Standard-dose Epinephrine Research Articles

Epinephrine in Out-of-Hospital Cardiac Arrest: A Network Meta-analysis and Subgroup Analyses of Shockable and Nonshockable Rhythms

Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed. What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA? In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95%CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome. We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95%CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95%CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95%CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95%CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95%CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95%CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95%CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95%CI, 0.39-1.85). Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm. Center for Open Science: (https://osf.io/arxwq).

Establishing a multicenter, preclinical consortium in resuscitation: A pilot experimental trial evaluating epinephrine in cardiac arrest

BackgroundLarge animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results. MethodsForty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy. ResultsThere were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004). ConclusionThis study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo.

Timing of Intravenous Epinephrine Administration During Out-of-Hospital Cardiac Arrest.

Current guidelines for cardiopulmonary resuscitation recommend that standard dose of epinephrine be administered every 3 to 5 min during cardiac arrest. However, there is controversy about the association between timing of epinephrine administration and outcomes after out-of-hospital cardiac arrest (OHCA). This study aimed to determine whether the timing of intravenous epinephrine administration is associated with outcomes after OHCA. We analyzed Japanese government-led nationwide population-based registry data for OHCA. Adult OHCA patients who received intravenous epinephrine by emergency medical service personnel in the prehospital setting from 2011 to 2017 were included. Multivariable logistic regression models were used to assess the associations between time to first epinephrine administration and outcomes after OHCA. Subsequently, associations between early (≤20 min) versus delayed (>20 min) epinephrine administration and outcomes after OHCA were examined using propensity score-matched analyses. The primary outcome was 1-month neurologically favorable survival. A total of 119,946 patients (mean [SD] age, 75.2 [14.8] years; 61.4% male) were included. The median time to epinephrine was 23 min (interquartile range, 19-29). Longer time to epinephrine was significantly associated with a decreased chance of 1-month neurologically favorable survival (multivariable adjusted OR per minute delay, 0.91 [95% CI, 0.90-0.92]). In the propensity score-matched cohort, when compared with early (≤20 min) epinephrine, delayed (>20 min) epinephrine was associated with a decreased chance of 1-month neurologically favorable survival (959/42,804 [2.2%] vs. 330/42,804 [0.8%]; RR, 0.34; 95% CI, 0.30-0.39; NNT, 69). Delay in epinephrine administration was associated with a decreased chance of 1-month neurologically favorable survival among patients with OHCA.

After a century, Epinephrine's role in cardiac arrest resuscitation remains controversial.

Epinephrine is recommended in contemporary educational efforts by the American Heart Association (AHA) as central to adult Advanced Cardiac Life Support (ACLS). However, the International Liaison Committee on Resuscitation (ILCOR) 2019 recommendations update describes large evidentiary gaps for epinephrine use in cardiopulmonary resuscitation, highlighting that clinical and experimental evidence do not support the current AHA recommendations. This controversies article was written as a response to updated AHA and ILCOR adult ACLS recommendations in late 2019. This report summarizes and evaluates the evidence surrounding epinephrine for cardiac arrest with a focus on the historical perspective of epinephrine research. According to the 2019 AHA ACLS guidelines, epinephrine is an integral component of adult out-of-hospital cardiac arrest resuscitation. Epinephrine improves rates of return of spontaneous circulation and might provide benefit at different doses or in select resuscitation scenarios, such asystole as an initial rhythm at onset of resuscitation efforts. However, evidence indicates potential harms with routine use of standard dose epinephrine (1mg/10mL), with no improvement in neurologic or long-term outcomes. Despite years of use and inclusion in resuscitation guidelines, epinephrine is not associated with improved neurologic outcomes. The AHA Emergency Cardiovascular Care committee should revise ACLS guidelines reflecting evidence that standard-dose epinephrine offers little benefit to successful patient recovery including neurologic outcomes. Future resuscitation guidelines should reflect this important consideration.

