血清降钙素原水平.

1、Serum Procalcitonin LevelsIt Is All About Confidence1Albrich and colleagues successfully orchestratedan observational, multinational, multicenter, prospective study of the influence of serum procalcitonin (PCT) levels on the care of patients with lower respiratory tract infections (LRTIs). Specifica

2、lly, does access to PCT levels plus the use of an interpretative advice algorithm influence the duration of antibiotic therapy? The comparison was between patients whose physicians were compliant with the algorithm vs patients whose physicians were noncompliant. Noncompliance was defined as failure

3、to follow the algorithm by either initiation of antibiotic therapy or failure to discontinue therapy despite low PCT levels in the absence of predefined criteria that allowed the algorithm to be overruled. In short, the algorithm advice was overruled and managed based on clinical judgment.The primar

4、y end point was duration of antibiotic therapy. Of 1208 patients who received at least 1 dose of an antibiotic, the mean duration of therapy was 5.9 days when the algorithm was followed and 7.4 days (P.001) when physicians did not comply with the algorithm. The shorter duration stood the test of mul

5、tivariable analyses looking for confounders; of course, some important confounder may have been missed.Of interest, algorithm compliance was substantively better in those centers that had participated in earlier PCT studies. I suggest that algorithm compliance, or lack thereof, is a direct reflectio

6、n of the confidence level of physicians in the interpretation of the meaning of serum PCT levels.1The study by Albrich et al is the latest of several studies of patients with LRTIs and PCT treatment guidance. In most studies, compliance with the PCT algorithm shortened the duration of antibiotic the

7、rapy.2,3 Nonetheless, a healthy skepticism persists. Critics worry about the specificity of an increase in PCT levels for bacterial as opposed to viral infection. Physicians wonder what happens to serum PCT levels if there is dual infection, eg, pneumonia due to Streptococcus pneumoniae concomitant

8、with influenza tracheobronchitis. Why dose the serum PCT level increase in patients after aortocoronary bypass surgery or in patients with cardiogenic shock? In short, does the serum PCT level help the clinician beyond the usual markers of activation of an innate immune response, ie, erythrocyte sed

9、imentation rate (ESR), C-reactive protein (CRP), and white blood cell and differential counts?With the caveat that we need a lot more information, the emerging data suggest that PCT levels add value. Like ESR and CRP, PCT is part of the early phases of an innate immune response. A virtue of PCT leve

10、ls is that they increase within 4 to 6 hours of initiation of bacterial infection or intravenous endotoxin, while increases in CRP level and ESR require 24 or more hours.4,5Serum PCT levels do not increase substantively after uncomplicated viral respiratory tract in fecti ons (RTIs). The mecha nism

11、is believed to be viral-in duced in creases in -i nterfero n, which in turn represses PCT gene rean scripti on6 Retrospective studies of childre n with RTIs in dicate little to no in crease in serum PCT levels in resp onse to viral or mycoplasma in fectio n.7 Note also that serum PCT levels in creas

12、ed in patie nts with bacterial menin gitis but did not in crease in patie nts with viral menin gitis8 Clearly, there is an urge nt n eed to use the powerful moder n tools of molecular diagnostics in patients of all ages with RTIs to establish a more defi nite microbial etiology (perhaps mixed pathog

13、e n etiology) of the RTI and correlate the results with serum PCT levels.Con fide nce in PCT levels would also be enhan ced if the basic biology was better understood. In vitro, PCT synthesis is stimulated by bacterial lipopolysaccharide (en dotox in), tumor n ecrosis factor, and4-6in terleuk in 1.O

14、f in terest, the magn itude of PCT producti on was greaterin patie nts with bacteremia due to gram-n egative bacteria as opposed to bacteremia with gram-positive bacteria.9 This observati on is pert inent to clinical low intestinal perfusion states that are associated with elevations in serum PCT le

15、vels.Bacterial en dotox in is detectable in huma n serum duri ng and after aortocor onary bypass surgery!0 Bacterial en dotox in is detectable in human serum in profound cardiogenic shock, some general surgery patients, patients with severe pancreatitis, and other patients with poor perfusion of the

16、 mucosa of the intestinal tract. 4,10 The supposition is that the gut bacteria “translocate” into the submucosa and then to the bloodstream with concomitant elevation of PCT levels as a market of activation of an innate immune response.Understanding the science will increase confidence. However, for

