Epinephrine In Cardiac Arrest Research Articles

Hospitalized patients’ attitudes towards participating in a randomized control trial in case of a cardiac arrest

BackgroundNo previous study has evaluated patients attitudes towards inclusion in an ongoing cardiac arrest clinical trial. The aim of this study was to assess patientś willingness and motives to participate in the ongoing randomized controlled drug trial “Vasopressin and Steroids in addition to Adrenaline in cardiac arrest” (VAST-A trial) in case of an in-hospital cardiac arrest (IHCA). ObjectivesHospitalized patients, men ≥ 18 and women ≥ 50 years, were asked for informed consent for inclusion in the VAST-A trial in case of an IHCA, the reason for approving or declining inclusion in the trial and baseline characteristics. MethodsPatients admitted to hospital were asked to give informed consent of inclusion in VAST-A in case of an IHCA during their hospital stay. Patients were also asked why they approved or declined inclusion as well as baseline characteristics questions. Results1,064 patients were asked about willingness to participate in the VAST-A trial, of these 902 (84.8%) patients approved inclusion. A subgroup of 411 patients were, except willingness, also asked about motives to participate or not and basic characteristics. The main reason for approving inclusion was to contribute to research (n = 328, 83.9%). The main reason for declining inclusion was concerns regarding testing the drug treatment (n = 6, 30%). ConclusionAmong hospitalized patients the vast majority gave informed consent to inclusion in an ongoing randomized cardiac arrest drug trial. The main reason for approving inclusion was to contribute to research.

Epinephrine in Cardiac Arrest: Identifying a Potential Limit for Resuscitation.

Epinephrine continues to be a fundamental part of the Advanced Cardiac Life Support algorithm despite a lack of evidence that it improves neurologically intact survival. Our aim was both to identify a potential upper limit of epinephrine use in resuscitations and to demonstrate real-world epinephrine use in different patient subgroups. This was a single-center, retrospective cohort study, conducted between August 1, 2016-July 1, 2021, of patients with medical cardiac arrest who were administered a known number of epinephrine doses. The primary outcome was neurologically intact discharge defined by a modified Rankin scale ≤3, with secondary outcomes of comparing epinephrine doses by age, rhythm, and emergency medical services vs emergency department administration of epinephrine. The study included 1,330 patients, with 184 patients (13.8%) surviving to neurologically intact discharge. The primary outcome of neurologically intact discharge was found in 89 (65.4%) patients in the zero epinephrine dose group, 75 (20.0%) in the 1-3 dose group, 15 (4.3%) in the 4-6 dose group, and one (0.002%) in the ≥7 dose group (P < 0.001). Patients received similar amounts of epinephrine when stratified by age, while patients with shockable rhythms received more epinephrine than patients with non-shockable rhythms. There was a significant decrease in neurologically intact discharge with increasing number of epinephrine doses, and our data suggests that seven or more doses of epinephrine is almost always futile. While further prospective studies are needed, clinicians should consider epinephrine doses when weighing the futility or benefit of continued resuscitation efforts.

Use of adrenaline in cardiac arrest - impact on survival to discharge from the hospital

Introduction and objective: Epinephrine is the most important and primary drug that resuscitation team use to reverse cardiac arrest. The provision of epinephrine is currently suggested by both the American Heart Association and the European Resuscitation Council. It is vital to improving the return of spontaneous circulation (ROSC), however the evidence for the use of adrenaline in resuscitation is inconclusive.&#x0D; Materials and methods: The literature was reviewed in the Pubmed database, in the Via Medica Journals database, and in the guidelines of the Polish Society of Anesthesiology, European Resuscitation Council and the American Heart Association with the use of keywords.&#x0D; State of knowledge: There is a clear evidence of an association between epinephrine and increased return of spontaneous circulation (ROSC). Its action is based on stimulation of alpha- and beta-adrenergic receptors. Epinephrine have a role in resuscitation, during CPR it increases the probability of restoring cardiac activity with pulses, which is intermediate step toward long-term survival. However, there are conflicting results regarding long-term survival and functional recovery, particularly neurological outcome.&#x0D; Conclusions: Research shows that epinephrine administration in patients with cardiac arrest increases the chance of restoring spontaneous circulation and patient survival to hospital admission and discharge. However, there are arguments questioning the validity of using epinephrine in resuscitation. Publications show that the compound contributes to post-resuscitation syndrome, which reduces a patient's chance of long-term survival. There are a number of conflicting studies that vary widely in the results presented. The current evidence is insufficient to either confirm or exclude the efficacy of epinephrine, which is why it is still recommended in the latest resuscitation guidelines by the European Resuscitation Council (ERC 2021) and the American Heart Association (AHA 2020).

