Neuroprognostication after Cardiac Arrest: Who Recovers? Who Progresses to Brain Death?

Abstract

Approximately 15% of deaths in developed nations are due to sudden cardiac arrest, making it the most common cause of death worldwide. Though high-quality cardiopulmonary resuscitation has improved overall survival rates, the majority of survivors remain comatose after return of spontaneous circulation secondary to hypoxic ischemic injury. Since the advent of targeted temperature management, neurologic recovery has improved substantially, but the majority of patients are left with neurologic deficits ranging from minor cognitive impairment to persistent coma. Of those who survive cardiac arrest, but die during their hospitalization, some progress to brain death and others die after withdrawal of life-sustaining treatment due to anticipated poor neurologic prognosis. Here, we discuss considerations neurologists must make when asked, “Given their recent cardiac arrest, how much neurologic improvement do we expect for this patient?”

Keywords

cardiac arrest - prognostication - brain death

Publication History

Article published online:
07 October 2021

• References

• 1 Cronberg T. Neuroprognostication of cardiac arrest patients: outcomes of importance. Semin Respir Crit Care Med 2017; 38 (06) 775-784
• 2 Maciel CB, Barden MM, Greer DM. Neurologic recovery after cardiac arrest: a multifaceted puzzle requiring comprehensive coordinated care. Curr Treat Options Cardiovasc Med 2017; 19 (07) 52
• 3 Greer DM. Cardiac arrest and postanoxic encephalopathy. Continuum (Minneap Minn) 2015; 21 (5 Neurocritical Care): 1384-1396
• 4 Callaway CW, Donnino MW, Fink EL. et al. Part 8: Post-cardiac arrest care: 2015 American Heart Association Guidelines Update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2015; 132 (18, Suppl 2): S465-S482
• 5 Girotra S, Chan PS, Bradley SM. Post-resuscitation care following out-of-hospital and in-hospital cardiac arrest. Heart 2015; 101 (24) 1943-1949
• 6 Horstmann A, Frisch S, Jentzsch RT, Müller K, Villringer A, Schroeter ML. Resuscitating the heart but losing the brain: brain atrophy in the aftermath of cardiac arrest. Neurology 2010; 74 (04) 306-312
• 7 Elmer J, Callaway CW. The brain after cardiac arrest. Semin Neurol 2017; 37 (01) 19-24
• 8 González-Ibarra FP, Varon J, López-Meza EG. Therapeutic hypothermia: critical review of the molecular mechanisms of action. Front Neurol 2011; 2: 4
• 9 Silva S, Peran P, Kerhuel L. et al. Brain gray matter MRI morphometry for neuroprognostication after cardiac arrest. Crit Care Med 2017; 45 (08) e763-e771
• 10 Nakayama S, Amiry-Moghaddam M, Ottersen OP, Bhardwaj A. Conivaptan, a selective arginine vasopressin V1a and V2 receptor antagonist attenuates global cerebral edema following experimental cardiac arrest via perivascular pool of aquaporin-4. Neurocrit Care 2016; 24 (02) 273-282
• 11 Rahaman P, Del Bigio MR. Histology of brain trauma and hypoxia-ischemia. Acad Forensic Pathol 2018; 8 (03) 539-554
• 12 Horn M, Schlote W. Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia. Acta Neuropathol 1992; 85 (01) 79-87
• 13 Mentzelopoulos SD, Malachias S, Chamos C. et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA 2013; 310 (03) 270-279
• 14 Sondergaard KB, Riddersholm S, Wissenberg M. et al. Out-of-hospital cardiac arrest: 30-day survival and 1-year risk of anoxic brain damage or nursing home admission according to consciousness status at hospital arrival. Resuscitation 2020; 148: 251-258
• 15 Holzer M, Sterz F, Darby JM. et al; Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346 (08) 549-556
• 16 Bernard SA, Gray TW, Buist MD. et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346 (08) 557-563
• 17 Donnino MW, Andersen LW, Berg KM. et al. Temperature management after cardiac arrest. an advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation. Resuscitation 2016; 98: 97-104
• 18 Kirkegaard H, Søreide E, de Haas I. et al. Targeted temperature management for 48 vs 24 hours and neurologic outcome after out-of-hospital cardiac arrest: a randomized clinical trial. . JAMA 2017; 318 (04) 341-350
• 19 Rittenberger JC, Friess S, Polderman KH. Emergency neurological life support: resuscitation following cardiac arrest. Neurocrit Care 2015; 23 (Suppl. 02) S119-S128
• 20 Agarwal S, Morris N, Der-Nigoghossian C, May T, Brodie D. The influence of therapeutics on prognostication after cardiac arrest. Curr Treat Options Neurol 2019; 21 (12) 60
