Was there a follow-up study to the Paramedic2 (Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest 2) trial?

From the Guidelines

Yes, there was a follow-up study to the PARAMEDIC2 trial, which examined the long-term outcomes of survivors from the original trial. The PARAMEDIC2 trial, published in 2018, was a landmark study that evaluated the effectiveness of epinephrine (adrenaline) in out-of-hospital cardiac arrest 1. Although the provided evidence does not explicitly mention a follow-up study published in 2021, it does discuss the outcomes of the PARAMEDIC2 trial, including survival and neurological outcomes at 3 months 1. The trial found that epinephrine improved survival at 30 days and increased return of spontaneous circulation (ROSC), but there was no significant difference in survival to hospital discharge with a favorable neurological outcome 1.

Key Findings

• The PARAMEDIC2 trial showed that epinephrine increased survival to hospital admission and to 30 days compared to placebo 1
• The trial found no difference in survival with favorable or unfavorable neurological outcome at 3 months 1
• Epinephrine improved ROSC and survival to hospital discharge, but its impact on neurological outcome remains uncertain 1

Clinical Implications

• The use of epinephrine in cardiac arrest with nonshockable rhythms is recommended as soon as feasible, unless there is a clearly reversible cause that can be addressed rapidly 1
• The optimal timing for epinephrine in patients with shockable rhythms is unknown, but it is suggested to administer epinephrine after initial defibrillation attempts have been unsuccessful 1
• The standard dose of epinephrine (1 mg intravenous or intraosseous every 3-5 minutes) is recommended, based on the evidence from the PARAMEDIC2 trial and other studies 1

From the Research

Follow-up Study to Paramedic2 Trial

• A follow-up study to the Paramedic2 trial was conducted to report long-term survival, quality of life, functional and cognitive outcomes at 3,6 and 12-months 2.
• The study found that adrenaline improved survival through to 12-months follow-up, but did not find evidence of improvements in favourable neurological outcomes 2.
• The follow-up study analyzed data from 8014 patients who were randomized to either adrenaline or placebo, with confirmed trial drug administration 2.

Key Findings

• At 6-months, 78 (2.0%) of the patients in the adrenaline group and 58 (1.5%) of patients in the placebo group had a favourable neurological outcome (adjusted odds ratio 1.35 [95% confidence interval: 0.93,1.97]) 2.
• 117 (2.9%) patients were alive at 6-months in the adrenaline group compared with 86 (2.2%) in the placebo group (1.43 [1.05,1.96]), reducing to 107 (2.7%) and 80 (2.0%) respectively at 12-months (1.38 [1.00,1.92]) 2.
• Measures of 3 and 6-month cognitive, functional and quality of life outcomes were reduced, but there was no strong evidence of differences between groups 2.

Related Studies

• Other studies have investigated the effects of adrenaline in out-of-hospital cardiac arrest, including the relationship between repeated doses of adrenaline and survival 3, and the effects of early pre-hospital adrenaline administration 4.
• A study combining the results of the PARAMEDIC-2 and PACA trials found that the effect of adrenaline on return of spontaneous circulation was greater in patients with non-shockable cardiac rhythms compared to shockable rhythms 5.
• A secondary analysis of the PARAMEDIC2 trial compared the effectiveness of intravenous and intraosseous administration of adrenaline in patients with out-of-hospital cardiac arrest 6.