Washington University Emergency Medicine Journal Club – May 2025
Vignette
You are doing a ride along with EMS on your EMS rotation when your crew is called to the scene of a cardiac arrest. The patient is a 50-year woman with cardiac arrest witnessed by coworkers. Per bystanders the patient began complaining of chest pain before collapsing into a coworker’s arms. A witness started CPR but no AED was available at the scene. You arrive approximately 10 minutes after arrest to find that the patient remains pulseless. The initial rhythm on your monitor is ventricular fibrillation (VF). You take over CPR as the paramedics place pads on the patient and start an IV. You shock the patient (biphasic, 200 J) and continue CPR. After 2 minutes, the rhythm remains VF. At that time the paramedics administer 300 mg of IV amiodarone as you shock the patient a 2nd time and load them on the truck. You continue CPR, shock the patient a 3rd time, and administer a 2nd dose of amiodarone (150 mg). After arrival to the ED, the patient is found to be in asystole, and after an additional 10 minutes of resuscitative efforts the code is called due to futility.
During a debriefing with the ED team, somebody mentions a recent pair of articles from the Annals of Emergency Medicine Clinical Controversies series in which authors debate the efficacy of amiodarone and lidocaine for pulseless ventricular tachycardia (VT) and VF. After the debrief you decide to check out these articles, then look at the articles cited by the authors to see which treatment you think is truly superior.
PICO Question
Population: Adult patients suffering out-of-hospital cardiac arrest with ventricular
fibrillation or ventricular tachycardia the persists after at least one attempt at
defibrillation
Intervention: IV amiodarone
Comparison: IV lidocaine
Outcome: ROSC, survival to hospital admission, survival to hospital discharge,
survival with a good neurologic outcome
Search Strategy
Articles were selected from references made in the above-mentioned Clinical
Controversies series.
Article 1: Dorian P, Cass D, Schwartz B, Cooper R, Gelaznikas R, Barr A. Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation. N Engl J Med. 2002 Mar 21;346(12):884-90. doi: 10.1056/NEJMoa013029. Erratum in: N Engl J Med 2002 Sep 19;347(12):955. PMID: 11907287. (Answer Key)
Article 2: Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P; Resuscitation Outcomes Consortium Investigators. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2016 May 5;374(18):1711-22. doi: 10.1056/NEJMoa1514204. Epub 2016 Apr 4. PMID: 27043165. (Answer Key)
Article 3: Wang Q, Lin Z, Chen H, Pan B. Comparison the efficacy of amiodarone and lidocaine for cardiac arrest: A network meta-analysis. Medicine (Baltimore). 2023 Apr 14;102(15):e33195. doi: 10.1097/MD.0000000000033195. PMID: 37058064; PMCID: PMC10101268. (Answer Key)
Article 4: Ali MU, Fitzpatrick-Lewis D, Kenny M, Raina P, Atkins DL, Soar J, Nolan J, Ristagno G, Sherifali D. Effectiveness of antiarrhythmic drugs for shockable cardiac arrest: A systematic review. Resuscitation. 2018 Nov;132:63-72. doi: 10.1016/j.resuscitation.2018.08.025. Epub 2018 Sep 1. PMID: 30179691. (Answer Key)
Bottom Line
In a recent contribution to the Annals of Emergency Medicine Clinical Controversies series, the relative benefits of amiodarone and lidocaine in the management of ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) were debated. Proponents of lidocaine highlighted its ease of administration, favorable pharmacokinetics, lack of significant drug interactions, and relative paucity of short-term adverse effects. Proponents of amiodarone, on the other hand, noted robust data demonstrating increased rates of return of spontaneous circulation (ROSC), especially if used early, and broader receptor targets relative to lidocaine. We sought to review the data comparing these two drugs for this application, with a focus on those trials and meta-analyses highlighted by the authors of the Clinical Controversies articles.
