First Documented Rhythm and Clinical Outcome From In-Hospital Cardiac Arrest Among Children and Adults

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1 ORIGINAL CONTRIBUTION First Documented Rhythm and Clinical Outcome From In-Hospital Among Children and s Vinay M. Nadkarni, MD Gregory Luke Larkin, MD Mary Ann Peberdy, MD Scott M. Carey William Kaye, MD Mary E. Mancini, PhD Graham Nichol, MD Tanya Lane-Truitt, RN Jerry Potts, PhD Joseph P. Ornato, MD Robert A. Berg, MD for the National Registry of Cardiopulmonary Resuscitation Investigators THE APPROACH TO CARDIOPULMOnary resuscitation (CPR) differs for children and adults because of presumed differences in the etiology and pathophysiology of cardiac arrests. 1-4 s with cardiac arrest typically have sudden, unexpected ventricular fibrillation (VF) and often have underlying coronary artery disease with myocardial ischemia. 5,6 The focus of adult-oriented treatment is prompt defibrillation. 7 Outcomes from witnessed VF are often excellent, but outcomes from asystole and pulseless electrical activity (PEA) are generally poor. 8 In contrast, children who experience cardiac arrest rarely have coronary artery disease. Instead, cardiac ar- See also p 96 and Patient Page. Context Cardiac arrests in adults are often due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), which are associated with better outcomes than asystole or pulseless electrical activity (PEA). Cardiac arrests in children are typically asystole or PEA. Objective To test the hypothesis that children have relatively fewer in-hospital cardiac arrests associated with VF or pulseless VT compared with adults and, therefore, worse survival outcomes. Design, Setting, and Patients A prospective observational study from a multicenter registry (National Registry of Cardiopulmonary Resuscitation) of cardiac arrests in 253 US and Canadian hospitals between January 1, 2000, and March 30, A total of adults ( 18 years) and 880 children ( 18 years) with pulseless cardiac arrests requiring chest compressions, defibrillation, or both were assessed. Cardiac arrests occurring in the delivery department, neonatal intensive care unit, and in the out-of-hospital setting were excluded. Main Outcome Measure Survival to hospital discharge. Results The rate of survival to hospital discharge following pulseless cardiac arrest was higher in children than adults (27% [236/880] vs 18% [6485/36 902]; adjusted odds ratio [OR], 2.29; 95% confidence interval [CI], ). Of these survivors, 65% (154/236) of children and 73% (4737/6485) of adults had good neurological outcome. The prevalence of VF or pulseless VT as the first documented pulseless rhythm was 14% (120/880) in children and 23% (8361/36 902) in adults (OR, 0.54; 95% CI, ; P.001). The prevalence of asystole was 40% (350) in children and 35% (13 024) in adults (OR, 1.20; 95% CI, ; P=.006), whereas the prevalence of PEA was 24% (213) in children and 32% (11 963) in adults (OR, 0.67; 95% CI, ; P.001). After adjustment for differences in preexisting conditions, interventions in place at time of arrest, witnessed and/or monitored status, time to defibrillation of VF or pulseless VT, intensive care unit location of arrest, and duration of cardiopulmonary resuscitation, only first documented pulseless arrest rhythm remained significantly associated with differential survival to discharge (24% [135/ 563] in children vs 11% [2719/24 987] in adults with asystole and PEA; adjusted OR, 2.73; 95% CI, ). Conclusions In this multicenter registry of in-hospital cardiac arrest, the first documented pulseless arrest rhythm was typically asystole or PEA in both children and adults. Because of better survival after asystole and PEA, children had better outcomes than adults despite fewer cardiac arrests due to VF or pulseless VT. JAMA. 2006;295: Author Affiliations are listed at the end of this article. Corresponding Author: Vinay M. Nadkarni, MD, Departments of Anesthesia, Critical Care, and s, University of Pennsylvania School of Medicine, 34th Street and Civic Center Boulevard, South Tower, Room 7C-08, Philadelphia, PA (nadkarni@ .chop.edu). 50 JAMA, January 4, 2006 Vol 295, No. 1 (Reprinted) 2006 American Medical Association. All rights reserved.

