Skip to main content
Download PDF

A prospective observational study on impact of epinephrine administration route on acute myocardial infarction patients with cardiac arrest in the catheterization laboratory (iCPR study)

Critical Care volume 26, Article number: 393 (2022) Cite this article

Abstract

Background

Epinephrine is routinely utilized in cardiac arrest; however, it is unclear if the route of administration affects outcomes in acute myocardial infarction patients with cardiac arrest.

Objectives

To compare the efficacy of epinephrine administered via the peripheral intravenous (IV), central IV, and intracoronary (IC) routes.

Methods

Prospective two-center pilot cohort study of acute myocardial infarction patients who suffered cardiac arrest in the cardiac catheterization laboratory during percutaneous coronary intervention. We compared the outcomes of patients who received epinephrine via peripheral IV, central IV, or IC.

Results

158 participants were enrolled, 48 (30.4%), 50 (31.6%), and 60 (38.0%) in the central IV, IC, and peripheral IV arms, respectively. Peripheral IV epinephrine administration route was associated with lower odds of achieving return of spontaneous circulation (ROSC, odds ratio = 0.14, 95% confidence interval = 0.05–0.36, p < 0.0001) compared with central IV and IC administration. (There was no difference between central IV and IC routes; p = 0.9343.) The odds of stent thrombosis were significantly higher with the IC route (IC vs. peripheral IV OR = 4.6, 95% CI = 1.5–14.3, p = 0.0094; IC vs. central IV OR = 6.0, 95% CI = 1.9–19.2, p = 0.0025). Post-ROSC neurologic outcomes were better for central IV and IC routes when compared with peripheral IV.

Conclusion

Epinephrine administration via central IV and IC routes was associated with a higher rate of ROSC and better neurologic outcomes compared with peripheral IV administration. IC administration was associated with a higher risk of stent thrombosis.

Trial registration This trial is registered at NCT05253937.

Graphical Abstract

Introduction

In-hospital cardiac arrest (IHCA) is a major challenge experienced by all healthcare systems worldwide [1, 2]. Despite significant progress in cardiopulmonary resuscitation (CPR) in recent years, outcomes remain poor, with only approximately 49% survival to hospital discharge [3]. Epinephrine administration remains a cornerstone in the treatment of IHCA [4]. However, the optimal administration route remains controversial [5, 6]. Various routes of administration, including intravenous, intramuscular, intraosseous, and endotracheal routes, have been studied [7,8,9]. Initially, the American guidelines for the treatment of IHCA recommended injection of 0.5 mg of epinephrine directly into the right ventricle via a parasternal approach, aiming to rapidly achieve higher peak intracardiac concentrations and a more central effect; however, the intravenous route remains preferred due to feasibility and safety [5, 6, 10].

The incidence of cardiac arrest in the cardiac catheterization laboratory is relatively low, approximately 1% during the past few decades [11]. However, with approximately 1 million percutaneous coronary procedures performed every year in the USA, roughly 10,000 patients will suffer in-catheterization laboratory cardiac arrest annually [12]. Arrest in the cardiac catheterization laboratory allows intracoronary (IC) epinephrine administration as part of resuscitative efforts. To our knowledge, IC epinephrine administration for intraprocedural cardiac arrest has not been compared with other routes of administration. The purpose of the present study was to compare the efficacy of peripheral IV, central IV, and IC epinephrine administration in achieving the return of spontaneous circulation (ROSC) in a cohort of acute myocardial infarction patients who underwent primary percutaneous coronary intervention and experienced cardiac arrest in the cardiac catheterization laboratory.

Methods

Study design

This was a prospective two-center pilot cohort study conducted in the Hospital of the Lithuanian University of Health Sciences Kaunas Clinics and the Republican Hospital of Panevezys. Both cardiac centers cover six out of ten administrative regions in the republic of Lithuania. The study enrolled acute myocardial infarction patients who suffered a cardiac arrest in the cardiac catheterization laboratory during percutaneous coronary intervention. Cardiac resuscitation was performed according to the European Resuscitation Council (ERC) Guidelines [13]. Because the preferred route of epinephrine administration is through a central venous catheter (via internal jugular or subclavian vein), it was the first choice for epinephrine administration when available [6]. In cases where a central venous catheter had not been placed, the route of epinephrine administration (peripheral IV catheter or IC catheter) during cardiac arrest was left to the discretion of the treating physician.

Study inclusion and exclusion criteria

The study included patients from April 1, 2018, to June 1, 2021, aged 18 years or older with either non-ST elevation myocardial infarction (NSTEMI) or ST elevation myocardial infarction (STEMI) who received dual antiplatelet therapy (acetylsalicylic acid 300 mg and ticagrelor 180 mg), or triple therapy (oral anticoagulant, acetylsalicylic acid 300 mg and clopidogrel 300 or 600 mg) at least 30 min prior to primary percutaneous intervention and had a cardiac arrest during their procedure.

