Resuscitation Science. Outcomes After In-Hospital Cardiac Arrest in Children With Cardiac Disease A Report From Get With the Guidelines Resuscitation

Transcription

1 Resuscitation Science Outcomes After In-Hospital Cardiac Arrest in Children With Cardiac Disease A Report From Get With the Guidelines Resuscitation Laura Ortmann, MD; Parthak Prodhan, MBBS; Jeffrey Gossett, MS; Stephen Schexnayder, MD; Robert Berg, MD; Vinay Nadkarni, MD; Adnan Bhutta, MBBS; for the American Heart Association s Get With the Guidelines Resuscitation (formerly National Registry of Cardiopulmonary Resuscitation) Investigators Background Small studies suggest that children experiencing a cardiac arrest after undergoing cardiac surgery have better outcomes than other groups of patients, but the survival outcomes and periarrest variables of cardiac and noncardiac pediatric patients have not been compared. Methods and Results All cardiac arrests in patients 18 years of age were identified from Get With the Guidelines Resuscitation from 2000 to Cardiac arrests occurring in the neonatal intensive care unit were excluded. Of 3323 index cardiac arrests, 19% occurred in surgical-cardiac, 17% in medical-cardiac, and 64% in noncardiac (trauma, surgical-noncardiac, and medical-noncardiac) patients. Survival to hospital discharge was significantly higher in the surgical-cardiac group (37%) compared with the medical-cardiac group (28%; adjusted odds ratio, 1.8; 95% confidence interval, ) and the noncardiac group (23%; adjusted odds ratio, 1.8; 95% confidence interval, ). Those in the cardiac groups were younger and less likely to have preexisting noncardiac organ dysfunction, but were more likely to have ventricular arrhythmias as their first pulseless rhythm, to be monitored and hospitalized in the intensive care unit at the time of cardiac arrest, and to have extracorporeal cardiopulmonary resuscitation compared with those in the noncardiac group. There was no survival advantage for patients in the medical-cardiac group compared with those in the noncardiac group when adjusted for periarrest variables. Conclusion Children with surgical-cardiac disease have significantly better survival to hospital discharge after an in-hospital cardiac arrest compared with children with medical-cardiac disease and noncardiac disease. (Circulation. 2011;124: ) Key Words: cardiac arrest cardiac surgery cardiopulmonary resuscitation pediatrics Children with underlying cardiac disease are at a greater risk of experiencing a cardiac arrest compared with those without a cardiac diagnosis. Although the incidence of cardiac arrest in pediatric intensive care units (ICUs) is 2%, 1 3 a report from a specialized pediatric cardiac ICU found a rate of arrest of 4%. 4 Cardiac surgery confers an even greater risk, with cardiac arrest occurring in 6% of infants in the postoperative period. 5 Clinical Perspective on p 2337 Survival after an in-hospital cardiac arrest is poor, with only a quarter of pediatric patients surviving to hospital discharge. 6 No large outcome studies specific to pediatric cardiac patients exist, although survival to hospital discharge in smaller series varies between 19% and 42%. 4,5,7 This wide variability in outcomes is typical of single-institution studies because different centers have various levels of acuity and there are differences in definitions used and data collection methods. The American Heart Association s Get With the Guidelines Resuscitation (GWTG-R) (formerly the National Registry of Cardiopulmonary Resuscitation) is a large multicenter database of in-hospital cardiac arrests with standardized definitions and data reporting methodology. 8 The purpose of this study was to use GWTG-R data to evaluate outcomes after in-hospital cardiac arrest in children with cardiac disease and to study factors associated with survival to hospital discharge. We hypothesize that children who have undergone cardiac surgery during the same admission as their cardiac arrest have better outcomes after in-hospital cardiac arrest Received December 29, 2010; accepted September 16, From the Department of Pediatrics, Section of Critical Care (L.O., P.P., S.S., A.B.) and Department of Pediatrics, Section of Cardiology (P.P., J.G., A.B.), University of Arkansas for Medical Sciences, Arkansas Children s Hospital, Little Rock, and Department of Anesthesia and Critical Care, University of Pennsylvania School of Medicine, Children s Hospital of Philadelphia, Philadelphia (R.B., V.N.). Correspondence to Laura Ortmann, MD, Children s Mercy Hospitals and Clinics, 2401 Gillham Rd, Kansas City, MO lort8112@yahoo.com 2011 American Heart Association, Inc. Circulation is available at DOI: /CIRCULATIONAHA

