why is a pediatric dose of epinephrine more

The patients were critically ill children in whom aggressive critical care management was failing, and their cardiac arrests were promptly diagnosed and treated.

A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital.

From the Department of Pediatrics, Children's Institute (M.B.M.P., A.G.R.

However, the author group is responsible for the conception of the project, all data analyses, and manuscript writing. A total of 1558 patients (median age, 9 months [interquartile range [IQR], 13 days5 years]) were included in the final cohort.

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Our findings do suggest, however, that there is room for improvement, with 15% of pediatric patients getting their first epinephrine dose more than 5 minutes after loss of pulse. As such, a time to epinephrine of 0 minutes represents that epinephrine was given within the same whole minute that the patient lost their pulse, a time of 1 minute represents that epinephrine was given within the next whole minute, etc. RA. et al.

Chan

10. Suominen P, Olkkola KT, Voipio V, Korpela R, Palo R, Rasanen J. Utstein style reporting of in-hospital paediatric cardiopulmonary resuscitation.

Comparative effect of graded doses of epinephrine on regional brain blood flow during CPR in a swine model.

Children who have more prolonged, untreated cardiac arrests, those who have undergone cardiac surgery, and those in ventricular fibrillation were underrepresented. Current guidelines recommend giving epinephrine at 0.01 mg/kg (maximum, 1 mg) as soon as vascular or intraosseous access is obtained and subsequently every 3 to 5 minutes for patients with a nonshockable rhythm.6,8 Epinephrines beneficial effects are thought to be mediated predominantly through -adrenergic increase in aortic diastolic pressure and increased coronary perfusion pressurean important determinant of return of spontaneous circulation (ROSC).9-11 Despite this, to our knowledge, no randomized trial comparing epinephrine with placebo has been conducted in this population,7 and the ethics of such a trial may currently be questionable.

Assessing the outcome of pediatric intensive care. Longer time to epinephrine administration was also associated with decreased risk of ROSC (multivariable-adjusted RR per minute delay, 0.97 [95% CI, 0.96-0.99]), decreased risk of survival at 24 hours (multivariable-adjusted RR per minute delay, 0.97 [95% CI, 0.95-0.99]), and decreased risk of survival with favorable neurological outcome (multivariable-adjusted RR per minute delay, 0.95 [95% CI, 0.91-0.99]).

In this multicenter cohort study of in-hospital pediatric cardiac arrest, delay in administration of epinephrine was associated with a decreased chance of ROSC, 24-hour survival, survival to hospital discharge, and survival to hospital discharge with a favorable neurological outcome among patients with an initial nonshockable rhythm.

and Participants Time to Epinephrine and Survival After Pediatric In-Hospital Cardiac Arrest. et al.

Carpenter TC, Stenmark KR.

Michael JR, Guerci AD, Koehler RC, et al.

In the instructor group, a significantly larger dose was being taught "informally" than "formally" (P < 0.001).

Furthermore, attainment of an adequate sample size for assessment of that outcome would require a prolonged study period, thereby complicating the study with potentially different resuscitation strategies and protocols over time. CPR denotes cardiopulmonary resuscitation, and ROSC return of spontaneous circulation. LW, Saindon We found that a delay in epinephrine administration was associated with a significantly decreased chance of good outcomes. Goetting MG, Paradis NA.

Effects of graded doses of epinephrine on both noninvasive and invasive measures of myocardial perfusion and blood flow during cardiopulmonary resuscitation.

JAMA 1992;268:2667-2672, 17. RA. However, the AHA provides standardized reporting guidelines and training of all entry personnel to ensure accuracy of entered data. Get With the GuidelinesResuscitation Investigators: In addition to the authors Tia T. Raymond, MD, and Vinay M. Nadkarni, MD, members of the Get With the GuidelinesResuscitation Pediatric Task Force include Alexis A. Topjian, MD, MSCE, Elizabeth Foglia, MD, MA, and Robert Sutton, MD, The Childrens Hospital of Philadelphia; Emilie Allen, MSN, RN, CCRN, Parkland Health and Hospital System; Melania Bembea, MD, MPH, Johns Hopkins University School of Medicine; Ericka Fink, MD, University of Pittsburgh School of Medicine; Michael G. Gaies, MD, MPH, University of Michigan; Anne-Marie Guerguerian, MD, PhD, and Chris Parshuram, MB ChB, DPhil, The Hospital for Sick Children; Monica Kleinman, MD, Boston Childrens Hospital; Lynda J. Knight, RN, CCRN, CPN, Stanford Childrens Health Hospital; Peter C. Laussen, MB BS, University of Toronto; Taylor Sawyer, DO, MEd, Seattle Childrens Hospital; and Stephen M. Schexnayder, MD, Arkansas Childrens Hospital.

