The role of antiarrhythmic drugs in cardiac arrest has gradually shifted over the decades. Only amiodarone remains, among drugs which are used as a part of the cardiac arrest algorithm. Even amiodarone's position in the ALS algorithm is not perpetually assured.
Question 26 from the second paper of 2005 pre-dated the changes in ARC guidelines which have done away with lignocaine and atropine.
In brief, the objective of giving amiodarone after the third cycle of CPR for a shockable rhythm is to convert a defibrillation-refractory VF into one which is defibrillation-sensitive. The evidence for its use is supported by two trials (Dorian et al 2002, and Somberg et al 2002) which found some benefit of amiodarone over lignocaine in the context of shock refractory or recurrent VT and VF. There was no benefit in survival to hospital discharge. However, Kudenchuk et al (1999) found some benefit in survival to hospital admission. A meta-analysis in 2013 (Huang et al) re-analysed the data and came to the same depressing conclusion. This better than the evidence for any other anitarrhytmic drug, and thus amiodarone remains in the guidelines ...for now.
If one only had time to read only one source for this, the LITFL page would be enough to write an SAQ answer. There, one may also find a link to the 2011 review article by Ong et al, which is an excellent detailed overview.
All of this information is available in the ARC Guideline 11.5: Medications in Adult Cardiac Arrest. In brief summary, other drugs which are covered by this guidelines statement are as follows:
Numerous papers have been published, and only a selection of a few interesting ones is offered here.
Kudenchuk et al (1999) - randomized, double-blind, placebo-controlled study in the prehospital setting; amiodarone (246 patients) or placebo (258 patients). Methodology resembles current practice (maybe because current practice is based mainly on this study) - 300mg amiodarone was given after the third shock. Survival to admission was improved (44% vs 34%). There was no significant improvement in survival until hospital discharge, nor was the study powered to detect such an improvement anyway.
Dorian et al (2002) performed a randomized, double-blind, placebo-controlled study in the prehospital setting; 347 patients in total. Methodology near-identical to Kudenchuk et al, except the authors compared amiodarone (2.5mg/kg) to lignocaine (1.5mg/kg). Unlike Kudenchuk et al, the protocol allowed repeated doses of either drug if the arrest continued. Amiodarone was the clear winner again: survival to admission was improved (22.8% vs 12.0%). Again there was no statistically significant difference in survival until discharge (5% vs 3%) in this grim pre-hypothermia dark age.
A double-blind, parallel-design cross-over trial; 29 patients with shock-resistant VT received either two boluses 150mg amiodarone or two boluses of 100mg lignocaine, and crossed over to the other drug if the first one didn't work. The first line treatment was always cardioversion: patients were only eligible for enrolment if the first shock had failed. Amiodarone was markedly better at lignocaine, both at terminating the arrhythmia (78% vs 27%) and in terms of 24-hour survival (39% vs 9%).
Of the lignocaine group, only one patient survived the first hour after VT termination. The rest ended up failing two boluses of lignocaine, then got shocked and crossed over to amiodarone. Then, the majority failed two boluses of that, developed asystole or brady-PEA and died. This brings up some questions. What the hell kind of resuscitation were these patients receiving? Was there even CPR? The average heart rate was 120; what about overdrive pacing?
In 2014 Kudenchuk et al published the rationale and methodology of their large scale of amiodarone vs. lignocaine vs. nothing. They expected n=3000, providing 90% power to detect a 6.3% survival benefit (from 23.4% to 29.7%). By the end of enrolment in 2015, they had 3026 patients. The detected survival benefit for amiodarone (vs placebo) was unfortunately only 3.2%, and 2.6% for lignocaine (i.e. a statistically insiginificant 0.7% difference). The treatment effect was somewhat better in the group of patients with witnessed arrest, suggesting that bystander CPR maintains some myocardial oxygenation so that the antiarrhythmics can have a chance to work. Ultimately, the authors were forced to conclude that on the basis of their data it was impossible to tell which drug was better, and in fact neither performed much better than placebo.
Huang et al (2013) a meta-analysis of the above trials, plus a whole bunch of others. In total ten RCTs and seven observational studies were scraped together. The authors were able to firmly conclude in favour of amiodarone (vs. lignocaine and nifekalant) and against sotalol or bretylium. However, all the improvement was focused on surviving the arrest, rather than the hospital admission. Similarly, the 2016 meta-analysis by Laina et al redemonstrated the trend towards better prehospital survival and unchanged in-hospital mortality. On the basis of this, one may continue to make an argument for the ongoing use of amiodarone in cardiac arrest: the first step to overall survival is survival to hospital admission.