Hypothermia Post Cardiac Arrest: An Update

Transcription

1 Hypothermia Post Cardiac Arrest: An Update Justin Lundbye, M.D., FACC Hospital of Central Connecticut

2 Outline Background Whom to Cool How to Cool Post Cardiac Arrest Care Other uses for TTM 2

3 Definition Therapeutic hypothermia can be defined as the reduction of the core body temperature of a patient to 32 C - 34 C in order to prevent or reduce neurologic (end-organ) injury. 3

4 Protection Mechanisms of Hypothermia Ischemic brain protection from therapeutic Hypothermia may be: attenuation of biosynthesis, release and uptake of excitatory amino acids diminished hydroxyl radical production protection of cell membranes attenuation of intracellular acidosis reduction of oxygen demand by the injured cells (5-7%/ºC) Metabolic Respite N Engl J Med 2002;346:

5 Hypothermia Therapy the history TH used acute brain injury stems back to the 1950s TH (28/32/8C) before CA has been used successfully since the 1950s to protect the brain against the global ischemia Results were inconclusive up until late 1990s HACA & Bernard TTM Study Group 5

6 National Statistics 382,800 patients with OHCA 60% of OHCA are treated by EMS 23% are shockable rhythm on presentation Survival to D/C is 11.4% 209,000 patients treated for IHCA 23 % survival to discharge Circulation. 2012;125:e2-e Survival 6

7 Whom to Cool Shockable Rhythm

8 Ventricular Fibrillation 8

9 Bladder Temperature in the Normothermia and Hypothermia Groups 9

10 Ventricular Fibrillation Outcome Normothermia Hypothermia RR (95% CI) P Value Favorable Neurologic Outcome* 54/137 (39) 75/136 (55) 1.40 ( ) NNT=6.25 Death 76/138 (55) 56/137 (41) 0.74 ( ) N Engl J Med 2002;346, No 8

11 Ventricular Fibrillation Outcome Hypothermia (n=43) Normothermia (n=34) Normal/Minimal Disability % 26% Moderate Disability 6 2 Severe Disability 0 1 Unconscious 0 1 Death N Engl J Med, Vol. 346, No. 8

12 Recommendation for Shockable Rhythm at Presentation Cool if the patient is: S/P VF/VT arrest with ROSC Unresponsive No major co-morbidities Class I Don t Cool if the patient is: Fully responsive 12

13 Pulseless Electrical Activity (PEA) & Asystole

14 Definition PEA Defined as organized electrical activity without detectable pulse. Asystole Defined as absence of electrical activity and pulse. 14

15 Epidemiology About 77% of OHCA is non-shockable 58.5% of in-patient have non-shockable cardiac arrest 15

16 Etiology PEA frequently results from a primary condition that profoundly decreases preload/after load or causes severe inflow/outflow obstruction. The most common cause of PEA is severe respiratory insufficiency or respiratory arrest causing myocyte depression through metabolic derangement 16

17 Reversible Causes Tension pneumothorax Metabolic acidosis. Hypothermia. Hypoxia. Pulmonary embolism. Hypovolemia. Hyperkalemia. Cardiac Tamponade. 17

18 The Hypoxic Cause Hypoxia ensue HR & BP HR & BP Loss of Aortic Fluctuation Further decrease in HR Asystole Time in Minutes T 0 T 2-3 T 7 T 11.4 T 31 Following loss of aortic fluctuations in animal models, pulseless electrical activity can remain for up to 20 min Resuscitation 30 (1995)

19 The Hypoxic Cause Resuscitation 30 (1995)

20 The cardiac Effect Hydrogen ions compete with calcium for binding to the myocardial protein troponin. concentrations of intracellular H +, a smaller percentage of the available Ca is able to react with troponin, fewer actin-myosin interactions occur, and the strength of contraction is reduced. Kidney International, Vol. 1 (1972), p

21 The Hypoxic Cause Hypoxic Cardiac Arrest Early profound metabolic derangement Early tachycardia then bradycardia Prolonged electrical activity without pulse 21

