マニトールの頭蓋内圧下降作用の機序について

THE MECHANISM OF ICP REDUCING EFFECT OF MANNITOL

　抄録　脳浮腫を伴った頭蓋内圧（ICP）亢進時，マニトール投与によって生ずるICP下降現象の主因子は何かを，頭蓋腔が閉鎖腔であるという条件を崩さずに解明することを目的とした。実験動物はネコを用い，脳浮腫モデルとしてinfusion edema modelを作成した。マニトール2g／kgを3分以内に静脈内投与した後，最もICPが下降する時点と，マニトール投与前とのserum osmolarity，血液生化学，脳組織水分含有量，髄液産生量，髄液吸収抵抗，頭蓋腔のcomplianceの変化を比較，検討した。マニトール投与前，後では，serum osmolarityは有意に上昇，hematocrit値は下降した。脳組織水分含用量は，正常側，脳浮腫側ともに変化しなかった。髄液産生量は減少しなかったが，髄液吸収抵抗は用意に下降し，頭蓋腔のcomplianceは上昇した。本実験で得られた所見は，マニトール投与による頭蓋内圧下降現象の主因子は，急激なserumosmolarityの上昇による正常脳組織，脳浮腫組織からの脱水による脳容積の減少ではなく，髄液の頭蓋腔外への移動による髄液量の減少であると推定された。

The effect of mannitol to decrease the raised ICP is well documented and mannitol is now widely used in clinical practice. However, its mechanism of lowering ICP still remains cont-roversial, especially under the condition of vaso-genic edema. The objective of this study is to reexamine and delineate the mechanism of ICP reducing effect of mannitol, using quantitative vasogenic edema model, specific gravimetric tech-nique to measure the brain water content, and the method to estimate the CSF dynamics without disturbing the physiological condition of intra-cranial compartments in cats.

Quantitative increase of water content of the white matter was produced by the infusion of 0.5 ml of normal saline through stereotaxically inserted 25-G needle into the left frontal white matter. In control group, cats were sacrificed and water content of the gray and white matter of each coronally sliced brain was measured by specific gravimetric technique. In the mannitol group, 20% of mannitol (2g/kg) was administrated via femoral vein within 3 minutes. The maximum reduction of ICP was achieved at the average of 30 minutes. At this time, the cats were sacrificed and the water content of brain was measured in the same way as in the control group. PVI, Ro, It (Marmarou) were calculated before and after mannitol administration. In parameter group, BP, ICP, CVP, serum osmotic pressure and osmolarity were measured without terminating the experi-ment.

The changes of water content of the gray and white matter before and after mannitol adminis-tration in the area of infusion edema were 80.7% to 80.8% and 76.8% to 77.1% respectively. There was no significant difference. The changes of these of normal side were 80.7% to 80.9% and 68.9% to 69.0% respectively. There was also no signifi-cant difference. PVI and Ro were changed signifi-cantly, but If showed no significane difference. The changes of colloid osmotic pressure indicated the movement of water was reversed from blood stream to CSF space at the lowest level of ICPby mannitol administration.

It can be speculated that the main mechanism of reducing the raised ICP with vasogenic edema by acute administration of mannitol seems not due to the decrease of brain volume by the de-hydrating action of both edematous and normal area of brain parenchyma, but to the decrease ofCSF volume either by the movement of water from CSF to brain or from CSF to circulation system. The increase of intracranial compliance indicates that this factor may be playing an ad-ditional factor in lowering the ICP after the administration of mannitol.