Summary
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.
Similar content being viewed by others
References
Anderson P, Boreus L, Gordon E, Lagerkranser M, Rudehill A, Lindquist C, Öhmann G (1988) Use of mannitol during neurosurgery: interpatient variability in the plasma and CSF levels. Eur J Clin Pharmacol 35: 643–649
Bayer AJ, Pathy MSJ, Newcombe R (1987) Double-blind randomized trial of intravenous glycerol in acute stroke. Lancet I: 405–408
Cantore GP, Guidetti B, Virno M (1964) Oral glycerol for the reduction of intracranial pressure. J Neurosurg 21: 278–283
Carpentier YA, Jeevanandam M, Robin AP, Nordenström J, Burr RE, Leibel RL, Hirsch J, Elwyn DH, Kinney JM (1984) Measurement of glycerol turnover by infusion of nonisotopic glycerol in normal and injured subjects. Am J Physiol 247: E405-E411
Cserr HF, Cooper DN, Suri PK, Patlak CS (1981) Efflux of radiolabeled polyethylene glycols and albumin from rat brain. Am J Physiol 240: F319-F328
Di Mattio J, Hochwald GM, Maltran C (1975) Effects of changes in serum osmolality on bulk flow of fluid into cerebral ventricles and on brain water content. Pflüger's Archiv 359: 253–264
Fawer R, Justafre JC, Berger JP, Schelling JL (1978) Intravenous glycerol in cerebral infarction: a controlled 4 month trial. Stroke 9: 484–486
Frank MSB, Nahata MC, Hilty MD (1981) Glycerol: a review of its pharmacology, pharmacokinetics, adverse reactions, and clinical use. Pharmacotherapy 1: 147–160
Frei A, Cottier C, Wunderlich P, Lüdin E (1987) Glycerol and dextran combined in the therapy of acute stroke. Stroke 18: 373–379
Friedli W, Imbach P, Ghisleni-Steinegger S, Schwarz C, Maire P (1979) Infusionsbehandlung des akuten ischämischen Hirn-infarkts mit Glycerin 10%. Schweiz Med Wochenschr 109: 737–742
Frithz G, Werner I (1975) The effect of glycerol infusion in acute cerebral infarction. Acta Med Scand 198: 287–289
Gaab M, Pflughaupt KW (1977) Experimentelle und klinische Untersuchungen zur intravenösen Glyzerintherapie beim Hirnödem. Acta Neurochir 37: 17–31
Gilsanz V, Rebollar JL, Buencuerpo J, Chantres MT (1975) Controlled trial of glycerol versus dexamethasone in the treatment of cerebral oedema in acute cerebral infarction. Lancet I: 1049–1051
Guisado R, Arieff AI, Massry SG (1974) Effects of glycerol infusions on brain water and electrolytes. Am J Physiol 227: 865–872
Guisado R, Tourtellotte WW, Arieff AI, Tomiyasu U, Mishra SK, Schotz MC (1975) Rebound phenomenon complicating cerebral dehydration with glycerol. J Neurosurg 42: 226–228
Haaß A, Kloß R, Brenner M, Hamann G, Harms M, Schimrigk K (1987) ICP-gesteuerte Hirnödembehandlung mit Glyzerin und Sorbit bei intrazerebralen Blutungen. Nervenarzt 58: 22–29
Klein HJ, Schmidt K (1982) Hyperosmolar solutions and diuretics in the treatment of brain edema. In: Hartmann A, Brock M (Eds.) Treatment of cerebral edema. Springer, Berlin Heidelberg New York
Krämer W, Rompel C, Umlauf B, Ulm K (1981) Kontrollierte, vergleichende Blindstudie zur Wirkung von Glyzerin-Infusionen beim frischen ischämischen Insult. Med Welt 32: 813–816
Larsson O, Marinovich N, Barber K (1976) Double-blind trial of glycerol therapy in early stroke. Lancet I: 832–834
Meyer JS, Charney JZ, Rivera VM, Mathew NT (1971) Treatment with glycerol of cerebral oedema due to acute cerebral infarction. Lancet II: 993–997
Nau R, Prange HW, Martell J, Sharifi S, Kolenda H, Bircher J (1990) Penetration of ciprofloxacin into the cerebrospinal fluid of patients with uninflamed meninges. J Antimicrob Chemother 25: 965–973
Olbermann M, Grünert A, Bässler KH (1977) Biokinetische Charakterisierung der Glyzerinverwertung beim Menschen. Infusionstherapie 4: 68–70
Oldendorf WH, Davson H (1967) Brain extracellular space and the sink action of cerebrospinal fluid. Arch Neurol 17: 196–205
Pelkonen R, Nikkilä EA, Kekki M (1967) Metabolism of glycerol in diabetes mellitus. Diabetologia 3: 1–8
Pitlick WH, Pirikitakuhir P, Painter MJ, Wessel HB (1982) Effects of glycerol and hyperosmolality on intracranial pressure. Clin Pharmacol Ther 31: 466–471
Rottenberg DA, Hurwitz BJ, Posner JB (1977) The effect of oral glycerol on intraventricular pressure in man. Neurology 27: 600–608
Rowland M, Tozer TN (1989) Clinical pharmacokinetics. Concepts and applications, 2nd ed. Lea and Febiger, Philadelphia-London
Senior B, Loridan L (1968) Studies of liver glycogenoses with particular reference to the metabolism of intravenously administered glycerol. N Engl J Med 279: 958–965
Shafrir E, Gorin E (1963) Release of glycerol in conditions of fat metabolization and deposition. Metabolism 12: 580–587
Sloviter HA, Shimkin P, Suhara K (1966) Glycerol as a substrate for brain metabolism. Nature 210: 1334–1336
Tibbling G (1969) Glycerol turnover in hyperthyroidism. Clin Chim Acta 24: 121–130
Tourtellotte WW, Reinglass JC, Newkirk TA (1972) Cerebral dehydration action of glycerol. I. Historical aspects with emphasis on the toxicity and intravenous administration. Clin Pharmacol 13: 159–171
Wald SL, McLaurin RL (1982) Oral glycerol for the treatment of traumatic intracranial hypertension. J Neurosurg 56: 323–331
Waterhouse JM, Coxon RV (1970) The entry of glycerol into brain tissue. J Neurol Sci 10: 305–311
Wieland OH (1984) Glycerol. UV-method. In: Bergmeyer HU (ed) Methods of enzymatic analysis, Vol. 6; Metabolites I. Verlag Chemie, Weinheim
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nau, R., Prins, FJ., Kolenda, H. et al. Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol. Eur J Clin Pharmacol 42, 181–185 (1992). https://doi.org/10.1007/BF00278481
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00278481