Lindner KH, Ahnefeld FW, Prengel AW. R, Eich
et al; American Heart Associations Get With the Guidelines-Resuscitation Investigators. In a retrospective study of out-of-hospital cardiac arrest in children, 1 of 44 patients given a high dose of epinephrine at some point during resuscitative efforts, as compared with 1 of 13 given only the standard dose, survived to hospital admission.28 The high rate of death precluded assessment of the epinephrine dose in relation to outcomes. Kleinman
Subsequent doses were high because the epinephrine routinely stocked at our hospital is the 1:1000 solution. Anaesth Intensive Care 1993;21:192-196, 19. 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. Patients who did not receive epinephrine were therefore excluded. High-dose epinephrine improves outcome from pediatric cardiac arrest. Children who have more prolonged, untreated cardiac arrests, those who have undergone cardiac surgery, and those in ventricular fibrillation were underrepresented. Chan
Careers. M, Berg
A number of limitations should be considered when interpreting the current study. Protocol violations occurred during resuscitative efforts in 18 of the 68 cardiac arrests we studied. Similarly, outcomes were poor in the only randomized, controlled trial of high-dose epinephrine versus standard-dose epinephrine as rescue therapy for out-of-hospital cardiac arrest in adults.20 None of 140 patients survived to hospital discharge. 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). Time to Epinephrine and Survival After Pediatric In-Hospital Cardiac Arrest. Information and tools for librarians about site license offerings. Although some of these patients met other exclusion criteria, 362 patients were excluded solely on the basis of not having received epinephrine. et al; Pediatric Basic and Advanced Life Support Chapter Collaborators. Koehler RC, Michael JR, Guerci AD, et al. G. A modified Poisson regression approach to prospective studies with binary data. Hornchen U, Lussi C, Schuttler J. Main Outcomes and Measures
J,
S. A prospective study of outcome of in-patient paediatric cardiopulmonary arrest. The trial included 68 children, and Utstein-style reporting guidelines were used. Critical revision of the manuscript for important intellectual content: All authors. Jacobs
Pediatrics 1995;95:901-913, 29. The administration of dextrose during in-hospital cardiac arrest is associated with increased mortality and neurologic morbidity. government site. VM. Reynolds
et al. All Rights Reserved. FOIA Based on this difference, we consider this patient population to be substantially different from the one included and believe that a meaningful comparison would be problematic, especially given the relatively low overall sample size. Cumulative epinephrine dose during cardiopulmonary resuscitation and neurologic outcome. Brown CG, Werman HA, Davis EA, Hobson J, Hamlin RL. Young KD, Seidel JS. 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. This association remained significant in multivariable analysis (RR per minute delay, 0.95 [95% CI, 0.93-0.98]; P<.001) (eFigure 1 in the Supplement), accounting for potentially confounding variables, displayed in Table 2. Statistical analysis: Andersen, Saindon, Massaro, Donnino. JP, Niskanen
AG, Paiva
HF, Thompson
MD,
We used the Get With the GuidelinesResuscitation (GWTG-R) registry, an AHA-sponsored, national, prospective, quality improvement registry of US in-hospital cardiac arrests. Hagihara
Ornato
Survival to discharge was 31.3% (487/1558). 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). Standard-dose epinephrine (SDE) currently recommended by the American Heart Association for pediatric resuscitation is 0.01 mg/kg (0.1 ml/kg of 1:10,000 solution). The expected dismal outcomes preclude meaningful evaluation of the effects of the epinephrine dose on shock-precipitated arrests. These associations remained statistically significant in multivariable analysis for ROSC (RR per minute delay, 0.97 [95% CI, 0.96-0.99]; P<.001), for survival at 24 hours (RR per minute delay, 0.97 [95% CI, 0.95-0.99]; P=.003), and for survival with favorable neurological outcome (RR per minute delay, 0.95 [95% CI, 0.91-0.99]; P=.02) using our primary definition. Biarent
S. Medications in neonatal resuscitation: epinephrine and the search for better alternative strategies. Olasveengen
