Bayesian analysis of amiodarone or lidocaine versus placebo for out-of-hospital cardiac arrest

Lane, Daniel; Grunau, Brian; Kudenchuk, Peter J.; Dorian, Paul; Wang, Henry E.; Daya, Mohamud; Lupton, Joshua R.; Vaillancourt, Christian; Okubo, Masashi; Davis, Daniel P.; Rea, Thomas D.; Yannopoulos, Demetris; Christenson, Jim; Scheuermeyer, Frank

doi:10.1136/heartjnl-2021-320513

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…In a recent reanalysis of the ROC ALPS data using a Bayesian framework, treatment with amiodarone had higher probabilities of improved survival and neurologic outcome while treatment with lidocaine had a smaller probability of benefit (20). This aligns with our results, which suggest that lidocaine is not more effective than placebo if given very early after cardiac arrest but its potential relative benefit may increase progressively with increased time intervals to drug.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Time to Treatment With Antiarrhythmic Drugs on Survival and Neurological Outcomes in Shock Refractory Out-of-Hospital Cardiac Arrest

Rahimi

Dorian²,

Cheskes

et al. 2023

Critical Care Medicine

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Objectives: Examining the association of time to treatment (drug or placebo) with survival to hospital discharge and neurologic outcome. Design: Post hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo randomized controlled trial. Setting: Emergency medical services enrolled patients with out-of-hospital cardiac arrest (OHCA) at multiple North American sites. Patients: Adults with nontraumatic OHCA and an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia refractory to at least one defibrillation attempt were included. Interventions: None. Measurements and Main Results: We used logistic regression to examine the association of time to treatment with survival to hospital discharge and favorable neurologic status at discharge (modified Rankin Scale ≤ 3) for the three treatment groups including an interaction term between treatment and time to treatment to determine the effect of time on treatment effects. Time to treatment data were available for 2,994 out of 3,026 patients (99%). The proportion of patients who survived to hospital discharge decreased as time to drug administration increased, in amiodarone (odds ratio [OR], 0.91; 95% CI, 0.90–0.93 per min), lidocaine (OR, 0.93; 95% CI, 0.91–0.96), and placebo (OR, 0.91; 95% CI, 0.90–0.93). Comparing amiodarone to placebo, there was improved survival at all times of drug administration (OR, 1.32; 95% CI, 1.05–1.65). Comparing lidocaine to placebo, survival was not different with shorter times to drug administration (< 11 min), whereas survival was higher with lidocaine at longer times to drug administration with an interaction between treatment effect and time to treatment (p = 0.048). Survival with good neurologic outcome showed similar results for all analyses. Conclusions: Survival and favorable neurologic outcomes decreased with longer times to drug administration. Amiodarone improved survival at all time points whereas lidocaine improved survival only at later time points, compared with placebo.

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Section: Discussionmentioning

confidence: 99%

The Effect of Time to Treatment With Antiarrhythmic Drugs on Survival and Neurological Outcomes in Shock Refractory Out-of-Hospital Cardiac Arrest

Rahimi

Dorian²,

Cheskes

et al. 2023

Critical Care Medicine

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“…For example, one strategy might use the algorithm to provide earlier or higher-dose antiarrhythmic treatment or a lower or delayed dose of a vasopressor such as epinephrine (given its potential proarrhythmic effects) for those at high risk of refractory VF. [8][9][10][11][12][13][14][15] The algorithm might also be used to inform which patients could be considered for modified shock delivery strategies (vector change or double sequential defibrillation) or early transport for advanced hospital care such as an emergent coronary artery intervention or extracorporeal CPR. [16][17][18][19][20][21]…”

Section: Clinical Implications Of Algorithm Performancementioning

confidence: 99%

“…[5][6][7] Hence, the ability to predict refractory VF in advance of repeated shock failure could enable preemptive interventions targeted at improving the relatively poor outcomes of the refractory VF subgroup. Such therapies might include earlier or increased antiarrhythmic dose administration, [8][9][10][11][12] reconsideration of epinephrine use or dosage, [13][14][15] changes in how shocks are administered, 16 or expedited invasive interventions. [17][18][19][20][21] By contrast, empiric treatment of all patients with VF OHCA using such strategies may unnecessarily expose patients who achieve best outcomes under the current protocol, introducing potential risk among those unlikely to benefit.…”

