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1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Girotra S, Nallamothu BK, Spertus JA, Li Y, Krumholz HM, Chan PS. Trends in survival after inhospital cardiac arrest. N Engl J Med 2012;367: DOI: /NEJMoa

2 Supplementary Appendix Trends in Survival After In-Hospital Cardiac Arrest Saket Girotra M.D., S.M.; Brahmajee K. Nallamothu M.D., M.P.H.; John A. Spertus M.D., M.P.H.; Yan Li, Ph.D; Harlan M. Krumholz M.D., S.M.; Paul S. Chan M.D. 1

3 TABLE OF CONTENTS 1. American Heart Association Get With the Guidelines-Resuscitation Investigators Figure S1. Proportion of Cardiac Arrests Due to Asystole or Pulseless Electrical Activity and Ventricular Fibrillation or Pulseless Ventricular Tachycardia by Calendar Year Figure S2. Time to Defibrillation in Patients with Ventricular Fibrillation or Pulseless Ventricular Tachycardia by Calendar Year Table S1. Characteristics of Study Hospitals Table S2. Variables Included in the Multivariable Models Table S3. Observed Rates of Survival & Neurological Outcomes by Calendar Year Table S4. Independent Predictors of Survival to Hospital Discharge for In-hospital Cardiac Arrest Table S5. Calendar-Year Trends in Risk-adjusted Rates of Survival and Neurological Outcomes by Rhythm type Table S6. Calendar-Year Trends in Risk-Adjusted Rates of Survival to Discharge among Patients at Hospitals Participating for at least 8 years in Get With The Guidelines-Resuscitation..20 2

4 American Heart Association Get With the Guidelines Resuscitation (formerly National Registry of Cardiopulmonary Resuscitation) Investigators Besides the author Paul S. Chan MD, MSc, members of Get With The Guidelines- Resuscitation include: Robert A. Berg, MD, Children's Hospital of Philadelphia; Emilie Allen, MSN, RN, Parkland Health & Hospital System; Michael W. Donnino, MD, Beth Israel Deaconess Medical Center; Dana P. Edelson, MD, MS, University of Chicago Medical Center; Kathy Duncan, Institute for Healthcare Improvement; Brian Eigel, PhD and Lana Gent, PhD, American Heart Association; Robert T. Faillace, MD, St. Joseph's Regional Medical Center; Romergryko G. Geocadin, MD, Johns Hopkins School of Medicine; Elizabeth A. Hunt, MD, MPH, PhD, Johns Hopkins Medicine Simulation Center; Lynda Knight, RN, Lucile Packard Children's Hospital at Stanford; Kenneth LaBresh, MD, RTI International; Mary E. Mancini, RN, PhD, University of Texas at Arlington; Vinay M. Nadkarni, MD, University of Pennsylvania School of Medicine; Graham Nichol, MD, MPH and Samuel A. Warren, MD, University of Washington; Mary Ann Peberdy, MD and Joseph P. Ornato, MD, Virginia Commonwealth University Health System; Comilla Sasson, MD, MS, University of Colorado; and Mindy Smyth, MSN, RN. 3

5 Figure S1. Proportion of Cardiac Arrests Due to Asystole or Pulseless Electrical Activity and Ventricular Fibrillation or Pulseless Ventricular Tachycardia by Calendar Year.* Over the past decade, the proportion of cardiac arrests treatable by defibrillation (ventricular fibrillation and pulseless ventricular tachycardia) has decreased (P for trend <0.001). * PEA denotes pulseless electrical activity; VF, ventricular fibrillation; and VT, ventricular tachycardia. Girotra et al 4

6 Figure S2. Time to Defibrillation in Patients with Ventricular Fibrillation or Pulselsess Ventricular Tachycardia by Calendar Year. Over the past decade, mean time to defibrillation among patients with ventricular fibrillation and pulseless ventricular tachycardia has not changed (P for trend = 0.08). Girotra et al 5

7 Table S1. Characteristics of Study Hospitals Hospital Characteristic no./total no. (%) N=374 Geographic Region* Northeast 52/359 (14.5) Southeast 91/359 (25.3) Midwest 80/359 (22.3) Southwest 68/359 (18.9) West 68/359 (18.9) Location* Urban 322/359 (89.7) Rural 37/359 (10.3) Ownership* Private 47/359 (13.1) Government 55/359 (15.3) Non-profit 257/359 (71.6) Hospital Bed Size < /361 (39.0) /361 (39.9) > /361 (21.1) Academic Status Hospital with fellowship program (Major) 76/361 (21.1) Hospital with residency program (Minor) 116/361 (32.1) Non-teaching hospital 169/361 (46.8) * Geographic Region, location and ownership data were missing for 15 (4.0%) hospitals. Hospital bed size and academic status data were missing for 13 (3.5%) hospitals. Girotra et al 6