2 2330 Circulation November 22, 2011 compared with children with medical-cardiac disease and those with noncardiac disease. Methods Design and Setting GWTG-R is sponsored by the American Heart Association and is the only national registry of in-hospital resuscitation events. The primary purpose of GWTG-R is quality improvement, and all data are deidentified in compliance with the Health Insurance Portability and Accountability Act. Participating hospitals are not required to obtain Institutional Review Board approval, although this study was approved by the Institutional Review Board of the University of Arkansas for Medical Sciences. GWTG-R uses a standardized form to report patient characteristics and conditions, details of the resuscitation event, processes of care, and outcomes. All adult patients, pediatric patients, employees, and visitors who have a resuscitation event in a hospital facility are eligible for inclusion in the registry. There are 6 categories of data collected: (1) facility data, (2) patient demographic data, (3) pre-event data, (4) event data, (5) outcome data, and (6) quality improvement data. Explicit definitions have been generated for every data element. The registry is based on the Utstein-style template, which was developed to help standardize the collection and review of resuscitation data. 9 The GWTG-R process for data collection and integrity has been described in detail previously. 6,10,11 Inclusion and Exclusion Criteria All children 18 years of age having an in-hospital cardiac arrest were eligible for inclusion in this study. Cardiac arrest was defined as the cessation of cardiac mechanical activity with the absence of palpable central pulse, apnea, and unresponsiveness. Subjects were excluded if resuscitation began outside a hospital, involved a newborn in the delivery room, occurred in the neonatal ICU, involved an obstetrics patient, or was limited to a shock by an implanted defibrillator or if the cardiac arrest was in an inpatient with a do not resuscitate order. For patients having multiple qualifying events during a single admission, only the first pulseless cardiac arrest (index event) was included in the analysis. All patients included in the registry are categorized into 1 of 8 illness categories by the reporting hospital: medical-cardiac, medical-noncardiac, surgical-cardiac, surgical-noncardiac, newborn, obstetric, trauma, and other (visitor/employee). Newborn, obstetric, and other were excluded. All medical-noncardiac, surgicalnoncardiac, and trauma patients were included in the noncardiac group for this study. Surgical-cardiac patients are defined as patients who are postoperative from cardiac surgery occurring during the same hospital admission as the cardiac arrest. Medical-cardiac patients are defined as patients whose primary diagnosis is a medical illness that is cardiovascular in origin. This group includes patients who are admitted for congenital heart disease but are not postoperative at the time of their cardiac arrest. Medical-noncardiac patients are defined as patients with a primary diagnosis of medical illness at the time of the event that is not cardiovascular. Surgical-noncardiac patients are defined as patients who are preoperative or postoperative with a surgical illness as the primary diagnosis that is not cardiac surgery at the time of the event. The last 2 groups include patients with underlying cardiac disease who are admitted for noncardiac medical or surgical illnesses. Outcomes Primary outcome was survival to hospital discharge. Secondary outcome measures included return of circulation with no need for chest compressions for 20 minutes, 24-hour survival, and neurological outcome. Patients whose resuscitation ended after being placed on cardiopulmonary bypass or extracorporeal cardiopulmonary resuscitation (ECPR) were considered to have return of circulation according to GWTG-R definition. Neurological outcome was assessed at discharge with the Pediatric Cerebral Performance Category scale, 11 which divides outcome into the following 6 categories: (1) normal age-appropriate neurodevelopmental function, (2) mild disability, (3) moderate disability, (4) severe disability, (5) coma or vegetative state, and (6) brain death. Good neurological outcome was defined as a score of 1, 2, or 3 or no change from admission Pediatric Cerebral Performance Category. Statistical Analysis Select hospital characteristics, patient demographic data, prearrest data, and resuscitation characteristics were compared between surgical-cardiac, medical-cardiac, and noncardiac disease groups. The 2 test or Fisher exact test was used to analyze associations between disease groups and categorical variables, depending on the sparseness of the data. For continuous variables, the Kruskal-Wallis test was used. Wilcoxon rank-sum tests were used to make comparisons between pairs of disease categories. A Bonferroni correction was made to the P values to adjust for the 3 group comparisons made for each characteristic. All P values are 2 sided; the significance level was set at Multivariable logistic regression models were used to examine the association of independent variables on survival to hospital discharge. Factors were separated into prearrest and arrest factors, and separate models were fit to each type within each disease group. A complete list of variables can be found in Tables 1 and 2. Backward variable selection was used to eliminate prearrest or postarrest factors not significant at P 0.5 with era and hospital characteristics forced into the model. Variables missing 20% of the values were excluded. A linear time effect was included in each model to adjust for changes in survival over time. Duration of cardiopulmonary resuscitation (CPR) event was parameterized with a log transformation. A log base 2 was used so that the interpretation of the odds ratios for CPR duration