime based on anti-Xa measurements in a total of 26 studies on 2086 patients. Overall, bleeding was registered in 34.2% of anti-Xa-guided patients and in 41.0% of a time-guided group. Regarding efficacy, thrombotic events happened in 32.6% and 38.4% and the all-cause mortality rate reached 35.4% and 42.9%, both numerically lower in the anti-Xa-based group. However, only seven studies included results from both strategies. While only data from those were selected for comparison, the bleeding rate remained significantly lower in the anti-Xa-based group (adjusted OR 0.49 (95%CI 0.32;0.74), p < 0.001) and so was all-cause mortality (adjusted OR 0.61 (95%CI 0.40;0.95), p = 0.03). The rate of thrombotic events was without statistical difference.

 

Though the anti-Xa-based strategy seems safer without increasing the risk of thrombotic events, the authors admitted that most patients in the seven selected trials were pediatric, and the sample size was insufficient for the analysis regarding the ECMO type. The quality of evidence was also only moderate. On the other hand, they mentioned that based on previous data, anti-Xa is the only test to strongly correlate with heparin dose, unlike ACT or aPTT. The investigators also discussed possible future anticoagulation strategies that will couple anti-Xa measurements with point-of-care functional coagulation tests, such as TEG or ROTEM.

Willems, A., Roeleveld, P. P., Labarinas, S., Cyrus, J. W., Muszynski, J. A., Nellis, M. E., & Karam, O. (2020). Anti-xa versus time-guided anticoagulation strategies in Extracorporeal Membrane Oxygenation: A systematic review and meta-analysis. Perfusion, 36(5), 501–512. https://doi.org/10.1177/0267659120952982

Thrombotic complications remain a major limitation of ECMO use. Lately, real-time, non-invasive sensors of thrombus formation in extracorporeal circuits are being developed. A Japanese emerging micro-optical thrombus sensor performance was evaluated in a recent study. The investigators installed one sensor at the rotary blood pump and the second on a flow channel of an in vitro circuit with porcine blood. To evaluate the variation in the ratio of incident light intensity at each wavelength of the two sensors, Rfluct (for 660 nm) and Ifluct (for 855 nm) were defined. Thrombus tests were terminated after Rfluct or Ifluct showed a more profound change than the maximum range of those in the hematocrit (Hct) and oxygen saturation (SaO2) variation test. In all three thrombus detection tests, Ifluct showed a larger change than the maximum range of those in the Hct and SaO2 variation test. After the tests, thrombus formation was confirmed in the pump, and there was no thrombus in the flow channel. The results indicate that Ifluct is an effective parameter for identifying the presence of a thrombus.

 

The authors also claimed that the full data suggest a potential proportional relationship between Ifluct and the thrombus volume, but this needs to be established by further testing. For now, the nature of the study was fully preclinical on an ECMO circuit model. If the method will continue to show promising results, the conduction of clinical testing and confirming real-life benefits is necessary.

 

Morita, N., Sakota, D., Oota-Ishigaki, A., Kosaka, R., Maruyama, O., Nishida, M., Kondo, K., Takeshita, T., & Iwasaki, W. (2020). Real-time, non-invasive thrombus detection in an extracorporeal circuit using micro-optical thrombus sensors. The International Journal of Artificial Organs, 44(8), 565–573. https://doi.org/10.1177/0391398820978656

Refractory cardiogenic shock after cardiac surgery is a critical condition that has been increasingly treated with VA-ECMO. Current trends have been described in a recent analysis of the multicenter data about a total of 7185 patients from the ELSO registry, gathered between 2010 to 2018. The data suggested that VA-ECMO for a postcardiotomy refractory cardiogenic shock is used with an increasing frequency over the aforementioned period. Although the mean age in the whole cohort was 56,3 years, treated patients also tended to be older over time as a spectrum of potential candidates broadened. VA-ECMO was mostly used after coronary artery bypass (CABG, 26.8%) and valvular surgery (25.6%), followed by heart transplantation (20.7%). Weaning was possible in 56.4% of the subjects, and 41.7% survived until discharge. In-hospital mortality rates remained constant over time, whereas complication rates were significantly reduced. While the highest mortality rate was seen after CABG (65.4%) and combined coronary artery bypass surgery with valve (68.4%), and aortic (69.6%) procedures, the lowest mortality was recorded in heart transplantation recipients (46.0%). Older age, central cannulation, and complications while on the ECMO circuit were all independent predictors of poorer prognosis. Interestingly, the current report confirms the protective effect of peripheral cannulation for ECMO on survival. Patients undergoing peripheral ECMO for PCS had over 25% higher odds of survival compared with their centrally cannulated counterparts, which was maintained after matching for pre-ECMO variables (OR, 0.48 [0.40–0.58]; p < 0.001).

 

It is stressed in the present study that cardiac surgical patients suffer from substantial pre-ECMO comorbidities, prolonged ECMO support, and more advanced age than in other ECMO populations. The study also demonstrates a trend towards an increasing number of ECMO procedures in recent years, yet no signs of increased mortality rates over time were observed. While the authors suggested it might be surprising in the face of improvements in ECMO care, it can be also explained by the application of VA-ECMO for PCS in increasingly older and sicker patients. They suggested that rather than searching for alternatives to mechanical circulatory support, which seems the best solution in circulatory collapse, further improvements in clinical management must be sought, e.g. coupling VA-ECMO with left ventricular unloading. According to them, ECMO also shouldn’t be withheld from patients based on advanced age alone. According to the previous data, in the elderly without severe comorbidities and the potential for a short recovery time, the advanced age itself was not linked to increased mortality.

Kowalewski, M., Zieliński, K., Brodie, D., MacLaren, G., Whitman, G., Raffa, G. M., Boeken, U., Shekar, K., Chen, Y.-S., Bermudez, C., D’Alessandro, D., Hou, X., Haft, J., Belohlavek, J., Dziembowska, I., Suwalski, P., Alexander, P., Barbaro, R. P., Gaudino, M., … Lorusso, R. (2021). Venoarterial extracorporeal membrane oxygenation for postcardiotomy shock—analysis of the Extracorporeal Life Support Organization Registry. Critical Care Medicine, Publish Ahead of Print. https://doi.org/10.1097/ccm.0000000000004922

Based on the present data, the authors suggested a revision of the anticoagulation goals, especially in the VA-ECMO setting. While in the VV-ECMO patients, the mean anti-Xa activity was in the range from 0.2 to 0.4 IU/mL, lower than the critical value of 0.46 IU/mL and well within the recommended thresholds, in the VA-ECMO, anti-Xa targets are usually 0.3 and 0.7 IU/mL and predominantly above the critical value. Unfortunately, the literature regarding systemic anticoagulation in nonsurgical VA-ECMO patients is poor. However, for both VV and VA-ECMO, downgrading anticoagulation targets should be done with caution, as even in this study the mean anti-Xa was significantly lower in patients with thrombotic events.

Descamps, R., Moussa, M. D., Besnier, E., Fischer, M.-O., Preau, S., Tamion, F., Daubin, C., Cousin, N., Vincentelli, A., Goutay, J., & Du Cheyron, D. (2021). Anti-xa activity and hemorrhagic events under Extracorporeal Membrane Oxygenation (ECMO): A Multicenter Cohort Study. Critical Care, 25(1). https://doi.org/10.1186/s13054-021-03554-0

Based on the previous data, not being intubated at cannulation is a determinant for remaining awake later. The authors of the present study, therefore, recommended a trial of alternative management of respiratory insufficiency (high-flow oxygen, non-invasive ventilation), if clinically possible. In intubated patients, the earliest possible extubation after VA-ECMO implantation should be considered, since the reported data show that the impact of ‘awake’ ECMO management on outcome occurred early and the survival differences among groups remained steady later. Although extubation of patients under ECMO is not a standard practice in most centers, the Extracorporeal Life Support Organization guidelines suggest the ‘awake ECMO’ strategy as one of the possible alternatives. The investigators also stressed additional benefits of the awake status, such as physical rehabilitation, oral feeding, communication with relatives, and interactive information about the medical decision. In their opinion, factors including avoidance of VAP, immobilization, cardiac arrest at anesthetic induction and prompt detection of ECMO-related complications (e.g. stroke, limb ischemia) may also contribute to better survival rates and overall outcome.
Montero, S., Huang, F., Rivas-Lasarte, M., Chommeloux, J., Demondion, P., Bréchot, N., Hékimian, G., Franchineau, G., Persichini, R., Luyt, C.-É., Garcia-Garcia, C., Bayes-Genis, A., Lebreton, G., Cinca, J., Leprince, P., Combes, A., Alvarez-Garcia, J., & Schmidt, M. (2021). Awake venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock. European Heart Journal. Acute Cardiovascular Care, 10(6), 585–594. https://doi.org/10.1093/ehjacc/zuab018

Acute, severe mitral regurgitation (MR) poses a difficult-to-manage situation because the patients are often too ill for immediate surgery. Less invasive solutions are therefore sought, such as hemodynamic stabilization with left Impella support before percutaneous MitraClip implantation. This strategy was evaluated in a recent study. Since the condition is rather rare, only six INTERMACS-1 CS, surgery ineligible patients on mechanical ventilation due to pulmonary edema were included. The mean EURO-II score was 39 ± 19%, age 66.8 ± 4.9 years, and all had an initial pulmonary capillary wedge pressure (PCWP) >20 mmHg. Their cardiac output was severely impaired (left ventricular outflow tract velocity time index 9.8 ± 1.8 cm), requiring MCS (Impella®-CP; mean flow 2.9 ± 1.8 L per minute; mean support 9.7 ± 6.0 days). Impella alone did not allow weaning from the mechanical ventilation in any of the subjects, so MitraClip was implanted in all. This strategy resulted in a reduction of MR from severe to mild and successful weaning. Survival to discharge reached 86%, and all discharged patients were alive after six months.

 

Cardiac output in acute severe MR is not limited by left ventricular function, but by a strong backward flow causing pulmonary edema and weak forward flow resulting in hypoperfusion of the tissues. The authors of the present study appreciated the feasibility of the Impella/MitraClip strategy that was carried out in all of the subjects. Post-procedure, PCWP in all patients was below 15 mmHg, further allowing rapid ventilator and sedation weaning. None of the patients had to be upgraded to a permanent LVAD. Although they were considered inoperable and their prognosis without Impella/Mitraclip was poor, five out of six survived over six months. Within this period, two subjects needed to be readmitted, the reason was in both cases mild decompensation of heart failure due to atrial fibrillation. Both were successfully medically treated.