22 Survival Pre-Hypothermia Patients who have SCA due to PEA have outcome with only 11 percent survived until hospital discharge N Engl J Med. 1997;337(5):301 When initial rhythm is asystole, survival is only ~2 percent until hospital discharge N Engl J Med. 1991;325(20):

23 Therapies Should Therapeutic Hypothermia be used for the PEA/Asystole patient population? 23

24 Non-Shockable Rhythms Author n Control TH P-value Sunde et al 15 Not Reported Oddo et al 23 0/11 2/12 NS Bernard et al 10 Not Reported Busch et al 20 Not Reported Don et al /19(19%) 26/122(21%) NS Arrich /73(19%) 35/124(28%) NS Dumas /176(17%) 38/261 (15%) NS Lundbye 100 5/48(10.4%) 15/52(28.8%) 0.02 Grossestreuer 405 (13.7%) (21.4%)

25 Therapeutic Hypothermia vs. Historic Control at Hartford Hospital 40% 35% 30% 25% 20% 15% 10% 5% 0% P= % 28.8% Favorable Neurologic outcome P= % 34.4% P= % 20.0% All Patients PEA Asystole Resuscitation 2012 Feb;83(2): Epub 2011 Aug Control (N=48) Hypothermia (N=52)

26 UPENN PEA Experience 35% 30% Survival CPC 1 or % 25% 20% 15% 17.60% 13.70% 21.40% Control Hypothermia 10% 5% N=405 0% PEA/Asys PEA/Asys Grossestreuer, AHA ReSS

27 Meta-analysis Good CPC Critical Care :215 27

28 Meta-analysis - Survival Critical Care :215 28

29 Recommendation for Non-Shockable Rhythm at Presentation Cool if the patient has: PEA or Asystole with ROSC Reversal of cause Unresponsive Class IIb Don t Cool if the patient has: Irreversible cause 29

30 In-Hospital Cardiac Arrest The rates of survival to discharge after in-hospital cardiac arrest is 23% among adults. 18% have VF or pulseless VT as the first recorded rhythm. Of these, 43% survive to discharge More common to see non-shockable rhythms 30

31 Outcomes of Mild Therapeutic Hypothermia After In-Hospital Cardiac Arrest A total of 33 IHCA patients met inclusion The MTH group had 24% (4/17) CPC 1 & 2 The control group had 31% (5/16, P =.70) CPC 1 & 2 Kory et al, Neurocrit Care (2012) 16: Lundbye TH /6/

32 Survival with Good Neurologic Outcome (CPC 1 or2) P=0.037 Lundbye TH /6/

33 Recommendations by In-Hospital Cool if the patient: Has ROSC with any rhythm Unresponsive Class IIb Don t Cool if the patient is: DNR Prolonged downtime (>30 minutes) 33

34 Inclusion Criterion Survivors of cardiac arrest (In- & out-patient) VT/VF/Asystole/PEA Non-responsive off sedation (GCS<8) Blood pressure > 90 systolic (On or off pressors) Downtime < 30 minutes 34

35 Acute Coronary Syndrome Patients

36 Special Populations - STEMI Patients Initiate cooling in ED or EMS Ice packs Administer Loading dose of a P 2 Y 12 inhibiting agent After Revascularization CL team inserts cooling catheter Patient continues therapy in CCU STEMI patients TH Does not effect D2B time Improves mortality & neurologic outcome Trend towards more bleed Crit Care Med 2008 Vol. 36, No. 6 36

37 Cardiac Catheterization - timing CAD is present in the majority of out-of-hospital cardiac arrest patients. Acute myocardial infarction is the most common cause of sudden cardiac death. 37

38 Immediate Coronary Angiography in Survivors of Cardiac Arrest 48% of those with significant CAD had fresh thrombus that did not correlate with ECG findings Normal coronary arteries 20% Non critical <50% CAD 8% Significant CAD (>70%) 72% Single vessel disease 37% Two vessel disease 22% Three vessel disease 40% Isolated LM disease 1% Spaulding et al. NEJM 1997;336:

