The effect of mild hypothermia on plasma fentanyl concentration and biotransformation in juvenile pigs
The effect of mild hypothermia on plasma fentanyl concentration and biotransformation in juvenile pigs
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DOI：
10.1213/01.ane.0000146517.17910.54
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发表时间：
2005-04-01
影响因子：
5.7
通讯作者：
Bauer, R
中科院分区：
文献类型：
--
作者：
Fritz, HG;Holzmayr, M;Bauer, R
Therapeutic hypothermia may alter the required dosage of analgesics and sedatives, but no data are available. on the effects of mild hypothermia on plasma fentanyl concentration during continuous, long-term administration. We therefore assessed in a porcine model the effect of prolonged hypothemia on plasma fentanyl concentration during 33 h of continuous fentanyl administration. Seven female piglets (weight: 11.8 +/- 1.1 kg) were anesthetized by IV fentanyl (15 mu g (.) kg(-1) (.) h(-1)) and midazolam (1.0 mg (.) kg(-1) (.) h(-1)). After preparation and stabilization (12 h), the animals were cooled to a core temperature of 31.6 degrees +/- 0.2 degrees C for 6 h and were then rewarmed and kept normothermic at 37.7 degrees +/- 0.3 degrees C for 6 more hours. Plasma fentanyl concentrations were measured by radioimmunoassay, cardiac index by thermodilution, and blood flows of the kidney, spleen, pancreas, stomach, gut, and hepatic artery by a colored microspheres technique. Furthermore, in an additional 4 pigs, temperature dependency of hepatic microsomal cytochrome P450 3A4 (CYP3A4) was determined in vitro by ethylmorphine N-demethylation. Plasma fentanyl concentration increased by 25% +/- 11% (P < 0.05) during hypothermia and remained increased for at least 6 h after rewarming. Hypothermia reduced the cardiac index (41% +/- 15%, P < 0.05), as well as all organ blood flows except the hepatic artery. A strong temperature dependency of CYP3A4 was found (P < 0.01). Mild hypothermia induced a distribution and/or elimination-dependent increase in plasma fentanyl concentration which remained increased for several hours after rewarming. Consequently, a prolonged increase of the plasma fentanyl concentration should be anticipated for appropriate control of the analgesia/sedatives during and early after therapeutic hypothermia.
