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Semin Neurol 2021; 41(04): 388-397
DOI: 10.1055/s-0041-1731310
Review Article

Updates on the Management of Neurologic Complications of Post–Cardiac Arrest Resuscitation

Yunis Mayasi
1   Division of NeuroCritical Care, Avera McKennan Hospital and University Health Center, Sioux Falls, South Dakota-University of South Dakota Medical School, Sioux Falls, South Dakota
,
Romergryko G. Geocadin
2   Division of Neurosciences Critical Care, Neurology, Neurosurgery and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Abstract

Sudden cardiac arrest (SCA) is one of the leading causes of mortality and morbidity in the United States, and survivors are frequently left with severe disability. Of the 10% successfully resuscitated from SCA, only around 10% of these live with a favorable neurologic outcome. Survivors of SCA commonly develop post–cardiac arrest syndrome (PCAS). PCAS is composed of neurologic, myocardial, and systemic injury related to inadequate perfusion and ischemia–reperfusion injury with free radical formation and an inflammatory cascade. While targeted temperature management is the cornerstone of therapy, other intensive care unit–based management strategies include monitoring and treatment of seizures, cerebral edema, and increased intracranial pressure, as well as prevention of further neurologic injury. In this review, we discuss the scientific evidence, recent updates, future prospects, and knowledge gaps in the treatment of post–cardiac arrest patients.

Keywords

cardiac arrest - anoxic injury - post–cardiac arrest syndrome - secondary brain injury - outcomes