39 Post Cardiac Arrest Angiogram Immediately if STEMI on ECG Treat pharmacologically if NSTEMI/UA Take to CL once neurologically improved or persistent ischemia 39

40 How to Cool

41 The Protocol Induction Cool as rapid as possible to a target of 33 C (32-34) Maintenance: Maintain the patient at target temp for 24 hrs Rewarming: Rewarm slowly and controlled 41

42 Application of Therapeutic Hypothermia Iced Packs Started by EMS/ED Iced Saline? Patient Controlled Cooling 42

43 Cooling Techniques How do we cool: IV 4 Celsius Intravascular Heat Exchange Ice Packs 43

44 Cold Infusions Alone This study investigated if hypothermia could be induced and maintained by repetitive infusions of cold fluids < 32 ºC N=0 1 Patient Died Cooling Start N= ºC N=13 > 34 ºC N=7 Endovascular Cooling ml/kg/30 min for induction > 34 ºC within 6 Hours N=9 > 34 ºC after 6 Hours N= ºC Remaining N=2 Resuscitation (2007) 73, Endovascular Cooling Additional Fluid Bolus ºC Remaining 44

45 RCT out of University of Washington JAMA. 2014;311(1): doi: /jama

46 JAMA. 2014;311(1): doi: /jama

47 JAMA. 2014;311(1): doi: /jama

48 IVTM - Catheter Intravascular Surface Cooling 48

49 Surface vs. Intravascular Multivariate Analysis Failure related to weight Male Sex Early Angiogram Temp on admission Intensive Care Med Jan

50 Time to Hypothermia METHODS: 49 consecutive patients successfully resuscitated from CA were enrolled. Based on the neurologic outcome at discharge, the patient group was dichotomized into good and poor outcomes RESULTS: 28 patients were discharged with a good outcome. MVA showed time to Goal temp. (odds ratio for every h TTT: 0.69 [95% confidence interval: ]) to be independent predictors for good outcome. CONCLUSIONS: Early achievement of therapeutic hypothermia favor a good neurologic outcome. Int.J.Cardiology

51 Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest: Evaluation of a Regional System to Increase Access to Cooling 140 OHCA patients who remained unresponsive after ROSC were cooled A 20% increase in the risk of death (95% CI, 4% to 39%) was observed for every hour of delay to initiation of cooling Circulation. 2011;124:

52 Time to Target Temperature N = 172 patients Resuscitation 83 (2012)

53 What s the correct target temp? (if any)

54 The Importance of Post-Cardiac Arrest Care 33 C Control 33 C Control 32 C 34 C 33 C 36 C 55

55 TTM Trial Investigators Multicenter, randomized trial, compared patients who had been resuscitated after OHCA a target body temperature of 33 C a target body temperature of 36 C 36 intensive care units (ICUs) in Europe and Australia (950 pt.) Nielsen N et al. N Engl J Med 2013;369:

56 TTM Trial Investigators Nielsen N et al. N Engl J Med 2013;369:

57 TTM Trial Investigators Nielsen N et al. N Engl J Med 2013;369:

58 TTM Trial Investigators Nielsen N et al. N Engl J Med 2013;369:

59 TTM Trial Bystander witnessed/performed CPR arrest 90/72% 80% of patients were shockable Only 10 hours where Temp was statistically different between the 36 C and 33 C Large temperature variations 36 C is still an active management arm 60

60 Degree of injury Mild Will do well regardless of therapy Moderate Requires dosed TTM? Longer? Cooler Severe Poor outcome with any TTM Short Down Time VT/VF Long Down Time PEA/Asys 61

