Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark.
Crit Care Med. 2011 Sep;39(9):2048-58. doi: 10.1097/CCM.0b013e31821e8791.
For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival.
Randomized controlled open-label trial.
Nine multidisciplinary intensive care units across Denmark.
A total of 1,200 critically ill patients were included after meeting the following eligibility requirements: expected intensive care unit stay of ≥ 24 hrs, nonpregnant, judged to not be harmed by blood sampling, bilirubin <40 mg/dL, and triglycerides <1000 mg/dL (not suspensive).
: Patients were randomized either to the "standard-of-care-only arm," receiving treatment according to the current international guidelines and blinded to procalcitonin levels, or to the "procalcitonin arm," in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements.
The primary end point was death from any cause at day 28; this occurred for 31.5% (190 of 604) patients in the procalcitonin arm and for 32.0% (191 of 596) patients in the standard-of-care-only arm (absolute risk reduction, 0.6%; 95% confidence interval [CI] -4.7% to 5.9%). Length of stay in the intensive care unit was increased by one day (p = .004) in the procalcitonin arm, the rate of mechanical ventilation per day in the intensive care unit increased 4.9% (95% CI, 3.0-6.7%), and the relative risk of days with estimated glomerular filtration rate <60 mL/min/1.73 m was 1.21 (95% CI, 1.15-1.27).
Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit. The procalcitonin strategy like the one used in this trial cannot be recommended.
对于重症监护病房的患者来说，败血症是一种常见且可能致命的并发症，及时启动适当的抗菌治疗可改善预后。本试验的目的是确定一种基于降钙素原（一种生物标志物）的每日测量来指导抗菌谱升级的策略是否可以减少获得适当治疗的时间，从而提高生存率。
随机对照开放标签试验。
丹麦 9 个多学科重症监护病房。
符合以下纳入标准的 1200 名重症患者被纳入研究：预计 ICU 入住时间≥24 小时、非孕妇、认为采血不会对其造成伤害、胆红素<40mg/dL 且甘油三酯<1000mg/dL（非暂停治疗）。
患者被随机分为“仅接受标准护理组”，即根据当前国际指南进行治疗，且对降钙素原水平设盲；或“降钙素组”，即在现有指南的基础上，增加药物升级算法，并根据每日降钙素原测量结果进行强化诊断。
主要终点为 28 天内任何原因导致的死亡；降钙素组有 31.5%（190/604）的患者和仅接受标准护理组有 32.0%（191/596）的患者死亡（绝对风险降低，0.6%；95%置信区间[CI]，-4.7%至 5.9%）。降钙素组 ICU 住院时间延长 1 天（p=0.004），ICU 内机械通气天数增加 4.9%（95%CI，3.0-6.7%），估计肾小球滤过率<60mL/min/1.73m2的天数的相对风险为 1.21（95%CI，1.15-1.27）。
在重症监护病房中，降钙素指导的抗菌药物升级并不能改善生存率，反而会导致与器官相关的损害和 ICU 住院时间延长。像本试验中使用的降钙素策略不能被推荐。
