EBQ:Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest

Complete Journal Club Article

Kudenchuk P, Brown S, et al.. "Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest". New England Journal of Medicine. 2016. :.
PubMed Full text PDF

Clinical Question

Does amiodarone or lidocaine improve survival in patients with OHCA caused by shock-refractory Vfib or pulseless Vtach?

Conclusion

Neither amiodarone nor lidocaine resulted in a significantly higher survival rate or favorable neurologic outcome among patients with OHCA due to initial shock-refractory Vfib or pulseless Vtach. There was, however, heterogeneity of treatment effect with respect to whether the arrest was witnessed or not; both drugs were associated with a significant increase in survival rate amongst patient's whose arrest was bystander-witnessed.

Major Points

OHCA arrest takes more than 300,000 lives ever year in the United States, with many of these due to Vfib or Vtach. Since, prehospital care is essential to improving survival for these patients, the medical community looks in this study to determine the effectiveness of currently used drugs for these conditions. Current ACLS standards entail the use of Amiodarone or Lidocaine for cardiac arrest secondary to ventricular fibrillation or pulseless ventricular tachycardia. While many studies have shown improved ROSC with use of these drugs, none yet have definitively spoken to improved hospital discharge or neurologic outcome. While this study did not show a survival benefit for either drug, sub group analysis suggests a benefit in witnessed OHCA.

Study Design

Randomized, double blinded placebo controlled trial
Paramedics from 55 EMS services
10 sites across North America, part of the Resuscitation Outcomes Consortium (ROC)

Population

Patient Demographics

No major differences amongst the three groups with respect to baseline patients demographics.

Inclusion Criteria

Patients 18 years of age or older + non traumatic OHCA + shock refractory ventricular fibrillation or pulseless ventricular tachycardia.
Patients needed to have IV or IO access

Exclusion Criteria

Patients who had already received open label medications
Known hyper sensitivity to one of the trial drugs

Interventions

Group 1: Amiodarone 300 mg. A additional dose of 150 mg was given if rhythm was not terminated.
Group 2: Lidocaine 120 mg. An additional dose of 60 mg was given if rhythm was not terminated.
Group 3: Normal Saline (control group)

Outcomes

Primary Outcome

Survival to Hospital Discharge

Amiodarone 237/970 (24.4%)
Lidocaine 233/985 (23.7%)
Placebo 222/1056 (21%)

When comparing the interventions head to head, no significant ARR was found:

Amio vs. Placebo ARR 3.2 (P Value 0.08)
Lido vs. Placebo ARR 2.6 (P Value 0.16)
Amio vs. Lido ARR 0.7 (P Value 0.7)

Secondary Outcomes

Survival with a favorable neurologic outcome (Modified Rankin < 3). No significant differences were found:

Amiodarone 18.8%
Lidocaine 17.5%
Placebo 16.6%

Subgroup analysis

Bystander Witnessed Arrest was notable for a statistically significant increase in survival to discharge for both Amio and Lidocaine compared to placebo. No difference between the two active drugs were noted.

Amiodarone 27.7%
- vs. placebo ARR 5% (P 0.04)
Lidocaine 27.8%
- vs. placebo ARR 5.2% (P 0.03)
Placebo 22.7%

EMS Witnessed Arrest was notable for a statistically significant increase in survival in the amiodarone group vs placebo.

Amiodarone 38.6%
- vs. placebo ARR 21.9 (P 0.01)
Lidocaine 23.3%
Placebo 16.7%

Criticisms & Further Discussion

Trial may be underpowered to detect a statistically significant result.
The 3% difference in survival may be clinically significant, even though not statistically.
Some results seem puzzling, such as the Lidocaine group having lower survival odds with EMS witnessed vs bystander or overall Lidocaine group.
As the subgroup analysis suggests, there may be a benefit in particular cardiac arrest patients for these drugs (e.g. witnessed) - so further trials should isolate these demographics and confirm the results.

External Links

Funding

The trial was sponsored by the NHLBI, the Canadian Institutes of Health Research. Baxter Healthcare provided all the drugs.

Authors: