Probability of survival based on etiology of cardiopulmonary arrest in pediatric patients

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1 Pediatric Anesthesia ISSN ORIGINAL ARTICLE Probability of survival based on etiology of cardiopulmonary arrest in pediatric patients Richard J. Berens 1,2, Laura D. Cassidy 1,2, Jennifer Matchey 3, Deborah Campbell 4, Krista D. Colpaert 2, Tangela Welch 5, Michelle Lawson 6, Cheryl Peterson 7, Justine O Flynn 4, Mary Dearth 8 & Kelly S. Tieves 5 1 Medical College of Wisconsin, Milwaukee WI 2 Children s Hospital of Wisconsin, Milwaukee, WI 3 Children s Health Center St. Joseph s Hospital and Medical Center, Phoenix, AZ 4 Kosair Children s Hospital Norton Healthcare Inc., Louisville, KY 5 Children s Mercy Hospitals and Clinics, Kansas City, MO 6 Seattle Children s Hospital, Seattle, WA 7 Cook Children s Medical Center, Fort Worth, TX 8 Mary Bridge Children s Hospital and Health Center, Tacoma, WA, USA Keywords cardiopulmonary resuscitation; pediatrics; survival; cardiopulmonary code event Correspondence Richard Berens, 9000 W Wisconsin Ave MS 735, Wauwatosa, WI 53226, USA RBerens@chw.org Section Editor: Brian Anderson Accepted 6 November 2010 doi: /j x Summary Objective: To aggregate data across institutions to identify, characterize, and differentiate potential survivors from nonsurvivors based on etiology of event. Aim: To evaluate the association of the cardiopulmonary resuscitation (CPR) duration and probability of survival (Ps), stratified by etiology of arrest. Background: In-hospital cardiac arrests occur in 2 6% of pediatric patients with poor survival rates resulting in significant expenditures of time and resources. Methods: Retrospective data from six pediatric hospitals on patients suffering from pulseless cardiac arrests receiving CPR for over one minute were analyzed. Data included demographics, reason for code, precardiac arrest diagnosis, devices and treatment, management strategies during cardiac arrest, compression duration, outcome at hospital discharge, and neurologic outcome of survivors at hospital discharge. Results of logistic regression analysis generated predicated probabilities of survival for duration of compression. Patients were stratified by cardiac-induced cardiac arrests (CICA) and respiratory-induced cardiac arrest (RICA). Results: A total of 257 patients were included, and 27% of CICA and 35% of RICA patients survived to hospital discharge. Ps was initially lower for the CICA patients (Ps at 1 min = 29%) and remained constant (Ps at 60 min = 25%). RICA patients Ps was higher initially (Ps at 1 min = 62%) but demonstrated a dramatic drop within the first 60 min of CPR (Ps at 60 min = 0.2%). Conclusions: Probability of survival curves based on duration of CPR was statistically significantly different for CICA patients compared to RICA patients. 834 Pediatric Anesthesia 21 (2011) ª 2010 Blackwell Publishing Ltd

2 R.J. Berens et al. Probability of survival and CPR in children Introduction Cardiopulmonary code events (code) are defined as emergent management of circulation and/or airway management. In-hospital cardiac arrest occurs in two to six percent of pediatric patients resulting in poor survival rates and significant expenditures of time and resources (1 7). Resuscitation strategies for the code patients may differ because of the etiology of the disease processes leading to cardiopulmonary collapse and variability in skill sets between practitioners. The association between cardiopulmonary resuscitation (CPR) duration and survival to hospital discharge for patients experiencing a cardiac arrest has not been fully evaluated in the published literature (4,8). Initially, the literature supported early termination of resuscitation at min of compression suggesting futility in care beyond that time frame (9,10). More recently, pediatric reviews identified reasonable, functional survival in patients with prolonged resuscitation (8,11 13). The etiology of arrest has been identified as an important factor in resuscitation (5,11,14). Identifying the presence of gas exchange abnormalities leading to hypoxemia in respiratory-induced cardiac arrest (RICA) and therapies to improve these disorders have been a focus of the rapid response team initiatives (15,16). The etiology may dictate varying pathways of resuscitation. A cardiac-induced cardiac arrest (CICA) may focus attention on correction of dysrhythmia and maintenance of circulation as opposed to the standard ABC