Variation in osmotic response to sustained mannitol administration.
BACKGROUND
Osmotic agents such as mannitol remain a mainstay in the management of cerebral edema and raised intracranial pressure. Some patients do not respond to sustained mannitol administration with the expected rise in serum osmolality, and this may correlate with lack of therapeutic efficacy.


OBJECTIVE
To examine the variation in osmotic response to mannitol therapy and identify factors associated with a lack of an osmotic response to sustained mannitol administration.


METHODS
Data on consecutive patients admitted to a Neurology/Neurosurgery Intensive Care Unit who received scheduled doses of mannitol for at least 48 h were extracted from a prospectively collected database. All patients received intravenous isotonic saline solutions and had serial measurements of serum sodium and osmolality, at least twice daily. Non-responders were defined using two thresholds, a rise in serum sodium of < or =1 or < or =5 mEq/l over the 48-hour period.


RESULTS
The cohort included 167 patients the majority with intracerebral and subarachnoid hemorrhage and brain tumors. 73 patients (44%) did not respond to mannitol with a rise in sodium of > or =5 mEq/l, and 37 (22%) did not see a rise of 1 mEq/l over 48 h of treatment. There were minor differences between responders and non-responders (> or =5 mEq/l) in terms of age (56 +/- 15 vs. 48 +/- 14), total mannitol dose (0.9 +/- 0.2 vs. 0.7 +/- 0.2 g/kg), and cumulative fluid balance at 72 h (91 +/- 1653 vs. -610 +/- 1692 ml). Multivariate analysis found that younger age, lower weight-adjusted mannitol dose, and more negative fluid balance were associated with lack of osmotic response.


CONCLUSIONS
A substantial proportion of patients receiving sustained mannitol do not manifest the expected osmotic response. This lack of response may correlate with the failure of clinical efficacy seen in a subgroup of patients, who then require alternate agents such as hypertonic saline. This association merits further exploration.
Keyrouz
Salah G
SG
Department of Neurology and Neurological Surgery, Washington University, St. Louis, MO, 63110, USA.
Dhar
Rajat
R
Diringer
Michael N
MN
D000328:Adult; D000368:Aged; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D001932:Brain Neoplasms / Q000150:complications / Q000378:metabolism; D016208:Databases, Factual; D004234:Diuretics, Osmotic / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D019586:Intracranial Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage*; D008875:Middle Aged; D009994:Osmolar Concentration; D009997:Osmotic Pressure / Q000187:drug effects; D012044:Regression Analysis; D012189:Retrospective Studies; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism; D016896:Treatment Outcome
D004234:Diuretics, Osmotic; D008353:Mannitol