Neurologic Recovery and Prognostication

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Neurologic Recovery and Prognostication Sudden Cardiac

Disclosures Employer: University of Pittsburgh/ UPMC

Medical - NIH KL2 Clinical Scholar- University of

Steering Committee: Zoll Cool Arrest Speaker: Sacramento

1 Neurologic Recovery and Prognostication Sudden Cardiac Arrest Association Jon Rittenberger, MD, MS October 8, 2010 Disclosures Employer: University of Pittsburgh/ UPMC Grants: - National Association of EMS Physicians/Zoll Medical - NIH KL2 Clinical Scholar- University of Pittsburgh Clinical and Translational Science Institute Steering Committee: Zoll Cool Arrest Speaker: Sacramento EMS- conference sponsored by Zoll/Medtronic/Medi-Therm NIRS devices on loan from Somanetics 1

Describe new model for early stratification of postcardiac arrest illness Discuss benefits and pitfalls of prognostication during the post-arrest phase: - Clinical Examination -

2 Describe new model for early stratification of postcardiac arrest illness Discuss benefits and pitfalls of prognostication during the post-arrest phase: - Clinical Examination - Electroencephalography (EEG) - Brain Imaging (CT, MRI) - Evoked Potentials - Biomarkers Americans will suffer OOHCA today 300,000 Americans suffer OOHCA yearly 25+ will suffer OOHCA during this talk High morbidity and mortality - ~50% never make it to the hospital 2

3 Multiple Ways to Die 100% 80% 60% 40% 20% 0% Out-of-Hospital In-Hospital Location of Cardiac Arrest Survive without Symptoms Survive with Neurological Deficit Neurological Death Cardiovascular Death Multi-System Organ Failure Laver (2004) 3

4 Brain Injury after Cardiac Arrest Brain Dead Severity of Injury Normal If you have acute, severe cerebral edema, no therapy will help Duration of Ischemia Neurological Intensive Care Brain Dead Severity of Injury Normal Proper care can improve outcome for those who are in the salvageable range Duration of Ischemia 4

5 An Integrated Approach Physical / Occupational Therapy Neurology Neurophysiology Cardiology PM&R EMS Emergency Medicine Critical Care Medicine Renal Medicine Surgery Toxicology Internal Medicine Palliative Care Titrating Care - Patients are Different - Not just on Protocol Type 1 Type 2 Type 3 Type 4 5

6 Exam in Coma FOUR score has been proposed as a scale with more resolution for the intubated ICU patient. Incorporates four exams Eye movements (0-4) Motor response (0-4) Brainstem response (0-4) Respiratory pattern (0-4) Wijdicks Ann Neurol 2005;58:585 Assessment for Shock - Injury Severity Scores Serial Organ Function Assessment (SOFA) SOFA Respiratory PaO2 / >400 <400 <300 <200 <100 FIO2 Renal Creat Urine Out < <500 ml/d >5.0 <200 ml/d Hepatic Bili < >12.0 Cardiac MAP < 70 No MAP<70 Dop <5 Dop > 5 Pressors Dobut Epi < 0.1 Dop>15 Epi>0.1 NE>0.1 NE < 0.1 Hematologic Platelet >150 <150 <100 <50 <20 Neurological GCS <6 TOTAL 6

7 Classification of Post-CPR Patients Neurological Injury None Some Lots Complete Shock None Mild Severe Type 1 Type 2 Type 3 Type 4 Shock Neurological Injury Awake or waking up quickly; Combined FOUR Motor-Brainstem Score=8 7

8 Shock Neurological Injury Moderate or deep coma, but with some signs of neurological function; University of Pittsburgh Combined School of FOUR Medicine Motor-Brainstem - Department of Emergency Score Medicine 4-7 Combined SOFA Cardiac and Respiratory Score <4 Shock Neurological Injury Moderate or deep coma, but with some signs of neurological function; University of Pittsburgh Combined School of Medicine FOUR Motor-Brainstem - Department of Emergency Score Medicine 4-7 Combined SOFA Cardiac-Respiratory Score 4 8

9 Shock Neurological Injury Coma with minimal or absent brainstem reflexes University of Pittsburgh Combined School of Medicine FOUR Motor-Brainstem - Department of Emergency Scores Medicine 4 Survival and Good Outcome Good Poor