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.

Efficacy of combination triple therapy with vasopressin, steroid, and epinephrine in cardiac arrest: a systematic review and meta-analysis of randomized-controlled trials

BackgroundThis study investigated whether combination therapy with vasopressin, steroid, and epinephrine (VSE) improves in-hospital survival and return of spontaneous circulation (ROSC) during and after resuscitation in-hospital cardiac arrest (CA).Materials and methodsVarious databases were explored from inception until October 2021 for relevant published clinical trials and cohort studies.ResultsThree clinical trials were included. Pooled analysis suggested that VSE was significantly associated with increased ROSC in patients with in-hospital CA (IHCA) (odds ratio (OR): 2.281, 95% confidence interval (CI): 1.304–3.989, P value = 0.004). Meta-analysis of two studies (368 patients) demonstrated a significant difference in the reduction of mean arterial pressure (MAP) during and 15–20 min after cardiopulmonary resuscitation (standardized mean difference (SMD): 1.069, 95% CI: 0.851–1.288, P value < 0.001), renal failure free days (SMD = 0.590; 95% CI: 0.312–0.869 days; P value < 0.001), and coagulation failure free days (SMD = 0.403; 95% CI: 0.128–0.679, P value = 0.004). However, no significant difference was observed for survival-to-discharge ratio (OR: 2.082, 95% CI: 0.638–6.796, P value = 0.225) and ventilator free days (SMD = 0.201, 95% CI: − 0.677, 1.079 days; P value = 0.838).ConclusionsVSE combination therapy during and after IHCA may have beneficial effects in terms of the ROSC, renal and circulatory failure free days, and MAP.Prospero registration: CRD42020178297 (05/07/2020).

Time to Give It Arrest? Preclinical Evidence of Epinephrine-associated Worsening of Outcomes in a Novel Mouse Model of Cardiac Arrest

Epinephrine (EPI) use in the resuscitation of cardiac arrest (CA) patients improves short-term recovery of spontaneous circulation (ROSC) with paradoxically equal or worse long-term outcomes. Due to nuanced cofounding variables in the clinical setting (e.g., early spontaneous recovery precluding use of epinephrine) there is critical need for preclinical models to interrogate the impact of epinephrine in CA.

Epinephrine for cardiac arrest: knowns, unknowns and controversies.

The aim of this study was to describe our knowledge about the use of epinephrine in cardiac arrest and discuss the unknowns and current controversies. A recent large, well conducted, double-blind, randomized placebo-controlled trial of over 8000 patients with out-of-hospital cardiac arrest (PARAMEDIC-2) showed that epinephrine increased return of spontaneous circulation and survival to hospital discharge. The trial's secondary outcomes have raised concerns that epinephrine increases the number of brain damaged survivors. Systematic review and meta-analysis suggest that epinephrine has more pronounced effects for nonshockable rhythms, when given early, and probably increases the number of both good and poor survivors. There remains uncertainty about the optimal use of epinephrine in terms of patient groups, rhythms, dose and timing. Epinephrine still has a role in the treatment of cardiac arrest; the best way to use epinephrine remains uncertain.

