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The Influence of Therapeutics on Prognostication After Cardiac Arrest

  • Critical Care Neurology (H Hinson, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Abstract

Purpose of review

The goal of this review is to highlight the influence of therapeutic maneuvers on neuro-prognostication measures administered to comatose survivors of cardiac arrest. We focus on the effect of sedation regimens in the setting of targeted temperature management (TTM), one of the principle interventions known to improve neurological recovery after cardiac arrest. Further, we discuss the critical need for novel markers, as well as refinement of existing markers, among patients receiving extracorporeal membrane oxygenation (ECMO) in the setting of failed conventional resuscitation, known as extracorporeal cardiopulmonary resuscitation (ECPR).

Recent findings

Automated pupillometry may have some advantage over standard pupillary examination for prognostication following TTM, sedation, or the use of ECMO after cardiac arrest. New serum biomarkers such as Neurofilament light chain have shown good predictive abilities and need further validation in these populations. There is a high-level uncertainty in brain death declaration protocols particularly related to apnea testing and appropriate ancillary tests in patients receiving ECMO.

Summary

Both sedation and TTM alone and in combination have been shown to affect prognostic markers to varying degrees. The optimal approach to analog-sedation is unknown, and requires further study. Moreover, validation of known prognostic markers, as well as brain death declaration processes in patients receiving ECMO is warranted. Data on the effects of TTM, sedation, and ECMO on biomarkers (e.g., neuron-specific enolase) and electrophysiology measures (e.g., somatosensory-evoked potentials) is sparse. The best approach may be one customized to the individual patient, a precision-medicine approach.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S. 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;67:203–10.

    PubMed  CAS  Google Scholar 

  2. Sandroni C, Cariou A, Cavallaro F, Cronberg T, Friberg H, Hoedemaekers C, 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):1816–31.

    PubMed  PubMed Central  Google Scholar 

  3. Lan, Chinchun, Pi-Ru Tsai, Yih-Sharng Chen, and Wen-Je Ko. "Prognostic factors for adult patients receiving extracorporeal membrane oxygenation as mechanical circulatory support-a 14-year experience at a medical center." Artif Organs 34, no. 2 (2010).

    PubMed  Google Scholar 

  4. Bridwell A, Tymkew H. Physical therapy for patients with a centralized insertion of extracorporeal membrane oxygenation: a case series. Cardiopulm Phys Ther J. 2014;25(4):132–3.

    Google Scholar 

  5. •• 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):S465–82. This 2015 systematic review examined numerous studies of the diagnostic accuracy of clinical findings, electrophysiological modalities, imaging modalities, and blood markers for predicting neurologic outcome in comatose post–cardiac arrest patients who receive TTM, as well as who do not receive TTM.

    PubMed  PubMed Central  Google Scholar 

  6. Tømte Ø, Drægni T, Mangschau A, Jacobsen D, Auestad B, Sunde K. A comparison of intravascular and surface cooling techniques in comatose cardiac arrest survivors. Crit Care Med. 2011;39(3):443–9.

    PubMed  Google Scholar 

  7. Deye N, Cariou A, Girardie P, Pichon N, Megarbane B, Midez P, et al. Endovascular versus external targeted temperature management for patients with out-of-hospital cardiac arrest: a randomized , controlled study. Circulation. 2015;132(3):182–93.

    PubMed  Google Scholar 

  8. Glover GW, Thomas RM, Vamvakas G, al-Subaie N, Cranshaw J, Walden A, et al. Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest - an analysis of the TTM trial data. Crit Care. 2016;20(1):381.

    PubMed  PubMed Central  Google Scholar 

  9. Polderman KH, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med. 2009;37(3):1101–20.

    PubMed  Google Scholar 

  10. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197–206.

    PubMed  CAS  Google Scholar 

  11. Badjatia N, Strongilis E, Gordon E, Prescutti M, Fernandez L, Fernandez A, et al. Metabolic impact of shivering during therapeutic temperature modulation: the bedside shivering assessment scale. Stroke. 2008;39(12):3242–7.