10 Multiple Organ Failure Rhythm and Category VF/VT PEA Asystole Unknown Category I Category II Category III Category IV

Neurologic Prognostication One Potential Model CT

Consider Stimulants Optimize Perfusion and

11 Neurologic Prognostication One Potential Model CT scan EEG SSEP* Consider Repeat EEG, SSEP Consider MRI Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Hypothermia Physical / Occupational Therapy; Consider Stimulants Optimize Perfusion and Metabolic Status Discuss long-term support; tracheostomy, feeding tube 11

12 Prognostication Wijdicks (2006) American Academy of Neurology Prognostication Wijdicks (2006) American Academy of Neurology Easter Syndrome At 72 hours, the doctor will tell us if he is going to make it 12

13 Clinical Examination A Cautionary Case Day male arrived in ED after resuscitation from PEA - likely overdose of heroin and xanax - found in arrest by girlfriend who saw him snoring 30 minutes prior - Epi x 3 mg, naloxone x 2 mg, bicarb x 2 amps, amiodarone (300 mg) Surprised we got him back - Sluggish pupils; No gag or cough; Decorticate - Pressure 80/p --> dopamine, norepinephrine - ABG- ph 6.86; pco2 81; po2 373; Lactate = LFT s - ASL 1551; ALT Hypothermia --> 32º for 24 hours 13

14 Early CT/MR Findings Whole brain is tight. Basal ganglia have edema / ischemic changes. (More common with asphyxial / respiratory events) A Cautionary Case Day 1 (24 hrs) - - Sluggish pupils, weak cough, decorticate - Rhabdomyolysis - renal failure - CVVHD Day 2 (48 hrs) - Pupils react, decorticate, some shaking tremor Day 3 (72 hrs) - Pupils react, no oculocephalic reflex, decorticate, shaking all over, eyes closed 14

15 A Cautionary Case Day 1 (24 hrs) - - Sluggish pupils, weak cough, decorticate - Rhabdomyolysis - renal failure - CVVHD Day 2 (48 hrs) - Pupils react, decorticate, some shaking tremor Day 3 (72 hrs) - Pupils react, no oculocephalic reflex, decorticate, shaking all over, eyes closed Day 4 (96 hrs) - Withdrawal of leg from pain Day 5 (120 hrs) - Awake A Cautionary Case Day 17 - Transfer to Rehab (still on dialysis) Day 34 - Home Six-Month Follow-up - Off dialysis; Running 4-5 miles / day; just returned from Caribbean vacation; Continues in drug rehab. 15

16 Local Data: Motor Examination at 72 hours 272 patients treated between cooled, 111 normothermia GCS Motor >3 GCS Motor 3 Odds Ratio (95% CI) 72 hour- Not Cooled (Survival) 33/63 (52%; 95% CI 14, 33%) 4/12 (33%; 95% CI 2, 64%) 2.2 (0.60, 8.06) 72 hour- Cooled (Survival) 44/69 (64%; 95% CI 52, 76%) 4/28 (14%; 95% CI 0, 29%) (3.29, 33.92) Rittenberger et al. Resuscitation 2010;81(9): Local Data: Motor Examination at 72 hours 272 patients treated between cooled, 111 normothermia GCS Motor >3 GCS Motor 3 Odds Ratio (95% CI) 72 hour- Not Cooled (Survival) 33/63 (52%; 95% CI 14, 33%) 4/12 (33%; 95% CI 2, 64%) 2.2 (0.60, 8.06) 72 hour- Cooled (Survival) 44/69 (64%; 95% CI 52, 76%) 4/28 (14%; 95% CI 0, 29%) (3.29, 33.92) Rittenberger et al. Resuscitation 2010;81(9):

17 Local Data: Brainstem Examination at 72 hours 72 hour not cooled (survival) 72 hour cooled (survival) Pupil Present 2/39 (56%; 95% CI 40, 73%) 41/56 (73%; 95% CI %) Pupil Absent 0/1 (0%; 95% CI 0, 50%) 0/16 (0%; 95% CI 0, 3%) 72 hour not cooled (survival) 72 hour cooled (survival) Corneal Present 22/39 (56%; 95% CI 40, 73%) 42/53 (79%; 95% CI 67, 91%) Corneal Absent 0/1 (0%; 95% CI 0, 50%) 0/20 (0%; 95% CI 0, 3%) Local Data: Brainstem Examination at 72 hours 72 hour not cooled (survival) 72 hour cooled (survival) Pupil Present 2/39 (56%; 95% CI 40, 73%) 41/56 (73%; 95% CI %) Pupil Absent 0/1 (0%; 95% CI 0, 50%) 0/16 (0%; 95% CI 0, 3%) 72 hour not cooled (survival) 72 hour cooled (survival) Corneal Present 22/39 (56%; 95% CI 40, 73%) 42/53 (79%; 95% CI 67, 91%) Corneal Absent 0/1 (0%; 95% CI 0, 50%) 0/20 (0%; 95% CI 0, 3%) 17

