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 (PaO₂ ) 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 (PaO₂ ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO₂ ≤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.

FIGURE 1

Participants, initial surge (March–July 2020). CUIMC = Columbia University Irving Medical Center; GCS = Glasgow Coma Scale; MGH = Massachusetts General Hospital; PaO₂ = arterial partial pressure of oxygen; WCMC = Weill Cornell Medical College.

FIGURE 2

Kaplan–Meier cumulative incidence curves for recovery of command‐following in patients with and without hypoxemia, for initial surge (March–July 2020) and second surge (October 2020 to April 2021). Kaplan–Meier curves for recovery of command‐following in patients grouped by minimum PaO₂ ≤55 mmHg versus >55 (A) initial surge, (C) second surge. Kaplan–Meier curves for patients grouped according to number of days of PaO₂ ≤55 mmHg (B) initial surge, (D) second surge). CI = confidence interval; PaO₂ = partial pressure of arterial oxygen.

FIGURE 3

Pooled univariate and multivariable hazard ratios of primary hypoxemia exposure from Cox proportional hazard regressions clustered by site among initial surge. Each point estimate represents an independent regression model; 95% CIs are indicated with corresponding bars. Multivariable regressions included the exposure listed as well as covariates for demographics (age, sex, and race/ethnicity), level of sedation (cumulative analgesic and sedative dose, duration of continuous analgesic and sedative), and severity of illness (ARDS severity, neuromuscular blockade, CRRT). ARDS = acute respiratory distress syndrome; CI = confidence interval; CRRT = continuous renal replacement therapy.

FIGURE 4

Kaplan–Meier cumulative incidence curves for recovery of command‐following by hypoxemia category (PaO₂ ≤70 mmHg) and minimal PaO₂ value for initial surge (March–July 2020) and second surge (October 2020 to April 2021). CI = confidence interval; PaO₂ = partial pressure of arterial oxygen. Kaplan–Meier curves for recovery of command‐following in patients grouped by minimum PaO₂ ≤ 70 mmHg versus >70 (A) initial surge, (D) second surge. Kaplan–Meier curves for patients grouped according to number of days of PaO₂ ≤70 mmHg (B) initial surge, (E) second surge, and minimum PaO₂ per patient (C) initial surge, (F) second surge. CI = confidence interval; PaO₂ = partial pressure of arterial oxygen.

FIGURE 5

Kaplan–Meier cumulative incidence curves for recovery of command‐following in patients with head imaging and without evidence of structural injury. Kaplan–Meier curves for recovery of command following in patients grouped by (A) minimum PaO₂ ≤55 mmHg versus >55, (B) minimum PaO2 ≤70 mmHg versus >70, (C) number of days of PaO₂ ≤ 55 mmHg, (D) minimum PaO₂ per patient. CI = confidence interval; PaO₂ = partial pressure of arterial oxygen.