Comparative effect of graded doses of epinephrine on regional brain blood flow during CPR in a swine model. The main limitations of this investigation are related to the small sample size, use of the 24-hour survival rate as the primary outcome measure, the occurrence of protocol violations, and the extent to which the results may be generalized to other populations of children. Myocardial dysfunction after resuscitation from cardiac arrest: an example of global myocardial stunning. Goetting MG, Paradis NA. Distribution of Time to Epinephrine in Pediatric In-Hospital Nonshockable Cardiac Arrest (N=1558), Figure 3. We excluded patients with the following: (1) cardiac arrest in the delivery room, (2) an illness category of trauma or an illness category of hospital visitor, (3) vasopressor (epinephrine, norepinephrine, phenylephrine, and/or dopamine [for dopamine, at least 3 g/kg/min]) infusion at the time of cardiac arrest, (4) treatment with extracorporeal membrane oxygenation during the event, (5) vasopressin received before epinephrine, (6) epinephrine given before loss of pulse, (7) epinephrine received after ROSC, (8) epinephrine given more than 20 minutes after loss of pulse, (9) missing data on covariates, (10) missing data on time to first epinephrine dose, and (11) missing data on in-hospital survival (Figure 1). Duration of CPR and Doses of Epinephrine. She labeled the treatment packages with consecutive numbers provided by a random-number generator to ensure consistency with the randomization scheme. Cardiac surgery and trauma care are not provided. S. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. Fifty-one (49%) had completed fellowship training, and 81 (77%) were either PALS or APLS instructors (referred to as "instructors" below). In children who had more than one cardiac arrest, only the initial cardiac arrest was evaluated. Fiser
EP,
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. NA, Martin
VR, Dhindsa
Fish SS. RI, Watson
The patients in this previous study and those in our study were similar. Callaway
The association between time to epinephrine and the various outcomes remained statistically significant when using propensity score analyses and when using multiple imputation techniques for missing data. No other disclosures were reported. The median time to first epinephrine dose was 1 minute (IQR, 0-4; range, 0-20; mean [SD], 2.6 [3.4] minutes). A favorable neurological outcome was defined as a score of 1 to 2 on the Pediatric Cerebral Performance Category scale. 2005 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and neonatal patients: pediatric basic life support. Propensity score analysis and multiple imputations, eTable 4. In a previous investigation at the Children's Institute of the University of So Paulo School of Medicine, 61 percent of the cardiac arrests were precipitated by asphyxia, and 36 percent occurred in children who had received catecholamine infusions before the arrest.24 The Children's Institute is a 122-bed, tertiary-care children's hospital that admits more than 6000 patients each year. CPR denotes cardiopulmonary resuscitation, and ROSC return of spontaneous circulation. Whether this association is true in the pediatric in-hospital cardiac arrest population remains unknown. However, the previous study was neither randomized nor blinded, and the standard-dose group was composed of historical controls. Overall, 72% (76/105) indicated that they use doses larger than SDE. After two mailings, 105 of 162 surveys (65%) were completed by members in practice. Case Records of the Massachusetts General Hospital, Monkeypox Virus Infection in Humans across 16 Countries AprilJune 2022, Protection Associated with Previous SARS-CoV-2 Infection in Nicaragua, Nirmatrelvir for Nonhospitalized Adults with Covid-19, Efficacy of Antibodies and Antiviral Drugs against Omicron BA.2.12.1, BA.4, and BA.5 Subvariants, Effectiveness of BNT162b2 Vaccine against Omicron in Children 5 to 11 Years of Age, Evidence for Step Therapy in Diabetic Macular Edema, Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults, Case 23-2022: A 49-Year-Old Man with Hypoglycemia, Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus, Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkins Lymphoma, NEJM Catalyst Innovations in Care Delivery. Only 1 of the 38 survived at 24 hours, and none survived to hospital discharge. Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. VM, Berg
Randomization was performed by a single pharmacist, who prepared the treatment packages, each containing 10 1-ml vials of epinephrine in a solution of 1:1000 or 1:10,000. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. The rate of survival at 24 hours was lower in the group assigned to a high dose of epinephrine as rescue therapy than in the group assigned to a standard dose: 1 of the 34 patients in the high-dose group survived for 24 hours, as compared with 7 of the 34 patients in the standard-dose group (unadjusted odds ratio for death with the high dose, 8.6; 97.5 percent confidence interval, 1.0 to 397.0; P=0.05). Goto
Potential risks of high-dose epinephrine for resuscitation from ventricular fibrillation in a porcine model. RA, Alferness