Vandenbriele, C., Balthazar, T., Wilson, J., Adriaenssens, T., Davies, S., Droogne, W., Dubois, C., Caetano, A. F., Goetschalckx, K., Jacobs, S., Janssens, S., Ledot, S., Meyns, B., Soliman-Aboumarie, H., Verbrugghe, P., & Price, S. (2020). Left Impella®-device as bridge from cardiogenic shock with acute, severe mitral regurgitation to MitraClip®-procedure: A new option for critically ill patients. European Heart Journal. Acute Cardiovascular Care, 10(4), 415–421. https://doi.org/10.1093/ehjacc/zuaa031

Neurologic adverse events (NAEs) are a common complication of centrifugal-flow LVADs, although the incidence is decreasing with technological advances. The group of researchers from Johns Hopkins Hospital analyzed the data from a total of 6205 patients from the Intermacs registry for NAEs associated with two such devices – HeartMate3 (HM3, implanted in 50.4% patients) and HeartWare HVAD (HVAD, in 49.6%). The major events included transient ischemic attack (TIA), ischemic (ICVA), or hemorrhagic cerebrovascular accident (HCVA). The median follow-up for the respective devices was 9 and 12 months. HVAD was associated with more NAEs than HM3 (16.4% vs. 6.4%, P<0.001), driven by all three subtypes (TIA: 3.3% vs. 1.0%; ICVA: 7.7% vs 3.4%; HCVA: 7.2% vs. 2.0%, P for all <0.001). The results were consistent across a propensity-matched analysis, Kaplan-Meier analyses of freedom from first major NAE (80% vs. 93% at 1 year) as well as hazard analysis (HR 5.71). Although HM3 was associated with an overall lower hazard of major NAEs, there was no significant difference in their incidence during the early postimplantation period.

 

The authors stressed that on June 3, 2021, the vendor for the HVAD announced that the distribution and sale of the device would stop. At the same time, the FDA issued a warning that HVAD “demonstrate a higher frequency of neurologic adverse events and mortality when compared with other commercially available devices”, which is consistent with their results. In their study, the hazard remained constant even after adjusting for surgical technique, center volume, and different years of implantation.

Cho, S.-M., Mehaffey, J. H., Meyers, S. L., Cantor, R. S., Starling, R. C., Kirklin, J. K., Jacobs, J. P., Kern, J., Uchino, K., & Yarboro, L. T. (2021). Cerebrovascular events in patients with centrifugal-flow left ventricular assist devices: Propensity score–matched analysis from the INTERMACS Registry. Circulation, 144(10), 763–772. https://doi.org/10.1161/circulationaha.121.055716

The use of venoarterial-extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock (CS) is limited by a high complication rate frequently related to deep sedation and mechanical ventilation (MV). A group of predominantly Spanish authors evaluated the impact of an ‘awake’ (invasive MV used during ≤50% of the time) vs. ‘non-awake’ VA-ECMO in this clinical setting. They retrospectively searched a 7-year single-center database and performed a propensity-score-matched analysis on a total of 231 patients (39 % ‘awake’). Those who were ‘awake’ had significantly lower rates of pneumonia (35% vs. 59%, P = 0.017), tracheostomy, renal replacement therapy, less antibiotic and sedative consumption and reduced 60-day (20% vs. 41%, P = 0.018) and 1-year mortality rates (31% vs. 54%, P = 0.021). Lastly, MV at ECMO cannulation was the most significant independent factor associated with 60-day mortality.

Based on the previous data, not being intubated at cannulation is a determinant for remaining awake later. The authors of the present study, therefore, recommended a trial of alternative management of respiratory insufficiency (high-flow oxygen, non-invasive ventilation), if clinically possible. In intubated patients, the earliest possible extubation after VA-ECMO implantation should be considered, since the reported data show that the impact of ‘awake’ ECMO management on outcome occurred early and the survival differences among groups remained steady later. Although extubation of patients under ECMO is not a standard practice in most centers, the Extracorporeal Life Support Organization guidelines suggest the ‘awake ECMO’ strategy as one of the possible alternatives. The investigators also stressed additional benefits of the awake status, such as physical rehabilitation, oral feeding, communication with relatives, and interactive information about the medical decision. In their opinion, factors including avoidance of VAP, immobilization, cardiac arrest at anesthetic induction and prompt detection of ECMO-related complications (e.g. stroke, limb ischemia) may also contribute to better survival rates and overall outcome.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) can be an alternative for patients with refractory OHCA, especially in a traumatic setting and when ECPR is not clinically or logistically available. The use of REBOA in the Emergency Department and by the aerial emergency services was analyzed by a research group from Bologna in Italy. The catheter placement was achieved in 18 out of a total of 20 patients. The two non-successes were related to repeated arterial puncture failure. The median time between the EMS dispatch and REBOA catheter placing attempt was 46 min. An increase in etCO2 over 10 mmHg was observed after balloon inflation in 12 out of 18 patients (8/11 non-traumatic and 4/7 traumatic), and a sustained ROSC was recorded in 5 patients (1 traumatic and 4 non-traumatic). However, 4/5 patients reached the criteria for brain death in the subsequent 24 h while one patient experienced another episode of refractory cardiac arrest in ICU and subsequently died.

 

The authors confirmed the feasibility of REBOA both in the ED and in an out-of-hospital environment, although they admit that none of the patients treated on the field survived until hospital admission, despite reaching a transient ROSC. In the whole cohort, 72% of the treated population experienced a transient ROSC after balloon inflation, and sustained ROSC was recorded in 36 %. Even though none of the non-traumatic OHCA patients survived, those four patients which underwent brain death after resuscitation were judged suitable for organ donation, despite long cardiac arrest times. The organs of two of them were successfully donated. The authors, therefore, argue that the potential effect of REBOA in increasing ROSC probability may still be of interest from the perspective of organ harvesting. In the traumatic cases, the most interesting aspect of the study according to them was that a stable ROSC was achieved after balloon inflation in a patient without any documented evidence of massive hemorrhage, therefore reinforcing the concept that this technique could enhance the probability of ROSC independently from its bleeding-control effects. Finally, even though none of the subjects of the present study survived, the risks of potential harms of REBOA in the salvage setting are overwhelmed by a potential benefit.

Gamberini, L., Coniglio, C., Lupi, C., Tartaglione, M., Mazzoli, C. A., Baldazzi, M., Cecchi, A., Ferri, E., Chiarini, V., Semeraro, F., & Gordini, G. (2021). Resuscitative endovascular occlusion of the aorta (REBOA) for refractory out of hospital cardiac arrest. an utstein-based case series. Resuscitation, 165, 161–169. https://doi.org/10.1016/j.resuscitation.2021.05.019

LVADs provide haemodynamic support for patients with advanced heart failure. The present retrospective study evaluated outcomes of LVADs implantation in such a population between 2010 and 2020. The results of 107 critically ill INTERMACS 1-2 subjects were compared with results of 100 INTERMACS 3-5 controls. INTERMACS 1-2 developed more major infections during the hospitalisation following implantation (41.1% vs. 23.0%, P = 0.005), more respiratory failures (57.9% vs. 25.0%, P <0.001), mild (20.6% vs. 8.0%, P =0.010), and moderate (31.8% vs. 7.0%, P <0.001) right heart failures, and acute renal dysfunctions (56.1% vs. 6.0%, P < 0.001). They also experienced a higher incidence of thoracic (15.9% vs. 4.0%, P = 0.005) and gastrointestinal bleeding (21.5% vs. 11.0%, P =0.042), as well as right heart failure (18.7% vs. 1%, P < 0.001) during a median follow-up of 2.0 years. This resulted in a significally higher risk of death (HR 1.64, 95% CI 1.12-2.40, P = 0.011).

 

Preoperative leukocytes, CRP, PCT, bilirubin, ALT, and LD were all significantly higher in INTERMACS 1-2 when compared to controls. These markers did not further deteriorate within the first week after the procedure, except for WBC and CRP, which can be interpreted as a general response to perioperative stress. Previous studies have demonstrated that markers of organ function usually decrease by the end of the first year following device implantation, suggesting that the recovery of organ function is possible.

 

Based on the present data with increased morbidity and mortality in advanced disease, the authors emphasized timely implantation of LVADs. The current trend tends to the LVADs implantation in INTERMACS 1. According to them, the procedure should be considered in selected INTERMACS 1-2 patients, in all INTERMACS 3 patients, and in severely symptomatic and motivated INTERMACS 4-7 patients. They also stressed that the decision is complex and should involve the whole clinical picture. An early referral for evaluation in an LVAD or transplant center is, therefore, essential. An alternative strategy may include ECMO as a bridge to the next therapy, possibly with an Impella, to facilitate the transition from ECMO to LVAD.

Zhigalov, K., Van den Eynde, J., Chrosch, T., Goerdt, L., Sá, M. P., Zubarevich, A., Papathanasiou, M., Wendt, D., Luedike, P., Pizanis, N., Koch, A., Schmack, B., Rassaf, T., Kamler, M., Ruhparwar, A., & Weymann, A. (2021). Outcomes of left ventricular assist device implantation for advanced heart failure in critically ill patients (INTERMACS 1 and 2): A retrospective study. Artificial Organs, 45(7), 706–716. https://doi.org/10.1111/aor.13897

Since the profile of the hemodynamic effect on multiple variables (LVEDV, ventricular stroke work – SW, LAP, MPAP, cardiac output – CO) differed significantly between the strategies, the authors argue that in the real clinical practice it will need to be chosen based on individual patient characteristics and disease etiology. They also acknowledged that more factors than a pure effect on hemodynamics need to be considered, e.g. necessity for surgical cut-downs. On the other hand, nonsurgical vents can be placed, but these are limited in size, which may affect unloading efficacy. Thirdly, implanting a VAD is a method of choice in many centers as it is relatively easy to use. In the present study, the VAD demonstrated a reduction in SW from baseline 0.143 W to between 0.065 W at 1 L/min ECMO flow to 0.078 W at 4 L/min ECMO flow. Efficacy of the VAD at unloading LVEDV and MPAP decreased as ECMO flow was increased, due to the increasing pressure head across the VAD caused by the ECMO outflow. Conversely, the intra-aortic balloon pump (IABP) improved CO slightly compared with no unloading technique (1.1 compared with 1.0 L/min) but was the least effective at reducing LVEDV, MPAP, LAP, and SW.