17、 serum PCT levels to influence patient care, the clinician needs the PCT result at point of care. Similar to white blood cell count, it is strongly suggestedthat, if offered, serum PCT levels should be available at all times with results within 1 hour of receipt of serum in the laboratory. The promp

18、t report of a low PCT level, within the context of the rest of the clinical assessment,could influence the decision to start, continue, or discontinue antibiotic therapy.1In the study by Albrich et al, compliance with the PCT algorithm in the participating US hospital was only 35%. Compliance would

19、surely increase if physicians had more confidence in their understanding of the factors that drive an increase or decrease of serum PCT levels.David Gilbert, MD1. Albrich WC, Dusemund F, Bucher B, et al. Effectiveness and safety of procalcitonin-guided antibiotic therapy in lower respiratory tract i

20、nfections in “real life ”:an international, multicenter post-study survey (ProREAL). Arch Intern Med . 2012;172(9):715-722.2. Li H, Luo Y=F, Blackwell TS, Xie C-M. Meta-analysis and systematic review of procalcitonin-guided therapy in respiratory tract infections. Antimicrob Agent Chemother. 2011;55

21、(12):5900-5906.3. Schuetz P, Chiappa V , Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med . 2011;171(15):1322-1331.4. Becker KL, Nylen ES, White JC, Mulle

22、r B, Snider RHJr. Clinical review 167: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab . 2004;89(4)1512-1525.5. Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic in

23、flammation, infection, and sepsis: clinical utility and limitations. Crit Care Med . 2008;36(3):941-952.6. Linscheid P, Seboek D, Nylen ES, et al. In vitro and in vivo calcitonin I gene expression in parenchymal cells : a novel product of human adipose tissue. Endocrinology . 2003;144(12):5578-5584.

24、7. Schutzle H, Forster J, Superti-Furga A, Berner R. Is serum procalcitonin a reliable disgnostic marker in children with acute respiratory tract infections? a retrospective analysis. Eur J Pediatr . 2009;168(9):1117-1124.8. Schwarz S, Bertram M, Schwab S, Andrassy K, Hacke W. Serum procalcitonin le

25、vels in bacterial and abacterial meningitis. Crit Care Med . 2000;28(6):1828-1832.9. Charles PE, Ladoire S, Aho S, et al. Serum procalcitonin elevation in critically ill patients at the onset of bacteremia caused by either Gram negative or Gram positive bacteria. BMC Infect Dis . 2008;8:38=46.10. Pa

26、tham N, Burmester M, Adamovic T, et al. Intestinal injury and endotoxemia in children undergoing surgery for congenital heart disease. Am J Respir Crit Care Med. 2011;184(11):1261-1269.血清降钙素原水平一切和信心相关内科医学档案2012年5月14日172卷9号P722-723Albrich 和同事们通过精心策划，成功进行了一个可观测的跨国 多中心的前瞻性研究， 即血清降钙素原水平对关怀病人而降低下呼吸 道感染的影

27、响研究。 具体说， 降钙素原水平通道会增加一个解释性的 规则建议从而抗生素疗法的持续时间吗？这个比较只是针对那些规 则遵从性主治医生的病人与非规则遵从性主治医生的病人。 非规则遵 从性是在抗生素疗法一开始就没能根据规则进行治疗的或是在缺乏 预判标准的前提下尽管降钙素原水平偏低却没能中止治疗的情况等， 都属于规则无效。 简而言之， 运算法则已宣布无效并只能设法根据临 床诊断而判断。最早的终点在于抗生素疗法的持续时间。在 1208 例接受了至少 1 剂抗生素的病人中，根据运算规则进行的话平均持续时间需要 5.9 天；而医生没有按照预算规则进行的话则需要 7.4天(Pv.001)。当然， 试验中较短

28、的持续时间维持需要共同创始人的多变量分析， 而一些重 要的创始人也有可能被漏掉。有趣的是，那些曾经参与过早期降钙素原研究的中心在规则遵循 上实际要好。笔者建议规则遵循，或是缺乏规则遵循，会直接反应医 生在解释血清降钙素原水平意义上的信心。在数个类似的研究中， Albrich 等人的研究是下呼吸道感染和血 清降钙素原治疗病人的指导上市最新的。 许多的研究中， 遵循血清降 钙素原原则缩短了抗生素疗法的疗程。 尽管如此， 我们仍需要有一个 合理的怀疑态度。 批评者担心在细菌的血清降钙素原水平特异性的增加与病毒感染正好相反。医生们想看看如果存在双倍的感染血清降钙素原水平会发生怎样的变化，比如说，急性肺

