Neurological outcome in adult out-of-hospital cardiac arrest – Not all doom and gloom!

McKenzie, Nicole; Ball, Stephen; Bailey, Paul; Finn, Lyndall; Arendts, Glenn; Celenza, Antonio; Fatovich, Daniel M; Jenkins, Ian; Mukherjee, Ashes; Smedley, Ben; Ghedina, Nicole; Bray, Janet; Ho, Kwok M.; Dobb, Geoffrey; Finn, Judith

doi:10.1016/j.resuscitation.2021.08.042

Cited by 10 publications

(9 citation statements)

References 16 publications

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“…Further improvement between 3 and 6 months was as expected: half improved toward CPC 1 or 2 at 6 months. The final proportion of CPC 3 outcomes in this study is in accordance with the reported 6% to 10% in previous studies …”

Section: Discussionsupporting

confidence: 93%

Ghrelin for Neuroprotection in Post–Cardiac Arrest Coma

Nutma,

Beishuizen,

van den Bergh

et al. 2024

JAMA Neurol

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ImportanceOut-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human study populations.ObjectiveTo determine safety and potential efficacy of intravenous acyl-ghrelin to improve neurological outcome in patients in a coma after cardiac arrest.Design, Setting, and ParticipantsA phase 2, double-blind, placebo-controlled, multicenter, randomized clinical trial, Ghrelin Treatment of Comatose Patients After Cardiac Arrest: A Clinical Trial to Promote Cerebral Recovery (GRECO), was conducted between January 18, 2019, and October 17, 2022. Adult patients 18 years or older who were in a comatose state after cardiac arrest were assessed for eligibility; patients were from 3 intensive care units in the Netherlands. Expected death within 48 hours or unfeasibility of treatment initiation within 12 hours were exclusion criteria.InterventionsPatients were randomized to receive intravenous acyl-ghrelin, 600 μg (intervention group), or placebo (control group) within 12 hours after cardiac arrest, continued for 7 days, twice daily, in addition to standard care.Main Outcomes and MeasuresPrimary outcome was the score on the Cerebral Performance Categories (CPC) scale at 6 months. Safety outcomes included any serious adverse events. Secondary outcomes were mortality and neuron-specific enolase (NSE) levels on days 1 and 3.ResultsA total of 783 adult patients in a coma after cardiac arrest were assessed for eligibility, and 160 patients (median [IQR] age, 68 [57-75] years; 120 male [75%]) were enrolled. A total of 81 patients (51%) were assigned to the intervention group, and 79 (49%) were assigned to the control group. The common odds ratio (OR) for any CPC improvement in the intervention group was 1.78 (95% CI, 0.98-3.22; P = .06). This was consistent over all CPC categories. Mean (SD) NSE levels on day 1 after cardiac arrest were significantly lower in the intervention group (34 [6] μg/L vs 56 [13] μg/L; P = .04) and on day 3 (28 [6] μg/L vs 52 [14] μg/L; P = .08). Serious adverse events were comparable in incidence and type between the groups. Mortality was 37% (30 of 81) in the intervention group vs 51% (40 of 79) in the control group (absolute risk reduction, 14%; 95% CI, −2% to 29%; P = .08).Conclusions and RelevanceIn patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence.Trial RegistrationClinicaltrialsregister.eu: EUCTR2018-000005-23-NL

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Section: Discussionsupporting

confidence: 93%

Ghrelin for Neuroprotection in Post–Cardiac Arrest Coma

Nutma,

Beishuizen,

van den Bergh

et al. 2024

JAMA Neurol

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“…We did not report the neurological status of survivors, however we have previously shown that the majority (93%) of OHCA patients in Perth who STHD have a good cerebral performance category score (CPC 1-2) at hospital discharge. 19 Finally, we acknowledge that our results may not be applicable to other OHCA registries with different cultural backgrounds and health systems.…”

Section: Limitationsmentioning

confidence: 89%

Survival to hospital discharge is equivalent to 30-day survival as a primary survival outcome for out-of-hospital cardiac arrest studies

et al. 2021

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“…Current CCPR treatment after OHCA shows low survival rates (10–14%) for both OHCA [ 4 , 5 , 6 , 7 , 8 , 9 , 29 , 30 , 31 ] and IHCA [ 10 ]. These low CCPR survival rates arise from the delayed initiation of basic or advanced life support, the generation of a very low cardiac output (≤20–25%) from chest compressions [ 9 , 32 ], an inconsistent return of a robust cardiopulmonary function after CCPR, and complex pathophysiological and metabolic events after prolonged CA and CCPR.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body: A Multicenter, Prospective Observational Study

Trummer,

Benk,

Pooth

et al. 2023

JCM

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Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6–26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area.

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Neurological outcome in adult out-of-hospital cardiac arrest – Not all doom and gloom!

Cited by 10 publications

References 16 publications

Ghrelin for Neuroprotection in Post–Cardiac Arrest Coma

Ghrelin for Neuroprotection in Post–Cardiac Arrest Coma

Survival to hospital discharge is equivalent to 30-day survival as a primary survival outcome for out-of-hospital cardiac arrest studies

Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body: A Multicenter, Prospective Observational Study

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