Automated pupillometry to detect residual consciousness in acute brain injury

Abstract Background. Identifying residual consciousness in patients with disorders of consciousness (DoC) in the intensive care unit (ICU) is crucial for treatment decisions, but sensitive low-cost bedside markers are missing. We investigated whether automated pupillometry combined with passive and active cognitive paradigms can identify residual consciousness in ICU patients with traumatic or non-traumatic DoC. Methods. In a prospective observational cohort study, clinically low- or unresponsive ICU patients with traumatic and non-traumatic DoC were enrolled from neurological and non-neurological ICUs at a tertiary referral center (Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark). Age- and sex-matched healthy volunteers served as controls. Participants with eye disorders were excluded. Patients were categorized into those without (coma or unresponsive wakefulness syndrome, ≤UWS) or with (minimally conscious state or better, ≥MCS) clinical signs of residual consciousness. Using automated pupillometry, we recorded pupillary dilation as a response to passive (visual and auditory stimuli) and active (mental arithmetic) cognitive paradigms, with success criteria depending on the specific task (e.g., ≥ 3 of 5 pupillary dilations on 5 consecutive mental arithmetic tasks). Results. We obtained 699 pupillometry recordings at 178 time points from 91 brain-injured ICU patients (mean age 60±13.8 years; 31% women; 49.5% non-traumatic brain injuries). Recordings were also obtained from 26 matched controls (59±14.8 years, 38% women). Passive paradigms yielded limited distinctions between patient groups and controls. However, active paradigms involving mental arithmetic enabled discrimination between different states of consciousness. With mental arithmetic of moderate complexity, ≥ 3 pupillary dilations were seen in 50.0% ≥MCS patients and 17.8% ≤UWS patients (OR 4.56; 95% CI 2.09–10.10, p < 0.001). In comparison, 76.9% healthy controls responded with ≥ 3 pupillary dilations (p = 0.028). Results remained consistent across sensitivity analyses using different thresholds for success. Spearman's Rank analysis underscored the robust association between pupillary dilations during mental arithmetic and consciousness levels (rho = 1, p = 0.017). Notably, one behaviorally unresponsive patient demonstrated persistent command-following behavior two weeks before overt signs of awareness, suggesting a state of prolonged CMD. Conclusions. Automated pupillometry combined with mental arithmetic can identify cognitive efforts, and hence residual consciousness, in ICU patients with acute DoC.