Stephens, A. F., Wanigasekara, D., Pellegrino, V. A., Burrell, A. J. C., Marasco, S. F., Kaye, D. M., Steinseifer, U., & Gregory, S. D. (2020). Comparison of circulatory unloading techniques for venoarterial extracorporeal membrane oxygenation. ASAIO Journal, 67(6), 623–631. https://doi.org/10.1097/mat.0000000000001268

Acute myocardial infarction (AMI) complicated by an OHCA and subsequent cardiogenic shock is a major emergency. Early MCS with Impella might improve the survival of such patients. The group of German investigators retrospectively compared the timing of the MCS initiation with an Impella 2.5 before percutaneous coronary intervention (pre-PCI) and after-PCI. They identified 81 patients who received Impella 2.5 in this clinical setting. All patients were in profound cardiogenic shock requiring catecholamines at admission. Despite the retrospective design, the baseline characteristics of the groups were well balanced, especially for initial hemodynamics, admission lactate, and cardiac arrest variables as well as delays concerning the transfer to the hospital. Patients in the pre-PCI group had a higher survival to discharge (54.3% vs 30.4%; p = 0.04) and at 6 months (51.4% vs 28.2%; p = 0.04) as compared to patients of the post-PCI group. Pre-PCI patients also achieved a greater functional recovery of the left ventricle and a better restoration of the end-organ function

 

According to the present study, the pre-PCI approach was associated with favorable results, despite an average 25-minutes delay in crossing the infarct-related artery. Furthermore, Kaplan-Meier curves separated very early in the clinical course of the patients, indicating that early circulatory support unloading the LV and restoring end-organ perfusion are major determining factors of outcomes. Similarly, the pre-PCI group demonstrated quicker biomarker normalization and a decline in the use of vasopressors and inotropes. This suggests a faster restoration of end-organ perfusion when Impella is initiated early. Moreover, inotropes and vasopressors may further aggravate myocardial ischemia, amplify the neurohormonal cascade, and activate proapoptotic signals in CS, which all negatively affect cardiac and end-organ function.

Chatzis, G., Markus, B., Luesebrink, U., Ahrens, H., Divchev, D., Syntila, S., Scheele, N., Al Eryani, H., Tousoulis, D., Schieffer, B., & Karatolios, K. (2021). Early impella support in postcardiac arrest cardiogenic shock complicating acute myocardial infarction improves short- and long-term survival. Critical Care Medicine, Publish Ahead of Print. https://doi.org/10.1097/ccm.0000000000004915

Preoperative leukocytes, CRP, PCT, bilirubin, ALT, and LD were all significantly higher in INTERMACS 1-2 when compared to controls. These markers did not further deteriorate within the first week after the procedure, except for WBC and CRP, which can be interpreted as a general response to perioperative stress. Previous studies have demonstrated that markers of organ function usually decrease by the end of the first year following device implantation, suggesting that the recovery of organ function is possible.

Based on the present data with increased morbidity and mortality in advanced disease, the authors emphasized timely implantation of LVADs. The current trend tends to the LVADs implantation in INTERMACS 1. According to them, the procedure should be considered in selected INTERMACS 1-2 patients, in all INTERMACS 3 patients, and in severely symptomatic and motivated INTERMACS 4-7 patients. They also stressed that the decision is complex and should involve the whole clinical picture. An early referral for evaluation in an LVAD or transplant center is, therefore, essential. An alternative strategy may include ECMO as a bridge to the next therapy, possibly with an Impella, to facilitate the transition from ECMO to LVAD.

Zhigalov, K., Van den Eynde, J., Chrosch, T., Goerdt, L., Sá, M. P., Zubarevich, A., Papathanasiou, M., Wendt, D., Luedike, P., Pizanis, N., Koch, A., Schmack, B., Rassaf, T., Kamler, M., Ruhparwar, A., & Weymann, A. (2021). Outcomes of left ventricular assist device implantation for advanced heart failure in critically ill patients (INTERMACS 1 and 2): A retrospective study. Artificial Organs, 45(7), 706–716. https://doi.org/10.1111/aor.13897

Since the profile of the hemodynamic effect on multiple variables (LVEDV, ventricular stroke work – SW, LAP, MPAP, cardiac output – CO) differed significantly between the strategies, the authors argue that in the real clinical practice it will need to be chosen based on individual patient characteristics and disease etiology. They also acknowledged that more factors than a pure effect on hemodynamics need to be considered, e.g. necessity for surgical cut-downs. On the other hand, nonsurgical vents can be placed, but these are limited in size, which may affect unloading efficacy. Thirdly, implanting a VAD is a method of choice in many centers as it is relatively easy to use. In the present study, the VAD demonstrated a reduction in SW from baseline 0.143 W to between 0.065 W at 1 L/min ECMO flow to 0.078 W at 4 L/min ECMO flow. Efficacy of the VAD at unloading LVEDV and MPAP decreased as ECMO flow was increased, due to the increasing pressure head across the VAD caused by the ECMO outflow. Conversely, the intra-aortic balloon pump (IABP) improved CO slightly compared with no unloading technique (1.1 compared with 1.0 L/min) but was the least effective at reducing LVEDV, MPAP, LAP, and SW.

Stephens, A. F., Wanigasekara, D., Pellegrino, V. A., Burrell, A. J. C., Marasco, S. F., Kaye, D. M., Steinseifer, U., & Gregory, S. D. (2020). Comparison of circulatory unloading techniques for venoarterial extracorporeal membrane oxygenation. ASAIO Journal, 67(6), 623–631. https://doi.org/10.1097/mat.0000000000001268

02 / 2022

The use of venoarterial-extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock (CS) is limited by a high complication rate frequently related to deep sedation and mechanical ventilation (MV). A group of predominantly Spanish authors evaluated the impact of an ‘awake’ (invasive MV used during ≤50% of the time) vs. ‘non-awake’ VA-ECMO in this clinical setting. They retrospectively searched a 7-year single-center database and performed a propensity-score-matched analysis on a total of 231 patients (39 % ‘awake’). Those who were ‘awake’ had significantly lower rates of pneumonia (35% vs. 59%, P = 0.017), tracheostomy, renal replacement therapy, less antibiotic and sedative consumption and reduced 60-day (20% vs. 41%, P = 0.018) and 1-year mortality rates (31% vs. 54%, P = 0.021). Lastly, MV at ECMO cannulation was the most significant independent factor associated with 60-day mortality.

Based on the previous data, not being intubated at cannulation is a determinant for remaining awake later. The authors of the present study, therefore, recommended a trial of alternative management of respiratory insufficiency (high-flow oxygen, non-invasive ventilation), if clinically possible. In intubated patients, the earliest possible extubation after VA-ECMO implantation should be considered, since the reported data show that the impact of ‘awake’ ECMO management on outcome occurred early and the survival differences among groups remained steady later. Although extubation of patients under ECMO is not a standard practice in most centers, the Extracorporeal Life Support Organization guidelines suggest the ‘awake ECMO’ strategy as one of the possible alternatives. The investigators also stressed additional benefits of the awake status, such as physical rehabilitation, oral feeding, communication with relatives, and interactive information about the medical decision. In their opinion, factors including avoidance of VAP, immobilization, cardiac arrest at anesthetic induction and prompt detection of ECMO-related complications (e.g. stroke, limb ischemia) may also contribute to better survival rates and overall outcome.
Montero, S., Huang, F., Rivas-Lasarte, M., Chommeloux, J., Demondion, P., Bréchot, N., Hékimian, G., Franchineau, G., Persichini, R., Luyt, C.-É., Garcia-Garcia, C., Bayes-Genis, A., Lebreton, G., Cinca, J., Leprince, P., Combes, A., Alvarez-Garcia, J., & Schmidt, M. (2021). Awake venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock. European Heart Journal. Acute Cardiovascular Care, 10(6), 585–594. https://doi.org/10.1093/ehjacc/zuab018

Although prone positioning (PP) improves oxygenation and respiratory mechanics in acute respiratory distress syndrome (ARDS), some patients develop refractory hypoxemia and hypercapnia requiring venovenous ECMO (VV-ECMO) support and are usually cared for in a supine position. Since the impact of PP in this setting remains unclear, a group of Singaporean investigators conducted a systematic review and meta-analysis of a total of 11 studies on 640 subjects. Cumulative survival (primary outcome) in patients that underwent PP was 57% (95% CI 41.9–71.4, high certainty). Patients who were not treated with PP during VV-ECMO had a statistically non-significant lower pooled survival of 47% (95% CI 33.4–61.8). Those that underwent PP demonstrated longer ICU lenght of stay (+ 14.5 days, 95% CI 3.4–25.7, p = 0.01) and ECMO duration (+ 9.6 days, 95% CI 5.5–13.7, p < 0.0001) as compared with controls. After PP, patients had a significantly higher PaO2/FiO2 ratio, lower PaCO2, and reduced ventilator driving pressure. No major complications of PP were reported.

 

The authors noted that while gas exchange indices and driving pressure improved from PP during ECMO, other respiratory mechanics including compliance or plateau pressure did not significantly change. The limitation of this conclusion is, however, that only a few of the included studies comprehensively reported these parameters. Based on their opinion, improved oxygenation may have resulted from more efficient ventilation: perfusion matching upon PP, but in the absence of randomized controlled trials, it is difficult to conclusively determine if PP during VV ECMO has meaningful benefit. Therefore, the present meta-analysis should be considered hypothesis-generating. The authors also admitted that the patients subjected to PP during ECMO were sicker, which explains the need for the intervention, as well as the longer duration of ECMO. Alternatively, given the immortal time bias associated with interventions like ECMO, it is also plausible that sicker patients could have died earlier and thus did not undergo prone positioning, thereby accounting for the higher mortality.

