Tai Dessmon Y H
Department of Respiratory Medicine, Tan Tock Seng Hospital, Singapore.
Ann Acad Med Singap. 2007 Jun;36(6):438-43.
The severe acute respiratory syndrome (SARS) pandemic caught the world by surprise in 2003 and spread rapidly within a relatively short period of time. Hence, randomised placebo-controlled clinical trials on the treatment of SARS were not possible. Our understanding was obtained from observational, cohort studies, case series and reports. Nevertheless, such information is useful in providing clinical management guidelines and directing future research in case SARS recurs. Early in the pandemic, a combination of ribavirin and corticosteroids was adopted as the standard treatment in Hong Kong, Canada and elsewhere because of the apparent good results of the first few patients. Subsequent reports showed that ribavirin was associated with a high rate of toxicity and lacked in vitro antiviral effect on SARS-coronavirus (SAR-CoV). The timing and dosage regimens of steroid in the treatment of SARS are controversial. Pulse methylprednisolone 250 to 500 mg/day for 3 to 6 days has been reported to have some efficacy in a subset of patients with "critical SARS", i.e., critically ill SARS patients with deteriorating radiographic consolidation, increasing oxygen requirement with PaO2 <10 kPa or SpO2 <90% on air, and respiratory distress (rate of 30/min). Prolonged therapy with high-dose steroids, in the absence of an effective antimicrobial agent, could predispose patients to complications such as disseminated fungal infection, and avascular necrosis. Kaletra (400 mg ritonavir and 100 mg lopinavir), a protease inhibitor used in the treatment of human immunodeficiency virus infection, may be considered for early treatment of SARS patients, preferably in a randomised double-blind placebo-controlled clinical trial setting. Interferon (IFN) is not recommended as standard therapy in SARS. However, there are enough data on in vitro activity of IFN preparations and a few clinical studies for these products to support a controlled trial if SARS recurs. Many other experimental treatments have been tried in an uncontrolled manner, and they should not be recommended as standard therapy.
2003年，严重急性呼吸综合征（SARS）大流行令全球猝不及防，并在相对短的时间内迅速传播。因此，针对SARS治疗开展随机安慰剂对照临床试验是不可能的。我们的认知来自观察性队列研究、病例系列报道和病例报告。尽管如此，这些信息对于制定临床管理指南以及指导未来SARS复发时的研究仍很有用。在大流行初期，由于最初几名患者取得了明显良好的疗效，香港、加拿大及其他地区采用利巴韦林和皮质类固醇联合治疗作为标准疗法。随后的报告显示，利巴韦林毒性发生率高，且对严重急性呼吸综合征冠状病毒（SARS-CoV）缺乏体外抗病毒作用。皮质类固醇治疗SARS的时机和给药方案存在争议。据报道，对于一部分“重症SARS”患者，即胸部影像学实变加重、吸氧需求增加（空气中氧分压<10kPa或脉搏血氧饱和度<90%）且有呼吸窘迫（呼吸频率30次/分钟）的重症SARS患者，每日静脉注射甲泼尼龙250至500mg，持续3至6天，有一定疗效。在缺乏有效抗菌药物的情况下，长期大剂量使用类固醇可能使患者易发生播散性真菌感染和无菌性坏死等并发症。洛匹那韦利托那韦片（400mg利托那韦和100mg洛匹那韦）是一种用于治疗人类免疫缺陷病毒感染的蛋白酶抑制剂，可考虑用于SARS患者的早期治疗，最好在随机双盲安慰剂对照临床试验环境中使用。不建议将干扰素（IFN）作为SARS的标准疗法。然而，关于干扰素制剂的体外活性有足够的数据，并且有一些针对这些产品的临床研究，如果SARS复发，可支持开展对照试验。许多其他实验性治疗方法已在非对照情况下进行尝试，不应推荐将它们作为标准疗法。