• 21 Perman SM, Kirkpatrick JN, Reitsma AM. et al. Timing of neuroprognostication in postcardiac arrest therapeutic hypothermia*. Crit Care Med 2012; 40 (03) 719-724
• 22 Wijdicks EFM, Hijdra A, Young GB, Bassetti CL, Wiebe S. Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 67 (02) 203-210
• 23 Long B, Koyfman A, Gottlieb M. Targeted temperature management in post cardiac arrest patients. Acad Emerg Med 2020; 27 (06) 517-519
• 24 Coppler PJ, Elmer J, Calderon L. et al; Post Cardiac Arrest Service. Validation of the Pittsburgh Cardiac Arrest Category illness severity score. Resuscitation 2015; 89: 86-92
• 25 Scarpino M, Carrai R, Lolli F. et al. Neurophysiology for predicting good and poor neurological outcome at 12 and 72 h after cardiac arrest: the ProNeCA multicentre prospective study. Resuscitation 2020; 147: 95-103
• 26 Nair SU, Lundbye JB. The occurrence of shivering in cardiac arrest survivors undergoing therapeutic hypothermia is associated with a good neurologic outcome. Resuscitation 2013; 84 (05) 626-629
• 27 Rittenberger JC, Raina K, Holm MB, Kim YJ, Callaway CW. Association between cerebral performance category, modified Rankin scale, and discharge disposition after cardiac arrest. Resuscitation 2011; 82 (08) 1036-1040
• 28 Rossetti AO, Rabinstein AA, Oddo M. Neurological prognostication of outcome in patients in coma after cardiac arrest. Lancet Neurol 2016; 15 (06) 597-609
• 29 Hsu CH, Li J, Cinousis MJ. et al. Cerebral performance category at hospital discharge predicts long-term survival of cardiac arrest survivors receiving targeted temperature management. Crit Care Med 2014; 42 (12) 2575-2581
• 30 Balouris SA, Raina KD, Rittenberger JC, Callaway CW, Rogers JC, Holm MB. Development and validation of the cerebral performance categories-extended (CPC-E). Resuscitation 2015; 94: 98-105
• 31 Fillbrandt A, Frank B. Gender differences in cognitive outcome after cardiac arrest: A retrospective cohort study. Brain Inj 2020; 34 (01) 122-130
• 32 Mulder M, Gibbs HG, Smith SW. et al. Awakening and withdrawal of life-sustaining treatment in cardiac arrest survivors treated with therapeutic hypothermia*. Crit Care Med 2014; 42 (12) 2493-2499
• 33 Dragancea I, Wise MP, Al-Subaie N. et al; TTM Trial investigators. Protocol-driven neurological prognostication and withdrawal of life-sustaining therapy after cardiac arrest and targeted temperature management. Resuscitation 2017; 117: 50-57
• 34 Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Plum F. Predicting outcome from hypoxic-ischemic coma. JAMA 1985; 253 (10) 1420-1426
• 35 Oddo M, Sandroni C, Citerio G. et al. Quantitative versus standard pupillary light reflex for early prognostication in comatose cardiac arrest patients: an international prospective multicenter double-blinded study. Intensive Care Med 2018; 44 (12) 2102-2111
• 36 Kavi T, Desai M, Yilmaz FM, Kakadia B, Burakgazi-Dalkilic E, Shrestha GS. Inter-predictability of neuroprognostic modalities after cardiac arrest. Cureus 2019; 11 (04) e4489
• 37 Sandroni C, D'Arrigo S. Neurologic prognostication: neurologic examination and current guidelines. Semin Neurol 2017; 37 (01) 40-47
• 38 Maciel CB, Youn TS, Barden MM. et al. Corneal reflex testing in the evaluation of a comatose patient: an ode to precise semiology and examination skills. Neurocrit Care 2020; 33 (02) 399-404
• 39 Hofmeijer J, van Putten MJAM. EEG in postanoxic coma: prognostic and diagnostic value. Clin Neurophysiol 2016; 127 (04) 2047-2055
• 40 Mani R, Schmitt SE, Mazer M, Putt ME, Gaieski DF. The frequency and timing of epileptiform activity on continuous electroencephalogram in comatose post-cardiac arrest syndrome patients treated with therapeutic hypothermia. Resuscitation 2012; 83 (07) 840-847
• 41 Oddo M, Friberg H. Neuroprognostication after cardiac arrest in the light of targeted temperature management. Curr Opin Crit Care 2017; 23 (03) 244-250
• 42 Backman S, Cronberg T, Friberg H. et al. Highly malignant routine EEG predicts poor prognosis after cardiac arrest in the Target Temperature Management trial. Resuscitation 2018; 131: 24-28
• 43 Sivaraju A, Gilmore EJ, Wira CR. et al. Prognostication of post-cardiac arrest coma: early clinical and electroencephalographic predictors of outcome. Intensive Care Med 2015; 41 (07) 1264-1272
• 44 Werhahn KJ, Brown P, Thompson PD, Marsden CD. The clinical features and prognosis of chronic posthypoxic myoclonus. Mov Disord 1997; 12 (02) 216-220