Abstract 165: Impact of Prehospital Epinephrine for Patients Treated With Extracorporeal Cardiopulmonary Resuscitation After Refractory Out-Of-Hospital Shockable Cardiac Arrest

Background: The 2015 CoSTR recommended that standard-dose epinephrine (SDE) was reasonable for patients with out-of-hospital cardiac arrest (OHCA) and extracorporeal cardiopulmonary resuscitation (ECPR) was reasonable rescue therapy for selected patients with ongoing cardiac arrest when initial conventional CPR was unsuccessful. We investigated the effect of prehospital SDE for patients who met the criteria of ECPR. Methods: From the All-Japan OHCA Utstein Registry between 2007 and 2015, we included 22,552 patients who met the criteria of ECPR of the SAVE-J study (age between 20 and 75, witnessed shockable OHCA, cardiac arrest on hospital arrival, cardiac etiology, and collapse-to-ECPR interval within 60 minutes). Study patients were divided into two groups according to prehospital SDE or not. Primary endpoint was favorable 30-day neurological outcome after OHCA. Results: Of the 22,552 study patients, 5,659 (25%) received prehospital SDE and 16,893 (75%) did not. The SDE group resulted in lower proportion of favorable 30-day neurological outcome than the no-SDE group (5.6% versus 8.4%, p<0.001) with longer collapse-to-hospital-arrival interval (36.7±9.8 min vs. 29.6±11.3 min, p<0.001). After adjustment for independent predictors of resuscitation, prehospital SDE did not impact on neurological benifit (adjusted OR,1.13; 95%CI,0.98-1.29), but the collapse-to-hospital-arrival interval was associated with neurological benefit (adjusted OR, 0.94; 95% CI, 0.93-0.95). In curve estimation of the SDE group, when collapse-to-hospital-arrival interval was delayed, proportion of the favorable neurological outcome decreased to about 25% at 1 minute and about 0% at 54 minutes (R=0.14). In the 274 patients undergoing ECPR of the SAVE-J study, however, it was about 43% at 1 minute and about 0% at 96 minutes (R=0.17). Conclusions: Prehospital SDE did not improve likelihood of favorable neurological outcome for patients who met the criteria of ECPR (age between 20 and 75, witnessed shockable OHCA, cardiac arrest on hospital arrival, cardiac etiology and collapse-to-ECPR interval within 60 minutes), because SED administration delayed the collapse-to-hospital-arrival interval which was closely related to the neurologically intact survival on ECPR.

2019 American Heart Association Focused Update on Advanced Cardiovascular Life Support: Use of Advanced Airways, Vasopressors, and Extracorporeal Cardiopulmonary Resuscitation During Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

The fundamentals of cardiac resuscitation include the immediate provision of high-quality cardiopulmonary resuscitation combined with rapid defibrillation (as appropriate). These mainstays of therapy set the groundwork for other possible interventions such as medications, advanced airways, extracorporeal cardiopulmonary resuscitation, and post-cardiac arrest care, including targeted temperature management, cardiorespiratory support, and percutaneous coronary intervention. Since 2015, an increased number of studies have been published evaluating some of these interventions, requiring a reassessment of their use and impact on survival from cardiac arrest. This 2019 focused update to the American Heart Association advanced cardiovascular life support guidelines summarizes the most recent published evidence for and recommendations on the use of advanced airways, vasopressors, and extracorporeal cardiopulmonary resuscitation during cardiac arrest. It includes revised recommendations for all 3 areas, including the choice of advanced airway devices and strategies during cardiac arrest (eg, bag-mask ventilation, supraglottic airway, or endotracheal intubation), the training and retraining required, the administration of standard-dose epinephrine, and the decisions involved in the application of extracorporeal cardiopulmonary resuscitation and its potential impact on cardiac arrest survival.

Adrenaline and vasopressin for cardiac arrest.

Adrenaline and vasopressin for cardiac arrest.