is such that for each doubling of CPR duration, the odds of death in the hospital decrease by the estimate of the odds ratio. Model performance was assessed by the area under the receiver-operator characteristic curve (discrimination) and the Hosmer-Lemeshow goodness-of-fit statistic (calibration). Statistical analyses were performed with Stata 11.0 MP-Parallel Edition (Stata- Corp LP, College Station, TX). Odds of survival to hospital discharge were adjusted for all variables retained in multivariable analysis. To validate multivariate results, missing values were imputed and models were rerun with the Harrell method with the rms package in r software ( Results From January 2000 to August 2008, 3323 index pulseless pediatric in-hospital cardiac arrests were documented among the illness categories of interest at 265 institutions. Of these, 640 (19%) were classified as surgical-cardiac, 574 (17%) as medical-cardiac, and 2109 (64%) as noncardiac. The prearrest and arrest characteristics of the 3 groups are presented in Tables 1 and 2, respectively. Patients in the cardiac groups were significantly younger than those in the noncardiac group, with surgical-cardiac patients being younger than medical-cardiac patients. Cardiac arrests among the surgical-cardiac patients were more likely to occur in an ICU setting. The cardiac groups had less preexisting organ dysfunction, including fewer central nervous system abnormalities, less hepatic insufficiency, less diabetes mellitus, less trauma, less malignancy, fewer metabolic abnormalities, and less sepsis. Renal insufficiency was not different among groups. As would be expected, both cardiac groups had higher rates of preexisting arrhythmias and congestive heart failure. Patients in the surgical-cardiac group had more intensive monitoring and more interventions before arrest compared with those in the medical-cardiac and noncardiac groups. They were also more likely to have vascular access in place,

3 Ortmann et al Cardiac Arrest in Children With Cardiac Disease 2331 Table 1. Prearrest and Hospital Characteristics Table 1. Continued Surgical-Cardiac Group (n 640), Medical-Cardiac Group (n 574), Noncardiac Group (n 2109), Age 0 28 d 48 (308) 18 (104)* 12 (257)* 29 d 12 mo 28 (176) 32 (182) 24 (496) 12 mo 8 y 15 (93) 25 (146) 27 (578) 8y 18 y 10 (62) 19 (111) 34 (707) Male sex 56 (357) 52 (299) 57 (1202) Event location Intensive care unit 86 (553) 64 (370)* 63 (1331)* Emergency 0 (2) 18 (105) 17 (365) department Other (wards, 13 (85) 17 (99) 20 (413) diagnostic areas) Weekend 26 (165) 33 (188) 32 (682) Night 30 (192) 30 (172) 30 (639) Preexisting conditions Arrhythmia 34 (211) 35 (190) 18 (355)* Central nervous 7 (42) 15 (84)* 34 (654)* system dysfunction Congestive heart failure this or previous admission 54 (335) 49 (266) 6 (124)* Diabetes mellitus 0 (1) 3 (15)* 2 (40) Hepatic insufficiency 4 (22) 3 (18) 7 (136) Hypotension/ 55 (339) 35 (193)* 38 (738)* hypoperfusion Major trauma 0 (2) 1 (5) 19 (360)* Malignancy 0 (2) 2 (9) 8 (153)* Metabolic or electrolyte abnormality 17 (107) 17 (94) 22 (428) Myocardial ischemia this or previous admission 3 (20) 7 (36) 1 (18)* Pneumonia 4 (22) 8 (45) 12 (229)* Renal insufficiency 9 (59) 11 (59) 12 (239) Respiratory 59 (369) 56 (305) 61 (1191) insufficiency Septicemia 9 (56) 12 (66) 18 (348)* Interventions in place at time of arrest Antiarrhythmic 7 (47) 8 (43) 1 (28)* infusions# Arterial line 53 (337) 23 (132)* 23 (487)* Dialysis# 5 (33) 1 (4)* 4 (72) ECG monitor 97 (621) 84 (485)* 84 (1779)* Mechanical 74 (473) 53 (307)* 63 (1338)* ventilation Pacemaker 21 (137) 6 (35)* 1 (13)* Vascular access 96 (612) 85 (489)* 88 (1854)* Vasoactive infusions# 60 (381) 35 (201)* 33 (670)* (Continued) Surgical-Cardiac Group (n 640), Medical-Cardiac Group (n 574), Noncardiac Group (n 2109), Hospital characteristics Children s hospital 56 (334) 43 (228)* 43 (839)* Facility beds, n (191) 29 (182) 26 (511) (183) 42 (223) 43 (849) (235) 30 (159) 31 (606) Pediatric intensive care unit beds, n 0 2 (11) 18 (89) 16 (303)* 10 2 (13) 9 (47) 11 (202) (131) 20 (101) 24 (438) (397) 52 (258) 49 (917) Teaching hospital 73 (443) 62 (331)* 61 (1206)* Immediate factors related to event** Acute respiratory 38 (240) 46 (264) 53 (1073)* insufficiency Arrhythmia 54 (343) 61 (349) 46 (940) Hypotension or 63 (400) 52 (298)* 53 (1086)* hypoperfusion Airway compromise 5 (33) 5 (21) 9 (183) Metabolic or electrolyte abnormality 11 (68) 12 (66) 18 (368)* Night is defined as 11 PM to 6:59 AM. Weekend was defined as 11 PM Friday to 6:59 AM Monday. Central nervous system dysfunction includes the variables depression in central nervous system function and acute nonstroke central nervous system event. A Bonferroni adjustment was made to P values to adjust for multiple comparisons. *P vs surgical-cardiac group. P vs medical-cardiac group. P 0.05 vs surgical-cardiac group. P 0.05 vs medical-cardiac group. Data collected from 3108 patients. #Data collected from 3247 patients. **Data collected from 3245 patients. an arterial catheter, ECG monitoring, mechanical ventilation, and pacemakers and to be receiving vasoactive infusions compared with the other groups. Cardiac arrests among patients in the surgical and medicalcardiac groups were more likely to be the result of arrhythmias or hypotension, whereas those in the noncardiac group were more likely to be precipitated by respiratory difficulties. Patients in both the surgical-cardiac and medical-cardiac groups were significantly more likely to have ventricular arrhythmias as their first observed pulseless rhythm; CPR duration was significantly longer and extracorporeal support was used more often compared with the noncardiac group. Outcomes are presented in Table 3. Survival to hospital discharge was 37% in the surgical-cardiac group compared with 28% in the medical-cardiac group (adjusted odds ratio, 1.8; 95% confidence interval, ; P 0.001) and 23% in