8 Table S2. Variables Included in the Multivariable Models* Variable Demographics Age Sex Race Definition Age in years Self reported (male or female) Self reported (white, black or other) Cardiac arrest characteristics Initial cardiac arrest rhythm Hospital location Time of cardiac arrest Day of cardiac arrest Use of a hospital-wide cardiopulmonary arrest alert ( Code Blue ) Assessed with AED First documented rhythm at the time of cardiac arrest (asystole, PEA, VF, or pulseless VT) Location of patient in the hospital at the time of cardiac arrest (ICU, monitored unit [telemetry], or non-monitored unit) Time of day when cardiac arrest occurred (working hours [7:00 AM 10:59] or after hours [11:00 PM 6:59 AM] Day of the week when cardiac arrest occurred (weekday [Monday-Friday] or weekend [Saturday, Sunday]) Use of a general hospital broadcast method for cardiac arrest notification (e.g., overhead pagers or audio alert) Use of an AED for automated rhythm analysis and defibrillation when appropriate during resuscitation Amiodarone use during resuscitation Use of amiodarone during resuscitation Time to defibrillation Time to first defibrillation shock in minutes (only for patients with VF or pulseless VT) Co-morbidities Heart failure, this admission Prior heart failure Documented diagnosis of congestive heart failure during this admission Documented diagnosis of congestive heart failure prior to this admission Girotra et al 7

9 Variable Myocardial infarction, this admission Prior myocardial infarction Arrhythmia Definition Documented diagnosis of myocardial ischemia (acute coronary syndrome) or myocardial infarction during this admission Documented diagnosis of myocardial ischemia (acute coronary syndrome) or myocardial infarction prior to this admission Documented diagnosis of a cardiac arrhythmia Evidence of hypotension within 4 hours up to the time of the event, defined by ANY of the following Hypotension 1. SBP < 90 or MAP < 60 mmhg 2. Vasopressor or inotropic requirement after volume expansion (except for dopamine 3 mcg/kg/min) 3. Intra-aortic balloon pump Evidence of acute or chronic respiratory insufficiency within 4 hours up to the time of the event, defined by ANY of the following Respiratory insufficiency 1. PaO2/FiO2 ratio < 300 (in the absence of pre-existing documented cyanotic heart disease) 2. PaO2 < 60 mm Hg (in the absence of pre-existing documented cyanotic heart disease) 3. SaO2 < 90 %, (in the absence of pre-existing documented cyanotic heart disease) 4. PaCO2, EtCO2 or TcCO2 > 50 mm Hg 5. Spontaneous respiratory rate > 40/min or < 5/min 6. Need for non-invasive ventilation (e.g., Bag-Valve- Mask, Mask CPAP or BiPAP, Nasal CPAP or BiPAP, negative pressure ventilation) 7. Need for ventilation via invasive airway (e.g., T-piece, assist control, IMV, pressure support, high frequency) Girotra et al 8

10 Variable Definition Evidence of renal insufficiency prior to the event, defined by ANY of the following Renal insufficiency 1. Requiring ongoing dialysis or extracorporeal filtration therapies 2. Creatinine > 2 mg/dl within 24 hours up to the time of the event Hepatic insufficiency Evidence of hepatic insufficiency within 24 hours up to the time of the event, defined by ANY of the following 1. Total bilirubin > 2 mg/dl and AST > 2x normal 2. Cirrhosis Evidence of metabolic/electrolyte abnormality within 4 hours up to the time of the event, defined by ANY of the following Metabolic or electrolyte abnormality 1. Sodium < 125 or > 150 meq/l 2. Potassium < 2.5 or > 6 meq/l 3. Arterial ph < 7.3 or > Lactate > 2.5 mmol/l 5. Blood glucose < 60 mg/dl Diabetes mellitus Baseline evidence of motor, cognitive, or functional deficits (CNS depression) Acute stroke Pre-arrest CPC score Documented diagnosis of Type I or Type II diabetes mellitus Evidence of a motor, cognitive, or functional baseline deficit (at time of system entry) Documented diagnosis of an intracranial or intraventricular hemorrhage or thrombosis during this admission CPC score at the time of cardiac arrest Girotra et al 9