Abstract 210: Goal-Directed CPR is Less Effective With an Increased Interval From Cardiac Arrest Onset to Initiation of Chest Compressions

Introduction: The interval from cardiac arrest (CA) to initiation of chest compressions (no-flow time) plays an important role in outcome of CA. The purpose of this study was to evaluate impact of no-flow time on the effectiveness of a goal-direct CPR strategy during prolonged cardiac arrest. Hypothesis: The effectiveness of goal-directed CPR declines with increased no-flow time. Methods: Porcine model of CA was utilized with a period of untreated ventricular fibrillation of 4 or 8 min (groups CA-4, CA-8, n=5/group) followed by a goal-directed CPR protocol for up to 40 minutes. Manual and mechanical chest compressions with impedance threshold device were used sequentially to achieve PetCO2 goal >20 mmHg. Epinephrine infusion and boluses were adjusted with the goal of achieving an arterial diastolic blood pressure >35 mmHg. Hemodynamic parameters were collected throughout the protocol, averaged in 5-minute intervals and compared between groups by an unpaired t-test. Results: A higher average DBP was achieved in the CA-4 vs. CA-8 group during CPR (19 ± 11 mmHg vs. 12 ± 9 mmHg: p<0.04) with stronger responses to epinephrine boluses (max increase 23 vs. 11 mmHg). Brain perfusion through internal carotid artery during CPR relative to baseline averaged 24 ± 34 % vs. 10 ± 12 % in the CA-4 vs. CA-8 group respectively (p<0.006). PetCO2 remained above 20 mmHg 71 ± 35 % vs. 31 ± 13 % of time during CPR in the CA-4 vs. CA-8 group respectively (p<0.001). Conclusion: In this swine model of prolonged VF cardiac arrest, increased no-flow time limits the effectiveness of a goal-directed CPR strategy. Moreover, the response to standard dose of epinephrine was higher after shorter no-flow time.

Abstract 10437: Epinephrine in Cardiac Arrest: A Randomized, Multicenter, Double-blinded, Placebo-Controlled Experimental Trial

Introduction: Epinephrine is universally used in cardiac arrest primarily to increase coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR). The effect of different modes of epinephrine administration and the persistence of effect with repeated doses are not known. Methods: We conducted a preclinical, randomized, multicenter, double-blinded, placebo-controlled experimental trial of 45 swine from five different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous CPR, which included mechanical chest compressions (100/min) and manual ventilations using a bag-valve-mask with 100% O2 (10 breaths/min). After 2 min of CPR onset, nine animals from each lab were centrally randomized to one of three treatment arms: 1) Continuous IV epinephrine infusion (0.00375mg/kg/min) for 12 min and placebo IV normal saline (NS) boluses every 4 min, 2) Three IV epinephrine boluses (0.015mg/kg) every 4 min and placebo IV NS infusion, or 3) Placebo NS infusion and boluses. The primary outcome was mean CPP during the drug therapy period (2-14 minutes after CPR onset). Differences in CPP were analyzed using repeated measures regression modeling. Results: There was no statistical difference in mean minute CPP (mmHg) between the three groups: 14.4±6.8 (infusion), 16.9±5.9 (bolus), and 14.4±5.5 (placebo) (p=NS). Repeated bolus doses of epinephrine caused transient increases in CPP that tended to peak at ~2 min after drug administration (Figure). Conclusion: Standard dose epinephrine, whether given by infusion or repeated boluses during CPR, did not significantly improve average CPP over time compared to placebo. Tachyphylaxis to epinephrine may occur regardless of mode of administration. This study raises important questions about optimal epinephrine dosing and administration strategy.

Could the survival and outcome benefit of adrenaline also be dependent upon the presence of gasping upon arrival of emergency rescuers?

A recent systematic review and meta-analysis of randomized controlled trials of adrenaline use during resuscitation of out-of-hospital cardiac arrest found no benefit of adrenaline in survival to discharge or neurological outcomes. It did, however, find an advantage of standard dose adrenaline (SDA) over placebo and high dose adrenaline over SDA in overall survival to admission and return of spontaneous circulation (ROSC), which was also consistent with previous reviews. As a result, the question that remains is "Why is there no difference in the rate of survival to discharge when there are increased rates of ROSC and survival to admission in patients who receive adrenaline?" It was suggested that the lack of efficacy and effectiveness of adrenaline may be confounded by the quality of cardiopulmonary resuscitation (CPR) during cardiac arrest, which has been demonstrated in animal models. CPR quality was not measured or reported in the included randomized controlled trials. However, the survival and outcome benefit of adrenaline may also depend upon the presence of witnessed gasping and/or gasping upon arrival of emergency rescuers, which is a critical factor not accounted for in the analyses of the cited animal studies that allowed gasping but showed the survival and neurological outcome benefits of adrenaline use. Moreover, without the aid of gasping, very few rescuers can provide high-quality CPR. Also, age and the absence of gasping observed by bystanders and/or upon arrival of emergency- rescuers may be important factors in the determination of whether vasopressin instead of adrenaline should be used first.

