Standard-dose Epinephrine Research Articles

Application of normothermic cardiac arrest algorithms to hypothermic cardiac arrest in a canine model

International guidelines (2000) do not recommend vasopressor and antiarrhythmic medications during ventricular fibrillation (VF) with a core temperature below 30 degrees C. The efficacy of normothermic AHA algorithms using standard doses of epinephrine (EPI) (adrenaline) followed by amiodarone (AMIO) in hypothermic VF is uncertain. To determine the effects of EPI followed by the combination of EPI/AMIO in the treatment of VF in a canine model of severe hypothermia. An un-blinded, placebo controlled experiment using 21 mechanically ventilated dogs. Coronary perfusion pressure (CPP), temperature, and electrocardiogram (ECG) were monitored. Animals were cooled to 22 degrees C or the onset of spontaneous VF. VF was induced if necessary. Animals in the treatment group received EPI (0.01 mg/kg IV) and defibrillation. This was followed by EPI (0.01 mg/kg IV), AMIO (10 mg/kg IV) and defibrillation if there was no sustained return of spontaneous circulation (ROSC) for 15 min. Mean CPP in the treatment group increased after the administration of EPI/AMIO (24.7+/-13.3 mmHg to 46.6+/-7.7 mmHg, p<0.004). Cumulatively, the administration of EPI followed by EPI/AMIO achieved ROSC after defibrillation in 10 of 11 animals compared to 3 of 10 in the control group (91% versus 30%, n=21, p=0.0075). In this model of severe hypothermia, the use of standard 2000 protocols for VF resulted in a significant increase of CPP, and, a higher ROSC rate compared to placebo controls. This study suggests that AHA normothermic algorithms may be beneficial in severe hypothermia.

Out-of-Hospital Pediatric Cardiac Arrest: Where Are We Now and Where Do We Need to Go?

Out-of-hospital pediatric cardiac arrest is difficult to study, and I congratulate the authors in this month’s Annals of Emergency Medicine for their thorough systematic review of the current state of knowledge. With due respect to the investigators who contributed to this knowledge base and to the authors of this report, I suspect that many Annals readers may feel uncertain about what we really know about out-of-hospital pediatric cardiac arrest and, more importantly, how that knowledge can be used to improve outcome. Other than knowing that outcome after out-of-hospital pediatric cardiac arrest is poor, this systematic review illustrates important limitations of this type of review because of the limitations of the studies on which it is based. The author’s initial goals of clearly identifying gaps in our knowledge and determining the effects of commonly used interventions on outcome are difficult to deduce from the available data. Although 41 studies and more than 5,300 children are included in the identified studies, a minority of these studies could be evaluated when looking at the association of specific interventions on outcome, such as bystander cardiopulmonary resuscitation or the association of the initial rhythm with outcome in various patient causal categories. As the authors discuss under study limitations, observational studies often use inconsistent study designs. This inconsistency is clearly true for cardiac arrest studies and is illustrated by the more than 7-fold variation in the reported incidence of cardiac arrest (2.6 to 19.7 cases per 100,000 pediatric population) and the surprising results about outcome after traumatic-induced arrest. As the authors correctly note, however, the method of patient inclusion into the National Pediatric Trauma Registry database likely included children who were not in cardiac arrest. Once children in these National Pediatric Trauma Registry reports were excluded, traumatic cardiac arrest resulted in poor outcome, as expected. Throughout the more than 20 years of reports included in this review, imprecise inclusion and exclusion criteria were used. The pediatric Utstein guidelines for reporting data were not published until 1995 and were incorporated to various degrees in subsequent reports. In addition to variable inclusion criteria, different outcome definitions were used. Furthermore, the most commonly used functional outcome used was designed

What is the right dose of epinephrine?

