medwireNews: The Neurological Pupil index (NPi) appears to be a useful measure of pupillary reactivity and global midbrain function in patients with brain injury that could improve evaluation of disease progression, suggest findings from the ORANGE study.
The results showed a strong association between abnormal NPi scores and poor neurologic outcomes as well as increased mortality, report Giuseppe Citerio (University of Milano-Bicocca, Milan, Italy) and colleagues.
The investigators conducted a multicentre observational cohort study across 13 hospitals in eight countries in Europe and North America between 2020 and 2022.
The participants comprised 514 patients (median age 61 years, 60% men, median Glasgow Coma Scale [GOSE] score of 8) who were admitted to intensive care after traumatic brain injury (44%), aneurysmal subarachnoid hemorrhage (27%), or intracerebral hemorrhage (29%) and required intubation and mechanical ventilation.
The patients underwent automated infrared pupillometry assessment every 4 hours for 7 days after admission (a total of 40,071 measurements from both eyes at a median 40 per patient; a minimum six measurements per day) to compute NPi. Overall distributions of NPi scores peaked at 0 and 4.7 (median score of 4.3) out of a possible 5, with scores below 3 considered abnormal, the researchers explain.
In all, 47% of patients had at least one NPi measure below 3, and 26% had at least one below 0 (indicating no reactivity), the latter of which was most common among those in the intracerebral hemorrhage group.
At 6 months, 59% of 497 available patients had a poor neurologic outcome, based on a GOSE score of 4 or below, and 41% had a good neurologic outcome, while 32% had died.
Citerio et al report that the median NPi score was lower in patients with a poor neurologic outcome than in those with a good neurologic outcome, at 4.0 versus 4.7, and a respective 39% and 8% of patients had an NPI of 0, with an abnormal NPi measured at least once in a corresponding 62% and 29% of patients.
After accounting for the age, acute brain injury diagnosis, and motor Glasgow Coma Scale score of patients when admitted, the risk for poor neurologic outcome increased significantly with every 10% increase in the frequency of an abnormal NPi or an NPi of 0 (odds ratio [OR]= 1.42 and 1.70, respectively). This finding was consistent across each of the brain injury types when considered separately.
In addition, the risk for death at 6 months increased significantly among patients with abnormal NPi or an NPi of 0 (hazard ratio [HR]= 5.58 and 12.05), with each unit decrease in NPi associated with a significant 80% increased risk for death.
When the researchers looked at changes in NPi over time, they found that the risk for death increased significantly among patients with two consecutive NPi scores of 0 versus above 0 (HR=13.92), and in patients whose NPi score deteriorated to 0 (OR=8.37). Moreover, patients with NPi scores below 3 and 3–4 had a significantly greater risk for death than those with scores above 4 (HR=7.10 and 1.70).
By contrast, there was no significantly increased risk for death among patients whose NPi improved from 0 to a higher score.
“These findings indicate the importance of the trajectories and NPi,” say the investigators, adding that “repeated measurements would enable clinicians to assess the efficacy of therapeutic interventions over time.”
They note that pupillary light reactivity can be modified by increased intracranial pressure and so they assessed this in 320 patients, observing that abnormal NPi values occurred more frequently when intracranial pressure exceeded 20 mmHg, at 25% compared with 13% when intracranial pressure was below 20 mmHg. The same trend was observed for NPi scores of 0 (20% vs 7%, respectively).
Citerio et al say that “patients exhibiting elevated intracranial pressure alongside altered NPi values might have an increased risk of brainstem injury, necessitating immediate intervention.”
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