Epinephrine May Be of No Survival Benefit in Cardiac Arrest

Standard advanced cardiac life support guidelines recommend administration of epinephrine at a dose of 1 mg every 3 to 5 minutes, but is there evidence that this therapy improves outcomes? To answer this question, researchers performed a meta-analysis of 14 randomized, controlled trials (12,250 total patients) in nine countries that compared standard-dose epinephrine with high-dose epinephrine (>1 mg per dose), vasopressin, or placebo in …

Epinephrine for Cardiac Arrest

Epinephrine for Cardiac Arrest: Are We Doing More Harm Than Good? Vijay Krishnamoorthy;Monica Vavilala;Michael Fettiplace;Guy Weinberg; Anesthesiology

Outcomes by rescue shock number during the metabolic phase of porcine ventricular fibrillation resuscitation

BackgroundOptimal resuscitation duration before the first rescue shock (RS) to maximize the probability of success after prolonged ventricular fibrillation (VF) cardiac arrest remains unknown. The purpose of this study was to determine the occurrence of return of spontaneous circulation (ROSC) and survival by RS attempt after 12 minutes of untreated VF. MethodsThis was a secondary analysis of prospectively collected data from an institutional animal care and use committee-approved protocol. Fifty-three swine (30-35 kg) were instrumented under anesthesia. Ventricular fibrillation was electrically induced. After 12 minutes of untreated VF, cardiopulmonary resuscitation (CPR) was initiated (and continued as necessary (prn)) and a standard dose of epinephrine (0.01 mg/kg) was given (and repeated every 3 (q3) minutes prn). The first RS was delivered after 3 minutes of CPR (and q3 minutes thereafter prn). Each failed RS was followed (in series) by vasopressin (0.57 mg/kg), amiodarone (4.3 mg/kg), and sodium bicarbonate (1 mEq/kg) prn. Resuscitation continued until ROSC or 20-minute elapsed time. The primary outcomes were ROSC and 20-minute survival. Data were analyzed using descriptive statistics. ResultsAfter 3 minutes of resuscitation, 1 animal (1.9% [95% confidence interval {CI, 0.3-10.0]) achieved ROSC on RS1 and survived. After 6 minutes of resuscitation, 17 animals (32.1% [95% CI, 21.1-45.5]) achieved ROSC on RS2 and 15 (28.3% [95% CI, 18.0-41.6]) survived. Twelve additional animals had ROSC and survival with continued resuscitation. In 23 animals, ROSC was never achieved and efforts were terminated per protocol. ConclusionOur data suggest that during the metabolic phase of VF, 3 minutes of CPR and 1 standard dose of epinephrine may be insufficient to achieve ROSC on the first RS attempt. A longer duration of CPR and/or additional vasopressors may increase the likelihood of successful defibrillation.

Coronary Perfusion Pressure Response to High-Dose Intraosseous versus Standard-Dose Intravenous Epinephrine Administration after Prolonged Cardiac Arrest