    PubMed  Google Scholar 

  12. Oddo M, Frangos S, Maloney-Wilensky E, Andrew Kofke W, Le Roux PD, Levine JM. Effect of shivering on brain tissue oxygenation during induced normothermia in patients with severe brain injury. Neurocrit Care. 2010;12(1):10–6.

    PubMed  CAS  Google Scholar 

  13. Choi HA, Ko SB, Presciutti M, Fernandez L, Carpenter AM, Lesch C, et al. Prevention of shivering during therapeutic temperature modulation: the Columbia anti-shivering protocol. Neurocrit Care. 2011;14(3):389–94.

    PubMed  Google Scholar 

  14. • Rey A, Rossetti AO, Miroz JP, et al. Late awakening in survivors of post-anoxic coma: early neurophysiologic predictors and association with ICU and long-term neurologic recovery. Crit Care Med. 2019;47:85–92 A single-center, observational cohort study examining the neurophysiologic predictors and outcomes of patients with late awakening following cardiac arrest. The study showed delaying prognostication will permit late awakening with favorable outcomes.

    PubMed  Google Scholar 

  15. • Paul M, Bougouin W, Dumas F, et al. Comparison of two sedation regimens during targeted temperature management after cardiac arrest. Resuscitation. 2018;128:204–10. The potential advantages of short-acting agents for sedation use during TTM has not been studied well. This multi-center study showed that sedation with propofol-remifentanil was associated with significantly earlier awakening and more ventilator-free days as compared with midazolam-fentanyl.

    PubMed  CAS  Google Scholar 

  16. Sunjic KM, Webb AC, Šunjić I, et al. Pharmacokinetic and other considerations for drug therapy during targeted temperature management. Crit Care Med. 2015;43:2228–38.

    PubMed  CAS  Google Scholar 

  17. Tortorici MA, Kochanek PM, Poloyac SM, et al. Effects of hypothermia on drug disposition, metabolism, and response: a focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system. Crit Care Med. 2007;35:2196–204.

    PubMed  CAS  Google Scholar 

  18. Fritz HG, Holzmayr M, Walter B, Moeritz KU, Lupp A, Bauer R. The effect of mild hypothermia on plasma fentanyl concentration and biotransformation in juvenile pigs. Anesth Analg. 2005;100:996–1002.

    PubMed  CAS  Google Scholar 

  19. Fukuoka N, Aibiki M, Tsukamoto T, Seki K, Morita S. Biphasic concentration change during continuous midazolam administration in brain-injured patients undergoing therapeutic moderate hypothermia. Resuscitation. 2004;60:225–30.

    PubMed  CAS  Google Scholar 

  20. Leslie K, Sessler DI, Bjorksten AR, et al. Mild hypothermia alters propofol pharmacokinetics and increases the duration of action of atracurium. Anesth Analg. 1995;80:1007–14.

    PubMed  CAS  Google Scholar 

  21. Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009;37(7 Suppl):S186–202.

    PubMed  Google Scholar 

  22. 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):211–4.

    PubMed  Google Scholar 

  23. Grossestreuer AV, Abella BS, Leary M, Perman SM, Fuchs BD, Kolansky DM, et al. Time to awakening and neurologic outcome in therapeutic hypothermia-treated cardiac arrest patients. Resuscitation. 2013;84(12):1741–6.

    PubMed  Google Scholar 

  24. Eid SM, Albaeni A, Vaidya D, Nazarian SM, Llinas R, Chandra-Strobos N. Awakening following cardiac arrest: determined by the definitions used or the therapies delivered? Resuscitation. 2016;100:38–44.

    PubMed  Google Scholar 

  25. Mulder M, Gibbs HG, Smith SW, Dhaliwal R, Scott NL, Sprenkle MD, et al. Awakening and withdrawal of life-sustaining treatment in cardiac arrest survivors treated with therapeutic hypothermia. Crit Care Med. 2014;42(12):2493–9.

    PubMed  PubMed Central  CAS  Google Scholar 

  26. Irisawa T, Vadeboncoeur TF, Karamooz M, Mullins M, Chikani V, Spaite DW, et al. Duration of coma in out-of-hospital cardiac arrest survivors treated with targeted temperature management. Ann Emerg Med. 2017;69(1):36–43.