2 rests in children generally result from progressive tissue hypoxia and acidosis due to respiratory failure, circulatory shock, or both. 9 Electrocardiographic rhythms of cardiac arrests in children usually progress through bradyarrhythmias to asystole or PEA rather than to VF. Although the outcomes from respiratory arrest or shock in children are generally good, the outcomes from pulseless cardiac arrests in children are poor. 1-3 Characterization of in-hospital cardiac arrests has been limited by the lack of consistent data collection and analysis. 10,11 Reports of pediatric arrests often have not clearly differentiated between respiratory arrest, severe bradycardia, and pulseless cardiac arrest. 12,13 In the early 1990s, international experts developed guidelines for uniform data reporting of cardiac arrests and resuscitation, the Utstein style. 10,12,14-16 To attain a robust database of in-hospital cardiac arrests and resuscitation with Utstein style definitions and outcome measures, the American Heart Association developed a National Registry of Cardiopulmonary Resuscitation (NRCPR). In our analysis of pediatric and adult sequential index cardiac arrest events reported to the NRCPR, we characterized and compared the pediatric and adult outcomes following confirmed in-hospital pulseless cardiac arrests. We hypothesized that children would have relatively fewer inhospital cardiac arrests associated with VF and pulseless ventricular tachycardia (VT) than adults and, therefore, worse survival outcomes. METHODS Design and Setting The NRCPR is a prospective multicenter observational registry of inhospital cardiac arrest and resuscitation. Our analysis reports on patients from 253 US and Canadian medical and surgical hospitals that provided at least 6 months of data between January 1, 2000, and March 30, Participating hospitals join the registry voluntarily and pay an annual fee for data support and report generation. On enrollment in NRCPR, hospitals complete a form characterizing their facilities, staff, patients, and resuscitation services. Because the primary purpose of the NRCPR is quality improvement and data are de-identified in compliance with the Health Insurance Portability and Accountability Act, participating hospitals are not required to obtain institutional review board approval or individual informed consent. This study was approved by the institutional review boards of the University of Arizona, Tucson, and The Children s Hospital, Philadelphia, Pa. Data Collection The Utstein style definitions and database elements, including self-reported race/ethnicity, have recently been reviewed and updated. 10,12,14 These definitions are used consistently in the registry database. Specially trained NRCPR-certified research coordinators at each institution enter information for each cardiac arrest abstracted from hospital medical records, including the patient s chart, cardiac arrest forms, and hospital paging system records, into a computer database that contains precisely defined variables. Data abstractors are required to successfully complete a certification examination consisting of multiplechoice questions and a mock scenario covering operational definitions and inclusion/exclusion criteria. Case-study methods are used to evaluate data abstraction, entry accuracy, and operational definition compliance before acceptance of data transmission. Data are collected in 6 major categories of variables: facility data, patient demographic data, pre-event data, event data, outcome data, and quality improvement data. 17 Explicit operational definitions have been generated for every data element. First documented pulseless rhythm was defined as the first electrocardiogram rhythm documented at the time the patient became pulseless and, for those patients with unwitnessed/unmonitored arrests, it represents the first rhythm documented at the time a monitor arrives and is applied. Index events are defined as the patient s first cardiac arrest event during this hospitalization. Each patient is assigned a unique code and no specific patient identifiers are transmitted to the central database repository, in compliance with the Health Insurance Portability and Accountability Act regulations. Hospitals submit data on diskette or via encrypted, secure Internet transmission. A central data repository (Digital Innovation Inc, Forest Hill, Md) facilitates data management and provides sites with quarterly reports summarizing their data and comparisons with grouped data. The American Heart Association provides oversight for the entire process of data collection, integrity, analysis, and reporting through staff, a scientific advisory board, and an executive database steering committee. Inclusion and Exclusion Criteria All adult ( 18 years) and pediatric ( 18 years) patients, visitors, employees, and staff within a facility who experienced a cardiac arrest resuscitation were eligible for inclusion. A resuscitation event was defined as a pulseless cardiopulmonary arrest requiring chest compressions, defibrillation, or both that elicited an emergency resuscitation response by facility personnel and resulted in a resuscitation record. Pulseless cardiac arrest was defined as cessation of cardiac mechanical activity, determined by the absence of a palpable central pulse, unresponsiveness, and apnea. Events were excluded if the cardiac arrest began out-of-hospital, involved a newborn in the delivery department or neonatal intensive care unit, or was limited to a shock by an implanted cardioverter-defibrillator. Patients who had do not attempt resuscitation or not for resuscitation status before their first inhospital cardiac arrest event were excluded from the registry. Outcome Measures The prospectively selected primary outcome measure was survival to hospital discharge. 10 Consistent with the Ut American Medical Association. All rights reserved. (Reprinted) JAMA, January 4, 2006 Vol 295, No. 1 51

