胸膜内组织纤溶酶原激活物/脱氧核糖核酸酶（tPA/DNase）治疗越来越多地用于胸膜感染。与tPA相关的出血风险和成本仍然是临床关注的问题。我们的剂量递减系列旨在建立tPA/DNase的最低有效给药方案。这项研究评估了2.5mgtPA/5mgDNase用于胸膜感染的胸膜内使用。
来自澳大利亚和英国两个中心的连续胸膜感染患者采用2.5mgtPA/5mgDNase的起始方案进行治疗。如果临床反应不充分,则允许tPA剂量的升级。
69例患者（平均年龄61.0岁）胸膜腔内接受2.5mgtPA/5mgDNase。大多数（88.4％）成功治疗，90天后出院，无需手术。患者接受5[四分位间距[IQR]=3-6]剂量的tPA/DNase的中位数。每位患者使用的tPA总量为12.5mg[中位数，IQR=7.5-15.0]。17例患者需要tPA的剂量递增；大多数（n=12）用于尝试引流远处的非交流室。X线照片上胸膜混浊的清除证实了治疗的成功（从27.0％[IQR=17.1-44.5]到11.0％[IQR=6.4-23.3]，p<0.0001),胸腔积液引流增加(1.98L[中位数，在tPA/DNase开始后72小时内，IQR=1.38-2.68]）和血清C反应蛋白水平降低（第5天从基线降低45.0％[IQR=39.3-77.0]，p<0.0001）。两名患者需要手术。6名具有显著合并症的患者(例如，晚期癌症）缓解并死亡时持续感染。两名患者经历了自限性胸膜出血并接受了输血。
2.5mgtPA/5mgDNase的胸膜内起始方案，如果需要，使用向上滴定，可以是有效的，值得进一步探索。
Intrapleural tissue plasminogen activator/
deoxyribonuclease (tPA/DNase) therapy is increasingly used in pleural infection. Bleeding risks and costs associated with tPA remain the clinical concerns. Our dose de-escalation series aims to establish the lowest effective dosing regimen for tPA/DNase. This
study assesses the intrapleural use of 2.5 mg tPA/5 mg DNase for pleural infection.
Consecutive patients with pleural infection treated with a starting regime of 2.5 mg tPA/5 mg DNase were included from two centres in Australia and UK. Escalation of tPA dose was permitted if clinical response was inadequate.
Sixty-nine patients (mean age 61.0 years) received intrapleural 2.5 mg tPA/5 mg DNase. Most (88.4%) were treated successfully and discharged from hospital without surgery by 90 days. Patients received a median of 5 [interquartile range [IQR] = 3-6] doses of tPA/DNase. Total amount of tPA used per patient was 12.5 mg [median, IQR = 7.5-15.0]. Seventeen patients required dose escalation of tPA; most (n = 12) for attempted drainage of distant non-communicating locule(s). Treatment success was corroborated by clearance of pleural opacities on radiographs (from median 27.0% [IQR = 17.1-44.5] to 11.0% [IQR = 6.4-23.3] of hemithorax, p < 0.0001), increased pleural fluid drainage (1.98 L [median, IQR = 1.38-2.68] over 72 h following commencement of tPA/DNase) and reduction of serum C-reactive protein level (by 45.0% [IQR = 39.3-77.0] from baseline at day 5, p < 0.0001). Two patients required surgery. Six patients with significant comorbidities (e.g., advanced cancer) had ongoing infection when palliated and died. Two patients experienced self-limiting pleural bleeding and received blood transfusion.
A starting intrapleural regime of 2.5 mg tPA/5 mg DNase, with up-titration if needed, can be effective and deserves further exploration.
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