Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia

Greer Waldrop; Seyed A. Safavynia; Megan E. Barra; Sachin Agarwal; David A. Berlin; Amelia K. Boehme; Daniel Brodie; Jacky M. Choi; Kevin Doyle; Joseph J. Fins; Wolfgang Ganglberger; Katherine Hoffman; Aaron M. Mittel; David Roh; Shibani S. Mukerji; Caroline Der Nigoghossian; Soojin Park; Edward J. Schenck; John Salazar-Schicchi; Qi Shen; Evan Sholle; Angela G. Velazquez; Maria C. Walline; M. Brandon Westover; Emery N. Brown; Jonathan Victor; Brian L. Edlow; Nicholas D. Schiff; Jan Claassen

doi:10.1002/ana.26342

Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia

Greer Waldrop, Seyed A. Safavynia, Megan E. Barra, Sachin Agarwal, David A. Berlin, Amelia K. Boehme, Daniel Brodie, Jacky M. Choi, Kevin Doyle, Joseph J. Fins, Wolfgang Ganglberger, Katherine Hoffman, Aaron M. Mittel, David Roh, Shibani S. Mukerji, Caroline Der Nigoghossian, Soojin Park, Edward J. Schenck, John Salazar-Schicchi, Qi ShenEvan Sholle, Angela G. Velazquez, Maria C. Walline, M. Brandon Westover, Emery N. Brown, Jonathan Victor, Brian L. Edlow, Nicholas D. Schiff, Jan Claassen

Houston Methodist

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

OBJECTIVE: The purpose of this study was to estimate the time to recovery of command-following and associations between hypoxemia with time to recovery of command-following.

METHODS: In this multicenter, retrospective, cohort study during the initial surge of the United States' pandemic (March-July 2020) we estimate the time from intubation to recovery of command-following, using Kaplan Meier cumulative-incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID-19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6).

RESULTS: Five hundred seventy-one patients of the 795 patients recovered command-following. The median time to recovery of command-following was 30 days (95% confidence interval [CI] = 27-32 days). Median time to recovery of command-following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO 2 ) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command-following was associated with hypoxemia (PaO 2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO 2 ≤70 HR = 0.88, 95% CI = 0.85-0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non-overlapping second surge cohort (N = 427, October 2020 to April 2021).

INTERPRETATION: Survivors of severe COVID-19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life-sustaining therapies. ANN NEUROL 2022;91:740-755.

Original language	English (US)
Pages (from-to)	740-755
Number of pages	16
Journal	Annals of Neurology
Volume	91
Issue number	6
DOIs	https://doi.org/10.1002/ana.26342
State	Published - Jun 2022

Keywords

Brain Injuries/complications
COVID-19/complications
Cohort Studies
Humans
Hypoxia
Retrospective Studies
Unconsciousness/complications

ASJC Scopus subject areas

Clinical Neurology
Neurology

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10.1002/ana.26342

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Waldrop, G., Safavynia, S. A., Barra, M. E., Agarwal, S., Berlin, D. A., Boehme, A. K., Brodie, D., Choi, J. M., Doyle, K., Fins, J. J., Ganglberger, W., Hoffman, K., Mittel, A. M., Roh, D., Mukerji, S. S., Der Nigoghossian, C., Park, S., Schenck, E. J., Salazar-Schicchi, J., ... Claassen, J. (2022). Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia. Annals of Neurology, 91(6), 740-755. https://doi.org/10.1002/ana.26342

Waldrop, G, Safavynia, SA, Barra, ME, Agarwal, S, Berlin, DA, Boehme, AK, Brodie, D, Choi, JM, Doyle, K, Fins, JJ, Ganglberger, W, Hoffman, K, Mittel, AM, Roh, D, Mukerji, SS, Der Nigoghossian, C, Park, S, Schenck, EJ, Salazar-Schicchi, J, Shen, Q, Sholle, E, Velazquez, AG, Walline, MC, Westover, MB, Brown, EN, Victor, J, Edlow, BL, Schiff, ND & Claassen, J 2022, 'Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia', Annals of Neurology, vol. 91, no. 6, pp. 740-755. https://doi.org/10.1002/ana.26342

