Are You Stopping Too Soon? OUTCOMES OF PEDIATRIC CPR

Transcription

1 Are You Stopping Too Soon? OUTCOMES OF PEDIATRIC CPR Renée I. Matos, MD, MPH, FAAP Maj, USAF, MC Pediatric Critical Care Medicine San Antonio Military Medical Center

2 Disclosure I have no significant financial interest or other relationship with any products, manufacturers, or providers of service I will not be discussing any non FDA-approved or off-label uses of any products/providers of service The views expressed herein are mine and do not reflect the official policy or position of San Antonio Military Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, Department of the Air Force, or U.S. Government.

3 Learning Objectives Analyze current literature regarding resuscitative outcomes in children Recognize that some children may benefit from prolonged CPR for an in-hospital cardiac arrest Estimate outcomes for specific patient groups after in-hospital cardiac arrests Evaluate your role in improving outcomes of resuscitation through CPR duration

4

5 Photos courtesy of Stewart Elder

6 RATE PER 1000 HOSPITAL ADMISSIONS Epidemiology of Pediatric In-Hospital Cardiac Arrests INCIDENCE OF IN-HOSPITAL CARDIAC ARRESTS CHILDREN ADULT Morrison LJ, et al. Circulation 2013;127:

7 RATE PER 1000 HOSPITAL ADMISSIONS Epidemiology of Pediatric In-Hospital Cardiac Arrests INCIDENCE OF IN-HOSPITAL CARDIAC ARRESTS ,000 per year ,000 per year CHILDREN ADULT Morrison LJ, et al. Circulation 2013;127:

8

9 120 school busses per year

10 In-Hospital Cardiac Arrest Survival 27% of children vs. 18% of adults survive Excluded delivery room arrests and arrests in an ICU More children (65%) than adults (45%) arrest in ICUs Good neurologic outcome in 65% of pediatric and 73% of adult survivors Nadkarni VM, et al. JAMA. 2008;295:50-7.

11 Variability in Survival 22% survival to hospital discharge for children in asystole vs. 29% for VF/VT Nadkarni VM, et al. JAMA. 2008;295:50-7.

12 Chan PS, et al. JAMA. 2009;302: Ehlenbach WJ, et al. NEJM. 2009;361:22-31.

13 Chan PS, et al. JAMA. 2009;302: Ehlenbach WJ, et al. NEJM. 2009;361:22-31.

14 Peberdy MA, et al. JAMA. 2008;299:

15 80% 70% 60% 50% 40% 30% 20% 10% 0% ROSC 24 hr Survival Survival to Hospital Discharge #REF! Surgical-Cardiac #REF! Medical-Cardiac Noncardiac Ortmann L, et al. Circulation. 2011;124:

16 What Other Factors Impact Outcomes? PATIENT FACTORS: Age Race Comorbidities Rhythm Time of day of arrest (nights/weekends) Patient classification TEAM FACTORS: Rapid defibrillation CPR Quality Rate, Depth, Recoil Minimize interruptions Physiologic feedback (ETCO 2 ) Data review/pi

17

18 What Other Factors Impact Outcomes? PATIENT FACTORS: Age Race Comorbidities Rhythm Time of day of arrest (nights/weekends) Patient classification TEAM FACTORS: Rapid defibrillation CPR Quality Rate, Depth, Recoil Physiologic feedback (ETCO 2 ) Data review/pi What about CPR duration?

19 CPR Duration Prolonged CPR has poorer outcomes Some experts previously considered CPR futile after >20 minutes of chest compressions or after >2 doses of epinephrine Case reports and recent literature of intact survival after prolonged resuscitation

20 It took 26 minutes and a total of 13 shocks to restore a pulse. Successful resuscitation of a child after cardiac arrest of 88 minutes. How do you know if 15 minutes is enough? Photos from: Today.com; heatandstroke.on.ca

21 CPR Duration Is prolonged CPR really futile? No. Not for some patients. How do we know which children will survive prolonged resuscitative efforts?

22 Objective Evaluate the relationship between CPR duration and intact survival to hospital discharge after in-hospital pediatric cardiac arrest Evaluate this relationship based upon patient illness category

23 Methods: Data Source AHA Get with the Guidelines-Resuscitation (GWTG-R) Prospectively collected multicenter registry for in-hospital cardiac arrests Utstein standard reporting Rigorous data collection and abstraction Pre-defined Illness Categories based on primary dx: General Medical General Surgical Trauma Surgical Cardiac Medical Cardiac Newborn Obstetric

24 Methods A priori variables: Initial pulseless rhythm Age Event time of day Event day of week ECMO Calcium bolus Underlying sepsis or renal insufficiency Vasoactive infusion when arrest occurred P<0.2 model additions: Event location Sodium bicarb admin Prior history of arrest Prearrest apnea monitor Prearrest pulse oximeter Patient hypotension before arrest

25 Study Cohort 5,922 children (<18 years) index cardiac arrests in hospitals over 10 years

26 Exclusion Criteria Event not pulseless (n = 1318) Illness category newborn (n=762), obstetric (n=44), or other (n=4) CPR <1 minute (n=34) or missing duration of CPR (n=326) Missing primary outcome (survival to hospital discharge, n=15) 3,419 children at 328 hospitals

27 INDEX PEDIATRIC EVENTS N = 5,922 EXCLUDED: N = 2,503 EVENTS ANALYZED N = 3,419 GENERAL SURGICAL 268 (8%) SURGICAL CARDIAC 711 (21%) MEDICAL CARDIAC 572 (17%) GENERAL MEDICAL 1,477 (43%) TRAUMA 391 (11%)

28 Results 56% of the arrests occurred in hospitals with 80 pediatric beds 86% occurred in hospitals with 20 pediatric beds Mean Age: 4.9 years Nearly all were witnessed (92%) and monitored (91%)

29 Patient Illness Category Trauma 11% General Medical 43% General Surgical 8% Surgical Cardiac 21% Medical Cardiac 17% VT 5% VF 8% Unkn 15% Location of Arrest Ward 10% ED 14% Asystole 38% OR/ PACU 9% ICU 67% PEA 36% First Documented Rhythm

30 Results 27.9% survived to hospital discharge 64% survived the event (ROSC >20 min) 40% survived 24 hrs 19% (68% of the survivors) had favorable neurologic outcomes CPR 1-15 min: Probability of survival decreased linearly by 2.1% per minute Probability of favorable neurologic outcome decreased by 1.2% per minute

31 Neurologic Outcome Pediatric Cerebral Performance Category (PCPC) Score Category Description 1 Normal Normal; at age-appropriate level 2 Mild disability 3 Moderate disability 4 Severe disability 5 Coma or vegetative state Conscious, alert, able to interact at age-appropriate level; possibility of mild neurologic deficit Conscious; sufficient cerebral function for age-appropriate independent activities of daily life Conscious; dependent on others for daily support because of impaired brain function Any degree of coma without the presence of all brain death criteria; possibility of some reflexive response 6 Brain death Apnea, areflexia, and/or electroencephalographic silence Favorable neurologic outcome was defined as a PCPC of 1, 2, or 3 upon hospital discharge, or no change from baseline. Fiser DH. J Peds. 1992;121:68-74.

32 Matos R, et al. Circulation. 2013;127: Outcomes by Illness Category Gen Surg (268) Surg Card (711) Med Card (572) Gen Med (1477) Trauma (391) All (3419) Surv to d/c 38% 39% 30% 25% 10% 28% ROSC 70% 72% 63% 61% 55% 64% Surv 24hr 51% 61% 41% 34% 19% 40% Fav Neuro 27% 29% 20% 16% 6% 19% Favorable neurologic outcome was defined as a PCPC of 1, 2, or 3 upon hospital discharge, or no change from baseline. * Also re-did analysis using PCPC of 1 or 2 only as favorable

33 Results Surgical Cardiac group: Youngest group (50% <28 days) 26% had cyanotic CHD Less underlying organ dysfunction (CNS, renal, liver) Better monitoring and IV access prior to arrest More ECMO (21%) 98% inpatient, 86% in ICU Both cardiac groups had more underlying arrhythmias and less underlying metabolic derangements Trauma group: Oldest group (61% >8 years) 27% in ER, 10% in OR 27% had a pre-hospital arrest