Poon, W. H., Ramanathan, K., Ling, R. R., Yang, I. X., Tan, C. S., Schmidt, M., & Shekar, K. (2021). Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: A systematic review and meta-analysis. Critical Care, 25(1). https://doi.org/10.1186/s13054-021-03723-1

Mechanical circulatory support (MCS) with either ECMO or Impella is increasingly used in refractory out-of-hospital cardiac arrest (OHCA). The Danish retrospective, observational cohort study monitored gradual implementation, survival, and adherence to the national consensus, as well as factors associated with an outcome between years 2011 and 2020. In a total of 259 patients, 30-day survival was 26% and 25% survived until hospital discharge. Good neurological outcome (Glasgow–Pittsburgh Cerebral Performance Categories 1–2) was observed in 94% of these patients. The factors associated with increased risk of 30-day mortality were asystole (RR 1.36), pulseless electrical activity (RR 1.20), initial pH < 6.8 (RR 1.28), and lactate levels > 15 mmol/L (RR 1.16). Conversely, signs of life during CPR were a positive prognostic factor (RR 0.63). Strict adherence to the national consensus showed a 30-day survival rate of 30% vs. 22% in patients violating one or more criteria. Expanding additional criteria increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort.

 

The authors concluded that one in four MCS patients survived until hospital discharge with a good neurological outcome. However, they warned that by offering MCS only to patients meeting the strictest criteria, life-saving treatment would be withheld in the majority of subjects who were saved in this cohort. Therefore, stringent selection should not be appropriate in such a salvage setting.

Mørk, S. R., Stengaard, C., Linde, L., Møller, J. E., Jensen, L. O., Schmidt, H., Riber, L. P., Andreasen, J. B., Thomassen, S. A., Laugesen, H., Freeman, P. M., Christensen, S., Greisen, J. R., Tang, M., Møller-Sørensen, P. H., Holmvang, L., Gregers, E., Kjaergaard, J., Hassager, C., Terkelsen, C. J. (2021). Mechanical circulatory support for refractory out-of-hospital cardiac arrest: A Danish nationwide Multicenter Study. Critical Care, 25(1). https://doi.org/10.1186/s13054-021-03606-5

For ECMO, a certain level of anticoagulation is necessary, however, it needs to be carefully balanced with a risk of bleeding. A group of French investigators evaluated the association between anti-Xa activity and hemorrhagic events in a retrospective multicenter cohort study. Out of 121 adult patients treated with VV-ECMO or VA-ECMO, 29% experienced a hemorrhagic event. Additionally, anti-Xa activities were significantly higher in the bleeding group than in the non-bleeders, both for the mean (0.38 [0.29–0.67] vs 0.33 [0.22–0.42] IU/mL; p = 0.01) and the maximal value (0.83 [0.47–1.46] vs 0.66 [0.36–0.91] IU/mL; p = 0.05). Moreover, the probability of survival under ECMO without bleeding was significantly lower when the mean anti-Xa was > 0.46 IU/mL (p = 0.0006). Mean anti-Xa activity was an independent risk factor for hemorrhagic complications.

 

Based on the present data, the authors suggested a revision of the anticoagulation goals, especially in the VA-ECMO setting. While in the VV-ECMO patients, the mean anti-Xa activity was in the range from 0.2 to 0.4 IU/mL, lower than the critical value of 0.46 IU/mL and well within the recommended thresholds, in the VA-ECMO, anti-Xa targets are usually 0.3 and 0.7 IU/mL and predominantly above the critical value. Unfortunately, the literature regarding systemic anticoagulation in nonsurgical VA-ECMO patients is poor. However, for both VV and VA-ECMO, downgrading anticoagulation targets should be done with caution, as even in this study the mean anti-Xa was significantly lower in patients with thrombotic events.

Descamps, R., Moussa, M. D., Besnier, E., Fischer, M.-O., Preau, S., Tamion, F., Daubin, C., Cousin, N., Vincentelli, A., Goutay, J., & Du Cheyron, D. (2021). Anti-xa activity and hemorrhagic events under Extracorporeal Membrane Oxygenation (ECMO): A Multicenter Cohort Study. Critical Care, 25(1). https://doi.org/10.1186/s13054-021-03554-0

Based on the previous data, not being intubated at cannulation is a determinant for remaining awake later. The authors of the present study, therefore, recommended a trial of alternative management of respiratory insufficiency (high-flow oxygen, non-invasive ventilation), if clinically possible. In intubated patients, the earliest possible extubation after VA-ECMO implantation should be considered, since the reported data show that the impact of ‘awake’ ECMO management on outcome occurred early and the survival differences among groups remained steady later. Although extubation of patients under ECMO is not a standard practice in most centers, the Extracorporeal Life Support Organization guidelines suggest the ‘awake ECMO’ strategy as one of the possible alternatives. The investigators also stressed additional benefits of the awake status, such as physical rehabilitation, oral feeding, communication with relatives, and interactive information about the medical decision. In their opinion, factors including avoidance of VAP, immobilization, cardiac arrest at anesthetic induction and prompt detection of ECMO-related complications (e.g. stroke, limb ischemia) may also contribute to better survival rates and overall outcome.
Montero, S., Huang, F., Rivas-Lasarte, M., Chommeloux, J., Demondion, P., Bréchot, N., Hékimian, G., Franchineau, G., Persichini, R., Luyt, C.-É., Garcia-Garcia, C., Bayes-Genis, A., Lebreton, G., Cinca, J., Leprince, P., Combes, A., Alvarez-Garcia, J., & Schmidt, M. (2021). Awake venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock. European Heart Journal. Acute Cardiovascular Care, 10(6), 585–594. https://doi.org/10.1093/ehjacc/zuab018

It is not clear whether a choice between single- (SL) vs. double-lumen (DL) catheters for VV-ECMO impacts the risk of neurological complications. Based on a recent ELSO registry retrospective observational study it does not. A total of 6245 adult patients were included in the propensity score-matched analysis. The proportion of patients with at least one neurological complication was similar in the SL and DL group (7.2 vs. 7.7%; odds ratio 1.10 [95% confidence intervals 0.91–1.32]; p = 0.33) and so was an occurrence of specific neurological complications, including intracerebral hemorrhage, acute ischemic stroke, seizures or brain death. Moreover, in a subgroup of subjects who experienced a neurological event, overall mortality was comparable.

 

Advantages of a DL strategy include easier ambulation and reduced recirculation, as well as the need for only one venous access to provide full ECMO support. However, DL cannulas are significantly larger and it is unclear whether large cannulas can be safely accommodated in the internal jugular veins without affecting cerebral blood flow dynamics. The authors of the present study noted that the pathophysiology of neurologic injury during VV-ECMO is multifactorial and relates to frequent changes in PaO2 and PCO2, formation of cerebral micro-emboli, and venous congestion from cannulation of the internal jugular veins. Abrupt changes in local and systemic blood pressure, ischemia/reperfusion, anticoagulation, and venous hypertension caused by distal internal vein ligation also play a contributory role. It is difficult to cover such a complex issue in a retrospective study. Several other limitations mostly related to the lack of specific information and comprehensive neurologic monitoring within the limited registry data were identified. To further confirm the findings of this study, preferably a randomized controlled trial should be, therefore, performed.

Lorusso, R., Belliato, M., Mazzeffi, M., Di Mauro, M., Taccone, F. S., Parise, O., Albanawi, A., Nandwani, V., McCarthy, P., Kon, Z., Menaker, J., Johnson, D. M., Gelsomino, S., & Herr, D. (2021). Neurological complications during veno-venous extracorporeal membrane oxygenation: Does the configuration matter? A retrospective analysis of the Elso Database. Critical Care, 25(1). https://doi.org/10.1186/s13054-021-03533-5

The timing of enteral feeding in the critically ill is still controversial and there is not enough data for its initiation after OHCA and extracorporeal cardiopulmonary resuscitation (ECPR). Investigators from the University of Minnesota performed a retrospective non-randomized analysis of 142 patients with OHCA and ECPR after ventricular fibrillation or tachycardia, who were also treated by targeted temperature management. Enteral nutrition was initiated in 63% of the group, out of which 38% received early (commenced <48 h after admission) and 62% delayed feeding (>48 h, mean of 79.2 h). There were no significant differences in baseline characteristics of both groups. Delayed enteral feeding was associated with increased odds of neurologically favorable survival (29 vs. 54%, CI 1.04−7.25, p = 0.04). Rates of pneumonia, gastrointestinal bleeding, intestinal ischemia, ileus, or need for tracheostomy were comparable.

 

Nutrition support was well tolerated in the refractory cardiac arrest population with low rates of feeding-related adverse events, regardless of the timing of feeding initiation. The authors argued that the difference in neurologically favorable survival might be driven by secretion of vasoactive hormones in the small intestine after the feed, which may lead to redistribution of the cardiac output and potentially decrease brain perfusion. They also considered metabolic differences, e.g. increased serum glucose after the feed, however, all patients received adjusted insulin drip. The third reason they mentioned was delayed gastric emptying and potential gut dysmotility while therapeutically hypothermic, which might increase the risk of gut ischemia, aspiration, and pneumonia. Therefore, outcomes may improve if feeding begins after the patient is euthermic. To further test this hypothesis, ideally, a randomized clinical trial should be performed.

Gutierrez, A., Carlson, C., Kalra, R., Elliott, A. M., Yannopoulos, D., & Bartos, J. A. (2021). Outcomes associated with delayed enteral feeding after cardiac arrest treated with veno-arterial extracorporeal membrane oxygenation and targeted temperature management. Resuscitation, 164, 20–26. https://doi.org/10.1016/j.resuscitation.2021.04.029

The use of venoarterial-extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock (CS) is limited by a high complication rate frequently related to deep sedation and mechanical ventilation (MV). A group of predominantly Spanish authors evaluated the impact of an ‘awake’ (invasive MV used during ≤50% of the time) vs. ‘non-awake’ VA-ECMO in this clinical setting. They retrospectively searched a 7-year single-center database and performed a propensity-score-matched analysis on a total of 231 patients (39 % ‘awake’). Those who were ‘awake’ had significantly lower rates of pneumonia (35% vs. 59%, P = 0.017), tracheostomy, renal replacement therapy, less antibiotic and sedative consumption and reduced 60-day (20% vs. 41%, P = 0.018) and 1-year mortality rates (31% vs. 54%, P = 0.021). Lastly, MV at ECMO cannulation was the most significant independent factor associated with 60-day mortality.

