Hamilton David D, Cotton Bryan A
Department of Surgery, The University of Texas Health Science Center, Houston, TX, USA.
Clin Pharmacol. 2010;2:77-82. doi: 10.2147/CPAA.S6475. Epub 2010 Apr 27.
Adrenocortical insufficiency occurs when there is inadequate release of cortisol from the adrenal cortex. Disturbances of the hypothalamic-pituitary-adrenal axis are common following trauma, surgical stress, and critical illness. While this is often a protective mechanism, these responses may become "uncoupled" or maladaptive resulting in an exacerbation of organ failure and higher mortality rates. In these clinical settings, the patient presents with a persistent systemic inflammation state, a hyperdynamic cardiovascular response, and vasopressor dependent shock. As such, the occurrence of adrenal insufficiency in the setting of critical illness is most appropriately termed critical illness-related corticosteroid insufficiency. In these settings, recent data suggests that these patients may benefit from a short course of low-dose steroid replacement therapy. Cosyntropin, a synthetic derivative of adrenocorticotropic hormone, is being used with increased frequency in the evaluation and diagnosis of adrenocortical insufficiency in this patient population. A random cortisol level is checked before a 250-μg injection of cosyntropin and then 30-60 minutes later. The cortisol levels and response to cosyntropin may be interpreted to identify an insufficient adrenal response. Of note, the setting of critical illness can greatly affect the cosyntropin test sensitivity on identifying adrenal insufficiency. Changes in the stress response during critical illness combined with the resuscitation and management of these patients greatly disturbs serum protein levels, especially those of albumin and transcortin. Common intensive care unit (ICU) diagnoses such as sepsis and malnutrition can increase baseline levels and blunt the cortisol response to cosyntropin stimulation, respectively. As well, numerous pharmacological agents routinely used in the ICU have been shown to interfere with cortisol levels and cosyntropin responsiveness. While steroids have a place in the ICU, specific dosing and length of administration remain inconsistent.
当肾上腺皮质释放的皮质醇不足时,就会发生肾上腺皮质功能不全。下丘脑 - 垂体 - 肾上腺轴紊乱在创伤、手术应激和危重病后很常见。虽然这通常是一种保护机制,但这些反应可能会变得“失调”或适应不良,导致器官功能衰竭加剧和死亡率升高。在这些临床情况下,患者表现为持续的全身炎症状态、高动力性心血管反应和依赖血管升压药的休克。因此,在危重病情况下发生的肾上腺功能不全最恰当地称为危重病相关皮质类固醇不足。在这些情况下,最近的数据表明这些患者可能从短期低剂量类固醇替代治疗中获益。促肾上腺皮质激素的合成衍生物考的松,在评估和诊断该患者群体的肾上腺皮质功能不全时使用频率越来越高。在注射250μg考的松前及之后30 - 60分钟检查随机皮质醇水平。皮质醇水平和对考的松的反应可用于判断肾上腺反应不足。值得注意的是,危重病情况会极大地影响考的松试验在识别肾上腺功能不全方面的敏感性。危重病期间应激反应的变化以及这些患者的复苏和管理极大地干扰了血清蛋白水平,尤其是白蛋白和皮质素转运蛋白的水平。常见的重症监护病房(ICU)诊断如脓毒症和营养不良,可分别提高基线水平并减弱皮质醇对考的松刺激的反应。此外,ICU中常规使用的许多药物已被证明会干扰皮质醇水平和考的松反应性。虽然类固醇在ICU中有一定作用,但具体剂量和给药时长仍不一致。