Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection
Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection
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DOI：
10.1056/nejmoa1012740
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发表时间：
2011-08-11
影响因子：
158.5
通讯作者：
Davies, Robert J. O.
中科院分区：
文献类型：
--
作者：
Rahman, Najib M.;Maskell, Nicholas A.;Davies, Robert J. O.
背景：超过30%的胸膜感染患者不是死亡就是需要手术。引流感染液体是成功治疗的关键，但在早期的一项大型随机试验中，胸膜内纤溶治疗并没有改善结果。方法：我们进行了一项2 × 2的盲法试验，其中210例胸膜感染患者被随机分配接受4种研究治疗中的一种，为期3天：双重安慰剂、胸膜组织内纤溶酶原激活剂（t-PA）和dna酶、t-PA和安慰剂、或dna酶和安慰剂。主要结果是胸膜混浊的变化，以胸腔积液占半胸的百分比来衡量，胸片在第7天与第1天相比。次要结局包括转诊手术、住院时间和不良事件。结果t-PA-DNase组胸膜混浊的平均（+/- SD）变化大于安慰剂组（-29.5 +/- 23.3% vs -17.2 +/- 19.6%，差异为-7.9%，95%可信区间[CI]， -13.4 ~ -2.4, P = 0.005）；单独使用t-PA和单独使用DNase观察到的变化（分别为-17.2 +/- 24.3和-14.7 +/- 16.4%）与安慰剂观察到的变化无显著差异。3个月时，t-PA-DNase组的手术转诊频率低于安慰剂组（48例患者中有2例[4%]比51例患者中有8例[16%]；手术转诊的优势比为0.17；95% CI为0.03 ~ 0.87;P = 0.03），但DNase组（46例患者中有18例[39%]）高于安慰剂组（优势比为3.56；95% CI为1.30 ~ 9.75;P = 0.01）。与安慰剂相比，联合t-PA-DNase治疗与住院时间缩短相关（差异为-6.7天；95% CI, -12.0至-1.9;P = 0.006）；单独使用任何一种药物的住院时间与使用安慰剂的住院时间没有显著差异。不良事件发生的频率在两组间无显著差异。结论胸膜内t-PA-DNase治疗可改善胸膜感染患者的液体引流，减少手术转诊次数和住院时间。单用DNase或t-PA治疗无效。
BackgroundMore than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial.MethodsWe conducted a blinded, 2-by-2 factorial trial in which 210 patients with pleural infection were randomly assigned to receive one of four study treatments for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events.ResultsThe mean (+/- SD) change in pleural opacity was greater in the t-PA-DNase group than in the placebo group (-29.5 +/- 23.3% vs. -17.2 +/- 19.6%; difference, -7.9%; 95% confidence interval [CI], -13.4 to -2.4; P = 0.005); the change observed with t-PA alone and with DNase alone (-17.2 +/- 24.3 and -14.7 +/- 16.4%, respectively) was not significantly different from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P = 0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P = 0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P = 0.006); the hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups.ConclusionsIntrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of the hospital stay. Treatment with DNase alone or t-PA alone was ineffective.