Consequences of cytomegalovirus reactivation in patients with severe sepsis

Introduction

Sepsis has been identified as a risk factor for cyto-megalovirus (CMV) reactivation in nonimmunosuppressed patients in the ICU setting. Here we present a double-blinded prospective study assessing the consequences of CMV reactivation in non-immunosuppressed patients with severe sepsis.

Methods

In three (two surgical, one medical) ICUs of a German university hospital, adult patients were screened for severe sepsis. Patients with recently occurring severe sepsis (<72 hours) were enrolled if their anti-CMV IgG titer was positive. The exclusion criterion was a manifest immunodeficiency. At enrollment the SAPS II was assessed. Patients were monitored for CMV reactivation weekly until death or hospital discharge by qualitative and quantitative PCR and virus culture. CMV reactivation was defined as CMV DNA detection or virus isolation. Patients with (CMV+) and without CMV reactivation (CMV-) were compared regarding inhospital mortality, duration of mechanical ventilation, length of stay (LOS) in the ICU and the hospital. Data were analysed using the Wilcoxon score rank sum test and chi-square test. The level of significance was set to 0.05.

Results

CMV reactivation was observed in 38 out of 99 patients. Both groups (CMV+/CMV- patients) were quite similar in regard to gender and age at study enrollment. Interestingly, the median SAPS II was higher in CMV- patients (47 vs 42; P < 0.013). Accordingly, a lower mortality rate was anticipated for CMV+ patients compared with the CMV- group. Contrary to expectations, mortality did not differ between both groups (CMV+ 36.8% vs CMV- 42.6%; P > 0.67). This may point to a relatively increased mortality in CMV+ patients, although CMV disease did not occur. There was a striking difference between the groups in respect to the period on ventilator: 21.5 days vs 8.0 days (median) in CMV+ and CMV- patients, respectively (P < 0.005). Similarly, CMV+ patients had a longer median LOS after enrollment either in the ICU (29.5 days vs 10 days, P < 0.001) and in the hospital (49 days vs 23 days, P < 0.001). This difference was assured when the analysis was restricted to survivors.

Conclusion

Our data suggest that CMV reactivation leads to increased morbidity and treatment expenditure independently from CMV disease. Further analysis points at a crucial role of lung pathology due to CMV reactivation.