To review the findings and discuss implications of studies on high-dose epinephrine (0.1 mg/kg) during cardiopulmonary resuscitation in children. A critical appraisal of "A Comparison of High-Dose and Standard-Dose Epinephrine in Children with Cardiac Arrest" by Perondi et al. (N Engl J Med 2004; 350:1722-1730), with literature review. Retrospective studies investigating the use of high-dose epinephrine during pediatric cardiopulmonary resuscitation demonstrate conflicting results with respect to return of spontaneous circulation and survival. The randomized controlled trial by Perondi et al. demonstrates decreased survival with the use of high-dose epinephrine and no difference in return of spontaneous circulation when compared with the standard dose. There is no benefit from the use of high-dose epinephrine in pediatric cardiopulmonary resuscitation. There is potential harm from such dosing. The cumulative evidence against the use of high-dose epinephrine during pediatric cardiopulmonary resuscitation is strong.

The Use of High-Dose Epinephrine for Patients With Out-of-Hospital Cardiopulmonary Arrest Refractory to Prehospital Interventions

To determine if high-dose epinephrine (HDE) used during out-of-hospital cardiopulmonary arrest refractory to prehospital interventions improves return of spontaneous circulation, 24-hour survival, discharge survival, and neurological outcomes. A multicenter randomized controlled trial was conducted between May 1991 and October 1996 to compare the effectiveness of HDE versus standard-dose epinephrine (SDE) in patients having out-of-hospital cardiopulmonary arrest refractory to prehospital resuscitation efforts. Cardiopulmonary arrest was classified as "medical" or "traumatic." Two hundred thirty patients were enrolled in 7 pediatric emergency departments. Ages ranged from newborn to 22 years. Seventeen patients met exclusion criteria. Patients were assigned to receive HDE (0.1 mg/kg for the initial dose and 0.2 mg/kg for subsequent doses) or SDE (0.01 mg/kg). The main end points evaluated were return of spontaneous circulation, 24-hour survival, discharge survival, and neurological outcome. One hundred twenty-seven patients received HDE (32 trauma patients), and 86 patients received SDE (27 trauma patients). Among medical patients, 24 (25%) of 95 experienced return of spontaneous circulation in the HDE group as compared with 9 (15%) of 59 in the SDE group (P = 0.14, chi2 = 2.17, relative risk = 1.66 [0.83-3.31]). Sixteen (17%) of 95 HDE patients and 5 (8%) of 59 SDE patients survived at least 24 hours (P = 0.14, chi2 = 2.16, relative risk = 1.99 [0.77-5.14]). Nine survivors to discharge received HDE, and 2 received SDE (P = 0.21, Fisher exact test, relative risk = 2.75 [0.61-12.28]). There were no long-term survivors among the trauma patients. Eight of 11 long-term survivors had severe neurological outcomes defined by the Glasgow Outcome Scale (2/2 SDE, 6/9 HDE; P = 0.51, Fisher exact test). HDE does not improve or diminish return of spontaneous circulation, 24-hour survival, long-term survival, or neurological outcome compared with SDE in out-of-hospital cardiopulmonary arrest.

Update on pediatric resuscitation drugs: high dose, low dose, or no dose at all

Pediatric resuscitation has been a topic of discussion for years. It is difficult to keep abreast of changing recommendations, especially for busy pediatricians who do not regularly use these skills. This review will focus on the most recent guidelines for resuscitation drugs. Three specific questions will be discussed: standard dose versus high-dose epinephrine, amiodarone use, and the future of vasopressin in pediatric resuscitation. The issue of using high-dose epinephrine for cardiopulmonary resuscitation refractory to standard dose epinephrine has been a topic of debate for many years. Recently, a prospective, double-blinded study was performed to help settle the debate. These results will be reviewed and compared with previous studies. Amiodarone is a medication that was added to the pediatric resuscitation algorithms with the most recent recommendations from the American Heart Association in 2000. Its use and safety will also be discussed. Another topic that is resurfacing in resuscitation is the use of vasopressin. Its mechanism and comparisons to other agents will be highlighted, although its use in the pediatric patient has not been thoroughly studied. Pediatric resuscitation is a constantly evolving subject that is on the mind of anyone taking care of sick children. Clinicians are continually searching for the most effective methods to resuscitate children in terms of short- and long-term outcomes. It is important to be familiar with not only the agents being used but also the optimal way to use them.

Improved resuscitation outcome in emergency medical systems with increased usage of sodium bicarbonate during cardiopulmonary resuscitation

The use of sodium bicarbonate (SB) in cardiopulmonary resuscitation (CPR) is controversial. This study analyzes the effects of SB use on CPR outcome in the Brain Resuscitation Clinical Trial III (BRCT III), which was a multicenter randomized trial comparing high-dose to standard-dose epinephrine during CPR. Sodium bicarbonate use in BRCT III was optional. The entire BRCT III database was reviewed. Analysis included only patients who arrested out of the hospital and whose time from collapse to initiation of ACLS was no longer than 30 min (total n = 2122 patients). Sodium bicarbonate use by the 16 participating study sites was analyzed. The study sites were divided according to their SB usage profile: 'low SB user' sites administered SB in less than 50% of CPRs and their first epinephrine to SB time exceeded 10 min; and 'high SB user' sites used SB in over 50% of CPRs and their first epinephrine to SB time was <10 min. Sites' SB usage rates ranged between 3.1% and 98.2% of CPRs. Sodium bicarbonate usage rates correlated inversely with the sites' intervals from collapse (r = - 0.579 P = 0.018) from initiation of ACLS (r = - 0.685 P = 0.003) and from first epinephrine (r = - 0.611 P = 0.012) to SB administration. Mean ROSC rate in the 'high SB user' sites was 33.5% (CI = 30.0-37.0) compared to 25.7% (CI = 23.1-28.4) in the 'low SB user' sites. In the 'high SB user' sites, hospital discharge rate was 5.3% (CI = 3.6-7.0) compared to 3% (CI = 2.0-4.0) in the 'low SB user' sites, and 5.3% (CI = 3.6-7.0) had a favorable neurological outcome compared to 2.1% (CI = 1.2-3.0) in the 'low SB user' sites. Collapse to ACLS interval was 8.5 min (CI = 8.1-9.0) in the 'high SB user' sites compared to 10.2 min (CI = 9.8-10.6) in the 'low SB user' sites, and their ACLS to first epinephrine interval was 7.0 min (CI = 6.5-7.5) compared to 9.7 min (CI = 9.3-10.2). Multivariate regression analysis found that belonging to 'high SB user' sites independently increased the chances for ROSC (OR 1.36, CI 1.08-1.7) and for achieving a good neurological outcome (OR 2.18, CI 1.23-3.86). Earlier and more frequent use of SB was associated with higher early resuscitability rates and with better long-term outcome. Sodium bicarbonate may be beneficial during CPR, and it should be subjected to a randomized clinical trial.

A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest

A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest

A Comparison of High-Dose and Standard-Dose Epinephrine in Children With Cardiac Arrest

A Comparison of High-Dose and Standard-Dose Epinephrine in Children With Cardiac Arrest

A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest

A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest

Clinical use of sodium bicarbonate during cardiopulmonary resuscitation—is it used sensibly?

This study retrospectively analyzed the pattern of sodium bicarbonate (SB) use during cardiopulmonary resuscitation (CPR) in the Brain Resuscitation Clinical Trial III (BRCT III). BRCT III was a prospective clinical trial, which compared high-dose to standard-dose epinephrine during CPR. SB use was left optional in the study protocol. Records of 2915 patients were reviewed. Percentage, timing and dosage of SB administration were correlated with demographic and cardiac arrest variables and with times from collapse to Basic Life Support, to Advanced Cardiac Life Support (ACLS) and to the major interventions performed during CPR. SB was administered in 54.5% of the resuscitations. The rate of SB use decreased with increasing patient age—primarily reflecting shorter CPR attempts. Mean time intervals from arrest, from start of ACLS and from first epinephrine to administration of the first SB were 29±16, 19±13, and 10.8±11.1 min, respectively. No correlation was found between the rate of SB use and the pre-ACLS hypoxia times. On the other hand, a direct linear correlation was found between the rate of SB use and the duration of ACLS. We conclude that when SB was used, the time from initiation of ACLS to administration of its first dose was long and severe metabolic acidosis probably already existed at this point. Therefore, if SB is used, earlier administration may be considered. Contrary to physiological rationale, clinical decisions regarding SB use did not seem to take into consideration the duration of pre-ACLS hypoxia times. We suggest that guidelines for SB use during CPR should emphasize the importance of pre-ACLS hypoxia time in contributing to metabolic acidosis and should be more specific in defining the duration of ‘protracted CPR or long resuscitative efforts’, the most frequent indication for SB administration.

