Systemic inflammation after critical illness: relationship with physical recovery and exploration of potential mechanisms

Background Physical recovery following critical illness is slow, often incomplete and is resistant to rehabilitation interventions. We aimed to explore the contribution of persisting inflammation to recovery, and investigated the potential role of human cytomegalovirus (HCMV) infection in its pathogenesis. Methods In an a priori nested inflammatory biomarker study in a post-intensive care unit (ICU) rehabilitation trial (RECOVER; ISRCTN09412438), surviving adult ICU patients ventilated >48h were enrolled at ICU discharge and blood sampled at ICU discharge (n=184) and 3month follow-up (N=123). C-reactive protein (CRP), human neutrophil elastase (HNE), interleukin (IL)-1, IL-6, IL-8, transforming growth factor 1 (TGF1) and secretory leucocyte protease inhibitor (SLPI) were measured. HCMV IgG status was determined (previous exposure), and DNA PCR measured among seropositive patients (lytic infection). Physical outcome measures including the Rivermead Mobility Index (RMI) were measured at 3months. Results Many patients had persisting inflammation at 3months (CRP >3mg/L in 59%; >10mg/L in 28%), with proinflammatory phenotype (elevated HNE, IL-6, IL-8, SLPI; low TGF1). Poorer mobility (RMI) was associated with higher CRP (=0.13; p<0.01) and HNE (=0.32; p=0.03), even after adjustment for severity of acute illness and pre-existing co-morbidity (CRP =0.14; p<0.01; HNE =0.30; p=0.04). Patients seropositive for HCMV at ICU discharge (63%) had a more proinflammatory phenotype at 3months than seronegative patients, despite undetectable HMCV by PCR testing. Conclusions Inflammation is prevalent after critical illness and is associated with poor physical recovery during the first 3months post-ICU discharge. Previous HCMV exposure is associated with a proinflammatory phenotype despite the absence of detectable systemic viraemia. Trial registration number ISRCTN09412438, post results.