Closed-loop continuous infusions of etomidate and etomidate analogs in rats: a comparative study of dosing and the impact on adrenocortical function.
Closed-loop continuous infusions of etomidate and etomidate analogs in rats: a comparative study of dosing and the impact on adrenocortical function.
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DOI：
10.1097/aln.0b013e31821950de
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发表时间：
2011-10
期刊：
影响因子：
8.8
通讯作者：
Raines DE
中科院分区：
文献类型：
--
作者：
Cotten JF;Le Ge R;Banacos N;Pejo E;Husain SS;Williams JH;Raines DE
依托咪酯是一种镇静催眠药，由于其抑制肾上腺皮质功能，通常单次静脉推注给药，但很少输注给药。甲氧羰基依托咪酯和（R）-乙基1-（1-苯乙基）-1H-吡咯-2-羧酸酯（carboetomidate）是依托咪酯类似物，单次推注给药时不会产生显著的肾上腺皮质抑制。然而，持续输注对肾上腺皮质功能的影响尚不清楚。在这项研究中，我们比较了连续输注依托咪酯，甲氧羰基依托咪酯和碳依托咪酯对大鼠模型肾上腺皮质功能的影响。使用脑电图爆发抑制率作为反馈的闭环系统，用于对Sprague-Dawley大鼠连续输注依托咪酯、甲氧羰基依托咪酯或碳依托咪酯。在输注期间和输注后，通过重复给予促肾上腺皮质激素1-24和每30分钟测量一次血清皮质酮浓度来评估肾上腺皮质功能。在1%异氟烷存在下维持40%爆发抑制比所需的镇静催眠剂量和输注终止时爆发抑制比恢复率各不相同（甲氧羰基依托咪酯>碳依托咪酯>依托咪酯）。依托咪酯和甲氧羰基依托咪酯30分钟输注期间，血清皮质酮浓度分别降低85%和56%。输注终止时，甲氧羰基依托咪酯组血清皮质酮浓度在30分钟内恢复，但依托咪酯组持续超过1小时。碳依托咪酯在连续输注期间或之后对血清皮质酮浓度没有影响。我们的研究结果表明，甲氧羰基依托咪酯和碳依托咪酯可能有临床效用，作为镇静催眠维持剂时，血流动力学稳定性是可取的。
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. 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. 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 terminationvaried(methoxycarbonyletomidate>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. Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative–hypnotic maintenance agents when hemodynamic stability is desirable.