Patients were excluded from the study if cardiac arrest occurred prior to being transported to the cardiac catheterization laboratory. Similarly, patients who suffered cardiac arrest for less than 60 s were excluded as they would not have received epinephrine in this timeframe. Those who presented with a rhythm other than sinus rhythm or atrial fibrillation/flutter or received vasopressor and/or antiarrhythmic medication prior to CPR were excluded to limit confounding by medications given prior to CPR. Patients who required mechanical circulatory support, had a concomitant acute illness (infection, etc.), significant comorbid disease (liver disease, end-stage renal failure, solid organ malignancy), prior coronary artery disease, or underwent primary fibrinolysis were excluded to limit the study to those who would have a similar prognosis in the event of cardiac arrest [14]. Patients who received targeted temperature management post-CPR were excluded as it is not the standard of care in in-hospital cardiac arrest [15]. Lastly, those with an allergy to contrast media were also excluded.

Data collection

Data collected included patient demographics such as age, sex, body mass index, primary diagnosis, clinical history, and comorbidities. Cardiac rhythm on admission and prior to cardiac arrest were recorded. In addition to routine laboratory tests, additional blood samples were drawn into vacutainer tubes (Greiner Bio-One Vacuette North America, Inc., Monroe, NC) that contained 3.2% sodium citrate for measurement of platelet aggregation with adenosine diphosphate (ADP) and international normalized ratio (INR) values. Data such as time-to-first epinephrine administration, the route of administration of epinephrine, the total dose of epinephrine administered, the total number of electric cardioversions attempted during the cardiac arrest, and the total time of resuscitation until ROSC or death were recorded. Furthermore, post-resuscitation left ventricular ejection fraction (LVEF), clinical course (stent thrombosis, KILLIP classification, length of stay in CCU, and ICD implantation), short-term outcomes (in-hospital death), and neurological outcomes (cerebral performance category (CPC)) were recorded [16].

Study endpoints

The primary endpoint was (the rate of) ROSC. In-hospital stent thrombosis was the secondary endpoint, and survival-to-discharge with favorable neurologic status (CPC score 1–2) was the tertiary endpoint [16].

Definition

Cardiac arrest was defined as a sudden cessation of cardiac function, precipitated by ventricular fibrillation (VF), pulseless electrical activity (PEA), or asystole requiring CPR [5, 6]. Time-to-epinephrine administration and time-to-ROSC were measured in minutes starting from the initiation of CPR until the first epinephrine dose and first ROSC, respectively. ROSC was defined as the return of spontaneous sustained cardiac activity for more than three consecutive minutes. STEMI and NSTEMI were defined according to the fourth universal definition of myocardial infarction [17]. Door-to-cath laboratory time was defined as the time (in minutes) from first medical contact at the facility to reaching the catheterization laboratory. Dyslipidemia was defined as a fasting total cholesterol level of more than 100 mg/dl or the use of lipid-lowering medications [18]. Hypertension was defined as systolic blood pressure higher than or equal to 130 mmHg and diastolic higher than 80 mmHg or the use of blood pressure-lowering medication [19]. Electrolyte imbalance was defined as abnormal potassium (< 3.6 mEq/L or > 5.2 mEq/L) or abnormal magnesium (< 1.3 mEq/L or > 2.1 mEq/L) just prior to catheterization. Obesity was defined as having a body mass index (BMI) over 30 kg/m2. Diabetes mellitus was defined as a fasting plasma glucose level ≥ 126 mg/dL, or the use of blood glucose-lowering medication [20]. Cardiogenic shock was defined as in-hospital use of vasopressors or persistent hypotension with evidence of hypo-perfusion caused by severe cardiac dysfunction despite adequate fluid administration [21]. Successful PCI was defined as the implantation of a second-generation drug-eluting stent resulting in the reduction in a coronary artery lesion to less than 20%. In-stent thrombosis was defined as new ST elevation with anginal symptoms or an equivalent due to thrombotic occlusion of the stent placed at the culprit lesion confirmed by coronary angiography during the index hospitalization. All patients who developed in-stent thrombosis were additionally treated with a GP IIb/IIIa inhibitor according to ESC guidelines [22]. Linear measurements of cardiac chambers and LVEF were obtained according to the recommendations of the European Association of Cardiovascular Imaging [23].

Statistical analysis

Categorical variables are presented as frequencies and percentages. Most continuous variables were skewed and are presented as median [quartile 1, quartile 3]. Differences in patient characteristics between epinephrine administration routes were assessed by chi-square (or Fisher’s exact test) and Kruskal–Wallis tests (or analysis of variance), as appropriate. We created multivariable logistic regression models via stepwise selection (which was confirmed via backward and forward selection) to preserve degrees of freedom, to investigate the association of epinephrine route with the outcomes of interest (i.e., ROSC, in-stent thrombosis, hospital survival with favorable neurologic status) while accounting for potential confounders (i.e., heart rhythm prior to CPR, age, and baseline serum potassium, hemoglobin, and LVEF) identified as having significant associations with epinephrine administration route (Table 1). We additionally tested for associations in time-to-ROSC across treatment groups and between neurologic outcomes (favorable or not) via the Kruskal–Wallis test.