34 Matos R, et al. Circulation. 2013;127: Proportion of Survival to Hospital Discharge by Illness Category 1-15 minutes minutes >35 minutes

35 Matos R, et al. Circulation. 2013;127: Proportion of Intact Survivors by Illness Category 1-15 minutes minutes >35 minutes

36 Probability of Outcome 0.6 Matos R, et al. Circulation. 2013;127: Survival to Hospital Discharge Survival is better for a Surgical Cardiac patient after 90 min of CPR than for a Trauma patient after 1 min of CPR. General Surgical Surgical Cardiac Medical Cardiac General Medical Trauma All Patients CPR Duration (minutes)

37 Probability of Outcome 0.6 Matos R, et al. Circulation. 2013;127: Favorable Neurologic Outcome Time is heart and time is brain! General Surgical Surgical Cardiac Medical Cardiac General Medical Trauma All Patients CPR Duration (minutes)

38 Matos R, et al. Circulation. 2013;127: Adjusted Odds Ratios for Survival to Hospital Discharge by Patient Illness Category

39 Neurologic Outcomes Matos R, et al. Circulation. 2013;127: , Too few cases to report (only 3 patients of 63 had favorable neurologic outcome in this category).

40 Why Surgical Cardiac?

41 Why Surgical Cardiac? Younger, more likely to have shockable rhythms (adjusted for in model) May be related to better monitoring? Telemetry May be related to less organ dysfunction? Cardiac disease in isolation as opposed to cardiac failure due to multi-organ failure Could it be related to preconditioning? hypoxia associated with cardiac anomaly or previous surgery makes them better able to withstand low-flow hypoxic conditions of an arrest

42 A Note on E-CPR Adjusted for ECMO in the model a priori 168/227 received ECMO and CPR>35 min Image:

43 % Survival to Hospital Discharge Matos R, et al. Circulation. 2013;128:e Unadjusted Survival with E-CPR and 50% CPR >35 minutes 40% 30% 20% E-CPR No E-CPR 10% 0% General Surgical Surgical Cardiac Medical Cardiac General Medical Trauma ALL

44 Conclusions CPR Duration is associated with survival Some patients are more likely to survive prolonged resuscitation than others Surgical cardiac > trauma Many survivors of prolonged resuscitation can have good neurologic outcomes

45 Limitations Observational voluntary registry May not be generalizable (10% US hospitals) Excluded infants cared for in NICU Including surgical cardiac patients Illness categories don t lump patients by cause of arrest, so there may be better ways to estimate prognosis Limited by lack of physiologic variables Data does not adequately reflect care since AHA change in guidelines Lack of long-term follow-up

46 Next Steps Would more children survive if we did CPR longer? How do we know when to consider E-CPR as a bridge for reversible causes? If we improve CPR quality, could we do even better?

47 Consider Individual patients have individual outcomes.

48 Acknowledgements R. Scott Watson, MD, MPH Vinay M. Nadkarni, MD Hsin-Hui Huang, MD, MPH Robert A. Berg, MD Peter A. Meaney, MD, MPH Christopher L. Carroll, MD Richard J. Berens, MD Amy Praestgaard, MS Lisa Weissfeld, PhD Philip C. Spinella, MD

49 Zachary D. Goldberger, MD, MSc, FAHA, FACP Assistant Professor of Medicine University of Washington School of Medicine Harborview Medical Center Division of Cardiology Seattle, WA Duration of Resuscitation During In-Hospital Cardiac Arrest

50 FINANCIAL OR OTHER RELATIONSHIP DISCLOSURE: None

51 Outline Epidemiology of cardiac arrest Duration of in-hospital resuscitation prior investigations Reassessment of in-hospital resuscitation recent investigations Questions and discussion

52 Epidemiology ~570,000 arrests / year in US ~360,000 Out-of-hospital ~210,000 In-hospital >1000 crashes/year ~3 crashes/day Go AS, et al. Circulation 2013;127:e-6-e245 Merchant RM, et al. Crit Care Med 2011; 39: Analogy courtesy of Peter Kudenchuk, MD

