Advanced care in patients with out-of-hospital cardiac arrest

Out-of-hospital cardiac arrest (OHCA) is one major cause of mortality and is responsible for up to one fifth of deaths globally. Despite intense efforts to improve survival only one out of ten patients survive and even in cases with favourable resuscitation characteristics, survival chances decline fast if initial treatment fails. These patients are often referred to as refractory OHCA and the overall aim of this thesis is to characterize and investigate whether survival in this group can be improved using advanced circulatory support, compared to standard treatment alone. Additionally, treatment of OHCA with hypothermia at the intensive care unit is investigated.

Methods and results

Study I is a registry-based observational cohort study evaluating the change in use of target temperature management (TTM) in Sweden following the TTM-trial and whether the treatment shift from 33 ℃ to 36 ℃ had any impact on 6-month survival. A total of 2,899 patients with OHCA were included for analysis of which 1,402 were treated with TTM. Following the publication of the TTM-trial, treatment with TTM declined, against guideline recommendations, from 70.5% to 54.5% but without significant impact on 6-month survival between the groups TTM33 (47.2%) and TTM36 (47.3%) (adjusted OR 1.12, 95% CI 0.8 - 1.56).

Study II is an observational study evaluating the implementation of an extracorporeal cardiopulmonary resuscitation (ECPR) program for refractory OHCA in Stockholm, Sweden. Data were prospectively collected and outcomes included feasibility, safety and clinical aspects. A total of 95 patients with refractory OHCA were included for analysis of which 22/95 (23%) achieved ROSC prior to ECPR, 39/95 (41%) were excluded for extracorporeal membrane oxygenation (ECMO), 34/95 (36%) had ECMO initiated and finally 23 patients on ECMO were admitted alive to the ICU. The target time interval of ECMO-initiation within 60 minutes was met in 9% of cases. The most reported safety aspect among those cannulated were complicated vascular access (n=6) and severe bleeding at access site requiring intervention (n=2). Survival to discharge among those admitted to ICU on ECMO was 23% (9/23) of which 78% (7/9) had good neurologic function. Overall survival was 25% (24/95) and most of the survivors treated with ECMO, 8 out of 9 patients, had more than the intended 60 minutes to ECMO-initiation.

Study III is a registry-based observational study investigating the burden of coronary artery disease in relation to the number of defibrillations among patients with OHCA. Patients with initial shockable rhythm who underwent coronary angiography were included and grouped according to number of defibrillations: 1-3, 4-6, 7-9 and ≥ 10. Outcomes included coronary angiography findings described as acute occlusion, chronic occlusion, multivessel disease and percutaneous coronary intervention (PCI) as well as 1-year survival. In total 2,594 patients were included for analysis. Most patients had significant stenosis (84% - 69%) with the highest prevalence among those receiving 1-3 defibrillations. PCI was also more common among those receiving 1-3 defibrillations (74%) compared to the other groups of defibrillations (62-54%). Acute coronary occlusions were similar between the groups (44% - 38%). One- year survival declined with increased number of defibrillations regardless of adjustment of coronary angiography findings and percutaneous coronary intervention.

Study IV is a registry-based observational study exploring whether a simple combination of patient and prehospital characteristics can identify patients with initial shockable rhythm with high risk of not achieving ROSC and who might benefit from early transport. Multiple variables were analysed for importance using random forest and the proportion of patients without ROSC based on resuscitation time were analysed using Kaplan Meier curves. Outcome was "no ROSC" at hospital arrival. A subgroup analysis was performed on patients fulfilling the ECPR-criteria from study II. In total 10,651 patients were included of which 5,390 patients (51%) did not achieve ROSC. The most important variables for predicting "no ROSC" was absence of ROSC ten minutes after EMS arrival and adrenaline administered, both for the overall cohort and the subgroup meeting ECPR-criteria. Combining these two variables identified 83% (n=2592/3108) without ROSC in the full cohort and 81% (n=464/572) in ECPR subgroup.

Conclusions

Following the publication of the TTM-trial, the use of TTM in Sweden decreased, against guideline recommendations, but without any effect on 6-month survival.

The implementation of an ECPR program in Stockholm, Sweden, was feasible without any major safety aspects but the intended time intervals were not met.

Despite this survival rates were comparable to previous ECPR studies, and most survivors had more than 60 minutes to ECMO initiation.

Among patients with shockable OHCA undergoing coronary angiography we did not observe an increase in burden of coronary artery disease with increased number of defibrillations.

In cases of shockable OHCA, absence of ROSC 10 minutes after EMS arrival and adrenaline administered had the highest impact on predicting "no ROCS" and combined they identified 83% without ROSC in the full cohort and 81% in the ECPR subgroup.

List of scientific papers

I. Abazi L, Awad A, Nordberg P, Jonsson M, Taccone FS, Wickerts CJ, Svensson L, Hollenberg J, Ringh M, Forsberg S. Long-term survival in out-of-hospital cardiac arrest patients treated with targeted temperature control at 33 ℃ or 36 ℃: A national registry study. Resuscitation. 2019;143:142-147. https://doi.org/10.1016/j.resuscitation.2019.08.029

II. Lis Frykler Abazi, Andreas Liliequist, Felix Böhm, Magnus Hedberg, Moa Simonsson, Anders Backman, Malin Ax, Frieder Braunschweig, Linda Mellbin, Rickard Linder, Leif Svensson, Juliane Jurga, Per Nordberg, Mattias Ringh, Sune Forsberg, Jacob Hollenberg Implementation of an extracorporeal resuscitation (ECPR) program for out-of-hospital cardiac arrest in Stockholm, Sweden: Feasibility, safety, and outcome Resusc Plus. 2024;18:100596. https://doi.org/10.1016/j.resplu.2024.100596

III. Lis Frykler Abazi, Sune Forsberg, Felix Böhm, Martin Jonsson, Mattias Ringh, Gabriel Riva, Ludvig Elfwén, Per Nordberg, Akil Awad, Charlotte Miedel, Anette Nord, Andreas Claesson, Nils Witt, Jacob Hollenberg Burden of coronary artery disease in relation to the number of defibrillations in out-of-hospital cardiac arrest. [Submitted]

IV. Lis Frykler Abazi, Mattias Ringh, Per Nordberg, Martin Jonsson, Araz Rawshani, Anette Nord, Andreas Claesson, Gabriel Riva, Jacob Hollenberg, Sune Forsberg On-scene identification of refractoriness in out-of-hospital cardiac arrest with shockable rhythm. [Manuscript]