(ABSTRACT TRUNCATED AT 250 WORDS), MeSH HS; NRCPR Investigators. We furthermore included only hospitals with at least 6 months of data and at least 5 cases reported to ensure high quality of the data. Before the arrest, the majority of the patients were being monitored electrocardiographically (78 percent), were receiving mechanical ventilation (68 percent), or were being treated with catecholamine infusions (53 percent). We included US pediatric patients (age <18 years) with an in-hospital cardiac arrest and an initial nonshockable rhythm who received at least 1 dose of epinephrine. Because of the need for immediate intervention in cardiac arrest, inadvertent deviations from the research protocol in terms of dosing occurred in 10 of the 68 patients: 3 assigned to the standard-dose group, and 7 to the high-dose group. AJ, Nadkarni
We found no sign of nonlinear (ie, quadratic or cubic) associations between time to epinephrine and survival to hospital discharge (all P>.05). A randomized, blinded trial of high-dose epinephrine versus standard-dose epinephrine in a swine model of pediatric asphyxial cardiac arrest. Tibballs
Pediatric advanced life support. We included US pediatric patients (age <18 years) with an in-hospital cardiac arrest and an initial nonshockable rhythm who received at least 1 dose of epinephrine. The data suggest that high-dose therapy may be worse than standard-dose therapy. JP, Peberdy
N Engl J Med 1998;339:1595-1601, 18. ), So Paulo, Brazil; the Department of Anesthesiology, University of Pennsylvania School of Medicine and the Children's Hospital of Philadelphia, Philadelphia (V.M.N. MA,
Chase PB, Kern KB, Sanders AB, Otto CW, Ewy GA. High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs: a prospective, randomized study. A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. Pediatrics. Patient Flowchart for Study of Timing of Epinephrine and Pediatric In-Hospital Nonshockable Cardiac Arrest, Figure 2. Impact of resuscitation system errors on survival from in-hospital cardiac arrest. Twenty-two were assigned to high-dose epinephrine, and 16 to standard-dose epinephrine. Y, Berg
Circulation 1988;78:382-389, 34. Effects of prehospital epinephrine during out-of-hospital cardiac arrest with initial non-shockable rhythm: an observational cohort study. J, Takahashi
For all definitions of neurological outcome, approximately 11% of patients had missing data. TV. Among the 1558 patients, 487 (31.3%) survived to hospital discharge. Donoghue
Prognostic and therapeutic importance of the aortic diastolic pressure in resuscitation from cardiac arrest. Nevertheless, most reported cases of in-hospital cardiac arrest in children were precipitated by asphyxia or shock and were promptly diagnosed and treated.10,24,37 We therefore believe that our findings are relevant to most populations of children who have in-hospital cardiac arrest. Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry. The primary outcome measure was survival at 24 hours. M, Abe
Berg RA, Kern KB, Hilwig RW, Ewy GA. Girotra
Outcomes according to epinephrine category. Niemann
The classification of the time variables was done in whole minutes, and the actual time might therefore have been slightly misclassified. HM, Nichol
MW, Salciccioli
Outcomes were dismal among the 38 patients whose cardiac arrest had been precipitated by some form of shock. et al; American Heart Association. 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. Seven hundred forty patients did not receive epinephrine (Figure 1). ME, de Caen
Pediatrics 1997;99:403-408, 28. The remaining 68 children were randomly assigned to the high-dose treatment regimen (34 patients) or the standard regimen (34 patients). Torres A Jr, Pickert CB, Firestone J, Walker WM, Fiser DH. ME, Chameides
Results from the multivariable regression models are reported as RRs with 95% CIs. A total of 1558 patients (median age, 9 months [interquartile range [IQR], 13 days5 years]) were included in the final cohort. Although long-term survival with a good neurologic outcome is the ultimate goal of resuscitation from cardiac arrest, that end point is more strongly influenced by underlying conditions that are not related to resuscitative efforts during cardiac arrest. The characteristics of the patients and their outcomes were similar to those previously described at the Children's Institute.24 More than 90 percent of these cardiac arrests were monitored and witnessed, typically in the intensive care unit. Gonzalez ER, Ornato JP, Garnett AR, et al. Demographic Characteristics of the Patients at the Time of Cardiac Arrest. Pediatric cardiopulmonary resuscitation: a collective review. Myocardial perfusion pressure: a predictor of 24-hour survival during prolonged cardiac arrest in dogs. Outcomes for Patients with Cardiac Arrest Precipitated by Asphyxia. C, Thowsen
