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

Ibrahim Migdady, Alexis Roy, Jonathan A. Duskin, Morgan E. McKeown, David Fischer, Megan E. Barra, Michael Schontz, Janewit Wongboonsin, Matthew B. Bevers, Omar Arnaout, Saef Izzy, Samuel B. Snider

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number106867
JournalJournal of Stroke and Cerebrovascular Diseases
Issue number12
StatePublished - Dec 2022


  • Cerebral edema
  • Hyperosmolar therapy
  • Intracranial pressure
  • Mannitol

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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