29、炎病源是由于链球菌肺 炎伴随流行性感冒支气管炎。病人在主动脉冠状动脉分流术手术后或 有急性心肌炎的情况下血清降钙素原水平上升的原因何在？简而言 之，血清降钙素原水平堆临床医生在超出固有免疫反应通常的活化特 征中会有帮助吗？如红细胞沉淀率(erythrocyte sedime ntati onrate， ESR)，C-反应蛋白(C-reactive protein ， CRP)，以及白细 胞和不同的计数方面等。对于这样的警告我们需要大量更多的信息，新兴的数据提示血清 降钙素原水平价值增加。像对红细胞沉淀率和C-反应蛋白来说，血清降钙素原只是固有免疫反应早期表述的一部分。血清降钙素原水平 的长处之

30、一即它们能在4至6小时内增强细菌感染或静脉注射内毒素 的起始作用，而增强C-反应蛋白的水平和红细胞沉淀率则需要 24小 时或者更多的时间。事实上，血清降钙素原水平在无合并症病毒性呼吸道感染下并不 会增强。这种机制被认为是-感染中病毒诱导的增加，其反过来会抑 制降钙素原基因的复制。对患有呼吸道感染儿童的可追溯性研究基本 不能暗示血清降钙素原水平在对病毒性或支原体感染反应中没有增强。还需强调的是细菌性脑膜炎患者的血清降钙素原水平会增强，而病毒性脑膜炎患者则不会。显然，这样的结论急切需要使用强有力的 现代化分子诊断工具对所有年龄段呼吸道感染病患者进行诊断的支 撑，从而建立一个更完整的呼吸道感染的微生

31、物病因学 (也许是混合 型病原体病因学）及纠正血清降钙素原水平的结果如果对基本的生物学有一个更好的理解， 那么对血清降钙素原水 平的信心也会增强。 在试管中， 降钙素原合成是通过刺激细菌脂多糖 （内毒素），肿瘤坏疽因素，和白细胞介素 1。有趣的是，巨大的降 钙素原产物对患革兰氏阴性菌血症患者的作用大于革兰氏阳性菌血 症患者。这一观察有关临床降低肠灌注状态并与血清降钙素原水平的 上升相关联。细菌内毒素在进行主动脉冠状动脉分流术中或结束后的人的血 清中可检测得到。 其也可在患有深度急性心肌炎的患者、 经历数次手 术患者、急性胰腺炎患者以及其他肠粘膜轻度充盈患者的血清中检 出。这一猜测是因大肠菌转移

32、到黏膜下层再与伴随物进入血液引起降 钙素原水平的上升，如同一个激活原始免疫反应的市场。了解科学可以增加信心。 然而，血清降钙素原水平会影响患者关 怀，也正因为这一点， 临床医生需要降钙素原的结果。 作者强烈建议， 如果可能， 与白细胞计数相似， 血清降钙素原水平将在任何时间段在 实验室收集血清样本 1 小时内得到结果。速得的地降钙素原水平报 告，可影响抗生素疗法决定的开始、持续或中断。在 Albrich 等人的研究中， 美国参与医院的降钙素原规则遵循率 仅 35%。如果医生对他们在自身对因素的了解有更多的信心，遵循率 还会增加，并推动血清降钙素原水平的上升或下降。医学博士 David Gilb

33、ert参考文献：1. Albrich WC, Dusemund F, Bucher B, et al. Effectiveness and safety of procalcitonin-guided antibiotic therapy in lower respiratory tract infections in“real life ”:an international, multicenterpost-study survey (ProREAL). Arch Intern Med . 2012;172(9):715-722.2. Li H, Luo Y=F, Blackwell TS,

34、 Xie C-M. Meta-analysis and systematic review of procalcitonin-guided therapy in respiratory tract infections. Antimicrob Agent Chemother. 2011;55(12):5900-5906.3. Schuetz P, Chiappa V , Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomiz

35、ed controlled trials and recommendations for clinical algorithms. Arch Intern Med . 2011;171(15):1322-1331.4. Becker KL, Nylen ES, White JC, Muller B, Snider RHJr. Clinical review 167: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab .