Reed J R, Palmisano P A
Clin Toxicol. 1975;8(6):623-31. doi: 10.3109/15563657508990087.
The poor correlation between clinical salicylate toxicity and serum blood levels is reapproached in light of recent evidence linking clinical severity with initial volume of distribution (Vd). It is recognized that two variables alter salicylate Vd in such manner that serum salicylate levels are misleading (thus, the change in Vd is not detected by present methods). These variables are serum protein binding and the pH-dependent ionized/un-ionized ratio in the unbound salicylate fraction. Measurements of salicylate concentration in the cerebro spinal fluid (CSF) would circumvent these variables, but would be clinically impractical. Thus, an alternative is sought to the inexact total serum salicylate levels and the impractical CSF salicylate levels for assessment of the severity of salicylate poisoning. This study indicates that, in dogs, serum unbound salicylate levels closely reflect CSF salicylate levels, even as a decrease in serum protein binding is in progress. However, serum unbound salicylate concentration does not reflect CSF salicylate concentration as a decrease in serum pH is elicited (CSF salicylate actually increased as serum unbound salicylate decreased). On the other hand, serum unbound salicylate measurement would seem preferable to total serum salicylate measurements now used in that the total value decreased markedly as either protein binding change or acidosis produced a change in distribution and the resultant increase in CSF salicylate.
鉴于最近有证据表明临床严重程度与初始分布容积（Vd）相关，临床水杨酸盐毒性与血清水平之间的低相关性再次受到关注。人们认识到，有两个变量会以某种方式改变水杨酸盐的Vd，使得血清水杨酸盐水平产生误导性（因此，目前的方法无法检测到Vd的变化）。这些变量是血清蛋白结合以及未结合水杨酸盐部分中pH依赖的离子化/非离子化比率。测量脑脊液（CSF）中的水杨酸盐浓度可以规避这些变量，但在临床上不实用。因此，人们寻求一种替代方法，以取代不准确的血清水杨酸盐总水平和不实用的脑脊液水杨酸盐水平，用于评估水杨酸盐中毒的严重程度。这项研究表明，在狗身上，即使血清蛋白结合正在减少，血清未结合水杨酸盐水平也能密切反映脑脊液水杨酸盐水平。然而，当引起血清pH下降时，血清未结合水杨酸盐浓度并不能反映脑脊液水杨酸盐浓度（随着血清未结合水杨酸盐下降，脑脊液水杨酸盐实际上增加了）。另一方面，血清未结合水杨酸盐测量似乎比目前使用的血清水杨酸盐总测量更可取，因为当蛋白结合变化或酸中毒导致分布改变以及脑脊液水杨酸盐相应增加时，总值会显著下降。
