Schulte H M, Benker G, Reinwein D, Sippell W G, Allolio B
I. Medizinische Klinik und Kinderklinik, Christian-Albrecht-Universität zu Kiel, West Germany.
J Clin Endocrinol Metab. 1990 May;70(5):1426-30. doi: 10.1210/jcem-70-5-1426.
To investigate the adrenostatic potential of a nonhypnotic low dose etomidate infusion, we administered 0.03 mg/kg etomidate in a bolus injection, followed by constant infusion of 0.3 mg/kg.h for 24 h to 6 patients with severe Cushing's syndrome. The dose-response relationship also was determined in 15 normal subjects. Three groups of 5 received, respectively, doses of 0.03, 0.1, and 0.3 mg/kg.h etomidate for 5 h after an initial bolus dose of 0.03 mg/kg. The response to exogenously administered ACTH [0.25 mg ACTH-(1-24)], injected after the etomidate or control infusion, was determined in all normal subjects. In the six hypercortisolemic patients, serum cortisol concentrations decreased from 1374 +/- 436 nmol/L (mean +/- SEM) to 188 +/- 91 nmol/L after 11 h of etomidate infusion and remained low until the end of the infusion. Cortisol levels returned to pretreatment concentrations by 24 h. Excretion of urinary free cortisol decreased from 1180 +/- 196 to 185 +/- 66 nmol/day. In the normal subjects, administration of etomidate led to a dose-dependent decrease in serum cortisol from about 550 to 83 nmol/L, while 11-deoxycortisol rose from low or undetectable levels up to 346 nmol/L. In response to ACTH, cortisol levels rose in inverse proportion to the etomidate dose. It was, however, significantly reduced compared to normal saline infusion even after the lowest dose. Changes in aldosterone and corticosterone concentrations were similar to those in cortisol, and 11-deoxycorticosterone changed in a pattern similar to that of 11-deoxycortisol. Two of five normal subjects reported tiredness during the highest etomidate infusion. No other side-effects were noted. We conclude that iv administered etomidate in a low nonhypnotic dose reduces serum cortisol concentrations in a dose-dependent manner in both hyper- and eucortisolemic subjects. This study suggests that etomidate at a dose of 0.1 mg/kg.h or lower may be an effective strategy for the control of severe hypercortisolemia.
为研究非催眠剂量的依托咪酯低剂量输注的肾上腺抑制作用，我们对6例重度库欣综合征患者先静脉推注0.03mg/kg依托咪酯，随后以0.3mg/kg·h的速度持续输注24小时。还在15名正常受试者中确定了剂量 - 反应关系。三组受试者各5名，在初始静脉推注0.03mg/kg后，分别接受0.03、0.1和0.3mg/kg·h的依托咪酯输注5小时。在所有正常受试者中，在依托咪酯或对照输注后，测定对外源性给予促肾上腺皮质激素[0.25mg促肾上腺皮质激素-(1 - 24)]的反应。在6例高皮质醇血症患者中，依托咪酯输注11小时后，血清皮质醇浓度从1374±436nmol/L（均值±标准误）降至188±91nmol/L，并在输注结束前一直保持在低水平。皮质醇水平在24小时时恢复到治疗前浓度。尿游离皮质醇排泄量从1180±196降至185±66nmol/天。在正常受试者中，给予依托咪酯导致血清皮质醇从约550nmol/L剂量依赖性地降至83nmol/L，而11 - 脱氧皮质醇从低水平或未检测到的水平升至346nmol/L。对促肾上腺皮质激素的反应中，皮质醇水平升高与依托咪酯剂量成反比。然而，即使是最低剂量，与生理盐水输注相比，其升高也显著降低。醛固酮和皮质酮浓度的变化与皮质醇相似，11 - 脱氧皮质酮的变化模式与11 - 脱氧皮质醇相似。5名正常受试者中有2名在接受最高剂量依托咪酯输注时报告有疲劳感。未观察到其他副作用。我们得出结论，静脉给予非催眠剂量的依托咪酯在高皮质醇血症和正常皮质醇血症受试者中均以剂量依赖性方式降低血清皮质醇浓度。本研究表明，剂量为0.1mg/kg·h或更低的依托咪酯可能是控制严重高皮质醇血症的有效策略。