Table 1 Characteristics of acute myocardial infarction patients undergoing cardiopulmonary resuscitation by epinephrine administration route
Full size table

Analyses were performed in SAS version 9.4 (Cary, NC). p values less than 0.05 were considered statistically significant; we performed Tukey’s pairwise comparisons or Dunn’s post hoc tests for normal or skewed continuous variables, respectively, and we preserved family-wise error in post hoc tests using the Holm–Bonferroni adjustment for categorical analyses.

Ethical disclosure

We conducted this study in compliance with the ethical standards of the Regional Bioethics Committee of Kaunas, Lithuania (the permission number is BE-2-4), and the World Medical Association Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects.

Results

There were 158 participants in this study (Fig. 1): 48 (30.4%), 50 (31.6%), and 60 (38.0%) received epinephrine via central IV, IC, and peripheral IV routes, respectively. The median age was 71 [61, 80] years and 56% of the participants were men. Patient characteristics did not differ across administration routes, except for age (higher for peripheral IV than IC route), LVEF (lowest in peripheral IV route), serum potassium (although no significant post hoc differences), hemoglobin (lowest in peripheral IV route), and heart rhythm before cardiopulmonary resuscitation (higher rates of electromechanical dissociation in peripheral IV route) (Tables 1 and 2).

Fig. 1
figure 1

Consort diagram detailing the analysis

Full size image
Table 2 Heart rhythm, laboratory and instrumental tests of acute myocardial infarction patients undergoing cardiopulmonary resuscitation classified by epinephrine administration route
Full size table

There were 111 (70%) patients who achieved the primary outcome of ROSC (Table 3). Receiving epinephrine via peripheral IV administration was associated with lower odds of achieving ROSC (OR: 0.14, 95% CI 0.05–0.36, p < 0.0001) compared with central IV and IC. (There was no difference between central and IC; p = 0.9343.) Epinephrine administration route yielded an area under the receiver operating characteristic curve (AUC) of 0.73, indicating good predictive ability. On multivariable analysis, after adjusting for age and heart rhythm prior to CPR, the peripheral IV route was associated with 5.5-fold lower odds (OR: 0.18, 95% CI 0.07–0.49, p = 0.0007) of achieving ROSC compared with the central IV route and there was still no difference between central IV and IC routes (p = 0.9516) (Table 4, Fig. 2). Each year increase in age was associated with 5% lower odds of achieving ROSC and that patients with VF instead of EMD prior to CPR had 2.5 times the odds of achieving ROSC (Table 4).

Table 3 Clinical course and in-hospital outcomes of acute myocardial infarction patients undergoing cardiopulmonary resuscitation by epinephrine administration route
Full size table
Table 4 Adjusted odds ratios for return of spontaneous circulation
Full size table
Fig. 2
figure 2

Forest plot for the outcome of return of spontaneous circulation

Full size image

A total of 31 (20%) patients developed stent thrombosis, 19 of whom had received epinephrine via the IC route (Table 3). This higher risk of thrombosis remained true after adjusting for age, LVEF, and hemoglobin, with the odds of stent thrombosis for patients with IC route being 4.6–6 times higher than for the others (IC vs. peripheral IV OR: 4.6, 95% CI 1.5–14.3, p = 0.0094; IC vs. central IV OR: 6.0, 95% CI 1.9–19.2, p = 0.0025) (Fig. 3). We performed two sensitivity analyses. The first (not shown) considered thrombosis-specific variables (thrombocyte ADP and platelets) as covariates and confirmed the finding of higher odds of thrombosis with the IC route than in the other two routes. The second considered the outcome of thrombosis, conditional on achieving ROSC. For the 111 patients who achieved ROSC, there was no significant difference in the odds of thrombosis between those who had IC versus peripheral IV administration (OR: 2.3, 95% CI 0.8–6.5, p = 0.1277); however, the odds were still nearly sixfold higher compared with central IV administration (OR: 5.7, 95% CI 1.9–17.2, p = 0.0022).

Fig. 3
figure 3

Forest plot for the outcome of stent thrombosis

Full size image

A total of 75 (47%) patients survived to discharge and had a good neurologic status; those with peripheral IV administration were the least likely to achieve this outcome (Table 3). After adjusting for age, LVEF, and hemoglobin, the odds of achieving this outcome for those who had IC versus peripheral IV administration were 7.8 (95% CI 2.2–27.0, p = 0.0013). There was not a significant difference in the odds for those who had IC versus central (OR = 3.6, 95% CI = 0.96–13.2, p = 0.0585).

