Comparison of epinephrine administration intervals in out-of-hospital cardiac arrest: a retrospective study

1. Introduction

While patients die from various causes, all patients experience cardiopulmonary arrest (CPA) at the end of their life. In cases of cardiac arrest, medical personnel administer cardiopulmonary resuscitation (CPR) [1]. Performing CPR involves several components, including chest compressions, airway management, defibrillation, drugs, postcardiac arrest care and other treatments [2, 3]. Among these, epinephrine administration is important for CPR because it contracts the arteries and arterioles through the alpha-adrenergic receptor, which can be helpful in achieving return of spontaneous circulation (ROSC) [4, 5]. However, the frequent use of epinephrine can increase oxygen demand, which is harmful [5]. Currently, according to the latest American Heart Association CPR guideline algorithm, epinephrine is recommended to be administered at 1 mg every 3–5 minutes [1, 6].

In several CPR training programs, such as advanced cardiovascular life support (ACLS) and Korean advanced life support, instructors encourage the use of epinephrine every 4 minutes during CPR, which is the same as every two cycles of rhythm checks. Administering epinephrine every two cycles of rhythm check can simplify the process of CPR. Studies on the prognosis of patients who were administered epinephrine for less than 3 minutes, more than 5 minutes, or every 3–5 minutes are relatively common [7, 8, 9, 10]. However, studies investigating the prognosis of patients who are administered epinephrine every 3 and 4 minutes have not yet been reported. Thus, we investigated whether the rate of ROSC in initial CPR and neurological outcome depended on the epinephrine interval. If the outcomes differ, it may be helpful to establish an accurate interval for epinephrine administration. If the outcomes do not differ, administering epinephrine every 4 minutes can be helpful for beginner medical personnel.

2. Materials and methods

3. Results

In total, 240 patients were enrolled in this study. A total of 190 (79.2%) patients received epinephrine every 3 minutes, and 50 (20.8%) patients received epinephrine every 4 minutes (Fig. 1).

Fig. 1.Flowchart of enrollment in this study. ED, Emergency Department.

There were no significant differences in sex and age between the groups. There were no significant differences in the factors closely related to the possibility of ROSC, such as initial rhythm, shock before hospital arrival, cause of arrest, witnessed status, bystander CPR performed, administration of epinephrine before ED arrival, and prehospital CPR time. There were more patients with diabetes mellitus or stroke in the 3-minute group than in the 4-minute group; there were no differences in other medical history (Table 1).

After propensity score matching, there were no differences in ROSC in the ED, survival rate until admission to the ICU, or CPC scale scores at hospital discharge between the two groups. The total CPR time and epinephrine dose used during CPR did not differ significantly between the two groups (Table 2).

4. Discussion

The current CPR guidelines suggest that epinephrine should be administered during CPR every 3–5 minutes [1], but to our knowledge, no studies have analyzed the interval for epinephrine administration in detail. To establish simpler and more efficient CPR protocols, we investigated resuscitation outcomes following intervals for epinephrine administration of 3 and 4 minutes. There was no significant difference in the ROSC rate, survival rate until admission to the ICU, and CPC scale score at discharge from the hospital between the two groups (Table 2).

In previous studies, the survival rate of CPA improved when there was good teamwork between nurses and ED doctors [11, 12, 13]. In other studies, job training for nurses was found to improve the ROSC rate of CPR [14, 15]. In the current ACLS guidelines, pulse and rhythm checks are performed every 2 minutes, and epinephrine administration is performed every 3–5 minutes [1]. If the CPR leader orders the administration of epinephrine every 3 minutes, then the timing of epinephrine administration and rhythm checks can be confused. This increases workload during ACLS and harms teamwork between nurses and doctors [11]. If there is no significant difference in prognosis between the administration of epinephrine every 3 minutes and every 4 minutes, then a 4-minute interval is consistent with two cycles of ACLS, which can be helpful for simplifying the process of CPR. Epinephrine administration during CPR has both advantages and disadvantages, which can explain our study outcomes. There was no significant difference in resuscitation outcome. Considering the above findings, we suggest that epinephrine administration every 4 minutes should be considered in ACLS. The strategy of administering epinephrine every two cycles of CPR can be expected to improve the efficiency of the ED, where ACLS needs to be performed with limited human resources and time. For example, simplifying the CPR protocol can enhance other CPR processes, such as accurate chest compression and detailed monitoring, which can help to achieve ROSC. Considering other studies that have suggested the nurse-to-bed ratio as the only factor controlling the incidence of CPA, it is predicted that more efficient bed management will be possible in the ED if fewer nursing personnel are deployed through efficient ACLS [16]. This can be particularly helpful for novice medical personnel [12].

One limitation of this study was that its data quality was lower than that of prospective studies due to the retrospective nature of the study design, despite performing propensity score matching to increase statistical power [17]. Given the limitations of retrospective studies, there were many patients whose medical records for underlying diseases were not accurately recorded, and there is a possibility that the evaluation of underlying diseases was not accurately performed, considering that they were tied to the presence or absence of underlying diseases. As this was a single-center study that did not include data from several other emergency centers, it could lead to biased research results, considering that the environment varies from hospital to hospital [18]. In addition, local prehospital CPR rescue protocols might vary, so the results in other cities may differ. The CPC scale could only be evaluated at the time of discharge and subsequent outpatient follow-up at this hospital, and there were limitations to this because it was difficult to clearly evaluate the CPC scale for patients who did not or rarely visit the hospital after long-term hospitalization [19]. If the CPC scale is used for follow-up after the same period, the prognostic evaluation will be more accurate. To proceed with more advanced research, two groups with consistent baseline characteristics should be selected through prospective research so that the prognosis between the two groups can be accurately compared. Such a prospective study will help to confirm whether the 4-minute interval for epinephrine administration has positive effects on outcomes following CPR. Securing a larger number of cases by performing a multicenter study between hospitals could lead to more accurate research results when compared with a single-center study. Considering the nature of the ED, even if a patient visited the hospital because of cardiac arrest, there were some cases in which the family wanted to stop CPR immediately after the visit [20, 21]. In this case, there was a limitation that could have led to bias in determining the patient’s prognosis.

5. Conclusions

In this study, there were no significant differences in the ROSC rate and other resuscitation outcomes between patients who received epinephrine at 3-minute and 4-minute intervals during CPR. We suggest the “epinephrine for every 2 cycles of CPR” strategy as a simple protocol for medical personnel performing CPR.

Abbreviations

CPA, cardiopulmonary Arrest; CPR, Cardiopulmonary Resuscitation; ROSC, Return of Spontaneous Circulation; ACLS, Advanced Cardiovascular Life Support; ED, Emergency Department; OHCA, Out of Hospital Cardiac Arrest; ICU, Intensive Care Unit; CPC, Cerebral Performance Categories; DM, Diabetes Mellitus; HTN, Hypertension; CAD, Coronary Artery Disease; HF, Heart Failure.

Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author contributions

MGJ, JSH and SHK—designed the research study. MGJ—performed the research. JSH and SHK—provided help and advice on this study. MGJ and JSH—analyzed the data and wrote the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

This study was reviewed and approved by the Institutional Review Board of the Ulsan University Hospital (UUH-IRB-2024-02-019). The data used in this study were anonymized before use. All the methods used in this study were performed in accordance with the Declaration of Helsinki guidelines. The requirement for informed consent was waived by the Institutional Review Board because of the retrospective nature of this study.

Acknowledgment

Thanks for supporting by the Big Data Center of Ulsan University Hospital for statistical analysis.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.