18 Patience mon Capitan! GCS is most predictive for good outcome at day 4. Sensitivity 84%, PPV 92.5% Schefold, et al. Resuscitation 2009;80(6): CT Imaging Review of 182 CT s obtained within 24 hours of arrest Analyzed results based on initial Glasgow Coma Scale 18

19 CT Imaging by Coma Severity Normal Acute Diffuse Ischemia Acute Focal Ischemia Old Changes Ageindetermi nate changes Acute Bleed Unable to interpret GCS (32%) 33 (32%) 6 (6%) 22 (21%) 2 (2%) 3 (3%) 4 (4%) GCS (59%) 4 (9%) 2 (4%) 8 (17%) 1 (2%) 1 (2%) 3 (7%) Peoples J. Acad Emerg Med 2010 CT Imaging: Survivorship Normal Acute Difuse Ischemia Acute Focal Ischemia Old Changes Ageindetermi nate changes Acute Bleed Unable to interpret Survived 20 (67%) 1 (3%) 3 (10%) 3 (10%) 1 (3%) 0 (0%) 2 (7%) Died 40 (34%) 36 (30%) 5 (4%) 27 (23%) 2 (2%) 4 (3%) 5 (4%) Peoples J. Acad Emerg Med

survival in pediatric drowning victims 1.

20 Grey to White Matter Ratio Proposed as an early predictor of survival Associated with survival in pediatric drowning victims Decreasing GWR * * * *p<

21 ROC Curve: Predicting Death Avg GWR is 100% predictive of death Cutoff =1.2 GWR<1.2 GWR>1.2 Surv 0% (0/47) 95% CI 0-1% Surv 58% (76/130) 95% CI 50-67% CT scan EEG SSEP* Consider Repeat EEG, SSEP Consider MRI Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Hypothermia Physical / Occupational Therapy; Consider Stimulants Optimize Perfusion and Metabolic Status Discuss long-term support; tracheostomy, feeding tube 21

22 Comparison to Other Studies Torbey (2000) - 25 adult pts, Ratio < % specificity - Ctrl group GWR (median range) Choi (2008) - 28 adult pts, ratio < % specificity - Ctrl group GWR 1.32 (0.05) Rafaat (2008) peds drowning pts, abnormal CT + GCS=3, 100% specificity EEG 22

incidence of 47% in pediatric CA subjects - Myoclonic status epilepticus -

23 Brain Monitoring- EEG Several bad findings possible - Nonconvulsive status epilepticus (NCSE) HACA (2002) estimated incidence of 7-8% Abend (2009) noted incidence of 47% in pediatric CA subjects - Myoclonic status epilepticus - Isoelectric baseline Most literature is pre-hypothermia EEG Post-Arrest: Shivering 23

24 EEG Post-Arrest: Paralyzed, on propofol EEG Post-Arrest: Paralyzed, Off propofol 24

25 Across the hall 25

26 Seizures are Common %: Incidence of electrographic seizure Progression of EEG patterns Epileptiform Discharges: 50% GPED: 22% NCSE: 10% Burst Suppression: 55% MSE: 24% 26

27 Not all patients are at equal risk Electrographic seizure incidence varied by category of arrest (p=0.045) - Category II: 3/31 (10%) - Category III: 4/10 (40%) - Category IV: 10/35 (29%) Electrographic seizure incidence did not vary by rhythm of arrest (p=0.141) or location of arrest (p=0.842) Seizures occur early Time from arrest to ceeg placement is 8 (IQR 6, 11) hours. - Increasing time to diagnosis of nonconvulsive seizures is associated with increased mortality (Young GB, et al. Neurology 1996;47:83-89.) Most (53%) electrographic seizures on ceeg are evident in the first 30 minutes of the recording 27

