Solubility of haloether anesthetics in human and animal blood.
Solubility of haloether anesthetics in human and animal blood.
复制标题
卤醚麻醉剂在人类和动物血液中的溶解度。
DOI：
10.1097/aln.0b013e3182557cc9
复制
发表时间：
2012
期刊：
影响因子：
8.8
通讯作者：
Liu,Hong
中科院分区：
文献类型：
--
作者：
Soares,JoaoHN;Brosnan,RobertJ;Fukushima,FabiolaB;Hodges,Joanne;Liu,Hong
背景 麻醉剂的血液溶解度可预测吸入药物的药代动力学，对于使用亨利定律从呼气末气体浓度确定血液麻醉剂浓度至关重要。尽管用于模拟人类的麻醉效果，但包括现代卤醚在内的物种间溶解度比较有限。本研究旨在测量人类和动物中地氟烷、七氟烷、异氟烷和甲氧氟烷的血细胞比容调整后的血液：气体麻醉分配系数 (λB:G)。方法 采集 20 只大鼠、8 匹马以及猫、牛、人、狗、山羊、猪、兔和绵羊各 4 只的全血。去除血浆或细胞体积以将所有样品调整至40%的堆积细胞体积。将单一试剂校准气体顶空添加到玻璃注射器中的血液中，并在 37°C 下混合和平衡 2 小时。使用气相色谱法测量校准气体和注射器顶部空间中的试剂浓度。类似地测量了麻醉剂在盐水、柠檬酸盐-磷酸盐-葡萄糖-腺嘌呤和橄榄油中的溶解度。结果 除山羊外，所有动物物种都至少有一项与人类显着不同的 λB:G 测量值。对于每种药物，λB:G 与血清甘油三酯浓度呈正相关，但这只能解释 25% 的种间变异。在某些物种（例如人类）中，地氟醚在血液中的溶解度明显低于七氟醚，但在其他物种（例如兔子）中则不然。结论 对于卤醚麻醉剂，人类和大多数动物之间的麻醉分配系数存在显着差异。由于它们相似的 λB:G 值，山羊可能是人类吸入麻醉药代动力学更好的动物模型。
Background Anesthetic blood solubility predicts pharmacokinetics for inhaled agents and is essential for determination of blood anesthetic concentrations from end-tidal gas concentrations using Henry’s Law. Though used to model anesthetic effects in humans, there are limited interspecies solubility comparisons that include modern haloethers. This study aimed to measure hematocrit-adjusted blood:gas anesthetic partition coefficients (λB:G) for desflurane, sevoflurane, isoflurane, and methoxyflurane in humans and animals. Methods Whole blood was collected from 20 rats, 8 horses, and 4 each of cats, cattle, humans, dogs, goats, pigs, rabbits, and sheep. Plasma or cell volume was removed to adjust all samples to a packed cell volume of 40%. A single agent calibration gas headspace was added to blood in a glass syringe and was mixed and equilibrated at 37°C for 2 hours. Agent concentrations in the calibration gas and syringe headspace were measured using gas chromatography. Anesthetic solubility in saline, citrate-phosphate-dextrose-adenine, and olive oil were similarly measured. Results Except for goats, all animal species had at least one λB:G measurement that differed significantly from humans. For each agent, λB:G positively correlated with serum triglyceride concentrations, but this only explained 25% of interspecies variability. Desflurane was significantly less soluble in blood than sevoflurane in some species (e.g., humans) but not in others (e.g., rabbits). Conclusions Anesthetic partition coefficients differ significantly between humans and most animals for haloether anesthetics. Because of their similar λB:G values, goats may be a better animal model for inhaled anesthetic pharmacokinetics in people.