High-dose versus standard-dose epinephrine treatment of cardiac arrest after failure of standard therapy.

Potential risks of high-dose epinephrine for resuscitation from ventricular fibrillation in a porcine model.

In-hospital cardiac arrest patients with prior do-not-resuscitate orders or cardiopulmonary resuscitation (CPR) events that began outside the hospital are excluded.

Epinephrine is currently recommended in pediatric cardiac arrests as the first-line pharmacological intervention despite no randomized placebo-controlled trials in this patient population.6,8 One randomized placebo-controlled study in the adult out-of-hospital cardiac arrest population found improved ROSC and short-term survival with administration of epinephrine.31 However, the study was underpowered to detect any difference in long-term outcome because of unanticipated lack of enrollment.36 Similar results were reported in a study comparing intravenous drug administration (with 79% receiving epinephrine) vs no intravenous drug administration in out-of-hospital cardiac arrest.37 In addition to these randomized studies, a number of large observational studies have been published about the adult out-of-hospital cardiac arrest population with conflicting results, even within the same data set, because of different statistical approaches.32-34 These conflicting studies have added to the complexity of clinical decision making.36,38.

L. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. We included all patients younger than 18 years who received chest compressions while pulseless with a documented nonshockable initial rhythm and who received at least 1 epinephrine bolus during resuscitation.

Instructors were more likely to use larger doses than were noninstructors (83% compared with 38%; P < 0.001).

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In contrast, 7 of the 18 patients who were assigned to the standard dose after asphyxia-precipitated arrest survived at 24 hours (P=0.02) (Table 4). Results Y, Maeda Both investigations were in-hospital studies, and the cardiac arrests were typically precipitated by asphyxia.

VM, Berg

J, Steen Pediatrics 2002;109:200-209, 25.

Delay in administration of the first epinephrine dose is associated with decreased survival among adults after in-hospital, nonshockable cardiac arrest.

In contrast, none of 20 historical controls who had been given standard-dose epinephrine as rescue therapy had even a transient return of spontaneous circulation.

GY, Donner

Crit Care Med 1993;21:678-686, 12.

D, Hazinski Crit Care Med 1996;24:1695-1700. The effect of standard- and high-dose epinephrine on coronary perfusion pressure during prolonged cardiopulmonary resuscitation.

Survival to discharge was 31.3% (487/1558).

Subsequent doses were high because the epinephrine routinely stocked at our hospital is the 1:1000 solution.

Furthermore, time variables may have been classified incorrectly on the code sheets from which data were abstracted.

GL,

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

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Most of these studies have focused on the treatment of ventricular fibrillation.1,6,14-22 Although the outcomes in the two groups did not differ in any single investigation, a meta-analysis of five studies involving a total of 3199 patients suggested that survival to hospital discharge is worse with high-dose epinephrine than with standard-dose epinephrine.29 In addition, a retrospective investigation in adults indicated that neurologic outcomes are worse among those who receive a higher cumulative dose of this drug.30.

Myocardial dysfunction after resuscitation from cardiac arrest: an example of global myocardial stunning.

Additional Contributions: We thank Francesca Montillo, MM, Emergency Department, Beth Israel Deaconess Medical Center, Boston, for editorial assistance and Valerie Teal, MS, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, for assisting with data acquisition. In another retrospective study of in-hospital cardiac arrest in children, nearly half of 51 patients were treated with high-dose epinephrine at some point during resuscitative efforts.27 Although this group and a group given standard-dose epinephrine did not differ with respect to the rates of return of spontaneous circulation, 24-hour survival, or survival to hospital discharge, the 24-hour survival rate tended to be worse in the group given high-dose epinephrine: 7 of 24 patients in that group survived, as compared with 17 of 34 patients in the group given only the standard dose (P=0.12). Vandycke C, Martens P. High dose versus standard dose epinephrine in cardiac arrest -- a meta-analysis.

