Adrenaline is a hot topic in emergency care in terms of whether its use actually improves survival for patients in cardiac arrest. The aim for this double-blind randomized placebo-controlled trial was to establish the efficacy of adrenaline in out-of-hospital cardiac arrest.
The study's primary outcome measure was survival to hospital discharge with secondary outcomes being prehospital return of spontaneous circulation (ROSC), and the patient's cerebral performance category (CPC) score at hospital discharge (scale ranges from 1 being normal function, through to 5 where the patient is dead).
Initially, it was determined that the study required 2213 patients per group to be adequately powered to detect clinically important treatment effects. To achieve this sample size, the researchers approached five centres within Australia and New Zealand.
However, for various reasons (including negative media coverage and political pressures prior to the commencement of the trial) four of the services did not participate. This resulted in the study becoming a single-centre trial within the ambulance service covering Perth.
Before the trial started, each paramedic completed specific training including pharmacology of adrenaline; input about the study protocol; additional practice in IV cannulation; and clinical simulations around management of cardiac arrest.
A total of 4103 out-of-hospital cardiac arrests were attended by the ambulance service in Perth during the trial period (11 August 2006 to the end of November 2009). In total, 601 patients were randomized to receive either sodium chloride 0.9% (placebo) or adrenaline 1:1000 during advanced life support.
Of these, 67 had to be excluded as the randomization number was not recorded, leaving 262 patients in the placebo group, and 272 in the adrenaline group. For the purposes of the study, the adrenaline and the placebo were produced in identical vials with tamperproof seals and issued to paramedics using the same distribution process as normal within the participating ambulance service.
Patients' characteristics such as age and gender, and whether or not the patient received bystander CPR were similar in each group. With reference to the primary outcome of survival to hospital discharge, the results did not show a statistical difference with 5 people surviving in the placebo group, and 11 survivors in the adrenaline group (OR=2.2; 95% CI 0.76.3).
Of these patients, 14 had a CPC score of either 1 or 2, and of the remaining two individuals (both assigned to the adrenaline group) one scored 3, and one scored 4.
Patients receiving adrenaline demonstrated a statistically significant increase in ROSC when compared to the placebo group (23.5% vs 8.4%; OR 3.4; 95% CI 2.0–5.6) which, while not the primary outcome for the study, is nonetheless an important clinical endpoint.
The researchers are transparent about the limitations of their trial. For example, the study was substantially underpowered with the withdrawal of four of the five study sites; and the researchers were unable to assess the quality of delivered CPR which should be an important consideration in any research into cardiac arrest, as if the quality of the CPR is variable then this could impact on patient outcome.
In conclusion, the authors suggest that this study should be considered a platform for further research as although it makes an important contribution to the current evidence base in this area, significant questions still remain unanswered.