Finally, we investigated the time-to-ROSC between groups (Fig. 4) and the relationship with favorable neurologic outcomes (CPC score 1–2). Although there were only 4 cases of poor CPC scores, we identified a significant association between time-to-ROSC and CPC score. Specifically, those with good CPC scores had a median time-to-ROSC of 8 [5, 10] minutes compared to 26 [27.5, 32] minutes for those with poor CPC scores (p = 0.0025) (Fig. 5).

Fig. 4
figure 4

Cumulative density functions (CDFs) comparing time-to-return of spontaneous circulation (ROSC), for those who achieved ROSC

Full size image
Fig. 5
figure 5

Relationship between time-to-return of spontaneous circulation (ROSC) and CPC score

Full size image

Discussion

In this prospective study of 158 patients who presented with NSTEMI or STEMI, suffered cardiac arrest in the catheterization laboratory, and received epinephrine during CPR, we found that the rates of ROSC were substantially higher with central IV and IC epinephrine administration compared to peripheral IV administration. Furthermore, the rates of in-stent thrombosis were higher in the IC route than the other two routes. Central IV and IC epinephrine administration was associated with a higher survival to discharge with a good neurological outcome (CPC score of 1 or 2) compared with the peripheral IV route. Overall, the central IV route was superior as it was equally effective in achieving ROSC as the IC route, while maintaining a lower rate of stent thrombosis.

The vascular physiology of epinephrine and the role of coronary blood flow

Epinephrine is a catecholamine that binds to α1, β1, and β2 adrenergic receptors in cardiac and smooth muscle tissue. It directs blood flow away from mesenteric circulation and toward skeletal muscle tissue and vital organs via selective arteriolar constriction mediated by α1 receptors. Activation of α1 receptors results in an overall increase in peripheral resistance which augments aortic pressures and increases venous return. This increases preload and coronary blood flow. Coronary blood flow is further increased by the β receptor-mediated relaxation of coronary arteries [24, 25]. While it is unclear whether epinephrine bolsters microcirculation and tissue oxygenation, coronary blood flow appears critical to achieving ROSC [26, 27]. A study of 100 patients with out-of-hospital cardiac arrest measured coronary perfusion pressure via pressure catheters. Patients who achieved ROSC had a significantly higher maximal coronary perfusion pressure than those who did not achieve ROSC (25.6 ± 7.7 vs 8.4 ± 10.1, p < 0.001) [28]. Epinephrine is unlikely to bolster coronary blood flow unless it circulates effectively.

Systemic blood flow and drug circulation during external chest compressions

One reason for the poor performance of the peripheral IV group may be the failure of epinephrine to reach the systemic circulation. During normal flow states, drugs can be given via both peripheral and central routes effectively [29]. During cardiac arrest, however, cardiac output is dramatically reduced with the redistribution of blood flow [30]. Two proposed mechanisms describe the movement of blood flow during external chest compressions. The ‘cardiac pump’ mechanism proposes that direct compression of the ventricles generates antegrade flow, while the ‘thoracic pump’ mechanism proposes that dynamic changes in intrathoracic pressures during chest compression drive blood flow. Prior studies suggest that both proposed mechanisms are responsible for blood flow during CPR [31].

Echocardiographic data suggest that retrograde flow commonly occurs due to the incomplete closure of the atrioventricular valves, regardless of the predominant mechanism of blood flow [32,33,34]. Tricuspid regurgitation, combined with the local veno-constrictive effect of peripherally administered epinephrine, and an increase in circulation time due to decreased cardiac output during CPR work synergistically to greatly reduce the amount of epinephrine reaching the systemic circulation [30, 35].

Several studies comparing simulated drug delivery via central IV and peripheral IV routes during CPR have found a significant reduction in the time to rise to half of the left ventricular peak concentration with the central IV administration compared to peripheral IV administration [36]. These studies, along with our analysis, suggest that central IV drug administration is a superior method of drug administration during CPR compared with peripheral IV administration [29, 30, 36].

Epinephrine administration during CPR and neurological outcomes

Data regarding neurological outcomes with epinephrine use during in-hospital CPR are sparse. The Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug administration In Cardiac arrest II trial was a randomized double-blind trial comparing epinephrine to placebo in 8014 patients with out-of-hospital cardiac arrest [37]. It found that epinephrine resulted in a higher rate of ROSC and 30-day survival, but that survivors had worse neurological outcomes than those in the placebo group. However, epinephrine was administered over 20 min after the ambulance was called. Given that neuronal death can occur within minutes, it is difficult to conclusively attribute worse neurological outcomes to epinephrine administration alone.