Main Outcomes and Measures European Resuscitation Council Guidelines for Resuscitation 2010 section 6: paediatric life support. D; American Heart Association National Registry of Cardiopulmonary Resuscitation Investigators. Twenty-one percent use SDE less than half of the time, and 16% use a dose 10 to 20 times larger at least half of the time. As such, we consider it unlikely that this limitation would bias our results.

Prior studies have addressed the dosage of epinephrine (standard vs high dose) in pediatric cardiac arrest.12-14 We have not identified any studies examining the association between delay in epinephrine dose and outcomes in pediatric cardiac arrest.

I, Nadkarni

Whether this association is true in the pediatric in-hospital cardiac arrest population remains unknown. Sherman BW, Munger MA, Foulke GE, Rutherford WF, Panacek EA.

Data from all the enrolled patients were analyzed on an intention-to-treat basis.

J Cardiothorac Vasc Anesth 1993;7:184-187, 36.

Time to epinephrine and survival to hospital discharge (n = 1,558) Multivariable analysis, eTable 1. The median time to first epinephrine dose was 1 minute (IQR, 0-4; range, 0-20; mean [SD], 2.6 [3.4] minutes).

Torres A Jr, Pickert CB, Firestone J, Walker WM, Fiser DH. HM, Nichol ME, de Caen Survival from in-hospital cardiac arrest during nights and weekends.

Error bars indicate exact binomial 95% confidence intervals. VM, Chan Because of the emergency nature of cardiac arrest, protocol violations occasionally occurred.

In children who had more than one cardiac arrest, only the initial cardiac arrest was evaluated.

To further characterize the relationship between time to epinephrine and outcomes, we conducted a preplanned analysis in which time to epinephrine was categorized into 5 minutes or less or longer than 5 minutes, as previously used as a quality metric in the adult cardiac arrest population.29 Using this definition, we conducted similar analyses as described earlier in this section. Pharmacotherapy 1997;17:242-247, 21. Ten were inadvertent deviations in dosing from the research protocol due to the urgency of the CPR efforts, which apparently resulted in incorrect guesses at the patients' weights or doses. Among the patients whose cardiac arrest had been precipitated by asphyxia, none of the 12 who were assigned to high-dose rescue epinephrine survived at 24 hours.

We performed an analysis of data from the Get With the GuidelinesResuscitation registry. The remaining 68 children were randomly assigned to the high-dose treatment regimen (34 patients) or the standard regimen (34 patients). PS, Krumholz This site needs JavaScript to work properly. A PCPC score of 1 to 2 was considered a favorable neurological outcome, and a PCPC score of 3 to 6 (death) was considered a poor neurological outcome. government site.

Although the data raise the possibility that high-dose epinephrine as rescue therapy may reduce the probability of survival at 24 hours, the evidence is limited by the small sample. Corresponding Author: Michael W. Donnino, MD, Beth Israel Deaconess Medical Center, One Deaconess Road, W/CC 2, Boston, MA 02215 (mdonnino@bidmc.harvard.edu).

We tried to account for this by multivariable regression modeling, including adjusting for time to CPR and hospital center as well as multiple patient and event characteristics. Cardiac surgery and trauma care are not provided. Callaham M, Madsen CD, Barton CW, Saunders CE, Pointer J. For all definitions of neurological outcome, approximately 11% of patients had missing data. Administration of epinephrine during cardiopulmonary resuscitation (CPR) consistently improves coronary and cerebral perfusion.1 Doses of epinephrine ranging from 0.05 to 0.2 mg per kilogram of body weight increase coronary and cerebral perfusion during CPR more than does the lower, standard dose, which is 0.01 mg per kilogram.2-7 The American Heart Association guidelines for pediatric advanced life support recommend use of the standard dose of epinephrine, given intravenously, as the initial dose for children with cardiac arrest.1 However, if subsequent doses are necessary, the guidelines recommend use of either the standard dose or a higher dose (0.1 mg per kilogram).

L,

All Rights Reserved, Challenges in Clinical Electrocardiography, Clinical Implications of Basic Neuroscience, Health Care Economics, Insurance, Payment, Scientific Discovery and the Future of Medicine, 2015;314(8):802-810. doi:10.1001/jama.2015.9678.

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Part 14: Pediatric advanced life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2000;102:Suppl I:I-291, 2.

