Neurological Pupil Index Prognostic of Outcomes, Mortality in Acute Brain Injury

The Neurological Pupil index (NPi) can be used as a predictor of neurologic outcomes and mortality in patients with acute brain injury, according to study findings published in the Lancet Neurology. 

NPi is a measure of pupillary reactivity that is used to assess acute brain injury. Pupillary light reactivity is typically conducted using a handheld flashlight and is sometimes conducted using automated infrared pupillometry.

Researchers conducted Outcome pRognostication of Acute Brain Injury With the NeuroloGical Pupil index (ORANGE; ClinicalTrials.gov Identifier: NCT04490005), a prospective, observational, multicenter, international cohort study that took place in 13 European and US teaching hospitals in 8 countries. All hospitals had NPi as part of standard monitoring prior. The researchers assessed the association of NPi, 6-month neurologic outcome, and mortality in patients with neurologic brain injury.

Study participants were aged 18 and older and had either traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage. Patients required intensive care unit (ICU) admission and mechanical ventilation and were followed up for 6 months after the injury. 

Participants were excluded if they had facial trauma that made NPi unable to be assessed. The care teams were not blinded to NPi measurements and procedures followed standard processes. 

NPi is a composite score ranging from 0 to 5, with a score of 3 and above considered normal and scores below 3 considered pathological. Pupils were observed at least every 4 hours in both eyes from ICU admission until day 7. The Glasgow Outcome Scale-Extended (GOSE) score was collected through a questionnaire, with a score of 4 or less indicating poor neurologic outcomes. 

The co-primary endpoints were mortality and functional neurologic outcomes at 6 months post-injury. 

A total of 1938 participants with acute brain injury were screened and 514 met the inclusion criteria. Of these patients, 224 (44%) had a TBI, 139 (27%) had an aneurysmal subarachnoid hemorrhage, and 151 (29%) had an intracerebral hemorrhage. 

Study participants were median age of 61 (interquartile range [IQR], 46-71 years) and more than half (n=309 [60%]) were men. The median Glasgow Coma Scale score when admitted was 8 (IQR, 5-11). 

Of the 514 participants, 497 (97%) of patients had outcomes reported at 6 months, with 206 (41%) alive with good neurologic outcomes (GOSE >4) and 291 (59%) with poor outcomes (GOSE ≤4). Within the follow up-period, 160 (32%) participants died.

The median NPi overall was 4.3 (IQR, 3.7-4.7) and 241 (47%) participants had at least 1 abnormal NPi reading. The researchers found that abnormal NPi reading was associated with poorer neurologic outcomes.

A total of 241 (47%) patients had at least 1 recording of abnormal NPi, which was associated with poor neurologic outcome for each 10% increase in abnormal NPi frequency (adjusted odds ratio [aOR], 1.42; 95% CI, 1.27-1.64; P <.0001). In addition, abnormal NPi was associated with in-hospital mortality (adjusted hazard ratio [aHR], 5.58; 95% CI, 3.92-7.95; P <.0001).

“Simple, automatic, repeat automated pupillometry assessment could improve the continuous monitoring of disease progression and the dynamics of outcome prediction at the bedside,” the researchers noted.

Study limitations included a lack of standardized treatment protocol, not blinding the clinical staff, and not assessing other variables of automated pupillometry. 

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.