sequence of resuscitation. Animal studies have demonstrated a difference in PO 2, PCO 2, arterial, and venous saturations and tissue lactate levels depending on the sequence of resuscitation (17 19). A method to identify, characterize, and differentiate potential survivors from nonsurvivors during the resuscitative process remains an important focus of resuscitation research efforts. The purpose of this study was to evaluate the association of the CPR duration and probability of survival (Ps) as it is stratified by etiology of arrest. Materials and methods The National Association of Children s Hospitals and Related institutions (NACHRI) Pediatric Intensive Care Unit FOCUS Group consists of members from seven children hospitals representing both academic and private/community practices. Six of those hospitals submitted data for this study. Institutional Review Board approval was obtained at each hospital. A retrospective chart review from June 1, 2006 to May 31, 2008 included children from birth to 19 years of age, who suffered a pulseless, cardiopulmonary arrest that required CPR for >1 min. The first inhospital cardiac arrest for each patient was used as the cardiopulmonary arrest for the analysis. Patients who had a previous out-of-hospital, cardiac arrest were excluded. Prior to data abstraction, the NACHRI group identified a set of variables from the National Registry CardioPulmonary Resuscitation (NRCPR) data entry forms that would be abstracted from each patient s record. Each hospital identified up to two individuals responsible for data abstraction. All individuals were trained using the NRCPR-defined variables ( forms). The data were abstracted from each patient s code sheet, anesthesia record, trauma room record, and any other relevant hospital data sources. In addition, the group assessed the immediate precipitating cause of cardiac arrest as precipitated by a primary cardiac, respiratory, or neurologic cause. CICA was defined as derangement in preload, afterload, contractility or rhythm. RICA was defined as loss of airway, obstruction of airway, or pneumonic processes leading to hypoxemia. Neurologic-induced cardiac arrests were defined as arrests precipitated by increased intracranial pressure or seizures. Relevant variables describing patient condition and code management were collected including patient demographics, location of cardiac arrest, precode and intracode management and procedures, medication administration, respiratory treatments, and interventions. The CPR duration was determined by the sum of time in minutes during which the patient had chest compressions. Pediatric cerebral performance category (PCPC) (20) scores before cardiac arrest and at hospital discharge were used to assess the functional outcome in survivors. Statistical methods The primary outcome variable was survival to hospital discharge. A univariate analysis was first conducted to identify associations between the individual variables and survival. Proportions were compared using a Chisquare test, and if the expected value of any cell was less than five, a Fisher s exact test was used. Means of normally distributed data were compared using a t-test, and medians were compared for data that were not normally distributed using a Mann Whitney. All tests were conducted as two-tail tests with a = Logistic regression analysis (21) was used to generate predicated probabilities of survival for duration of Pediatric Anesthesia 21 (2011) ª 2010 Blackwell Publishing Ltd 835

3 Probability of survival and CPR in children R.J. Berens et al. compression as a continuous variable. And the Ps was based on the logistic function. Statistical analyses were conducted using stata 10 (22). To generate predicted Ps graphs over the duration of compression time, the predxcon command was used. Predxcon calculates and prints predicted values, and 95% confidence logistic model estimates for a continuous X variable, adjusted for covariates. Results Survival Two hundred and sixty-four patients suffered an inhospital cardiac arrest and met the inclusion criteria. All patients had a witnessed arrest, with initiation of compressions upon identification of pulselessness. Of the 264 patients, 186 (70.5%) survived the initial cardiac arrest, 150 (56.8%) with return of spontaneous circulation and 36 (13.6%) with extracorporeal membrane oxygenation (ECMO). Eighty-two (31.1% of the total and 44% of the initial survivors) survived to hospital discharge. The majority of events occurred