Abstract : 
Awake Venoarterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock: a Propensity Score Matched Analysis

Introduction / Rationale :
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is the first-line therapy for refractory cardiogenic shock (CS), but its applicability is undermined by the high morbidity associated with its complications, especially those related to mechanical ventilation (MV). We aimed at assessing the impact on survival of keeping patients awake during the VA-ECMO run in the context of refractory CS.

Méthodes / Patients and Methods :
A 7-year database of CS-patients supported with peripheral VA-ECMO was used to perform a propensity score (PS) matched analysis in order to balance their clinical profile. Patients were classified as “awake and partially awake” or “non-awake” if mechanical ventilation was present ≤50% or >50% of the ECMO run. Primary outcomes were 60-day and 1-year mortality, and secondary outcomes included rates of ventilator-associated pneumonia (VAP) and ECMO-related complications. A multivariate logistic regression analysis was performed to identify if respiratory status at cannulation was independently associated with 60-day mortality.

Résultats / Results :
Out of 231 patients included, 91 (39%) were “awake and partially awake” and 140 (61%) “non-awake”. After PS matching adjustment, the “awake and partially awake” group had significantly better 60-day (19% vs 46%, p<0.006; 95% CI, OR 0.36 [0.17-0.79], p=0.01) and 1-year survival (32% vs 57%, p<0.018; 95% CI, OR 0.43 [0.22-0.82], p=0.01) compared to the “non-awake” group, as well as reduced rates of VAP (34% vs 64%, p=0.004) and less antibiotic and sedative drugs consumption. However, MV at ECMO cannulation was not independently related to 60-day mortality.

Discussion / Discussion :
Previous clinical series have suggested better survival and less VAP rates in ECLS-supported patients, but the small number of patients and the inclusion of non-arousable patients with likely neurological impairment hampered the interpretation and validity of this strategy. Although the likelihood of remaining awake seem to increase in vigil patients at cannulation, we did not find an independent association between this fact and 60-day mortality. Therefore, it is likely that the earliest possible extubation represents the main message in this setting, allowing to longer time on spontaneous breathing whilst on VA-ECMO support. Beyond better outcome, physical rehabilitation, communication with relatives and, specifically, interactive information of the medical decisions, are key potential benefits from a non-intubation or an early-extubation management in these patients. Indeed, the avoidance of relevant complications (mainly VAP) may additionally contribute to these advantages.

Conclusion / Conclusion :
An “awake and partially awake” VA-ECMO strategy in CS is safe and is associated with improved short- and long-term survival compared to mechanically ventilated patients.
 

Abstract : 
Impact of pulmonary hypertension on post heart transplant outcome

Introduction / Rationale :
Pulmonary hypertension (PH) is associated with a higher risk of early right ventricular graft failure after heart transplantation, and poorer short and long-term outcomes. However, improvements in short term extra corporeal life support in the past decades allows an easier supply of early graft failure. Thereby, we aimed to compare the outcome of patients undergoing heart transplantation with or without elevated pulmonary vascular resistances (PVR), in an expert center for mechanical circulatory support.

Méthodes / Patients and Methods :
We conducted a retrospective monocentric cohort study including all consecutive patients receiving a heart transplant in our center from 2011 to 2017, with an assessment by right heart catheterization in the year before transplantation.

Résultats / Results :
Among the 304 patients included, 129 (42%) had low PVR (PVR≤2,5 WU), and 175 (58%) had high PVR (PVR>2,5 WU) before transplant. 82% of patients with high PVR and 81% of patients with low PVR were alive at 1year follow-up (p=0.6). Patients with high PVR were more likely to require immediate post-transplant circulatory support by veno-arterial extracorporeal membrane oxygenation (VA-ECMO) (58% vs 44%, p=0,02), as well as a pulmonary vasodilator treatment by Sildenafil (14% vs 7%, p=0,045). PVR were not associated with 1-year post-transplant mortality in multivariate analysis. At 1-year follow-up, right and left ventricular graft function were preserved for all survivors, and did not differ between high and low PVR groups. Even in the subgroup of the 24 patients transplanted with PVR>5WU, unresponsive to vasodilator challenge, 1-year survival was 92%, with preserved right and left ventricular function.

Discussion / Discussion :


Conclusion / Conclusion :
PH was not associated with a poor outcome in our cohort, even when it was severe and unresponsive to vasodilator challenge. However, the rate of VA-ECMO support immediately after heart transplant was higher in patients with high PVR. Cardiac transplantation as first line strategy may be a valuable option in patients with elevated pre-transplant PVR.
 