    PubMed  Google Scholar 

  27. Zanyk-McLean K, Sawyer KN, Paternoster R, Shievitz R, Devlin W, Swor R. Time to awakening is often delayed in patients who receive targeted temperature management after cardiac arrest. Ther Hypothermia Temp Manag. 2017;7(2):95–100.

    PubMed  Google Scholar 

  28. Lybeck A, Friberg H, Aneman A, Hassager C, Horn J, Kjærgaard J, et al. Prognostic significance of clinical seizures after cardiac arrest and target temperature management. Resuscitation. 2017;114:146–51.

    PubMed  Google Scholar 

  29. Dragancea I, Horn J, Kuiper M, et al. Neurological prognostication after cardiac arrest and targeted temperature management 33°C versus 36°C: results from a randomised controlled clinical trial. Resuscitation. 2015;93:164–70.

    PubMed  Google Scholar 

  30. Sandroni C, Cariou A, Cavallaro F, Cronberg T, Friberg H, Hoedemaekers C, 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):1816–31.

    PubMed  PubMed Central  Google Scholar 

  31. •• 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):2102–11. In this prospective international multicenter study (10 centers), quantitative NPi was shown to have excellent ability to predict an unfavorable outcome from day 1 after cardiac arrest, with no false positives, and significantly higher specificity than standard manual pupillary examination.

    PubMed  PubMed Central  Google Scholar 

  32. Fugate JE, Wijdicks EF, Mandrekar J, Claassen DO, Manno EM, White RD, et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol. 2010;68(6):907–14.

    PubMed  Google Scholar 

  33. Bouwes A, Binnekade JM, Kuiper MA, et al. Prognosis of coma after therapeutic hypothermia: a prospective cohort study. Ann Neurol. 2012;71(2):206–12.

    PubMed  Google Scholar 

  34. Rossetti AO, Oddo M, Logroscino G, Kaplan PW. Prognostication after cardiac arrest and hypothermia: a prospective study. Ann Neurol. 2010;67(3):301–7.

    PubMed  Google Scholar 

  35. Tsetsou S, Novy J, Pfeiffer C, Oddo M, Rossetti AO. Multimodal outcome prognostication after cardiac arrest and targeted temperature management: analysis at 36 °C. Neurocrit Care. 2018;28(1):104–9.

    PubMed  CAS  Google Scholar 

  36. Suys T, Bouzat P, Marques-Vidal P, Sala N, Payen JF, Rossetti AO, et al. Automated quantitative pupillometry for the prognostication of coma after cardiac arrest. Neurocrit Care. 2014;21(2):300–8.

    PubMed  Google Scholar 

  37. Heimburger D, Durand M, Gaide-Chevronnay L, Dessertaine G, Moury PH, Bouzat P, et al. Quantitative pupillometry and transcranial Doppler measurements in patients treated with hypothermia after cardiac arrest. Resuscitation. 2016;103:88–93.

    PubMed  Google Scholar 

  38. Solari D, Rossetti AO, Carteron L, Miroz JP, Novy J, Eckert P, et al. Early prediction of coma recovery after cardiac arrest with blinded pupillometry. Ann Neurol. 2017;81(6):804–10.

    PubMed  Google Scholar 

  39. Rohaut B, Porcher R, Hissem T, et al. Brainstem response patterns in deeply-sedated critically-ill patients predict 28-day mortality. PLoS One. 2017;12:e0176012.

    PubMed  PubMed Central  Google Scholar 

  40. 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):113–9.

    PubMed  PubMed Central  Google Scholar 

  41. Crepeau AZ, Rabinstein AA, Fugate JE, Mandrekar J, Wijdicks EF, White RD, et al. Continuous EEG in therapeutic hypothermia after cardiac arrest: prognostic and clinical value. Neurology. 2013;80(4):339–44.

    PubMed  Google Scholar 

  42. Oddo M, Rossetti AO. Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia. Crit Care Med. 2014;42(6):1340–7.

    PubMed  Google Scholar 

  43. Seder DB, Sunde K, Rubertsson S, Mooney M, Stammet P, Riker RR, et al. Neurologic outcomes and postresuscitation care of patients with myoclonus following cardiac arrest. Crit Care Med. 2015;43(5):965–72.