Adrenaline in cardiac arrest

The use of adrenaline during a cardiac arrest is well-established and supported by international guidelines. However, recent studies1–2 have questioned the appropriateness of adrenaline administration whereas other papers indicate that any benefit from adrenaline maybe time-sensitive.3–4 Two recently published studies have both challenged the use of adrenaline during resuscitation and whilst both papers used different methodologies they demonstrated similar results. The Paramedic 2 study1 was a placebo-based randomised control trial whereas the paper by Loomba et al.,2 used a meta-analysis of 14 peer-reviewed publications recruiting 655,853 patients, 7.4% of whom received adrenaline. Neither study was able to demonstrate any meaningful survival benefit associated with adrenaline administration (Table 1 and 2). However, both studies noted poor neurological outcome in post-cardiac survivors. It is noteworthy that both of these studies used different, but validated,5 neurological scoring systems (either the Modified Rankin Scale or the Cerebral Performance Category).Whilst there is an acceptable correlation between the Modified Rankin Scale or the Cerebral Performance Category (Table 3) there is a degree of variation.5 This variation is partly due to what the two scales accept as being a good neurological outcome as well as an inbuilt degree of subjectiveness of any assessment of neurological status.5 Whilst The Paramedic 2 study1 and Loomba et al.,2 meta-analysis demonstrated no benefit of adrenaline, studies by Goto et al.,3 and Donnino et al., (adults)4 have published contradictory findings. Importantly Donnino et al.,4 reported improved neurological status in non-shockable cardiac arrest when adrenaline was administered.2 However, to date no study has demonstrated a benefit of adrenaline when used to treat shockable cardiac arrest.Interestingly both Goto et al.,3 and Donnino et al.,4 indicated that any benefit from adrenaline administration was time-sensitive. Goto et al.,3 noted that the optimal time for adrenaline administration was < 9 minutes. Whereas, Donnino et al.,4 reported on the impact of increasing time delay to the first dose noting that when adrenaline was administered < 1 minute of confirmation of cardiac arrest, 12% of patients survived, but that this dropped to 9% after the fourth minute and was down to 7% after seven minutes (p < 0.001). The findings of Goto et al.,3 and Donnino et al.,4 represent a clinical challenge. Notably, during the Paramedic 2 study the average time of administration of adrenaline was approaching 20 minutes (6.6 minutes response time and 13.8 minutes) raising the question would the results of Paramedic 2 have been different if adrenaline was administered faster and whether adrenaline should only be administrated in witnessed cardiac arrest?The routine use of adrenaline as the mainstay of resuscitation is being challenged, especially with regards to long-term patient survival and its role in the management of shockable cardiac arrest. However, in specific patients, when given early, adrenaline may still have a role to play in resuscitation. The 2020 International Resuscitation Guidelines are eagerly awaited.

Effects of Endotracheal Administration of Epinephrine in Cardiac Arrest of Adult and Pediatric Swine

BACKGROUND: Few studies have investigated the effects of hypovolemia on area under the curve (AUC) and the return of spontaneous circulation (ROSC) comparing adults and children in cardiac arrest.AIMS: To compare the epinephrine endotracheal (ET) administration relative to AUC, rate, time to, and odds of achieving ROSC between hypovolemic adult and pediatric cardiac arrest models.METHODS: This was an experimental study using male Adult ET and Pediatric ET swine. Pediatric ET pigs (N=7) weighed 20-30 kg representing the average weight for a child between 5 and 6 years of age. Adult ET pigs (N=7) weighed 60 to 80 kg. All were exsanguinated 35% of their blood volume. Swine were put into arrest for 2 minutes. Cardiopulmonary resuscitation (CPR) was initiated for 2 minutes; epinephrine was then administered. Blood samples were collected over 5 minutes. RESULTS: No significant difference occurred in AUC between the groups (p &gt; 0.05). The Pediatric ET group had higher rates of ROSC and a shorter time to ROSC (p &lt; 0.05). Pediatric ET group had a 15 times greater odds of achieving ROSC compared to the Adult ET group. CONCLUSION: Based on the results of this study, we recommend epinephrine administration via ET within the pediatric arrest model, but not for the adult.

What's the Best Dosing Interval for Epinephrine in Cardiac Arrest?

Guidelines advise giving epinephrine every 3 to 5 minutes during cardiac arrest, but there is no evidence to support this dosing frequency. To study

'PARAMEDIC-2: Big study, small result'.

The PARAMEDIC-2 trial demonstrated that the use of adrenaline compared with placebo in out-of-hospital cardiac arrest (OHCA) resulted in a small increase in 30-day survival, but was associated with a higher number of survivors with severe neurological impairment. These findings received a lot of attention, and generated a widespread discussion about the role of adrenaline in cardiac arrest. In this point of view, we aim to place the PARAMEDIC-2 results in the right perspective by comparing the relative effect of adrenaline to other determinants of cerebral blood flow.

