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INTRODUCTION Previous research suggests there may be differences in the effects of adrenaline related to the initial cardiac arrest rhythm. The aim of this study was to assess the effect of adrenaline compared with placebo according to whether the initial cardiac arrest rhythm was shockable or non-shockable. METHODS Return of spontaneous circulation (ROSC), survival and neurological outcomes according to the initial arrest rhythm were compared amongst patients enrolled in the PARAMEDIC-2 randomised, placebo controlled trial. The results of the PARAMEDIC-2 and PACA out of hospital cardiac arrest trials were combined and meta-analysed. RESULTS The initial rhythm was known for 3929 (98.2%) in the placebo arm and 3919 (97.6%) in the adrenaline arm. The effect on the rate of ROSC of adrenaline relative to placebo was greater in patients with non-shockable cardiac rhythms (1002/3003 (33.4%) versus 222/3005 (7.4%), adjusted OR: 6.5, (95% CI 5.6-7.6)) compared with shockable rhythms 349/716 (48.7%) versus (208/702 (29.6%), adjusted OR: 2.3, 95%CI: 1.9-2.9)). The adjusted odds ratio for survival at discharge for non-shockable rhythms was 2.5 (1.3, 4.8) and 1.3 (0.9, 1.8) for shockable rhythms (P value for interaction 0.065) and 1.8 (0.8-4.1) and 1.1 (0.8-1.6) respectively for neurological outcome at discharge (P value for interaction 0.295). Meta-analysis found similar results. CONCLUSION Relative to placebo, the effects of adrenaline ROSC are greater for patients with an initially non-shockable rhythm than those with a shockable rhythms. Similar patterns are observed for longer term survival outcomes and favourable neurological outcomes, although the differences in effects are less pronounced. ISRCTN73485024.