Based on the previous data, not being intubated at cannulation is a determinant for remaining awake later. The authors of the present study, therefore, recommended a trial of alternative management of respiratory insufficiency (high-flow oxygen, non-invasive ventilation), if clinically possible. In intubated patients, the earliest possible extubation after VA-ECMO implantation should be considered, since the reported data show that the impact of ‘awake’ ECMO management on outcome occurred early and the survival differences among groups remained steady later. Although extubation of patients under ECMO is not a standard practice in most centers, the Extracorporeal Life Support Organization guidelines suggest the ‘awake ECMO’ strategy as one of the possible alternatives. The investigators also stressed additional benefits of the awake status, such as physical rehabilitation, oral feeding, communication with relatives, and interactive information about the medical decision. In their opinion, factors including avoidance of VAP, immobilization, cardiac arrest at anesthetic induction and prompt detection of ECMO-related complications (e.g. stroke, limb ischemia) may also contribute to better survival rates and overall outcome.
Montero, S., Huang, F., Rivas-Lasarte, M., Chommeloux, J., Demondion, P., Bréchot, N., Hékimian, G., Franchineau, G., Persichini, R., Luyt, C.-É., Garcia-Garcia, C., Bayes-Genis, A., Lebreton, G., Cinca, J., Leprince, P., Combes, A., Alvarez-Garcia, J., & Schmidt, M. (2021). Awake venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock. European Heart Journal. Acute Cardiovascular Care, 10(6), 585–594. https://doi.org/10.1093/ehjacc/zuab018

One of the main limitations of VA-ECMO is an overload of the left ventricle and subsequent pulmonary congestion. Several unloading techniques exist, including surgical and percutaneous pulmonary artery (PA) venting, surgical left atrial venting, surgical and percutaneous LV venting, atrial septal defect, partial support ventricular assist device, intraaortic balloon pump, and temporary ventricular assist device (VAD) with inline oxygenator (tVAD). A Group of Australian investigators compared those strategies on a mock circulatory loop simulating acute LV failure supported by ECMO. The most robust unloading effect was seen with the surgically placed LV vent and tVAD, which reduced LV end-diastolic volume (LVEDV) from 295 to 167 ml and 82 ml, respectively. Regarding the reduction of the mean PA pressure (MPAP), the most effective procedure was PA surgical vent (from 21.0 to 10.6 mm Hg), and for the reduction of left atrial pressure (LAP), the most effective was tVAD (from 13.3 to 4.4 mm Hg).

 

Since the profile of the hemodynamic effect on multiple variables (LVEDV, ventricular stroke work – SW, LAP, MPAP, cardiac output – CO) differed significantly between the strategies, the authors argue that in the real clinical practice it will need to be chosen based on individual patient characteristics and disease etiology. They also acknowledged that more factors than a pure effect on hemodynamics need to be considered, e.g. necessity for surgical cut-downs. On the other hand, nonsurgical vents can be placed, but these are limited in size, which may affect unloading efficacy. Thirdly, implanting a VAD is a method of choice in many centers as it is relatively easy to use. In the present study, the VAD demonstrated a reduction in SW from baseline 0.143 W to between 0.065 W at 1 L/min ECMO flow to 0.078 W at 4 L/min ECMO flow. Efficacy of the VAD at unloading LVEDV and MPAP decreased as ECMO flow was increased, due to the increasing pressure head across the VAD caused by the ECMO outflow. Conversely, the intra-aortic balloon pump (IABP) improved CO slightly compared with no unloading technique (1.1 compared with 1.0 L/min) but was the least effective at reducing LVEDV, MPAP, LAP, and SW.

Stephens, A. F., Wanigasekara, D., Pellegrino, V. A., Burrell, A. J. C., Marasco, S. F., Kaye, D. M., Steinseifer, U., & Gregory, S. D. (2020). Comparison of circulatory unloading techniques for venoarterial extracorporeal membrane oxygenation. ASAIO Journal, 67(6), 623–631. https://doi.org/10.1097/mat.0000000000001268

02 / 2019

General survival of patients managed by veno-arterial ECMO (VA-ECMO) is as low as 30%. Due to the very high resource utilization, there is a growing need for a reliable model for identifying patients with favorable or alternatively poor prognosis. Several scoring systems have been introduced in the past, including the ENCOURAGE or the SAVE score, but are mostly relying on baseline clinical data at the time of cannulation and were not validated for extracorporeal cardiopulmonary resuscitation patients. A more flexible and dynamic prognostic model is needed. An international group of investigators, therefore, suggested and validated the point-of-care biomarker-based PREDICT VA-ECMO score, that can be used during the post-implantation period and can aid in the difficult decision making to either continue or withdraw care. PREDICT VA-ECMO is based on lactate, pH and bicarbonate concentrations only.
 
A derivation cohort included a total of 205 subjects, 51% received VA-ECMO during resuscitation and 43% had a severe shock. Two prediction models based on point-of-care biomarkers were developed using penalized logistic regression in an elastic net approach. SAVE, SAPS, SOFA and APACHE scores were recorded for comparison for the prediction of hospital survival. PREDICT VA-ECMO was superior to all comparators regarding the area under the receiver operation characteristic curve (AUC) in both 6 and 12 hours of survival. Performance of the scores in the external validation cohort was also encouraging.

The PREDICT VA-ECMO score was designed to reflect the current effectiveness of organ perfusion by VA-ECMO regardless of initial indication or baseline parameters. It’s easy-to-calculate nature is suitable for acute emergency situations. The authors commented, that interestingly, adding age and gender to the model did not improve further prognostication, suggesting that, during this most critical, first phase of VA-ECMO therapy, perfusion parameters may be more important than underlying clinical characteristics. The limitation of the score is a lack of its information for neuroprognostication, which according to the guidelines, should be provided after cardiac arrest until 72 hours after the collapse and cannot be replaced by any clinical score designed for the other purposes.

Source: https://journals.sagepub.com/doi/abs/10.1177/2048872618789052?rfr_dat=cr_pub%3Dpubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&journalCode=acca 

Dual-lumen veno-venous ECMO cannulas (DLC) demonstrated an advantage of easier ambulation for patients, lower sedation levels and earlier extubation in comparison with a conventional two site cannulation (usually 19-23 French cannulas in adults). The risks, on the other site, include bleeding considered as, intracranial hemorrhage (ICH), migration to the right ventricle and right ventricular rupture and are mostly related to the large cannulae size. ICH during ECMO occurs in around 7 % of patients with DLC according to the previous literature and is caused by thrombocytopenia, anticoagulation and possibly intracranial venous hypertension from obstruction of the internal jugular vein and superior vena cava by the ECMO cannula or a deep venous thrombus. Although 31 French dual-lumen cannula enables greater blood flow with better oxygenation, according to a recent retrospective cohort study from the ELSO registry it also poses a greater risk of ICH when compared with a 27 French equivalent. The outcome of an ICH in ECMO patients (with DLC) is critical – one-month mortality after the event reaches 81 %.

This study used a retrospective propensity score matching within the ELSO database cohort (n=744). Patients with a 31 French DLC had an ICH rate of 4.3% compared with 1.6% in patients cannulated with a 27 French DLC (p = 0.03). There was no difference in mortality, hemolysis or cannula complications and, thus, smaller cannulas may be preferable when feasible. Maximal blood flow achievable by 27 French DLC is 4,5L/min, by 31 French up to 6L/min. Authors of the study, therefore, hypothesized that a 31 French DLC offers a theoretical advantage in patients with severely impaired oxygenation. However, there was no statistical difference between the groups regarding ECMO blood flow at 4 and 24 hours suggesting that optimal flow can be achieved with either cannula in most patients.

The limitations of the study included observational design, pooled data from multiple centers and lack of data regarding the quality of life and functional outcome after decannulation. Although propensity score matching was performed, residual confounding cannot be ruled out. The incidence of ICH in the cohort study was rather low in comparison with overall literature and ICH might have been underdiagnosed within the registry patients.

Source: https://journals.lww.com/asaiojournal/Abstract/2019/09000/Large_Dual_Lumen_Extracorporeal_Membrane.9.aspx

ECMO is used in patients with the most severe conditions and is, therefore, accompanied by difficult decision making and profound ethical considerations. In a recent electronic, cross-sectional, scenario-based survey, 539 senior physicians from 39 countries across six continents were questioned about their daily clinical practice and attitudes toward the initiation, limitation, and withdrawal of venovenous ECMO (VV-ECMO) for severe respiratory failure. The survey stressed the situation of ECMO-dependent patients, who are unlikely to be transitioned from ECMO to conventional mechanical ventilation and are not eligible for transplant. In these scenarios, ECMO support has been referred to as a “bridge to nowhere”.

There was no significant difference in respondent’s age, years of experience, or center characteristics between those who would or would not initiate ECMO. As a factor contributing to the decision not to cannulate for ECMO, most physicians mentioned older patient age (46.9%), additional organ failures (37.7%), and prolonged mechanical ventilation (35.1%). Factors influencing the decision to withdraw from ECMO were patient comorbidities (70.5%), patient’s wishes (56.0%), and etiology of respiratory failure (37.7%). Although the decision process was shared with another physician in a vast majority of cases (90.5%), only 53.2%, 45.3%, and 29.5% of respondents involved surrogates, awake patients, or bedside nurses. 15% of respondents also rarely or never discussed the possibility of ECMO withdrawal with the patient or surrogate at the time of ECMO initiation.

Authors commented that this low involvement of patients and their loved-ones into shared decision making may pose a significant ethical hazard and a need for a better education and communication was identified. Furthermore, the existence of a hospital mechanism to enable making medical decisions against patients or surrogate’s wishes was reported by over half of the physicians, however, details about its invocation in a real practice remain unclear. In the present survey, some respondents were more likely to not to escalate rather than withdraw treatment in this clinical setting.

Source: https://journals.lww.com/ccmjournal/Abstract/2019/10000/Practice_Patterns_and_Ethical_Considerations_in.9.aspx

Acute respiratory distress syndrome (ARDS) is a common reason for ICU hospitalization with acute mortality of 35-46%. The cornerstone of ARDS management is lung by higher levels of positive end-expiratory pressure (PEEP). Lung recruitment maneuvers (LRM) during mechanical ventilation are still controversial. The effect of PEEP and LRM is variable and dependent on the potential for lung recruitment (PLR), which might guide the ventilatory strategy. The situation is more complicated in patients with ARDS managed by ECMO. The data in this clinical setting are limited. An aim of a single-center, retrospective, observational cohort study of the British authors was to investigate the pattern of lung recruitability of patients with severe ARDS requiring ECMO.