53 Sandroni C, et al. Intensive Care Med 2007;33: Girotra S, et al. N Engl J Med 2012;367: In-Hospital Cardiac Arrest 1-5/1000 admissions ~50% return of spontaneous circulation (ROSC) ~15-20% survival to discharge VT/VF PEA/Asystole Long-term outcomes largely uncertain

54 Duration of Resuscitation Lack of empirical evidence regarding an appropriate length of attempts at resuscitation Reluctance to continue efforts when ROSC has not occurred early on Extremely difficult decision to make during course of arrest

55 Prior Investigations

56 Stemmler EJ. Ann Intern Med 1965;63:613-8.

57 95% died with resuscitation >15 minutes Since efforts at resuscitation lasting more than 30 minutes appear to be uniformly unsuccessful, they should be abandoned except in unusual circumstances. Bedell SE, et al. N Engl J Med 1983;309:

58 Survival 50% 40% 30% 20% 10% 0% 23 survivors/51 arrests 45.1% 10/ % N=313 arrests 8/ % 50 survivors P < / % < >20 Minutes 5/ % Modified from Ballew KA, et al. Arch Int Med 2004;154:

59 ROSC Died p < Patients (N=330) < >60 Minutes ROSC >90% for patients resuscitated <10 mins ROSC ~50 % for patients resuscitated >30 mins Modified from Shih CL, et al. Resuscitation 2007;72:

60 Eisenberg MS, Mengert TJ. N Engl J Med 2001;344:

61 Jacobs I, et al. Circulation 2004;110: Numerous psychological and situational factors influence the time at which CPR is stopped, and this time point often is imprecise. Nevertheless, this information may be useful for developing guidelines.

62 Prior Studies: Summary Clinicians have come to rely largely upon case series and expert opinion to guide their practice Current recommendations are limited: reasonable to terminate efforts from minutes These recommendations may have broad influence in contemporary practice

63 Problem Examining all cardiac arrest victims (survivors and non-survivors) Likelihood of survival based on real times of resuscitation: short durations are associated with higher survival Challenge of endogeneity: length of attempt inherent to the outcome of attempt successful or not

64 Problem Small numbers of patients, single-center studies Unable to account for institutional differences in resuscitation care Resuscitation duration influenced by hospital practice correlation in resuscitation duration among patients within the same hospital

65 Thought Experiment 15 minutes before stopping 30 minutes before stopping

66 Recent Investigations

67 Data Source GWTG R: large, multicenter observational registry of in-hospital cardiac arrests Participating hospitals (n~600) prospectively report information on in-hospital cardiac arrests (~200,000)

68 Endpoints Primary endpoints: ROSC Survival to hospital discharge Secondary Endpoint: Neurologic status at time of discharge

69 Study Cohort 93,535 adults with index cardiac arrests at 537 hospitals, Pulseless VT/VF Asystole / pulseless electrical activity

70 Exclusion Criteria ED, OR, PACU, procedure or rehab areas, location unknown / missing (n=18,604) Hospitals without 10 or more arrests and 6 months of data (n=6,099 patients, 96 hospitals) Cardiac arrests 2minutes (n=3,163) ICDs (1,330) 64,339 patients at 435 hospitals

71 Patient-Level Analysis

72 Results Patient-Level Analysis VT/VF: 20.1% PEA/asystole: 79.9% VT/VF PEA/Asystole ROSC: 48.5% Survival to D/C: 15.4% 100% 50% 0% 48.5 ROSC 15.4 Survival to D/C

73 Cumulative ROSC Cumulative ROSC, overall 41.6% 48.5% 21.7% Some patients required more than 30 minutes to achieve ROSC Time (min) Modified from Goldberger ZD, et al. Lancet 2012;380:

74 Non-survivors Resuscitation duration, non-survivors N=33,144 Fewer than 25% resuscitated beyond 30 minutes Time (min) Goldberger ZD, et al. Lancet 2012;380:

