Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome
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Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate the attributable effect of CMV reactivation on mortality in immunocompetent ARDS patients.
We prospectively studied immunocompetent ARDS patients who tested seropositive for CMV and remained mechanically ventilated beyond day 4 in two tertiary intensive care units in the Netherlands from 2011 to 2013. CMV loads were determined in plasma weekly. Competing risks Cox regression was used with CMV reactivation status as a time-dependent exposure variable. Subsequently, in sensitivity analyses we adjusted for the evolution of disease severity until onset of reactivation using marginal structural modeling.
Of 399 ARDS patients, 271 (68 %) were CMV seropositive and reactivation occurred in 74 (27 %) of them. After adjustment for confounding and competing risks, CMV reactivation was associated with overall increased ICU mortality (adjusted subdistribution hazard ratio (SHR) 2.74, 95 % CI 1.51–4.97), which resulted from the joint action of trends toward an increased mortality rate (direct effect; cause specific hazard ratio (HR) 1.58, 95 % CI 0.86–2.90) and a reduced successful weaning rate (indirect effect; cause specific HR 0.83, 95 % CI 0.58–1.18). These associations remained in sensitivity analyses. The population-attributable fraction of ICU mortality was 23 % (95 % CI 6–41) by day 30 (risk difference 4.4, 95 % CI 1.1–7.9).
CMV reactivation is independently associated with increased case fatality in immunocompetent ARDS patients who are CMV seropositive.
KeywordsCytomegalovirus Viremia Reactivation ARDS Mortality
We thank Huberta Dekker (Department of Medical Microbiology, University Medical Center Utrecht, the Netherlands) for her logistical support in this project, and the participating ICUs and research nurses of the two medical centers for their help in data acquisition. This work was supported by the Center for Translational Molecular Medicine (http://www.ctmm.nl), project MARS (Grant 04I-201). JK received a personal fee from Becton–Dickinson. The sponsor did not play a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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Conflicts of interest
The authors declare that they have no competing interests.
- 19.Ong DS, Spitoni C, Klein Klouwenberg P et al (2014) Cytomegalovirus reactivation in critically ill patients with acute respiratory distress syndrome (conference abstract ESICM 2014 Barcelona). Intensive Care Med 40:S127Google Scholar
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