Amiodarone and/or lidocaine for cardiac arrest: A Bayesian network meta-analysis.

INTRODUCTION: Although available studies have not demonstrated that antiarrhythmic drugs could increase long-term survival or survival with favorable neurological outcome, some studies have shown that the rate of hospital admission is higher with amiodarone or lidocaine than with placebo. To study the effects of antiarrhythmic drugs during cardiac arrest, a meta-analysis was conducted to assess the efficacy of amiodarone and/or lidocaine. METHODS: We searched studies from inception until Jan 21, 2020. The primary endpoint was survival to hospital discharge in cardiac arrest, and the secondary endpoints were survival to hospital admission/24 h and favorable neurological outcome. RESULTS: A total of 9 studies were included. In head-to-head studies, amiodarone (odds ratio [OR] 2.96, 95% credible interval [CrI] 1.02-8.53) and lidocaine (OR 3.12, 95% CrI 1.08-9.98) had superior effects on survival to hospital admission/24 h compared to the combination of the two drugs. In terms of survival to hospital discharge, amiodarone (OR 1.18, 95% CrI 1.03-1.35) and lidocaine (OR 1.22, 95% CrI 1.06-1.41) were more effective than placebo. Amiodarone (OR 1.20, 95% CrI 1.02-1.41) was significantly better than placebo in favorable neurological outcome. However, there was no significant difference in other pairwise comparisons. The surface under cumulative ranking curve (SUCRA) revealed that lidocaine was the most effective therapy for survival to hospital admission (84.1%) and discharge (88.4%), while amiodarone was associated with a more favorable neurological outcome (88.2%). CONCLUSIONS: Lidocaine had the best effect on both survival to hospital admission and discharge, while amiodarone was associated with a more favorable neurological outcome. TRIAL REGISTRATION: This study is registered with PROSPERO, number CRD42020171049.

Esmolol Compared with Amiodarone in the Treatment of Recent-Onset Atrial Fibrillation (RAF): An Emergency Medicine External Validity Study.

BACKGROUND: Recent-onset atrial fibrillation (RAF) is the most frequent supraventricular dysrhythmia in emergency medicine. Severely compromised patients require acute treatment with injectable drugs OBJECTIVE: The main purpose of this external validity study was to compare the short-term efficacy of esmolol with that of amiodarone to treat severe RAF in an emergency setting. METHODS: This retrospective survey was conducted in mobile intensive care units by analyzing patient records between 2002 and 2013. We included RAF with (one or more) severity factors including: clinical shock, angina pectoris, ST shift, and very rapid ventricular rate. A blind matching procedure was used to constitute esmolol group (n = 100) and amiodarone group (n = 200), with similar profiles for age, gender, initial blood pressure, heart rate, severity factors, and treatment delay. The main outcome measure was the percentage of patients with a ventricular rate control defined as heart frequency ≤ 100 beats/min. More stringent (rhythm control) and more humble indicators (20% heart rate reduction) were analyzed at from 10 to 120 min after treatment initiation. RESULTS: Patient characteristics were comparable for both groups: age 66 ± 16 years, male 71%, treatment delay < 1 h 36%, 1-2 h 29%, > 2 h 35%, chest pain 61%, ST shift 62%, ventricular rate 154 ± 26 beats/min, and blood pressure 126/73 mm Hg. The superiority of esmolol was significant at 40 min (64% rate control with esmolol vs. 25% with amiodarone) and for all indicators from 10 to 120 min after treatment onset. CONCLUSION: In "real life emergency medicine," esmolol is better than amiodarone in the treatment of RAF.

Antiarrhythmic drug therapy during cardiopulmonary resuscitation: should we use it?

PURPOSE OF REVIEW: The optimal antiarrhythmic drug therapy (amiodarone or lidocaine) in the treatment of ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) cardiac arrest that is refractory to defibrillation is uncertain. This article reviews the evidence for and against these drugs, alternatives treatments for refractory VF/pVT and aims to define the role of antiarrhythmic drugs during cardiopulmonary resuscitation (CPR). RECENT FINDINGS: A large randomized controlled trial that compared amiodarone, lidocaine and saline 0.9% sodium chloride for the treatment of refractory VF/pVT out-of-hospital cardiac arrest reported no difference in survival to hospital discharge or neurological outcome. In patients with witnessed arrest, survival was improved with antiarrhythmic drugs compared to saline. SUMMARY: The benefit of antiarrhythmic drugs appears to be for those patients in whom initial early CPR and defibrillation attempts fail and the antiarrhythmic drug is given early. There does not appear to be any clear survival benefit for any one particular drug and other factors such as availability and cost should be considered when deciding which drug to use. Furthermore, other interventions (e.g. percutaneous coronary intervention and extra-corporeal CPR) may provide additional survival benefit when defibrillation attempts and antiarrhythmic drugs are not effective.

Quality by design (QbD) based development and validation of an HPLC method for amiodarone hydrochloride and its impurities in the drug substance.

The USP monograph describes an HPLC method for seven impurities in the amiodarone drug substance using a L1 column, 4.6mm×150mm, 5µm packing (PF listed ODS2 GL-Science, Inertsil column) at 30°C with detection at 240nm. The standard contains 0.01mg/mL of amiodarone, and USP specified impurities D and E with a resolution requirement of NLT 3.5 between peaks D and E. Impurities in a 5mg/mL sample are quantitated against the standard. Impurity A peak elutes just before peak D. We observed two problems with the method; the column lot-to-lot variability resulted in unresolved A, D, and E peaks, and peak D in the sample preparation eluted much later than that in the standard solution. Therefore, optimization experiments were conducted on the USP method following the QbD approach with Fusion AE™ software (S-Matrix Corporation). The resulting optimized conditions were within the allowable changes per USP 〈621〉. Lot-to-lot variability was negligible with the Atlantis T3 (Waters Corporation) L1 column. Peak D retention time remained constant from standard to sample. The optimized method was validated in terms of accuracy, precision, linearity, range, LOQ/LOD, specificity, robustness, equivalency to the USP method, and solution stability. The QbD based development helped in generating a design space and operating space with knowledge of all method performance characteristics and limitations and successful method robustness within the operating space.

Assessment and monitoring in clinical trials when survival curves have distinct shapes: a Bayesian approach with Weibull modelling.

The comparison of Weibull distributions with unequal shape parameters, in the case of right censored survival data obtained from independent samples, is considered within the framework of Bayesian statistical methodology. The procedures are illustrated with the example of a mortality study where a new treatment is compared to a placebo. The posterior distributions about relevant parameters, which may provide support for a conclusion of clinical superiority of the treatment, and the predictive distributions, which may guide decision about early stopping at an interim analysis, are considered for a class of appropriate priors.

[Method of evaluating antiarrhythmic therapy in patients with paroxysms of supraventricular tachycardia]. / Sposob otsenki antiaritmicheskoi terapii u bol'nykh s paroksizmami nadzheludochkovoi takhikardii.

Potentialities of the non-invasive method of trans-esophagus electrostimulation of the heart were studied with regard to the selection and assessment of the effectiveness of antiarrhythmic therapy in 16 patients with paroxysms of supraventricular reciprocal tachycardia. The antiarrhythmic therapy selected by this method proved effective in 13 patients following a prolonged course of treatment. The method was highly informative in predicting the efficacy of the systemic course treatment of patients with supraventricular tachycardia paroxysms.