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These associations remained when accounting for multiple predetermined potentially confounding patient, event, and hospital characteristics and in multiple different sensitivity analyses.

R. High-dose epinephrine in pediatric out-of-hospital cardiopulmonary arrest.

Circulation 1988;78:382-389, 34.

The unadjusted 24-hour survival rate was again lower with high-dose epinephrine than with standard-dose epinephrine: only 1 of 27 patients in the former group was alive at 24 hours, as compared with 6 of 23 in the latter group. VM, Zuercher In general, the two groups were similar before the cardiac arrest (Table 1). 2022 American Medical Association. No time point had zero observations. Dr K. Berg is supported by the AHA (13CRP16930000).

1997 Oct;13(5):320-4. doi: 10.1097/00006565-199710000-00005.

A recent report found that delay in epinephrine administration for adult in-hospital, nonshockable cardiac arrest was associated with decreased chance of ROSC, survival to discharge, and good neurological outcome.15 We hypothesized that delay in epinephrine administration for pediatric in-hospital, nonshockable cardiac arrest would likewise be associated with decreased survival.

Data abstractors were not blinded to the outcomes. Additional patient, event, and hospital characteristics are presented in Table 1 and in eTable 1 in the Supplement. S. A prospective study of outcome of in-patient paediatric cardiopulmonary arrest. When efforts to resuscitate a child after cardiac arrest are unsuccessful despite the administration of an initial dose of epinephrine, it is unclear whether the next dose of epinephrine (i.e., the rescue dose) should be the same (standard) dose or a higher dose. We believe that this potential misclassification is likely undifferentiated and that, in most cases, this would lead to bias toward the null.

VM.

T, Goto

Adrenaline for out of hospital cardiac arrest? G, Nallamothu Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries: a statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Councils of Southern Africa). Objective

The rate of survival at 24 hours was again lower in the high-dose epinephrine group: 1 of 27 patients survived, as compared with 6 of 23 in the standard-dose group (odds ratio for death with the high dose, 9.2; 97.5 percent confidence interval, 1.3 to 63.3; P=0.04).

PL.

Pediatr Emerg Care. Am Heart J 1994;127:324-330, 35.

BK; American Heart Association National Registry of Cardiopulmonary Resuscitation Investigators.

Jacobs

Members of the pediatric intensive care and emergency medicine faculty were in the hospital 24 hours a day and were available to participate on the cardiac-resuscitation team.

Therefore, continued use of the same milligram-per-kilogram dose resulted in a 10-fold dose increase in these patients after the experimental vials containing epinephrine in a 1:10,000 solution had been emptied. N Engl J Med 1992;327:1045-1050, 20. 2005 Apr;17(2):223-6. doi: 10.1097/01.mop.0000150949.12567.11.

Time to Epinephrine and Survival to Hospital Discharge After Pediatric In-Hospital Nonshockable Cardiac Arrest (N=1558), Table 1.

We also included whether the hospital was primarily a pediatric hospital and hospital teaching status (major [with fellowship program], minor [with residency program], or nonteaching [no residency program]). We further hypothesized that the differences would be most clearly demonstrable in the subgroup of patients with asphyxia-precipitated arrests, who are more homogeneous and have a better response to therapy than the group as a whole.

Despite our findings, it is reasonable to speculate that some patients may benefit from high-dose epinephrine as rescue therapy.

Berg RA, Otto CW, Kern KB, et al. However, the possibility remains that time to epinephrine is a marker of other aspects of the resuscitation processes and not the causal mediator.

); and Steele Memorial Children's Research Center and the Department of Pediatrics, University of Arizona College of Medicine, Tucson (R.A.B.).

Additional analyses were conducted after the exclusion of data from patients whose treatment involved protocol violations. Role of the Funder/Sponsor: The NHLBI had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Ortmann

No other disclosures were reported.

Donnino

Longer time to epinephrine administration was associated with lower risk of survival to discharge in multivariable analysis (multivariable-adjusted risk ratio [RR] per minute delay, 0.95 [95% CI, 0.93-0.98]). None of the patients in the high-dose group, as compared with four of those in the standard-dose group, survived to hospital discharge.

Comparison of standard and high-dose adrenaline in the resuscitation of asystole and electromechanical dissociation.

