Plasma thioredoxin levels during post-cardiac arrest syndrome: relationship with severity and outcome

International audienceIntroductionDespite experimental evidence, clinical demonstration of acute state of oxidative stress and inflammation during post-cardiac arrest syndrome is lacking. Plasma level of thioredoxin (TRX), a redox-active protein induced under conditions of oxidative stress and inflammation, is increased in various critical care conditions. We determined plasma TRX concentrations after cardiac arrest and assessed relationships with severity and outcome.MethodsRetrospective study of consecutive patients admitted to a single academic intensive care unit (ICU) for out-of-hospital cardiac arrest (between July 2006 and March 2008). Plasma levels of TRX were measured at admission, day (D) 1, 2 and 3.ResultsOf 176 patients included, median TRX values measured in ICU survivors and non-survivors were, respectively: 22 ng/mL (7.8 to 77) vs. 72.4 (21.9 to 117.9) at admission (P TRX levels on admission were significantly correlated with 'low-flow' duration (P = 0.003), sequential organ failure assessment (SOFA) score (P ConclusionsOur data show for the first time that TRX levels were elevated early following cardiac arrest, suggestive of oxidative stress and inflammation occurring with this condition. Highest values were found in the most severe patients. TRX could be a useful tool for further exploration and comprehension of post-cardiac arrest syndrome

Increased plasma thioredoxin levels in patients with sepsis: positive association with macrophage migration inhibitory factor.

PURPOSE: To establish the relationship between plasma levels of thioredoxin (Trx) and macrophage migration inhibitory factor (MIF) in systemic inflammatory stress syndrome (SIRS)/sepsis. METHODS: Enzyme-linked immunosorbent assay measurements of Trx, MIF, IL-6, -8, and -10 and enzyme-linked fluorescent assay determination of procalcitonin (PCT) in plasma from patients with SIRS/sepsis, neutropenic sepsis, healthy volunteers and pre-oesophagectomy patients. RESULTS: Thioredoxin was significantly higher in SIRS/sepsis patients [101.3 ng ml(−1), interquartile range (IQR) 68.7–155.6, n = 32] compared with that in healthy controls (49.5 ng ml(−1), IQR 31.4–71.1, P < 0.001, n = 17) or pre-oesophagectomy patients (40.5 ng ml(−1), IQR 36.9–63.2, P < 0.01, n = 7), but was not raised in neutropenics (n = 5). MIF levels were also significantly higher in SIRS/sepsis patients (12.1 ng ml(−1), IQR 9.5–15.5, n = 35), but not in the neutropenic group, when compared with healthy controls (9.3 ng ml(−1), IQR 7.3–10.7, P < 0.01, n = 20). Trx levels correlated, positively, with MIF levels and APACHE II scores. Plasma levels of IL-6, -8 and -10 and PCT increased significantly in patients with SIRS/sepsis (P < 0.001) and with neutropenic sepsis, but did not correlate with Trx or MIF levels. CONCLUSION: Plasma levels of Trx, MIF, IL-6, -8, -10 and PCT were raised in patients with SIRS/sepsis. Comparisons between mediators suggest a unique correlation of Trx with MIF. Moreover, Trx and MIF differed from cytokines and PCT in that levels were significantly lower in patients with neutropenia compared with the main SIRS/sepsis group. By contrast, IL-8 and PCT levels were significantly greater in the neutropenic patient group. The link between MIF and Trx highlighted in this study has implications for future investigations into the pathogenesis of SIRS/sepsis

Clinical solutions: Not always what they seem?

Brenner and colleagues, in their article published in Critical Care, showed elevated levels of the reactive carbonyl species (RCS) methylglyoxal (MG) in the circulation of patients with septic shock. We commend the authors’ bravery in launching this molecule into a field well-populated with biomarkers and where clinical diagnosis persists as the ‘gold standard’

SRAGE: A useful biomarker in acute lung injury?

Numerous studies of putative biomarkers in patients with acute lung injury (ALI) have been conducted to date, but none has proved worthy of entering routine clinical practice, largely because they have shown no clear advantage over clinical predictors (1, 2). Furthermore, the exemplar biomarker for ALI would be biologically plausible, sensitive, and highly specific, adding prognostic information independent of existing systems. The marker should also vary in proportion to the severity of injury and reflect the effects of therapeutic intervention. Conceivably, it would identify subgroups of patients who would benefit from specific therapies targeted at relevant pathogenetic pathways. Ideally, it would be inexpensive and rapidly quantified in a highly reproducible fashion. In this context, a prospective study published in this issue of Critical Care Medicine by Jabaudon et al (3) investigates whether the soluble form of the receptor for advanced glycation end products (sRAGE), is a valuable biomarker in patients with ALI regardless of whether it was associated with severe sepsis or septic shock

The receptor for advanced glycation end-products (RAGE) and its ligands in systemic inflammation following surgery necessitating cardiopulmonary bypass

Surgery necessitating cardiopulmonary bypass (snCPB) is associated with systemic inflammation which can be severe. Systemic inflammation is common in the critically ill, is associated with adverse outcome and currently has no specific therapy. Insight into the pathogenesis of systemic inflammation may lead to therapies. The receptor for advanced glycation end-products (RAGE) may represent a novel target for intervention. RAGE is a ubiquitous multi-ligand receptor that is up-regulated in the presence of its ligands. Initially characterised as a receptor for glycated proteins, it is also binds the S100 proteins and high mobility group box 1 (HMGB1); causing pro-inflammatory responses via NF-κB and the MAP kinases. RAGE inhibition has been associated with improved outcomes in animal models of infectious and sterile systemic inflammation. Of the snCPB patients assessed (n=2440) for relationships between age (associated with RAGE up-regulation) with systemic inflammation and clinical outcome, the oldest patients met more SIRS criteria in the first 1h and 24h following snCPB than those aged 40-80 y. This was accompanied by higher scores of organ dysfunction. Also, plasma levels of RAGE ligands and soluble RAGE increased (n=18-120) around surgery with pre-operative levels correlating with duration of intensive care. Leukocyte cell-surface and intracellular levels of RAGE were assessed and cell surface levels on neutrophils decreased following surgery, possibly contributing to the sRAGE levels in plasma. Cytokine release from whole blood increased following incubation with RAGE ligands, with a diminished effect on whole blood obtained after snCPB, suggesting leukocyte hypo-responsiveness. Finally, genotyping 8 single nucleotide polymorphisms in the RAGE, HMGB1 and S100A8 genes in 187 snCBP patients indicated statistically significant relationships to clinical outcomes such as impaired oxygenation and incidence of acute kidney injury. The findings from these investigations, inform understanding of the involvement of the RAGE axis in systemic inflammation.EThOS - Electronic Theses Online ServiceRoyal Brompton Hospital, Dovedale Trust, Transtech PharmaGBUnited Kingdo