    PubMed  Google Scholar 

  44. •• Rossetti AO, Rabinstein AA, Oddo M. Neurological prognostication of outcome in patients in coma after cardiac arrest. Lancet Neurol. 2016;15(6):597–609. This review emphasized the important of utilizing multimodal neuroprognostication paradigm and the fact that multimodal assessment could provide reassurance about the reliability of a prognostic estimate by offering concordant evidence.

    PubMed  Google Scholar 

  45. Reynolds AS, Rohaut B, Holmes MG, Robinson D, Roth W, Velazquez A, et al. Early myoclonus following anoxic brain injury. Neurol Clin Pract. 2018;8(3):249–56.

    PubMed  PubMed Central  Google Scholar 

  46. Dhakar MB, Sivaraju A, Maciel CB, Youn TS, Gaspard N, Greer DM, et al. Electro-clinical characteristics and prognostic significance of post anoxic myoclonus. Resuscitation. 2018;131:114–20.

    PubMed  Google Scholar 

  47. •• Geocadin RG, Callaway CW, Fink EL, et al. Standards for studies of neurological prognostication in comatose survivors of cardiac arrest: a scientific statement from the American Heart Association. Circulation. 2019:CIR0000000000000702. https://doi.org/10.1161/CIR.0000000000000702. This a scientific statement from The American Heart Association Emergency Cardiovascular Care Science Subcommittee comprising of adult and pediatric experts from neurology, cardiology, emergency medicine, intensive care medicine, and nursing to review existing neurological prognostication studies, the practice of neurological prognostication, and withdrawal of life-sustaining treatment.

  48. Amorim E, Rittenberger JC, Baldwin ME, Callaway CW, Popescu A; Post Cardiac Arrest Service. Malignant EEG patterns in cardiac arrest patients treated with targeted temperature management who survive to hospital discharge. Resuscitation 2015;90:127–132.

    PubMed  PubMed Central  Google Scholar 

  49. Mettenburg JM, Agarwal V, Baldwin M, Rittenberger JC. Discordant observation of brain injury by MRI and malignant electroencephalography patterns in comatose survivors of cardiac arrest following therapeutic hypothermia. AJNR Am J Neuroradiol. 2016;37:1787–93.

    PubMed  PubMed Central  CAS  Google Scholar 

  50. Andresen JM, Girard TD, Pandharipande PP, Davidson MA, Ely EW, Watson PL. Burst suppression on processed electroencephalography as a predictor of post-coma delirium in mechanically ventilated ICU patients. Crit Care Med. 2014;42:2244–51.

    PubMed  PubMed Central  Google Scholar 

  51. 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;85:137–43.

    PubMed  PubMed Central  Google Scholar 

  52. Sivaraju A, Gilmore EJ, Wira CR, Stevens A, Rampal N, Moeller JJ, et al. Prognostication of post-cardiac arrest coma: early clinical and electroencephalographic predictors of outcome. Intensive Care Med. 2015;41:1264–72.

    PubMed  Google Scholar 

  53. Dragancea I, Backman S, Westhall E, Rundgren M, Friberg H, Cronberg T. Outcome following postanoxic status epilepticus in patients with targeted temperature management after cardiac arrest. Epilepsy Behav. 2015;49:173–7.

    PubMed  Google Scholar 

  54. Geocadin RG, Ritzl EK. Seizures and status epilepticus in post cardiac arrest syndrome: therapeutic opportunities to improve outcome or basis to withhold life sustaining therapies? Resuscitation. 2012;83:791–2.

    PubMed  Google Scholar 

  55. Mikhaeil-Demo Y, Gavvala JR, Bellinski II, Macken MP, Narechania A, Templer JW, et al. Clinical classification of post anoxic myoclonic status. Resuscitation. 2017;119:76–80.

    PubMed  Google Scholar 

  56. Alvarez V, Oddo M, Rossetti AO. Stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) in comatose survivors of cardiac arrest: characteristics and prognostic value. Clin Neurophysiol. 2013;124:204–8.