While the nature of cardiac arrest makes it difficult to conduct high-quality randomized controlled trials on this subject, other studies indicate that epinephrine may have a beneficial effect on outcomes. A large observational study of 119,639 patients with an observed out-of-hospital cardiac arrest found that early epinephrine administration (within 5–18 min of emergency call) was associated with better neurological outcomes than later epinephrine administration [38]. A retrospective study utilizing the Get With The Guidelines-Resuscitation database of 25,095 patients with non-shockable in-hospital cardiac arrest found that the administration of epinephrine had a significant impact on outcomes [39]. When examining the data in 3-min intervals, there was an associated decrease in ROSC and 24-h survival for patients who received epinephrine within 4–6 min, 7–9 min, or > 9 min after cardiac arrest compared to receipt within 1–3 min. Similarly, survival with good neurological function (CPC score 1–2) decreased in a stepwise manner if epinephrine was administered 7–9 min or > 9 min when compared with 1–3 min or 3–6 min. These studies are concordant with our findings.

Conversely, another study from the same registry examined 2978 patients with shockable in-hospital cardiac arrest who underwent defibrillation within the first 2 minutes of CPR [40]. Epinephrine administered within 2 minutes of defibrillation was associated with decreased rates of ROSC, survival to hospital discharge, and survival with good neurological function (CPC score 1–2). This may be due to increased myocardial oxygen consumption or degeneration of a shockable rhythm to PEA arrest from β receptor activation by epinephrine [41]. Unfortunately, our study design did not allow us to repeat this analysis.

Intracoronary epinephrine administration and stent thrombosis

We found that IC epinephrine was associated with substantially higher rates of stent thrombosis, even when adjusting for platelet and thrombocyte ADP levels. The INR did not differ between the three groups, and all patients were on dual antiplatelet medications. Multiple prior case reports describe epinephrine-associated stent thrombosis in anaphylaxis patients [42,43,44,45]. Epinephrine increases platelet aggregation, in part by increasing thromboxane A2 synthesis and synergistically increasing ADP binding to its target receptors [46]. Epinephrine has also been shown to decrease the rate of fibrinolysis, further promulgating a procoagulant environment [47]. Even at low doses, epinephrine counteracts the effect of both aspirin, which decreases thromboxane A2 levels by inhibiting cyclooxygenase 1 and 2, and P2Y12 receptor inhibitors, as P2Y12 receptors are activated by ADP binding [48]. Most likely, IC epinephrine reached the super-therapeutic level, decreasing the efficacy of antiplatelet medications and increasing the risk of stent thrombosis [47]. While this did not decrease the rate of ROSC, survival-to-discharge, or neurological outcomes, these findings highlight the need for more investigation of the impact of IC epinephrine injection on thrombosis.

Limitations

The most notable limitation of this study is the lack of treatment randomization. The effort made to limit cofounders by expanding the exclusion criteria resulted in a smaller sample size; of 352 patients experiencing cardiac arrest at the catheterization laboratory, only 152 qualified for inclusion in the analysis. The multicenter design of this study helps to improve the generalizability of findings. Because there were only two centers, we were unable to consider the center as a random effect in the model. However, we observed few differences in patient/treatment characteristics between the two centers and the center was nonsignificant on multivariable analysis. We only studied patients with AMI who had a cardiac arrest in the cardiac catheterization laboratory; hence, our findings may not apply to patients without AMI or patients with OHCA.

Conclusion

Current guidelines do not specify the route of administration of epinephrine during CPR, and it is typically given through a peripheral IV. Our study suggests significant benefits of delivering epinephrine via the central IV or IC routes, rather than via a peripheral IV route, in terms of the rates of ROSC and survival to hospital discharge. These findings support obtaining a central IV line for patients being administered to the catheterization laboratory with a higher risk of developing cardiac arrest. If central IV access is not obtained prior to cardiac arrest, our findings support the administration of epinephrine via the IC route instead of the peripheral IV route. However, IC administration was associated with a higher risk of stent thrombosis. Future randomized trials comparing these routes are needed to replicate our findings and further investigate the relationship between IC epinephrine and coronary thrombotic events.

Availability of data and materials

The datasets used in this study are available from the corresponding author upon reasonable request.

References

  1. Madotto F, McNicholas B, Rezoagli E, et al. Death in hospital following ICU discharge: insights from the LUNG SAFE study. Crit Care. 2021. https://doi.org/10.1186/s13054-021-03465-0.

    Article  Google Scholar 

  2. Kolte D, Khera S, Aronow WS, et al. Regional variation in the incidence and outcomes of in-hospital cardiac arrest in the United States. Circulation. 2015. https://doi.org/10.1161/circulationaha.114.014542.

    Article  Google Scholar 

  3. Nolan JP, Soar J, Smith GB, et al. Incidence and outcome of in-hospital cardiac arrest in the United Kingdom National Cardiac Arrest Audit. Resuscitation. 2014. https://doi.org/10.1016/j.resuscitation.2014.04.002.

    Article  Google Scholar 

  4. Okubo M, Komukai S, Callaway CW, Izawa J. Association of timing of epinephrine administration with outcomes in adults with out-of-hospital cardiac arrest. JAMA Netw Open. 2021. https://doi.org/10.1001/jamanetworkopen.2021.20176.

    Article  Google Scholar 

  5. Soar J, Böttiger BW, Carli P, Guidelines ERC, et al. Adult advanced life support. Resuscitation. 2021;2021:115–51. https://doi.org/10.1016/j.resuscitation.2021.02.010.

