Neurologic Prognostication: Neurologic Examination and Current Guidelines

Abstract

Clinical examination is paramount for prognostication in patients who are comatose after resuscitation from cardiac arrest. At 72 hours from recovery of spontaneous circulation (ROSC), an absent or extensor motor response to pain (M ≤ 2) is a very sensitive, but not specific predictor of poor neurologic outcome. Bilaterally absent pupillary or corneal reflexes are less sensitive, but highly specific predictors. Besides the clinical examination, investigations such as somatosensory evoked potentials (SSEPs), electroencephalography (EEG), blood levels of neuron-specific enolase (NSE), or imaging studies can be used for neuroprognostication. In patients who have not been treated using targeted temperature management (TTM), the 2006 Practice Parameter of the American Academy of Neurology suggested a unimodal approach for prognostication within 72 hours from ROSC, based on status myoclonus (SM) within 24 hours, SSEP, or NSE at 24 to 72 hours and ocular reflexes or M ≤ 2 at 72 hours. The 2015 guidelines from the European Resuscitation Council and the European Society of Intensive Care Medicine suggest a multimodal prognostication algorithm, to be used in both TTM-treated and non-TTM-treated patients with M ≤ 2 at ≥ 72 hours from ROSC. Ocular reflexes (pupillary and corneal) and SSEPs should be used first, followed by a combination of other predictors (SM, EEG, NSE, imaging) if results of the first predictors are normal.