in the intensive care unit (ICU) as shown in Table 1. The survivors and nonsurvivors were similar demographically (Table 1); however, the proportion of women surviving was marginally significantly higher than men (36.7% vs 25.8%, P = 0.06). The median duration of compression was 17 min for the nonsurvivors and 6 min for the survivors (P < ). A total of 133 patients experienced a CICA and 124 experienced a RICA. The overall proportion of patients surviving was slightly higher in the RICA patients compared to the CICA, although not statistically significant (35.2% vs 27.3%, P = 0.17). Only seven experienced a neurologic-induced cardiac arrest, and of these, only one survived. Therefore, the neurologic-induced patients were excluded from the analyses. Table 1 Demographics by hospital survival Total (n = 264) Survivors (n = 82) Nonsurvivors (n = 182) % Survival by category P-value Age category 0 30 days days 1 year years years years years Gender Female Male Race African American Alaska Native/Asian Caucasian Hispanic Pacific Islander Mixed Other Unable to determine Location Intensive care unit <0.001 Medical/Surgical floor Emergency Department Clinic Operating room or Cardiac Catheterization Lab Undetermined Precipitating cause of code event Cardiac-induced cardiac arrest (CICA) Respiratory-induced cardiac arrest (RICA) * Neurologic-induced cardiac arrest *A chi-square test was conducted between CICA and RICA patients only. 836 Pediatric Anesthesia 21 (2011) ª 2010 Blackwell Publishing Ltd

4 R.J. Berens et al. Probability of survival and CPR in children Figure 1 Cardiopulmonary resuscitation duration by hospital survival for cardiac- and respiratory-induced cardiac event patients. Figure 1 displays a box plot of actual survival stratified by CICA and RICA patients. The RICA patients who survived required a much shorter CPR duration than the other three groups. The Ps with increasing CPR duration based on the logistic regression analysis is shown in Figure 2 stratified by CICA and RICA. The y-axis indicates the probability of patients surviving based on the logistic regression analysis. The x-axis reflects the duration of CPR in minutes. While the difference in overall survival between groups was not statistically significant (Table 1), the difference in the Ps with increasing duration of CPR between the CICA and RICA patients was statistically significantly different (P = 0.001). The Ps was initially lower for the CICA patients (Ps at 1 min = 29%) with a slight linear decrease over time (Ps at 60 min = 25%). The Ps for the RICA patients was higher initially (Ps at 1 min = 62%) but Figure 2 Probability of hospital survival by cardiopulmonary resuscitation duration by cardiac- and respiratory-induced cardiac events. Pediatric Anesthesia 21 (2011) ª 2010 Blackwell Publishing Ltd 837

5 Probability of survival and CPR in children R.J. Berens et al. Figure 3 Probability of Hospital Survival for Cardiac- and Respiratory-induced Cardiac Arrests by location: ICU versus non-icu locations of arrest demonstrated a dramatic drop within the first 60 min of CPR (Ps at 60 min = 0.2%). The CICA and RICA patients were stratified further by whether the code occurred in the ICU or elsewhere. Overall, 20% of the 105 CICA patients in the ICU survived compared to 30% of the 92 RICA patients (P = 0.09). In comparison, 57% of the 28 CICA patients who coded outside of the ICU survived compared to 50% of the 32 RICA patients (P = 0.58). Figure 3 shows the Ps graphs over duration of compression for CICA and RICA patients whose code occurred in the ICU and outside the ICU. While the Ps initially for patients who coded outside of the ICU was high (RICA Ps = 93%, CICA Ps = 78%), there was a dramatic decrease in Ps over the first 30 min for RICA patients and a decrease in Ps over time for the CICA patients over the first 100 min. The difference in the slopes was marginally statistically significant (P = 0.06). RICA patients who coded in the ICU had a higher Ps initially (Ps = 53%) with a rapid decrease over time (Ps = 8% at 30 min) compared to the CICA patients who initially had a lower Ps (Ps = 20%) that remained relatively constant over time (Ps = 19% at 30 min). The difference in the slopes was statistically significant (P = 0.01). Only nine of the RICA patients were placed on ECMO, and therefore, no statistical comparisons were conducted on the RICA patients. Of the 133 CICA patients, 34 (25.8%) were placed on ECMO and 13 (38.2%) survived compared to 23.5% of