The foregoing discussion is in the situation of a normal blood brain barrier about blood brain barrier crossing drugs. In a brain lesion, where the integrity of BBB varies according to the severity of damage, the control of fluid molecules is further complex. The osmotic/oncotic gradient will not be effective in areas of complete blood brain barrier breakdown, whereas in areas of normal blood brain barrier, this gradient will be totally effective. In areas of mild damage where there are minor openings of the BBB, with the pore size similar to the periphery, the colloid oncotic gradient may be effective.
Due to the heterogeneous nature of BBB in brain injury, the choice of resuscitation fluid after head trauma is a matter of ongoing debate. Avoidance of hypotonic solutions is generally agreed upon and the therapy should rely on fluids with osmolalities around 300 mOsm/L. Hypertonic saline solutions have been used successfully to treat hypovolaemia and intracranial hypertension. But the fear of risks of this therapy has been a concern limiting its use. In large volume resuscitation, there may be an increased risk of cerebral oedema due to decrease in oncotic pressure. Colloid solutions may be administered as required in such situations. Colloid solutions have inherent side effects, thereby warranting a dosage limit for certain solutions, e.g., coagulopathy may be a clinical problem with >1 L or 25 mL/kg administration of hetastarch.
Another area of difference in opinion among the experts is the amount of maintenance fluid therapy in patients at risk of cerebral oedema or intracranial hypertension. In spite of a lack of convincing experimental evidence on the detrimental effects of iso-osmolar crystalloids, fluid restriction is still widely practiced. Although progressive reduction in serum osmolality with standard maintenance fluid therapy) and progressive increase in serum osmolality with restricted fluid therapy have been documented, no CNS related parameters were measured in either study. Therefore, no conclusive recommendations can be drawn on restricted fluid therapy.
According to Miller’s Anesthesia, 7th edition about blood brain barrier crossing drugs
In the majority of the body’s capillary beds, there are fenestrations approximately 65 Å in diameter between endothelial cells. In the brain, with the exception of the choroid plexus, the pituitary, and the area postrema, tight junctions reduce this pore size to approximately 8 Å. As a result, large molecules and most ions are prevented from entering the brain’s interstitium. There is little evidence that anesthetics alter the function of this “blood-brain barrier” in most circumstances. However, acute hypertension can breach the barrier, and certain anesthetics facilitate this phenomenon. Forster and colleagues observed that extravasation of Evan blue into rabbit brain was greater when acute hypertension occurred during anesthesia with halothane than with thiopental. It is likely that the effect is a nonspecific result of cerebral vasodilation rather than a specific effect of halothane. These results were obtained in the setting of extreme, abrupt hypertension in animals with an initially normal BBB. To our knowledge, no peer-reviewed investigation has attempted a comparison of anesthetic effects on BBB function during anesthesia in normotensive humans.