Quantitative pupillometry for the monitoring of intracranial hypertension in patients with severe traumatic brain injury

Background: Elevated intracranial pressure (ICP) is frequent after traumatic brain injury (TBI) and may cause abnormal pupillary reactivity, which in turn is associated with a worse prognosis. Using automated infrared pupillometry, we examined the relationship between the Neurological Pupil index (NPi) and invasive ICP in patients with severe TBI. Methods: This was an observational cohort of consecutive subjects with severe TBI (Glasgow Coma Scale [GCS] <9 with abnormal lesions on head CT) who underwent parenchymal ICP monitoring and repeated NPi assessment with the NPi-200 (R) pupillometer. We examined NPi trends over time (four consecutive measurements over intervals of 6h) prior to sustained elevated ICP >20mmHg. We further analyzed the relationship of cumulative abnormal NPi burden (%NPi values <3 during total ICP monitoring time) with intracranial hypertension (ICHT)categorized as refractory (ICHT-r; requiring surgical decompression) vs. non-refractory (ICHT-nr; responsive to medical therapy)and with the 6-month Glasgow Outcome Score (GOS). Results: A total of 54 patients were studied (mean age 54 +/- 21years, 74% with focal injuries on CT), of whom 32 (59%) had ICHT. Among subjects with ICHT, episodes of sustained elevated ICP (n=43, 172 matched ICP-NPi samples; baseline ICP [T-6h] 14 +/- 5mmHg vs. ICPmax [T-0h] 30 +/- 9mmHg) were associated with a concomitant decrease of the NPi (baseline 4.2 +/- 0.5 vs. 2.8 +/- 1.6, p<0.0001 ANOVA for repeated measures). Abnormal NPi values were more frequent in patients with ICHT-r (n=17; 38 [3-96]% of monitored time vs. 1 [0-9]% in patients with ICHT-nr [n=15] and 0.5 [0-10]% in those without ICHT [n=22]; p=0.007) and were associated with an unfavorable 6-month outcome (15 [1-80]% in GOS 1-3 vs. 0 [0-7]% in GOS 4-5 patients; p=0.002). Conclusions: In a selected cohort of severe TBI patients with abnormal head CT lesions and predominantly focal cerebral injury, elevated ICP episodes correlated with a concomitant decrease of NPi. Sustained abnormal NPi was in turn associated with a more complicated ICP course and worse outcome.