3 Table 1. Patient Characteristics of and s* Characteristic stein style registry guidelines, only the first in-hospital index cardiac arrest and resuscitation were described and analyzed for patients with multiple arrests. Secondary survival measures included any return of spontaneous circulation, a return of spontaneous circulation of more than 20 minutes, and 24-hour survival. Neurological outcome was determined using adult cerebral performance category (CPC) and pediatric CPC (PCPC) scales. 10,18,19 The CPC category 1 is good cerebral performance; (n = 880) (n = ) P Value Age, y Mean (SD) 5.6 (6.4) 65.3 (15.2).001 Median (range) 1.8 (0-17.0) 71 (18-111) Sex Male 473 (54) (57) Female 407 (46) (43).04 Race/ethnicity White 447 (51) (67).001 Black 226 (26) 7217 (20).001 Hispanic 105 (12) 1758 (5).001 Other/unknown 102 (12) 3127 (8).001 Patient type Inpatient 750 (85) (88).02 Emergency department 121 (14) 4079 (11).01 Other (outpatient, visitor, or employee) 9 (1) 412 (1).99 Illness category Medical, cardiac 158 (18) (38).001 Medical, noncardiac 402 (46) (41).01 Surgical, cardiac 150 (17) 2617 (7).001 Surgical, noncardiac 62 (7) 4030 (11).001 Trauma 91 (10) 915 (3).001 Other 17 (2) 122 (0.3).001 Preexisting conditions Respiratory insufficiency 511 (58) (40).001 Hypotension and hypoperfusion 319 (36) (27).001 Congestive heart failure 273 (31) (33).15 Pneumonia, septicemia, or other infection 259 (29) (27).18 Arrhythmia 182 (21) (32).001 Metabolic and electrolyte abnormality 178 (20) 6692 (18).11 Baseline depression in CNS function 151 (17) 4653 (13).001 Renal insufficiency 104 (12) (31).001 Major trauma 97 (11) 1277 (4).001 Acute CNS nonstroke event 94 (11) 2574 (7).001 None 69 (8) 1760 (5).001 Hepatic insufficiency 55 (6) 2502 (7).58 Metastatic or hematologic malignancy 43 (5) 4136 (11).001 Myocardial infarction 21 (2) (35).001 Toxicological problem 12 (1) 651 (2).44 Diabetes mellitus 11 (1) (29).001 Acute stroke 5 (1) 1509 (4).001 Abbreviation: CNS, central nervous system. *Data are expressed as No. (%) unless otherwise specified. Because of rounding, percentages may not all total 100. Preexisting conditions total more than the total number of patients due to patients having more than 1 preexisting condition present at the time of admission to hospital. See Methods for definitions of race/ethnicity. For pediatric cardiac arrest, all 17 were obstetrics; for adult cardiac arrest, 20 were unknown or not documented, 60 were obstetrics, and 42 were visitors or employees (not designated because they were not inpatients with charts and known illness categories). No documented preexisting conditions. CPC category 2, moderate cerebral disability; CPC category 3, severe cerebral disability; CPC category 4, coma/ vegetative state; and CPC category 5, brain death. The PCPC category 1 is normal age-appropriate neurodevelopmental functioning; PCPC category 2, mild cerebral disability; PCPC category 3, moderate cerebral disability; PCPC category 4, severe disability; PCPC category 5, coma/vegetative state; and PCPC category 6, brain death. The pre-cpr neurological categorization was based on historical data and chart review. Categorization at the time of discharge was determined by the discharge examination documentation. Good neurological outcome was prospectively defined as CPC category 1 or 2 for adults, the comparable PCPC category of 1, 2, or 3 for children on hospital discharge, or no change from baseline CPC or PCPC. Statistical Analysis The primary hypothesis that children would have worse discharge survival outcomes compared with adults was tested using 2 with adjusted odds ratios (ORs). All reported P values are 2-tailed. Ninety-five percent confidence intervals (CIs) were calculated for the absolute difference in survival rates following cardiac arrest. The minimum sample size for comparing overall survival to hospital discharge between pediatric and adult patients with pulseless cardiac arrest was estimated to be 600 patients in each group, on the basis of 2-sided =.05 and =.10, assuming a baseline expected pediatric survival to discharge rate of 15%, yielding 90% power to detect a 35% difference in survival (eg, a difference in absolute survival rate from 15% to 20%). The 2 populations were compared by univariate analysis with regard to preexisting conditions, interventions in place at time of arrest, witnessed and/or monitored cardiac arrest, first documented pulseless arrest rhythm, time to defibrillation of VF or pulseless VT, and duration of CPR. Differences between children and adults for other data were analyzed with the Wilcoxon rank sum 52 JAMA, January 4, 2006 Vol 295, No. 1 (Reprinted) 2006 American Medical Association. All rights reserved.

