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 >48 h were enrolled at ICU discharge and blood sampled at ICU discharge (n=184) and 3 month follow-up (N=123). C-reactive protein (CRP), human neutrophil elastase (HNE), interleukin (IL)-1ß, IL-6, IL-8, transforming growth factor ß1 (TGFß1) 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 3 months. RESULTS: Many patients had persisting inflammation at 3 months (CRP >3 mg/L in 59%; >10 mg/L in 28%), with proinflammatory phenotype (elevated HNE, IL-6, IL-8, SLPI; low TGFß1). Poorer mobility (RMI) was associated with higher CRP (ß=0.13; p<0.01) and HNE (ß=0.32; p=0.03), even after adjustment for severity of acute illness and pre-existing co-morbidity (CRP ß=0.14; p<0.01; HNE ß=0.30; p=0.04). Patients seropositive for HCMV at ICU discharge (63%) had a more proinflammatory phenotype at 3 months 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 3 months 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.

Persistent inflammation and recovery after intensive care: A systematic review.

PURPOSE: Physical weakness is common after critical illness; however, it is not clear how best to treat it. Inflammation characterizes critical illness, is associated with loss of muscle mass during critical illness, and potentially modifies post-intensive care unit (ICU) recovery. We sought to identify published reports on the prevalence of systemic inflammation after critical illness and its association with physical recovery. METHODS: This is a systematic review of the literature from MEDLINE, EMBASE, CINAHL, CPCI-SSH, and CPCI-S from January 1982 to December 2011. RESULTS: From 7433 references, 207 full-text articles were reviewed, 57 were eligible, and 22 were included. Inflammation was present in most patients at ICU discharge according to C-reactive protein concentration (range, 70%-100%), procalcitonin (range, 89%-100%), tumor necrosis factor α (100%), and systemic inflammatory response syndrome criteria (range, 92%-95%). Fewer patients had elevated myeloperoxidase concentrations (range, 0%-56%). At hospital discharge, 9 (90%) of 10 chronic obstructive pulmonary disease patients had elevated C-reactive protein. No studies tested the association between inflammation and physical recovery. CONCLUSIONS: Inflammation is present in most patients at ICU discharge, but little is known or has been investigated about persistent inflammation after this time point. No studies have explored the relationship between persistent inflammation and physical recovery. Further research is proposed.

Early physical rehabilitation in intensive care patients with sepsis syndromes: a pilot randomised controlled trial.

RATIONALE: Survivors of sepsis syndromes have poor outcomes for physical and cognitive function. No investigations of early physical rehabilitation in the intensive care unit have specifically targeted patients with sepsis syndromes. OBJECTIVE: To determine whether early physical rehabilitation improves physical function and associated outcomes in patients with sepsis syndromes. METHODS: Fifty critically ill adults admitted to a general intensive care unit with sepsis syndromes were recruited into a prospective double-blinded randomised controlled trial investigating early physical rehabilitation. MEASUREMENTS: Primary outcomes of physical function (acute care index of function) and self-reported health-related quality of life were recorded at ICU discharge and 6 months post-hospital discharge, respectively. Secondary measures included inflammatory biomarkers; Interleukin-6, Interleukin-10 and tumour necrosis factor-α, blood lactate, fat-free muscle mass, exercise capacity, muscle strength and anxiety. MAIN RESULTS: A significant increase in patient self-reported physical function (81.8 ± 22.2 vs. 60.0 ± 29.4), p = 0.04) and physical role (61.4 ± 43.8 vs. 17.1 ± 34.4, p = 0.005) for the SF-36 at 6 months was found in the exercise group. Physical function scores were not significantly different between groups. Muscle strength scores were (51.9 ± 10.5 vs. 47.3 ± 13.6, p = 0.24) with the standard care mean Medical Research Council Muscle Score (MRC) <48/60. The mean change of Interleukin-10 increased and was significantly higher in the exercise group (1.8 pg/ml, 180 % vs. 0.9 pg/ml, 90 %, p = 0.04). There was no significant difference between groups for lactate, Interleukin-6, tumour necrosis factor-α, muscle strength, exercise capacity, fat-free mass or hospital anxiety. CONCLUSION: Implementation of early physical rehabilitation can improve self-reported physical function and induce systemic anti-inflammatory effects.

Evidence-based practice: fever evaluation and early recognition of systemic inflammatory response syndrome in critical care patients.

Fever is very often the first sign of sepsis and systemic inflammatory response syndrome, both of which can be life-threatening. This article presents various guidelines for the treatment and prevention of fever using evidence-based practice guidelines from a variety of sources.

Usefulness of a clinical diagnosis of ICU-acquired paresis to predict outcome in patients with SIRS and acute respiratory failure.

PURPOSE: Neuromuscular abnormalities are common in ICU patients. We aimed to assess the incidence of clinically diagnosed ICU-acquired paresis (ICUAP) and its impact on outcome. METHODS: Forty-two patients with systemic inflammatory response syndrome on mechanical ventilation for >or=48 h were prospectively studied. Diagnosis of ICUAP was defined as symmetric limb muscle weakness in at least two muscle groups at ICU discharge without other explanation. The threshold Medical Research Council (MRC) Score was set at 35 (of 50) points. Activities in daily living were scored using the Barthel Index 28 and 180 days after ICU discharge. RESULTS: Three patients died before sedation was stopped. ICUAP was diagnosed in 13 of the 39 patients (33%). Multivariate regression analysis yielded five ICUAP-predicting variables (P < 0.05): SAPS II at ICU admission, treatment with steroids, muscle relaxants or norepinephrine, and days with sepsis. Patients with ICUAP had lower admission SAPS II scores [37 +/- 13 vs. 49 +/- 15 (P = 0.018)], lower Barthel Index at 28 days and lower survival at 180 days after ICU discharge (38 vs. 77%, P = 0.033) than patients without ICUAP. Daily TISS-28 scores were similar but cumulative TISS-28 scores were higher in patients with ICUAP (664 +/- 275) than in patients without ICUAP (417 +/- 236; P = 0.008). The only independent risk factor for death before day 180 was the presence of ICUAP. CONCLUSIONS: A clinical diagnosis of ICUAP was frequently established in this patient group. Despite lower SAPS II scores, these patients needed more resources and had high mortality and prolonged recovery periods after ICU discharge.