Old News and New News for Cardiac Arrest

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Anyone who’s faced a patient with refractory V fib or V Tac, knows the certain pang of hopelessness that strikes when round and round of epi, CPR, and shocks fails to deliver a return to organized rhythm. ECMO is an option. Baring the availability of perhaps one of the most resource-intensive procedures in medicine, what option does one have? If nothing is working what do you change? Beta blockers? Change up the shocks? Is that bicarb you’re giving doing any good? This post and the affiliated podcast will cover 3 articles looking at the evidence for these new and old treatments for cardiac arrest.

This is our first of 3 podcasts recapping our most recent journal club. In this podcast, Dr. Sarah Wolochatiuk summarizes the meta-analysis by Gottlieb et al entitled "Beta-blockade for the treatment of cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia: A systematic review and meta-analysis" published in Resuscitation in 2019.

Gottlieb, M., Dyer, S. & Peksa, G. D. Beta-blockade for the treatment of cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia: A systematic review and meta-analysis. Resuscitation 146, 118–125 (2020).

This journal article is a meta-analysis of the data that exists on beta blocker therapy vs control for refractory VF/VT arrest. The authors felt that this patient demographic was important given the poor outcomes of arrest patients in refractory shockable rhythms that do not respond to ACLS.

Using a fairly comprehensive literature search, they reviewed almost 3,000 abstracts, narrowing it down to 3 observational studies with an n of 115.Using pooled data, the authors found a significant difference in both temporary (>30 sec, <20 min) and sustained (>20 min) ROSC for those received beta blockers during arrest as opposed to typical ACLS or "control", with respective odds ratios of 14.46 and 5.76. The odds ratio for survival to admission was the same as that for sustained ROSC at 5.76. Additionally, there was higher odds ratio of survival to discharge at 7.92 and survival with favorable neurologic outcome at 4.42 in those who had received beta blockade vs control.

Both Driver in 2014 and Lee in 2016 looked at all of the aforementioned measures in the meta-analysis. Unfortunately, the Nademanee study from 2000 only evaluated survival to discharge, and thus these data are only included for that particular measure and corresponding forest plot. Most notably, in this study from 2000, the authors included different methods of beta blockade, including Metoprolol, Propranolol and left stellate ganglionic block (LSGB). Unfortunately, the data regarding outcomes stratified by type (pharmacologic vs LSGB) of beta blockade was no longer available at the time of meta-analysis publishing. Nonetheless, even when we assume that all patients receiving LSGB died before discharge, thus removing the heterogeneity, the difference in survival to discharge still remains statistically significant.

The pharmacology of why beta blockade in VF/VT arrest works hinges on the fact that it protects against the beta agonism effects of exogenous Epinephrine that is given during arrest. In myocardial ischemia, sympathetic activity is reflexively increased endogenously as well. Beta agonism increases the myocardial O2 requirement, worsens ischemia, and in turn decreases the threshold of VF/VT. Sympathetic blockade may increase this threshold.

Ultimately, after this small meta-analysis, the authors report that beta blockade may lead to better outcomes. Based on the pooled analyses, beta blockers have a NNT of 3 to improve survival to discharge and a NNT of 6 to improve the number of patients with favorable neurologic outcome after refractory VF/VT arrest. Unfortunately, given the dearth of studies with control groups that fit the inclusion criteria, the small number of patients has the potential to skew or magnify results. This study certainly poses some interesting questions for future research, potentially involving randomized controlled trials.

In this, our second podcast recapping our most recent journal club, Dr. Colleen Laurence summarizes a recent pilot study by Cheskes et al looking at standard defibrillation vs vector change defibrillation vs dual sequence defibrillation. Could we be on the verge of a significant practice change in how we deliver defibrillation to patients with refractory V Fib/Tac?

Why we chose this article

Patients with refractory ventricular fibrillation can be challenging to treat and carry a high mortality. This study revisits the contentious topic of double sequence defibrillation (DSED) for refractory ventricular fibrillation.  The rationale for this practice is that placing pads in the anterior-posterior position permits direct delivery of shocks to the most frequently affected, posterior aspect of the myocardium, thus decreases potential impedance. DSED also adds voltage through the second shock, which may capitalize on the “conditioning” of the first shock.

Previous research on this topic have been mostly case series and observational studies, and they have been inconsistent in their definition of refractory ventricular fibrillation and timing of intervention. Furthermore, many providers remain concerned about the safety of DSED for patients and potential for defibrillator dysfunction.

This study evaluates the feasibility and safety of a cluster randomized controlled trial with crossover assessing vector change defibrillation (VC) and double sequence defibrillation compared to standard defibrillation for patients with refractory ventricular fibrillation.  

Study details

  • Study conducted in rural and urban regions of Ontario, Canada from March 2018 to September 2019.

  • Inclusion: All patients aged ≥ 18 noted to be in refractory ventricular fibrillation - defined as three failed defibrillation attempts with pads in the anterior-lateral position. Exclusion: traumatic arrests, patients with DNR orders, cardiac arrests secondary to hypothermia, suspected overdose, hanging, drowning

  • Four Canadian paramedic services were randomized to VC, DSED, or standard defibrillation, which they performed for 6 months before transitioning to a second, randomized arm for at least three additional months.

