Diuretics

Diuretics are used widely in neurosurgery to reduce the volume of the brain's intracellular and extracellular fluid compartments. It is probably largely the extracellular compartment that is influenced because neurons and glia have quick and efficient cell volume regulation mechanisms. Both osmotic and loop diuretics have been used. Although data suggest that loop diuretics can be effective, ^[57] osmotic diuretics, principally mannitol, are preferred clinically because of their speed and efficacy. The only osmotic diuretic available in most formularies is mannitol, although urea once had its proponents. However, urea is a smaller molecule that clearly has greater potential to enter brain parenchyma. That is not to say that mannitol does not enter brain parenchyma. Data indicate that it enters brain tissue and, over a reasonably short time course, appears in the CSF space.^[58] The possibility that the mannitol that gains access to the parenchyma can aggravate swelling has resulted in varying degrees of reluctance among clinicians to administer mannitol.^[59] Most, nonetheless, find it a mainstay of ICP management. There is the concern that it will be effective only when some degree of blood-brain barrier integrity is preserved in a significant portion of the brain. Most clinicians respond to this concern by making empirical use of mannitol; that is, if it is effective in reducing ICP or improving conditions in the surgical field, repeated doses can be administered or will be administered. If it is ineffective (or if serum osmolarity reaches the traditional limit of 320 mOsm/L), its administration is withheld.

The dosages of mannitol used vary from 0.25 g/kg to 100 g "for all comers." One gram per kilogram appears to be the most common dose. However, a systematic study in head-injured patients demonstrated that an equivalent initial ICP-reducing effect can be achieved with 0.25 g/kg, although that effect may not be as sustained as with larger doses.^[60]

Some clinicians advocate the combined administration of a loop diuretic (usually furosemide) and an osmotic diuretic. The superficial rationale is that mannitol establishes an osmotic gradient that draws fluid out of brain parenchyma and that the furosemide, by hastening excretion of water from the intravascular space, facilitates the maintenance of that gradient. A second mechanism may add additional justification for the practice of combining the two diuretics. Neurons and glia, as mentioned earlier, appear to have powerful homeostatic mechanisms to ensure regulation of cell volume. Neurons and glia that shrink in response to increased osmolarity in the external environment recover their volume rapidly as a consequence of the accumulation of so-called idiogenic osmoles that serve to minimize the gradient between the internal and external environment. One of these idiogenic osmoles is chloride. It has been demonstrated in the laboratory that loop diuretics inhibit the chloride channel through which this ion must pass and thereby retard the normal volume-restoring mechanism.^{[61] [62]}

The normal volume regulatory mechanisms of neurons and glia may also be relevant to the phenomenon of rebound swelling. Rebound is commonly attributed to the previous use of mannitol and assumed to be a function of the accumulation of mannitol in cerebral tissue. Although this may be part of the story, the rebound may in fact be "hypertonic rebound" rather than "mannitol rebound." It seems reasonable to be concerned that after a sustained period of hyperosmolarity of any cause, rebound swelling of neurons and glia (which have accumulated idiogenic osmoles) may occur in the event that systemic osmolarity decreases rapidly toward normal levels. It is certainly well known that rebound cerebral swelling can occur after an episode of extreme blood glucose elevation. Accordingly, it should not be assumed that the use of, for instance, hypertonic saline rather than mannitol will obviate this phenomenon.