47 patients with severe ARDS mainly of pulmonary origin (86%) on ECMO were included in the study. PLR and the weight of nonaerated, poorly aerated, normally aerated, and hyperaerated lung tissue was assessed at low (5 cmH2O) and high (45 cmH2O) airway pressures. Patients were classified into the high or low PLR group based on the median potential for lung recruitment value of the study population. The percentage of potentially recruitable lung was defined as the proportion of the total lung weight accounted for by nonaerated lung tissue in which aeration was restored, according to CT, by an airway pressure of 45 cmH2O from an airway pressure of 5 cmH2O. To evaluate difference in pre-ECMO clinical and demographical variables and differences in outcomes, patients were subdivided into two PLR categories with a group with PLR below the median (PLRlow) and a group with PLR above the median (PLRhigh). The median PLR was relatively high (24.3%, interquartile range = 11.4–37%) with a large variation ranging from –2% to 76.3% of the total lung weight. Subjects with above the median PLR demonstrated shorter ECMO duration (8 vs 13 d; p = 0.013) and shorter ICU stay (15 vs 22 d; p = 0.028), mortality was not statistically different (24% vs 46%; p = 0.159).

Although PLR increases with total lung weight, that is, with ARDS severity, a higher PLR in this study was associated with a better prognosis even when recruitment was not attempted and mechanical ventilation was not adapted to the degree of PLR due to absence of clear data guiding mechanical ventilation during ECMO and observational nature of the study. All patients were ventilated with standard settings regardless of PLR and the authors commented that it is difficult to say whether patients with higher PLR would have benefitted from a more aggressive lung recruitment or higher PEEP levels.

Source: https://journals.lww.com/ccmjournal/Fulltext/2019/09000/Lung_Recruitability_in_Severe_Acute_Respiratory.2.aspx

ECMO is turning from an experimental to a well-established method in critical care and the first long-term outcome data are becoming available. Cognitive function of 38 patients treated with ECMO for respiratory failure between the years 1995 and 2009 was investigated in a recent Swedish single-center retrospective cohort study, assessing a combination of brain imaging, neurocognitive testing, and interview. Originally, 73 eligible patients were identified, but 23 died after discharge and 19 were lost to follow-up. The likely limitation of the study is, therefore, selection bias.

Besides the usual ICU impact on neurological function, the use of ECMO adds an extra burden of altered coagulation, hemodynamics, and risk of prolonged hospitalization and immobilization. Many patients with respiratory failure on ECMO are subjected to permissive hypoxemia (defined as a median peripheral saturation of less than 93% during the observation period) in order to protect them from ventilator-induced lung injury as per ELSO guidelines. The safety of permissive hypoxemia has been questioned due to the risk of cognitive dysfunction. The authors of the present study, however, hypothesized that it is unlikely for irreversible hypoxic cerebral dysfunction to occur when hypoxemia is present with preserved sufficient oxygen delivery to the brain. Indeed, the original treatment protocol was designed in order to compensate for a reduction in oxygen saturation by increasing the ECMO flow.

Median follow-up time was 9.0 years after treatment. Median full-scale intelligence quotient, memory index, and executive index were 97, 101, and 104, respectively (normal, 100±15) and cognitive function was not reduced in the group which experienced prolonged hypoxemia. There was no overall significant difference between patients who received veno-venous (VV-ECMO) and veno-arterial (VA-ECMO) treatment, however, in VA-ECMO group, brain imaging showed cerebrovascular lesions more often (64% in VA-ECMO, 26% in VV-ECMO). In patients with cerebrovascular lesions, memory function and executive function were significantly reduced. Permissive hypoxemia was not correlated with long-term cognitive dysfunction. Return to work or school occurred in half of the cohort within one year after discharge. The authors concluded that patients treated with ECMO for respiratory failure may have normal cognitive function years after treatment, if not affected by cerebrovascular lesions.

Source: https://journals.lww.com/ccmjournal/Abstract/2018/05000/Long_Term_Cognitive_Outcome_and_Brain_Imaging_in.36.aspx

Early revascularization remains standard treatment of acute myocardial infarction complicated by cardiogenic shock (AMI-CS) . Medical therapies such as inotropes failed to improve outcomes. The comparison of the intra-aortic balloon pump (IABP), and best medical care, was published in IABP-SHOCK II clinical trial in 2012 and showed no survival benefit. The need for an improved device design is, therefore, prudent and great expectations were put on Impella device, a catheter-based micro-axial flow pump. The group of European investigators built a multi-national database of AMI-CS cases treated with an Impella device in order to compare the outcome to patients from the IABP-SHOCK II trial in a matched fashion. 237 patients with cardiogenic shock (definition in accordance with IABP-SHOCK II trial, systolic blood pressure below 90 mm Hg or need of inotropes, and clinical signs of pulmonary congestion, and signs of impaired end-organ perfusion12) complicating acute myocardial infarction (either ST-segment–elevation myocardial infarction or non–ST-segment–elevation myocardial infarction) who were treated with an Impella device and who underwent early revascularization were matched to 237 subjects from the IABP-SHOCK II cohort. All patients underwent early revascularization and received optimal medical treatment per current guidelines.
There was no significant difference regarding the primary outcome of 30-day all-cause mortality when Impella was compared with IABP or best medical treatment (48.5% vs. 46.4%, p=0.64), but the incidence of adverse events was higher in the Impella group (severe or life-threatening bleeding 8.5% vs. 3.0%, p<0.01, peripheral vascular complications 9.8% vs. 3.8%, p=0.01.) The increase in peripheral vascular and bleeding complications might be related to the larger lumen of the vascular access needed for the Impella devices – the Impella 2.5 and CP are placed via 12 and 14 French sheaths, respectively, as compared to the 7-8 French sheath or sheath-less insertion for the IABP device. There were no increased risks for stroke, re-infarction and stent thrombosis in the Impella group. The analysis is limited to IABP-treated patients as a control group, but itdid not change the results.

In this retrospective analysis of patients with AMI-CS, the use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy. The limitation of the present study is its population in profound CS and inclusion of a large proportion of post-resuscitation cases with a poor prognosis. Also, according to recent evidence, early Impella implantation seems superior to later intervention, however, this effect was not observed in the present analysis. Prospective, randomized clinical trial, preferably with an early Impella implantation, is, therefore, warranted.

Source: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.036614

Heparin-induced thrombocytopenia (HIT) is caused by antibodies binding to the complex of heparin and platelet factor and typically occurs four days after heparin administration. Without immediate discontinuation, almost half of the patients develop thrombosis and the mortality rate increases to 30%. According to previous literature, the prevalence of HIT while on ECMO is approximately 8%. Change to an alternative of systemic heparin is paramount, data on a continuation of using heparin-bonded ECMO circuit after HIT diagnosis are limited. In a recent retrospective single-center analysis published in Perfusion, further use of a heparin-bonded ECMO system did not lead to adverse clinical outcomes.

Out of 455 patients who underwent ECMO during a nine-year period, 3,1% tested positive on HIT. Highly specific serotonin release assay was used because the cause for thrombocytopenia in ECMO patients could be the ECMO system itself. Systemic heparin was discontinued and heparin-bonded ECMO circuit maintained in all 14 subjects. 78,6% survived to discharge which did not significantly differ from the rest of the study population. Mean platelet count increased from 59.8k/µL at the time of HIT diagnosis to 280.2k/µL 14 days after heparin discontinuation, when it did not differ from the rest of the cohort. There was no decrease in platelet count after systemic heparin discontinuation. Platelet count further increased after decannulation from ECMO device and it is difficult to evaluate if that happened because of the general negative ECMO effect on platelet count or discontinuation of exposure to the heparin-bonded circuit. Out of 14 patients with HIT, 3 died during hospitalization (two due to multiorgan failure, one due to intracranial hemorrhage).

Authors pointed out that so far, there is no existing data proving if heparin, chemically bonded to the ECMO system, affects the generation of HIT antibodies. The bonded heparin is biologically inactive and has almost no anti-factor Xa activity. However, small parts of the heparin can leak out and eventually become biologically active. The present study did not show any signals of a detrimential effect of keeping HIT patients on heparin-bonded circuit though. The appropriate management of HIT while on ECMO is, therefore, immediate discontinuation of systemic heparin, but the continuation of heparin-coated extracorporeal membrane oxygenation circuits appears to be safe. Larger prospective trials will be needed to confirm that.

Source: https://journals.sagepub.com/doi/full/10.1177/0267659119842056

Systemic anticoagulation mostly with unfractionated heparin is necessary to prevent thrombosis during ECMO. Titration and monitoring of an anticoagulation therapy are challenging due to the combined impact of the underlying disease (e.g. sepsis), the drug and circuit effects. Thromboelastography (TEG) is widely used in the setting of major hemorrhage management. Adaptation of those methods for the monitoring of systemic anticoagulation therapy during ECMO was evaluated in the multicenter pilot trial in comparison with an activated partial thromboplastin time (aPTT). A total of 42 patients with acute respiratory failure and veno-venous ECMO were randomized either to TEG (target 16–24 min of the R parameter) or aPTT-based protocol (target 1.5–2 of aPTT ratio.)

