title: Formula for use of mannitol in patients with intracerebral haemorrhage and high intracranial pressure.
abstract: OBJECTIVE
  Although mannitol has been widely used in hospitals to treat patients with high intracranial pressure (ICP) secondary to intracerebral haemorrhage (ICH), no universal agreement has been reached regarding the optimal dosage of this agent for achieving appropriate intracranial decompression. The aim of this study was to investigate the effects of different mannitol dosages on ICP and the effects of other factors, such as sex, age, haemorrhage location and haematoma volume, on the ICP-lowering effect of mannitol. The data obtained were then used to construct a formula for estimating the total dosage of mannitol required to reduce ICP in individual patients with ICH.
  
  
  METHODS
  A total of 72 patients with ICH and elevated ICP monitored in our intensive care unit were included in this study. Patients with ICH who had hypoxaemia (arterial oxygen saturation <90%), severe functional disturbances of the liver or kidney, acidosis or pathological changes in the visual conducting pathway were not included in this study. Each patient received 20% intravenous mannitol 125 mL every 4, 6 or 8 hours per day to treat elevated ICP, with ICP levels being measured before administration of mannitol and at least three times per day during administration of the drug. When the ICP reached a fixed level, the dosage of mannitol was gradually reduced. The total dosage of mannitol used to reduce the ICP from the highest value to the fixed value was calculated. Data on the patients' sex, age, haemorrhage location and haematoma volume were also obtained. Multivariate regression analysis of the results enabled development of a formula for use of mannitol in patients with ICH and elevated ICP.
  
  
  RESULTS
  Use of mannitol significantly decreased ICP in all patients. The effect of mannitol on ICP reduction was dose-dependent during the period of ICP reduction (p < 0.05) but not after the ICP had reached a fixed level; this limited effectiveness of mannitol when its dosage reaches a certain level was termed 'mannitol saturation dosage'. The reduction in ICP with mannitol was not statistically significantly affected by the patient's sex or age, but was significantly correlated with both haemorrhage location and haematoma volume (p < 0.05). The reduction in ICP with mannitol was greater in patients with supratentorial ICH compared with those with infratentorial ICH (p < 0.0001).
  
  
  CONCLUSIONS
  The total mannitol dosage required for individual patients with ICH and elevated ICP can be calculated by considering the location of the haemorrhage, the volume of the haematoma and the pretreated ICP reading. To this end, the following formula was derived in the study: Total dosage of mannitol (mL of 20% mannitol) = (x + 31.17900 x y - 3.39853 x z - 244.47590)/0.00752, where x = the pretreated ICP (mmH(2)O), y = the haemorrhage location (supratentorial ICH: y = 0, infratentorial ICH: y = 1) and z = the volume of haematoma (mL). Use of this formula in the clinical setting should help reduce the possibility of adverse effects resulting from administration of excessive dosages of mannitol.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Tan
authors.forename: Jiying
authors.initials: J
authors.lastname: Zhou
authors.forename: Dongli
authors.initials: D
authors.lastname: Yuan
authors.forename: Shanquan
authors.initials: S
authors.lastname: Sun
mesh_terms: D000367:Age Factors; D000368:Aged; D002543:Cerebral Hemorrhage / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D002985:Clinical Protocols; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007362:Intensive Care Units; D019586:Intracranial Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D016018:Least-Squares Analysis; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D010343:Patient Admission; D012737:Sex Factors; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome
chemical_list: D008353:Mannitol