4 testing for ordinal variables, Fisher exact test, 2 test, or t test, as appropriate. Univariate and multivariable regression analyses were conducted on all index cardiac arrests using Wilcoxon rank sum testing for continuous variables and 2 analysis for dichotomous variables with SAS version 8 (SAS Institute, Cary, NC). Multivariable logistic regression analysis was performed on factors associated with survival in the univariate analysis (P.10) to control for patient and event variables that may confound the relationship between age category and survival. Odds ratios for survival and 95% CIs were determined for prognostic factors that were independently associated with survival. RESULTS During the study period, adult and 880 pediatric consecutive index pulseless cardiac arrests were reported. These cardiac arrests required chest compressions for more than 1 minute in 99.7% of adults and 99.9% of children. Patient characteristics and comparisons are shown in TABLE 1 and event characteristics and comparisons are shown in TABLE 2. Data were contributed by 253 hospitals (10 pediatric facilities [4%], 136 mixed pediatric-adult facilities [54%], and 107 adult facilities [42%]). The median size of contributing hospitals contained 260 beds. The regional distribution of NRCPR participating hospitals included 46 states, District of Columbia, and Ontario, Canada. Major pre cardiac arrest and event therapeutic interventions and time intervals are shown in TABLE 3. Children had substantially higher prevalence of arterial catheters, vasoactive infusions, and mechanical ventilation support before cardiac arrest. In addition, the median duration of pediatric CPR was longer than adult CPR (25 minutes [interquartile range, minutes] vs 18 minutes [10-29 minutes]). The mean (SD) duration of CPR was significantly longer in children vs adults (32.8 [30.0] vs 22.3 [18.9] minutes, P.001). Events were monitored (electrocardiogram, pulse oximeter, apnea monitor), witnessed, or both in 87.4% overall; more frequently in children than in adults (95% vs 88%, P.001). The prevalence of VF or pulseless VT as the first documented pulseless arrest rhythm was 14% (120/880) of pediatric and 23% (8361/36 902) of adult pulseless cardiac arrests (OR, 0.54; 95% CI, ; P.001). The relative prevalence of asystole was higher in children than in adults (40% vs 35%; OR, 1.20; 95% CI, ; P=.006) and the relative prevalence of VF was lower (8% vs 14%; OR, 0.54; 95% CI, Data Integrity Data were checked for fidelity using a detailed periodic reabstraction process. The NRCPR participants submitted randomly selected records each quarter. A random sampling of event records and corresponding NRCPR data sheets were reabstracted and reviewed for errors by NRCPR scientific advisory board members. Mean (SD) error rates for all data were 2.4% (2.7%). Software data checks for out-of-range entries and a Web-based remediation program were developed to continuously remediate and support data integrity. Enrollment of new hospitals involves certification by testing accuracy of data abstraction before allowing data submission into the central database. Table 2. Event Characteristics of and s* Characteristic (n = 880) (n = ) P Value Event location Intensive care unit 570 (65) (45).001 Emergency department 116 (13) 4018 (11).03 General inpatient 123 (14) (35).001 Diagnostic area 21 (2) 1555 (4).008 Outpatient, other, or unknown 20 (2) 908 (2).99 Operating department or postanesthetic care 30 (3) 899 (2).07 First documented pulseless rhythm Asystole 350 (40) (35).006 VF or pulseless VT 120 (14) 8361 (23).001 VF 71 (8) 5170 (14).001 Pulseless VT 49 (6) 3191 (9).001 PEA 213 (24) (32).001 Unknown by documentation 197 (22) 3554 (10).001 Discovery status at time of event Witnessed and/or monitored 834 (95) (88).001 Witnessed and monitored 727 (83) (66).001 Witnessed and not monitored 73 (8) 4472 (12).001 Monitored and not witnessed 34 (4) 3473 (9).001 Not monitored and not witnessed 46 (5) 4517 (12).001 Immediate cause(s) of event Hypotension 483 (61) (44).001 Acute respiratory insufficiency 455 (57) (41).001 Arrhythmia 392 (49) (65).001 Metabolic and electrolyte disturbance 95 (12) 3406 (11).24 Airway obstruction 41 (5) 668 (2).001 Acute pulmonary edema 33 (4) 798 (3).004 Acute myocardial infarction or ischemia 12 (2) 3634 (11).001 Toxicological problem 9 (1) 324 (1).72 Acute pulmonary embolism 6 (1) 706 (2).005 Abbreviations: PEA, pulseless electrical activity; VF, ventricular fibrillation; VT, ventricular tachycardia. *Data are expressed as No. (%). Because of rounding, percentages may not all total 100. Totals do not sum to total number of pediatric and adult patients for discovery status at time of event and immediate cause(s) of event characteristics due to patients having more than 1 characteristic. The National Registry of Cardiopulmonary Resuscitation definition of monitored includes electrocardiogram, apnea/ bradycardia, or pulse oximeter American Medical Association. All rights reserved. (Reprinted) JAMA, January 4, 2006 Vol 295, No. 1 53

5 ; P.001). Thus, pulseless cardiac arrest in children was approximately 20% more likely to present with asystole and only approximately 50% less likely to present with VF. The prevalence of PEA was 24% (213/880) in children and 32% (11 963/36 902) in adults (OR, 0.67; 95% CI, ; P.001). A specific first documented pulseless arrest rhythm was reported in 78% of children and 90% of adults (P.001) (Table 2). The major outcome data are displayed in TABLE 4 and TABLE 5. The rate of survival to hospital discharge following pulseless cardiac arrest was higher in children than in adults (27% vs 18%; adjusted OR, 2.29; 95% CI, ). Of these survivors, 65% (154/236) of children and 73% (4737/ 6485) of adults had good neurological outcome. For the entire cohort, after adjustment by logistic regression for differences in preexisting conditions, interventions in place at time of Table 3. Cardiopulmonary Resuscitation Interventions Interventions arrest, witnessed and/or monitored status, time to defibrillation of VF or pulseless VT, intensive care unit location of arrest, and duration of CPR, only first documented pulseless arrest rhythm remained significantly associated with differential survival to hospital discharge. Rates of survival to hospital discharge for first documented pulseless cardiac arrest rhythms of asystole and PEA were higher in children than in adults (24% [135/563] vs 11% [2719/ ]; adjusted OR, 2.73; 95% CI, ). In contrast, no demonstrable difference in survival to hospital discharge was associated with VF or pulseless VT (29% [35/120] of children vs 36% [3013/8361] of adults; adjusted OR, 0.83; 95% CI, ). In a secondary analysis, we examined the association between initial cardiac arrest rhythm and outcomes for patients who were admitted to the intensive care unit at the time of cardiac arrest because P Value Interval to initiation of CPR, min Mean (SD) 0.8 (3.2) 0.5 (2.1).61 Median (IQR) 0 (0-0) 0 (0-0) Interval to first attempted defibrillation, min Mean (SD) 2.8 (4.2) 2.1 (3.7).93 Median (IQR) 1 (0-4) 1 (0-3) Duration of CPR, min Mean (SD) 32.8 (30.0) 22.3 (18.9).001 Median (IQR) 25 (12-45) 18 (10-29) Duration of CPR for survivors to hospital discharge, min Mean (SD) 27.3 (32.0) 16.0 (17.9).001 Median (IQR) 15 (7-36) 10 (5-21) Duration of CPR for nonsurvivors to hospital discharge, min Mean (SD) 33.8 (28.0) 23.4 (19.8).001 Median (IQR) 29 (15-49) 20 (12-30) Interval to first epinephrine during cardiac arrest, min Mean (SD) 3.1 (4.7) 3.1 (3.9).90 Median (IQR) 1 (0-5) 2 (0-5) No. of doses of epinephrine Mean (SD) 4.6 (4.3) 3.3 (2.3).64 Median (IQR) 3 (2-6) 4 (3-5) In place at time of event, No. (%) Arterial catheter 256 (29) 2993 (8).001 Vasoactive infusion 337 (38) 9935 (27).001 Mechanical/assisted ventilation 501 (57) 9561 (26).001 Abbreviations: CPR, cardiopulmonary resuscitation; IQR, interquartile range. the documentation of time and intervention variables was thought to be most reliable in this highly monitored environment. The rate of survival to hospital discharge following pulseless cardiac arrest was higher in children than in adults (25% vs 15%; unadjusted OR, 1.80; 95% CI, ). Of these survivors, 72% (101/141) of children and 71% (1816/2570) of adults had good neurological outcome. After adjustment by logistic regression for differences in preexisting conditions, interventions in place at time of arrest, witnessed and/or monitored status, time to defibrillation of VF or pulseless VT, and duration of CPR, only initial rhythm remained significantly associated with differential survival to hospital discharge. Rates of survival to hospital discharge for initial cardiac arrest rhythms of asystole and PEA were higher in children than in adults (23% vs 10%; adjusted OR, 2.80; 95% CI, ). In contrast, there was no demonstrable difference in rates of survival to hospital discharge for VF or pulseless VT (30% of children vs 32% of adults; adjusted OR, 0.90; 95% CI, ). All of the above data refer to children and adults who were pulseless and received chest compressions. A total of 200 children and 583 adults who received chest compressions for any reason during this time were excluded from analysis because they initially had bradycardia with pulses and did not lose the pulse during the event. Proportionately more children received chest compressions for bradycardia with pulses (18% [200/1106] vs 2% [583/37 697], P.001). Nearly all adults who received chest compressions for their initial event fit the definition of pulseless cardiac arrest vs only 82% of children. As expected, children who received chest compressions for bradycardia with pulses had a much higher rate of survival to hospital discharge than those with pulseless cardiac arrest (60% vs 27%, P.001). COMMENT In this large, multicenter, in-hospital cardiac arrest database, children sur- 54 JAMA, January 4, 2006 Vol 295, No. 1 (Reprinted) 2006 American Medical Association. All rights reserved.

6 vived to hospital discharge more frequently following cardiac arrest than adults did, predominantly because of better outcomes following asystole and PEA. Most cardiac arrests in both adults and children were not sudden shockable cardiac arrhythmias, VF or pulseless VT. Instead, most of these arrests were associated with progressive respiratory failure, circulatory shock, or both. Nevertheless, shockable rhythms (VF or pulseless VT) were relatively common among both groups. The ultimate goal of resuscitation is to improve survival with good neurological outcome. In our study, most pediatric and adult survivors had good neurological outcomes (65% and 73%, respectively). The proportion of patients discharged with good neurological outcome is similar to that reported in other smaller in-hospital cardiac arrest studies. 20,21 Although asystole and PEA are often considered futile cardiac arrest rhythms, substantial numbers of children and adults with these rhythms survived to hospital discharge (24% and 11%, respectively). Specifically, children had better survival outcomes than adults, mostly attributable to differences in outcome following asystole and PEA. The outcomes from shockable rhythms were similar in both pediatric and adult patients. An important decision for treatment of pulseless cardiac arrest is the separation of nonshockable from shockable rhythms (ie, VF and pulseless VT). The prevalence of VF or pulseless VT as the first documented pulseless electrocardiographic rhythm was 14% in children and 23% in adults. Although these data support our hypothesis that shockable rhythms are more common as initial cardiac arrest rhythms in adults than in children, they also indicate that most adult in-hospital cardiac arrests are not due to sudden shockable rhythms and many pediatric cardiac arrests are due to shockable rhythms. Table 4. Outcomes of In-Hospital Pulseless s by First Documented Pulseless Arrest Rhythm* No. (%) of Patients VF or Pulseless VT Asystole PEA Unknown Rhythm (n = 120) (n = 8361) (n = 350) (n = ) (n = 213) (n = ) (n = 197) (n = 3554) Any ROSC 80 (66.7) 5629 (67.3) 184 (52.6) 5858 (45.0) 123 (57.7) 6270 (52.4) 137 (69.5) 2062 (58.0) ROSC 20 min 74 (61.7) 5185 (62.0) 157 (44.9) 4997 (38.4) 108 (50.7) 5135 (42.9) 120 (60.9) 1866 (52.5) Survival to discharge 35 (29.2) 3013 (36.0) 78 (22.3) 1379 (10.6) 57 (26.8) 1340 (11.2) 66 (33.5) 753 (21.2) Neurological outcome Good 22 (62.9) 2268 (75.3) 43 (55.1) 841 (61.0) 36 (63.2) 834 (62.2) 35 (53.0) 447 (59.4) Poor 1 (2.9) 264 (8.8) 16 (20.5) 243 (17.6) 13 (22.8) 222 (16.6) 11 (16.7) 111 (14.7) Unknown 12 (34.3) 481 (16.0) 19 (24.4) 295 (21.4) 8 (14.0) 284 (21.2) 20 (30.3) 195 (25.9) Abbreviations: PEA, pulseless electrical activity; ROSC, return of spontaneous circulation; VF, ventricular fibrillation; VT, ventricular tachycardia. *First documented pulseless rhythm (VF or pulseless VT, asystole, PEA, and unknown) was defined as the first electrocardiographic rhythm documented at the time the patient became pulseless. Good neurological outcome was prospectively defined as cerebral performance category (CPC) 1 or 2 for adults; the comparable pediatric CPC (PCPC) of 1, 2, or 3 for children on hospital discharge; or no change from baseline CPC or PCPC. Table 5. Comparison of vs Outcomes Among All Patients and Patients in the ICU at the Time of Asystole and PEA VF or Pulseless VT Overall No. of Patients/Total (%) No. of Patients/Total (%) No. of Patients/Total (%) Outcomes OR (95% CI) OR (95% CI) OR (95% CI) All Patients* ROSC 20 min 265/563 (47) / (41) 1.27 ( ) 74/120 (62) 5185/8361 (62) 0.97 ( ) 459/880 (52) / (47) 1.32 ( ) 24-Hour survival 178/563 (32) 5704/ (23) 1.62 ( ) 57/120 (48) 3959/8361 (47) 1.03 ( ) 317/880 (36) / (30) 1.57 ( ) Survival to 135/563 (24) 2719/ (11) 2.73 ( ) 35/120 (29) 3013/8361 (36) 0.83 ( ) 236/880 (27) 6485/ (18) 2.29 ( ) hospital discharge Patients in the ICU ROSC 20 min 171/346 (49) 4947/ (43) 1.29 ( ) 58/94 (62) 2451/3903 (63) 0.95 ( ) 301/570 (53) 8059/ (48) 1.09 ( ) 24-Hour survival 125/346 (36) 2417/ (21) 2.12 ( ) 47/94 (50) 1825/3903 (47) 1.14 ( ) 226/570 (40) 4619/ (28) 1.70 ( ) Survival to hospital discharge 81/346 (23) 1128/ (10) 2.80 ( ) 28/94 (30) 1247/3903 (32) 0.90 ( ) 141/570 (25) 2570/ (15) 1.80 ( ) Abbreviations: CI, confidence interval; ICU, intensive care unit; OR, odds ratio; PEA, pulseless electrical activity; ROSC, return of spontaneous circulation; VF, ventricular fibrillation; VT, ventricular tachycardia. *Odds ratios and 95% CIs are based on multivariable logistic regression controlled for preexisting conditions, renal dysfunction, prematurity ( 37 weeks gestation), myocardial ischemia, ICU location of arrest, and monitored status. For the overall group, the multivariable logistic regression also controlled for initial rhythm (asystole and PEA vs VF or pulseless VT). Odds ratios and 95% CIs are based on multivariable logistic regression controlled for initial rhythm, preexisting illness, renal dysfunction, prematurity, myocardial ischemia, and monitored status American Medical Association. All rights reserved. (Reprinted) JAMA, January 4, 2006 Vol 295, No. 1 55