Keywords

cardiac arrest - prognostication - clinical examination

• References

• 1 Willoughby JO, Leach BG. Relation of neurological findings after cardiac arrest to outcome. BMJ 1974; 3 (5928): 437-439
• 2 Snyder BD, Ramirez-Lassepas M, Lippert DM. Neurologic status and prognosis after cardiopulmonary arrest: I. A retrospective study. Neurology 1977; 27 (9) 807-811
• 3 Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Plum F. Predicting outcome from hypoxic-ischemic coma. JAMA 1985; 253 (10) 1420-1426
• 4 Wijdicks EF. From clinical judgment to odds: a history of prognostication in anoxic-ischemic coma. Resuscitation 2012; 83 (8) 940-945
• 5 Zandbergen EG, de Haan RJ, Reitsma JB, Hijdra A. Survival and recovery of consciousness in anoxic-ischemic coma after cardiopulmonary resuscitation. Intensive Care Med 2003; 29 (11) 1911-1915
• 6 Wijdicks EF, 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 (2) 203-210
• 7 Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346 (8) 549-556
• 8 Zandbergen EG, Hijdra A, Koelman JH , et al; PROPAC Study Group Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology 2006; 66 (1) 62-68
• 9 Sandroni C, Cavallaro F, Callaway CW , et al. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 1: patients not treated with therapeutic hypothermia. Resuscitation 2013; 84 (10) 1310-1323
• 10 Zingler VC, Krumm B, Bertsch T, Fassbender K, Pohlmann-Eden B. Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal approach combining neurobiochemical and electrophysiological investigations may provide high prognostic certainty in patients after cardiac arrest. Eur Neurol 2003; 49 (2) 79-84
• 11 Reisinger J, Höllinger K, Lang W , et al. Prediction of neurological outcome after cardiopulmonary resuscitation by serial determination of serum neuron-specific enolase. Eur Heart J 2007; 28 (1) 52-58
• 12 Steffen IG, Hasper D, Ploner CJ , et al. Mild therapeutic hypothermia alters neuron specific enolase as an outcome predictor after resuscitation: 97 prospective hypothermia patients compared to 133 historical non-hypothermia patients. Crit Care 2010; 14 (2) R69
• 13 Geocadin RG, Peberdy MA, Lazar RM. Poor survival after cardiac arrest resuscitation: a self-fulfilling prophecy or biologic destiny?. Crit Care Med 2012; 40 (3) 979-980
• 14 Sandroni C, Taccone FS. Does early withdrawal of life-sustaining treatment increase mortality after cardiac arrest?. Resuscitation 2016; 102: A3-A4
• 15 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
• 16 Cronberg T, Brizzi M, Liedholm LJ , et al. [New support for assessment of neurologic prognosis after cardiac arrest. Recommendations from the Swedish CPR Council Expert Group]. Lakartidningen 2012; 109 (47) 2146-2150
• 17 Cronberg T, Brizzi M, Liedholm LJ , et al. Neurological prognostication after cardiac arrest--recommendations from the Swedish Resuscitation Council. Resuscitation 2013; 84 (7) 867-872
• 18 Samaniego EA, Mlynash M, Caulfield AF, Eyngorn I, Wijman CA. Sedation confounds outcome prediction in cardiac arrest survivors treated with hypothermia. Neurocrit Care 2011; 15 (1) 113-119
• 19 Bouwes A, Binnekade JM, Kuiper MA , et al. Prognosis of coma after therapeutic hypothermia: a prospective cohort study. Ann Neurol 2012; 71 (2) 206-212
• 20 Rossetti AO, Urbano LA, Delodder F, Kaplan PW, Oddo M. Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest. Crit Care 2010; 14 (5) R173
• 21 Rundgren M, Westhall E, Cronberg T, Rosén I, Friberg H. Continuous amplitude-integrated electroencephalogram predicts outcome in hypothermia-treated cardiac arrest patients. Crit Care Med 2010; 38 (9) 1838-1844
• 22 Sandroni C, Cariou A, Cavallaro F , et al. Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine. Intensive Care Med 2014; 40 (12) 1816-1831
• 23 Kamps MJ, Horn J, Oddo M , et al. Prognostication of neurologic outcome in cardiac arrest patients after mild therapeutic hypothermia: a meta-analysis of the current literature. Intensive Care Med 2013; 39 (10) 1671-1682
• 24 Sandroni C, Cavallaro F, Callaway CW , et al. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia. Resuscitation 2013; 84 (10) 1324-1338
• 25 Friberg H, Cronberg T, Dünser MW, Duranteau J, Horn J, Oddo M. Survey on current practices for neurological prognostication after cardiac arrest. Resuscitation 2015; 90: 158-162
• 26 Sandroni C, Nolan JP. Neuroprognostication after cardiac arrest in Europe: new timings and standards. Resuscitation 2015; 90: A4-A5
• 27 Andrews J, Guyatt G, Oxman AD , et al. GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol 2013; 66 (7) 719-725
• 28 Andrews JC, Schünemann HJ, Oxman AD , et al. GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation's direction and strength. J Clin Epidemiol 2013; 66 (7) 726-735
• 29 Nolan JP, Soar J, Cariou A , et al; European Resuscitation Council European Society of Intensive Care Medicine European Resuscitation Council and European Society of Intensive Care Medicine 2015 guidelines for post-resuscitation care. Intensive Care Med 2015; 41 (12) 2039-2056
• 30 Bisschops LL, van Alfen N, Bons S, van der Hoeven JG, Hoedemaekers CW. Predictors of poor neurologic outcome in patients after cardiac arrest treated with hypothermia: a retrospective study. Resuscitation 2011; 82 (6) 696-701
• 31 Bouwes A, Binnekade JM, Zandstra DF , et al. Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation. Neurology 2009; 73 (18) 1457-1461
• 32 Fugate JE, Wijdicks EF, Mandrekar J , et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol 2010; 68 (6) 907-914
• 33 Wu O, Batista LM, Lima FO, Vangel MG, Furie KL, Greer DM. Predicting clinical outcome in comatose cardiac arrest patients using early noncontrast computed tomography. Stroke 2011; 42 (4) 985-992
• 34 Greer DM, Yang J, Scripko PD , et al. Clinical examination for prognostication in comatose cardiac arrest patients. Resuscitation 2013; 84 (11) 1546-1551
• 35 Rossetti AO, Oddo M, Logroscino G, Kaplan PW. Prognostication after cardiac arrest and hypothermia: a prospective study. Ann Neurol 2010; 67 (3) 301-307
• 36 Rossetti AO, Carrera E, Oddo M. Early EEG correlates of neuronal injury after brain anoxia. Neurology 2012; 78 (11) 796-802
