Effects of Osmotic Therapy on Pupil Reactivity: Quantification Using Pupillometry in Critically Ill Neurologic...

Osmotic therapy is a critical component of medical management for cerebral edema. While up to 90% of neurointensivists report using these treatments, few quantitative clinical measurements guide optimal timing, dose, or administration frequency. Its use is frequently triggered by a qualitative assessment of neurologic deterioration and/or pupil size, and anecdotally appears to improve pupil asymmetry suggestive of uncal herniation. However, subjective pupil assessment has poor reliability, making it difficult to detect or track subtle changes. We hypothesized that osmotic therapy reproducibly improves quantitative pupil metrics.

We included patients at two centers who had recorded quantitative pupil measurements within 2 h before and after either 20% mannitol or 23.4% hypertonic saline in the neurosciences intensive care unit. The primary outcome was the Neurologic Pupil Index (NPi), a composite metric ranging from 0 to 5 in which > 3 is considered normal. Secondary outcomes included pupil size, percent change, constriction and dilation velocity, and latency. Results were analyzed with Wilcoxon signed-rank tests, Chi-square and multi-level linear regression to control for other edema-reducing interventions.

Out of 72 admissions (403 paired pupil observations), NPi significantly differed within 2 h of osmotic therapy when controlling for other commonly used interventions in our whole cohort (β = 0.08, p = 0.0168). The effect was most pronounced (β = 0.57) in patients with abnormal NPi prior to intervention (p = 0.0235).

Pupil reactivity significantly improves after osmotic therapy in a heterogenous critically ill population when controlling for various other interventions. Future work is necessary to determine dose-dependent effects and clinical utility.