Cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis.

Cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis.
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DOI:
10.1186/cc10069
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发表时间:
2011
期刊:
Critical care (London, England)
影响因子:
--
通讯作者:
Hamprecht K
Hamprecht K
中科院分区:
其他
文献类型:
--
作者:
Heininger A;Haeberle H;Fischer I;Beck R;Riessen R;Rohde F;Meisner C;Jahn G;Koenigsrainer A;Unertl K;Hamprecht K

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脓毒症已被确定为危重患者中人巨细胞病毒(CMV)再激活的危险因素。然而,CMV再激活对发病率和死亡率的影响仍有争议。因此,我们分析了严重脓毒症患者CMV再激活的发生率及其对预后的影响。在一项前瞻性纵向双盲观察性研究中,纳入了97例新发严重脓毒症的成人非免疫抑制CMV血清阳性患者。每周用PCR法检测白细胞、血浆和气管分泌物中的CMV-DNA。另外检测气管分泌物的HSV(单纯疱疹病毒)-DNA。通过考克斯比例风险回归分析分析CMV再激活对终点的影响。时间依赖性通过界标分析进行评价。97人中有6人死亡,5人在72小时内出院,并被排除在分析之外。86例分析患者中有35例(40.69%)发生CMV再激活。HSV感染发生在23(65.7%)的35个CMV再激活剂。在10例患者中,CMV血浆DNA血症出现,其中4例DNA含量低于600拷贝/ml,平均峰值为2,830拷贝/ml。在有和无CMV再激活的患者中,死亡率相似(分别为37.1%和35.3%,P = 0.861)。然而,在多变量考克斯回归分析中,CMV再激活与ICU住院时间的增加独立相关(30.0,四分位距14至48 vs. 12.0,四分位距7至19天; HR(风险比)3.365; 95% CI(置信区间)1.233至9.183,P = 0.018)和在医院(33.0,四分位距24 - 62 vs. 16.0,四分位距10 - 24天,HR 3.3,95% CI 1.78 - 6.25,P < 0.001)以及延长机械通气(22.0,四分位距6 ~ 36 vs. 7.5,四分位距5 ~ 15.5天; HR 2.6,CI 95%1.39 ~ 4.94; P < 0.001)和肺气体交换受损(6天,四分位数范围1至17,与3天,四分位数范围1至7,再活化剂与非再活化剂的天数,P = 0.038)。HSV再激活被证明不是这些不良反应的风险因素。这些数据表明,在明确定义的非免疫抑制的严重脓毒症患者组中,CMV再激活与发病率增加之间存在独立相关性,但在CMV-DNA血浆水平较低的该组中,CMV再激活对死亡率没有影响。因此,在严重脓毒症或脓毒性休克患者中,抗病毒治疗的潜在危害和益处必须谨慎权衡。
Sepsis has been identified as a risk factor for human cytomegalovirus (CMV) reactivation in critically ill patients. However, the contribution of CMV reactivation on morbidity and mortality is still controversial. Therefore, we analyzed the incidence and impact of CMV reactivation on outcome in patients with severe sepsis. In a prospective longitudinal double-blinded observational study, 97 adult nonimmunosuppressed CMV-seropositive patients with new onset of severe sepsis were included. Leukocytes, plasma and tracheal secretions were examined weekly for CMV-DNA by PCR. Tracheal secretions were additionally tested for HSV (Herpes Simplex Virus)-DNA. The influence of CMV-reactivation on the endpoints was analysed by Cox proportional-hazard regression analysis. Time-dependency was evaluated by landmark analysis. Six out 97 died and five were discharged from the hospital within 72 hours and were excluded of the analysis. CMV reactivation occurred in 35 of the 86 (40.69%) analysed patients. HSV infection occurred in 23 of the 35 (65.7%) CMV reactivators. In 10 patients CMV-plasma-DNAemia appeared with a DNA-content below 600 copies/ml in four cases and a peak amount of 2,830 copies/ml on average. In patients with and without CMV reactivation mortality rates were similar (37.1% vs. 35.3%, P = 0.861), respectively. However, in the multivariate COX regression analyses CMV reactivation was independently associated with increased length of stay in the ICU (30.0, interquartile range 14 to 48 vs. 12.0, interquartile range 7 to 19 days; HR (hazard ratio) 3.365; 95% CI (confidence interval) 1.233 to 9.183, P = 0.018) and in the hospital (33.0, interquartile range 24 to 62 vs. 16.0, interquartile range 10 to 24 days, HR 3.3, 95% CI 1.78 to 6.25, P < 0.001) as well as prolonged mechanical ventilation (22.0, interquartile range 6 to 36 vs. 7.5, interquartile range 5 to 15.5 days; HR 2.6,CI 95% 1.39 to 4.94; P < 0.001) and impaired pulmonary gas exchange (six days, interquartile range 1 to 17, vs. three, interquartile range 1 to 7, days in reactivators vs. non-reactivators, P = 0.038). HSV reactivation proved not to be a risk factor for these adverse effects. These data indicate an independent correlation between CMV reactivation and increased morbidity in the well-defined group of nonimmunosuppressed patients with severe sepsis, but CMV reactivation had no impact on mortality in this group with low CMV-DNA plasma levels. Thus, the potential harms and benefits of antiviral treatment have to be weighed cautiously in patients with severe sepsis or septic shock.
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