Antiarrhythmic drugs for cardiac arrest - Pediatric

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This CoSTR is a draft version prepared by ILCOR, with the purpose to allow the public to comment and is labeled “Draft for Public Comment". The comments will be considered by ILCOR. The next version will be labelled “draft" to comply with copyright rules of journals. The final COSTR will be published on this website once a summary article has been published in a scientific Journal and labeled as “final”.

Pediatric Life Support Task Force

Dianne Atkins, Richard Aickin, Robert Bingham, Keith Couper, Thomaz Couto, Allan de Caen. Anne-Marie Guerguerian, Mary Fran Hazinski, Eric Lavonas, Peter Meaney, Vinay Nadkarni, Kee-Chong Ng, Gabrielle Nuthall, Shinichiro Ohshimo, Gene Yong-Kwang Ong, Amelia Reis, Steven Schexnayder, Barney Scholefield, Naoki Shimizu, Janice Tijssen, Patrick Van de Voorde, Ian Maconochie,

The PICOST: Population, Intervention, Comparator, Outcome, Study Designs, and Time Frame

Population: Patients of all ages (neonates, children and adolescents < 18) in any setting (in-hospital or out-of-hospital) with cardiac arrest and a shockable rhythm at any time during cardiopulmonary resuscitation (CPR) or immediately after Return of Spontaneous Circulation (ROSC). Studies that included animals were not eligible.

Intervention: Administration (intravenous or intra-osseous) of an antiarrhythmic drug during CPR and immediately after ROSC.

Comparators: Another anti-arrhythmic drug or placebo or no drug during CPR or immediately after ROSC.

Outcome: The critical outcome was ranked as survival to hospital discharge with good neurologic outcome and survival to hospital discharge. The important outcome was ranked as return of spontaneous circulation (ROSC)

Study Design: Randomised controlled trials (RCTs) and non-randomised studies (non-randomised controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) are eligible for inclusion.

Timeframe: All years and all languages were included as long as there was an English abstract; unpublished studies (e.g., conference abstracts, trial protocols) were excluded. The literature search was updated to August 15, 2017


Summary

One observational study provided direct evidence on the outcomes of survival to hospital discharge and return of spontaneous circulation in an in-hospital patient population. (Valdes, 2014). The study was from the in-hospital cardiac arrest registry maintained by the American Heart Association: Get With the Guidelines-Resuscitation. There were no additional studies beyond the ones that formed the basis of the 2015 CoSTR treatment recommendation.


Consensus on Science:


Amiodarone versus Lidocaine

For the critical outcome of survival to hospital discharge, one observational study with 302 patients found no difference in effect for lidocaine as compared to amiodarone (25% versus 17%; P=NS; RR 1.50; 95% CI 0.90-2.52). (Valdes, 2014)

For the important outcome of ROSC, one observational study with 302 patients showed significant increase in ROSC for the lidocaine group as compared with amiodarone (64% versus 44%; P=0.004; RR 1.46; 95% CI 1.13-1.88). (Valdes, 2014)

Treatment Recommendation

We suggest amiodarone or lidocaine be used in the treatment of pediatric shock-refractory VF/pVT (weak recommendation, very low quality evidence).

Values, Preferences, and Task Force Insights

We place a higher value on the use of pediatric registry data over the adult literature. While there are several adult RCTs comparing lidocaine, amiodarone and placebo, the populations studied are substantially different from both pediatric (pre-pubertal) or adolescent populations. The adult studies were heavily concentrated in populations > 50 years. The Task Force felt that the etiologies of arrest in the adult populations, most commonly myocardial ischemia, are sufficiently different from pediatric and adolescent populations that extrapolation from these data was not valid. Although the etiologies of in-hospital and out- of hospital cardiac arrest in children may differ, we feel that extrapolation to pediatric out-of-hospital cardiac arrest is reasonable.

The Task Force has serious concerns about the quality of the data. The available study included data collected prior to 2005 when the guidelines emphasized the quality of CPR as an important variable that influences outcomes. However, there is no new pediatric evidence or compelling extrapolated adult evidence that suggests councils should remove amiodarone or lidocaine from usual care, and no pediatric studies that directly compare either with placebo.

Knowledge Gaps

1. Randomized studies on anti-arrhythmic use during both out-of-hospital and in-hospital pediatric cardiac arrest are lacking. Ideally, outcomes should include survival to hospital discharge, neurodevelopmental outcomes and patient centered outcomes. .

2. Timing of medication administration with respect to defibrillation or epinephrine is unknown.

3. Anti-arrhythmic effectiveness and adverse events with respect to etiology of arrest (i.e. channelopathy vs structural vs ischemic), primary versus secondary VF/pVT and developmental age is unknown.

References

Valdes SO, Donoghue AJ, Hoyme DB, Hammond R, Berg MD, Berg RA, et al. Outcomes associated with amiodarone and lidocaine in the treatment of in-hospital pediatric cardiac arrest with pulseless ventricular tachycardia or ventricular fibrillation. Resuscitation. 2014;85(3):381-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24361455.

Maconochie IK, de Caen AR, Aickin R, Atkins DL, Guerquerian AM, Kleinman ME, et al. Part ^: Pediatric basic life support and pediatric advanced life support: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation 2015;95:e147-68. Available from https://www.ncbi-nlm-nih-gov/pubmed/26477423.


Discussion

GUEST
Antonio Rodriguez-Nunez
I would suggest to interchange the order of the drugs in the Treatment Recommendation: we suggest Lidocaine or Amiodarone... The basis is that Lidocaine is that the limited evidences indicate an advantage for lidocaine in terms of ROSC and a possible trend in terms of survival. Although both are considered similar, the wording should consider these facts.
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GUEST
Jesús López Herce
The study of Valdes et al did not compare the time to lidocaine or amiodarone administration and the defibrillation doses between both groups. These facts could influence the final results. A multicenter international study to compare lidocaine and amiodarone in children is necessary to obtain evidences.
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