A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. Protocol violations occurred during resuscitative efforts in 18 of the 68 cardiac arrests we studied. Similar multivariable regression models were used to analyze secondary outcomes (ROSC, 24-hour survival, and survival to discharge with favorable neurological outcome), including different definitions of favorable neurological outcome.

Young KD, Seidel JS. Because data are used primarily at the local site for quality improvement, sites are granted a waiver of informed consent under the common rule. Resuscitative efforts during cardiac arrest were similar in the two groups, although more patients in the high-dose group than in the standard-dose group received only two or three doses of epinephrine, and more patients in the standard-dose group received more than six doses (Table 2). Multivariable Model With Survival to Discharge as the Outcome of Pediatric In-Hospital Cardiac Arrest. The classification of the time variables was done in whole minutes, and the actual time might therefore have been slightly misclassified.

PA, Wik

et al. VR, Dhindsa

M, Abe

JAMA. Berg Information and tools for librarians about site license offerings.

There are notable differences between pediatric and adult cardiac arrest in etiology, epidemiology, and treatment, including that more children have a nonshockable rhythm.3 Despite this, the current findings in the pediatric population are in line with those previously reported for adults.15 The current study included only patients who initially had a nonshockable rhythm.

), and the Department of Medicine, University of So Paulo School of Medicine (E.F.P. The results of the post hoc sensitivity analyses are presented in eTable 3 in the Supplement. No responder used doses smaller than SDE.

Paradis NA, Martin GB, Rosenberg J, et al.

The site is secure. The rate of survival at 24 hours was lower in the high-dose group than in the standard-dose group: 1 of the 34 patients assigned to the high dose of rescue epinephrine survived at 24 hours, as compared with 7 of the 34 patients assigned to the standard dose (unadjusted odds ratio for death with the high dose, 8.6; 97.5 percent confidence interval, 1.0 to 397.0; P=0.05) (Table 3). Pediatrics.

J, Kinney Drafting of the manuscript: Andersen, K. Berg, Donnino.

Do practice guidelines augment drug utilisation review. HS; NRCPR Investigators. The quality of data across sites may therefore vary.

Differences between the two treatment groups were assessed by chi-square analysis or Fisher's exact test for discrete variables and by unpaired t-tests for continuous variables.

A favorable neurological outcome was defined as a score of 1 to 2 on the Pediatric Cerebral Performance Category scale. The trial included 68 children, and Utstein-style reporting guidelines were used.

In conclusion, the results of this study suggest that high-dose epinephrine rescue therapy in children with in-hospital cardiac arrest does not improve the rate of survival at 24 hours.

Myocardial perfusion pressure: a predictor of 24-hour survival during prolonged cardiac arrest in dogs.

PA, Nadkarni JP,

GL, Peberdy Dieckmann RA, Vardis R. High-dose epinephrine in pediatric out-of-hospital cardiopulmonary arrest.

All reported P values are two-sided. Gueugniaud P-Y, Mols P, Goldstein P, et al.

J, RA, Alferness Dr Donnino reported being a paid consultant for the American Heart Association.

Categorical variables are presented with counts and frequencies and continuous variables in means with standard deviations or medians with interquartile ranges (IQRs) depending on the normality of the data. D, Bingham The results of the multivariable analyses when using the 3 different sensitivity definitions of favorable neurological outcome were similar to the main definition (eTable 2 in the Supplement).

We used the Get With the GuidelinesResuscitation (GWTG-R) registry, an AHA-sponsored, national, prospective, quality improvement registry of US in-hospital cardiac arrests. In addition, among patients with asphyxia-precipitated arrests and no protocol violations, the 24-hour survival rate was also lower in the high-dose epinephrine group: none of 8 patients in that group survived, as compared with 6 of 13 in the standard-dose group. 2019 Feb;49(2):46-49. doi: 10.1097/01.NURSE.0000552705.65749.a0. Residents, nurses, and faculty members provided CPR according to American Heart Association guidelines, without interference from the observing research team. Berg RA, Otto CW, Kern KB, et al.

Differences between the groups in the rate of 24-hour survival were further evaluated by multiple logistic-regression analysis, including all base-line factors for which the two groups differed at a level of P<0.10.

Ann Intern Med 1998;129:450-456, 31.

For example, the cardiac arrests in this study were witnessed, monitored, promptly recognized, and promptly treated.

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