Prognostic value of automated pupillometry in traumatic brain injury: a systematic review and meta-analysis

Traumatic brain injury (TBI) remains a major global cause of mortality and long-term disability. Early prognostication is critical for guiding management decisions. Quantitative pupillometry (QP), using automated devices such as the NeurOptics NPi-200/300, enables bedside measurement of pupillary reactivity through indices like the Neurological Pupil Index (NPi), constriction velocity (CV), and dilation velocity (DV). We conducted a PRISMA-compliant systematic review and meta-analysis to evaluate the prognostic value of QP in adults with TBI. Observational studies of quantitative pupillometry within 72 h of traumatic brain injury in adult ICU patients were included. Studies limited to mild TBI were excluded, although mixed-severity cohorts were eligible. Primary outcomes were mortality and poor functional outcome at 3-6 months (GOS ≤ 3 or mRS ≥ 3). Secondary analyses assessed differences in pupillometry metrics according to intracranial hypertension defined by direct ICP measurements (> 20-25 mmHg) or proxy markers reflecting ICP-directed interventions. Odds ratios were pooled for dichotomous outcomes and mean differences for continuous outcomes using random-effects models, with heterogeneity quantified by I². Four studies (n = 354) reported mortality data. Abnormal quantitative pupillary metrics (most commonly NPi < 3 or absent reflexes) were associated with increased odds of in-hospital death (OR 1.84, 95% CI 1.01-3.35; I² = 84%). Five studies (n = 384) assessed functional outcomes, showing significantly greater odds of poor outcome among patients with abnormal pupillary metrics (OR 3.64, 95% CI 1.63-8.10; I² = 39%). Three studies (n = 190) evaluated intracranial pressure, demonstrating lower NPi values in patients with intracranial hypertension compared with those without elevated ICP, though this difference did not reach statistical significance (MD - 1.05, 95% CI - 2.65 to 0.54). Early quantitative pupillometry is associated with increased mortality and worse functional outcomes in TBI in observational studies. Lower quantitative pupillary metrics were also observed in the presence of intracranial hypertension. Despite substantial heterogeneity, these findings support its potential as a prognostic tool. Further standardization, validation and controlled studies are needed to refine its clinical application.