• 37 Bouwes A, van Poppelen D, Koelman JH , et al. Acute posthypoxic myoclonus after cardiopulmonary resuscitation. BMC Neurol 2012; 12: 63
• 38 Thömke F, Marx JJ, Sauer O , et al. Observations on comatose survivors of cardiopulmonary resuscitation with generalized myoclonus. BMC Neurol 2005; 5: 14
• 39 Crepeau AZ, Rabinstein AA, Fugate JE , et al. Continuous EEG in therapeutic hypothermia after cardiac arrest: prognostic and clinical value. Neurology 2013; 80 (4) 339-344
• 40 Legriel S, Hilly-Ginoux J, Resche-Rigon M , et al. Prognostic value of electrographic postanoxic status epilepticus in comatose cardiac-arrest survivors in the therapeutic hypothermia era. Resuscitation 2013; 84 (3) 343-350
• 41 Oddo M, Rossetti AO. Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia. Crit Care Med 2014; 42 (6) 1340-1347
• 42 Seder DB, Sunde K, Rubertsson S , et al. International Cardiac Arrest Registry Neurologic outcomes and postresuscitation care of patients with myoclonus following cardiac arrest. Crit Care Med 2015; 43 (5) 965-972
• 43 Sandroni C, Nolan JP. Neurologically favorable outcome is still possible despite myoclonus in comatose survivors of cardiac arrest. Crit Care Med 2015; 43 (9) e396-e397
• 44 Rittenberger JC, Popescu A, Brenner RP, Guyette FX, Callaway CW. Frequency and timing of nonconvulsive status epilepticus in comatose post-cardiac arrest subjects treated with hypothermia. Neurocrit Care 2012; 16 (1) 114-122
• 45 Krumholz A, Stern BJ, Weiss HD. Outcome from coma after cardiopulmonary resuscitation: relation to seizures and myoclonus. Neurology 1988; 38 (3) 401-405
• 46 Wijdicks EFY, Young GB. Myoclonus status in comatose patients after cardiac arrest. Lancet 1994; 343 (8913): 1642-1643
• 47 Arnoldus EP, Lammers GJ. Postanoxic coma: good recovery despite myoclonus status. Ann Neurol 1995; 38 (4) 697-698
• 48 Datta S, Hart GK, Opdam H, Gutteridge G, Archer J. Post-hypoxic myoclonic status: the prognosis is not always hopeless. Crit Care Resusc 2009; 11 (1) 39-41
• 49 English WA, Giffin NJ, Nolan JP. Myoclonus after cardiac arrest: pitfalls in diagnosis and prognosis. Anaesthesia 2009; 64 (8) 908-911
• 50 Greer DM. Unexpected good recovery in a comatose post-cardiac arrest patient with poor prognostic features. Resuscitation 2013; 84 (6) e81-e82
• 51 Lucas JM, Cocchi MN, Salciccioli J , et al. Neurologic recovery after therapeutic hypothermia in patients with post-cardiac arrest myoclonus. Resuscitation 2012; 83 (2) 265-269
• 52 Hofmeijer J, Beernink TM, Bosch FH, Beishuizen A, Tjepkema-Cloostermans MC, van Putten MJ. Early EEG contributes to multimodal outcome prediction of postanoxic coma. Neurology 2015; 85 (2) 137-143
• 53 Hofmeijer J, Tjepkema-Cloostermans MC, van Putten MJ. Burst-suppression with identical bursts: a distinct EEG pattern with poor outcome in postanoxic coma. Clin Neurophysiol 2014; 125 (5) 947-954
• 54 Geocadin RG, Buitrago MM, Torbey MT, Chandra-Strobos N, Williams MA, Kaplan PW. Neurologic prognosis and withdrawal of life support after resuscitation from cardiac arrest. Neurology 2006; 67 (1) 105-108
• 55 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
• 56 Oksanen T, Tiainen M, Skrifvars MB , et al. Predictive power of serum NSE and OHCA score regarding 6-month neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic hypothermia. Resuscitation 2009; 80 (2) 165-170
• 57 Storm C, Nee J, Jörres A, Leithner C, Hasper D, Ploner CJ. Serial measurement of neuron specific enolase improves prognostication in cardiac arrest patients treated with hypothermia: a prospective study. Scand J Trauma Resusc Emerg Med 2012; 20: 6
• 58 Tiainen M, Roine RO, Pettilä V, Takkunen O. Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke 2003; 34 (12) 2881-2886
• 59 Cronberg T, Rundgren M, Westhall E , et al. Neuron-specific enolase correlates with other prognostic markers after cardiac arrest. Neurology 2011; 77 (7) 623-630
• 60 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
• 61 Huntgeburth M, Adler C, Rosenkranz S , et al. Changes in neuron-specific enolase are more suitable than its absolute serum levels for the prediction of neurologic outcome in hypothermia-treated patients with out-of-hospital cardiac arrest. Neurocrit Care 2014; 20 (3) 358-366
• 62 Lee BK, Jeung KW, Lee HY, Jung YH, Lee DH. Combining brain computed tomography and serum neuron specific enolase improves the prognostic performance compared to either alone in comatose cardiac arrest survivors treated with therapeutic hypothermia. Resuscitation 2013; 84 (10) 1387-1392
• 63 Jørgensen EO, Holm S. The natural course of neurological recovery following cardiopulmonary resuscitation. Resuscitation 1998; 36 (2) 111-122
• 64 Sharshar T, Citerio G, Andrews PJ , et al. Neurological examination of critically ill patients: a pragmatic approach. Report of an ESICM expert panel. Intensive Care Med 2014; 40 (4) 484-495
• 65 Stammet P, Wagner DR, Gilson G, Devaux Y. Modeling serum level of s100β and bispectral index to predict outcome after cardiac arrest. J Am Coll Cardiol 2013; 62 (9) 851-858
• 66 Al Thenayan E, Savard M, Sharpe M, Norton L, Young B. Predictors of poor neurologic outcome after induced mild hypothermia following cardiac arrest. Neurology 2008; 71 (19) 1535-1537
• 67 Nielsen N, Wetterslev J, Cronberg T , et al; TTM Trial Investigators Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med 2013; 369 (23) 2197-2206
• 68 Grossestreuer AV, Abella BS, Leary M , et al. Time to awakening and neurologic outcome in therapeutic hypothermia-treated cardiac arrest patients. Resuscitation 2013; 84 (12) 1741-1746
• 69 Gold B, Puertas L, Davis SP , et al. Awakening after cardiac arrest and post resuscitation hypothermia: are we pulling the plug too early?. Resuscitation 2014; 85 (2) 211-214
• 70 Paul M, Bougouin W, Geri G , et al. Delayed awakening after cardiac arrest: prevalence and risk factors in the Parisian registry. Intensive Care Med 2016; 42 (7) 1128-1136
• 71 Sandroni C, Dell'anna AM, Tujjar O, Geri G, Cariou A, Taccone FS. Acute kidney injury (AKI) after cardiac arrest: a systematic review and meta-analysis of clinical studies. Minerva Anestesiol 2016; ; 2016; 82 (9) 989-999