The use of arginine vasopressin during cardiopulmonary resuscitation. An analysis of experimental and clinical experience and a view of the future

The risks and benefits of epinephrine given during cardiopulmonary resuscitation (CPR) are controversially discussed. Animal experiments revealed beta-receptor-mediated adverse effects of epinephrine such as increased myocardial oxygen consumption, ventricular arrhythmia, ventilation-perfusion defects, and cardiac failure in the postresuscitation phase. In clinical studies, high-dose vs. standard-dose epinephrine was unable to improve resuscitation success. During CPR in patients, endogenous arginine vasopressin (AVP) levels were increased and surviving vs. non-surviving patients had significantly higher AVP levels. This may indicate that the human body discharges AVP during life-threatening situations as an additional vasopressor to catecholamines in order to maintain cardiocirculatory homeostasis. In different experimental CPR models, AVP compared with epinephrine given during CPR significantly improved vital organ blood flow, coronary perfusion pressure, resuscitability, and long-term survival. During prolonged CPR with repeated drug administration, AVP but not epinephrine maintained coronary perfusion pressure on a level that ensured return of spontaneous circulation. Also, AVP can be administered successfully in the intravenous dose into the endobronchial tree, and also intraosseously. When given during CPR, AVP induces a transient splanchnic hypoperfusion, and an increase in systemic vascular resistance, both of which normalized spontaneously; furthermore, an oligo-anuric state was not observed. In two clinical studies, AVP vs. epinephrine improved 24-h survival during out-of-hospital CPR, and comparable CPR outcome during in-hospital CPR. The new CPR guidelines of both the American Heart Association and the European Resuscitation Council assign a given CPR intervention into classes of recommendation [class 1 (definitely recommended), class 2 A (intervention of choice), class 2B (alternative intervention), class X (neutral), or class 3 (not recommended)]. For CPR of adults with shock-refractory ventricular fibrillation, 40 units AVP or 1 mg epinephrine is recommended (class 2B); patients with asystole or pulseless electrical activity should be resuscitated with epinephrine. AVP is not recommended for adult cardiac arrest patients with asystole or pulseless electrical activity; or pediatric cardiac arrest patients due to a lack of clinical data. Until definitive data about AVP vs. epinephrine effects during CPR are available, the present state of knowledge should be interpreted that two vasopressors are available for use instead of one.