Publication History

Article published online:
19 August 2021

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  • References

  • 1 Andersen LW, Holmberg MJ, Berg KM, Donnino MW, Granfeldt A. In-hospital cardiac arrest: a review. JAMA 2019; 321 (12) 1200-1210
    CrossrefPubMedGoogle Scholar
  • 2 Girotra S, Chan PS, Bradley SM. Post-resuscitation care following out-of-hospital and in-hospital cardiac arrest. Heart 2015; 101 (24) 1943-1949
    CrossrefPubMedGoogle Scholar
  • 3 Greer DM. Mechanisms of injury in hypoxic-ischemic encephalopathy: implications to therapy. Semin Neurol 2006; 26 (04) 373-379
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Saver JL. Time is brain--quantified. Stroke 2006; 37 (01) 263-266
    CrossrefPubMedGoogle Scholar
  • 5 Elmer J, Callaway CW. The brain after cardiac arrest. Semin Neurol 2017; 37 (01) 19-24
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Neumar RW. Molecular mechanisms of ischemic neuronal injury. Ann Emerg Med 2000; 36 (05) 483-506
    CrossrefPubMedGoogle Scholar
  • 7 Hansen FB, Secher N, Jensen MS, Østergaard L, Tønnesen E, Granfeldt A. Cortical spreading depolarizations in the postresuscitation period in a cardiac arrest male rat model. J Neurosci Res 2017; 95 (10) 2040-2050
    CrossrefPubMedGoogle Scholar
  • 8 Schock SC, Munyao N, Yakubchyk Y. et al. Cortical spreading depression releases ATP into the extracellular space and purinergic receptor activation contributes to the induction of ischemic tolerance. Brain Res 2007; 1168: 129-138
    CrossrefPubMedGoogle Scholar
  • 9 Binks A, Nolan JP. Post-cardiac arrest syndrome. Minerva Anestesiol 2010; 76 (05) 362-368
    PubMedGoogle Scholar
  • 10 Kang Y. Management of post-cardiac arrest syndrome. Acute Crit Care 2019; 34 (03) 173-178
    CrossrefPubMedGoogle Scholar
  • 11 Neumar RW, Nolan JP, Adrie C. et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation 2008; 118 (23) 2452-2483
    CrossrefPubMedGoogle Scholar
  • 12 Berg KM, Soar J, Andersen LW. et al. Adult advanced life support: 2020 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 2020; 142 (16, Suppl 1): S92-S139
    CrossrefPubMedGoogle Scholar
  • 13 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
    CrossrefPubMedGoogle Scholar
  • 14 Lascarrou JB, Merdji H, Le Gouge A. et al; CRICS-TRIGGERSEP Group. Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med 2019; 381 (24) 2327-2337
    CrossrefPubMedGoogle Scholar
  • 15 Johnson NJ, Danielson KR, Counts CR. et al. Targeted temperature management at 33 versus 36 degrees: a retrospective cohort study. Crit Care Med 2020; 48 (03) 362-369
    CrossrefPubMedGoogle Scholar
  • 16 Mongardon N, Dumas F, Ricome S. et al. Postcardiac arrest syndrome: from immediate resuscitation to long-term outcome. Ann Intensive Care 2011; 1 (01) 45-5820
    CrossrefPubMedGoogle Scholar
  • 17 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
    CrossrefPubMedGoogle Scholar
  • 18 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
    CrossrefPubMedGoogle Scholar
  • 19 Chandrasekaran PN, Dezfulian C, Polderman KH. What is the right temperature to cool post-cardiac arrest patients?. Crit Care 2015; 19: 406
    CrossrefPubMedGoogle Scholar
  • 20 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
    CrossrefPubMedGoogle Scholar
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Callaway CW. Targeted temperature management after cardiac arrest: finding the right dose for critical care interventions. JAMA 2017; 318 (04) 334-336
    CrossrefPubMedGoogle Scholar
  • 23 Moskowitz A, Berg KM, Donnino MW. Targeted temperature management after cardiac arrest. N Engl J Med 2020; 382: e109
    CrossrefPubMedGoogle Scholar
  • 24 Influence of cooling duration on efficacy in cardiac arrest patients - a multicenter, randomized, adaptive clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose survivors of cardiac arrest. November 30, 2020. ClinicalTrials.gov Identifier: NCT04217551
    PubMedGoogle Scholar
  • 25 O'Driscoll BR, Howard LS, Davison AG. British Thoracic Society. BTS guideline for emergency oxygen use in adult patients. Thorax 2008; 63 (Suppl. 06) vi1-vi68
    PubMedGoogle Scholar
  • 26 Sinha N, Parnia S. Monitoring the brain after cardiac arrest: a new era. Curr Neurol Neurosci Rep 2017; 17 (08) 62
    CrossrefPubMedGoogle Scholar
  • 27 Thal SC. Impact of NIRS-guided cardiopulmonary resuscitation after cardiac arrest on resuscitation rate (NICA). Updated 2019. Accessed December 25, 2019 at: https://clinicaltrials.gov/ct2/show/NCT03911908
    PubMedGoogle Scholar
