Adrenocortical suppression and recovery after continuous hypnotic infusion: etomidate versus its soft analogue cyclopropyl-methoxycarbonyl metomidate
Adrenocortical suppression and recovery after continuous hypnotic infusion: etomidate versus its soft analogue cyclopropyl-methoxycarbonyl metomidate
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DOI：
10.1186/cc12494
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发表时间：
2013-01-01
期刊：
影响因子：
15.1
通讯作者：
Raines, Douglas E.
中科院分区：
文献类型：
--
作者：
Ge, Rile;Pejo, Ervin;Raines, Douglas E.
简介：依托咪酯不再作为麻醉维持或镇静的连续输注给药，因为它会导致严重和持续的肾上腺皮质类固醇合成抑制，对危重患者可能造成致命后果。我们假设，可以开发快速代谢的依托咪酯类似物，即使在长时间连续输注后也不会产生持续的肾上腺皮质功能障碍。我们希望这些药物也可以提供更快速和可预测的麻醉出现。我们已经开发了软依托咪酯类似物环丙基甲氧羰基依托咪酯（CPMM）。在120分钟的连续输注结束后，催眠和脑电图在4分钟内恢复。本研究的目的是评估肾上腺皮质功能期间和120分钟连续输注CPMM和比较结果与依托咪酯。方法：地塞米松抑制大鼠随机分为依托咪酯组，CPMM组，或对照组。依托咪酯组和CPMM组大鼠分别接受依托咪酯和CPMM连续输注120分钟。对照组大鼠不给予催眠药。在第一项研究中，通过在催眠药输注开始后90分钟给予促肾上腺皮质激素（ACTH）并在30分钟后输注结束时测量血浆皮质酮浓度来评估催眠药输注期间的肾上腺皮质功能。在第二项研究中，通过在输注终止后每30分钟给予ACTH并在每次ACTH剂量后30分钟测量血浆皮质酮浓度来评估催眠输注后肾上腺皮质的恢复。在注射催眠药时，CPMM和依托咪酯组ACTH刺激的血清皮质酮浓度显著低于对照组（分别为100 +/- 64 ng/ml和33 +/- 32 ng/ml与615 +/- 265 ng/ml）。催眠输液后，ACTH刺激的血清皮质酮浓度恢复到控制值在CPMM组，但相对于那些在对照组中持续抑制超过3小时，在依托咪酯group.Conclusions：CPMM和依托咪酯抑制肾上腺皮质功能在连续输液。然而，输注CPMM后恢复明显更快。
Introduction: Etomidate is no longer administered as a continuous infusion for anesthetic maintenance or sedation, because it results in profound and persistent suppression of adrenocortical steroid synthesis with potentially lethal consequences in critically ill patients. We hypothesized that rapidly metabolized soft analogues of etomidate could be developed that do not produce persistent adrenocortical dysfunction even after prolonged continuous infusion. We hope that such agents might also provide more rapid and predictable anesthetic emergence. We have developed the soft etomidate analogue cyclopropyl-methoxycarbonyl etomidate (CPMM). Upon termination of 120-minute continuous infusions, hypnotic and encephalographic recoveries occur in four minutes. The aims of this study were to assess adrenocortical function during and following 120-minute continuous infusion of CPMM and to compare the results with those obtained using etomidate.Methods: Dexamethasone-suppressed rats were randomized into an etomidate group, CPMM group, or control group. Rats in the etomidate and CPMM groups received 120-minute continuous infusions of etomidate and CPMM, respectively. Rats in the control group received neither hypnotic. In the first study, adrenocortical function during hypnotic infusion was assessed by administering adrenocorticotropic hormone (ACTH) 90 minutes after the start of the hypnotic infusion and measuring plasma corticosterone concentrations at the end of the infusion 30 minutes later. In the second study, adrenocortical recovery following hypnotic infusion was assessed by administering ACTH every 30 minutes after infusion termination and measuring plasma corticosterone concentrations 30 minutes after each ACTH dose.Results: During hypnotic infusion, ACTH-stimulated serum corticosterone concentrations were significantly lower in the CPMM and etomidate groups than in the control group (100 +/- 64 ng/ml and 33 +/- 32 ng/ml versus 615 +/- 265 ng/ml, respectively). After hypnotic infusion, ACTH-stimulated serum corticosterone concentrations recovered to control values within 30 minutes in the CPMM group but remained suppressed relative to those in the control group for more than 3 hours in the etomidate group.Conclusions: Both CPMM and etomidate suppress adrenocortical function during continuous infusion. However, recovery occurs significantly more rapidly following infusion of CPMM.