11 Variable Pneumonia Septicemia Major Trauma Metastatic Cancer Definition Documented diagnosis of active pneumonia, where antibiotics have not yet been started or the pneumonia is still being treated with antibiotics Bloodstream infection where antibiotics have not yet been started or the infection is still being treated with antibiotics Evidence of multi-system injury or single system injury associated with shock or altered mental status (during this hospitalization) Any solid tissue malignancy with evidence of metastasis, or any blood borne malignancy Therapeutic interventions in place at the time of cardiac arrest Mechanical ventilation Anti-arrhythmic drugs Including use of ventilation via invasive airway or noninvasive ventilation (CPAP or BiPAP) Use of amiodarone, lidocaine, procainamide, or other antiarrhythmic agents ongoing at the time of the event Intravenous vasopressors Use of dobutamine, dopamine > 3 mcg/kg/min, epinephrine, norepinephrine, phenylephrine, other vasoactive agent ongoing at the time of the event Dialysis Pulmonary artery catheter Intra-aortic balloon pump Use of hemodialysis, peritoneal dialysis, continuous arteriovenous or veno-venous hemofiltration/dialysis ongoing at time of the event Use of invasive hemodynamic monitoring with a pulmonary artery catheter ongoing at the time of the event Use of intra-aortic balloon pump counterpulsation ongoing at the time of the event Girotra et al 10

12 Variable Length of a hospital s participation in Get With The Guidelines-Resuscitation Definition Number of years a hospital had participated in Get With The Guidelines-Resuscitation for each cardiac arrest Hospital characteristics (Source: American Hospital Association Data Year 2009) Geographic region Hospital ownership Hospital location Hospital bed size Categorized as northeast, southeast, midwest, southwest, and west census regions based on the United States Census 2000 Categorized as for-profit, government, and not-profit Categorized as urban and rural location Categorized as less than 250, , and 500 or more Teaching status Categorized as major teaching (hospitals with a residency and a fellowship program), minor teaching (hospitals with a residency program but no fellowship program), and non-teaching (hospitals without a residency or fellowship program) * AED denotes automated external defibrillator; AST, aspartate amiotransferase; BiPAP, bilevel positive airway pressure; CNS, central nervous system; CPAP, continuous positive airway pressure; CPC, cerebral performance category; EtCO2, end-tidal CO2; FiO2, fraction of oxygen in the inspired air; ICU, intensive care unit; MAP, mean arterial pressure; PaCO2, partial pressure of carbon dioxide; PaO2, partial pressure of oxygen; PEA, pulseless electrical activity; SBP: systolic blood pressure; SaO2, saturation of oxygen; TcCO2, transcutaneous CO2; VF, ventricular fibrillation; and VT, ventricular tachycardia. Girotra et al 11

13 Table S3. Observed Rates of Survival and Neurological Outcomes by Calendar Year* OVERALL no./total no. (%) Survival to Discharge 192/1405 (13.7) 712/4524 (15.7) 1219/7687 (15.9) 1516/10017 (15.1) 1741/10794 (16.1) 1870/10999 (17.0) 1859/10810 (17.2) 1862/10665 (17.5) 2128/10959 (19.4) 1258/6765 (18.6) Acute Resuscitation 600/ / / / / / / / / /6765 Survival (42.7) (44.4) (45.2) (46.7) (48.3) (49.7) (51.3) (54.2) (57.8) (57.3) Post-Resuscitation 192/ / / / / / / / / /3875 Survival (32.0) (35.4) (35.1) (32.4) (33.4) (34.2) (33.5) (32.2) (33.6) (32.5) Neurological Outcome in Survivors Clinical Significant 49/ / / / / / / / / /1120 Disability (32.9) (46.9) (42.3) (51.4) (54.1) (51.5) (52.7) (52.8) (49.8) (40.8) (CPC > 1) Severe Disability 15/149 (10.1) 84/524 (16.0) 139/953 (14.6) 225/1296 (17.4) 286/1447 (19.8) 324/1684 (19.2) 298/1692 (17.6) 350/1620 (21.6) 367/1881 (19.5) 184/1120 (16.4) Asystole and PEA no./total no. (%) Survival to Discharge 66/965 (6.8) 331/3315 (10.0) 629/5940 (10.6) 786/7866 (10.0) 958/8510 (11.3) 1058/8725 (12.1) 1108/8684 (12.8) 1140/8578 (13.3) 1370/8978 (15.3) 782/5574 (14.0) Acute Resuscitation 344/ / / / / / / / / /5574 Survival (35.7) (38.6) (40.5) (42.3) (44.0) (45.7) (47.9) (50.8) (55.1) (54.2) Post-Resuscitation 66/ / / / / / / / / /3019 Survival (19.2) (25.9) (26.2) (23.6) (25.6) (26.6) (26.6) (26.2) (27.7) (25.9) Girotra et al 12