Abstract : 
Hemodynamic and microcirculation evaluation of Vasopressin versus Norepinephrine in a porcine model of refractory cardiac arrest resuscitated by venous-arterial ECMO.

Introduction / Rationale :
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to support tissue perfusion during extracorporeal cardiopulmonary resuscitation (e-CPR). Shock, resuscitation and the extracorporeal circuit may trigger a capillary leakage and a vasoplegic shock. Currently, in these situations, high doses of Norepinephrine (NE) are required. Because high NE doses may have significant cardiovascular side effects, alternative options to support arterial blood pressure are needed. In recent years, several approaches to decrease the administration of high NE doses have been tested, one of them is the administration of Vasopressin (AVP). Randomized trials have shown that AVP infusion increases arterial pressure and systemic vascular resistance, decreases catecholamine requirements in patients with or at high risk of vasoplegic syndrome and attenuates vascular dysfunction. Currently, no data are available for the study of the effects of AVP in shock state in post refractory cardiac arrest.

Méthodes / Patients and Methods :
20 pigs were randomized into two groups, in order to receive AVP or NE. A refractory cardiac arrest of ischemic origin was surgically created and VA-ECMO was started after a 30 min period of cardio-pulmonary resuscitation. Then, resuscitation lasted six hours in each randomization group. The evolution of the consequences of the shock was evaluated by lactatemia and microcirculation (SDF and NIRS) at basal hour, H0 (when ECMO starts), H3 and H6. Renal and hepatic functions were assessed.

Résultats / Results :
Experimental conditions were met for 16 animals (AVP, n = 8 ; NE, n = 8). The groups were comparable on the shock impact and its severity. No significant differences were found between populations for ECMO flow and MAP. There was a significant difference on fluid volume resuscitation amount (14000 [11250 – 15250] milliliters in the NE group versus 3500 [1750 - 4000] milliliters in the AVP group, p < 0.05). No significant difference between the NE and AVP groups for lactate clearance (%) between H0 and H6 (25,66 [-7,31 – 35,34) vs 47,84 [13,42 – 82,73], p=0.686). We did not find any significant for sublingual microcirculation indices and NIRS values. Renal and liver function evolution were similar in the two groups during the protocol.

Discussion / Discussion :


Conclusion / Conclusion :
AVP administration in refractory cardiac arrest resuscitated by VA-ECMO when compared to NE is associated with less fluid volume for similar global and regional hemodynamic effects.
 

Abstract : 
Veno-arterial Extracorporeal Membrane Oxygenation flow or Dobutamine to increase microcirculation for Refractory Cardiogenic Shock

Introduction / Rationale :
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an effective technique to support refractory cardiogenic shock (CS) and increase macro- and microcirculation. Given that major and persistent microcirculation alterations are associated with worse outcome, we investigated the respective impact of an increase of either the VA-ECMO flow and or dobutamine dose on microcirculation in stabilized patients with refractory CS on VA-ECMO.

Méthodes / Patients and Methods :
Prospective study in academic medical intensive unit. Consecutive patients with ECMO-supported CS instability, who were able to tolerate a stepwise increment of the dobutamine dose and the ECMO flow.
Baseline was defined by the lowest VA-ECMO flow and dobutamine 5 µg/kg/min for PAM ≥ 65 mmHg. Starting from the baseline, VA-ECMO flow was progressively increased by 25% (ECMO125%, ECMO150%, ECMO175%, ECMO200%). Back at baseline, a stepwise increase of the dobutamine to 10, 15 and 20 µg/kg/min (DOBU10, DOBU15, DOBU20) were performed. Macro- and microcirculatory evaluations were made after 30 min in each condition.

Résultats / Results :
Fourteen patients (median age 52 [40-61] years; SAPS II 68 [52-76]) were included. Acute myocardial infarction was the main cause of cardiogenic shock (64%). Macro- and microcirculation were assessed 2 [2-5] days after ECMO start. The increment of the dobutamine dose did not modify microcirculation parameters. De Backer score tended to be reduced (p=0,08), with a significant mean arterial pressure (MAP) increase during the ECMO flow increment. These findings were not different between patients successfully weaned-off ECMO (n=6) and those who did not.

Discussion / Discussion :


Conclusion / Conclusion :
When macro and microcirculation are already restored on ECMO-supported refractory CS, increasing dobutamine (above 5 µg/kg/min) or ECMO flow did not further improve microcirculation. For now, ECMO flow and dobutamine should be set as the minimum flow to get a MAP ≥ 65mmHg and lactate < 2.5 mmol/L, and the minimal dose to maintain aortic valve opened, respectively.