Favorable resuscitation characteristics in patients undergoing extracorporeal cardiopulmonary resuscitation:A secondary analysis of the INCEPTION-trial

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used as a supportive treatment for refractory out-of-hospital cardiac arrest (OHCA). Still, there is a paucity of data evaluating favorable and unfavorable prognostic characteristics in patients considered for ECPR. Methods: We performed a previously unplanned post-hoc analysis of the multicenter randomized controlled INCEPTION-trial. The study group consisted of patients receiving ECPR, irrespective of initial group randomization. The patients were divided into favorable survivors (cerebral performance category [CPC] 1–2) and unfavorable or non-survivors (CPC 3–5).Results: In the initial INCEPTION-trial, 134 patients were randomized. ECPR treatment was started in 46 (66%) of 70 patients in the ECPR treatment arm and 3 (4%) of 74 patients in the conventional treatment arm. No statistically significant differences in baseline characteristics, medical history, or causes of arrest were observed between survivors (n = 5) and non-survivors (n = 44). More patients in the surviving group had a shockable rhythm at the time of cannulation (60% vs. 14%, p = 0.037), underwent more defibrillation attempts (13 vs. 6, p = 0.002), and received higher dosages of amiodarone (450 mg vs 375 mg, p = 0.047) despite similar durations of resuscitation maneuvers. Furthermore, non-survivors more frequently had post-ECPR implantation adverse events. Conclusion: The persistence of ventricular arrhythmia is a favorable prognostic factor in patients with refractory OHCA undergoing an ECPR-based treatment. Future studies are warranted to confirm this finding and to establish additional prognostic factors. Clinical trial Registration: clinicaltrials.gov</p

Favorable resuscitation characteristics in patients undergoing extracorporeal cardiopulmonary resuscitation:A secondary analysis of the INCEPTION-trial

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used as a supportive treatment for refractory out-of-hospital cardiac arrest (OHCA). Still, there is a paucity of data evaluating favorable and unfavorable prognostic characteristics in patients considered for ECPR. Methods: We performed a previously unplanned post-hoc analysis of the multicenter randomized controlled INCEPTION-trial. The study group consisted of patients receiving ECPR, irrespective of initial group randomization. The patients were divided into favorable survivors (cerebral performance category [CPC] 1–2) and unfavorable or non-survivors (CPC 3–5).Results: In the initial INCEPTION-trial, 134 patients were randomized. ECPR treatment was started in 46 (66%) of 70 patients in the ECPR treatment arm and 3 (4%) of 74 patients in the conventional treatment arm. No statistically significant differences in baseline characteristics, medical history, or causes of arrest were observed between survivors (n = 5) and non-survivors (n = 44). More patients in the surviving group had a shockable rhythm at the time of cannulation (60% vs. 14%, p = 0.037), underwent more defibrillation attempts (13 vs. 6, p = 0.002), and received higher dosages of amiodarone (450 mg vs 375 mg, p = 0.047) despite similar durations of resuscitation maneuvers. Furthermore, non-survivors more frequently had post-ECPR implantation adverse events. Conclusion: The persistence of ventricular arrhythmia is a favorable prognostic factor in patients with refractory OHCA undergoing an ECPR-based treatment. Future studies are warranted to confirm this finding and to establish additional prognostic factors. Clinical trial Registration: clinicaltrials.gov</p

Health-related quality of life one year after refractory cardiac arrest treated with conventional or extracorporeal CPR: a secondary analysis of the INCEPTION-trial

Background: Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal cardiopulmonary resuscitation (ECPR) or conventional CPR (CCPR) are scarce. We aimed to determine HRQoL during 1-year after refractory OHCA in patients treated with ECPR and CCPR. Methods: We present a secondary analysis of the multicenter INCEPTION-trial, which studied the effectiveness of ECPR versus CCPR in patients with refractory OHCA. HRQoL was prospectively assessed using the EQ-5D-5L questionnaire. Poor HRQoL was pragmatically defined as an EQ-5D-5L health utility index (HUI) &gt; 1 SD below the age-adjusted norm. We used mixed linear models to assess the difference in HRQoL over time and univariable analyses to assess factors potentially associated with poor HRQoL. Results: A total of 134 patients were enrolled, and hospital survival was 20% (27 patients). EQ-5D-5L data were available for 25 patients (5 ECPR and 20 CCPR). One year after OHCA, the estimated mean HUI was 0.73 (0.05) in all patients, 0.84 (0.12) in ECPR survivors, and 0.71 (0.05) in CCPR survivors (p-value 0.31). Eight (32%) survivors had a poor HRQoL. HRQoL was good in 17 (68%) patients, with 100% in ECPR survivors versus 60% in CCPR survivors (p-value 0.14). Conclusion: One year after refractory OHCA, 68% of the survivors had a good HRQoL. We found no statistically significant difference in HRQoL one year after OHCA in patients treated with ECPR compared to CCPR. However, numerical differences may be clinically relevant in favor of ECPR.</p