14 Neurological Outcome in Survivors Clinical Significant 16/47 137/ / / / / / / / /691 Disability (34.0) (56.6) (50.8) (58.4) (61.5) (61.0) (59.3) (56.7) (54.7) (48.3) (CPC > 1) Severe Disability 7/47 (14.9) 55/242 (22.7) 95/480 (19.8) 149/666 (22.4) 205/779 (26.3) 240/940 (25.5) 235/999 (23.5) 232/974 (23.8) 277/1204 (23.0) 149/691 (21.6) VF and Pulseless VT no./total no. (%) Survival to Discharge, 126/440 (28.6) 381/1209 (31.5) 590/1747 (33.8) 730/2151 (33.9) 783/2284 (34.3) 812/2274 (35.7) 751/2126 (35.3) 722/2087 (34.6) 758/1981 (38.3) 476/1191 (40.0) Acute Resuscitation Survival Post-Resuscitation Survival Neurological Outcome in Survivors Clinical Significant Disability (CPC > 1) Severe Disability 256/440 (58.2) 126/256 (49.2) 33/102 (32.4) 8/102 (7.8) 731/1209 (60.5) 381/731 (52.1) 109/282 (38.7) 29/282 (10.3) 1074/1747 (61.5) 590/1074 (54.9) 159/473 (33.6) 44/473 (9.3) 1347/2151 (62.6) 730/1347 (54.2) 277/630 (44.0) 76/630 (12.1) 1472/2284 (64.5) 783/1472 (53.2) 304/668 (45.5) 1484/2274 (65.3) 812/1484 (54.7) 295/744 (39.7) 1388/2126 (65.3) 751/1388 (54.1) 299/693 (43.1) 1429/2087 (68.5) 722/1429 (50.5) 303/646 (46.9) 1388/1981 (70.1) 758/1388 * CPC, denotes cerebral performance category; PEA, pulseless electrical activity; VF, ventricular fibrillation; VT, ventricular tachycardia. Acute Resuscitation Survival was determined by the number of patients with return of spontaneous circulation for at least 20 minutes divided by the number of patients with a cardiac arrest. Post-resuscitation Survival was determined by the number surviving to hospital discharge divided by the number surviving the acute resuscitation. Clinically Significant Disability was defined as a CPC score of more than 1 in patients surviving to hospital discharge. Severe Disability was defined as a CPC score of more than 2 in patients surviving to hospital discharge. 81/668 (12.1) 84/744 (11.3) 63/693 (9.1) 118/646 (18.3) (54.6) 277/677 (40.9) 90/677 (13.3) 856/1191 (71.9) 476/856 (55.6) 123/429 (28.7) 35/429 (8.2) Girotra et al 13

15 Table S4. Independent Predictors of Survival to Hospital Discharge for In-hospital Cardiac Arrest* Variable Risk Ratio 95% CI P value Calendar Year 2001 vs vs < vs < vs < vs < vs < vs < vs < vs <0.001 Age (per 1-year) <0.001 Sex (Female vs. Male) <0.001 Race Black vs. White <0.001 Other vs. White Initial Cardiac Arrest Rhythm PEA vs. Asystole VF vs. Asystole <0.001 Girotra et al 14

16 Variable Risk Ratio 95% CI P value VT vs. Asystole <0.001 Hospital Location Monitored unit vs. ICU Non-monitored Unit vs. ICU <0.001 Arrest after-hours <0.001 Arrest on weekend <0.001 Use of a hospital-wide cardiopulmonary arrest alert Code Blue Assessed with automated external defibrillator Amiodarone use during resuscitation <0.001 Heart failure, this admission Prior heart failure Myocardial infarction, this admission <0.001 Prior myocardial infarction Arrhythmia <0.001 Hypotension <0.001 Respiratory insufficiency Renal insufficiency <0.001 Hepatic insufficiency <0.001 Metabolic or electrolyte abnormality <0.001 Diabetes mellitus <0.001 Girotra et al 15

17 Variable Risk Ratio 95% CI P value Baseline depression in CNS function Acute stroke Pre-arrest CPC score CPC 2 vs. CPC CPC 3 vs. CPC <0.001 CPC 4 vs. CPC <0.001 Pneumonia Septicemia <0.001 Major trauma Metastatic Cancer <0.001 Mechanical ventilation <0.001 Intravenous antiarrhythmic therapy <0.001 Intravenous vasopressor medication <0.001 Dialysis <0.001 Intra-aortic balloon pump Pulmonary artery catheter <0.001 Length of participation in Get With The Guidelines- Resuscitation Geographic Region Southeast vs. Northeast Midwest vs. Northeast <0.001 Girotra et al 16

