Osmotherapy for Elevated Intracranial Pressure

A Critical Reappraisal

Abstract

The administration of osmotic agents is one of the principal strategies to lower elevated intracranial pressure (ICP) and to increase cerebral perfusion pressure. Of the 3 osmotic agents frequently used (mannitol, glycerol and sorbitol), each has characteristic advantages and disadvantages.

In addition to renal filtration, sorbitol [elimination half-life (t½β) approximately 1h] and glycerol (t½β 0.2 to 1h) are metabolised, mainly by the liver. The risk of these compounds accumulating in patients with renal insufficiency is low. However, both compounds frequently affect glucose metabolism, leading to an increase in the serum glucose concentration. Mannitol is almost exclusively renally filtered and possesses the slowest elimination from serum (t½β 2 to 4h). The t½β of mannitol is markedly increased in patients with renal insufficiency, but it does not interfere with glucose metabolism. Entry into the cerebrospinal fluid (CSF) is highest with glycerol [CSF: serum ratio of the areas under the concentration-time curves (AUCCSF: AUCS) ≈ 0.25], intermediate with mannitol (AUCCSF: AUCS ≈ 0.15) and lowest with sorbitol (AUCCSF: AUCS ≈ 0.10). The elimination of all osmotic agents from the CSF compartment is substantially slower than from serum. During the elimination phase, the CSF-to-serum osmotic gradient is temporarily reversed. This is one cause of the paradoxical rise of ICP above the pretreatment level sometimes observed with osmotherapeutics.

The ability of mannitol, glycerol and sorbitol to lower elevated ICP has been extensively documented. However, whether the use of osmotic agents, particularly with repeated application, improves outcome remains unproven. Therefore, these agents should only be used to treat manifest elevations of ICP, not for prophylaxis of brain oedema.

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Acknowledgements

This work is dedicated to Professor Dr W. Creutzfeldt, Professor Emeritus of Internal Medicine, University of Göttingen, on the occasion of his 75th birthday. I thank an anonymous reviewer for greatly improving the pathophysiology section of this manuscript.

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Correspondence to Professor Dr Roland Nau.

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Nau, R. Osmotherapy for Elevated Intracranial Pressure. Clin Pharmacokinet 38, 23–40 (2000). https://doi.org/10.2165/00003088-200038010-00002

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Keywords

  • Mannitol
  • Sorbitol
  • Brain Oedema
  • Cerebral Perfusion Pressure
  • Hypertonic Saline