    Article  Google Scholar 

  6. Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: adult basic and advanced life support: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2020. https://doi.org/10.1161/cir.0000000000000916.

    Article  Google Scholar 

  7. Neth MR, Daya MR. Intravenous versus intraosseous vascular access site for medication administration during cardiac arrest: Is one preferable than the other? Resuscitation. 2021. https://doi.org/10.1016/j.resuscitation.2021.08.018.

    Article  Google Scholar 

  8. Halling C, Sparks JE, Christie L, Wyckoff MH. Efficacy of intravenous and endotracheal epinephrine during neonatal cardiopulmonary resuscitation in the delivery room. J Pediatr. 2017. https://doi.org/10.1016/j.jpeds.2017.02.024.

    Article  Google Scholar 

  9. Pugh AE, Stoecklein HH, Tonna JE, Hoareau GL, Johnson MA, Youngquist ST. Intramuscular adrenaline for out-of-hospital cardiac arrest is associated with faster drug delivery: a feasibility study. Resuscitation Plus. 2021. https://doi.org/10.1016/j.resplu.2021.100142.

    Article  Google Scholar 

  10. Safar P. Community-wide cardiopulmonary resuscitation. J Iowa Med Soc. 1964;54:629–35.

    CAS  Google Scholar 

  11. Shaik FA, Slotwiner DJ, Gustafson GM, Dai X. Intra-procedural arrhythmia during cardiac catheterization: a systematic review of literature. WJC. 2020;12(6):269–84.

    Article  Google Scholar 

  12. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics—2022 update: a report from the American heart association. Circulation. 2022;145(8):e153-639.

    Article  Google Scholar 

  13. Soar J, Nolan JP, Böttiger BW, et al. European Resuscitation Council Guidelines for Resuscitation. Resuscitation. 2015;2015:100–47. https://doi.org/10.1016/j.resuscitation.2015.07.016.

    Article  Google Scholar 

  14. Stecker EC, Teodorescu C, Reinier K, et al. Ischemic heart disease diagnosed before sudden cardiac arrest is independently associated with improved survival. JAHA. 2014. https://doi.org/10.1161/jaha.114.001160.

    Article  Google Scholar 

  15. Wang C-J, Yang S-H, Chen C-H, Chung H-P. Targeted temperature management for in-hospital cardiac arrest: 6 years of experience. Therap Hypother Temp Manag. 2020. https://doi.org/10.1089/ther.2019.0019.

    Article  Google Scholar 

  16. Balouris SA, Raina KD, Rittenberger JC, Callaway CW, Rogers JC, Holm MB. Development and validation of the cerebral performance categories-extended (CPC-E). Resuscitation. 2015. https://doi.org/10.1016/j.resuscitation.2015.05.013.

    Article  Google Scholar 

  17. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD. Fourth universal definition of myocardial infarction. Circulation. 2018. https://doi.org/10.1161/CIR.0000000000000617.

    Article  Google Scholar 

  18. Mach F, Baigent C, Catapano AL, et al. ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2019;2019:111–88. https://doi.org/10.1093/eurheartj/ehz455.

    Article  Google Scholar 

  19. Williams B, Mancia G, Spiering W, et al. ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018;2018:3021–104. https://doi.org/10.1093/eurheartj/ehy339.

    Article  Google Scholar 

  20. Buse JB, Wexler DJ, Tsapas A, et al. Update to: management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the study of diabetes (EASD). Diabetologia. 2019;2019:221–8. https://doi.org/10.1007/s00125-019-05039-w.

    Article  Google Scholar 

  21. Vahdatpour C, Collins D, Goldberg S. Cardiogenic shock. JAHA. 2019. https://doi.org/10.1161/JAHA.119.011991.

    Article  Google Scholar 

  22. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2017;39(2):119–77. https://doi.org/10.1093/eurheartj/ehx393.

    Article  Google Scholar 

  23. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015. https://doi.org/10.1093/ehjci/jev014.

    Article  Google Scholar 

  24. Overgaard CB, Dzavík V. Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease. Circulation. 2008;118(10):1047–56.

    Article  Google Scholar 

  25. Lichtenstein SV, el-Dalati H, Panos A, Rice TW, Salerno TA. Systemic vascular effects of epinephrine administration in man. J Surg Res. 1987;42(2):166–78.

    Article  CAS  Google Scholar 

  26. Deakin CD, Yang J, Nguyen R, et al. Effects of epinephrine on cerebral oxygenation during cardiopulmonary resuscitation: a prospective cohort study. Resuscitation. 2016;109:138–44.

    Article  Google Scholar 

  27. Hardig BM, Götberg M, Rundgren M, et al. Physiologic effect of repeated adrenaline (Epinephrine) doses during cardiopulmonary resuscitation in the cath lab setting: a randomised porcine study. Resuscitation. 2016;101:77–83.