Health-related quality of life one year after refractory cardiac arrest treated with conventional or extracorporeal CPR: a secondary analysis of the INCEPTION-trial

Background: Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal cardiopulmonary resuscitation (ECPR) or conventional CPR (CCPR) are scarce. We aimed to determine HRQoL during 1-year after refractory OHCA in patients treated with ECPR and CCPR. Methods: We present a secondary analysis of the multicenter INCEPTION-trial, which studied the effectiveness of ECPR versus CCPR in patients with refractory OHCA. HRQoL was prospectively assessed using the EQ-5D-5L questionnaire. Poor HRQoL was pragmatically defined as an EQ-5D-5L health utility index (HUI) &gt; 1 SD below the age-adjusted norm. We used mixed linear models to assess the difference in HRQoL over time and univariable analyses to assess factors potentially associated with poor HRQoL. Results: A total of 134 patients were enrolled, and hospital survival was 20% (27 patients). EQ-5D-5L data were available for 25 patients (5 ECPR and 20 CCPR). One year after OHCA, the estimated mean HUI was 0.73 (0.05) in all patients, 0.84 (0.12) in ECPR survivors, and 0.71 (0.05) in CCPR survivors (p-value 0.31). Eight (32%) survivors had a poor HRQoL. HRQoL was good in 17 (68%) patients, with 100% in ECPR survivors versus 60% in CCPR survivors (p-value 0.14). Conclusion: One year after refractory OHCA, 68% of the survivors had a good HRQoL. We found no statistically significant difference in HRQoL one year after OHCA in patients treated with ECPR compared to CCPR. However, numerical differences may be clinically relevant in favor of ECPR.</p

Projet Seine-Aval 6 PHARESEE « Productivité microphytobenthique des HAbitats intertidaux en lien avec la dynamique sédimentaire, biogéochimique et les ingénieurs d'écosystème de la faune benthique : implication pour des enjeux de modélisation et de REhabilitation des vasières de la SEine Estuarienne »