7 The better survival outcomes observed in children could be due to differences in patient characteristics, prearrest conditions, earlier recognition and treatment of the cardiac arrest, interventions during CPR, and postresuscitation care. Children were monitored in an intensive care unit before the arrest more frequently than adults, perhaps because of the increased emphasis on early recognition and treatment of respiratory failure and shock in pediatric advanced life-support resuscitation training. Recent inhospital adult studies also indicate that earlier recognition and treatment of respiratory failure and shock can result in better outcomes. 22,23 Asphyxia and circulatory shock often result in bradycardia, hypotension, or both before progressing to pulseless cardiac arrest. One marker of aggressive early intervention is the provision of chest compressions before pulselessness. Ninety-eight percent of the adults treated with chest compressions were pulseless, whereas 18% of the children treated with chest compressions were at the earlier stage of bradycardia with pulses prior to becoming pulseless. These data suggest that an early aggressive approach to pediatric resuscitation may have contributed to the better outcomes. These issues may have important implications for training personnel involved with inhospital resuscitation efforts. To our knowledge, the NRCPR data provide the largest reported prospective cohort of pediatric in-hospital cardiac arrests and resuscitation. The previous largest report of pediatric inhospital CPR included only 129 patients from a single institution. 20 Previously published rates of survival to hospital discharge after pediatric cardiac arrests are 2% to 10% in most outof-hospital studies and 10% to 18% in most in-hospital studies. 2,3,13,20,21 Compared with imminent death, pediatric CPR was effective in our study and in the 2 previously published Utsteinstyle studies of pediatric in-hospital CPR (approximately 67% of the children had a return of a sustained circulation and approximately 50% of them were still alive 24 hours postresuscitation). 20,21 However, the rate of survival to hospital discharge following pulseless cardiac arrest in our study (27%) is substantially higher compared with those previous studies (16% and 18%, respectively). 20,21 The better postresuscitation outcomes are especially impressive because these 2 previous single-center studies reported all children who received CPR, including many for bradycardia with palpable pulses. It is not clear whether the better longer-term survival after initially successful resuscitation in our study is due to differences in patient population characteristics, resuscitation performance, reporting bias, or improvements in patient care during the postresuscitation phase (eg, better hemodynamic support, avoidance of postresuscitation hyperthermia). A rate of survival to hospital discharge of 18% in the adults is similar to that previously described in the first adults from this registry. 8 Similarly, other relatively recent series of adult in-hospital cardiac arrests reveal hospital discharge rates of 13%, 24 15%, 25 15%, 26 and 17%. 27 As with all multicenter registries, analysis of the data may be limited by data integrity and validation issues at multiple sites. The rigorous abstractor certification process, uniform data collection, consistent definitions, scientific advisory board reabstraction process, and large sample size were intended to minimize these sources of bias. Importantly, the data reabstraction results serve to verify the integrity of the data. Another potential limitation of our study was sampling bias. The patients reported represent consecutive, sequential data submission from volunteer centers. These centers comprise approximately 10% of all hospitals in the United States but are a voluntary, convenience sample of hospitals. Therefore, the quality of care and outcomes may be different than in other institutions. Nevertheless, the patient characteristics are generally similar to most previous studies. In addition, adult outcome data are similar to previously reported investigations. Although the pediatric survival to hospital discharge data are better than most previous pediatric studies, initial return of spontaneous circulation and 24-hour survival rates are remarkably similar to previous data. The final neurological outcome was determined at hospital discharge with no long-term neurocognitive follow-up. However, previous studies indicate that neurological status at discharge is not substantially different from status at 6 months and 1 year postarrest. 5,20,28,29 These findings have implications for in-hospital care. Physicians and other hospital personnel involved with inpatient resuscitations should recognize that most pediatric and adult in-hospital pulseless cardiac arrests are due to progressive respiratory failure and shock. Additional adult focus for Advanced Cardiac Life Support training should be directed to rapid recognition and treatment of respiratory failure and shock. physicians and other hospital personnel should have heightened sensitivity and training to recognize and treat shockable rhythms. In-hospital resuscitation from the common rhythms of asystole and PEA can result in good outcomes. In conclusion, in this large, multicenter cardiac arrest registry, children survived to hospital discharge more frequently following in-hospital cardiac arrest than adults did, predominantly because of better outcomes following asystole and PEA. Initial shockable rhythms (VF or pulseless VT) in cardiac arrest were more common among adults than among children, although shockable rhythms were more prevalent among children than expected. Most in-hospital cardiac arrests in adults and children were due to preexisting conditions, progressive respiratory failure, or shock and not due to sudden cardiac arrhythmia. These data suggest that resuscitation training and treatment protocols can be better tailored for in-hospital cardiac arrests. 56 JAMA, January 4, 2006 Vol 295, No. 1 (Reprinted) 2006 American Medical Association. All rights reserved.