    Article  Google Scholar 

  28. Paradis NA, Martin GB, Rivers EP, et al. Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. JAMA. 1990;263(8):1106–13.

    Article  CAS  Google Scholar 

  29. Barsan WG, Hedges JR, Nishiyama H, Lukes ST. Differences in drug delivery with peripheral and central venous injections: normal perfusion. Am J Emerg Med. 1986;4:1–3. https://doi.org/10.1016/0735-6757(86)90239-1.

    Article  CAS  Google Scholar 

  30. Lurie KG, Nemergut EC, Yannopoulos D, Sweeney M. The physiology of cardiopulmonary resuscitation. Anesth Analg. 2016;122:767–83. https://doi.org/10.1213/ANE.0000000000000926.

    Article  Google Scholar 

  31. Georgiou M, Papathanassoglou E, Xanthos T. Systematic review of the mechanisms driving effective blood flow during adult CPR. Resuscitation. 2014;85(11):1586–93.

    Article  Google Scholar 

  32. Ma MH, Hwang JJ, Lai LP, et al. Transesophageal echocardiographic assessment of mitral valve position and pulmonary venous flow during cardiopulmonary resuscitation in humans. Circulation. 1995;92(4):854–61.

    Article  CAS  Google Scholar 

  33. Kim H, Hwang SO, Lee CC, et al. Direction of blood flow from the left ventricle during cardiopulmonary resuscitation in humans: its implications for mechanism of blood flow. Am Heart J. 2008;156(6):1222.e1-7.

    Article  Google Scholar 

  34. Werner JA, Greene HL, Janko CL, Cobb LA. Visualization of cardiac valve motion in man during external chest compression using two-dimensional echocardiography. Implications regarding the mechanism of blood flow. Circulation. 1981;63(6):1417–21.

    Article  CAS  Google Scholar 

  35. Rudner XL, Berkowitz DE, Booth JV, et al. Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age. Circulation. 1999;100(23):2336–43.

    Article  CAS  Google Scholar 

  36. Hedges JR, Barsan WB, Doan LA, Joyce SM, Lukes SJ, Dalsey WC, Nishiyama H. Central versus peripheral intravenous routes in cardiopulmonary resuscitation. Am J Emerg Med. 1984;2:385–90. https://doi.org/10.1016/0735-6757(84)90038-X.

    Article  CAS  Google Scholar 

  37. Perkins GD, Ji C, Deakin CD, et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest. N Engl J Med. 2018;379(8):711–21.

    Article  CAS  Google Scholar 

  38. Tanaka H, Takyu H, Sagisaka R, et al. Favorable neurological outcomes by early epinephrine administration within 19 minutes after EMS call for out-of-hospital cardiac arrest patients. Am J Emerg Med. 2016;34(12):2284–90.

    Article  CAS  Google Scholar 

  39. Donnino MW, Salciccioli JD, Howell MD, et al. Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry. BMJ. 2014;348: g3028.

    Article  Google Scholar 

  40. Andersen LW, Kurth T, Chase M, et al. Early administration of epinephrine (Adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis. BMJ. 2016;353: i1577.

    Article  Google Scholar 

  41. Nordseth T, Olasveengen TM, Kvaløy JT, Wik L, Steen PA, Skogvoll E. Dynamic effects of adrenaline (Epinephrine) in out-of-hospital cardiac arrest with initial pulseless electrical activity (Pea). Resuscitation. 2012;83(8):946–52.

    Article  CAS  Google Scholar 

  42. Huda SA, Chaudhuri D. Very late stent thrombosis due to possible epinephrine-induced transient vasospasm. Am J Ther. Published online July 13, 2021.

  43. Park JS, Min JH, Kang JH, In YN. Acute myocardial infarction due to stent thrombosis after administration of intravenous epinephrine for anaphylaxis. Chin Med J (Engl). 2015;128(19):2692–3.

    Article  Google Scholar 

  44. Jackson CE, Dalzell JR, Hogg KJ. Epinephrine treatment of anaphylaxis: an extraordinary case of very late acute stent thrombosis. Circ Cardiovasc Interv. 2009;2(1):79–81.

    Article  Google Scholar 

  45. Kasim S, AbuBakar R, McFadden E. Anaphylaxis from wasp stings inducing coronary thrombus. Case Rep Cardiol. 2012;2012: 701753.

    Google Scholar 

  46. Béres BJ, Tóth-Zsámboki E, Vargová K, László A, Masszi T, Kerecsen G, Préda I, Kiss RG. Analysis of platelet alpha2-adrenergic receptor activity in stable coronary artery disease patients on dual antiplatelet therapy. Thromb Haemost. 2008;100(5):829–38 (PMID: 18989527).

    Article  Google Scholar 

  47. Golaszewska A, Misztal T, Marcinczyk N, Chabielska E, Rusak T. Adrenaline may contribute to prothrombotic condition via augmentation of platelet procoagulant response, enhancement of fibrin formation, and attenuation of fibrinolysis. Front Physiol Front Media SA. 2021. https://doi.org/10.3389/fphys.2021.657881.