• 45 Elmer J, Rittenberger JC, Faro J. et al; Pittsburgh Post-Cardiac Arrest Service. Clinically distinct electroencephalographic phenotypes of early myoclonus after cardiac arrest. Ann Neurol 2016; 80 (02) 175-184
• 46 Elmer J, Torres C, Aufderheide TP. et al; Resuscitation Outcomes Consortium. Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. Resuscitation 2016; 102: 127-135
• 47 Ruijter BJ, van Putten MJAM, Horn J. et al; TELSTAR Study Group. Treatment of electroencephalographic status epilepticus after cardiopulmonary resuscitation (TELSTAR): study protocol for a randomized controlled trial. Trials 2014; 15 (433) 433
• 48 Given II CA, Burdette JH, Elster AD, Williams III DW. Pseudo-subarachnoid hemorrhage: a potential imaging pitfall associated with diffuse cerebral edema. AJNR Am J Neuroradiol 2003; 24 (02) 254-256
• 49 Velly L, Perlbarg V, Boulier T. et al; MRI-COMA Investigators. Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study. Lancet Neurol 2018; 17 (04) 317-326
• 50 Bevers MB, Scirica BM, Avery KR, Henderson GV, Lin AP, Lee JW. Combination of clinical exam, MRI and EEG to predict outcome following cardiac arrest and targeted temperature management. Neurocrit Care 2018; 29 (03) 396-403
• 51 Wijdicks EFM, Varelas PN, Gronseth GS, Greer DM. American Academy of Neurology. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010; 74 (23) 1911-1918
• 52 Stammet P, Collignon O, Hassager C. et al; TTM-Trial Investigators. Neuron-specific enolase as a predictor of death or poor neurological outcome after out-of-hospital cardiac arrest and targeted temperature management at 33°C and 36°C. J Am Coll Cardiol 2015; 65 (19) 2104-2114
• 53 Daubin C, Quentin C, Allouche S. et al. Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: a prospective cohort study. BMC Cardiovasc Disord 2011; 11 (48) 48
• 54 Zellner T, Gärtner R, Schopohl J, Angstwurm M. NSE and S-100B are not sufficiently predictive of neurologic outcome after therapeutic hypothermia for cardiac arrest. Resuscitation 2013; 84 (10) 1382-1386
• 55 Moseby-Knappe M, Mattsson N, Nielsen N. et al. Serum neurofilament light chain for prognosis of outcome after cardiac arrest. JAMA Neurol 2019; 76 (01) 64-71
• 56 Taccone FS, Crippa IA, Dell'Anna AM, Scolletta S. Neuroprotective strategies and neuroprognostication after cardiac arrest. Best Pract Res Clin Anaesthesiol 2015; 29 (04) 451-464
• 57 Paskitti M, Reid KH. Use of an adenosine triphosphate-based ‘cocktail’ early in reperfusion substantially improves brain protein synthesis after global ischemia in rats. Neurosci Lett 2002; 331 (03) 147-150
• 58 Scarpino M, Lolli F, Lanzo G. et al; ProNeCAStudy Group. Neurophysiological and neuroradiological test for early poor outcome (Cerebral Performance Categories 3-5) prediction after cardiac arrest: prospective multicentre prognostication data. Data Brief 2019; 27: 104755
• 59 Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation 2013; 84 (03) 337-342
• 60 Lewis A, Bakkar A, Kreiger-Benson E. et al. Determination of death by neurologic criteria around the world. Neurology 2020; 95 (03) e299-e309
• 61 Russell JA, Epstein LG, Greer DM. et al. Brain death, the determination of brain death, and member guidance for brain death accommodation requests. Neurology 2019; 92 (05) 228-232
• 62 Wijdicks EFM. Determining brain death in adults. Neurology 1995; 45 (05) 1003-1011
• 63 Lewis A, Bernat JL, Blosser S. et al. An interdisciplinary response to contemporary concerns about brain death determination. Neurology 2018; 90 (09) 423-426
• 64 Youn TS, Greer DM. Brain death and management of a potential organ donor in the intensive care unit. Crit Care Clin 2014; 30 (04) 813-831
• 65 Webb AC, Samuels OB. Reversible brain death after cardiopulmonary arrest and induced hypothermia. Crit Care Med 2011; 39 (06) 1538-1542
• 66 Joffe AR, Kolski H, Duff J, deCaen ARA. A 10-month-old infant with reversible findings of brain death. Pediatr Neurol 2009; 41 (05) 378-382
• 67 Youn CS, Callaway CW, Rittenberger JC. Post Cardiac Arrest Service. Combination of initial neurologic examination, quantitative brain imaging and electroencephalography to predict outcome after cardiac arrest. Resuscitation 2017; 110: 120-125
• 68 Wijdicks EFM. The case against confirmatory tests for determining brain death in adults. Neurology 2010; 75 (01) 77-83
• 69 Nakagawa TA, Ashwal S, Mathur M, Mysore M. Committee For Determination Of Brain Death In Infants Children. Guidelines for the determination of brain death in infants and children: an update of the 1987 task force recommendations-executive summary. Ann Neurol 2012; 71 (04) 573-585