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March 02, 2021; 96 (9) Article

Brain Histopathology of Adult Decedents After Extracorporeal Membrane Oxygenation

View ORCID ProfileImad R. Khan, Yang Gu, View ORCID ProfileBenjamin P. George, Laura Malone, View ORCID ProfileKyle S. Conway, Fabienne Francois, Jack Donlon, Nadim Quazi, View ORCID ProfileAshwin Reddi, View ORCID ProfileCheng-Ying Ho, View ORCID ProfileDaniel L. Herr, Mahlon D. Johnson, View ORCID ProfileGunjan Y. Parikh
First published January 20, 2021, DOI: https://doi.org/10.1212/WNL.0000000000011525
Imad R. Khan
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
MD
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Yang Gu
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
MD
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Benjamin P. George
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
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Laura Malone
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
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Kyle S. Conway
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
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Fabienne Francois
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
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Jack Donlon
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
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Nadim Quazi
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
BS
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Ashwin Reddi
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
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Cheng-Ying Ho
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
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Daniel L. Herr
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
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Mahlon D. Johnson
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
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Gunjan Y. Parikh
From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.
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Citation
Brain Histopathology of Adult Decedents After Extracorporeal Membrane Oxygenation
Imad R. Khan, Yang Gu, Benjamin P. George, Laura Malone, Kyle S. Conway, Fabienne Francois, Jack Donlon, Nadim Quazi, Ashwin Reddi, Cheng-Ying Ho, Daniel L. Herr, Mahlon D. Johnson, Gunjan Y. Parikh
Neurology Mar 2021, 96 (9) e1278-e1289; DOI: 10.1212/WNL.0000000000011525

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Abstract

Objective To test the hypothesis that brain injury is more common and varied in patients receiving extracorporeal membrane oxygenation (ECMO) than radiographically observed, we described neuropathology findings of ECMO decedents and associated clinical factors from 3 institutions.

Methods We conducted a retrospective multicenter observational study of brain autopsies from adult ECMO recipients. Pathology findings were examined for correlation with demographics, clinical data, ECMO characteristics, and outcomes.

Results Forty-three decedents (n = 13 female, median age 47 years) received autopsies after undergoing ECMO for acute respiratory distress syndrome (n = 14), cardiogenic shock (n = 14), and cardiac arrest (n = 15). Median duration of ECMO was 140 hours, most decedents (n = 40) received anticoagulants; 60% (n = 26) underwent venoarterial ECMO, and 40% (n = 17) underwent venovenous ECMO. Neuropathology was found in 35 decedents (81%), including microhemorrhages (37%), macrohemorrhages (35%), infarctions (47%), and hypoxic-ischemic brain injury (n = 17, 40%). Most pathology occurred in frontal neocortices (n = 43 occurrences), basal ganglia (n = 33), and cerebellum (n = 26). Decedents with hemorrhage were older (median age 57 vs 38 years, p = 0.01); those with hypoxic brain injury had higher Sequential Organ Failure Assessment scores (8.0 vs 2.0, p = 0.04); and those with infarction had lower peak Paco2 (53 vs 61 mm Hg, p = 0.04). Six of 9 patients with normal neuroimaging results were found to have pathology on autopsy. The majority underwent withdrawal of life-sustaining therapy (n = 32, 74%), and 2 of 8 patients with normal brain autopsy underwent withdrawal of life-sustaining therapy for suspected neurologic injury.

Conclusion Neuropathological findings after ECMO are common, varied, and associated with various clinical factors. Further study on underlying mechanisms is warranted and may guide ECMO management.

Glossary

ARDS=
acute respiratory distress syndrome;
ECMO=
extracorporeal membrane oxygenation;
GCS=
Glasgow Coma Scale;
HIBI=
hypoxic-ischemic brain injury;
ICH=
intracranial hemorrhage;
IQR=
interquartile range;
MOF=
multiorgan failure;
SOFA=
Sequential Organ Failure Assessment;
UMD=
University of Maryland Medical Center;
UMI=
University of Michigan Medical Center;
UR=
University of Rochester Medical Center;
VA=
venoarterial;
VV=
venovenous

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received June 10, 2020.
  • Accepted in final form November 4, 2020.
  • © 2021 American Academy of Neurology
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