P REHOSPITAL C ARE AND O UTCOME OF P EDIATRIC O UT - OF - HOSPITAL C ARDIAC A RREST

Cardiac arrest in children outside the hospital is associated with high mortality rates. Recent investigations have suggested that the use of advanced life support (ALS) measures by emergency medical services (EMS) personnel may decrease survival. These studies have used the pediatric Utstein style of defining ALS and basic life support (BLS) measures. The pediatric Utstein style defines BLS as “an attempt to restore effective ventilation and circulation” using noninvasive means to open the airway but specifically excludes the use of bag-valve-mask devices. Advanced life support is defined as the “addition of invasive maneuvers to restore effective ventilation and circulation.” The authors of the study described below believe that using this definition would categorize some patients into an ALS group who would otherwise be categorized as having received BLS (i.E., “bag-valve-mask only”). Objective: To compare survival rates among children receiving BLS or ALS following out-of-hospital cardiac arrest using amended definitions of prehospital life support measures. Specifically, the definition of BLS was expanded to include the use of bag-valve-mask devices only. Methods: This was a retrospective chart review in an urban, pediatric emergency department. Patients included all children presenting to the emergency department between January 1, 1986, and December 31, 1999, following out-of-hospital cardiac arrest. The main outcome measure was survival to hospital discharge. Results: Two hundred ten children were identified. Twenty-one patients were excluded from further analysis because of absent or incomplete medical records. One hundred eighty-nine patients were studied. Five children (2.6%) survived to discharge from the hospital. Of 189 children, 39 (20.6%) were provided BLS measures by prehospital personnel; 150 (79.4%) received ALS. There was no significant difference between groups in survival to hospital discharge. Patients who survived to hospital discharge were more likely to be in sinus rhythm upon arrival in the emergency department (p < 0.001) and to have received fewer doses of standard-dose epinephrine in the emergency department (p < 0.001). Conclusion: The use of ALS by prehospital personnel for children with out-of-hospital cardiac arrest did not improve survival to discharge from the hospital when compared with the use of BLS.

Cerebral ischaemia in experimental cardiopulmonary resuscitation — comparison of epinephrine and aortic occlusion

The apparent inability of epinephrine to improve outcome after cardiopulmonary resuscitation (CPR) could be caused by direct negative effects on the cerebral circulation. Constant aortic occlusion with a balloon catheter could be an alternative way to improve coronary and cerebral perfusion during CPR. The objective of the present study was to compare the effects of standard-dose epinephrine with balloon occlusion of the descending aorta on cortical cerebral blood flow augmentation during CPR. Ventricular fibrillation was induced in 24 anaesthetised piglets. A non-intervention interval of 9 min was followed by open-chest CPR. The animals were randomised to receive repeated intravenous bolus doses of epinephrine 20 μg/kg or balloon occlusion of the descending aorta. Focal cortical cerebral blood flow was measured continuously using laser-Doppler flowmetry. Balloon occlusion of the aorta resulted in a significantly higher mean cortical cerebral blood flow and a lower cerebral oxygen extraction ratio than epinephrine during CPR. After restoration of spontaneous circulation the cerebral perfusion appeared compromised to the same extent in both groups, with lower blood flow compared to baseline, high cerebral oxygen extraction and cerebral tissue acidosis. No difference in cerebral cortical vascular resistance between the two groups could be detected. It is concluded that aortic balloon occlusion was superior to epinephrine in cerebral blood flow augmentation during resuscitation and did not generate adverse effects on cerebral blood flow, oxygenation or tissue pH after restoration of spontaneous circulation. No evidence of cerebral vasoconstriction induced by standard-dose epinephrine was found.

What Is on the Horizon for Neonatal Resuscitation?

After completing this article, readers should be able to: 1. Define the indeterminate class of recommendations for neonatal resuscitation. 2. Describe the two areas of current investigation within the indeterminate class recommendations. 3. Describe the application of two techniques from other settings within the indeterminate class recommendations. 4. Describe the indeterminate class recommendation for which conflicting evidence is emerging. With the shift to evidence-based guidelines, the process of revising the scientific framework for neonatal resuscitation and the derivative educational efforts will become more predictable and accessible. Beginning with the International Guidelines 2000, an Indeterminate Class of recommendations appeared. These focused on areas of intense scientific research that may lead to clinically important therapies; technological developments widely adopted for use in other age groups that may find a role in neonatal resuscitation; or emerging evidence that conflicts substantially with previous data, resulting in a revision of recommendations to withdraw support of a particular therapeutic approach. The advent of changes in evidence-based guidelines carries the obligation to monitor the impact of such changes. Finally, entirely new questions and proposed guideline recommendations will be submitted to evidence evaluation in the future. Five Indeterminate Class recommendations appeared in the neonatal resuscitation portion of the International Guidelines 2000 (Table⇓ ). Cerebral hypothermia following hypoxic-ischemic insult and positive-pressure ventilation with room air represent proposals in the translational research phase, moving from animal and molecular models into clinical trials. The recommendations relating to adjunctive airway techniques, laryngeal mask airway and exhaled carbon dioxide detection, recognize the importance of these techniques in the older pediatric and adult populations, but acknowledge the significant limitations in their application to neonates. The statement regarding high-dose epinephrine reinforces the conflicting nature of evidence relating to this therapy, yet it acknowledges that available evidence is extrapolated largely from older age groups and falls short of supporting …

