Impact of the route of adrenaline administration in patients suffering from out-of-hospital cardiac arrest on 30-day survival with good neurological outcome (ETIVIO study).

BACKGROUND: Over the past decades, international guidelines for cardiopulmonary resuscitation (CPR) have changed the recommendation for alternative routes for drug administration. Until now, evidence for the substantial superiority of one route with respect to treatment outcome after CPR has been lacking. The present study compares the effects of intravenous (IV), intraosseous (IO) and endotracheal (ET) adrenaline application during CPR in out-of-hospital cardiac arrest (OHCA) on clinical outcomes within the database of the German Resuscitation Registry (GRR). METHODS: This registry analysis was based on the GRR cohort of 212,228 OHCA patients between 1989 and 2020. Inclusion criteria were: OHCA, application of adrenaline, and out-of-hospital CPR. Excluded from the study were patients younger than 18 years, those who had trauma or bleeding as suspected causes of cardiac arrest, and incomplete data sets. The clinical endpoint was hospital discharge with good neurological outcome [cerebral performance category (CPC) 1/2]. Four routes of adrenaline administration were compared: IV, IO, IO + IV, ET + IV. Group comparisons were done using matched-pair analysis and binary logistic regression. RESULTS: In matched-pair group comparisons of the primary clinical outcome hospital discharge with CPC 1/2, the IV group (n = 2416) showed better results compared to IO (n = 1208), [odds ratio (OR): 2.43, 95% confidence interval (CI): 1.54-3.84, p < 0.01] and when comparing IV (n = 8706) to IO + IV (n = 4353), [OR: 1.33, 95% CI: 1.12-1.59, p < 0.01]. In contrast, no significant difference was found between IV (n = 532) and ET + IV (n = 266), [OR: 1.26, 95% CI: 0.55-2.90, p = 0.59]. Concurrently, binary logistic regression yielded a highly significant effect of vascular access type (χ² = 67.744(3), p < 0.001) on hospital discharge with CPC1/2, with negative effects for IO (regression coefficient (r.c.) = - 0.766, p = 0.001) and IO + IV (r.c. = - 0.201, p = 0,028) and no significant effect for ET + IV (r.c. = 0.117, p = 0.770) compared to IV. CONCLUSIONS: The GRR data, collected over a period of 31 years, seem to emphasize the relevance of an IV access during out-of-hospital CPR, in the event that adrenaline had to be administered. IO administration of adrenaline might be less effective. ET application, though removed in 2010 from international guidelines, could gain importance as an alternative route again.

Development of the epidemiology and outcomes of out-of-hospital cardiac arrest using data from the German Resuscitation Register over a 15-year period (EpiCPR study).

BACKGROUND: Sudden cardiac arrest is a relevant problem with a significant number of deaths in Europe. AIM: Using data from the German Resuscitation Register (GRR), we examined changes in epidemiology and therapeutic interventions over a 15-year period in order to identify key factors contributing to favourable outcome in out-of-hospital cardiac arrest (OHCA) patients. METHODS: GRR data were analysed in 5-year periods (2006-2010 vs 2011-2015 vs 2016-2020) representing changes in the European Resuscitation Council (ERC) guidelines. Group comparison of OHCA patients was made for epidemiological and resuscitation-associated factors. Endpoints included 30-day survival and hospital discharge with a good neurological outcome (CPC 1,2). Matched-pair analysis compared outcomes, and multivariate binary logistic regression analysis identified variables with effects on survival. RESULTS: A total of 42,997 GRR patients were studied (2006-2010: n = 3,471, 2011-2015: n = 16,122, 2016-2020: n = 23,404). Proportion of patients over 80 years, use of intraosseous (IO) access and supraglottic airway devices, rate of bystander CPR, and the proportion of telephone CPR increased over the study period. The 30-day survival, and hospital discharge rates with CPC1/2 were unchanged. After adjusting cohorts using matched pairs, a higher CPC1,2 rate was observed (8.8 vs 10.2%, p < 0.03). Logistic regression analysis showed that IO and SAD had an unfavourable impact on outcome. CONCLUSION: Despite a significant increase in bystander and telephone CPR rates, no improvement in 30-day survival and hospital discharge rate with CPC1,2 was observed. Initial rhythm (VF/VT), cardiac and hypoxic cause of CA, bystander CPR and IV access were identified as factors associated with a favourable neurological outcome.

Acute Lung Functional and Airway Remodeling Effects of an Inhaled Highly Selective Phosphodiesterase 4 Inhibitor in Ventilated Preterm Lambs Exposed to Chorioamnionitis.

Phosphodiesterase (PDE) inhibition has been identified in animal studies as a new treatment option for neonatal lung injury, and as potentially beneficial for early lung development and function. However, our group could show that the inhaled PDE4 inhibitor GSK256066 could have dose-dependent detrimental effects and promote lung inflammation in the premature lung. In this study, the effects of a high and a low dose of GSK256066 on lung function, structure and alveolar development were investigated. In a triple hit lamb model of Ureaplasma-induced chorioamnionitis, prematurity, and mechanical ventilation, 21 animals were treated as unventilated (NOVENT) or 24 h ventilated controls (Control), or with combined 24 h ventilation and low dose (iPDE1) or high dose (iPDE10) treatment with inhaled GSK 256066. We found that high doses of an inhaled PDE4 inhibitor impaired oxygenation during mechanical ventilation. In this group, the budding of secondary septae appeared to be decreased in the preterm lung, suggesting altered alveologenesis. Ventilation-induced structural and functional changes were only modestly ameliorated by a low dose of PDE4 inhibitor. In conclusion, our findings indicate the narrow therapeutic window of PDE4 inhibitors in the developing lung.