Gözübüyük Alper, Ozpolat Berkant, Ciçek Ali Fuat, Caylak Hasan, Yücel Orhan, Kavaklı Kuthan, Gürkök Sedat, Genç Onur
Department of Thoracic Surgery, Kırıkkale University, School of Medicine, Kırıkkale, Turkey.
J Cardiothorac Surg. 2010 Dec 13;5:128. doi: 10.1186/1749-8090-5-128.
Chemical pleurodesis is widely recommended in the treatment of refractory pleural effusion or pulmonary air leak of different etiologies. Although several agents have been used, many questions have remained unanswered about their toxicity. Talc is the most commonly used agent for the treatment, with rare, serious complications reported. Oxytetracycline pleurodesis in clinical practice has been described in a few studies, but literature reveals no experimental studies using this agent. We performed a prospective, randomized, observer-blinded, controlled study to evaluate the changes in lung histology and systemic response to pleurodesis with oxytetracycline and talc in acute and subacute phases in a rat model.
Forty-two male albino Wistar rats were divided into three groups and 3 subgroups with 7 animals in each. Group 1 was given oxytetracycline, 35 mg/kg; Group 2 was given talc slurry, 60 mg/kg in 0.5 mL saline solution, and Group 3 was given only 0.5 mL saline intrapleurally. In subgroups "a" the nimls were sacrificed at the postoperative 72nd hour and, in subgroups "b", on the postoperative day 7. The surfaces were graded by microscopic examination.
Oxytetracycline produced alveolar collapse, hemorrhage, edema, inflammation at the postoperative 72nd hour and hemorrhage on the postoperative day 7, while talc produced significant edema, inflammation, proliferation, fibrosis at the postoperative 72nd hour and hemorrhage, edema, inflammation, proliferation, and fibrosis on the postoperative day 7 (p < 0.0042). Talc produced significant edema compared to oxytetracycline on the postoperative day 7. On contralateral side, oxytetracycline and talc produced significant hemorrhage on the postoperative day 7 (p < 0.0042).
Both agents were shown to produce pulmonary lesions. In acute phase, the pulmonary side effects of oxytetracycline were more pronounced, whereas the side effects of talc were prolonged to subacute phase. We propose that the occasional side effects in humans may be related to these changes as were observed in our rat model, and like talc, oxytetracycline must be used cautiously in patients with limited respiratory function.
化学性胸膜固定术在治疗不同病因的难治性胸腔积液或肺漏气方面得到广泛推荐。尽管已使用多种药物，但其毒性仍存在许多未解答的问题。滑石粉是治疗中最常用的药物，报道的严重并发症罕见。临床实践中已有少数研究描述了土霉素胸膜固定术，但文献中未发现使用该药物的实验研究。我们进行了一项前瞻性、随机、观察者盲法、对照研究，以评估大鼠模型在急性和亚急性期使用土霉素和滑石粉进行胸膜固定术后肺组织学变化和全身反应。
42只雄性白化Wistar大鼠分为三组，每组再分为三个亚组，每组7只。第1组给予土霉素，35mg/kg；第2组给予滑石粉悬液，60mg/kg溶于0.5mL盐溶液中，第3组仅胸腔内注射0.5mL盐溶液。在亚组“a”中，大鼠在术后72小时处死，在亚组“b”中，在术后第7天处死。通过显微镜检查对表面进行分级。
土霉素在术后72小时导致肺泡塌陷、出血、水肿、炎症，在术后第7天导致出血；而滑石粉在术后72小时导致明显的水肿、炎症、增殖、纤维化，在术后第7天导致出血、水肿、炎症、增殖和纤维化（p<0.0042）。与土霉素相比，滑石粉在术后第7天导致明显的水肿。在对侧，土霉素和滑石粉在术后第7天导致明显的出血（p<0.0042）。
两种药物均显示会产生肺部病变。在急性期，土霉素的肺部副作用更明显，而滑石粉的副作用则延长至亚急性期。我们认为人类偶尔出现的副作用可能与我们在大鼠模型中观察到的这些变化有关，并且与滑石粉一样，呼吸功能受限的患者必须谨慎使用土霉素。
