pyrimidinones and Out-of-Hospital-Cardiac-Arrest

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Topics: Amiodarone; Anti-Arrhythmia Agents; Emergency Medical Services; Humans; Intensive Care Units; Lidocaine; Out-of-Hospital Cardiac Arrest; Placebos; Pyrimidinones; Ventricular Fibrillation

We evaluated the association between nifekalant or amiodarone on hospital admission and in-hospital mortality for cardiac arrest patients with persistent ventricular fibrillation on hospital arrival.. This was a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database. We identified 2961 patients who suffered cardiogenic out-of-hospital cardiac arrest and who had ventricular fibrillation on hospital arrival between July 2007 and March 2013. Patients were categorized into amiodarone (n=2353) and nifekalant (n=608) groups, from which 525 propensity score-matched pairs were generated.. We found a significant difference in the admission rate between the nifekalant and amiodarone groups in propensity score-matched groups (75.6% vs. 69.3%, respectively; difference, 6.3%; 95% confidence interval (CI), 0.9-11.7). An analysis using the hospital nifekalant/amiodarone rate as an instrumental variable found that receiving nifekalant was associated with an improved admission rate (22.2%, 95% CI, 11.9-32.4). We found no significant difference in in-hospital mortality between the nifekalant and amiodarone groups (81.5% vs. 82.1%, respectively; difference, -0.6%; 95% CI, -5.2 to 4.1). Instrumental variable analysis showed that receiving nifekalant was not associated with reduced in-hospital mortality (6.2%, 95% CI, -2.4 to 14.8).. This nationwide study suggested no significant in-hospital mortality association between nifekalant and amiodarone for cardiogenic out-of-hospital cardiac arrest patients with ventricular fibrillation/persistent ventricular tachycardia on hospital arrival. Although nifekalant may potentially improve hospital admission rates compared with amiodarone for these patients, further studies are required to confirm our results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Emergency Medical Services; Female; Hospital Mortality; Hospitalization; Humans; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Pyrimidinones; Retrospective Studies; Ventricular Fibrillation; Young Adult

Amiodarone (AMD), nifekalant (NIF), and lidocaine (LID) hydrochlorides are widely used for ventricular tachycardia/fibrillation (VT/VF). This study retrospectively investigated the NIF potency and the differential effects of 2 initial AMD doses (≤150 mg or 300 mg) in the Japanese SOS-KANTO 2012 study population.. From 16,164 out-of-hospital cardiac arrest cases, 500 adult patients using a single antiarrhythmic drug for shock-resistant VT/VF were enrolled and categorized into 4 groups (73 LID, 47 NIF, 173 AMD-≤150, and 207 AMD-300). Multivariate analyses evaluated the outcomes of NIF, AMD-≤150, or AMD-300 groups versus LID group. Odds ratios (ORs) for survival to admission were 3.21 [95% confidence interval (CI): 1.38-7.44, P < 0.01] in NIF and 3.09 (95% CI: 1.55-6.16, P < 0.01) in AMD-≤150 groups and significantly higher than those of the LID group. However, the OR was 1.78 (95% CI: 0.90-3.51, P = 0.10) in AMD-300 group and was not significant than LID group. ORs for 24-hour survival were 6.68 in NIF, 4.86 in AMD-≤150, and 2.97 in AMD-300, being significantly higher in these groups.. NIF and AMD result in similar improvements for 24-hour survival in cardiopulmonary arrest patients, and this suggest the necessity of a randomized control study.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Female; Humans; Japan; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Pyrimidinones; Survival Rate; Treatment Outcome

Nifekalant is a pure potassium channel blocker that has been used to treat ventricular tachyarrhythmias since 1999 in Japan. Intravenous amiodarone was approved later than nifekalant in Japan, and it is still unclear which of the two agents is superior. The aim of this study was to compare the efficacy of nifekalant and amiodarone for resuscitation of out-of-hospital cardiopulmonary arrest caused by shock-resistant ventricular fibrillation.. From December 2005 to January 2011, ambulance services transported 283 out-of-hospital cardiopulmonary arrest patients to our hospital. Of these, 25 patients were treated with nifekalant or amiodarone in response to ventricular fibrillation that was resistant to two or more shocks. We undertook a retrospective analysis of these 25 patients.. We enrolled 20 men and 5 women with a mean age (± standard deviation) of 61.1 ± 16.4 years. All 25 patients were treated with tracheal intubation and intravenous epinephrine. Fourteen patients received nifekalant and 11 patients received amiodarone. The rates of return of spontaneous circulation (ROSC) (nifekalant, 5/14, versus amiodarone, 4/11; P = 0.97) and survival to discharge (nifekalant, 4/14, versus amiodarone, 2/11; P = 0.89) were not significantly different between the two groups. The time from nifekalant or amiodarone administration to ROSC was 6.0 ± 6.6 and 20.3 ± 10.0 min, respectively, which was significantly different (P < 0.05).. In this small sample size study, nifekalant, compared with amiodarone, is equally effective for ROSC and survival to discharge after shock-resistant ventricular fibrillation and can achieve ROSC more quickly. Further prospective studies are needed to confirm our results.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Cardiopulmonary Resuscitation; Dose-Response Relationship, Drug; Electric Countershock; Female; Humans; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Prospective Studies; Pyrimidinones; Retrospective Studies; Ventricular Fibrillation

Nifekalant hydrochloride (NIF) is an intravenous class-III antiarrhythmic agent that purely blocks the K(+)-channel without inhibiting β-adrenergic receptors. The present study was designed to investigate the feasibility of NIF as a life-saving therapy for out-of-hospital ventricular fibrillation (VF).. The Japanese Population-based Utstein-style study with basic and advanced Life Support Education study was a multi-center registry study with 4 participating institutes located at the northern urban area of Osaka, Japan. Eligible patients were those treated with NIF because of out-of-hospital VF refractory to 3 or more precordial shocks and intravenous epinephrine. Between February 2006 and February 2007, 17 patients were enrolled for the study. The time from a call for emergency medical service to the first shock was 12(6-26)min. The time from the first shock to the NIF administration was 25.5(9-264)min and the usage dose of NIF was 25(15-210)mg. When excluding 3 patients in whom percutaneous extracorporeal membrane oxygenation was applied before NIF administration, the rate of return of spontaneous circulation was 86% and the rate of admission alive to the hospital was 79%. One patient developed torsade de pointes.. Intravenous administration of NIF seems to be feasible as a potential therapy for advanced cardiac life-support in patients with out-of-hospital VF, and therefore further study is warranted.

Topics: Aged; Anti-Arrhythmia Agents; Defibrillators; Electric Countershock; Electrocardiography; Feasibility Studies; Female; Humans; Japan; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Patient Admission; Pilot Projects; Prospective Studies; Pyrimidinones; Registries; Survival Analysis; Survival Rate; Time Factors; Torsades de Pointes; Treatment Failure; Ventricular Fibrillation

Topics: Anti-Arrhythmia Agents; Defibrillators; Electric Countershock; Humans; Out-of-Hospital Cardiac Arrest; Patient Admission; Pyrimidinones; Survival Rate; Tachycardia, Ventricular; Time Factors; Torsades de Pointes; Treatment Failure; Ventricular Fibrillation