title: Passage of mannitol into the brain around gliomas: a potential cause of rebound phenomenon. A study on 21 patients.
abstract: OBJECTIVE
  Widespread use of mannitol to reduce brain edema and lower elevated ICP in brain tumor patients continues to be afflicted by the so-called rebound phenomenon. Leakage of mannitol into the brain parenchyma through an altered BBB and secondary reversal of osmotic gradient is considered the major cause of rebound . This has only been demonstrated experimentally in animals. As a contribution to this issue we decided to research the possible passage of mannitol into the brain after administration to 21 brain tumor patients.
  
  
  METHODS
  Mannitol (18% solution; 1 g/kg) was administered as a bolus to patients (ten had malignant glioma, seven brain metastases and four meningioma) about 30 minutes before craniotomy. During resection, a sample of the surrounding edematous white matter was taken at the same time as a 10 ml venous blood sample. Mannitol concentrations were measured in plasma and white matter by a modified version of the enzyme assay of Blonquist et al.
  
  
  RESULTS
  In most glioma patients, mannitol concentrations in white matter were 2 to 6 times higher than in plasma (mean 3.5 times). In meningioma and metastases patients plasma concentrations of mannitol were higher than white matter concentrations except in three cases with infiltration by neoplastic cells.
  
  
  CONCLUSIONS
  The results of our study show that even after a single bolus, mannitol may leak through the altered BBB near gliomas, reversing the initial plasma-to-blood osmotic gradient, aggravating peritumoral edema and promoting rebound of ICP.
authors.affiliation: Neurological Clinic, Department of Ophthalmological and Neurosurgical Sciences University of Siena, Siena, Italy. palma@unisi.it
authors.forename: L
authors.initials: L
authors.lastname: Palma
authors.forename: G
authors.initials: G
authors.lastname: Bruni
authors.forename: A I
authors.initials: AI
authors.lastname: Fiaschi
authors.forename: A
authors.initials: A
authors.lastname: Mariottini
mesh_terms: D000328:Adult; D000368:Aged; D001769:Blood / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D001932:Brain Neoplasms / Q000150:complications* / Q000556:secondary / Q000601:surgery; D004234:Diuretics, Osmotic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000150:complications* / Q000601:surgery; D006801:Humans; D019586:Intracranial Hypertension / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D008577:Meningeal Neoplasms / Q000150:complications / Q000601:surgery; D008579:Meningioma / Q000150:complications / Q000601:surgery; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
chemical_list: D004234:Diuretics, Osmotic; D008353:Mannitol