4 2332 Circulation November 22, 2011 Table 2. Arrest Characteristics Table 3. Primary and Secondary Outcomes Surgical-Cardiac Group (n 640), Medical-Cardiac Group (n 574), Noncardiac (n 2109), First pulseless rhythm Asystole 24 (156) 37 (210)* 43 (911)* Pulseless electrical activity 42 (266) 29 (169) 31 (647) Ventricular 12 (76) 12 (68) 6 (125) fibrillation Ventricular 6 (38) 7 (42) 4 (91) tachycardia CPR duration, min Mean * Interquartile range Epinephrine doses 0 14 (79) 18 (87) 14 (257) (158) 26 (124) 32 (585) (108) 25 (123) 25 (451) 5 37 (204) 31 (152) 29 (535) Pharmacological interventions Alkalinizing agents (sodium bicarbonate, THAM) 70 (448) 64 (370) 59 (1245)* Atropine 30 (190) 42 (242)* 45 (942)* Calcium 64 (409) 47 (271)* 41 (874)* Epinephrine 88 (560) 86 (491) 87 (1845) Vasopressin 6 (31) 4 (18) 6 (102) ECPR# 19 (117) 6 (34)* 2 (34)* Pacemaker# 22 (136) 10 (55)* 3 (66)* CPR indicates cardiopulmonary resuscitation; THAM, tris-hydroxymethyl amino-methane; and ECPR, extracorporeal pulmonary resuscitation. A Bonferroni adjustment was made to P values to adjust for multiple comparisons. *P vs surgical-cardiac group. P vs medical-cardiac group. P 0.05 vs medical-cardiac group. Data collected from 2863 patients. Data collected from 3321 patients. Data collected from 2857 patients. #Data collected from 3275 patients. the noncardiac group (adjusted odds ratio, 1.8; 95% confidence interval, ; P 0.001). Surgical-cardiac patients were more likely to have return of circulation and to be alive after 24 hours after CPR. There was no difference in return of circulation between the medical-cardiac and noncardiac groups (53%); however, the medical-cardiac group was more likely to be discharged alive (P 0.022). After adjustment for other variables associated with outcome, there was no survival advantage for medical-cardiac patients compared with noncardiac patients. There was no difference in neurological outcome among survivors among the 3 groups. Year of arrest did not affect outcome in any group. Surgical-Cardiac Group (n 640), Medical-Cardiac Group (n 574), Noncardiac Group (n 2109), Return of 67 (427) 53 (306)* 53 (1109)* circulation Survived 24 h 60 (382) 42 (238)* 37 (770)* Survived to 37 (234) 28 (159)* 23 (489)* discharge Good neurological outcome among survivors 77 (180) 72 (115) 70 (347) Return of circulation indicates no need for chest compressions for 20 minutes. Patients whose resuscitation ended after being placed on cardiopulmonary bypass or extracorporeal membranous oxygenation were considered to have return of circulation. A Bonferroni adjustment was made to P to adjust for multiple comparisons. *P vs surgical-cardiac group. P 0.05 vs medical-cardiac group. A total of 626 patients (19%) had multiple cardiac arrests during their hospital admission. There was no difference between the 3 groups in likelihood of multiple events. Survival to hospital discharge after 1 cardiac arrest was 29% for the surgical-cardiac group, 20% for the medicalcardiac group, and 17% for the noncardiac group. Two separate multivariate logistic regression models were developed for each disease group: 1 to evaluate prearrest variables and 1 to evaluate arrest variables. The multivariate models for the surgical-cardiac and medical-cardiac groups are shown in Table 4 (prearrest variables) and Table 5 (arrest variables). For the surgical-cardiac group, preexisting renal insufficiency, congestive heart failure, 300 facility beds, arrest in a teaching hospital, and CPR duration were associated with decreased odds of survival. ECPR and age 28 days were associated with improved survival in multivariate analysis. For the medical-cardiac group, a cardiac arrest occurring in the emergency department rather than the ICU, metabolic or electrotype abnormalities as the cause of the arrest, use of atropine during CPR, and CPR duration were associated with decreased odds of survival. Airway compromise as the immediate cause of the cardiac arrest, preexisting arrhythmia, and ECPR significantly improved the odds of survival in the medical-cardiac group. Results for these models negligibly changed when validated with the Harrell method. Discussion Our analysis of this large multicenter database found significantly improved hospital survival after resuscitation from an in-hospital cardiac arrest in children who have undergone cardiac surgery compared with children without cardiac disease. Among the cardiac patients, the survival to hospital discharge of surgical-cardiac patients was significantly higher compared with patients with medical-cardiac disease. Better outcomes in this patient population may be related to multiple prearrest and postarrest characteristics.

5 Ortmann et al Cardiac Arrest in Children With Cardiac Disease 2333 Table 4. Multivariable Prearrest Predictors of Survival to Discharge for Surgical-Cardiac and Medical-Cardiac Groups: Within-Group Analysis Surgical-Cardiac Group Medical-Cardiac Group Prearrest Variable Adjusted OR (95% CI) P Adjusted OR (95% CI) P Age 28 d 1.0 (Reference) * 29 d 1 y 2.7 ( ) * 1y 8 y 2.6 ( ) * 8y 18 y 2.1 (1 4.3) 0.05 * Female * 1.2 (0.8 2) 0.43 Time interval from January 1, 2000, 1 ( ) ( ) 0.82 to event Arrest in ED (reference ICU) NE 0.3 ( ) Arrest is other non-ed/icu location 0.7 ( ) ( ) 0.76 (reference ICU) Day/evening (reference night) 1.5 ( ) * Preexisting conditions Acute stroke 0.3 ( ) 0.27 NE Arrhythmia 0.7 ( ) ( ) Diabetes mellitus NE * Hepatic insufficiency 0.4 (0.07 2) (0.07 2) 0.25 Hypotension/hypoperfusion * * Major trauma * 9.4 ( ) Malignancy NE NE Metabolic/electrolyte abnormality 0.6 ( ) ( ) 0.4 Myocardial ischemia 0.4 ( ) ( ) 0.36 Pneumonia NE * Renal insufficiency 0.1 ( ) * Respiratory insufficiency * * Septicemia 0.7 ( ) ( ) 0.24 Interventions in place at time of event Antiarrhythmic infusion 1.9 ( ) * Arterial line 1.3 (0.8 2) ( ) 0.45 Dialysis 0.7 ( ) (0.2 54) 0.36 ECG monitoring 0.3 ( ) * Mechanical ventilation * 0.7 ( ) 0.15 Pacemaker 1.3 ( ) 0.34 * Vascular access 0.5 ( ) 0.12 * Vasoactive infusions * 0.6 ( ) Immediate cause of arrest Acute pulmonary edema * 0.3 ( ) 0.19 Acute respiratory insufficiency 0.7 ( ) ( ) 0.28 Airway compromise * 8 (2.5 26) Central nervous system dysfunction * * Congestive heart failure 0.5 ( ) * Hypotension/hypoperfusion 0.7 ( ) ( ) 0.38 Metabolic/electrolyte abnormality 0.6 ( ) ( ) Facility beds, n ( ) ( ) (Reference) 1.0 (Reference) ( ) ( ) 0.6 (Continued)

6 2334 Circulation November 22, 2011 Table 4. Continued Surgical-Cardiac Group Medical-Cardiac Group Prearrest Variable Adjusted OR (95% CI) P Adjusted OR (95% CI) P Beds in pediatric ICU, n ( ) ( ) ( ) ( ) ( ) ( ) (Reference) 1.0 (Reference) Children s hospital 1.8 ( ) ( ) 0.35 Teaching hospital 0.7 ( ) ( ) 0.35 OR indicates odds ratio; CI, confidence interval; ED, emergency department; ICU, intensive care unit; and NE, variables dropped because of nonestimability secondary to low incidence. Central nervous system dysfunction includes variables depression in central nervous system function and acute nonstroke central nervous system event. The prearrest variables of continuous prostaglandins, acute pneumothorax, acute stroke, status epileptics, cause of malfunction of an assisted ventricular device, cardiac malformation acyanotic, cardiac malformation cyanotic, and congenital malformation/abnormality had excessive missing values and were not considered in multivariable modeling. *Predictor was not significant in backward selection with 0.5. These data confirm the findings of previous singleinstitution studies that have reported survival among pediatric postoperative cardiac patients after cardiac arrest requiring CPR to be as high as 42%. 4,5 This is in contrast to more dismal (22% to 27%) survival after cardiac arrest among more heterogeneous pediatric populations. 6,10 These reports are limited by their retrospective study design and small sample size ( 100 subjects). 4,5,7 GWTG-R size and use of standardized definitions and reporting improve on many of the limitations of these studies. Our study highlights the characteristics unique to the cardiac population that may influence their post cardiac arrest survival. In contrast to noncardiac patients, patients with cardiac disease were younger, had fewer preexisting conditions, and had increased monitoring and interventions at the time of cardiac arrest. Factors precipitating cardiac arrest and the type of cardiac rhythm present at the onset of the arrest in these patients are different from those found in noncardiac patients. Furthermore, resuscitative measures like the deployment of extracorporeal support are also far more likely to occur among cardiac patients. Age Among the prearrest variables, the patient s age in particular may have important clinical implications on survival. In the surgical-cardiac group, more than three quarters of cardiac arrests occurred in infants 1 year of age compared with one half among the medical-cardiac patients and one third among the noncardiac patients. Among surgical-cardiac patients, neonates ( 28 days of age) had worse survival to hospital discharge compared with older infants. Infants undergo more complex cardiac surgeries and thus are at a greater risk of postoperative cardiac arrest and mortality. 