Background: This study was done to compare coronary perfusion pressure (CPP) prior to the first rescue shock (RS) among a group of animals that received intraosseous (IO) epinephrine 0.1 mg/ kg (high-dose epinephrine [HDE]) with a group that received intravenous (IV) epinephrine 0.01 mg/kg (standard-dose epinephrine [SDE]) during cardiac arrest resuscitation using a swine model of prolonged out-of-hospital ventricular fibrillation (VF) cardiac arrest. Methods: This was a secondary analysis of prospectively collected data from two IACUC approved protocols. Seventy-nine Yorkshire swine (25 - 35 kg) were surgically instrumented under anesthesia and VF was electrically induced. After 10 minutes of untreated VF in the IO study (n = 26) and 12 minutes of untreated VF in the IV study (n = 53), resuscitation commenced with closed chest compressions (CCC). A single dose of epinephrine (HDE IO or SDE IV, respectively) was given and flushed with saline. The CCC and RS attempts were standardized for all animals. The CPP was defined as aortic diastolic pressure minus right atrial diastolic pressure measured 2.5 minutes after medication delivery. Descriptive statistics were used to analyze the data. Results: Baseline group characteristics were mathematically the same. Just prior to the first RS, HDE IO resulted in a mean CPP of 33.2 mmHg (95%CI: 26.6, 39.9), while SDE IV resulted in a mean CPP of 25.0 mmHg (95%CI: 20.5, 29.4). Conclusion: This observation study reaffirms the assertion that HDE IO may be required to generate CPP values similar to SDE IV during resuscitation of prolonged VF.

Usefulness of Medical Conferences

clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest. JAMA. 1992;268(19):2667-2672. 3. Kellermann AL, Hackman BB, Somes G. Predicting the outcome of unsuccessful prehospital advanced cardiac life support. JAMA. 1993;270(12):1433-1436. 4. Gum PA, Thamilarasan M, Watanabe J, Blackstone EH, Lauer MS. Aspirin use and all-cause mortality among patients being evaluated for known or suspected coronary artery disease: a propensity analysis. JAMA. 2001;286(10):11871194.

Usefulness of Medical Conferences

clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest. JAMA. 1992;268(19):2667-2672. 3. Kellermann AL, Hackman BB, Somes G. Predicting the outcome of unsuccessful prehospital advanced cardiac life support. JAMA. 1993;270(12):1433-1436. 4. Gum PA, Thamilarasan M, Watanabe J, Blackstone EH, Lauer MS. Aspirin use and all-cause mortality among patients being evaluated for known or suspected coronary artery disease: a propensity analysis. JAMA. 2001;286(10):11871194.

Vasopressors in cardiac arrest: A systematic review

ObjectivesTo review the literature addressing whether the use of vasopressors improves outcomes in patients who suffer cardiac arrest. MethodsDatabases were searched using the terms: “(adrenaline or noradrenaline or vasopressor) and (heart arrest or cardiac arrest) and therapy”. Inclusion criteria were human studies, controlled trials, meta-analysis or case series. Exclusion criteria were articles with no abstract, abstract-only citations without accompanying article, non-English abstracts, vasopressor studies without human clinical trials, case reports, reviews, and articles addressing traumatic arrest. Results1603 papers were identified of which 53 articles were included for review. The literature addressed 5 main therapeutic questions. (1) Outcomes comparing any vasopressor to placebo. (2) Outcomes comparing vasopressin (alone or in combination with epinephrine) to epinephrine. (3) Outcomes comparing high dose epinephrine to standard dose epinephrine. (4) Outcomes comparing any alternative vasopressor to epinephrine. (5) Outcomes examining vasopressor use in pediatric cardiac arrest. ConclusionThere are few studies that compare vasopressors to placebo in resuscitation from cardiac arrest. Epinephrine is associated with improvement in short term survival outcomes as compared to placebo, but no long-term survival benefit has been demonstrated. Vasopressin is equivalent for use as an initial vasopressor when compared to epinephrine during resuscitation from cardiac arrest. There is a short-term, but no long-term, survival benefit when using high dose vs. standard dose epinephrine during resuscitation from cardiac arrest. There are no alternative vasopressors that provide a long-term survival benefit when compared to epinephrine. There is limited data on the use of vasopressors in the pediatric population.

Variable effects of high-dose adrenaline relative to standard-dose adrenaline on resuscitation outcomes according to cardiac arrest duration