L'estuaire de la Seine est soumis à divers stress anthropiques et hydro-climatiques. Cet écosystème côtier perd son caractère estuarien à cause d'aménagements qui ont eu comme conséquence de voir disparaître de vastes surfaces de vasières intertidales. Ces habitats fonctionnels jouent un rôle majeur dans le fonctionnement écologique des estuaires, car ils abritent des communautés méio- et macro-benthiques très diversifiées et représentent la principale zone d’alimentation de nombreux vertébrés dont certains d’intérêt écologique ou commercial majeur (e.g. poissons, oiseaux). La dynamique des vasières intertidales est fortement influencée par les processus hydro-sédimentaires estuariens, étant tantôt source, tantôt puits de sédiment. Elles constituent ainsi un élément essentiel des cycles biogéochimiques se déroulant au sein des estuaires. Les caractéristiques morphologiques et biogéochimiques de ces zones vont directement influencer les échanges de matière et d’énergie qui s’y déroulent. Il est donc impératif d'avoir une approche pluridisciplinaire pour comprendre leur fonctionnement. Le projet PHARE-SEE avait pour objectif (i) de mieux comprendre le rôle des bioturbateurs et leur effet sur le microphytobenthos, les paramètres hydrosédimentaires et biogéochimiques dans les vasières de l’estuaire de Seine et (ii) de développer un modèle de production primaire microphytobenthique couplant l’ensemble des paramètres susmentionnés. Le premier objectif du projet a été réalisé en couplant expériences sur le terrain et en laboratoire. Ainsi, des expériences d’exclusion/ensemencement de faune ont été menées sur la vasière Nord, à l’aval de l’estuaire de Seine, et sur 2 faciès sédimentaires contrastés, avec un suivi de la dynamique saisonnière du microphytobenthos et de l’ensemble des paramètres biogéochimiques et hydrosédimentaires. De plus, des expériences en laboratoire ont été réalisées, avec une évaluation des flux diffusifs de nutriments à 2 saisons contrastées (hiver/été) en fonction du mélange sablo-vaseux et de l’intensité de la bioturbation par la macrofaune benthique dominante de la vasière (le ver Hediste diversicolor et le bivalve Scrobicularia plana). Les expériences de terrain ont montré que l’effet saisonnier était plus prononcé que celui des bioturbateurs sur l’ensemble des paramètres biogéochimiques dans le sédiment (matière organique sédimentaire, processus et biomasse microbiens). Contrairement à la matière organique sédimentaire, principalement d’origine terrigène, la matière organique dissoute présente dans les eaux interstitielles, majoritairement d’origine autochtone, est réactive et influencée par l’activité des bioturbateurs. Ces derniers ont une influence prononcée sur l’érodabilité, avec un rôle biostabilisateur efficace pour Hediste diversicolor en été comme en hiver et un rôle déstabilisateur pour Scrobicularia plana exclusivement en été. Malgré des processus de consommations primaires très élevés et des pertes par érosion, le niveau de production primaire microphytobenthique reste par ailleurs très important sur la vasière. Les analyses réalisées ont également révélé le rôle majeur du microphytobenthos dans le réseau trophique pour H. diversicolor, S. plana et la méiofaune (analyses isotopes stables, collaboration projet SA6 SENTINELLES). Les expériences en mésocosme, complémentaires de celles réalisées sur le terrain, ont montré que l’activité de bioturbation des deux ingénieurs d’écosystème diffère quelle que soit la saison. Ainsi, le processus de transport d’eau et des composés dissous (bioirrigation) domine chez H. diversicolor, alors que l’activité de S. plana est dominée par le remaniement sédimentaire. Les flux biogéochimiques à l’interface eau-sédiment sont principalement influencés par la bioirrigation. Enfin, il a été observé que S. plana consomme très activement les biofilms microphytobenthiques et limite fortement leur capacité de développement, alors que la biomasse microphytobenthique n’est pas affectée par les activités de Hediste. Cela démontre que la consommation herbivore est totalement compensée par des effets positifs liés probablement à la bioirrigation, activée de manière générale plus de 40 fois par Hediste. Dans un second temps, ce projet proposait de modéliser la production primaire microphytobenthique en relation avec la dynamique sédimentaire et les processus biogéochimiques. Les données acquises via expériences en laboratoire et sur le terrain ont servi à développer ce modèle. Ainsi, le modèle MARS3D en version Cross-shore 2DV a été implémenté sur la vasière intertidale étudiée avec une très bonne qualité des simulations des processus hydrosédimentaires et des variations altimétriques. L’intégration de l’effet de la bioturbation et de la régulation de l’érodabilité des sédiments a permis d’améliorer encore la qualité des simulations. Un modèle de diffusion thermique a été intégré, testé et amélioré en termes d’interaction avec la composition sédimentaire. Le modèle biogéochimique BLOOM a été intégré également dans le modèle MARS3D avec une dynamique biogéochimique saisonnière bien représentée. Le modèle prend en compte le rôle des bioturbateurs sur les flux diffusifs, mais une perspective d’amélioration doit être envisagée pour mieux reproduire les flux à l’interface eau-sédiment et l’assimilation du NH4 + par le microphytobenthos en surface. Enfin, le modèle de la production primaire microphytobenthique a été implémenté dans le code MARS3D et fournit des simulations de la dynamique spatio-temporelle des biomasses microphytobenthiques intéressantes, même si les flux sont encore sous-estimés dans le modèle et les interactions avec la faune doivent encore être améliorées. Au final, les très nombreuses données issues du projet PHARESEE et le modèle associé serviront à comprendre et relier les nombreux facteurs influençant le fonctionnement des vasières et leurs rôles écosystémiques essentiels – rôle physique, de régulation sur les cycles biogéochimiques et rôle de productivité biologique et soutien au réseau trophique. Des travaux de synthèse ont été engagés en particulier pour tenter d’expliquer le haut niveau de productivité actuel du système en lien avec la bonne santé des espèces sentinelles (ingénieurs d’écosystèmes) de la macrofaune benthique

Health-related quality of life one year after refractory cardiac arrest treated with conventional or extracorporeal CPR; a secondary analysis of the INCEPTION-trial