75

76 Patient-Level Analysis: Summary Length of resuscitation attempts in nonsurvivors varies substantially across hospitals A non-trivial number of patients need more than 30 minutes to achieve ROSC Attempts in most are rarely extended beyond 30 minutes Leveraged both these findings to construct next analysis

77 Hospital-Level Analysis

78 Key Concept Correlation in duration among patients within the same hospital Resuscitation durations for patients in a given hospital may not be entirely independent events Multilevel model to examine potential differences in local practice of resuscitation across hospitals

79 Multilevel models: Hierarchical linear models Mixed models Random-coefficients models Necessary to analyze certain data in a clustered manner Each level has its own variability Patients at hospitals

80 Key Question Does how long a hospital attempts resuscitation lead to successful outcomes? Using individual data would not answer this question (problem of endogeneity) How best to determine long attempts at hospitals?

81 Exposure Variable Measure of longer resuscitation best reflected by length of attempts in patients who ultimately did not survive How long did hospitals try to resuscitate those patients who ultimately died? Focus on patient survival at hospitals which try longer before stopping

82 Hypothesis Patients at hospitals, which on average, practice longer efforts in their non-survivors, have better survival, compared with hospitals that practice shorter attempts in their non-survivors Necessary to use averaged value for exposure rather than individual s observed value

83 Hospital Quartiles Stratified hospitals into quartiles, examined potential impact of longer duration Increasing median duration among non-survivors

84 Quartile Median Duration (mins) Hospital Quartiles Hospitals Patients 13,994 18,783 19,106 12,456 Hospitals in Quartile 4 had >50% longer median duration compared to hospitals in Quartile 1 Additional minutes have substantial implications when time spent evaluating clinical responses, offering additional therapy

85 Covariates Adjustment for patient level covariates that may be linked to outcomes: Shockable initial pulseless rhythms (PVT/VF) Age, race Illness category Pre-existing conditions: None, MI during hospitalization, hypotension, hepatic insufficiency, baseline depression in central nervous system function, acute stroke, infection or septicemia, metastatic or hematologic malignancy, renal failure, major trauma

86 Covariates, cont d Interventions at the time of cardiac arrest: Invasive airway, chest tube, assisted / mechanical ventilation, vasoactive agents, antiarrhythmics, arterial line Witnessed arrest Event location (ICU, general floor/telemetry) Time from admission to event Off-hours cardiac arrest (weekend or nights) Initiation and time to first chest compressions Study period ( , , ) Hospital characteristics: Geographic region Rural location Availability of cardiothoracic surgery Emergency department

87 Adjusted Survival Rate Total Cohort: ROSC 50% 45.3% p for trend: < % 48.8% 50.7% 25% 0% Q1 Q2 Q3 Q4 Adjusted Risk Ratio (95% CI) 1.00 (Ref) 1.04 ( ) 1.08 ( ) 1.12 ( )

88 Adjusted Survival Rate Total Cohort: Survival to D/C p for trend: % 14.5% 15.2% 15.2% 16.2% 10% 0% Q1 Q2 Q3 Q4 Adjusted Risk Ratio (95% CI) 1.00 (Ref) 1.05 ( ) 1.05 ( ) 1.12 ( )

89 By Rhythm: ROSC Adjusted Survival Rate p for trend, PEA/asystole: < p for trend VT/VF: % PEA/Asystole VT/VF 60.6% 62.4% 61.8% 64.1% 41.6% 43.1% 45.6% 47.7% 30% 0% Q1 Q2 Q3 Q4 Adjusted Risk Ratio (95% CI) 1.00 (Ref) 1.04 ( ) 1.10 ( ) 1.15 ( )

90 Adjusted Survival Rate By Rhythm: Survival to D/C 30% PEA/Asystole p for trend, PEA/asystole: p for trend, VT/VF: VT/VF 32.1% 33.2% 31.4% 32.8% 20% 10% 0% 10.2% 10.7% 11.1% 12.2% Q1 Q2 Q3 Q4 Adjusted Risk Ratio (95% CI) 1.00 (Ref) 1.06 ( ) 1.09 ( ) 1.20 ( )