8 Author Affiliations: Departments of Anesthesia, Critical Care, and s, University of Pennsylvania School of Medicine, Philadelphia (Dr Nadkarni); Departments of Surgery, Emergency Medicine, and Public Health, University of Texas Southwestern Medical Center, Dallas (Dr Larkin); Departments of Emergency and Internal Medicine, Virginia Commonwealth University Health Systems, Richmond (Drs Peberdy and Ornato); Digital Innovation Inc, Forest Hill, Md (Mr Carey); Departments of Surgery and Medicine, Brown University School of Medicine, Providence, RI (Dr Kaye); Undergraduate Nursing Programs (Dr Mancini) and Department of Nursing Education (Ms Lane-Truitt), University of Texas at Arlington, Arlington; University of Washington Harborview Prehospital Research and Training Center, Seattle (Dr Nichol); Emergency Cardiovascular Care, American Heart Association, Dallas, Tex (Dr Potts); and University of Arizona School of Medicine, Tucson (Dr Berg). Author Contributions: Dr Nadkarni had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Nadkarni, Larkin, Peberdy, Kaye, Ornato, Berg. Acquisition of data: Larkin, Peberdy, Carey, Mancini, Truitt, Potts, Berg. Analysis and interpretation of data: Nadkarni, Larkin, Carey, Nichol, Berg. Drafting of the manuscript: Nadkarni, Larkin, Berg. Critical revision of the manuscript for important intellectual content: Nadkarni, Larkin, Peberdy, Carey, Kaye, Mancini, Nichol, Truitt, Potts, Ornato, Berg. Statistical analysis: Nadkarni, Larkin, Carey, Berg. Obtained funding: Potts. Administrative, technical, or material support: Peberdy, Carey, Mancini, Truitt, Berg. Study supervision: Nadkarni, Nichol, Ornato, Berg. Financial Disclosures: Mr Carey performs data management for Digital Innovation Inc. Ms Truitt is a paid clinical consultant for National Registry of Cardiopulmonary Resuscitation (NRCPR), but received no payment for work associated with this article. Dr Potts is the Director of Science for the American Heart Association (AHA) Emergency Cardiovascular Care Programs (a sponsor of NRCPR). No other authors reported financial disclosures. Funding/Support: This study was funded by the Endowed Chair of Critical Care Medicine, The Children s Hospital of Philadelphia, and the Emergency Cardiovascular Care Committee of the AHA. Role of the Sponsors: The Children s Hospital of Philadelphia and the AHA did not influence the design, conduct, management, analysis, or interpretation of the data, or the preparation of the manuscript. The Scientific Advisory Board of the AHA and Endowed Chair of Critical Care Medicine provided review and approval of the manuscript, and the Executive Database Steering Committee of the AHA provided additional peer review of the manuscript. Distribution of Participating Hospitals in the NRCPR: Alaska (n=2), Alabama (n=2), Arkansas (n=6), Arizona (n=6), California (n=27), Colorado (n=5), Connecticut (n=3), Delaware (n=3), Florida (n=25), Georgia (n=7), Hawaii (n=1), Iowa (n=5), Idaho (n=1), Illinois (n=18), Indiana (n=19), Kansas (n=6), Kentucky (n=7), Louisiana (n=14), Massachusetts (n=3), Maryland (n=5), Michigan (n=3), Minnesota (n=3), Missouri (n=4), Mississippi (n=5), Montana (n=5), North Carolina (n=11), North Dakota (n=2), Nebraska (n=4), New Hampshire (n=4), New Jersey (n=5), New Mexico (n=1), New York (n=10), Ohio (n=10), Oklahoma (n=5), Oregon (n=7), Pennsylvania (n=13), South Carolina (n=6), South Dakota (n=2), Tennessee (n=4), Texas (n=13), Utah (n=2), Virginia (n=15), Washington (n=7), Wisconsin (n=9), West Virginia (n=6), Wyoming (n=2), District of Columbia (n=1), and Ontario, Canada (n=2). Acknowledgment: We thank the AHA, Brian Eigel, PhD, Yuling Hong, PhD, both from the AHA, and Mark A. Helfaer, MD, University of Pennsylvania and Children s Hospital of Philadelphia, for scientific review of the manuscript; Michael C. Bell, MBA, from the AHA, for unwavering support of the NRCPR; innumerable staff and data abstractors from NRCPR hospitals for their time and effort; and Terrilynn Honesty, for her secretarial support. No compensation was received from a funding sponsor for any contributions made by these individuals. REFERENCES 1. Sirbaugh PE, Pepe PE, Shook JE, et al. A prospective, population-based study of the demographics, epidemiology, management, and outcome of out-ofhospital pediatric cardiopulmonary arrest. Ann Emerg Med. 1999;33: Young KD, Seidel JS. cardiopulmonary resuscitation: a collective review. Ann Emerg Med. 1999; 33: Young KD, Gausche-Hill M, McClung CD, Lewis RJ. 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