EF, Nadkarni
Dallas: American Heart Association, 1997. L, Schexnayder
Callaham M, Madsen CD, Barton CW, Saunders CE, Pointer J. Neither received any specific financial compensation for their role in the current study. Time to Epinephrine and Survival to Hospital Discharge After Pediatric In-Hospital Nonshockable Cardiac Arrest (N=1558), Table 1. TM, Sunde
Vandycke C, Martens P. High dose versus standard dose epinephrine in cardiac arrest -- a meta-analysis. sharing sensitive information, make sure youre on a federal Prepare to become a physician, build your knowledge, lead a health care organization, and advance your career with NEJM Group information and services. Donnino
Crit Care Med 1994;22:282-290, 22. Crit Care Med 1993;21:413-419, 5. Crit Care Med 1993;21:111-117, 14. All eight were inadvertently treated with high-dose epinephrine after their experimental standard-dose vials had been emptied because the epinephrine routinely stocked at this hospital is the 1:1000 solution. The aim of the current study was not to answer the question of whether or not epinephrine should be given but to clarify whether there was an association between delay in epinephrine administration and outcome when epinephrine was given during in-hospital pediatric cardiac arrest. Median age was 9 months (IQR, 13 days5 years), and 46% were female. 2019 Feb;49(2):46-49. doi: 10.1097/01.NURSE.0000552705.65749.a0. J Am Coll Cardiol 1996;28:232-240, 37. Behringer W, Kittler H, Sterz F, et al. Ann Emerg Med 1986;15:1138-1144, 3. official website and that any information you provide is encrypted PS. JC, Rittenberger
The physiological rationale for epinephrine is primarily through -adrenergic increase in coronary perfusion pressure, which has been shown to be an important determinant of ROSC.9-11,30 The association between epinephrine administration and a better chance of ROSC is a consistent finding across studies.31-34 Because duration of CPR is associated with outcome21 and ROSC is a necessary first step to a meaningful recovery, the rationale for epinephrine administration as a time-sensitive intervention to improve long-term outcome becomes apparent. Dr K. Berg is supported by the AHA (13CRP16930000). KR. Valuable tools for building a rewarding career in health care. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. Berg RA, Padbury JF, Donnerstein RL, Klewer SE, Hutter JJ Jr. Dobutamine pharmacokinetics and pharmacodynamics in normal children and adolescents. Jacobs
Design, Setting. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. Acquisition, analysis, or interpretation of data: All authors. Time to epinephrine, defined as time in minutes from recognition of loss of pulse to the first dose of epinephrine. Berg RA, Donnerstein RL, Padbury JF. N Engl J Med 1992;327:1051-1055, 15. Funding/Support: Dr Donnino is supported by the National Heart, Lung, and Blood Institute (NHLBI) (1K02HL107447-01A1) and American Heart Association (AHA) (14GRNT2001002). Circulation 1987;75:491-497, 4. 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. Pharmacokinetics of exogenous epinephrine in critically ill children. 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. Instructors were more likely to use larger doses than were noninstructors (83% compared with 38%; P < 0.001). Guidelines for cardiopulmonary resuscitation and emergency cardiac care. 2015;314(8):802810. C. Predictive indices of successful cardiac resuscitation after prolonged arrest and experimental cardiopulmonary resuscitation. Drug administration in animal studies of cardiac arrest does not reflect human clinical experience. Half of the members of the American Academy of Pediatrics Emergency Medicine section, selected randomly, were surveyed by a mailed questionnaire. We decided to analyze data only from this patient population to avoid confounding by defibrillation, which has previously been found to be a time-sensitive component of cardiac arrest resuscitation in adult patients with a shockable rhythm.39 As such, the findings should not be extrapolated to patients with a shockable rhythm; neither should they be extrapolated to out-of-hospital cardiac arrest, for which the time to initiation of therapy is often much longer. A previous study of in-hospital cardiac arrest in children suggested that outcomes after rescue therapy with high-dose epinephrine were far superior to those after rescue therapy with standard-dose epinephrine.9 In that study, 14 of 20 patients given high-dose epinephrine had a return of spontaneous circulation, and 8 of those 20 survived to hospital discharge.
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