28 Survival and Good Neurologic Outcomes Same subject Electrographic Seizures GPEDS NCSE Survival Good Outcome 1/17 (6%) 0/17 (0%) 1/17 (6%) 1/8 (13%) 0/17 (0%) 0/8 (0%) Triphasic Waves 0/1 (0%) 0/1 (0%) BS MSE Epileptiform Discharges 5/42 (12%) 0/18 (0%) 3/42 (7%) 0/18 (0%) 5/38 (13%) 1/38 (3%) MRI 28

29 MRI Literature limited to small cohorts Diffusion Weighted Imaging (DWI) may allow quantification of injured brain One study noted that all survivors lacked temporal and parietal lobe injuries - Jarnum. Resuscitation 2009;80:

30 Bad Brain? Basal Ganglia Infarcts Watershed Infarcts Comatose after day 2 Yes Our Local Experience Survival 28/47 (60%) Good Outcome 15/47 (32%) MRI median 61 (IQR 34-97) hours Normal 10/47 (21%) Chronic Changes 17/47 (36%) Survive 8/10 (80%; 95%CI %) 12/17 (71%; 95%CI %) Good Outcome 6/10 (60%; 95%CI %) 4/17 (24%; 95%CI %) 8/14 (40%; 95%CI %) Acute Changes 14/39 (36%) 5/14 (25%; 95%CI %) 30

31 SSEP SSEP: Median Nerve Electrical Stimulation Picture from Rothstein

32 SEP- Short Latency Cortical Response (N20) Somatosensory Evoked Potential (SSEP) Determines presence of cortical response (N20) to peripheral stimuli Absence of N20 highly predictive of no cortical recovery - Bedside test - Not affected by most drugs (exception is midazolam) - Hypothermia does not abolish N20 until T<~20ºC - However, presence of N20 does not guarantee good recovery 32

SSEP after Cardiac Arrest Normal N20 Absent N20 Left Right Rothstein 2004 Jorgensen 2006 SSEP and Outcome Absent N20 performed >24 hours post-cpr has strong association with not awakening in

33 SSEP after Cardiac Arrest Normal N20 Absent N20 Left Right Rothstein 2004 Jorgensen 2006 SSEP and Outcome Absent N20 performed >24 hours post-cpr has strong association with not awakening in literature - 0/249 (0%) awaken - 95% CI (0-1.5%) Present N20 does not necessarily mean good outcome / 438 (32%) awaken - 95% CI (28-37%) All data are prehypothermia Zandbergen 1998; Zanbergen

34 A Case Report 43 year old male, asystolic arrest. Received hypothermia Day 3: intact pupils, no response to pain. Absent N20 response bilaterally Survived and awoke Leithner. Neurology 2010;74: N20 Response Normal Response No Response 34

35 Serum Biomarkers Serum Biomarkers of Injury Serum NSE of >33ug/L at 72 hours predicts poor outcome (pre-hypothermia) - Zandbergen. Neurology 2006;66:62-8. Serum NSE >25ug/L at 48 hours predicts poor outcome (hypothermic and normothermic patients) - Tiainen. Stroke 2003;34: Small sample size 35

36 NSE in a larger group 90 patients receiving hypothermia Increase in NSE of 6.4 ug/l between hours was 100% specific in predicting poor outcome. - Oksanen T. Resuscitation 2009;80: Prediction of outcome following cardiac arrest is difficult Early predictors - CT with G:W ratio of <1.2 appears to be predictive of death - Seizures portend poor outcome Late predictors (72+ hours) - Absent pupil or corneal response - Absent bilateral N20 on SSEP - Increasing NSE (but not an absolute value!) 36

Alexandra Popescu, MD Emanuel Kanal, MD Miguel Habeych, MD Margo Holm, PhD Dave

37 Acknowledgements Clif Callaway, MD, PhD Frank Guyette, MD, MPH Ankur Doshi, MD Jestin Carlson, MD Rene Alvarez, MD Samuel Tisherman, MD Richard Brenner, MD Alexandra Popescu, MD Emanuel Kanal, MD Miguel Habeych, MD Margo Holm, PhD Dave Hostler, PhD James Menegazzi, PhD Ron Roth, MD Mark Pinchalk, EMT-P, MS Curt Niel, EMT-P 37

Neurological Prognosis after Cardiac Arrest Guideline

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