the 98 patients who did not receive ECMO (P = 0.09). Figure 4 demonstrates the Ps curves for the CICA patients stratified by ECMO use. CICA patients on ECMO initially had a higher probability of survival (47% compared to 27%), and the decrease in Ps over duration of compression time is similar in both patients with and without ECMO (P = 0.91). Functional outcome Pediatric cerebral performance category scores at baseline and hospital discharge were compared for the CICA and RICA survivors overall and also stratified by ICU (Table 2). An increase in PCPC score suggests a decrease in cognitive function, while a zero indicates no change, and the largest observed change in score was two. Overall, a larger proportion of the CICA patients experienced a decline in cognitive function represented by the increase in PCPC score from baseline to discharge (P = 0.05). The most significant difference was the decline in cognitive function for the CICA patients who coded outside the ICU compared to the RICA patients with 50% of the CICA patients experiencing no change compared to 94% of the RICA patients. The median CPR duration was 22 min for the CICA patients who survived and had a detrimental change in the PCPC score compared to 10 min for those with no change in PCPC score. The median CPR duration was similar in the RICA patients for those with and without a change (5 min compared to 3.5 min) in PCPC score. Discussion Identifying patient characteristics that affect the Ps may allow clinicians to modify resuscitation techniques to improve outcome. The study reported here demon- 838 Pediatric Anesthesia 21 (2011) ª 2010 Blackwell Publishing Ltd

6 R.J. Berens et al. Probability of survival and CPR in children Figure 4 Probability of survival by cardiopulmonary resuscitation duration in cardiac-induced cardiac arrest patients rescued with and without ECMO during the code event. Table 2 Change in pediatric cerebral performance category (PCPC) score from baseline to hospital discharge for survivors PCPC difference 0 (%) 1 (%) 2 (%) Total P-value Overall CICA 20 (54) 14 (38) 3 (8) RICA 31 (76) 10 (24) 0 (0) 41 Outside of ICU CICA 8 (50) 7 (44) 1 (6) RICA 15 (94) 1 (6) 16 In ICU CICA 12 (57) 7 (33) 2 (10) RICA 16 (64) 9 (36) 0 (0) 25 CICA, cardiac-induced cardiac arrests; ICU, intensive care unit; RICA, respiratory-induced cardiac arrest. strated significant differences in survival over the course of CPR based on the cause of arrest suggesting the need for further research. Cardiac-induced and RICA may be a surrogate marker for some preconditioning scenarios. The sudden loss of circulation with prompt resuscitative support would seem to be the best candidate for intact survival. However, if resuscitation does not return the circulation within a prompt time frame, patients may have a lower Ps than those who were subject to challenging hemodynamic and biochemical situations, leading to a type of preconditioning that has been identified as a beneficial factor in many types of cellular, tissue, and whole animal survival (23 25). The CICA patient s predicted Ps remains fairly constant as the duration of compression increases. However, the RICA patients demonstrated a higher Ps initially with a sharp decline in Ps over time. The sharp decline in Ps with increasing duration of compression observed consistently in the RICA group is in part because of the fact only one RICA patient survived beyond 13 min (one survived 63-min duration of compression), and more than half (n = 43/80) of the nonsurvivor RICA patients died after 13 min of CPR. These data suggest that the RICA patients not resuscitated quickly have a poor chance of survival; however, the differences in CPR duration for the CICA patients are similar between survivors and nonsurvivors. The RICA curves early survival success may be as a result of improved oxygenation by recruitment of functional alveolar segments with airway maneuvers. Overall, there were a higher percentage of RICA patients with no difference in PCPC between baseline and hospital discharge compared to the CICA patients (76% vs 54%). This could be in part because of the short CPR duration for the RICA survivors. Only one RICA survivor underwent CPR for >13 min. This difference was most striking in the ICU population where 94% of the RICA survivors had no change in PCPC compared to 50% of the CICA patients. Pediatric Anesthesia 21 (2011) ª 2010 Blackwell Publishing Ltd 839