Heparin dosing was lower in the TEG group compared to the aPTT group (11.7 (9.5–15.3) IU/kg/h vs. 15.7 (10.9–21.3) IU/kg/h, respectively, p = 0.03) and the TEG group experienced a lower incidence of bleeding from surgical sites. Otherwise, the two groups did not significantly differ neither in a number of hemorrhagic or thrombotic events and transfusions given nor in the duration of ECMO. The TEG-based protocol triggered heparin infusion rate adjustments more frequently (p < 0.01) and results were less frequently in the target range compared to the aPTT-based protocol (p < 0.001). One of the major concerns of using a low level of anticoagulation during ECMO is the development of consumptive coagulopathy. Since the D-dimer levels were comparable in the two groups, this was not of a concern in the present study.

aPTT is a standard hemostatic profile used to monitor heparin treatment. It is performed on plasma samples in an absence of the cellular components and may not, therefore, provide a realistic picture of the in vivo hemostatic capacity. TEG is a whole blood point-of-care assay, that reflects the state of the entire coagulation cascade. The TEG-based protocol was safe and feasible and resulted in lower consumption of heparin with a statistically insignificant trend towards the reduction of bleeding events. However, the use of TEG-based protocol also resulted in a higher cost compared to the aPTT-based one.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770349/

01 / 2019

Refractory cardiogenic shock can occur after cardiac surgery, as an exacerbation of chronic heart failure with reduced ejection fraction, or from de novo heart failure, most commonly caused by acute coronary syndromes. V-A ECMO might be a game-changer in support of patients in such conditions. Despite being able to offer blood flow of more than 5 L/min of oxygenated blood, VA-ECMO can cause some adverse effects as increased afterload, LV dilation, myocardial ischemia, elevated pulmonary pressures and blood stasis with consecutive thrombus formation. A team of researchers from Ohio, USA, reviewed concomitant use of percutaneous left ventricular decompression with Impella Pump. The largest US-based retrospective study included data collected between 2014 and 2016. Two cohorts of patients were compared – V-A ECMO supported cohort  (n = 36) and ECPELLA cohort supported with a combination of V-A ECMO and Impella (n = 30). The primary outcome was all-cause mortality within 30 days of V-A ECMO implantation. Patients in the ECPELLA cohort experienced a higher incidence of ST-elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI), otherwise, the baseline characteristics were similar.

Thirty-day all-cause mortality was significantly lower in the ECPELLA cohort (57% vs. 78%; hazard ratio [HR] 0.51 [0.28–0.94], log rank p = 0.02), and this difference remained intact after correcting for STEMI and PCI. The secondary outcomes, including duration of support, stroke, major bleeding, hemolysis, and cardiac recovery, were comparable between the cohorts. The only difference was found in an inotropic score, which was greater in the V-A ECMO group by day 2 (11 vs. 0; p = 0.001). The addition of Impella to V-A ECMO for patients with refractory cardiogenic shock was associated with lower all-cause 30-day mortality, lower inotrope use, and comparable safety profiles as compared with V-A ECMO alone. 

Bottom Line: The study, therefore, suggests that the addition of Impella to V-A ECMO is associated with improved survival in this clinical setting. Randomized controlled trials are required to confirm these findings.

Patel, Sandeep M., et al. “Simultaneous Venoarterial Extracorporeal Membrane Oxygenation and Percutaneous Left Ventricular Decompression Therapy with Impella Is Associated with Improved Outcomes in Refractory Cardiogenic Shock.” ASAIO Journal, vol. 65, no. 1, 2019, pp. 21–28., doi:10.1097/mat.0000000000000767.

V-A ECMO is still associated with a relatively high incidence of vascular complications and especially femoral cannulation increases the risk of lower-limb hypoperfusion and ischemia. Those can lead to severe irreversible conditions, including a limb loss. Although clinical evaluation of the perfusion is recommended, technological advances offer comprehensive and quantitative monitoring. A team from the Columbia University Medical Center in New York, USA, evaluated use of non-invasive lower-limb oximetry, using near-infrared reflectance spectroscopy (NIRS) in this clinical setting.

Data were collected from 25 patients (age 22-78) receiving femoral V-A ECMO between June 2016 and January 2017. Subjects were continuously monitored using the CASMED Fore-Sight Elite tissue oximeter. A retrospective pilot study was conducted to review the correlation between NIRS tissue saturations (StO2) and clinical indications of limb ischemia. Evaluated events included StO2s less than 50% for more than four minutes or StO2 differentials between the cannulated and non-cannulated legs greater than 15%.

Clinical signs of lower-limb ischemia, e.g. cold limb, mottled skin and absent Doppler signal, were observed in six patients from the group. All of those events were matched with StO2s below 50% that persisted for longer than four minutes. One patient had a false-positive device indication of hypoperfusion with StO2 below 50% for more than four minutes due to a venous saturation below 30% without the localized clinical counterpart and another had a false-positive absent Doppler signal caused by high doses of vasopressors. Five patients had StO2s below 50% for less than four minutes and none of these patients had clinical indications of lower-limb hypoperfusion, suggesting the importance of a time frame. Cannula-related obstruction of flow to the distal portion of the leg was associated with StO2 differentials greater than 15% in all affected patients and conversely no patients without cannula-related obstruction to flow had StO2 differentials greater than 15%. Sensitivity and specificity were 100% for diagnosing cannula-related obstruction to flow when the StO2 in the cannulated leg was below 50% for longer than four minutes and a differential between the cannulated and non-cannulated legs was greater than 15%. This has made NIRS monitoring especially valuable during the initiation of ECMO with femoral cannulation and for the period immediately following initiation when these patients are at the greatest risk for developing lower-limb ischemia.

Bottom line: Continuous NIRS monitoring might be used in the future as a warning system for identifying lower-limb ischemia and can also increase the confidence of bedside support staff to care for ECMO patients.

Patton-Rivera, Killian, et al. “Using near-Infrared Reflectance Spectroscopy (NIRS) to Assess Distal-Limb Perfusion on Venoarterial (V-A) Extracorporeal Membrane Oxygenation (ECMO) Patients with Femoral Cannulation.” Perfusion, vol. 33, no. 8, 2018, pp. 618–623., doi:10.1177/0267659118777670.

ECMO has been used to stabilize patients with acute PE in order to prolong valuable time for possible interventions, such as systemic thrombolysis, catheter-directed therapy or surgical embolectomy. Because these patients are often too unstable to transfer to the operating room or catheterization laboratory, a bridge to definitive therapy is needed (bridge-to-advanced therapy). The recommendation of the European Society of Cardiology for ECMO in the setting of a massive PE is based on case reports and case series and, therefore, is not assigned a class or level of evidence. Moreover, the latest American Heart Association scientific statement on the management of PE did not include the use of ECMO, citing a lack of data. At the current time, decisions need to be made on a case-by-case basis. However, one of the new additions to the slowly growing evidence in this clinical setting is a case series and review of the literature, published in Perfusion journal in December last year. A consecutive cohort of patients with confirmed PE was described in a pulmonary embolism response team (PERT) registry. Data were captured prospectively for up to one year of follow-up.

In total, 13 patients were identified, with the mean age of 49 ± 19 years, 46% were female. All of them experienced a cardiac arrest, either as an initial presentation or as in-hospital event. Right ventricular (RV) dilation on echocardiogram with RV hypokinesis was present in the whole cohort. 62% of subjects received systemic thrombolysis with intravenous tissue plasminogen activator (tPA), 23% underwent catheter-directed thrombolysis therapy using the EKOS system and 31% underwent surgical embolectomy. Mean ECMO duration was 5.5 days, ranging from 2-18 days. Thirty-day mortality was 31% and one-year mortality was 54%. The majority of patients treated with ECMO after PE in the PERT registry cohort series survived for 30 days, despite the fact that most had suffered at least one cardiac arrest event.

Bottom line: Although ECMO may be helpful in many patients who have a low chance of surviving massive PE without hemodynamic support, it does come with complications, in particular, major bleeding, that was suffered by 54% of patients from the PERT registry.

Al-Bawardy, Rasha, et al. “Extracorporeal Membrane Oxygenation in Acute Massive Pulmonary Embolism: a Case Series and Review of the Literature.” Perfusion, vol. 34, no. 1, 2018, pp. 22–28., doi:10.1177/0267659118786830.

Use of extracorporeal life support (ECLS) has a major impact on a physiological systemic response and organ function of the organism. However, whether use of ECLS results in immune dysregulation of an innate immune response remains unclear. Animal studies demonstrate that exposure of blood to the ECLS circuit induces an inflammatory response, but its extent in humans has not been yet well described. The team based mostly at the University of Michigan, USA, obtained blood samples from a total of 19 patients, 7 adults and 12 children, before, during, and after ECLS. Median ECLS duration was 10 days (range: 3–108) and nine patients died during the ICU stay. A function of the innate immune system was measured by ex vivo lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) and plasma cytokine levels (interleukin [IL]- 6, IL-8, IL-10, and TNF-α). Immunoparalysis was defined as ex vivo TNF-α levels less than 200 pg/ml. After stratifying the cohort by the presence of immunoparalysis before ECLS, those immunoparalyzed showed increased response to LPS on days 1 and 3 (p = 0.016). Those without pre-ECLS immunoparalysis showed a transient decrease in response on day 3 (p = 0.008). Plasma IL-10 levels were elevated in those with pre-ECLS immunoparalysis and dropped significantly by day 1 (p = 0.031). The number treated with steroids was similar in the two groups.

In summary, the study demonstrated that patients who were immunoparalyzed before going on ECLS showed a gradual increase in levels of innate immune function (as indicated by increased ex vivo TNF-α production) over time. This increased responsiveness may be secondary to the decrease in the anti-inflammatory cytokine IL-10 between ECLS initiation and day 1, or could be due to the better oxygen delivery to different vital organs including the immune system. In addition, the data also showed a transient drop in innate immune system responsiveness in the group without pre-ECLS immunoparalysis.

Bottom line: These data suggest that the responsiveness of the immune system is changing during ECLS and that there exists a critical need for larger studies designed to obtain a more complete understanding of the relationship among ECLS, inflammation, and the immune system.

Beshish, Asaad G., et al. “The Functional Immune Response of Patients on Extracorporeal Life Support.” ASAIO Journal, vol. 65, no. 1, 2019, pp. 77–83., doi:10.1097/mat.0000000000000748.

