‘PARAMEDIC-2: Big study, small result’
The PARAMEDIC-2 trial demonstrated that the use of adrenaline compared with placebo in out-of-hospital cardiac arrest (OHCA) resulted in a small increase in 30-day survival, but was associated with a higher number of survivors with severe neurological impairment. These findings received a lot of attention, and generated a widespread discussion about the role of adrenaline in cardiac arrest. In this point of view, we aim to place the PARAMEDIC-2 results in the right perspective by comparing the relative effect of adrenaline to other determinants of cerebral blood flow.
KeywordsAdrenaline Out-of-hospital cardiac arrest OHCA
Point of view
Last year, the authors of the PARAMEDIC2 trial demonstrated that the use of adrenaline compared with placebo in out-of-hospital cardiac arrest (OHCA) resulted in a small increase in 30-day survival. In addition, they showed that no significant between-group difference in the rate of a favourable neurologic outcome was observed, as more survivors had severe neurologic impairment in the adrenaline group . These findings generated a widespread discussion around the use of adrenaline during cardiac arrest, and resulted in the publication of multiple commentaries focusing on the potential beneficial- or detrimental effects of adrenalin in OHCA [2, 3, 4].
Although this provides a pathophysiological mechanisms for the reported association between adrenaline and a bad neurological outcome in the PARAMEDIC-2 trial, other determinants of microcirculatory CBF likely had a far greater impact on neurological outcome: 37% of the arrests in the PARAMEDIC-2 trial were unwitnessed, and patients received on average 21 minutes of CPR before a first bolus of adrenaline was administered. These prolonged no-flow and resuscitation times likely had a far greater impact on neurological outcome than the (average dose of 4.9 mg) adrenaline administered (Fig. 1). This is supported by the (albeit not reported) high number needed to harm for adrenaline in the PARAMEDIC-2 trial: 39/4015 patients survived with modified Rankin score of 4 or 5 in the adrenaline group compared with 16/3999 in the placebo group, resulting in a number needed to harm of 175.
In our opinion, attention should therefore be focused on the improvement of bystander CPR and early defibrillation rather than focusing on marginal gains (or pains) of adrenaline administration during OHCA.
Conflict of interest
E. ter Avest and H. Lameijer declare that they have no competing interests.
- 2.Kuiper MA. Epinephrine, a double edged sword? Ned Tijdschr Geneeskd. 2018;162:D3519.Google Scholar
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