Anoxic Auguring: Neurological Prognostication After Cardiopulmonary Resuscitation

1. Anoxic Auguring:Neurological Prognostication After Cardiopulmonary Resuscitation Robert Altman PGY 4, Neurology Resident McGill University Where do we stand in 2011? Division of Neurology, McGill University Health Center May 18th 2011

2. πρόγνωση • Prognosis • “Fore-knowing” Φρόνησις • Phronesis • “Practical wisdom”

3. Case 1 • 55 M collapses while jogging • CPR immediately initiated by bystander • V-fib arrest; circulation restored after 6 minutes • Exam (day 1): comatose, absent pupillary and corneal reflexes, extensor posturing to pain, myoclonic status epilepticus • CT head (day 2): Normal study • SSEP (day 3): Absent N20 responses • Exam (day 3): Unchanged

4. Case 2 • 35 M collapses while playing basketball • CPR immediately initiated by bystander • PEA arrest; circulation restored after 20 minutes • Induced hypothermia x 24 hours (32 degrees C) • Exam (day 1):Comatose, pupils fixed, triggers ventilator but otherwise no evidence of intact brainstem function, no spontaneous movements or motor response to noxious stimuli • EEG (day 2): Severe diffuse slowing of cerebral activity • Exam (day 3): Comatose, pupils reactive, oculocephalic, corneal, and gag reflexes intact, triggers ventilator, flexor posturing of upper limbs to pain, no spontaneous movements

5. Case 3 • 71M with HTN, CAD (previous CABG), collapsed at home • No CPR administered • PEA arrest; circulation restored after 20 minutes • Exam (day 1): Comatose, R pupil reactive/L pupil fixed, corneal reflex present but sluggish, no ocular response to cold calorics, no spontaneous movements, left arm and leg withdraw to painful stimuli, bilateral Babinski signs • MRI brain (day 2): Cerebral infarctions in superficial and deep watershed territories bilaterally (L > R) • SSEP (day 3): N20 response present on right, absent on left • Exam (day 3): Unchanged

6. Why does neurology get called to evaluate these cases? Outcome? Poor or favourable? Why? What do you base your judgement on?

7. Outline • Cases • Historical Perspective • Prognostication Guidelines • The Era of Hypothermia • Approaching the Family • Return to Cases • Take Home Points

8. Mission (im)possible? The neurologists role: To predict with perfect accuracy the likelihood of awakening and (if the patient survives) future morbidity.

9. Self-fulfilling prophecy? • A physician’s negative expectation or overreliance on laboratory tests affects management decisions and thus outcome. • Therefore paramount that studies adhere strictly to independent assessment of prognostic indicators and outcomes

10. ‘Poor’ Prognosis • Glasgow Outcome Scale (GOS) ≤ 3 • Cerebral Performance Scale (CPC) ≥ 3 • Emphasis on the ‘poor’ because may facilitate decision for withdrawal of life-sustaining therapies • Tests ideally have a 0% FPR for determining poor prognosis, narrow CI’s N.B. No postarrest physical examination finding or diagnostic study has as yet predicted poor outcome of comatose cardiac arrest survivors during the first 24 hours after ROSC

11. N Engl J Med 2009;361:605-11

12. C. Booth JAMA, February 18, 2004—Vol 291, No. 7

13. Outcomes Bernat. Neurology® Clinical Practice 2010;75(Suppl 1):S33–S38

14. History of Prognostication • Levy et al (1985) establishes algorithms for neurological prognosis • Determinations derived from a single cohort study, 211 patients • Not without limitations • Statistical uncertainty • Since (late 70’s); revolution in critical care since this era • How many patients suffered from a cardiac arrest in the Levy cohort? How many were cooled? • Only 71% suffered cardiac arrest • TH only introduced in 2002 Levy DE, et al. JAMA 1985;253:1420-1426

15. Meta-analysis of relevant literature from 1966-2006; 391 papers reviewed and rated. E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203

16. AAN Recommendations E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203

17. The Tools • Physical exam, clinical findings • Blood work – Biochemical Signs • Neuroimaging (CT, MRI) • Electrophysiology (EEG, SSEP)

18. The Tools • Physical exam, clinical findings • Blood work – Biochemical Signs • Neuroimaging (CT, MRI) • Electrophysiology (EEG, SSEP) Clinical Exam Direct assessment Brainstem

19. Physical exam, clinical findings • Present vs. Absent (day 1 to 3) • Pupils (CN II,III) • Corneal reflex (CN V, VII) • Cold calorics(CN VIII, VI, III, MLF) • Motor responses (day 1 to 3) • Flexion vs. extension / none 0 % FPR for poor outcome, narrow CI’s, 10 studies.

21. Clinical Exam • Since Levy et al. • Prospective, class I studies. Zandbergen, et al. Neurology 2006;66:62–68.

22. Point in fact – Clinical Exam • The brainstem is more resistant to anoxia than the cortex, thus if abolished BS reflex, this generally implies a severely damage cortex • Preserved BS reflexes by no means imply intact cortical function • No direct way of evaluating cortical activity in an unconscious patients

23. Related to Poor Outcome but Insufficient Predictive Value • Age • Sex • Cause of arrest • Type of arrhythmia (vfib or asystole) • Total time of arrest • Duration of CPR Based in 2 large prospective studies involving 774 patients E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203

24. The Tools • Physical exam, clinical findings • Blood work – Biochemical Signs • Neuroimaging (CT, MRI) • Electrophysiology (EEG, SSEP)

25. Blood work – Biochemical Signs • NSE (neuron-specific enolase) • S100 (glial protein) • BB fraction of creatine kinase (serum or csf) • Neurofilament protein • Combination panels

26. Blood work – Biochemical Signs • NSE (neuron-specific enolase) • S100 (glial protein) • BB fraction of creatinekinase (serum or csf) • Neurofilament protein • Combination panels

27. Blood work – Biochemical Signs • NSE (neuron-specific enolase) • ≥33µg/L, b/w 1-3d post arrest • Reflects diffuse CNS injury • Only validated use in carcinoid & other tumors • Not commonly available in N. America • Not at MUHC, CHUM, Ontario • Variability in assays and cut-off values • Class B • 0 % FPR for poor outcome, CI 0-3; • One class I study

28. The Tools • Physical exam, clinical findings • Blood work – Biochemical Signs • Neuroimaging (CT, MRI) • Electrophysiology (EEG, SSEP)

29. The Tools • Physical exam, clinical findings • Blood work – Biochemical Signs • Neuroimaging (CT, MRI) • Electrophysiology (EEG, SSEP)

30. Neuroimaging • Findings correlate poorly with functional prognosis • Performed to rule out primary neurological catastrophe, as aetiology of cardiovascular event • However, • CT often normal on day 1 • Technical barriers may preclude neuroimaging • i.e. Hemodynamic instability, inability to transfer • Class U Diagnostic value not prognostic

31. The Tools • Physical exam, clinical findings • Blood work – Biochemical Signs • Neuroimaging (CT, MRI) • Electrophysiology (EEG, SSEP)

32. The Tools • Physical exam, clinical findings • Blood work – Biochemical Signs • Neuroimaging (CT, MRI) • Electrophysiology (EEG, SSEP) Cortical and subcortical GM indirectly EEG , SSEP

33. EEG • Early myoclonic status correlates with poor outcome • At 24hrs, 0% FP • Bilaterally synchronous twitches of limb, trunk or facial muscles • Supported by autopsy and multiple trials • Status epilepticus, GTC seizures, multifocal asynchronous myoclonus • Represent nonspecific indicator of metabolic encephalopathy without real prognostic value E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203

34. EEG • FPR for poor outcome 3%(95% CI: 0.9% to 11%) with malignant EEG patterns • Malignant categories include suppression, burst-suppression, alpha and theta pattern coma, and generalized periodic complexes combined; “(malignant EEG group)...therefore strongly but not invariably associated with poor outcome” E.F.M. Wijdicks, A. Hijdra, G. B. Young, et al. Neurology 2006;67;203

35. Status Epilepticus

36. Burst Suppression

37. Myoclonic Status 18 hours after resuscitation, patient was in coma with intact brainstem reflexes 86 F, post cardiac rest Etiology unclear Duration of downtime unknown Clinical movements q3-5

38. Video of myoclonic status epilepticus

39. What is SSEP? • SSEP = Somatosensory Evoked Potential • N20 response primary somatosensory cortex • 200 consecutive rapid stimulations are given to the median nerve • Recorded at • brachial plexus • cervical spinal cord • At 20 msec, contralateralsomatosensory cortex

40. N Engl J Med 2009;361:605-11

41. SSEP and Prognosis • Bilateral absence of the N20 component of the SSEP with median nerve stimulation recorded on days 1 to 3 after CPR accurately predicts a poor outcome Zandbergen, et al. Neurology 2006;66:62–68.

42. Pros/Cons of SSEP +: not influenced by medications, able to be performed when brainstem testing limited • mechanical or metabolic reasons; including hypothermia - : confounded in many ways • any interruption in somatosensory pathways invalidates test Tiainen M, et al. Crit Care Med 2005; 33: 1736–1740

43. SSEP’s: Clinical Practice • Physicians’ use of SSEP fuel decisions about withdrawal of life support. • 58 comatose CPR survivors referred for neurologic consultation • SSEP testing correlated best with waiting time to withdrawal of life-sustaining therapies. • 40 patients whose life support was eventually withdrawn, the median waiting time was 7 days for patients with preserved SSEPs and only 1 day in patients with bilaterally absent N20 SSEP components. Geocadin RG et al. Neurologic prognosis and withdrawal of life support after resuscitation from cardiac arrest. Neurology 2006 Jul 11; 67:105-8.

44. AAN 2006 Practice Parameter Confounders • Hypothermia • NM blocking agents • Large dose sedatives • Organ failure • Shock Absent pupils/corneal and extensor/no motor response.

45. Outline • Cases • Historical Perspective • Prognostication Guidelines • The Era of Hypothermia • Approaching the Family • Return to Cases • Take Home Points

46. History of Prognostication • Levy et al (1985) establishes algorithms for neurological prognosis • determinations derived from a single cohort study • Not without limitations • Therapeutic hypothermia early 2000’s, 2 major publications in the NEJM 2002 • TH Increased the rate of a favourable neurologic outcome and reduced mortality. Levy DE, et al. JAMA 1985;253:1420-1426 N Engl J Med 2002;346:549-56 N Engl J Med 2002;346:557-63

48. The Conundrum • TH now used for neurological protection for a multitude of other life-threatening catastrophes • Worldwide 25% - 75% of all admitted resuscitated patients • Prognostication tools thus need revalidation • Life-sustaining therapies outpacing our capacity for accurately predicting outcomes

50. Era of Therapeutic Hypothermia (TH) • Studies ongoing and constantly emerging • Single studies show cooling: • Delayed motor response up to 6 days; 3 of 37 regained awareness • E. Thenayan, M. Savard et al. Neurology 2008;71:1535–1537 • Hypothermia to 32°C or above increases latency of SSEP’s by approximately 15%, reductions of temperature below 30°C can decrease the N20 amplitude by up to 20% • Decreases NSE levels • May reflect neuroprotection? • M.Tiainen, Risto O. Roine. et al. Stroke 2003;34;2881-2886