    PubMed  Google Scholar 

  57. Westhall E, Rosén I, Rundgren M, Bro-Jeppesen J, Kjaergaard J, Hassager C, et al. Time to epileptiform activity and EEG background recovery are independent predictors after cardiac arrest. Clin Neurophysiol. 2018 Aug;129(8):1660–8.

    PubMed  CAS  Google Scholar 

  58. Sleigh JW, Vacas S, Flexman AM, Talke PO. Electroencephalographic arousal patterns under dexmedetomidine sedation. Anesth Analg. 2018 Oct;127(4):951–9.

    CAS  Google Scholar 

  59. Drohan CM, Cardi AI, Rittenberger JC, Popescu A, Callaway CW, Baldwin ME, et al. Effect of sedation on quantitative electroencephalography after cardiac arrest. Resuscitation. 2018 Mar;124:132–7.

    PubMed  Google Scholar 

  60. Noirhomme Q, Lehembre R, Lugo ZDR, Lesenfants D, Luxen A, Laureys S, et al. Automated analysis of background EEG and reactivity during therapeutic hypothermia in comatose patients after cardiac arrest. Clin EEG Neurosci. 2014;45:6–13.

    PubMed  Google Scholar 

  61. Admiraal MM, van Rootselaar AF, Horn J. International consensus on EEG reactivity testing after cardiac arrest: towards standardization. Resuscitation. 2018 Oct;131:36–41.

    PubMed  CAS  Google Scholar 

  62. • Ruijter BJ, van Putten MJAM, van de Bergh WM, et al. Propofol does not affect the reliability of early EEG for outcome prediction of comatose patients after cardiac arrest. Clin Neurophysiol. 2019;130:1263–70 In a prospective multicenter cohort study, Propofol induces changes of the postanoxic EEG were described and showed that those changes does not affect the value of EEG for the prediction of outcome.

    PubMed  Google Scholar 

  63. Tiainen M, Kovala TT, Takkunen OS, Roine RO. Somatosensory and brainstem auditory evoked potentials in cardiac arrest patients treated with hypothermia. Crit Care Med. 2005;33(8):1736–40.

    PubMed  Google Scholar 

  64. Leithner C, Ploner CJ, Hasper D, Storm C. Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest? Neurology. 2010;74(12):965–9.

    PubMed  Google Scholar 

  65. Maciel CB, Morawo AO, Tsao CY, Youn TS, Labar DR, Rubens EO, et al. SSEP in therapeutic hypothermia era. J Clin Neurophysiol. 2017;34(5):469–75.

    PubMed  Google Scholar 

  66. • Amorim E, Ghassemi MM, Lee JW, et al. Estimating the false positive rate of absent somatosensory evoked potentials in cardiac arrest prognostication. Crit Care Med. 2018;46(12):e1213–21 In a systematic review based on 35 studies in cardiac arrest, prognostication that reported somatosensory evoked potentials, a statistical model was created to estimate the false positive rate for poor outcome after cardiac arrest.

    PubMed  PubMed Central  Google Scholar 

  67. Endisch C, Storm C, Ploner CJ, Leithner C. Amplitudes of SSEP and outcome in cardiac arrest survivors: a prospective cohort study. Neurology. 2015;85(20):1752–60.

    PubMed  Google Scholar 

  68. Oh SH, Park KN, Choi SP, Oh JS, Kim HJ, Youn CS, et al. Beyond dichotomy: patterns and amplitudes of SSEPs and neurological outcomes after cardiac arrest. Crit Care. 2019;23(1):224.

    PubMed  PubMed Central  Google Scholar 

  69. 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):2881–6.

    PubMed  CAS  Google Scholar 

  70. Stammet P, Collignon O, Hassager C, Wise MP, Hovdenes J, Åneman A, et al. 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):2104–14.

    PubMed  CAS  Google Scholar 

  71. Duez CHV, Grejs AM, Jeppesen AN, Schrøder AD, Søreide E, Nielsen JF, et al. Neuron-specific enolase and S-100b in prolonged targeted temperature management after cardiac arrest: a randomised study. Resuscitation. 2018;122:79–86.