18 Variable Risk Ratio 95% CI P value Southwest vs. Northeast West vs. Northeast Ownership status Government vs. Private Non-profit vs. Private Location (Rural vs. Urban) Hospital Bed Size vs. < > 500 vs. < Teaching status Minor teaching vs. Major Non-teaching vs. Major * CI, confidence interval; CNS, central nervous system; CPC, cerebral performance category; ICU, Intensive Care Unit; PEA, pulseless electrical activity; VF, ventricular fibrillation; and VT, ventricular tachycardia. Adjusted risk ratio, 95% confidence intervals and P values are provided for all model covariates included in the multivariable model for survival to discharge in the overall cohort. Girotra et al 17

19 Table S5. Trends in Risk-Adjusted Rates of Survival and Neurological Outcomes by Rhythm Type* Risk-Adjusted Rates Adjusted RR P for Asystole and PEA per year (95% CI) Trend Survival to Discharge (1.04, 1.08) < Acute Resuscitation Survival (1.03, 1.05) < Post-Resuscitation Survival (1.01, 1.04) Neurological Outcome in Survivors Clinically Significant Disability (0.98, 1.01) 0.21 Severe Disability** (0.98, 1.04) 0.63 VF and Pulseless VT Survival to Discharge ( ) < Acute Resuscitation Survival (1.01, 1.03) < Post-Resuscitation Survival (1.00, 1.02) 0.05 Neurological Outcome in Survivors Clinically Significant Disability (0.96, 0.99) 0.01 Severe Disability** (0.96, 1.07) 0.57 * CI denotes confidence interval; CPC, cerebral performance category; PEA, pulseless electrical activity; RR, rate ratio; VF, ventricular fibrillation; and VT, ventricular tachycardia. Risk-adjusted rates of survival to discharge, acute resuscitation survival, post-resuscitation survival, and neurological disability for each calendar year are reported separately for patients with non-shockable rhythms (asystole and PEA) and shockable rhythms (VF and pulseless VT). Rates are adjusted for temporal changes in patient and hospital characteristics. Risk-adjusted rates for each calendar year were obtained by multiplying the observed rate for the reference year (2000) by the corresponding rate-ratios for 2001 through 2009 from a model evaluating calendar year as a categorical variable. Determined from a model evaluating calendar year as a continuous variable. Girotra et al 18

20 Acute Resuscitation Survival was determined by the number of patients with return of spontaneous circulation for at least 20 minutes divided by the number of patients with a cardiac arrest. Post-resuscitation Survival was determined by the number surviving to hospital discharge divided by the number surviving the acute resuscitation. Clinically Significant Disability was defined as a CPC score of more than 1 in patients surviving to hospital discharge ** Severe Disability was defined as a CPC score of more than 2 in patients surviving to hospital discharge. Girotra et al 19

21 Table S6. Trends in Risk-Adjusted Rates of Survival to Discharge by Calendar Year Among Patients at Hospitals Participating for at least 8 years in Get With The Guidelines-Resuscitation* Risk-Adjusted Rates OVERALL N=563 N=1690 N=3202 N=4206 N=4085 N=4439 N=4409 N=3987 N=4121 N=2762 Adjusted RR per year (95% CI) P for Trend Survival to Discharge (1.04, 1.07) <0.001 Asystole and PEA N=396 N=1231 N=2473 N=3296 N=3212 N=3550 N=3602 N=3261 N=3418 N=2293 Survival to Discharge (1.04, 1.08) <0.001 VF and Pulseless VT N=167 N=459 N=729 N=910 N=873 N=889 N=807 N=726 N=703 N=469 Survival to Discharge (1.02, 1.05) <0.001 * CI denotes confidence interval; PEA, pulseless electrical activity; RR, rate ratio; VF, ventricular fibrillation; and VT, ventricular tachycardia. Risk-adjusted rates of survival to discharge by calendar year are reported for the overall cohort and by rhythm type for 33,464 patients at 85 hospitals that participated in the registry for at least 8 years during Risk-adjusted rates for each calendar year were determined by multiplying the observed rate for the reference year (2000) by the corresponding rate-ratios for 2001 through 2009 from a model evaluating calendar year as a categorical variable. Determined from a model evaluating calendar year as a continuous variable Girotra et al 20

Supplementary Appendix

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