Background: Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal cardiopulmonary resuscitation (ECPR) or conventional CPR (CCPR) are scarce. We aimed to determine HRQoL during 1-year after refractory OHCA in patients treated with ECPR and CCPR. Methods: We present a secondary analysis of the multicenter INCEPTION-trial, which studied the effectiveness of ECPR versus CCPR in patients with refractory OHCA. HRQoL was prospectively assessed using the EQ-5D-5L questionnaire. Poor HRQoL was pragmatically defined as an EQ-5D-5L health utility index (HUI) > 1 SD below the age-adjusted norm. We used mixed linear models to assess the difference in HRQoL over time and univariable analyses to assess factors potentially associated with poor HRQoL. Results: A total of 134 patients were enrolled, and hospital survival was 20% (27 patients). EQ-5D-5L data were available for 25 patients (5 ECPR and 20 CCPR). One year after OHCA, the estimated mean HUI was 0.73 (0.05) in all patients, 0.84 (0.12) in ECPR survivors, and 0.71 (0.05) in CCPR survivors (p-value 0.31). Eight (32%) survivors had a poor HRQoL. HRQoL was good in 17 (68%) patients, with 100% in ECPR survivors versus 60% in CCPR survivors (p-value 0.14). Conclusion: One year after refractory OHCA, 68% of the survivors had a good HRQoL. We found no statistically significant difference in HRQoL one year after OHCA in patients treated with ECPR compared to CCPR. However, numerical differences may be clinically relevant in favor of ECPR

Cost-effectiveness of extracorporeal cardiopulmonary resuscitation vs. conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest: A pre-planned, trial-based economic evaluation

Aims: When out-of-hospital cardiac arrest (OHCA) becomes refractory, extracorporeal cardiopulmonary resuscitation (ECPR) is a potential option to restore circulation and improve the patient's outcome. However, ECPR requires specific materials and highly skilled personnel, and it is unclear whether increased survival and health-related quality of life (HRQOL) justify these costs. Methods and results: This cost-effectiveness study was part of the INCEPTION study, a multi-centre, pragmatic randomized trial comparing hospital-based ECPR to conventional CPR (CCPR) in patients with refractory OHCA in 10 cardiosurgical centres in the Netherlands. We analysed healthcare costs in the first year and measured HRQOL using the EQ-5D-5L at 1, 3, 6, and 12 months. Incremental cost-effectiveness ratios (ICERs), cost-effectiveness planes, and acceptability curves were calculated. Sensitivity analyses were performed for per-protocol and as-Treated subgroups as well as imputed productivity loss in deceased patients. In total, 132 patients were enrolled: 62 in the CCPR and 70 in the ECPR group. The difference in mean costs after 1 year was €5109 (95% confidence interval-7264 to 15 764). Mean quality-Adjusted life year (QALY) after 1 year was 0.15 in the ECPR group and 0.11 in the CCPR group, resulting in an ICER of €121 643 per additional QALY gained. The acceptability curve shows that at a willingness-To-pay threshold of €80.000, the probability of ECPR being cost-effective compared with CCPR is 36%. Sensitivity analysis showed increasing ICER in the per-protocol and as-Treated groups and lower probabilities of acceptance. Conclusion: Hospital-based ECPR in refractory OHCA has a low probability of being cost-effective in a trial-based economic evaluation

Cost-effectiveness of extracorporeal cardiopulmonary resuscitation vs. conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest:A pre-planned, trial-based economic evaluation

Aims: When out-of-hospital cardiac arrest (OHCA) becomes refractory, extracorporeal cardiopulmonary resuscitation (ECPR) is a potential option to restore circulation and improve the patient's outcome. However, ECPR requires specific materials and highly skilled personnel, and it is unclear whether increased survival and health-related quality of life (HRQOL) justify these costs. Methods and results: This cost-effectiveness study was part of the INCEPTION study, a multi-centre, pragmatic randomized trial comparing hospital-based ECPR to conventional CPR (CCPR) in patients with refractory OHCA in 10 cardiosurgical centres in the Netherlands. We analysed healthcare costs in the first year and measured HRQOL using the EQ-5D-5L at 1, 3, 6, and 12 months. Incremental cost-effectiveness ratios (ICERs), cost-effectiveness planes, and acceptability curves were calculated. Sensitivity analyses were performed for per-protocol and as-Treated subgroups as well as imputed productivity loss in deceased patients. In total, 132 patients were enrolled: 62 in the CCPR and 70 in the ECPR group. The difference in mean costs after 1 year was €5109 (95% confidence interval-7264 to 15 764). Mean quality-Adjusted life year (QALY) after 1 year was 0.15 in the ECPR group and 0.11 in the CCPR group, resulting in an ICER of €121 643 per additional QALY gained. The acceptability curve shows that at a willingness-To-pay threshold of €80.000, the probability of ECPR being cost-effective compared with CCPR is 36%. Sensitivity analysis showed increasing ICER in the per-protocol and as-Treated groups and lower probabilities of acceptance. Conclusion: Hospital-based ECPR in refractory OHCA has a low probability of being cost-effective in a trial-based economic evaluation.</p