Rational use of vasoactive drugs after cardiac resuscitation: focus on inotropic agents

Several large-scale multicenter prospective controlled studies have now been performed to investigate the use of different doses of adrenaline during cardiopulmonary resuscitation (CPR) [1– 5]. The execution of these studies demands great organisational skills and discipline, since studies in the acute situation are difficult to perform. Attention that has been drawn to these aspects is justified because, whereas the first hour after major trauma is called the golden hour, the minutes after cardiac arrest may be called the platinum minutes. However, in all of these studies little attention is given to the treatment after the platinum minutes. The importance of the post resuscitation phase is nonetheless significant. In approximately 30% of all successfully resuscitated patients, treated with either high or standard dose adrenaline, cardiac arrest recurred and 43% died within the initial 72 h after resuscitation [3,4]. In another resuscitation trial, examining the effects of a calcium antagonist on cerebral protection, approximately 50% of the successfully resuscitated patients died during the initial 7 day of follow-up, mainly due to cardiac causes [5]. The secondary stage after the initial treatment is therefore also of importance. In this review, the major vasoactive — mainly inotropic — drugs as used in the ICU will be discussed after a brief discussion of the available literature on the cardiovascular and general changes after successful resuscitation.

Effects of endothelin-1 on resuscitation rate during cardiac arrest

Objectives: Endothelin-1 (ET-1) is a potent peripheral and coronary artery vasoconstrictor and has been shown to improve coronary perfusion pressure (CPP) during cardiac arrest. The effect of ET-1 on return of spontaneous circulation (ROSC) following cardiac arrest has not been studied. Our hypothesis was that ET-1 does not improve ROSC from cardiac arrest when compared to placebo. Methods: A total of 11 immature swine were used in this laboratory study. Animals were randomized to receive 300 μg ET-1 and standard dose epinephrine (SDE) or placebo and SDE during arrest. After a 10-min period of no-flow ventricular fibrillation (VF), CPR was performed for 3 min followed by ET-1/SDE or placebo/SDE administration. Following drug administration, standard ACLS was followed with SDE given every 3 min. Aortic pressure was monitored during resuscitation. ROSC was defined as any perfusing rhythm with a systolic pressure greater than 60 mmHg for 60 s. Animals received post-ROSC care as needed for 2 h post-ROSC. CPP and ROSC were analyzed using repeated measures ANOVA and Fischer's exact test respectively. P<0.05 was considered significant. Results: Pre-arrest variables and CPP prior to ET-1 administration were not different between groups. Following ET-1 administration, CPP was significantly increased at all time points in ET-1/SDE versus placebo/SDE animals. ROSC was achieved in 1/5 (20%) ET-1/SDE versus 1/6 (16.7%) placebo/SDE animals ( P>0.05). The resuscitated ET-1/SDE animal survived 6.5 min compared to 120 min for the resuscitated placebo/SDE animal. Conclusions: In our study, ET-1 administration during cardiac arrest increases CPP but does not improve ROSC.

Part 6: Advanced Cardiovascular Life Support

Part 6: Advanced Cardiovascular Life Support

High dose versus standard dose epinephrine in cardiac arrest — a meta-analysis

In the management of cardiac arrest there is ongoing controversy concerning the optimal dose of epinephrine. To obtain the best available evidence regarding the current optimal dose, we performed a meta-analysis. We searched the Medline database online and reviewed citations in relevant articles to identify studies that met preset inclusion criteria (prospective, randomized, double-blind). Five trials were identified. The pooled odds ratio for return of spontaneous circulation favours the experimental dose. The pooled odds ratio for hospital discharge failed to demonstrate a statistically significant beneficial effect of high and/or escalating doses of epinephrine in comparison with standard dose of epinephrine. The possibility that patients who have already sustained irreversible neurologic injury will be resuscitated carries potential adverse social and economic implications.