    PubMed  Google Scholar 

  72. Stammet P, Dankiewicz J, Nielsen N, Fays F, Collignon O, Hassager C, et al. Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 C and 36 C. Crit Care. 2017;21(1):153.

    PubMed  PubMed Central  Google Scholar 

  73. 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):1382–6.

    PubMed  CAS  Google Scholar 

  74. Mlynash M, Buckwalter MS, Okada A, Caulfield AF, Venkatasubramanian C, Eyngorn I, et al. Serum neuron-specific enolase levels from the same patients differ between laboratories: assessment of a prospective post-cardiac arrest cohort. Neurocrit Care. 2013;19(2):161–6.

    PubMed  CAS  Google Scholar 

  75. Luescher T, Mueller J, Isenschmid C, et al. Neuron-specific enolase (NSE) improves clinical risk scores for prediction of neurological outcome and death in cardiac arrest patients: results from a prospective trial. Resuscitation. 2019.

  76. Gillick K, Rooney K. Serial NSE measurement identifies non-survivors following out of hospital cardiac arrest. Resuscitation. 2018;128:24–30.

    PubMed  Google Scholar 

  77. •• Moseby-Knappe M, Mattsson N, Nielsen N, Zetterberg H, Blennow K, Dankiewicz J, et al. Serum neurofilament light chain for prognosis of outcome after cardiac arrest. JAMA Neurol. 2019;76(1):64–71. In a prospective clinical biobank study of data from the randomized Target Temperature Management after Cardiac Arrest trial, an international, multicenter study with 29 participating sites, at comparable specificities, serum NFL levels had greater sensitivity for poor outcome compared with routine electroencephalogram, somatosensory-evoked potentials, head computed tomography, and both pupillary and corneal reflexes.

    PubMed  Google Scholar 

  78. Kim SH, Choi SP, Park KN, Youn CS, Oh SH, Choi SM. Early brain computed tomography findings are associated with outcome in patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest. Scand J Trauma Resusc Emerg Med. 2013;21:57.

    PubMed  PubMed Central  Google Scholar 

  79. Metter RB, Rittenberger JC, Guyette FX, Callaway CW. Association between a quantitative CT scan measure of brain edema and outcome after cardiac arrest. Resuscitation. 2011;82(9):1180–5.

    PubMed  PubMed Central  Google Scholar 

  80. 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):985–92.

    PubMed  PubMed Central  Google Scholar 

  81. Hong JY, Lee DH, Oh JH. Grey-white matter ratio measured using early unenhanced brain computed tomography shows no correlation with neurological outcomes in patients undergoing targeted temperature management after cardiac arrest. Resuscitation. 2019;140:161–9.

    PubMed  Google Scholar 

  82. Hirsch KG, Mlynash M, Eyngorn I, Pirsaheli R, Okada A, Komshian S, et al. Multi-center study of diffusion-weighted imaging in coma after cardiac arrest. Neurocrit Care. 2016;24(1):82–9.

    PubMed  CAS  Google Scholar 

  83. Ryoo SM, Jeon SB, Sohn CH, Ahn S, Han C, Lee BK, et al. Predicting outcome with diffusion-weighted imaging in cardiac arrest patients receiving hypothermia therapy: multicenter retrospective cohort study. Crit Care Med. 2015;43(11):2370–7.

    PubMed  CAS  Google Scholar 

  84. • Reynolds AS, Guo X, Matthews E, et al. Post-anoxic quantitative MRI changes may predict emergence from coma and functional outcomes at discharge. Resuscitation. 2017;117:87–90. Using a semi-automated algorithm to perform quantitative volumetric analysis of apparent diffusion coefficient (ADC) sequences at various thresholds, this single-center study showed MRI parameters to be superior in predicting failure to wake up from coma compared to bilateral absence of pupillary reflexes.

    PubMed  PubMed Central  Google Scholar 

  85. Greer D, Scripko P, Bartscher J, Sims J, Camargo E, Singhal A, et al. Clinical MRI interpretation for outcome prediction in cardiac arrest. Neurocrit Care. 2012;17(2):240–4.