7 These results are similar to those found by Meaney et al, 10 who analyzed pediatric ICU arrests reported to GWTG-R and found that newborns ( 1 month of age) had a lower hospital survival compared with infants (1 month 1 year of age), but both groups had significantly better survival compared with older children ( 1 year of age). They speculated that infants have better hemodynamics and perfusion during CPR as a result of their more compliant chest walls. Newborns and infants differ from older children in many other characteristics, and GWTG-R does not collect hemodynamic data, so it is not possible to assess other causes that may explain the differences in survival among age groups from this database. Preexisting Conditions Differences in the types of preexisting medical conditions may also have contributed to differences in hospital survival. For example, a history of trauma and malignancy, seen in 19% and 8% of noncardiac patients, respectively, are known to negatively affect survival, 3 but are rare in patients with cardiac disease and thus have negligible impact on their overall survival. Furthermore, as indicated by our study, children requiring cardiac surgery are less likely to have multiple organ dysfunction and had lower rates of preexisting central nervous system dysfunction, liver dysfunction, diabetes mellitus, and sepsis. In a review of all pediatric ICU arrests, de Mos et al 1 found that the number of dysfunctional organs before arrest was associated with hospital mortality. Monitoring Not surprisingly, surgical-cardiac patients had a greater number of interventions in place before their arrest, including venous and arterial access, mechanical ventilation, and cardiac monitoring, which may improve survival. Previous reports indicate that patients who have a cardiac arrest in a monitored setting or an arrest that is witnessed have improved survival. 12 It is possible that early detection of life-threatening arrhythmias or hypotension secondary to enhanced monitoring may have improved outcomes despite a longer duration of CPR in cardiac patients. Rhythm Differences between the groups in the type of first observed pulseless rhythm before onset of CPR may also have contributed to the variation in survival. Pulseless electric activity was the most common rhythm among the surgical-cardiac

7 Ortmann et al Cardiac Arrest in Children With Cardiac Disease 2335 Table 5. Multivariable Arrest Predictors of Survival to Discharge for Surgical-Cardiac and Medical-Cardiac Groups: Within-Group Analysis Surgical-Cardiac Group Medical-Cardiac Group Arrest Variables Adjusted OR (95% CI) P Adjusted OR (95% CI) P Time from January 1, 2000, to event 1.1 ( ) ( ) 0.25 Facility beds, n ( ) ( ) (Reference) 1.0 (Reference) ( ) ( ) 0.8 Beds in pediatric ICU, n (0.07 9) ( ) ( ) ( ) ( ) ( ) (Reference) 1.0 (Reference) Children s hospital 0.7 (0.2 3) (0.4 5) 0.65 Teaching hospital 0.3 ( ) (0.4 2) 0.74 First pulseless rhythm Asystole 1.0 (Reference) 1.0 (Reference) Pulseless electrical activity 1.5 ( ) ( ) 0.46 Ventricular tachycardia or fibrillation 1.6 ( ) ( ) 0.12 Pharmacological interventions Antiarrhythmic 1.4 ( ) 0.32 * Atropine * 0.4 ( ) Calcium bolus 0.7 ( ) 0.2 * Fluid bolus 1.2 ( ) 0.44 * Sodium bicarbonate/tham 0.6 ( ) (0.3 1) Vasopressin bolus * 0.6 ( ) 0.49 Vasopressor bolus (excluding * 0.7 ( ) 0.25 epinephrine and vasopressin) CPR duration log2 0.6 ( ) ( ) ECPR 2.5 ( ) ( ) Pacemaker * 2.1 ( ) 0.65 OR indicates odds ratio; CI, confidence interval; ICU, intensive care unit; THAM, tris-hydroxymethyl amino-methane; CPR, cardiopulmonary resuscitation; and ECPR, extracorporeal pulmonary resuscitation. *Predictor was not significant in backward selection with 0.5. With each doubling of CPR duration, the odds of surviving to discharge are attenuated by a factor of the OR. Therapeutic hypothermia was excluded owing to excessive missing data. group, whereas asystole was more common among the medical-cardiac and noncardiac groups. Children with pulseless electric activity as the first observed pulseless rhythm have been found to have better survival compared with those with asystole. 6 Some patients with pulseless electric activity may in fact have some pulsatile blood flow despite having no palpable pulses, which may result in better outcomes than seen with asystole and complete absence of flow. Children in the surgical-cardiac and medical-cardiac groups were more likely to have pulseless ventricular rhythms than those in the noncardiac group. The association between ventricular arrhythmias and improved survival is well documented in adults, 13 and similar findings have been published in children. 6,14 This improved survival is most likely related in part to these rhythms being more amenable to electric conversion. These data suggest that even though shockable rhythms are much less common among pediatric patients, early analysis of rhythm is important in pediatric CPR to identify patients who may benefit from timely defibrillation that could affect survival. Extracorporeal Cardiopulmonary Resuscitation In this study, we found that the use of ECPR was associated with improved survival in both cardiac groups. Prolonged duration of CPR is associated with dismal outcomes, and resuscitation beyond 30 minutes has been considered futile in the recent past. 15 However, with the availability of rapid deployment of extracorporeal support during CPR, survival with intact neurological function has been reported even with prolonged CPR durations. 16,17 A recent report from GWTG-R found that children with cardiac disease were more likely to survive to hospital discharge compared with children without cardiac disease when ECPR was used. 18 The improved survival in patients with cardiac disease may be explained in