7 Probability of survival and CPR in children R.J. Berens et al. The results of this study suggest differences in patient survival and neurocognitive outcome associated with the duration of compression based on the cause of the cardiac arrest. Patients with a cardiac-induced arrest have different risk factors and treatments than those with a RICA. A limitation of this retrospective study design was the inability to control for quality of compressions or type of ventilation strategy. Future studies with a larger patient population would benefit from inclusion of these and other relevant data elements to create patient profiles and treatment interventions to more clearly delineate the differences in Ps over duration of compression. Acknowledgments We acknowledge NACHRI s guidance to the FOCUS group to conduct this project. We thank Pat Conway RN for her help coordinating this effort. References 1 Suominen P, Olkkola KT, Voipio V et al. Utstein style reporting of in-hospital paediatric cardiopulmonary resuscitation. Resuscitation 2000; 45: Parra DA, Totapally BR, Zahn E et al. Outcome of cardiopulmonary resuscitation in a pediatric cardiac intensive care unit. Crit Care Med 2000; 28: Slonim AD, Patel KM, Ruttimann UE et al. Cardiopulmonary resuscitation in pediatric intensive care units. Crit Care Med 1997; 25: Sutton RM, Niles D, Nysaether J et al. Quantitative analysis of CPR quality during in-hospital resuscitation of older children and adolescents. Pediatrics 2009; 124: Topjian AA, Berg RA, Nadkarni VM. Pediatric cardiopulmonary resuscitation: advances in science, techniques, and outcomes. Pediatrics 2008; 122: Peterson AA. The pediatric arrest. Ann Intern Med 2006; 144: Duncan HP, Frew E. Short-term health system costs of paediatric in-hospital acute life-threatening events including cardiac arrest. Resuscitation 2009; 80: Meert KL, Donaldson A, Nadkarni V et al. Multicenter cohort study of in-hospital pediatric cardiac arrest. Pediatr Crit Care Med 2009; 10: Innes PA, Summers CA, Boyd IM et al. Audit of paediatric cardiopulmonary resuscitation. Arch Dis Child 1993; 68: Zaritsky A, Nadkarni V, Getson P et al. CPR in children. Ann Emerg Med 1987; 16: Nadkarni VM, Larkin GL, Peberdy MA et al. First documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults. JAMA 2006; 295: Bartels M, Tjan DH, Reussen EM et al. Therapeutic hypothermia after prolonged cardiopulmonary resuscitation for pulseless electrical activity. Neth J Med 2007; 65: Berg MD, Nadkarni VM, Zuercher M et al. In-hospital pediatric cardiac arrest. Pediatr Clin North Am 2008; 55: Peddy SB, Hazinski MF, Laussen PC et al. Cardiopulmonary resuscitation: special considerations for infants and children with cardiac disease. Cardiol Young 2007; 17(Suppl 2): Sharek PJ, Parast LM, Leong K et al. Effect of a rapid response team on hospitalwide mortality and code rates outside the ICU in a Children s Hospital. JAMA 2007; 298: Tibballs J, Kinney S, Duke T et al. Reduction of paediatric in-patient cardiac arrest and death with a medical emergency team: preliminary results. Arch Dis Child 2005; 90: Berg RA, Hilwig RW, Kern KB et al. Simulated mouth-to-mouth ventilation and chest compressions (bystander cardiopulmonary resuscitation) improves outcome in a swine model of pre-hospital pediatric asphyxial cardiac arrest. Crit Care Med 1999; 27: Berg RA, Hilwig RW, Kern KB et al. Bystander chest compressions and assisted ventilation independently improve outcome from piglet asphyxial pulseless cardiac arrest. Circulation 2000; 101: Ewy GA. Continuous-chest-compression cardiopulmonary resuscitation for cardiac arrest. Circulation 2007; 116: Fiser DH, Long N, Roberson PK et al. Relationship of pediatric overall performance category and pediatric cerebral performance category scores at pediatric intensive care unit discharge with outcome measures collected at hospital discharge and 1- and 6-month follow-up assessments. Crit Care Med 2000; 28: Hosmer DW, Lameshow S. Applied Logistic Regression Analysis. New York, NY: John Wiley and Sons, StataCorp. Stata Statistical Software: Release 11. College Station, TX: StataCorp LP, Alkan T. Neuroprotective effects of ischemic tolerance (preconditioning) and postconditioning. Turk Neurosurg 2009; 19: Shah AA, Arias JE, Thomson JG. The effect of ischemic preconditioning on secondary ischemia in myocutaneous flaps. J Reconstr Microsurg 2009; 25: Eichhorn W, Blake FA, Pohlenz P et al. Conditioning of myocutaneous flaps. J Craniomaxillofac Surg 2009; 37: Pediatric Anesthesia 21 (2011) ª 2010 Blackwell Publishing Ltd