  • 28 Lemiale V, Huet O, Vigué B. et al. Changes in cerebral blood flow and oxygen extraction during post-resuscitation syndrome. Resuscitation 2008; 76 (01) 17-24
    CrossrefPubMedGoogle Scholar
  • 29 Böttiger BW, Krumnikl JJ, Gass P, Schmitz B, Motsch J, Martin E. The cerebral ‘no-reflow’ phenomenon after cardiac arrest in rats--influence of low-flow reperfusion. Resuscitation 1997; 34 (01) 79-87
    CrossrefPubMedGoogle Scholar
  • 30 Böttiger BW, Arntz HR, Chamberlain DA. et al; TROICA Trial Investigators, European Resuscitation Council Study Group. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. N Engl J Med 2008; 359 (25) 2651-2662
    CrossrefPubMedGoogle Scholar
  • 31 Targeted therapeutic mild hypercapnia after resuscitated cardiac arrest (TAME). ClinicalTrials.gov Identifier: NCT03114033.. 2020
    PubMedGoogle Scholar
  • 32 Jakkula P, Pettilä V, Skrifvars MB. et al; COMACARE Study Group. Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial. Intensive Care Med 2018; 44 (12) 2091-2101
    CrossrefPubMedGoogle Scholar
  • 33 Buunk G, van der Hoeven JG, Meinders AE. Cerebrovascular reactivity in comatose patients resuscitated from a cardiac arrest. Stroke 1997; 28 (08) 1569-1573
    CrossrefPubMedGoogle Scholar
  • 34 Peberdy MA, Callaway CW, Neumar RW. et al; American Heart Association. Part 9: Post-cardiac arrest care: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2010; 122 (18, Suppl 3): S768-S786
    CrossrefPubMedGoogle Scholar
  • 35 Roberts BW, Kilgannon JH, Hunter BR. et al. Association between early hyperoxia exposure after resuscitation from cardiac arrest and neurological disability: prospective multicenter protocol-directed cohort study. Circulation 2018; 137 (20) 2114-2124
    CrossrefPubMedGoogle Scholar
  • 36 Oksanen T, Skrifvars MB, Varpula T. et al. Strict versus moderate glucose control after resuscitation from ventricular fibrillation. Intensive Care Med 2007; 33 (12) 2093-2100
    CrossrefPubMedGoogle Scholar
  • 37 Griesdale DE, de Souza RJ, van Dam RM. et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ 2009; 180 (08) 821-827
    CrossrefPubMedGoogle Scholar
  • 38 Nolan JP, Maconochie I, Soar J. et al. Executive summary: 2020 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 2020; 142 (16, Suppl 1): S2-S27
    CrossrefPubMedGoogle Scholar
  • 39 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 (09) 1180-1185
    CrossrefPubMedGoogle Scholar
  • 40 Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med 2004; 30 (11) 2126-2128
    CrossrefPubMedGoogle Scholar
  • 41 Jones S, Schwartzbauer G, Jia X. Brain monitoring in critically neurologically impaired patients. Int J Mol Sci 2016; 18 (01) 43
    CrossrefPubMedGoogle Scholar
  • 42 Cardim D, Griesdale DE, Ainslie PN. et al. A comparison of non-invasive versus invasive measures of intracranial pressure in hypoxic ischaemic brain injury after cardiac arrest. Resuscitation 2019; 137: 221-228
    CrossrefPubMedGoogle Scholar
  • 43 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 (01) 114-122
    CrossrefPubMedGoogle Scholar
  • 44 Vespa P, Martin NA, Nenov V. et al. Delayed increase in extracellular glycerol with post-traumatic electrographic epileptic activity: support for the theory that seizures induce secondary injury. Acta Neurochir Suppl (Wien) 2002; 81: 355-357
    PubMedGoogle Scholar
  • 45 Mangus DB, Huang L, Applegate PM, Gatling JW, Zhang J, Applegate II RL. A systematic review of neuroprotective strategies after cardiac arrest: from bench to bedside (Part I - Protection via specific pathways). Med Gas Res 2014; 4: 9
    CrossrefPubMedGoogle Scholar
  • 46 Kjaergaard J. GLP-1 analogs for neuroprotection after cardiac arrest (GLIP1). Updated 2017. Accessed December 25, 2019 at: https://clinicaltrials.gov/ct2/show/NCT02442791
    PubMedGoogle Scholar
  • 47 Hassager C. IL-6 inhibition for modulating inflammation after cardiac arrest (IMICA). Updated 2019. Accessed December 25, 2019 at: https://clinicaltrials.gov/ct2/show/NCT03863015
    PubMedGoogle Scholar
  • 48 Choi JH. Antioxidant and NMDA receptor blocker wins anoxic brain damage of KorEa OHCA patients (AWAKE). Updated 2019. Accessed December 25, 2019 at: https://clinicaltrials.gov/ct2/show/NCT03651557
    PubMedGoogle Scholar
  • 49 Geocadin RG, Wijdicks E, Armstrong MJ. et al. Practice guideline summary: Reducing brain injury following cardiopulmonary resuscitation: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology 2017; 88 (22) 2141-2149
    CrossrefPubMedGoogle Scholar
  • 50 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
    CrossrefPubMedGoogle Scholar
  • 51 Jung C, Janssen K, Kaluza M. et al. Outcome predictors in cardiopulmonary resuscitation facilitated by extracorporeal membrane oxygenation. Clin Res Cardiol 2016; 105 (03) 196-205