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title = "Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia",

abstract = "OBJECTIVE: The purpose of this study was to estimate the time to recovery of command-following and associations between hypoxemia with time to recovery of command-following.METHODS: In this multicenter, retrospective, cohort study during the initial surge of the United States' pandemic (March-July 2020) we estimate the time from intubation to recovery of command-following, using Kaplan Meier cumulative-incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID-19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6).RESULTS: Five hundred seventy-one patients of the 795 patients recovered command-following. The median time to recovery of command-following was 30 days (95% confidence interval [CI] = 27-32 days). Median time to recovery of command-following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO 2 ) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command-following was associated with hypoxemia (PaO 2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO 2 ≤70 HR = 0.88, 95% CI = 0.85-0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non-overlapping second surge cohort (N = 427, October 2020 to April 2021). INTERPRETATION: Survivors of severe COVID-19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life-sustaining therapies. ANN NEUROL 2022;91:740-755.",

keywords = "Brain Injuries/complications, COVID-19/complications, Cohort Studies, Humans, Hypoxia, Retrospective Studies, Unconsciousness/complications",

author = "Greer Waldrop and Safavynia, {Seyed A.} and Barra, {Megan E.} and Sachin Agarwal and Berlin, {David A.} and Boehme, {Amelia K.} and Daniel Brodie and Choi, {Jacky M.} and Kevin Doyle and Fins, {Joseph J.} and Wolfgang Ganglberger and Katherine Hoffman and Mittel, {Aaron M.} and David Roh and Mukerji, {Shibani S.} and {Der Nigoghossian}, Caroline and Soojin Park and Schenck, {Edward J.} and John Salazar-Schicchi and Qi Shen and Evan Sholle and Velazquez, {Angela G.} and Walline, {Maria C.} and Westover, {M. Brandon} and Brown, {Emery N.} and Jonathan Victor and Edlow, {Brian L.} and Schiff, {Nicholas D.} and Jan Claassen",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2022",

month = jun,

doi = "10.1002/ana.26342",

language = "English (US)",

volume = "91",

pages = "740--755",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley & Sons Inc.",

number = "6",

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TY - JOUR

T1 - Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia

AU - Waldrop, Greer

AU - Safavynia, Seyed A.

AU - Barra, Megan E.

AU - Agarwal, Sachin

AU - Berlin, David A.

AU - Boehme, Amelia K.

AU - Brodie, Daniel

AU - Choi, Jacky M.

AU - Doyle, Kevin

AU - Fins, Joseph J.

AU - Ganglberger, Wolfgang

AU - Hoffman, Katherine

AU - Mittel, Aaron M.

AU - Roh, David

AU - Mukerji, Shibani S.

AU - Der Nigoghossian, Caroline

AU - Park, Soojin

AU - Schenck, Edward J.

AU - Salazar-Schicchi, John

AU - Shen, Qi

AU - Sholle, Evan

AU - Velazquez, Angela G.

AU - Walline, Maria C.

AU - Westover, M. Brandon

AU - Brown, Emery N.

AU - Victor, Jonathan

AU - Edlow, Brian L.

AU - Schiff, Nicholas D.

AU - Claassen, Jan

PY - 2022/6

Y1 - 2022/6

N2 - OBJECTIVE: The purpose of this study was to estimate the time to recovery of command-following and associations between hypoxemia with time to recovery of command-following.METHODS: In this multicenter, retrospective, cohort study during the initial surge of the United States' pandemic (March-July 2020) we estimate the time from intubation to recovery of command-following, using Kaplan Meier cumulative-incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID-19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6).RESULTS: Five hundred seventy-one patients of the 795 patients recovered command-following. The median time to recovery of command-following was 30 days (95% confidence interval [CI] = 27-32 days). Median time to recovery of command-following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO 2 ) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command-following was associated with hypoxemia (PaO 2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO 2 ≤70 HR = 0.88, 95% CI = 0.85-0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non-overlapping second surge cohort (N = 427, October 2020 to April 2021). INTERPRETATION: Survivors of severe COVID-19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life-sustaining therapies. ANN NEUROL 2022;91:740-755.

AB - OBJECTIVE: The purpose of this study was to estimate the time to recovery of command-following and associations between hypoxemia with time to recovery of command-following.METHODS: In this multicenter, retrospective, cohort study during the initial surge of the United States' pandemic (March-July 2020) we estimate the time from intubation to recovery of command-following, using Kaplan Meier cumulative-incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID-19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6).RESULTS: Five hundred seventy-one patients of the 795 patients recovered command-following. The median time to recovery of command-following was 30 days (95% confidence interval [CI] = 27-32 days). Median time to recovery of command-following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO 2 ) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command-following was associated with hypoxemia (PaO 2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO 2 ≤70 HR = 0.88, 95% CI = 0.85-0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non-overlapping second surge cohort (N = 427, October 2020 to April 2021). INTERPRETATION: Survivors of severe COVID-19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life-sustaining therapies. ANN NEUROL 2022;91:740-755.

KW - Brain Injuries/complications

KW - COVID-19/complications

KW - Cohort Studies

KW - Humans

KW - Hypoxia

KW - Retrospective Studies

KW - Unconsciousness/complications

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Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia

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