Rethinking the role of epinephrine in cardiac arrest: the PARAMEDIC2 trial

Epinephrine (adrenaline) is the most commonly used medication in cardiac arrest, and is the only drug recommended by the American Heart Association (AHA) for all arrests regardless of cardiac rhythm (1). The use of epinephrine in cardiac arrest originated from studies in the 1960’s, when epinephrine was found to improve survival in dog models of asphyxia (2). Physiologically, epinephrine produces some effects that may be helpful and others that may be harmful. It is an agonist at both beta- and alpha-adrenergic receptors. The alpha effects cause peripheral vasoconstriction, which in turn leads to increased blood flow in the central circulation, improving perfusion of the heart and brain. These effects are potentially beneficial, and have been hypothesized to increase the likelihood of return of spontaneous circulation (ROSC) among cardiac arrest patients. The beta-adrenergic effects increase cardiac rate, contractility, and automaticity; these effects are potentially deleterious, leading to arrhythmias and increased myocardial oxygen demand.

Emergency Medicine Myths: Epinephrine in Cardiac Arrest

BackgroundSudden cardiac arrest accounts for approximately 15% of deaths in developed nations, with poor survival rate. The American Heart Association states that epinephrine is reasonable for patients with cardiac arrest, though the literature behind its use is not strong. ObjectiveTo review the evidence behind epinephrine for cardiac arrest. DiscussionSudden cardiac arrest causes over 450,000 deaths annually in the United States. The American Heart Association recommends epinephrine may be reasonable in patients with cardiac arrest, as part of Advanced Cardiac Life Support. This recommendation is partly based on studies conducted on dogs in the 1960s. High-dose epinephrine is harmful and is not recommended. Epinephrine may improve return of spontaneous circulation, but does not improve survival to discharge or neurologic outcome. Literature suggests that three phases of resuscitation are present: electrical, circulatory, and metabolic. Epinephrine may improve outcomes in the circulatory phase prior to 10 min post arrest, though further study is needed. Basic Life Support measures including adequate chest compressions and early defibrillation provide the greatest benefit. ConclusionsEpinephrine may improve return of spontaneous circulation, but it does not improve survival to discharge or neurologic outcome. Timing of epinephrine may affect patient outcome, but Basic Life Support measures are the most important aspect of resuscitation and patient survival.

Epinephrine in cardiac arrest: systematic review and meta-analysis.

abstractObjective:evaluate the effectiveness of epinephrine used during cardiac arrest and its effect on the survival rates and neurological condition. Method:systematic review of scientific literature with meta-analysis, using a random effects model. The following databases were used to research clinical trials and observational studies: Medline, Embase and Cochrane, from 2005 to 2015. Results:when the Return of Spontaneous Circulation (ROSC) with administration of epinephrine was compared with ROSC without administration, increased rates were found with administration (OR 2.02. 95% CI 1.49 to 2.75; I2 = 95%). Meta-analysis showed an increase in survival to discharge or 30 days after administration of epinephrine (OR 1.23; 95% IC 1.05-1.44; I2=83%). Stratification by shockable and non-shockable rhythms showed an increase in survival for non-shockable rhythm (OR 1.52; 95% IC 1.29-1.78; I2=42%). When compared with delayed administration, the administration of epinephrine within 10 minutes showed an increased survival rate (OR 2.03; 95% IC 1.77-2.32; I2=0%). Conclusion:administration of epinephrine appears to increase the rate of ROSC, but when compared with other therapies, no positive effect was found on survival rates of patients with favorable neurological status.

