Volume replacement is associated with a diminished osmolar effect of mannitol in patients with acute brain injury.

INTRODUCTION: Animal experiments recently demonstrated that replacing urinary loses with crystalloid diminishes the therapeutic effect of mannitol by reducing the increase in osmolality. We aimed to investigate whether this effect is similarly seen in in brain-injured patients by studying the association between total body fluid balance (TBB) and the osmolar response to mannitol. METHODS: We performed a retrospective cohort study of adult patients with acute brain injury between 2015 and 2021 who received ≥ 2 doses of mannitol within 8 hours and no intercurrent concentrated saline solution. We analyzed the association between the change in TBB (∆TBB) and change in osmolality (∆Osm) before and after mannitol in a linear model, both as univariate and after adjustment for common confounding factors. RESULTS: Of 6,145 patients who received mannitol, 155 patients met inclusion criteria (mean age 60 ± 17 years, 48% male, 83% white). The mean total mannitol dose was 2 ± 0.5 g/kg and the mean change in plasma osmolality was 7.9 ± 7.1 mOsm/kg. Each 1 L increase in ∆TBB was associated with a change of -1.1 mOsm/L in ∆Osm (95% CI [-2.2, -0.02], p = 0.045). The magnitude of association was similar to that of total mannitol dose and remained consistent in an adjusted model and after excluding outliers. CONCLUSIONS: In patients with acute brain injury, a positive TBB is associated with a diminished mannitol-induced increase in plasma osmolality. Future prospective studies are needed to confirm these findings and their influence on the therapeutic effect of mannitol.

Anisocoria and Poor Pupil Reactivity by Quantitative Pupillometry in Patients With Intracranial Pathology.

OBJECTIVES: To describe the prevalence and associated risk factors of new onset anisocoria (new pupil size difference of at least 1 mm) and its subtypes: new onset anisocoria accompanied by abnormal and normal pupil reactivities in patients with acute neurologic injuries. DESIGN: We tested the association of patients who experienced new onset anisocoria subtypes with degree of midline shift using linear regression. We further explored differences between quantitative pupil characteristics associated with first-time new onset anisocoria and nonnew onset anisocoria at preceding observations using mixed effects logistic regression, adjusting for possible confounders. SETTING: All quantitative pupil observations were collected at two neuro-ICUs by nursing staff as standard of care. PATIENTS: We conducted a retrospective two-center study of adult patients with intracranial pathology in the ICU with at least a 24-hour stay and three or more quantitative pupil measurements between 2016 and 2018. MEASUREMENTS AND MAIN RESULTS: We studied 221 patients (mean age 58, 41% women). Sixty-three percent experienced new onset anisocoria. New onset anisocoria accompanied by objective evidence of abnormal pupil reactivity occurring at any point during hospitalization was significantly associated with maximum midline shift (ß = 2.27 per mm; p = 0.01). The occurrence of new onset anisocoria accompanied by objective evidence of normal pupil reactivity was inversely associated with death (odds ratio, 0.34; 95% CI, 0.16-0.71; p = 0.01) in adjusted analyses. Subclinical continuous pupil size difference distinguished first-time new onset anisocoria from nonnew onset anisocoria in up to four preceding pupil observations (or up to 8 hr prior). Minimum pupil reactivity between eyes also distinguished new onset anisocoria accompanied by objective evidence of abnormal pupil reactivity from new onset anisocoria accompanied by objective evidence of normal pupil reactivity prior to first-time new onset anisocoria occurrence. CONCLUSIONS: New onset anisocoria occurs in over 60% of patients with neurologic emergencies. Pupil reactivity may be an important distinguishing characteristic of clinically relevant new onset anisocoria phenotypes. New onset anisocoria accompanied by objective evidence of abnormal pupil reactivity was associated with midline shift, and new onset anisocoria accompanied by objective evidence of normal pupil reactivity had an inverse relationship with death. Distinct quantitative pupil characteristics precede new onset anisocoria occurrence and may allow for earlier prediction of neurologic decline. Further work is needed to determine whether quantitative pupillometry sensitively/specifically predicts clinically relevant anisocoria, enabling possible earlier treatments.