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New additions to the intensive care armamentarium.

机译：重症监护室的新成员。

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Many advances have improved the care of critically ill patients, but only a few have been through the use of pharmaceutical agents. Recently, the US Food and Drug Administration (FDA) approved drotrecogin alfa (activated), or recombinant human activated protein C, for the treatment of patients with a high risk of death from severe sepsis. Drotrecogin alfa (activated) has antiinflammatory, antithrombotic and fibrinolytic properties. When given as a continuous intravenous infusion, recombinant human activated protein C decreases absolute mortality of severely septic patients by 6.1%, resulting in a 19.4% relative reduction in mortality. The absolute reduction in mortality increases to 13% if the population treated is restricted to patients with an APACHE II score greater than 24, as suggested by the FDA. The most frequent and serious side effect is bleeding. Severe bleeds increased from 2% in patients given placebo to 3.5% in patients receiving drotrecogin alfa (activated). The risk of bleeding was only increased during the actual infusion time of the drug, and the bleeding risk returned to placebo levels 24 hours after the infusion was discontinued. Patients treated in the intensive care unit frequently develop anemia, usually severe enough to require at least one transfusion of red blood cells. With the recent discovery of the harmful effects of allogeneic red blood cell transfusions and the increasing shortage of available red blood cell products, emphasis has been placed on minimizing transfusions. Patients who receive exogenous recombinant human erythropoietin maintain higher hemoglobin levels, in spite of requiring fewer transfusions during their stay in the intensive care unit. Recombinant human erythropoietin appears to be effective whether it is given as 300 units/kg of body weight subcutaneously every other day or as 40,000 units subcutaneously every week. Differences in hemoglobin values were not apparent until at least one week of therapy, but they continued to diverge after that initial week. Furthermore, the incidence of adverse events was similar to that of patients receiving placebo and there was no difference in mortality, suggesting that avoidance of blood transfusions did not translate into increased survival. Thus, recombinant human erythropoietin appears to be both safe and effective in treating the anemia found in critically ill patients, but it is less clear that such treatment is cost effective, especially in the higher dose regimens. Hypotension in patients with septic shock is often difficult to correct. Despite enormous dosages of catecholamines, many of these patients continue to have inadequate blood pressures. Inadequate levels of vasopressin have been identified in patients with septic shock, as well as in other patients with hypotension secondary to refractory vasodilatation. Vasopressin is a peptide hormone secreted from the posterior pituitary in response to hyperosmolality, hypovolemia or hypotension. Levels of vasopressin initially rise in patients with septic shock, but as hypotension persists, vasopressin levels fall below normal. Administration of exogenous vasopressin in physiologic dosages significantly increases blood pressure in patients with shock associated with sepsis and other vasodilatory states. This rise in blood pressure is often significant enough that endogenous catecholamines can be decreased and frequently discontinued entirely. Early withdrawal of the vasopressin replacement infusion results in recurrent hypotension. Unfortunately, randomized, blinded, placebo-controlled trials showing improvement in long-term outcomes such as mortality and length of stay are still lacking. (c) 2004 Prous Science. All rights reserved.
机译：许多进步改善了重症患者的护理，但只有少数通过药物的使用取得了进步。最近，美国食品药品监督管理局（FDA）批准了drotrecogin alfa（活化的）或重组人活化的蛋白C，用于治疗因严重败血症死亡的高风险患者。 Drotrecogin alfa（活化）具有抗炎，抗血栓形成和纤溶的特性。当以连续静脉输注方式给药时，重组人活化蛋白C可使重度脓毒症患者的绝对死亡率降低6.1％，导致相对死亡率降低19.4％。如FDA建议，如果治疗的人群仅限于APACHE II评分大于24的患者，则死亡率的绝对降低将增加到13％。最常见和最严重的副作用是出血。严重出血从接受安慰剂的患者中的2％增加到接受drotrecogin alfa（已激活）的患者中的3.5％。出血的风险仅在药物的实际输注时间内增加，并且在输液停止24小时后，出血风险恢复到安慰剂水平。在重症监护室接受治疗的患者经常会出现贫血，通常严重到需要至少输血一次红细胞。随着最近发现同种异体红细胞输血的有害影响以及可用红细胞产品的日益短缺，人们将重点放在了减少输血上。尽管在重症监护室住院期间需要输血的次数较少，但接受外源重组人促红细胞生成素的患者仍保持较高的血红蛋白水平。重组人促红细胞生成素似乎每隔一天皮下给予300单位/ kg体重或每周皮下给予40,000单位有效。血红蛋白值的差异直到至少治疗一周后才显现出来，但在开始的那一周之后它们仍在继续发散。此外，不良事件的发生率与接受安慰剂的患者相似，并且死亡率没有差异，这表明避免输血不会转化为存活率的提高。因此，重组人促红细胞生成素在治疗危重患者中发现的贫血方面似乎既安全又有效，但是还不清楚这种治疗是否具有成本效益，特别是在高剂量方案中。败血性休克患者的低血压通常难以纠正。尽管儿茶酚胺的剂量很大，但是许多这些患者的血压仍然不足。在败血性休克患者以及其他因难治性血管舒张引起的低血压患者中，血管加压素水平不足。加压素是垂体后叶分泌的一种肽激素，可响应高渗，低血容量或低血压。败血性休克患者中血管加压素的水平最初会升高，但随着低血压持续，血管加压素的水平会降至正常水平以下。在患有败血症和其他血管舒张状态相关的休克患者中，以生理剂量给予外源性加压素可显着提高血压。血压升高通常非常显着，以至于内源性儿茶酚胺可以降低并经常完全中断。尽早撤回加压素替代输注会导致低血压反复发作。不幸的是，仍然缺乏显示长期结果（例如死亡率和住院时间）改善的随机，盲法，安慰剂对照试验。 （c）2004 Prous科学。版权所有。

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