The effects of graded doses of endothelin-1 on coronary perfusion pressure and vital organ blood flow during cardiac arrest.

Endothelin-1 (ET-1) is a potent vasoconstrictor and has been shown to improve coronary perfusion pressure (CPP) during arrest. The effects of ET-1 on organ blood flow during arrest have not been extensively studied. To investigate the effects of ET-1 on myocardial and cerebral blood flow during cardiac arrest. Sixty immature swine were anesthetized and instrumented. The animals were randomized to receive one of three doses of ET-1 (50, 150, or 300 microg) or placebo with/without standard-dose epinephrine (SDE) during cardiac arrest. After a 10-minute period of no-flow ventricular fibrillation (VF), cardiopulmonary resuscitation (CPR) was performed for 3 minutes, followed by drug administration. Placebo or SDE was given every 3 minutes. Myocardial and cerebral blood flow was measured using a fluorescent microsphere technique. Prearrest and CPR variables were not different between groups. Beginning 4 minutes after giving 300 microg ET-1 with or without SDE, CPP was significantly increased compared with SDE alone. Total myocardial blood flow following ET-1 administration was no different than myocardial blood flow following SDE alone. Cerebral blood flow increased 3.5 minutes after administration of 300 microg ET-1 with SDE and reached significance 9.5 minutes after drug administration when compared with SDE alone [92.5 (48.8-117.9) vs 15.6 (7.7-23) mL/min/100 g]. Three hundred microg ET-1 with SDE increases CPP and improves cerebral blood flow but does not improve myocardial blood flow during cardiac arrest. The peripheral effects of ET-1 significantly improve CPP and cerebral blood flow, but myocardial blood flow is not increased due to coronary vasoconstriction.

High Dose Epinephrine (HDE) in Pediatric Cardiopulmonary Arrest (CPA) • 387

Purpose: To determine if HDE used during pediatric out-of-hospital CPA improves survival and neurologic outcomes. Methods: Seven pediatric emergency departments randomly assigned children in CPA to receive HDE (0.1 mg/kg for the initial dose and 0.2 mg/kg for subsequent doses) or standard dose epinephrine (SDE; 0.01 mg/kg). Resuscitations were conducted following ACLS guidelines. CPA was classified as “medical” or “traumatic”. Videotapes of the resuscitations were used to validate the accuracy of the written record in some centers. Primary outcome measures were return of spontaneous circulation(ROSC), long term survival, and neurologic outcome. Results: 213 patients were enrolled from May 1991 through October 1996. Ages ranged from 3 days to 22 years. 127 patients received HDE (32 trauma patients) and 86 patients received SDE (27 trauma patients). There was no significant difference in age, gender, prehospital intubation rate and prehospital epinephrine use between the HDE and SDE groups. Survivors to discharge included 11/154 medical and 0/59 trauma patients. 33/154 (21%) of medical patients experienced ROSC. ROSC occurred more frequently in the HDE group, 24/95 (25%), than in the SDE group, 9/59 (15%); this trend was not significant(p> 0.10, χ2=2.16). Mean number of doses to achieve ROSC was 3.33 in the HDE group and 3.00 in the SDE group. In the medical group, 9/95(9.5%) HDE patients and 2/59 (3.4%) SDE patients survived to discharge(p=0.134, Fisher's exact test). 8/11 long term survivors were vegetative or suffered severe neurologic outcome as defined by the Glasgow Outcome Scale(2/2 in the SDE group and 6/9 in the HDE group.) The difference in neurologically intact survivors was not significant between the two groups(p=0.24, Fisher's exact test). There was no significant difference in ROSC in the HDE versus SDE trauma patients. Conclusion: Long term survival and neurologic outcome are poor in CPA. The use of HDE does not significantly improve the outcome when compared to SDE.