内毒素血症对Sprague-Dawley大鼠氯胺酮和赛拉嗪麻醉药效学及药代动力学的影响。
Effects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine and xylazine anesthesia in Sprague-Dawley rats.
作者信息
Veilleux-Lemieux Daphnée, Beaudry Francis, Hélie Pierre, Vachon Pascal
机构信息
Department of Veterinary Biomedicine, University of Montreal, Saint-Hyacinthe,
Department of Veterinary Services, Laval University, Quebec.
出版信息
Vet Med (Auckl). 2012 Oct 4;3:99-109. doi: 10.2147/VMRR.S35666. eCollection 2012.
PURPOSE
To evaluate the effects of endotoxemia on the pharmacokinetics and pharmacodynamics of ketamine and xylazine anesthesia in Sprague-Dawley rats.
METHODS
Sprague-Dawley rats received ketamine (80 mg/kg) and xylazine (5 mg/kg) intramuscularly following the intraperitoneal administration of different lipopolysaccharide concentrations (1, 10, and 100 µg/kg) to simulate different levels of endotoxemia. Results were compared to control animals receiving saline intraperitoneally. During anesthesia, a toe pinch was performed to evaluate anesthesia duration, and selected physiological parameters (heart and respiratory rates, oxygen saturation, and rectal temperature) were taken. Blood samples were also taken during anesthesia at selected time points for the analysis of plasmatic ketamine and xylazine concentrations by liquid chromatography-mass spectrometry. Blood samples were taken 1 week prior to and 24 hours following anesthesia for blood biochemistry.
RESULTS
Anesthesia duration significantly increased for moderate (10 µg/kg) and high (100 µg/kg) lipopolysaccharide groups. Liver histopathology showed minor to moderate necrosis in all lipopolysaccharide groups in some animals. The most important physiological change that occurred was a decrease in oxygen saturation, and for blood biochemistry a decrease in serum albumin. Ketamine pharmacokinetics were not affected except for the moderate (10 µg/kg) lipopolysaccharide group where a decrease in the area under the plasma concentration-time curve from time zero to the last measurable concentration, a decrease in half-life, and an increase in the clearance were observed. For xylazine, the area under the plasma concentration-time curve increased and the clearance decreased in the moderate (10 µg/kg) and high (100 µg/kg) lipopolysaccharide groups.
CONCLUSION
During ketamine-xylazine anesthesia, endotoxemia may alter xylazine pharmacokinetics and selected biochemical and physiological parameters, suggesting that anesthetic drug dosages could be modified for a more rapid recovery.
目的
评估内毒素血症对Sprague-Dawley大鼠氯胺酮和赛拉嗪麻醉的药代动力学及药效学的影响。
方法
给Sprague-Dawley大鼠腹腔注射不同浓度（1、10和100 μg/kg）的脂多糖以模拟不同程度的内毒素血症，之后肌肉注射氯胺酮（80 mg/kg）和赛拉嗪（5 mg/kg）。将结果与腹腔注射生理盐水的对照动物进行比较。麻醉期间，通过夹趾评估麻醉持续时间，并记录选定的生理参数（心率、呼吸频率、血氧饱和度和直肠温度）。在麻醉期间的选定时间点采集血样，通过液相色谱-质谱法分析血浆中氯胺酮和赛拉嗪的浓度。在麻醉前1周和麻醉后24小时采集血样进行血液生化分析。
结果
中度（10 μg/kg）和高度（100 μg/kg）脂多糖组的麻醉持续时间显著延长。肝脏组织病理学显示，部分动物的所有脂多糖组均出现轻度至中度坏死。发生的最重要生理变化是血氧饱和度降低，血液生化方面则是血清白蛋白降低。氯胺酮的药代动力学未受影响，但在中度（10 μg/kg）脂多糖组中，观察到血浆浓度-时间曲线下面积从零时到最后可测浓度降低、半衰期缩短以及清除率增加。对于赛拉嗪，中度（10 μg/kg）和高度（100 μg/kg）脂多糖组的血浆浓度-时间曲线下面积增加，清除率降低。
结论
在氯胺酮-赛拉嗪麻醉期间，内毒素血症可能改变赛拉嗪的药代动力学以及选定的生化和生理参数，提示可调整麻醉药物剂量以实现更快恢复。
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