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Therapeutic opportunities for cerebral edema after resuscitation

      Early loss of gray-white differentiation and swelling of the brain on computed tomography (CT) imaging after resuscitation from cardiac arrest are ominous signs,
      • Esdaille C.J.
      • Coppler P.J.
      • Faro J.W.
      • et al.
      Pittsburgh Post Cardiac Arrest Service. Duration and clinical features of cardiac arrest predict early severe cerebral edema.
      • Sandroni C.
      • D'Arrigo S.
      • Cacciola S.
      • et al.
      Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review.
      but at Maine Medical Center, our therapeutic nihilism about cerebral edema after cardiac arrest was tempered by the case of a 24 year-old man treated in 2020 who suffered a prolonged PEA arrest and delayed cardiopulmonary resuscitation following an accidental opioid overdose. He presented in transfer from another institution with profound aspiration-related ARDS, a low-voltage and nonreactive EEG exhibiting very high suppression ratio, and cerebral edema by head CT, manifested by loss of gray-white differentiation, narrowing and distortion of the cisternal spaces, and bilateral uncal herniation. Eleven hours after resuscitation, we placed a right frontal parenchymal fiberoptic intracranial pressure (ICP) and brain tissue oxygen (PbtO2) monitor. The ICP was 25 cm H2O and PbtO2 < 5 mmHg despite FiO2 1.0. The ICP corrected with 50 grams of mannitol, but only after the patient was placed in prone, reverse-Trendelenburg positioning with the head up at 30 degrees, resulting in profound improvement in his systemic oxygenation, did the brain oxygen normalize. Over the next 24 hours, at 33 °C, we maintained ICP < 20 cm H2O, cerebral perfusion pressure (CPP) > 60 mmHg, and PbtO2 > 20 mmHg. We also delayed rewarming due to the ICP elevation, completing a full 48 hours at 33 °C, and then rewarmed the patient at 0.25 °C/hr until he reached 36.5 °C. At this point sedation was weaned and he awakened, was rapidly extubated, and within 24 hours left the hospital against medical advice. The case had not gone as expected, and we were left wondering if cerebral edema after cardiac arrest was in fact a plausible target for therapy.
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      References

        • Esdaille C.J.
        • Coppler P.J.
        • Faro J.W.
        • et al.
        Pittsburgh Post Cardiac Arrest Service. Duration and clinical features of cardiac arrest predict early severe cerebral edema.
        Resuscitation. 2020; 153 (Epub 2020 Jun 23. PMID: 32590271; PMCID: PMC7733324): 111-118https://doi.org/10.1016/j.resuscitation.2020.05.049
        • Sandroni C.
        • D'Arrigo S.
        • Cacciola S.
        • et al.
        Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review.
        Intensive Care Med. 2020; 46 (Epub 2020 Sep 11. PMID: 32915254; PMCID: PMC7527362): 1803-1851https://doi.org/10.1007/s00134-020-06198-w
        • Hinduja A.
        • Gokun Y.
        • Ibekwe E.
        • Senay B.
        • Elmer J.
        Risk factors for development of cerebral edema following cardiac arrest.
        Resuscitation. 2022; (S0300-9572(22)00692-X. Epub ahead of print. PMID: 36280215)https://doi.org/10.1016/j.resuscitation.2022.10.013
        • Yan J.
        • Zhang Z.
        • Shi H.
        HIF-1 is involved in high glucose-induced paracellular permeability of brain endothelial cells.
        Cell Mol Life Sci. 2012; 69: 115-128
        • Semenza G.L.
        HIF-1 and mechanisms of hypoxia sensing.
        Curr Opin Cell Biol. 2001; 13: 167-171
        • Zhang Z.G.
        • Zhang L.
        • Jiang Q.
        • et al.
        VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain.
        J Clin Invest. 2000; 106: 829-838
        • Pichiule P.
        • Chávez J.C.
        • Xu K.
        • LaManna J.C.
        Vascular endothelial growth factor upregulation in transient global ischemia induced by cardiac arrest and resuscitation in rat brain.
        Brain Res Mol Brain Res. 1999; 74: 83-90
        • Grunewald M.
        • Kumar S.
        • Sharife H.
        • et al.
        Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span.
        Science. 2021; 373: eabc8479
        • Higashida T.
        • Peng C.
        • Li J.
        • Dornbos 3rd, D.
        • Teng K.
        • Li X.
        • Kinni H.
        • Guthikonda M.
        • Ding Y.
        Hypoxia-inducible factor-1α contributes to brain edema after stroke by regulating aquaporins and glycerol distribution in brain.
        Curr Neurovasc Res. 2011; 8: 44-51
        • Manley G.T.
        • Fujimura M.
        • Ma T.
        • Noshita N.
        • Filiz F.
        • Bollen A.W.
        • Chan P.
        • Verkman A.S.
        Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke.
        Nat Med. 2000; 6: 159-163
        • Sonneville R.
        • Vanhorebeek I.
        • den Hertog H.M.
        • et al.
        Critical illness-induced dysglycemia and the brain.
        Intensive Care Med. 2015; 41 (Epub 2014 Dec 3 PMID: 25465908): 192-202https://doi.org/10.1007/s00134-014-3577-0
        • Dietrich W.D.
        • Alonso O.
        • Busto R.
        Moderate hyperglycemia worsens acute blood-brain barrier injury after forebrain ischemia in rats.
        Stroke. 1993; 24 (PMID: 8418533): 111-116https://doi.org/10.1161/01.str.24.1.111
        • Guo Y.
        • Dong L.
        • Gong A.
        • Zhang J.
        • Jing L.
        • Ding T.
        • Li P.A.
        • Zhang J.Z.
        Damage to the blood–brain barrier and activation of neuroinflammation by focal cerebral ischemia under hyperglycemic condition.
        Int J Mol Med. 2021; 48 (Epub 2021 Jun 3. PMID: 34080644; PMCID: PMC8175066): 142https://doi.org/10.3892/ijmm.2021.4975
        • Sonneville R.
        • den Hertog H.M.
        • Guiza F.
        • et al.
        Impact of hyperglycemia on neuropathological alterations during critical illness.
        J Clin Endocrinol Metab. 2012; 97: 2113-2123
        • Fuller Z.L.
        • Faro J.W.
        • Callaway C.W.
        • Coppler P.J.
        • Elmer J.
        University of Pittsburgh Post-Cardiac Arrest Service. Recovery among post-arrest patients with mild-to-moderate cerebral edema.
        Resuscitation. 2021; 162 (Epub 2021 Mar 1. PMID: 33662524; PMCID: PMC8096677): 149-153https://doi.org/10.1016/j.resuscitation.2021.02.033
        • Hofer B.
        • Dunzendorfer S.
        • Beer R.
        • Joannidis M.
        Cardiac arrest-Favorable functional outcome despite high NSE levels and early brain swelling.
        Resuscitation. 2017; 116 (Epub 2017 Apr 26 PMID: 28456656): e3https://doi.org/10.1016/j.resuscitation.2017.04.031
        • Hayman E.G.
        • Patel A.P.
        • Kimberly W.T.
        • Sheth K.N.
        • Simard J.M.
        Cerebral Edema After Cardiopulmonary Resuscitation: A Therapeutic Target Following Cardiac Arrest?.
        Neurocrit Care. 2018; 28 (PMID: 29080068): 276-287https://doi.org/10.1007/s12028-017-0474-8