ObjectiveAntiarrhythmic drugs are recommended for out of hospital cardiac arrest (OHCA) with shock-refractory ventricular fibrillation (VF). Amplitude Spectral Area (AMSA) of VF is a quantitative waveform measure that describes the amplitude-weighted mean frequency of VF, it correlates with intramyocardial adenosine triphosphate (ATP) concentration, it is a predictor of shock efficacy and an emerging indicator to guide defibrillation and resuscitation efforts. How AMSA might be influenced by amiodarone administration is unknown.MethodsIn this international multicentre observational study, all OHCAs receiving at least one shock were included. AMSA values were calculated by retrospectively analysing the pre-shock ECG interval of 2 s. Multivariable models were run and a propensity score based on the probability of receiving amiodarone was created to compare two randomly matched samples.Results2,077 shocks were included: 1,407 in the amiodarone group and 670 in the non-amiodarone group. AMSA values were lower in the amiodarone group [8.8 (6–12.7) mV·Hz vs. 9.8 (6–14) mV·Hz, p = 0.035]. In two randomly matched propensity score-based groups of 261 shocks, AMSA was lower in the amiodarone group [8.2 (5.8–13.5) mV·Hz vs. 9.6 (5.6–11.6), p = 0.042]. AMSA was a predictor of shock success in both groups but the predictive power was lower in the amiodarone group [Area Under the Curve (AUC) non-amiodarone group 0.812, 95%CI: 0.78–0.841 vs. AUC amiodarone group 0.706, 95%CI: 0.68–0.73; p < 0.001].ConclusionsAmiodarone administration was independently associated with the probability of recording lower values of AMSA. In patients who have received amiodarone during cardiac arrest the predictive value of AMSA for shock success is significantly lower, but still statistically significant.