    PubMed  Google Scholar 

  86. Mlynash M, Campbell DM, Leproust EM, Fischbein NJ, Bammer R, Eyngorn I, et al. Temporal and spatial profile of brain diffusion-weighted MRI after cardiac arrest. Stroke. 2010;41(8):1665–72.

    PubMed  PubMed Central  Google Scholar 

  87. • Greer DM, Rosenthal ES, Wu O. Neuroprognostication of hypoxic-ischaemic coma in the therapeutic hypothermia era. Nat Rev Neurol. 2014;10(4):190–203. In this review, was discussed the data and its limitations for neuroimaging to date. Promising results from advanced neuroimaging techniques, and practical advice for the clinician caring for these patients in the real world were presented.

    PubMed  CAS  Google Scholar 

  88. Extracorporeal Life Support Organization. ECLS registry report, international summary. Ann Arbor: Extracorporeal Life Support Organization; 2019.

    Google Scholar 

  89. •• Brodie D, Slutsky AS, Combes A. Extracorporeal life support for adults with respiratory failure and related indications: a review. JAMA. 2019;322(6):557–68. This review highlights the physiology and biology of extracorporeal support, and increased knowledge of how it might benefit the treatment of a variety of clinical conditions.

    PubMed  Google Scholar 

  90. Nasr DM, Rabinstein AA. Neurologic complications of extracorporeal membrane oxygenation. J Clin Neurol. 2015;11(4):383–9.

    PubMed  PubMed Central  Google Scholar 

  91. Maekawa K, Tanno K, Hase M, Mori K, Asai Y. Extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest of cardiac origin: a propensity-matched study and predictor analysis. Crit Care Med. 2013;41:1186–96.

    PubMed  Google Scholar 

  92. Lee JJ, Han SJ, Jin S, et al. Out-of-hospital cardiac arrest patients treated with cardiopulmonary resuscitation using extracorporeal membrane oxygenation: focus on survival rate and neurologic outcome. Scand J Trauma, Resusc Emerg Med. 2016;24:74.

    Google Scholar 

  93. • Miroz, JP, Solari D, Eckert, P, Oddo, M, Ben-Hamouda, N. Neurological Pupil Index for early neuroprognostication in ECMO patients. Conference: Proceedings of Réanimation 2018, The French Intensive Care Society international congress, at Paris (France), volume: annals of intensive care 2018, 8(Suppl 1): F-35. This conference paper for the first time showed pilot data on the feasibility and effectiveness of using quantitative pupillometry in cardiac arrest patients with ECMO.

  94. Schumacher RE, Spak C, Kileny PR. Asymmetric brain stem auditory evoked responses in infants treated with extracorporeal membrane oxygenation. Ear Hear. 1990;11(5):359–62.

    PubMed  CAS  Google Scholar 

  95. Amigoni A, Pettenazzo A, Biban P, Suppiej A, Freato F, Zaramella P, et al. Neurologic outcome in children after extracorporeal membrane oxygenation: prognostic value of diagnostic tests. Pediatr Neurol. 2005;32(3):173–9.

    PubMed  Google Scholar 

  96. Streletz LJ, Bej MD, Graziani LJ, Desai HJ, Beacham SG, Cullen J, et al. Utility of serial EEGs in neonates during extracorporeal membrane oxygenation. Pediatr Neurol. 1992;8(3):190–6.

    PubMed  CAS  Google Scholar 

  97. • Cho, Sung-Min, Wendy Ziai, Yunis Mayasi, Aaron M. Gusdon, Jennifer Creed, Matthew Sharrock, et. al. Noninvasive neurological monitoring in extracorporeal membrane oxygenation. ASAIO J, 2019. Through a small, single-center study optimal neurologic monitoring methods for cardiac arrest patients on ECMO were characterized.

  98. Lidegram M, Palmer K, Joruf H, et al. CT in the evaluation of patients on ECMO due to acute respiratory failure. Pediatr Radiol. 2002;32:567–74.

