Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol

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Abstract
Glycerol 50 g infused i.v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom was given 500 ml of a 10% solution IV over 4 h, serum and CSF were repeatedly sampled during and after the infusion and glycerol was measured enzymatically. The highest serum glycerol level of 191-923 mg/l was observed at the end of the infusion. The maximum CSF glycerol of 18.7-110.8 mg/l was attained 0-1 h after the end of the infusion. Elimination both from serum and CSF approximated a single-exponential decay; the elimination half-life from serum was 0.29-0.56 h compared to 1.03-3.68 h from CSF. In six of the seven cases there was a temporary reversal of the serum/CSF concentration gradient during glycerol elimination. The ratios of the AUCs of CSF and serum, which describe the overall penetration of glycerol into CSF, ranged from 0.09-0.31. In conclusion, the serum level of glycerol produced by giving 50 g IV glycerol over 4 h may not be sufficiently high reliably dehydrate to brain tissue in many patients, and the slow elimination of glycerol from the CSF may be related to the so-called rebound phenomenon.