The original trial comparing amiodarone and lidocaine shock-resistant VF and pVT was published in 2002 (Dorian 2002). This randomized controlled trial was conducted in the Toronto Emergency Medical Services system between November, 1995 and April, 2001. After randomizing 347 patients to receive either amiodarone (n = 180) or lidocaine (n = 167), those receiving amiodarone were more likely to survive to hospital admission compared to the lidocaine group (22.8% vs. 12.0%; odds ratio [OR] 2.17, 95% CI 1.21 to 3.83). While not statistically significant, there was also a trend towards improved survival to hospital discharge with amiodarone use (OR 1.69, 95% CI 0.56 to 5.16). This study did not look at long-term survival or neurologic outcomes.
Over a decade after the promising results of this initial trial, a much larger multicenter randomized controlled trial was conducted at 55 emergency medical services at 10 North American sites from May 7, 2012 to October 25, 2015 (Kudenchuk 2016). The ROC-ALPS study enrolled 3026 patients in its per protocol analysis (974 received amiodarone; 993 received lidocaine; and 1059 received placebo), and found that survival to hospital discharge occurred in 24.4% of patients receiving amiodarone, 23.7% of patients receiving lidocaine, and 21.0% of patients receiving placebo. For this outcome there was no significant difference between amiodarone and placebo (absolute risk reductio [ARR] 3.2%, 95% CI -0.4 to 7.0%), between lidocaine and placebo (ARR 2.6% 95% CI -1.0 to 6.3%) or between amiodarone and lidocaine (ARR 0.7%, 95% CI -3.2 to 4.7%). Rates of favorable neurologic outcomes were also similar between the amiodarone (18.8%), lidocaine (17.5%), and placebo groups (16.6%). In subgroup analysis, survival to hospital discharge in those patients with witnessed OHCA was higher among patients receiving amiodarone vs. placebo and among those receiving lidocaine vs. placebo.
The authors of the pro-lidocaine side of the Clinical Controversies article site a meta-analysis of 14 randomized controlled trials (RCTs) that demonstrate significantly higher rates of ROSC with lidocaine compared with amiodarone (Ali 2018). Unfortunately, this statement is quite misleading and actually untrue. The only RCTs comparing amiodarone and lidocaine identified in this meta-analysis were those discussed above (Dorian 2002, Kudenchuk 2016). Only Kudenchuk et al reported outcomes for ROSC with a slight trend in favor of lidocaine which did not achieve statistical significance (RR 0.90; 95% CI 0.80 to 1.01). The meta-analysis also found no difference in survival to hospital discharge (RR 1.04; 95% CI 0.89 to 1.22) or survival with favorable neurological function at hospital discharge (RR 1.08; 95% CI 0.89 to 1.30).
The pro-amiodarone authors from the Clinical Controversies article cite a network meta-analysis including 10980 patients from 5 studies (Wang 2023). While this paper found that amiodarone was superior to lidocaine with respect to survival to hospital admission (OR 1.49, 95% CI 1.12–1.98), survival to hospital discharge (OR 1.38, 95% CI 1.04–1.84), and survival with a favorable neurologic outcome (OR 1.5, 95% CI 1.09–2.07), analysis of their tables suggests that these findings are erroneous. As an example, in their Forest plot of survival to hospital admission (Figure 5, section C), none of the odds ratios match the outcomes reported in either Dorian et al or Kudenchuk et al, but rather all 6 odds ratios for the comparison of lidocaine with amiodarone demonstrate strong trends in favor of amiodarone. Additionally, there are numerous contradictory statements that demonstrate either language issues or lack of understanding of statistical concepts throughout article from the open-access Medicine journal.
This review highlights the importance of critical appraisal, as the authors of both aspects of the Clinical Controversies article make claims to support their sides which are either misleading or do not reflect the most patient-centered outcomes. While amiodarone demonstrated increased rates of ROSC in Dorian et al, there was a trend in favor of lidocaine in the subsequent trial by Kudenchuk et al. More importantly, neither drug demonstrated superiority in terms of survival to hospital discharge or rates of favorable neurologic outcomes. In fact, in the largest RCT available neither drug was superior to placebo. Given that there may some benefit to either drug in certain subgroups (i.e. those with EMS or bystander witnessed out-of-hospital and those receiving medication earlier) it is reasonable to administer either medication in cases of refractory VF or pVT, though the choice of medication does not appear to have a significant impact on key outcomes.