8 2336 Circulation November 22, 2011 part by the fact that these patients are more likely to be cared for at specialized centers with more intensive monitoring and the ability to deploy ECPR effectively. Limitations The limitations of our study are similar to those seen in all studies using large multicenter databases. Analysis of the data may be limited by data integrity and validation issues at the multiple sites submitting data to the registry. The rigorous abstractor training and certification process, uniform data collection, consistent definitions, scientific advisory board reabstraction process, and large sample size, unique to GWTG-R, are intended to minimize these sources of study bias. Participation in GWTG-R is voluntary; nearly 15% of the hospitals in the United States are represented in this database. It is possible that outcomes may be different at nonparticipating institutions, and this report does not reflect outcomes in those institutions. Much of these data were collected before the 2005 release of new American Heart Association CPR guidelines, 19 which emphasized the quality of chest compressions; recent studies have suggested improved outcomes with the implementation of these guidelines. 20,21 Another limitation is related to the heterogeneity of clinical diagnoses that constitute the 3 illness categories studied. The surgical-cardiac group includes patients undergoing simple repairs who do not require cardiopulmonary bypass and neonates undergoing palliation of complex congenital heart defects. Survival between these groups may be vastly different. 22,23 Differences in diagnosis may confound our analysis of facility data because more complex surgical patients will likely be cared for in children s hospitals and teaching hospitals that also have ECPR capabilities. GWTG-R is limited in this regard in that it does not provide specific information about diagnosis, so differences between cardiac subgroups cannot be elicited from this database. Data on individual institution use of ECPR were not available. GWTG-R does not collect data on whether patients later go on to require heart transplantation after ECPR, which may influence outcomes for cardiac patients. In addition, it is possible that children who are distant from surgery but are still hospitalized could be classified into either the medical or surgical-cardiac illness categories, confounding the analysis. Neonates with cardiac disease who were managed in the neonatal ICU are not included in this study because their resuscitation data were initially excluded by GWTG-R. Excluding these infants may bias our results because the youngest patients had lower odds of survival. Furthermore, other variables beyond those collected as part of the registry such as patient physiological and laboratory data may affect outcomes. Models selected by stepwise selection methods tend to be suboptimal because important predictors may not be included, and regression coefficients and their SEs and P values may be biased toward more extreme values. We used backward selection with an of 0.50 to reduce the number of covariates in the model. With the choice of a high (0.50), the bias should be minimal. Conclusions Children with surgical cardiac disease have significantly better survival after in-hospital cardiac arrest compared with those in other categories of illness. Multiple variables may contribute to differences in outcomes. Intensive monitoring of at-risk populations that allows early detection of pulseless rhythms and the institution of aggressive support modalities may contribute to improved outcome in pediatric cardiac patients. Acknowledgments The American Heart Association GWTG-R Investigators include Mary E. Mancini, Robert A. Berg, Emilie Allen, Elizabeth A. Hunt, Vinay M. Nadkarni, Joseph P. Ornato, R. Scott Braithwaite, Graham Nichol, Kathy Duncan, Tanya L. Truitt, Brian Eigel, Peter C. Laussen, Frank W. Moler, Marilyn Morris, and Chris Parshuram. Disclosures Dr Schexnayder is a compensated associate senior science editor for the American Heart Association Emergency Cardiac Care program. The other authors report no conflicts. References 1. De Mos N, Van Litsenberg RLR, McCrindle B, Bohn DJ, Parshuram CS. Pediatric in-intensive-care-unit arrest: incidence, survival and predictive factors. Crit Care Med. 2006;34: Tibballs J, Kinney S. A prospective study of outcome of in-patient paediatric cardiopulmonary arrest. Resuscitation. 2006;71: Slonim A, Patel K, Ruttimann U, Pollack M. Cardiopulmonary resuscitation in pediatric intensive care units. Crit Care Med. 1997;25: Parra DA, Totapally BR, Zahn E, Jacobs J, Aldousany A, Burke RP, Chang AC. Outcome of cardiopulmonary resuscitation in a pediatric cardiac intensive care unit. Crit Care Med. 2000;28: Rhodes JF, Blaufox AD, Seiden HS, Asnes JD, Gross RP, Rhodes JP, Griepp RB, Rossi AF. Cardiac arrest in infants after congenital heart surgery. Circulation. 