闭环连续输注依托咪酯及其类似物在大鼠中的应用：给药方案比较及对肾上腺皮质功能的影响
Closed-loop continuous infusions of etomidate and etomidate analogs in rats: a comparative study of dosing and the impact on adrenocortical function.
机构信息
Harvard Medical School, Boston, Massachusetts, USA.
出版信息
Anesthesiology. 2011 Oct;115(4):764-73. doi: 10.1097/ALN.0b013e31821950de.
BACKGROUND
Etomidate is a sedative-hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model.
METHODS
A closed-loop system using the electroencephalographic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague-Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1-24 and measuring serum corticosterone concentrations every 30 min.
RESULTS
The sedative-hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion termination varied (methoxycarbonyl etomidate > carboetomidate > etomidate). Serum corticosterone concentrations were reduced by 85% and 56% during 30-min infusions of etomidate and methoxycarbonyl etomidate, respectively. On infusion termination, serum corticosterone concentrations recovered within 30 min with methoxycarbonyl etomidate but persisted beyond an hour with etomidate. Carboetomidate had no effect on serum corticosterone concentrations during or after continuous infusion.
CONCLUSIONS
Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative-hypnotic maintenance agents when hemodynamic stability is desirable.
背景
依托咪酯是一种镇静催眠药，通常作为单次静脉推注给药，但很少作为输注给药，因为它会抑制肾上腺皮质功能。甲氧基羰基依托咪酯和（R）-乙基 1-（1-苯乙基）-1H-吡咯-2-羧酸酯（卡泊依托咪酯）是依托咪酯的类似物，作为单次推注给药时不会产生明显的肾上腺皮质抑制作用。然而，连续输注对肾上腺皮质功能的影响尚不清楚。在这项研究中，我们比较了依托咪酯、甲氧基羰基依托咪酯和卡泊依托咪酯在大鼠模型中的连续输注对肾上腺皮质功能的影响。
方法
使用脑电图爆发抑制比作为反馈的闭环系统，给 Sprague-Dawley 大鼠输注依托咪酯、甲氧基羰基依托咪酯或卡泊依托咪酯的连续输注。通过重复给予促肾上腺皮质激素 1-24 并每隔 30 分钟测量一次血清皮质酮浓度来评估输注期间和输注结束后的肾上腺皮质功能。
结果
在异氟烷 1%存在下维持 40%爆发抑制比所需的镇静催眠剂量不同（甲氧基羰基依托咪酯>卡泊依托咪酯>依托咪酯）。依托咪酯和甲氧基羰基依托咪酯分别进行 30 分钟输注时，血清皮质酮浓度降低了 85%和 56%。输注结束时，甲氧基羰基依托咪酯在 30 分钟内恢复血清皮质酮浓度，但依托咪酯持续超过 1 小时。卡泊依托咪酯在连续输注期间和之后对血清皮质酮浓度均无影响。
结论
我们的结果表明，甲氧基羰基依托咪酯和卡泊依托咪酯在需要血流动力学稳定时可能具有作为镇静催眠维持剂的临床应用价值。
Zotero 插件