61 Time from Collapse to ROSC Resuscitation 2014 Sep 2;85(9):e

62 Target Temperature 32 vs. 34 Celcius Lopez-de-Sa E et al. Circulation 2012;126:

63 Target Temperature 32 vs. 34 Celcius Asystole Only VF only 64

64 Peri and post Hypothermia Care

65 Pharmacologic Intervention Pepcid GI prophylaxis Heparin 5000 units SC Q8 hours Unasyn for 3 days Magnesium Sulfate All affected by MTH Aspirin 325mg NGT/PR Q Daily For ACS in the ED Propofol 66

66 Bleeding With MTH there is a theoretical increased risk of bleeding. Patients with active bleeding remain relative contraindicated receive MTH. HACA reported no statistical difference in bleeding rate. 67 N Engl J Med 2002

67 Infection Immune response during MTH is attenuated from reduced: Chemotactic activity Phagocytic activity Decreased phagocyte activity results in increased risk of infection. Data is limited 68

68 ICU Infection No Hypothermia 26 (46%) new infections in patients admitted to ICU after OHCA Source Number (n=56) Pneumonia 17 Vascular catheter 6 Blood stream 5 Urinary tract 4 Sinusitis 3 Cholecystitis 2 Pseudomembranous colitis 1 Meningitis 1 Wound 1 Resuscitation 60 (2004)

69 Infection - Hypothermia Lung infection is the most common site of infection: N= 421 Early Onset Pneumonia Late Onset Pneumonia BSI CRBSI GpB GnB Others Total % Critical Care Medicine. 39(6)

70 Hartford Hospital Experience Prompt cooling catheter & CVC removal Ampicillin-Sulbactam - CPOE Total no. of pts. with CLABSI n=0 (0%) Total no. of patients who underwent TH n=131 Total no. of pts. included in the study n=115 (88%) Total no. of pts. excluded n=16 (12%) Total no. of pts. with bacteremia* n=1 (0.9%) UTI n= 4 (3.5%) Pneumonia n=18 (16%) Patel et all, Conn Medicine 1/

71 Infection Summary and Recommendations Proinflametory cytokines are blunted during MTH Infection is a common complication of MTH Pneumonia (67% of patients undergoing MTH) Ampicillin-sulbactam has been instituted as a tool to reduce aspiration pneumonia at HHC Early removal of CVC is advocated as a means to reduce CLABSI 72

72 Shivering Increased metabolic demand Heat Production Increased oxygen demand 73

73 Shivering Summary Cutaneous Counter warming Buspirone 30 mg PO Q 8 Mepiridine mg IV Magsulfate 2 gm IV Dexmedetomidine µg/Kg/hr Propofol Vecuronium 0.1 mg/kg IV 74

74 The Cardiovascular System and Therapeutic Hypothermia

75 MTH & Cardiovascular Disorders Ejection fraction after 15 min of VF: A. Pre-arrest = 58% B. 30 minutes = 42% C. 2 hours = 33% D. 5 hours = 25% E. 48 hours = 54 Am Coll Cardiol, 1996; 28:

76 MTH and Shock Increase contractility Decrease oxygen demand (Up to 28%) Decrease inflammation Net increase in CI Ohman et al, JACC 59, (7) 2012, Pages

77 CHILL-MI & RAPID MI-ICE Pooled RAPID MI-ICE and Chill-MI data shows continued reduction in heart failure at 45 days % Heart Failure P= % Hypo (N= 69) 16% Control (N=69) Heart failure incidence lower in hypothermia group All heart failure occured in patients with anterior STEMI No mortality in either group 78

78 Other uses for TTM Myocardial infarction

79 Other Uses Rewarming trauma patients Fever Control Stoke Patients 80

80 Summary 1. National survival rates for cardiac arrest have improved 2. Cooling should be used in most patients with ROSC post cardiac arrest. 3. Intravascular cooling may be superior 4. TTM demonstrated that fever management is important more studies needed 5. Complications are minimal (Infection) 6. Stoke, trauma, burns and re-warming are other uses 81

81 Conclusion Mild Therapeutic Hypothermia improves the change of favorable neurologic outcome and recovery in patients that have Return of Spontaneous Circulation post cardiac arrest. 82