a,b,j , on behalf of GR-RéAC Background Adrenaline is recommended during cardio-pulmonary resuscitation. The optimal dose remains debated, and the effect of lower than recommended dose is unknown.Objective To compare the outcome of patients treated with the recommended, lower or higher cumulative doses of adrenaline.Design, settings, participants Patients were included from the French National Cardiac Arrest Registry and were grouped based on the received dose of adrenaline: recommended, higher and lower dose. Outcome measures and analysisThe primary endpoint was good neurologic outcome at 30 days post-OHCA, defined by a cerebral performance category (CPC) of less than 3. Secondary endpoints included return of spontaneous circulation and survival to hospital discharge. A multiple propensity score adjustment approach was performed.Main results 27 309 patients included from July 1st 2011 to January 1st 2019 were analysed, mean age was 68 (57-78) years and 11.2% had ventricular fibrillation. 588 (2.2%) patients survived with a good CPC score. After adjustment, patients in the high dose group had a significant lower rate of good neurologic outcome (OR, 0.6; 95% CI, 0.5-0.7). There was no significant difference for the primary endpoint in the lower dose group (OR, 0.8; 95% CI, 0.7-1.1). There was a lower rate of survival to hospital discharge in the high-dose group vs. standard group (OR, 0.5; 95% CI, 0.5-0.6). ConclusionThe use of lower doses of adrenaline was not associated with a significant difference on survival good neurologic outcomes at D30. But a higher dose of adrenaline was associated with a lower rate of survival with good neurological outcomes and poorer survival at D30.

Adrenaline is recommended for cardiac arrest resuscitation, but its effectiveness has been questioned recently. Achieving return of spontaneous circulation (ROSC) is essential and is obtained by increasing coronary perfusion pressure (CPP) after adrenaline injection. A threshold as high as 35 mmHg of CPP may be necessary to obtain ROSC, but increasing doses of adrenaline might be harmful to the brain. Our study aimed to compare the increase in CPP with reduced doses of adrenaline to the recommended 1 mg dose in a pig model of cardiac arrest. Fifteen domestic pigs were randomized into three groups according to the adrenaline doses: 1 mg, 0.5 mg, or 0.25 mg administered every 5 min. Cardiac arrest was induced by ventricular fibrillation; after 5 min of no-flow, mechanical chest compression was resumed. The Wilcoxon test and Kruskal–Wallis exact test were used for the comparison of groups. Fisher’s exact test was used to compare categorical variables. CPP, EtCO2 level, cerebral, and tissue near-infrared spectroscopy (NIRS) were measured. CPP was significantly lower in the 0.25 mg group 90 s after the first adrenaline injection: 28.9 (21.2; 35.4) vs. 53.8 (37.8; 58.2) in the 1 mg group (p = 0.008), while there was no significant difference with 0.5 mg 39.6 (32.7; 52.5) (p = 0.056). Overall, 0.25 mg did not achieve the threshold of 35 mmHg. EtCO2 levels were higher at T12 and T14 in the 0.5 mg than in the standard group: 32 (23; 35) vs. 19 (16; 26) and 26 (20; 34) vs. 19 (12; 22) (p < 0.05). Cerebral and tissue NIRS did not show a significant difference between the three groups. CPP after 0.5 mg boluses of adrenaline was not significantly different from the recommended 1 mg in our model of cardiac arrest.