Blood pressure targets in out-of-hospital cardiac arrest according to the time to return of spontaneous circulation

Abstract

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation and Lundbeck Foundation. Introduction Time to return of spontaneous circulation (ROSC) in patients resuscitated after out-of-hospital cardiac arrest (OHCA) is associated with the severity of brain damage and is an important predictor of mortality. We have recently shown no difference in mortality or neurological outcome with different mean arterial blood pressure targets (63 or 77 mmHg) in the initial phase of post-cardiac arrest management in resuscitated OHCA patients who remained comatose. Accordingly, in this post-hoc analysis, we explored whether time to ROSC modifies the effect of different blood pressure targets on mortality and neurological outcome. Method In a double-blind, randomized trial, a mean arterial blood-pressure target of 63 mm Hg vs. 77 mm Hg in comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause was investigated (BOX-trial, N Engl J Med 2022). Primary outcome for the present analysis was a composite of discharge from hospital severe brain damage or death from any cause within 365 days from randomization for the blood pressure target intervention was analyzed in a proportional hazard model with time to ROSC (tertiles: short, medium, and long) as a subgroup following testing for interaction. The analysis was conducted in the intention to treat the population. Results A total of 789 patients were included in the analysis. The time to ROSC in the three tertiles was: Short [0 min - 13 min], medium [14 min - 22 min], and long [23 min - 117 min]. The three groups were well balanced in the two blood pressure target groups (In the high group (77 mmHg): Short, n=124 (49%); medium, n= 133 (50%), long, n=136 (51%). Age (short: 62.7 (± 14), medium 62.4 (± 13), and 62.6 (± 13) and sex (short: 19.5% female, medium: 19.0% female, long: 19.4% female) were similar in the three groups. The first monitored rhythm did not differ in the three groups (shockable in 82.6%, 86.2%, and 85.3% of patients, respectively). Time to the first defibrillation did, however, differ between the three groups ((short 6.2 min (± 3.3), medium 9.0 min (± 3.8), and long 11.0 min (± 6.6), p<0.0001). The primary outcome occurred in 44 (17.3%), 92 (34.3%), and 153 (57.5%) in the short, medium, and long groups, respectively (p<0.0001). No interaction of time to ROSC and blood pressure target was found (p=0.62). Hazard ratios in the high (77 mmHg) group for the three tertiles were: short: HR 1.34 (95% CI: 0.75 – 2.40), medium: HR: 0.99 (95% CI: 0.68 – 1.45) and long: HR 0.97 (95% CI: 0.71 – 1.32). Conclusion Longer time to ROSC is associated with an adverse outcome, but it does not modify the effect of different blood pressure targets in comatose OHCA patients.