1999;100(suppl):II-194 II Nadkarni VM, Larkin GL, Peberdy MA, Carey SM, Kaye W, Mancini ME, Nichol G, Lane-Truitt T, Potts J, Ornato JP, Berg RA. First documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults. JAMA. 2006;295: Suominen P, Palo R, Sairanen H, Olkkola KT, Räsänen J. Perioperative determinants and outcome of cardiopulmonary arrest in children after heart surgery. Eur J Cardiothorac Surg. 2001;19: Peberdy MA, Kaye W, Ornato JP, Lerkin GL, Nadkarni V, Mancini ME, Berg RA, Nichol G, Lane-Trultt T. Cardiopulmonary resuscitation of adults in the hospital: a report of cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. Resuscitation. 2003;58: Cummins RO, Chamberlain D, Hazinski MF, Nadkarni V, Kloeck W, Kramer E, Becker L, Robertson C, Koster R, Zaritsky A, Bossaert L, Ornato JP, Callanan V, Allen M, Steen P, Connolly B, Sanders A, Idis A, Cobbe S. Recommended guidelines for reviewing, reporting and conduction research on in-hospital resuscitation: the in-hospital Utstein Style. Circulation. 1997;95: Meaney PA, Nadkarni VM, Cook EF, Testa M, Helfaer M, Kaye W, Larkin GL, Berg RA. Higher survival rates among younger patients after pediatric intensive care units cardiac arrests. Pediatrics. 2006;118: Fiser D. Assessing the outcome of pediatric intensive care. J Pediatr. 1992;121: Larkin G, Copes W, Nathanson B, Kaye W. Pre-resuscitation factors associated with mortality in 49,130 cases of in-hospital cardiac arrest: a report from the National Registry for Cardiopulmonary Resuscitation. Resuscitation. 2010;81: Meaney PA, Nadkarni VM, Kern KB, Inkik JH, Halperin HR, Berg RA. Rhythms and outcomes of adult in-hospital cardiac arrest. Crit Care Med. 2010;38: Samson RA, Nadkarni VM, Meaney PA, Carey SM, Berg MD, Berg RA. Outcomes of in-hospital ventricular fibrillation in children. N Engl J Med. 2006;354: Innes P, Summers C, Boyd M. Audit of paediatric cardiopulmonary resuscitation. Arch Dis Child. 1993;68:

9 Ortmann et al Cardiac Arrest in Children With Cardiac Disease Prodhan P, Fiser RT, Dyamenahali U, Gossett J, Imamura M, Jaquiss RDB, Bhutta AT. Outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) following refractory pediatric cardiac arrest is the intensive care unit. Resuscitation. 2009;80: Morris M, Wernovsky G, Nadkarni V. Survival outcomes after extracorporeal cardiopulmonary resuscitation instituted during active chest compressions following refractory in-hospital pediatric cardiac arrest. Pediatr Critical Care Med. 2004;5: Raymond TT, Cunnyngham CB, Thompson MT, Thomas JA, Dalton HJ, Nadkarnai VM. Outcomes among neonates, infants and children after extracorporeal cardiopulmonary resuscitation for refractory in-hospital pediatric cardiac arrest: a report from the National Registry of Cardiopulmonary Resuscitation. Pediatr Crit Care Med. 2010;11: International consensus on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) science with treatment recommendations. Circulation. 2005;112(suppl 1):III-1 III Olasveengen TM, Wik L, Dramer-Johansen J, Sunde K, Pytten M, Steen PA. Is CPR quality improving? A retrospective study of out-of-hospital cardiac arrest. Resuscitation. 2007;75: Steinmetz J, Barnung S, Nielsen SL, Risom M, Rasmussen LS. Improved survival after an out-of-hospital cardiac arrest. Acta Anaesthesiol Scand. 2008;52: Ramamoorthy C, Haberkern CM, Bhanaker SM, Domino KB, Posner KL, Campos JS, Morray JP. Anesthesia-related cardiac arrest in children with heart disease: data from the Pediatric Perioperative Cardiac Arrest (POCA) registry. Anesth Analg. 2010;110: O Brien S, Clarke D, Jacobs J, Jacobs M, Lacour-Gayet F, Pizarro C, Welke K, Maruszewski B, Tobota Z, Miller W, Hamilton L, Peterson E, Mauroudis C, Edwards F. An empirically based tool for analyzing mortality associated with congenital heart surgery. J Thorac Cardiovasc Surg. 2009;138: CLINICAL PERSPECTIVE Survival after cardiac arrest is poor; however, small case series have suggested that children with cardiac disease who experience a cardiac arrest have better outcomes. Our study of 3323 pediatric patients using Get With the Guidelines Resuscitation found that survival to hospital discharge was 37% in children with surgical cardiac disease compared with 28% in children with medical cardiac disease and 23% in children without cardiac disease. Although multiple previous studies have examined survival after cardiac arrest in the pediatric patients, children undergoing cardiac surgery are a unique population, and their survival after arrest has not been well studied. Children after cardiac surgery have a much higher risk of cardiac arrest compared with other pediatric populations, so this improved survival is encouraging for the providers who care for them. Notable is the higher odds of survival with the use of extracorporeal cardiopulmonary resuscitation, and this report adds to previous studies that have found extracorporeal cardiopulmonary resuscitation to be an effective rescue therapy. This study will be useful for medical providers when evaluating a patient s prognosis and provides information for researchers wanting to study this unique group of patients.