    Google Scholar 

  99. Liu KL, et al. Multislice CT scans in patients on extracorporeal membrane oxygenation: emphasis on hemodynamic changes and imaging pitfalls. Korean J Radiol. 2014;15(3):322–9. https://doi.org/10.3348/kjr.2014.15.3.322.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Susana M. Bowling, Joao Gomes and Michael S. Firstenberg (September 14th 2016). Neurologic issues in patients receiving extracorporeal membrane oxygenation support, extracorporeal membrane oxygenation - advances in therapy, Michael S. Firstenberg, IntechOpen: https://doi.org/10.5772/64269.

    Google Scholar 

  101. Bembea MM, Rizkall N, Freedy J, et al. Plasma biomarkers of brain injury as diagnostic tools and outcome predictors after extracorporeal membrane oxygenation. Crit Care Med. 2015;43(10):2202–11.

    PubMed  CAS  Google Scholar 

  102. Bembea MM, Savage W, Strouse JJ, Schwartz JM, Graham E, Thompson CB, et al. Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2011;12(5):572–9.

    PubMed  PubMed Central  Google Scholar 

  103. Gazzolo D, Masetti P, Meli M, Grutzfeld D, Michetti F. Elevated S100B protein as an early indicator of intracranial haemorrhage in infants subjected to extracorporeal membrane oxygenation. Acta Paediatr. 2002;91:218–21.

    PubMed  CAS  Google Scholar 

  104. • Zhang Y, Li CS, Yuan XL, Ling JY, Zhang Q, Liang Y. Association of serum biomarkers with outcomes of cardiac arrest patients undergoing ECMO. Am J Emerg Med. 2018;36(11):2020–8 A systematic review and meta-analysis with 17 papers containing 903 cases of CA patients treated with ECMO, high serum lactate level was associated with poor survival and poor neurological outcome.

    PubMed  Google Scholar 

  105. Wijdicks EF, Varelas PN, Gronseth GS, Greer DM, American Academy of Neurology. 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;74:1911–8.

    PubMed  Google Scholar 

  106. • Bein T, Müller T, Citerio G. Determination of brain death under extracorporeal life support. Intensive Care Med. 2019;45(3):364–6. This review highlights the technical challenges associated with brain death declaration in ECMO patients, as brain death sometimes marks the end of strenuous therapeutic efforts.

    PubMed  Google Scholar 

  107. Giani M, Scaravilli V, Colombo SM, Confalonieri A, Leo R, Maggioni E, et al. Apnea test during brain death assessment in mechanically ventilated and ECMO patients. Intensive Care Med. 2016;42(1):72–81.

    PubMed  Google Scholar 

  108. Van der Jagt M, Lin MS, Briegel J. Optimizing apnea testing to determine brain death. Intensive Care Med. 2016 Jan;42(1):117–8.

  109. • Sutter R, Tisljar K, Marsch S. Acute neurologic complications during extracorporeal membrane oxygenation: a systematic review. Crit Care Med. 2018;46(9):1506–13. In this systematic review, high occurrence rates of neurologic complications were reported, especially with venoarterial extracorporeal membrane oxygenation. Further highlighted was the low quality of evidence indicating the need for more high-quality studies.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Neurocritical Care and Hospitalist Neurology, Department of Neurology, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY, USA

    Sachin Agarwal MD, MPH

  2. Department of Neurology, Program in Trauma, University of Maryland Medical Center, Baltimore, MD, USA

    Nicholas Morris MD

  3. Clinical Pharmacy, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY, USA

    Caroline Der-Nigoghossian PharmD

  4. Division of Pulmonary and Critical Care Medicine, Maine Medical Center, Portland, ME, USA

    Teresa May DO

  5. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY, USA

    Daniel Brodie MD

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Correspondence to Sachin Agarwal MD, MPH.

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Sachin Agarwal, Nicholas Morris, Caroline Der-Nigoghossian, and Teresa May each declare no potential conflicts of interest.

Daniel Brodie reports a grant from ALung Technologies, personal fees from Baxter, and serves and/or served as a member of the Medical Advisory Boards for ALung Technologies, Hemovent, BREETHE, and Xenios.

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Agarwal, S., Morris, N., Der-Nigoghossian, C. et al. The Influence of Therapeutics on Prognostication After Cardiac Arrest. Curr Treat Options Neurol 21, 60 (2019). https://doi.org/10.1007/s11940-019-0602-1

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