体内薬物動態を基にした頭蓋内圧亢進時のマンニトールの至適投与方法

Pharmacokinetic Basis of Mannitol Administration for the Treatment of Raised ICP

I．はじめに

　頭蓋内圧亢進時に使用されるマンニトールは，その頭蓋内圧下降作用により，広く臨床に使用されている．しかしながら，数10年来の臨床使用にも拘わらず，その頭蓋内圧下降の作用機序^10,12），最も有効な投与量，投与方法^2,6-9,12）については未だ論議が残っている．この原因は，マンニトール投与後の，体内薬物動態とそれに伴う血漿浸透圧，電解質，そして頭蓋内圧との関係が明らかでない点にあると考えられる^1）．今回，われわれは，成猫で中程度の頭蓋内圧亢進状態を作成し，マンニトールの体内薬物動態を，2—compartment modelにて解析した．同時に，血漿浸透圧，電解質を測定し，経時的に変化する頭蓋内圧との関係を検索して，臨床に於けるマンニトールの至適投与方法について考察したので報告する．

Abstract

To study the most effective way of mannitol admini-stration for the treatment of raised intracranial pressure (ICP) , pharmacokinetics of mannitol were analysed, and the relationship among mannitol concentration, serum osmolality and changes of intracranial pressure (ICP) were examined in cats.

10%, 20% and 30% of mannitol were made and in-travenously administrated with the same volume and speed (0.667ml/kg/min) for 15 minutes to each man-nitol concentration group of cats. Sequential changes of ICP were monitored and serial mannitol concentration, serum osmolality and electrolytes were then performed. Changes of mannitol concentration showed a biex-ponential curve and best fitted to the two-compartment model analysis. There was a strong positive correlation (r=0.9286) between mannitol concentration and extrin-sic serum osmolality. The disposition of mannitol in cats was similar to that which had been reported in dogs and humans. The distribution half-time was faster in 30% mannitol, but the elimination half-time was simi-lar in all groups. The integrated values of mannitol con-centration difference between the central (Cc) and the peripheral compartment (Pc) were greatly correlated with the changes of ICP reduction during mannitol administration (for 15min) . The time to vanish the mannitol concentration difference between Cc and Pc showed strong reverse correlation with the time to reach the lowest ICP level.

The result indicates that the more rapidly mannitol was administrated, the more rapidly the concentration difference between the two compartments was created, and, the higher the effective osmolality was developed, then, the more profound and prolonged ICP reduction can be obtained.

In clinical practice, if we use 20% mannitol, not only the close per body weight (g/Kg) but also the speed of mannitol administration (g/Kg/min) are playing an im-portant role in the production of the most effective ICP reduction and prolongation of lower ICP for the treat-ment of raised ICP.