Out-of-hospital cardiac arrest (OHCA) is a serious public health problem with a reported average incidence of 52 emergency medical services (EMS) treated events per 100,000 of the population per year in North America. 

Despite the publication and widespread application of international advanced cardiac life support (ALS) guidelines, survival rates remain extremely low. As the lead author of the recent report by the Resuscitation Outcomes Consortium (ROC) published in the journal Resuscitation,¹ I wanted to show that there is a huge variability in the use of pharmacological therapies by the emergency medical services in the management of OHCA. 

ROC is a North American consortium of research groups engaged in studies in cardiac arrest and severe trauma funded by the National Heart, Lung and Blood Institute in partnership with the National Institute of Neurological Disorders and Stroke, the Canadian Institutes of Health Research (CIHR), the Institute of Circulatory and Respiratory Health, Defence Research and Development Canada, the Heart and Stroke Foundation of Canada and the American Heart Association. 

The consortium includes 264 EMS agencies across 11 geographically distinct sites. Data related to out-of-hospital treatments and outcomes were collected by use of standardised operational definitions, including initial cardiac rhythms, response times, descriptions of responders, timing of cardiopulmonary resuscitation (CPR) and defibrillation, response to interventions, return of spontaneous circulation (ROSC), the presence of a pulse at arrival to the emergency room and survival to hospital discharge.

Advanced cardiac life support guidelines

The aim of the ALS guidelines is to help to standardise the provision of basic and advanced level care based on the available evidence and expert opinion. In order to help optimise cardiac and cerebral perfusion during CPR, increase defibrillation success and achieve a good neurological outcome, the ALS guidelines recommend the administration of specific anti-arrhythmic and vasoactive drugs under certain conditions. However, interestingly, there are limited data regarding the beneficial effects of many of these agents, which prompted us to examine current practice in more detail. 

My colleagues and I studied a total of 16,221 OHCAs which were attended by 74 EMS agencies. This is the largest study describing the contemporary use of pharmacological agents in OHCA.

Anti-arrhythmic drugs

In terms of anti-arrhythmic drugs a large difference in the use of lignocaine and amiodarone was noted with fewer than half of agencies only administering one anti-arrhythmic drug (see Figure 1).¹

Within those agencies using lignocaine, the proportion of patients receiving the drug in cases with at least one shock ranged from 1-75%. For those who had shock-resistant arrhythmias, lignocaine administration rates ranged from 1-100% between agencies (mean 41 ± 31%). In agencies using amiodarone, the proportion receiving amiodarone ranged from 0.2-63% for patients who received at least one shock, and from 0.4-90% for shock-resistant ventricular arrhythmias (mean 26 ± 32%). 

After adjusting for age, gender, EMS-witnessed arrest, bystander-witnessed arrest, bystander CPR, shockable initial rhythm, time from 911 to EMS arrival and study site, the odds ratio for survival to hospital discharge was 1.11 for amiodarone and 1.28 for lidocaine. 

Like all data analysis we must treat this with caution and not draw too many conclusions or extrapolate these data.

Figure 1. Relation between use of amiodarone and lidocaine for all cardiac arrests across all agencies throughout the Epistry ROC database. Each point represents one agency with the exception of two agencies with zero use of both drugs(click to enlarge)

Vasopressor administration

In terms of vasopressor administration, adrenaline was administered in approximately 80% of ALS-treated cardiac arrests. All agencies used epinephrine in some cardiac arrests. The mean dose administered was 3.5mg with a range in the mean epinephrine dose of 1.9-5.5mg. 

There was an inverse association between adrenaline dose and survival to discharge (see Figure 2).¹ This relationship persisted after adjusting for age, gender, EMS-witnessed arrest, bystander-witnessed arrest, bystander CPR, shockable initial rhythm, time from 911 to EMS arrival, the duration of OHCA and study site. 

Again, I would urge caution with the interpretation of these data, describing it as a possible ‘chicken and egg’ situation. Atropine was administered in 71% (±14%) of all cardiac arrests. For non-VT/VF OHCAs the mean agency rate of use was 74% (±14%), ranging from 29-95%. Sodium bicarbonate was administered in 19% of OHCAs. 

Agency-specific rates ranged from 0.3-71% within agencies that ever used the drug. While seven agencies did not use sodium bicarbonate for any cardiac arrests, six agencies, all within one geographical region, used it in approximately half of all cardiac arrests. 

The administration of sodium bicarbonate for more prolonged cardiac arrests (greater than the median duration) was not significantly higher than for shorter arrests (23% for cardiac arrests greater than 25 minutes versus 18% overall use).

Figure 2. Relation of epinephrine dose to survival. Each point represents the total dose of epinephrine in milligram versus the rate of survival for individuals who received that dose(click to enlarge)

Summary

In my opinion, the overall reasons for the variability seen are multifactorial and include a lack of evidence from randomised clinical trials in terms of survival, resulting in class IIb recommendations for the majority of the agents, a variation in the time taken to incorporate the ALS guidelines into clinical practice as well as differences in the opinion of medical directors in different agencies. 

These data, I hope, not only highlight recent and current practice, but should prompt the need for future randomised trials which may help to optimise patient management.  

Reference

1. Glover BM, Brown SP, Morrison L et al. Wide variability in drug use in out-of-hospital cardiac arrest: a report from the Resuscitation Outcomes Consortium. Resuscitation 2012; 83(11): 1324-1330. doi: 10.1016/j.resuscitation.2012.07.008 [Epub 2012]