  • All groups followed standard ACLS treatment for ventricular fibrillation initially - including, immediate CPR, pad placement, rhythm analysis at 2 minute intervals with defibrillation as needed with pads in anterior-lateral position.

  • Feasibility criteria were determined a-priori as:

1.     Successful delivery of allocated intervention in 80% of eligible patients

2.     80% of enrolled patients received an intervention shock prior to 6th shock 

  • Safety was assessed through review of records, service reports for defibrillator damage and complaints or concerns by paramedics, EM department staff, patients, or families

  • Secondary outcomes included rate of ventricular fibrillation termination and ROSC. 

Results

  • Enrolled 152 patients

  • Demonstrated that this study is feasible with 89% of patients receiving the assigned therapy and 77% of patients receiving the assigned therapy by the fourth shock, which was the earliest possible time of intervention

  • There were no safety complaints.

  • ROSC was obtained in 25% of the standard defibrillation group compared to 39% of the VC group and 40% of the DSED group.

  • 66.6% of cases in the standard group resulted in VFT compared to 82% in VC, and 76.3% in DSED group.

  • No confidence intervals available for the secondary outcomes.

Limitations

  • Decreased enrollment in the standard defibrillation arm compared to intervention arms

  • Non-inclusion of shocks administered by fire departments prior to paramedic arrival for approximately 28% of patients

  • Majority of patients were from urban settings, which may limit generalizability given likely more ready access of second defibrillator.

  • Patient-oriented outcomes, such as neurologically intact survival, were not assessed.

Take home points
Ultimately, this is a really intriguing pilot study, but I’m not reaching for those extra pads just yet, even with some signal in the secondary outcomes suggesting improved VFT and ROSC with both VC and DSED. We often have other modalities of care - specifically, ECMO - that we should consider for our refractory ventricular fibrillation patients and which have demonstrated improved mortality and neurologic outcomes. Einstein said, “The definition of insanity is doing the same thing over and over again and expecting different results.” This seems pretty on the nose for these patients with refractory ventricular fibrillation, but I’m going to sit tight until we have more data in hand and, at most, consider VC as a last resort for certain patients.

This is the final of 3 podcasts recapping our most recent journal club. In this podcast Dr. Olivia Urbanowicz walks us through a meta-analysis by Wu et al published in the Journal of Emergency Medicine in 2020. We tackle the question as to whether or not there is evidence that supports the routine use of sodium bicarbonate in patients with cardiac arrest.

The universal use of sodium bicarbonate (SB) during cardiac arrest has been cautioned against beginning in the 2010 iteration of the ACLS guidelines, however, is still commonly used in clinical practice. Given frequent drug shortages and varying practice patterns, this group wished to reevaluate and collate the literature which might suggest or argue against using this agent routinely in code situations.

THE STUDY

Systemic analysis and meta-analysis of 6 eligible studies evaluating nontraumatic, adult, cardiac arrest patients comparing effect of SB administration on rates of ROSC and survival to discharge.

  • Database search from November 1962 through December 2019.

  • 15 eligible full text studies reviewed from a search return of 714 individual abstracts

  • 6 observational included in final review and meta-analysis involving 18,406 total patients.

Secondary subgroup analyses included years the studies were performed during (pre- and post-2010 ACLS update) and continent on which the resuscitations and data collection took place (Asia vs. North America).

Results showed no significant difference in rates of ROSC nor survival to hospital discharge in the patients who received SB compared to those who did not. This was demonstrated again in the year subgroup analysis. 

  • Continent subgroup analysis similarly showed no significant difference between SB and non-SB arms but suggested overall lower rates of ROSC and survival-to-discharge in North America compared to Asia.

Limitations: variability in treatment locations (ED only vs. ED/prehospital/in hospital), no data from other continents, does not take into consideration patient comorbidities or other potential confounders (pre-existing metabolic derangements, targeted temperature management, post-ROSC management, etc.) which could drastically alter neurologic outcomes regardless of ROSC status. 

TAKE HOME

This meta-analysis serves to highlight the need for caution in approaching arrest management as a of one-size-fits-all resuscitation and lends weight to the ongoing ACLS recommendation against routine use of sodium bicarbonate in cardiac arrest. Evaluation of individual patient circumstances and recommendation of restricting sodium bicarbonate use only to clinical situations where it may be specifically indicated (hyperkalemic arrest, known pre-existing severe metabolic acidosis, wide complex dysrhythmias, tricyclic antidepressant or other sodium channel blockade agent overdose should continue to be the standard of care for emergency medicine physician arrest management.

Authorship

Gottlieb et al - Sarah Wolochatiuk., PGY-3, University of Cincinnati Department of Emergency Medicine

Cheskes, et al - Colleen Laurence, PGY-3, University of Cincinnati Department of Emergency Medicine

Wu, et al - Olivia Urbanowicz, PGY-3, University of Cincinnati Department of Emergency Medicine

Audio Editing, Review, Posting - Jeffery Hill, MD MEd