Local anaesthetic systemic toxicity

Access the CPD MCQs for this issue online here ### Key points Well-placed local anaesthetics (LAs) can yield great clinical benefits. But systemic toxicity related to their use can be devastating. The highly publicized case in 2004 of Mayra Cabrera, a theatre nurse who died shortly after delivery of her baby boy when her epidural infusion of bupivacaine was mistakenly connected to her i.v. line, reminds us to be vigilant and to learn from such rare events. While prevention is clearly the most important element in avoiding morbidity and mortality associated with local anaesthetic systemic toxicity (LAST), such cases still occur despite best practice. Knowing how to manage these uncommon events is vital. In this review, we cover LA toxicity, its incidence, clinical features, risk factors, prevention, and management and examine i.v. lipid emulsion (ILE) therapy in more detail. LAST has been recognized for more than a hundred years, but the precise incidence is currently unknown. In 1928, the American Medical Association reported 40 deaths attributable to LAs.1 Cocaine was responsible for half of these deaths, but procaine was also implicated. These findings prompted the search for less toxic agents. Lidocaine, first synthesized in 1944, was the first amide LA to be used clinically. However, in 1979, the potentially fatal toxicity of amide LAs was highlighted by Albright.2 More recently, studies from 1993 …

Adrenaline in cardiac arrest: Prefilled syringes are faster

Standard ampoules and prefilled syringes of adrenaline are widely available in Australasian EDs for use in cardiac arrest. We hypothesise that prefilled syringes can be administered more rapidly and accurately when compared with the two available standard ampoules. This is a triple arm superiority study comparing the time to i.v. administration and accuracy of dosing of three currently available preparations of adrenaline. In their standard packaging, prefilled syringes were on average more than 12 s faster to administer than the 1 mL 1:1000 ampoules and more than 16 s faster than the 10 mL 1:10,000 ampoules (P < 0.01 in both comparisons). With packaging removed, the time to administration was equal for the 1 mL (1:1000) ampoule and the prefilled syringe. Accuracy of dosing was excellent with both the 10 mL (1:10 000) ampoules and prefilled syringes. The 1 mL (1:1000) ampoules delivered a small number of markedly inaccurate doses, but these did not reach statistical significance. The speed of administration of adrenaline utilising a Minijet (CSL Limited, Parkville, Victoria, Australia) is faster than using adrenaline in glass ampoules presented in their plastic packaging. Removing the plastic packaging from the 1 mL (1 mg) ampoule might result in more rapid administration similar to the Minijet. Resuscitation personnel requiring rapid access to adrenaline should consider storing it as either Minijets or ampoules devoid of packaging. These results might be extrapolatable to other clinical scenarios, including pre-hospital and anaesthesia, where other drugs are required for rapid use.

Epinephrine for Cardiac Arrest

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

Is there a role for adrenaline during cardiopulmonary resuscitation?

To critically evaluate the recent data on the influence adrenaline has on outcome from cardiopulmonary resuscitation. Two prospective controlled trials in out-of-hospital cardiac arrest (OHCA) have indicated that adrenaline increases the rate of return of spontaneous circulation (ROSC), but neither was sufficiently powered to determine the long-term outcomes. Several observational studies document higher ROSC rates in patients receiving adrenaline after OHCA, but these also document an association between receiving adrenaline and worse long-term outcomes. Appropriately powered prospective, placebo-controlled trials of adrenaline in cardiac arrest are essential if the role of this drug is to be defined reliably.

Epinephrine for cardiac arrest

Epinephrine is the primary drug administered during cardiopulmonary resuscitation (CPR) to reverse cardiac arrest. Epinephrine increases arterial blood pressure and coronary perfusion during CPR via alpha-1-adrenoceptor agonist effects. However, the dose, timing and indications for epinephrine use are based on limited animal data. Recent studies question whether epinephrine provides any overall benefit for patients. A randomized controlled trial indicates that epinephrine for out-of-hospital cardiac arrest increases return of pulses, but does not significantly alter longer-term survival. Very large, well-controlled, observational studies suggest that, despite increases in return of pulses, epinephrine reduces long-term survival and functional recovery after CPR. Detrimental effects were greatest in patients found in ventricular fibrillation. Laboratory data suggest that harmful epinephrine-induced reductions in microvascular blood flow during and after CPR may offset the beneficial epinephrine-induced increase in arterial blood pressure during CPR. The available clinical data confirm that epinephrine administration during CPR can increase short-term survival (return of pulses), but point towards either no benefit or even harm of this drug for more patient-centred outcomes (long-term survival or functional recovery). Prospective trials are needed to determine the correct dose, timing and patients for epinephrine in cardiac arrest.

Use of Epinephrine for Cardiac Arrest Prior to Hospital Arrival

Use of Epinephrine for Cardiac Arrest Prior to Hospital Arrival