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

doi:10.1016/j.jstrokecerebrovasdis.2022.106867

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

J Stroke Cerebrovasc Dis. 2022 Dec;31(12):106867. doi: 10.1016/j.jstrokecerebrovasdis.2022.106867. Epub 2022 Nov 2.

Authors

Affiliations

¹ Division of Neurocritical Care, Montefiore Medical Center, Albert Einstein College of Medicine, NY, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: migdadyiy@gmail.com.
² Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: aroy@bwh.harvard.edu.
³ Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: duskin@bwh.harvard.edu.
⁴ Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: mmckeown3@bwh.harvard.edu.
⁵ Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Division of Neurocritical Care, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: dfischer2@mgh.harvard.edu.
⁶ Department of Pharmacy, Massachusetts General Hospital, Boston, MA, USA.
⁷ Department of Pharmacy, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: mschontz@bwh.harvard.edu.
⁸ Renal Division, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand. Electronic address: jwongboonsin@research.bwh.harvard.edu.
⁹ Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: mbevers@bwh.harvard.edu.
¹⁰ Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: oarnaout@bwh.harvard.edu.
¹¹ Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: sizzy@bwh.harvard.edu.
¹² Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: ssnider@bwh.harvard.edu.

PMID: 36334372
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106867

Abstract

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.

Keywords: Cerebral edema; Hyperosmolar therapy; Intracranial pressure; Mannitol.

MeSH terms

Animals
Brain Injuries* / diagnosis
Brain Injuries* / drug therapy
Female
Male
Mannitol* / adverse effects
Osmolar Concentration
Retrospective Studies
Water-Electrolyte Balance

Substances

Mannitol