    Article  Google Scholar 

  48. Haaland HD, Holmsen H. Potentiation by adrenaline of agonist-induced responses in normal human platelets in vitro. Platelets. 2011;22:328–37. https://doi.org/10.3109/09537104.2011.551949.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors have nothing to declare.

Funding

Not applicable.

Author information

Author notes

  1. Ali Aldujeli and Ayman Haq contributed equally this project and are considered co-first authors

Authors and Affiliations

  1. Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Kaunas, Lithuania

    Ali Aldujeli, Zemyna Kurnickaite, Karolis Lickunas, Giedre Baksyte, Kasparas Briedis, Rasa Ordiene & Ramunas Unikas

  2. Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania

    Ali Aldujeli & Vacis Tatarunas

  3. Abbott Northwestern Hospital/Minneapolis Heart Institute Foundation, Minneapolis, MN, USA

    Ayman Haq & Emmanouil S. Brilakis

  4. Baylor Scott & White Research Institute, Dallas, TX, USA

    Kristen M. Tecson

  5. Medical City Fort Worth, Fort Worth, TX, USA

    Som Bailey

  6. Republican Hospital of Panevezys, Panevezys, Lithuania

    Rima Braukyliene

  7. University of Brescia, Brescia, Italy

    Montazar Aldujeili

  8. Kreiskrankenhaus Rotenburg, Rotenburg an der Fulda, Germany

    Hussein Khalifeh

  9. Texas Cardiovascular Institute, Fort Worth, TX, USA

    Anas Hamadeh

Authors
  1. Ali Aldujeli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ayman Haq
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kristen M. Tecson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zemyna Kurnickaite
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karolis Lickunas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Som Bailey
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vacis Tatarunas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rima Braukyliene
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Giedre Baksyte
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Montazar Aldujeili
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hussein Khalifeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kasparas Briedis
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Rasa Ordiene
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ramunas Unikas
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Anas Hamadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Emmanouil S. Brilakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AA, M.D., M.Sc., contributed to supervision, conceptualization, data curation, methodology, writing—original draft preparation, writing—(critical) reviewing and editing, final approval, and accountability. AH, M.D., contributed to supervision, conceptualization, data curation, methodology, writing—original draft preparation, writing—(critical) reviewing and editing, final approval, and accountability. KMT, Ph.D., contributed to formal analysis, writing—reviewing and editing, visualization, funding acquisition, writing—original draft preparation, final approval, and accountability. ZK contributed to investigation—data collection, validation, writing—(critical) reviewing and editing, final approval, and accountability. KL contributed to investigation—data collection, validation, writing—(critical) reviewing and editing, final approval, and accountability. SB, M.D, contributed to data interpretation, writing—(critical) reviewing and editing, final approval, and accountability. VT, Ph.D., contributed to data interpretation, writing—(critical) reviewing and editing, final approval, and accountability. RB, M.D., M.Sc., contributed to investigation—data collection, validation, writing—(critical) reviewing and editing, final approval, and accountability. GB contributed to methodology, validation, writing—(critical) reviewing and editing, final approval, and accountability. MA contributed to investigation—data collection, validation, writing—(critical) reviewing and editing, final approval, and accountability. HK, M.D., contributed to data interpretation, writing—(critical) reviewing and editing, final approval, and accountability. KB, M.D., M.Sc., contributed to investigation—data collection, validation, writing—(critical) reviewing and editing, final approval, and accountability. RO, M.D., M.Sc., contributed to investigation—data collection, validation, writing—(critical) reviewing and editing, final approval, and accountability. RU, M.D., M.Sc., Ph.D., contributed to data interpretation, writing—(critical) reviewing and editing, final approval, and accountability. AH, M.D., contributed to supervision, data interpretation, writing—(critical) reviewing and editing, final approval, and accountability. ESB, M.D., M.Sc., Ph.D., contributed to supervision, conceptualization, data curation, methodology, writing—original draft preparation, writing—(critical) reviewing and editing, final approval, and accountability. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Ali Aldujeli.

Ethics declarations

Ethics approval and consent to participate

We conducted this study in compliance with the ethical standards of the Regional Bioethics Committee of Kaunas, Lithuania (the permission number is BE-2-4), and the World Medical Association Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects. Clinical Trials registration number: NCT05253937, retrospectively registered. All subjects gave their informed consent to participate, and an information letter was given to them.

Consent to publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aldujeli, A., Haq, A., Tecson, K.M. et al. A prospective observational study on impact of epinephrine administration route on acute myocardial infarction patients with cardiac arrest in the catheterization laboratory (iCPR study). Crit Care 26, 393 (2022). https://doi.org/10.1186/s13054-022-04275-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13054-022-04275-8

Keywords

Critical Care

ISSN: 1364-8535