91 Hospital-Level Analysis: Summary Patients at hospitals with longer median resuscitation attempts, in their nonsurvivors, had better outcomes compared to those in hospitals with shorter attempts Independent of patient characteristics Particular benefit in PEA/asystole

92 Neurologic Outcomes

93 Cerebral Performance Categories Category Classification Description 1 Good performance Conscious, alert, able to work, lead normal life; minor psychologic and neuro deficits 2 Moderate disability Conscious, able to work part-time in sheltered environment, perform ADLs independently 3 Severe disability Conscious, dependent on others for daily support, limited cognition, major neurologic impairment 4 Coma/Vegetative Unconscious, unaware of surroundings, no cognitive ability, no verbal or psychological interaction with the environment 5 Death Certified as brain dead Jennett B, Bond M. Lancet 1975;1: Morrison LJ, et al. N Engl J Med 2006;355:

94 Cerebral Performance Category Classification Description 1 Good performance Conscious, alert, able to work, lead normal life; minor psychologic, neurologic deficits 2 Moderate disability Conscious, able to work part-time in sheltered environment, perform ADLs independently 3 Severe disability Conscious, dependent on others for daily support, limited cognition, major neurologic impairment 4 Coma/Vegetative Unconscious, unaware of surroundings, no cognitive ability, no verbal or psychological interaction with the environment 5 Death Certified as brain dead Favorable neurologic outcomes 2

95 Neurologic Status, Overall N=8,724 (88% of survivors to discharge) Proportion with CPC 2 p= % 80.6% 81.2% 80.0% 78.4% 50% 0% Overall <15 Minutes Minutes >30 Minutes

96 Neurologic Outcome by Rhythm PEA/Asystole: p=0.346 VT/VF: p=0.101 PEA/Asystole VT/VF 100% 88.1% 87.9% 84.0% 76.0% 74.2% 73.8% Proportion with CPC 2 50% 0% <15 Minutes Minutes >30 Minutes

97 Neurologic Outcomes: Summary Longer efforts not associated with significant detriment in discharge with favorable neurologic status, even with PEA/asystole Hospitals with longer efforts have similar neurologic outcomes and higher survival Likely due to in-hospital nature of arrests, with continuous chest compressions and other supportive measures

98 Thought Experiment Within those 15 minutes of additional treatment, something may change prognosis of the patient Large majority of gains in survival at some hospitals may be due to practice of continuing resuscitation efforts for longer periods of time than other hospitals These hospitals were able to rescue potentially salvageable patients

99 Limitations GWTG-R is observational registry: findings may not be representative of all hospitals Association does not equal causality Unmeasurable variables that affect duration of resuscitation, influence decision-making in regards to resuscitation care and outcomes, potential for residual confounding Unable to account for long-term outcomes after hospital discharge

100 Implications How best to favorably influence current practice without constraining individual decisions? Standardized approaches to ensure resuscitation attempts occur for minimum period of time could improve outcomes Extending resuscitation attempts by 10 or 15 minutes more may have marginal effects on resource utilization Time to utilize novel physiological predictors of prognosis obtained during arrest

101 Conclusions Significant variation across hospitals in duration of resuscitation attempts among non-survivors Increasing duration of resuscitation attempts prior to termination efforts may improve survival Hospitals with longer efforts had similar neurological outcomes but higher survival rates compared to those with shorter efforts Bedside clinical judgment will help balance potential benefits of longer efforts, and potential downside of futile care

102 Take Home Points No specific cut-off, but efforts to systematically increase duration of resuscitation attempts may improve survival Benefit months to years after cardiac arrest should be the ultimate measure of utility of resuscitation measures The optimal resuscitation duration for any individual patient will continue to remain a bedside decision, careful clinical judgment

103 Acknowledgments Brahmajee K. Nallamothu, MD, MPH Paul S. Chan, MD, MSc Harlan M. Krumholz, MD, SM Robert A. Berg, MD Steven L. Kronick, MD, MSc Colin R. Cooke, MD, MSc Mousumi Banerjee, PhD Mingrui Lu, MPH Graham Nichol, MD, MPH Peter J. Kudenchuk, MD