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[MEDSCAPE观点]:更昔洛韦能否防止危重病时CMV的复燃?
2017年11月14日 研究点评, 进展交流 暂无评论

COMMENTARY

Can Ganciclovir Thwart CMV Reactivation in Critical Illness?

Greg Martin, MD

October 30, 2017

CMV Reactivation: Can It Be Reduced? CMV复燃:能否减少?

Cytomegalovirus (CMV) is a widely prevalent human herpes virus found in most healthy adults and causes lifelong latent infection in many organs, such as the lung. Latent CMV commonly reactivates during immunosuppression or critical illness, and research shows an association of CMV reactivation with worse clinical outcomes. In a recent study, Limaye and colleagues[1] sought to determine whether empiric ganciclovir would reduce plasma interleukin (IL)-6 levels in CMV-seropositive critically ill adults with respiratory failure due to either sepsis or severe traumatic injuries.

巨细胞病毒(CMV)是一种广泛分布的人类疱疹病毒,可见于很多健康成人,并导致很多器官(如肺)终生潜在感染。在免疫功能抑制或危重病时,潜在CMV可发生复燃,研究表明,CMV复燃与不良临床预后密切相关。Limaye及其同事近期的一项研究试图确定,对于合并全身性感染或严重创伤导致的呼吸功能衰竭的CMV血清阳性成年危重病患者,经验性使用更昔洛韦能否降低血浆IL-6水平。

The Study 研究介绍

The study was a prospective, randomized controlled trial. Patients were randomly assigned 1:1 to receive either ganciclovir or placebo until hospital discharge. A total of 160 patients underwent randomization, and 132 completed the study. The mean change in IL-6 was not significantly different between groups, but CMV reactivation in plasma was significantly less in the ganciclovir group (12% vs 39%, P < .001). The ganciclovir group had more ventilator-free days in both the overall group and in the sepsis subgroup. There were no significant between-group differences in other secondary outcomes. The study authors concluded that among CMV-seropositive adults with critical illness due to sepsis or trauma, ganciclovir does not reduce IL-6 levels. Additional research is necessary to determine the clinical efficacy and safety of CMV suppression.

这是一项前瞻随机对照试验。按照1:1的比例将患者随机分组,使用更昔洛韦或安慰剂直至出院。共有160名患者接受随机分组,132名患者完成研究。两组间IL-6水平的平均变化值并无显著差异,但更昔洛韦组血浆CMV复燃的比例显著降低(12% vs 39%, P < .001)。全体患者分析及全身性感染亚组分析显示,更昔洛韦组患者无机械通气天数更多。两组间其他次要预后指标无显著差异。研究作者得出结论,在全身性感染或创伤导致的CMV血清阳性危重病患者,更昔洛韦不能降低IL-6水平。需要进行进一步研究以确定抑制CMV的临床疗效及安全性。

Viewpoint 观点

The past few years have seen a spate of studies documenting CMV reactivation in critically ill adults and associating CMV reactivation with worse clinical outcomes. It has been impossible to know with certainty whether the worse clinical outcomes were caused by CMV or whether the CMV was simply a marker of patients with worse critical illness and immune dysfunction. Sepsis, for example, is known to cause both an inflammatory and an anti-inflammatory response, and we increasingly are studying the immune paralysis that occurs with sepsis because of its potential to affect clinical outcomes. The ability to categorize patients with sepsis according to their immune phenotype, however, is not yet feasible in regular clinical settings.

过去数年间发表的大量研究表明成年危重病患者可表现CMV复燃,且CMV复燃与不良临床预后密切相关。然而,我们却未能确切了解不良临床预后是否由CMV引起,抑或CMV仅仅是不良危重病及免疫功能障碍的标志。例如,已知全身性感染能够导致炎症及抗炎症反应,我们对全身性感染患者发生的免疫瘫痪进行了越来越多的研究,这是因为免疫瘫痪可能影响临床预后。然而,根据免疫表型对全身性感染患者进行分组,在常规临床情况下尚不可行。

This study sought to move the field forward by testing whether empiric CMV suppression (in CMV-seropositive adults) would improve clinical outcomes. Had this study demonstrated improved clinical outcomes, it would have helped to close the loop from confounded observational studies to show a causal relationship of CMV in critical illness outcomes. The study, however, failed to demonstrate even a change in the primary outcome of a biological inflammatory marker (IL-6) with ganciclovir therapy. That makes interpreting the differences in CMV reactivation and ventilator-free days more difficult, and it is impossible to recommend routine use of ganciclovir in critically ill patients.

本研究在这一领域作出探索,验证经验性抑制CMV(在CMV血清阳性成人)能否改善临床预后。如果研究显示临床预后改善,则可能有助于弥补观察性研究的缺陷,表明CMV与危重病预后之间的因果关系。然而,这项研究未能发现更昔洛韦可引起主要预后指标即炎症标志物(IL-6)的改变。这一结果使得解读CMV复燃及无机械通气天数的差异更加困难,目前尚不能推荐危重病患者常规使用更昔洛韦。

References 参考文献

1. Limaye AP, Stapleton RD, Peng L, et al. Effect of ganciclovir on IL-6 levels among cytomegalovirus-seropositive adults with critical illness: a randomized clinical trial. JAMA. 2017;318:731-740. Abstract

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