Dear Editor,
Out-of-hospital cardiac arrest (OHCA) is associated with high morbidity and mortality. Only approximately 5–14% of patients who survive OHCA are discharged with favorable neurological outcome [1, 2]. No prehospitally administered drug has shown to improve neurological outcome in these patients. Acute myocardial infarction (AMI) is a major cause of OHCA. We recently found AMI in 48.2% of patients with OHCA and showed that prehospital administration of acetylsalicylic acid and heparin (AH) was associated with improved survival to hospital discharge, particularly in patients with AMI [3].
In this study, we evaluated the effect of prehospital AH administration on favorable neurological outcome after OHCA. Using data from the nationwide, prospective German Resuscitation Registry, we retrospectively analyzed 17,948 patients with a resuscitation attempt and a presumed cardiac or unknown cause of OHCA between 2013 and 2018. The consort flow-diagram for the study population is depicted in Figure S1. Patients with prehospital AH administration were matched in a 1:3 ratio with patients not treated with AH. The primary outcome was favorable neurological outcome at hospital discharge defined as cerebral performance category (CPC) 1 or 2. Secondary outcomes were return of spontaneous circulation (ROSC), ROSC at hospital admission, 24-h survival and survival to hospital discharge. Additional details can be found in the supplementary material.
In the matched cohort comprising 203 patients with and 609 patients without prehospital AH administration, baseline characteristics were comparable between groups (Table 1). Differences between the matched cohort and the full cohort are shown in Table S1. Prehospital AH administration was associated with favorable neurological outcome (OR 2.25 (1.31–3.87), p = 0.003, Table S2). Patients with AH were more likely to gain ROSC (OR 2.22 (1.45–3.42), p < 0.001, Table S3) despite similar ROSC after cardiac arrest (RACA) scores between groups [4]. Moreover, in AH patients, ROSC was more likely to be stable until hospital admission (OR 1.95 (1.26–3.00), p = 0.002, Table S3). No difference was observed in survival at 24 h (OR 1.30 (0.77–2.17), p = 0.322, Table S3), while AH was associated with increased survival to hospital discharge (OR 1.84 (1.09–3.09), p = 0.022, Table S3). Sensitivity analysis with all 17,491 patients with known CPC status confirmed the robustness of our findings (Table S4). Subgroup analysis revealed a significant interaction with male sex and bystander CPR, variables predominantly seen in patients with AMI as the underlying cause of OHCA (Figure S2) [5].
Table 1.
Patient, EMS and inhospital treatment characteristics of the matched cohort
| Characteristics | All patients (N = 812) | AH (N = 203) | noAH (N = 609) | p value |
|---|---|---|---|---|
| Age (mean ± SD) | 68.1 ± 13.3 | 68.6 ± 12.3 | 68.0 ± 13.6 | 0.820 |
| Age > 80 years (%) | 18.7 | 18.7 | 18.7 | 1.000 |
| Male sex (%) | 71.3 | 67 | 72.7 | 0.117 |
| Presumed cause of cardiac arrest (%) | ||||
| Cardiac or unknown cause | 100 | 100 | 100 | 1.000 |
| Pre-emergency status (%) | ||||
| Relevant preexisting illness | 33 | 33 | 33 | 1.000 |
| No or little preexisting illness | 63.1 | 63.1 | 63.1 | 1.000 |
| Unknown pre-emergency status | 3.9 | 3.9 | 3.9 | 1.000 |
| Place of collapse (%) | ||||
| Public space or doctor’s office | 22.7 | 22.7 | 22.7 | 1.000 |
| Apartment | 66.1 | 67 | 65.8 | 0.764 |
| Initial ECG rhythm (%) | ||||
| VF/VT | 48.3 | 48.3 | 48.3 | 1.000 |
| Asystole | 33.6 | 34.5 | 33.3 | 0.764 |
| Time of no-flow (min:s), mean ± SD (N) | ||||
| Collapse to CPR | 5:05 ± 6:18 (423) | 4:39 ± 6:02 (131) | 5:17 ± 6:24 (292) | 0.329 |
| Alarm to CPR | 8:52 ± 08:32 (529) | 9:05 ± 9:04 (161) | 8:47 ± 8:17 (368) | 0.943 |
| Collapse witnessed (%) | ||||
| Witnessed by lay people | 51.2 | 51.2 | 51.2 | 1.000 |
| Witnessed by first responder | 2 | 3 | 1.6 | 0.244 |
| Witnessed by EMS | 14.8 | 14.8 | 14.8 | 1.000 |
| CPR to arrival of EMS (%) | ||||
| Bystander CPR | 35 | 35 | 35 | 1.000 |
| First responder CPR | 4.6 | 4.9 | 4.4 | 0.771 |
| CPR via telephone instruction | 17.5 | 13.8 | 18.7 | 0.110 |
| Intervals of EMS, mean ± SD (N) | ||||
| Alarm to arrival (min:s) | 6:48 ± 3:56 (724) | 6:45 ± 3:50 (184) | 6:49 ± 3:58 (540) | 0.952 |
| Alarm to defib in VF/VT (min:s) | 12:50 ± 10:31 (294) | 12:40 ± 8:03 (83) | 12:54 ± 11:22 (211) | 0.198 |
| Alarm to VP in asystole (min:s) | 16:14 ± 9:27 (310) | 15:59 ± 8:02 (88) | 16:20 ± 09:58 (222) | 0.857 |
| Alarm to hospital admission (min:s) | 60:54 ± 19:22 (535) | 58:47 ± 17:58 (157) | 60:46 ± 19:53 (378) | 0.203 |
| Measures taken by EMS (%) | ||||
| Vasopressors | 85.2 | 85.2 | 85.2 | 1.000 |
| Amiodarone | 36 | 31.5 | 37.4 | 0.129 |
| Intubation | 64.5 | 64.5 | 64.5 | 1.000 |
| RACA score | 47.54 ± 17.21 | 47.48 ± 16.84 | 47.56 ± 17.35 | 0.952 |
| ECG signs of ACS or diagnosed ACS (%) | 18.2 | 18.2 | 18.2 | 1.000 |
| Coronary angiography undertaken (%) | 42.4 | 42.2 | 42.2 | 1.000 |
| Mild hypothermia (%) | 28.6 | 28.6 | 28.6 | 1.000 |
ACS acute coronary syndrome, AH aspirin and heparin have been given in the prehospital setting, CPR cardiopulmonary resuscitation, defib defibrillation, ECG electrocardiography, EMS emergency medical service (without first responder), noAH that no aspirin or heparin have been given in the prehospital setting, RACA score ROSC after cardiac arrest score, VF/VT ventricular fibrillation or ventricular tachycardia
In this registry, prehospital AH administration was associated with favorable neurological outcome, ROSC and survival to hospital discharge. Missing ICD-10 codes impede subgroup analysis stratified by definite diagnoses. However, existing interactions with male sex and bystander CPR in conjunction with published data support the hypothesis that our results are in line with our previous findings showing a benefit of AH administration especially in AMI patients [3, 5]. Further limitations are the low administration rate for AH, missing data on AH dosages and administration time, matching which resulted in the selection of patients with favorable conditions as well as the retrospective design. Our observational findings warrant a randomized clinical trial to assess the efficacy and safety of prehospital AH administration in patients with OHCA.
Electronic supplementary material
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Acknowledgements
Open Access funding provided by Projekt DEAL. Collaborating author: Martin von der Helm, MD affiliated at Department of Anaesthesiology, Ludwig-Maximilians-University, Munich, Germany.
Funding
This study has no funding source.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflict of interest.
Footnotes
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Ludwig Weckbach and Matthias Fischer share senior authorship.
Contributor Information
Ulrich Grabmaier, Email: ulrich.grabmaier@med.uni-muenchen.de.
Matthias Fischer, Email: matthias.fischer@af-k.de.
the German Resuscitation Registry Study Group:
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