Aim of the studyAdjustment of adrenaline (epinephrine) dosage according to cardiac arrest (CA) duration, rather than administering the same dose, may theoretically improve resuscitation outcomes. We evaluated variable effects of high-dose adrenaline (HDA) relative to standard-dose adrenaline (SDA) on resuscitation outcomes according to CA duration. MethodsTwenty-eight male domestic pigs were randomised to the following 4 groups according to the dosage of adrenaline (SDA 0.02mg/kg vs. HDA 0.2mg/kg) and duration of CA before beginning cardiopulmonary resuscitation (CPR): 6min SDA, 6min HDA, 13min SDA, or 13min HDA. After the predetermined duration of untreated ventricular fibrillation, CPR was provided. ResultsAll animals in the 6min SDA, 6min HDA, and 13min HDA groups were successfully resuscitated, while only 4 of 7 pigs in the 13min SDA group were successfully resuscitated (p=0.043). HDA groups showed higher right atrial pressure, more frequent ventricular ectopic beats, higher blood glucose, higher troponin-I, and more severe metabolic acidosis than SDA groups. Animals of 13min groups showed more severe metabolic acidosis and higher troponin-I than animals of 6min groups. All successfully resuscitated animals, except two animals in the 13min HDA group, survived for 7 days (p=0.121). Neurologic deficit score was not affected by the dose of adrenaline. ConclusionHDA showed benefit in achieving restoration of spontaneous circulation in 13min CA, when compared with 6min CA. However, this benefit did not translate into improved long-term survival or neurologic outcome.

Adequacy of Epinephrine Administration during Advanced Cardiovascular Life Support in terms of Dosing and Intervals between Doses

Background: Consensus guidelines clearly define how epinephrine is administered during cardiopulmonary resuscitation (CPR). In South Korea, it is not known whether epinephrine is administered in accordance with the current advanced cardiovascular life support (ACLS) guidelines during actual practice. We sought to investigate adherence to ACLS guidelines during actual CPR in terms of the dose of epinephrine and the interval between doses. Methods: A retrospective review of medical records was performed on 394 adult cardiac arrest patients who received CPR at an emergency room. Data including the duration of CPR, the dose of epinephrine, and the interval between doses was collected from CPR records. Results: Standard-dose epinephrine (1 mg) was used in 166 of 394 patients (42.1%). In 58.8% of patients, the average between-dose interval was within the 3−5 min recommended in the guidelines, whereas it was shorter than 3 min in 31.4% of patients. As a whole, epinephrine was administered in accordance with the current ACLS guidelines in only 96 of 394 patients (24.4%). Logistic regression analysis revealed the duration of CPR to be an independent factor affecting the use of standard-dose epinephrine and the adequate between-dose interval. Conclusions: Epinephrine was not administered according to the ACLS guideline in most patients. A national multi-center study is required to determine whether the poor adherence to the ACLS guideline is a widespread problem. In addition, efforts to improve adherence to the ACLS guideline are required.

Effect and mechanism of esmolol given during cardiopulmonary resuscitation in a porcine ventricular fibrillation model

Objectives The aim of the study was to investigate the effect on calcium cycling protein and electrical restitution of β 1-adrenergic receptor antagonist esmolol administered during cardiopulmonary resuscitation in the porcine ventricular fibrillation model. Methods Ventricular fibrillation untreated for four minutes was induced by dynamic steady state pacing protocol in 40 healthy male pigs, in which local unipolar electrograms were recorded using one 10-electrode catheter that was sutured to the left ventricular epicardium. During CPR, animals were randomized into two groups to receive saline as placebo or esmolol after two standard doses of epinephrine. At post-resuscitation 2-h, six pigs were randomly selected from each group and the second VF induction was performed. Local activation-recovery intervals (ARI) restitutions and the VF inducibility between control group and esmolol group were compared. Western blotting was performed to determine expression of Ca 2+/calmodulin-dependent protein kinase IIδ(CaMKIIδ) and cardiac ryanodine receptor (RyR2) protein, and their phosphorylation status. Results Injection of esmolol combined with epinephrine during CPR significantly decreased recurrent rate of ventricular fibrillation during 2-h post-resuscitation, meanwhile it has no adverse affect on the restore of spontaneous circulation. Esmolol significantly flattened ARI restitution slope, lessened regional difference of ARI restitution, decreased the VF inducibility, and alleviated CaMKIIδ hyper-activation and RyR2 hyper-phosphorylation. Conclusions Esmolol given during CPR has significant effects on modulating electrical restitution property and intracellular calcium handling, which contributes the most important reasons why β 1-blockade significantly reduced the onset and maintenance of VF.