    CrossrefPubMedGoogle Scholar
  • 52 Debaty G, Babaz V, Durand M. et al. Prognostic factors for extracorporeal cardiopulmonary resuscitation recipients following out-of-hospital refractory cardiac arrest. A systematic review and meta-analysis. Resuscitation 2017; 112: 1-10
    CrossrefPubMedGoogle Scholar
  • 53 Napp LC, Kühn C, Bauersachs J. ECMO in cardiac arrest and cardiogenic shock. Herz 2017; 42 (01) 27-44
    CrossrefPubMedGoogle Scholar
  • 54 Yannopoulos D, Bartos J, Raveendran G. et al. Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial. Lancet 2020; 396 (10265): 1807-1816
    CrossrefPubMedGoogle Scholar
  • 55 Migdady I, Rice C, Deshpande A. et al. Brain injury and neurologic outcome in patients undergoing extracorporeal cardiopulmonary resuscitation: a systematic review and meta-analysis. Crit Care Med 2020; 48 (07) e611-e619
    CrossrefPubMedGoogle Scholar
  • 56 Cho SM, Ziai W, Mayasi Y. et al. Noninvasive neurological monitoring in extracorporeal membrane oxygenation. ASAIO J 2020; 66 (04) 388-393
    CrossrefPubMedGoogle Scholar
  • 57 Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Plum F. Predicting outcome from hypoxic-ischemic coma. JAMA 1985; 253 (10) 1420-1426
    CrossrefPubMedGoogle Scholar
  • 58 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 (02) 203-210
    CrossrefPubMedGoogle Scholar
  • 59 Geocadin RG, Callaway CW, Fink EL. et al; American Heart Association Emergency Cardiovascular Care Committee. Standards for studies of neurological prognostication in comatose survivors of cardiac arrest: a scientific statement from the American Heart Association. Circulation 2019; 140 (09) e517-e542
    CrossrefPubMedGoogle Scholar
  • 60 Thenayan EA, Savard M, Sharpe MD, Norton L, Young B. Electroencephalogram for prognosis after cardiac arrest. J Crit Care 2010; 25 (02) 300-304
    CrossrefPubMedGoogle Scholar
  • 61 Endisch C, Waterstraat G, Storm C. et al. Cortical somatosensory evoked high-frequency (600Hz) oscillations predict absence of severe hypoxic encephalopathy after resuscitation. Clin Neurophysiol 2016; 127 (07) 2561-2569
    CrossrefPubMedGoogle Scholar
  • 62 Hirsch KG, Fischbein N, Mlynash M. et al. Prognostic value of diffusion-weighted MRI for post-cardiac arrest coma. Neurology 2020; 94 (16) e1684-e1692
    CrossrefPubMedGoogle Scholar
  • 63 Silva S, de Pasquale F, Vuillaume C. et al. Disruption of posteromedial large-scale neural communication predicts recovery from coma. Neurology 2015; 85 (23) 2036-2044
    CrossrefPubMedGoogle Scholar
  • 64 Sun F, Zhou G. Willful modulation of brain activity in disorders of consciousness. N Engl J Med 2010; 362 (20) 1937 , author reply 1937–1938
    PubMedGoogle Scholar
  • 65 Gul SS, Huesgen KW, Wang KK, Mark K, Tyndall JA. Prognostic utility of neuroinjury biomarkers in post out-of-hospital cardiac arrest (OHCA) patient management. Med Hypotheses 2017; 105: 34-47
    CrossrefPubMedGoogle Scholar
  • 66 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
    CrossrefPubMedGoogle Scholar
  • 67 Vondrakova D, Kruger A, Janotka M. et al. Association of neuron-specific enolase values with outcomes in cardiac arrest survivors is dependent on the time of sample collection. Crit Care 2017; 21 (01) 172
    CrossrefPubMedGoogle Scholar
  • 68 Rana OR, Schröder JW, Baukloh JK. et al. Neurofilament light chain as an early and sensitive predictor of long-term neurological outcome in patients after cardiac arrest. Int J Cardiol 2013; 168 (02) 1322-1327
    CrossrefPubMedGoogle Scholar
  • 69 Sawyer KN, Camp-Rogers TR, Kotini-Shah P. et al; American Heart Association Emergency Cardiovascular Care Committee; Council on Cardiovascular and Stroke Nursing; Council on Genomic and Precision Medicine; Council on Quality of Care and Outcomes Research; and Stroke Council. Sudden cardiac arrest survivorship: a scientific statement from the American Heart Association. Circulation 2020; 141 (12) e654-e685
    CrossrefPubMedGoogle Scholar
  • 70 Perez CA, Samudra N, Aiyagari V. Cognitive and functional consequence of cardiac arrest. Curr Neurol Neurosci Rep 2016; 16 (08) 70
    CrossrefPubMedGoogle Scholar
  • 71 Brierley JB, Graham DI, Adams JH, Simpsom JA. Neocortical death after cardiac arrest. A clinical, neurophysiological, and neuropathological report of two cases. Lancet 1971; 2 (7724): 560-565
    PubMedGoogle Scholar
  • 72 Nunes B, Pais J, Garcia R, Magalhães Z, Granja C, Silva MC. Cardiac arrest: long-term cognitive and imaging analysis. Resuscitation 2003; 57 (03) 287-297
    CrossrefPubMedGoogle Scholar