The role of V-A ECMO in severe pediatric septic shock remains controversial. Maintaining circulatory failure in a severe septic shock is challenging. However, whether the benefits of V-A ECMO outweigh the risks remains to be determined. The analysis by a multinational team led from Melbourne, Australia, represents the largest cohort study comparing extracorporeal circulatory support and conventional therapy in severe pediatric sepsis. Newly published data from a prospective cohort study followed a total of 164 children admitted to intensive care between the years 2006 and 2014. Children aged 30 days and more were treated in tertiary PICUs in Australia, New Zealand, the Netherlands, United Kingdom, and the United States. Majority of subjects was receiving conventional therapy only (n = 120), V-A ECMO was used in approximately one quarter (n = 44). Although the survival rate demonstrated the trend of superiority in V-A ECMO group (50 vs. 40%), it did not reach the statistical significance (p = 0.25; CI, –0.3 to 0.1). However, in children who suffered an in-hospital cardiac arrest, survival to hospital discharge was 18% with conventional therapy and 42% with V-A ECMO (p = 0.02; CI, 2.5–42%).  In this scenario, extracorporeal cardiorespiratory support was associated with a 24% survival advantage. Moreover, survival was significantly higher in patients who received ECMO flows higher than 150mL/kg/min compared with children who received standard flows or no ECMO (82%, 43%, and 48%; p = 0.03; CI, 0.1–0.7 and p < 0.01; CI, 0.2–0.7, respectively). The survival rate of children who received these very high-flow rates in two of the seven participating PICUs was almost 50% higher that seen in all other patients in the study, which supports the suggestion that maximizing extracorporeal circulatory output is fundamental to survival.

Lengths of ICU and hospital stay were significantly longer for children who had V-A ECMO, but this association was not present in survivors, indicating that VA ECMO resulted in non-survivors being kept alive for longer.

Bottom line: Based on these results, V-A ECMO did not appear to offer an advantage over conventional therapy but increased ICU and hospital resource use. However, this negative finding should be treated with some caution. Despite failing to reach statistical significance, the absolute difference in mortality of 10% between the two cohorts may be deemed clinically important, particularly in light of the study’s limits with regard to sample size and the relatively wide CI.

Oberender, Felix, et al. “Venoarterial Extracorporeal Membrane Oxygenation Versus Conventional Therapy in Severe Pediatric Septic Shock.” Pediatric Critical Care Medicine, 2018, p. 1., doi:10.1097/pcc.0000000000001660.

The use of LV unloading in V-A ECMO patients is controversial and currently a matter of a thorough debate. The implementation of percutaneous LV unloading modalities is obviously attractive and apparently efficient, although costs and peculiar adverse events may undermine its utilization. Axial continuous flow and transaortic devices may represent an advanced modality of combined LV unloading and circulatory support, making V-A ECMO + transaortic suction device an intriguing association for patients supported in cardiogenic shock.

The series of 106 patients from Hamburg is extremely interesting since reports about a robust clinical experience but shed some light also on the beneficial effects of the combination of assist systems.

Successful weaning was achieved in almost 52% of the patients, with a survival to discharge of 35.8%, which was higher than the predicted SAVE score (20%).
The performance of right heart catheterization clearly indicated a marked reduction of pulmonary capillary wedge pressure after the introduction of the transaortic device during the V-A ECMO run.

Bottom line: From this series, it appears that the combination of LV unloading with V-A ECMO is beneficial. However, the ultimate impact of such an association with respect to patient survival remains to be elucidated

Schrage, Benedikt, et al. “Unloading of the Left Ventricle During Venoarterial Extracorporeal Membrane Oxygenation Therapy in Cardiogenic Shock.” JACC: Heart Failure, vol. 6, no. 12, 2018, pp. 1035–1043., doi:10.1016/j.jchf.2018.09.009.

One of the most important controversies and a major limiting factor of ECMO use, particularly in relation to venoarterial support for cardiogenic shock and cardiac arrest, relates to the long-term results. A single-center study by Finnish authors assessed retrospectively 133 V-A ECMO patients with a follow-up of 10 years. Overall, almost 50% of the subjects were successfully weaned from ECMO, whereas 12% were bridged to heart transplantation, 11.3% to a ventricular assist device, and 0.8% to total artificial heart. Survival to discharge was 64%. A short Form Health Survey was also conducted among hospital survivors, and findings showed better emotional well-being and equal energy, pain and general health perception as compared to the general population. Limitations were perceived only in physical health with 56% of the patients younger than 60 years returning to work.

Bottom line: This single-center series provides an interesting picture of the in-hospital outcome, particularly in relation to the access to more advanced circulatory and heart therapies. Favorable post-discharge quality of life was noticed, slightly in contrast with previous publications showing a high impact on neuro-psychological and physical aspects of ECMO survivors.

Jäämaa-Holmberg, Salla, et al. “Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock: Patient Survival and Health-Related Quality of Life.” European Journal of Cardio-Thoracic Surgery, 2018, doi:10.1093/ejcts/ezy374.

The concept of “prophylactic ECMO” to improve critical preoperative modalities is not new and can be used in order to enhance perioperative course and outcome. This limited series of 12 patients in cardiogenic shock, who were evaluated for cardiac surgery, shows how the use of peripheral ECMO in the presence of a surgical diagnosis may significantly improve the preoperative conditions. Only 1 patient did not proceed to surgical correction of the underlying cardiac disease because of unknown anoxic brain injury. All the remaining patients survived to hospital discharge, with 2 death in the post-discharge period (at 76 and 230 days respectively) and with 6 patients surviving over 1 year.

 This outstanding experience, in patients who would otherwise have been excluded from surgery or most likely, would have a very complicated course and high perioperative mortality, confirm that ECMO may be effective. It could be used as a prophylactic tool to improve overall and organ conditions, enhance perioperative ICU stay, and successfully lead the patient to discharge with limited complications (in this series only 1 permanent stroke).

Bottom Line: ECMO can be used as a bridge-to-surgery in patients with mechanical complications of acute myocardial infarction and decompensated valvular disease in the presence of general conditions, which otherwise would define these patients inoperable or to transition patients from rescue to elective operation.

Watkins, A. Claire, et al. “Preoperative Venoarterial Extracorporeal Membrane Oxygenation Slashes Risk Score in Advanced Structural Heart Disease.” The Annals of Thoracic Surgery, vol. 106, no. 6, 2018, pp. 1709–1715., doi:10.1016/j.athoracsur.2018.07.038.

This retrospective study analyzed the very unique experience of the Karolinska hospital during a 21-year period. 908 patients were transported to the Stockholm hospital. Severe complications occurred in 20% of the patients, strongly associated with V-A configuration and fixed-wing transport. The occurrence of severe complications was not, however, associated with increased mortality. On-transport mortality occurred in only 2 patients.

 Bottom line: ECMO patient transport is a complex and dangerous situation. This unique series, however, demonstrates how experience and organization may allow a very safe provision of such a service, which, unfortunately, is not void of unexpected and dangerous events. Fatal cases were fortunately rare and severe complications were not associated with dismal outcome.

Fletcher-Sandersjöö, Alexander, et al. “A Single-Center Experience of 900 Interhospital Transports on Extracorporeal Membrane Oxygenation.” The Annals of Thoracic Surgery, vol. 107, no. 1, 2019, pp. 119–127., doi:10.1016/j.athoracsur.2018.07.040.

ECMO is routinely used to treat patients after cardiac arrest. This study of French authors analyzed a single-center experience with ECMO used in the setting of in-hospital (IHCA) and out-of-hospital (OHCA) cardiac arrests during a 10-year period. In total, 45 (34,4%) IHCA and 86 (65.6%) OHCA cases were included, mean age was 43.2 years and 72% were male. Patient profiles were comparable with an obvious exception of no flow and low-flow times, reaching 85.3 minutes in the OHCA group.

82.4% of the patients died on ECMO (79% for IHCA and 84% in OHCA, no significant difference). Also, the neurologic outcome at hospital discharge was not different between groups, and the presence of shockable rhythm was associated with better outcome.

 Bottom line: The study shows that even with appropriate ECMO program organization, the outcome of IHCA and OHCA do not differ. Another important issue, however, accounts for futile interventions which, for the time being, represent the major issue in this setting

 Pozzi, Matteo, et al. “Extracorporeal Life Support for Refractory Cardiac Arrest: A 10-Year Comparative Analysis.” The Annals of Thoracic Surgery, vol. 107, no. 3, 2019, pp. 809–816., doi:10.1016/j.athoracsur.2018.09.007.

Prolonged bed rest may lead to a deterioration in an overall physical condition. The retrospective study of the authors from the University of Maryland School of Medicine assessed the feasibility and outcome of patients cannulated for V-A ECMO peripherally, who were able to ambulate. Among 104 patients submitted to V-A ECMO in a 2-year period, 15 were able to ambulate at least once while on support. In 46% of the patients, the indication was decompensated heart failure, in 54% acute pulmonary embolism and 26% of the group had V-A ECMO during CPR. Mean time from ECMO implant-to-ambulation was 4 days (range 1-42 days) with a mean post-cannulation walking distance of 300 feet. No complication or dysfunction regarding patient-related or device-related function and state was observed. One-year survival was 100% for this patient group

Bottom line: This limited series demonstrates that peripheral ECMO with femoral cannulation does not preclude active movement and ambulation. In selected patients, this objective might be pursued and does not apparently induce any major complications

Pasrija, Chetan, et al. “Ambulation with Femoral Arterial Cannulation Can Be Safely Performed on Veno-Arterial Extracorporeal Membrane Oxygenation.” The Annals of Thoracic Surgery, 2018, doi:10.1016/j.athoracsur.2018.10.048.

Use of ECMO in the setting of a high-risk pulmonary embolism remains controversial. This multicenter study followed 180 patients over a period of 2 years, data were analyzed retrospectively. 128 patients were treated without ECMO, circulatory support was used in 52 subjects. Overall 30-day mortality was 48.3% with 43% in those treated without ECMO, and 61.5% in those with ECMO. In the patients who underwent ECMO+ fibrinolysis 30-day mortality was 76.5%, whereas 29.4% was the mortality for patients with ECMO +embolectomy, and 77.7% for those who had ECMO alone. In the patients who received ECMO, 38.5% had a major in-hospital bleeding event, without significant difference across groups.

The authors stated that based on the results, stand-alone ECMO does not appear as an effective strategy in this clinical setting. However, the combination of ECMO and surgical embolectomy provided a high success rate and might be the subject of dedicated investigation, especially with regards to recent favorable series.

 Bottom line: Apparently the use of ECMO in acute pulmonary embolism may account for significant mortality as compared to medical treatment alone. But, obviously, the patients undergoing ECMO were in more critical conditions and often after a cardiac arrest.

Meneveau, Nicolas, et al. “Outcomes after Extracorporeal Membrane Oxygenation for the Treatment of High-Risk Pulmonary Embolism: a Multicentre Series of 52 Cases.” European Heart Journal, vol. 39, no. 47, 2018, pp. 4196–4204., doi:10.1093/eurheartj/ehy464.