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confidence: 99%

Prediction of Shock-Refractory Ventricular Fibrillation During Resuscitation of Out-of-Hospital Cardiac Arrest

et al. 2023

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BACKGROUND: Out-of-hospital cardiac arrest due to shock-refractory ventricular fibrillation (VF) is associated with relatively poor survival. The ability to predict refractory VF (requiring ≥3 shocks) in advance of repeated shock failure could enable preemptive targeted interventions aimed at improving outcome, such as earlier administration of antiarrhythmics, reconsideration of epinephrine use or dosage, changes in shock delivery strategy, or expedited invasive treatments. METHODS: We conducted a cohort study of VF out-of-hospital cardiac arrest to develop an ECG-based algorithm to predict patients with refractory VF. Patients with available defibrillator recordings were randomized 80%/20% into training/test groups. A random forest classifier applied to 3-s ECG segments immediately before and 1 minute after the initial shock during cardiopulmonary resuscitation was used to predict the need for ≥3 shocks based on singular value decompositions of ECG wavelet transforms. Performance was quantified by area under the receiver operating characteristic curve. RESULTS: Of 1376 patients with VF out-of-hospital cardiac arrest, 311 (23%) were female, 864 (63%) experienced refractory VF, and 591 (43%) achieved functional neurological survival. Total shock count was associated with decreasing likelihood of functional neurological survival, with a relative risk (95% CI) of 0.95 (95% CI, 0.93–0.97) for each successive shock ( P <0.001). In the 275 test patients, the area under the receiver operating characteristic curve (95% CI) for predicting refractory VF was 0.85 (95% CI, 0.79–0.89), with specificity of 91%, sensitivity of 63%, and a positive likelihood ratio of 6.7. CONCLUSIONS: A machine learning algorithm using ECGs surrounding the initial shock predicts patients likely to experience refractory VF, and could enable rescuers to preemptively target interventions to potentially improve resuscitation outcome.

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“…Time to drug administration is hard to quantify in unwitnessed arrests, and prompt drug administration is difficult in CA trials, with a mean time to medication administration of approximately 19 minutes after emergency medical services activation [ 7 ]. A more recent study utilized a Bayesian approach to reanalyze the ALPS data and suggested a 2.9% overall survival benefit for amiodarone (interquartile range (IQR) 1.4–3.8%) and 1.7% for lidocaine (IQR 0.8–3.2%) as compared to placebo [ 98 ]. This study also showed that amiodarone offered a strong probability (96%–99%) to improve neurological outcomes in refractory VT/VF patients, higher than for lidocaine or placebo (96%) [ 98 ] and as such amiodarone should be strongly considered till further data emerge for clinical use.…”

Section: Antiarrhythmicsmentioning

confidence: 99%

A Narrative Review of Drug Therapy in Adult and Pediatric Cardiac Arrest

Jaeger¹,

Márquez²,

Kosmopoulos³

et al. 2023

Rev. Cardiovasc. Med.

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Drugs are used during cardiopulmonary resuscitation (CPR) in association with chest compressions and ventilation. The main purpose of drugs during resuscitation is either to improve coronary perfusion pressure and myocardial perfusion in order to achieve return of spontaneous circulation (ROSC). The aim of this up-to-date review is to provide an overview of the main drugs used during cardiac arrest (CA), highlighting their historical context, pharmacology, and the data to support them. Epinephrine remains the only recommended vasopressor. Regardless of the controversy about optimal dosage and interval between doses in recent papers, epinephrine should be administered as early as possible to be the most effective in non-shockable rhythms. Despite inconsistent survival outcomes, amiodarone and lidocaine are the only two recommended antiarrhythmics to treat shockable rhythms after defibrillation. Beta-blockers have also been recently evaluated as antiarrhythmic drugs and show promising results but further evaluation is needed. Calcium, sodium bicarbonate, and magnesium are still widely used during resuscitation but have shown no benefit. Available data may even suggest a harmful effect and they are no longer recommended during routine CPR. In experimental studies, sodium nitroprusside showed an increase in survival and favorable neurological outcome when combined with enhanced CPR, but as of today, no clinical data is available. Finally, we review drug administration in pediatric CA. Epinephrine is recommended in pediatric CA and, although they have not shown any improvement in survival or neurological outcome, antiarrhythmic drugs have a 2b recommendation in the current guidelines for shockable rhythms.

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Bayesian analysis of amiodarone or lidocaine versus placebo for out-of-hospital cardiac arrest

Cited by 7 publications

References 29 publications

The Effect of Time to Treatment With Antiarrhythmic Drugs on Survival and Neurological Outcomes in Shock Refractory Out-of-Hospital Cardiac Arrest

The Effect of Time to Treatment With Antiarrhythmic Drugs on Survival and Neurological Outcomes in Shock Refractory Out-of-Hospital Cardiac Arrest

Prediction of Shock-Refractory Ventricular Fibrillation During Resuscitation of Out-of-Hospital Cardiac Arrest

A Narrative Review of Drug Therapy in Adult and Pediatric Cardiac Arrest

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