Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study.

BACKGROUND: The use of hydroxocobalamin has long been advocated for treating suspected cyanide poisoning after smoke inhalation. Intravenous hydroxocobalamin has however been shown to cause oxalate nephropathy in a single-center study. The impact of hydroxocobalamin on the risk of acute kidney injury (AKI) and survival after smoke inhalation in a multicenter setting remains unexplored. METHODS: We conducted a multicenter retrospective study in 21 intensive care units (ICUs) in France. We included patients admitted to an ICU for smoke inhalation between January 2011 and December 2017. We excluded patients discharged at home alive within 24 h of admission. We assessed the risk of AKI (primary endpoint), severe AKI, major adverse kidney (MAKE) events, and survival (secondary endpoints) after administration of hydroxocobalamin using logistic regression models. RESULTS: Among 854 patients screened, 739 patients were included. Three hundred six and 386 (55.2%) patients received hydroxocobalamin. Mortality in ICU was 32.9% (n = 243). Two hundred eighty-eight (39%) patients developed AKI, including 186 (25.2%) who developed severe AKI during the first week. Patients who received hydroxocobalamin were more severe and had higher mortality (38.1% vs 27.2%, p = 0.0022). The adjusted odds ratio (95% confidence interval) of AKI after intravenous hydroxocobalamin was 1.597 (1.055, 2.419) and 1.772 (1.137, 2.762) for severe AKI; intravenous hydroxocobalamin was not associated with survival or MAKE with an adjusted odds ratio (95% confidence interval) of 1.114 (0.691, 1.797) and 0.784 (0.456, 1.349) respectively. CONCLUSION: Hydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03558646.

Low endocan levels are predictive of Acute Respiratory Distress Syndrome in severe sepsis and septic shock.

PURPOSE: Endocan is a circulating proteoglycan measured at high blood levels during severe sepsis, with a likely lung anti-inflammatory function. The aim of this study was to assess whether paradoxically low endocan levels at Intensive Care Unit (ICU) admission could predict Acute Respiratory Distress Syndrome (ARDS) within 72 h in severe septic patients. MATERIALS AND METHODS: Patients admitted for severe sepsis in the ICU of a French University Hospital were included in a prospective single-center observational study between October 2014 and March 2016. RESULTS: 72 patients admitted in ICU for severe sepsis were included. Endocan blood values at inclusion were significantly lower in patients who developed an ARDS at 72 h (p < 0.001). For endocan blood values > 5.36 ng/mL, the adjusted OR for development of ARDS at 72 h was of 0.001 (95% CI 0-0.215; p = 0.011). In our cohort, an endocan value < 2.54 ng/mL predicted ARDS at 72 h with a positive predictive value of 1 (Sp = 1 (95% CI 0.94-1)). CONCLUSIONS: In a cohort of severe septic patients, we observed that low blood levels of endocan at ICU admission were predictive of ARDS at 72 h.

Endocan is a stable circulating molecule in ICU patients.

BACKGROUND: Endocan is a lung endothelial cell secreted proteoglycan, possessing multiple physiological roles and potential therapeutic and diagnostic utility as biomarker in pneumonia and acute respiratory distress syndrome. Endocan synthesis and secretion can be induced by proinflammatory cytokines such as TNF-α, but can also be subject of proteolytic degradation causing preanalytical variation. METHODS: We investigated the stability of endocan in conventional serum, plasma, anticoagulated whole blood, as well as whole blood and plasma stabilized with protease inhibitors. RESULTS: Among the recipient tubes for blood collection, those with EDTA gave minimal interference. No dilution effect was observed on recovery tests from 1:2 to 1:16 (v:v). The recovery test in 10 plasma EDTA samples from healthy subjects or septic patients indicated a median recovery of 104.5% [104%-107.5%], and 97% [88.5%; 102.5%], respectively. Patient's plasma endocan remains stable when stored at room temperature till 72h, or following 3 freeze thaw cycles. Finally, no interference was observed with hemolytic, icteric or turbidic plasma samples. CONCLUSION: These results are consistent with the view that endocan measured in ICU patients is intact, stable, and accurate. Then, the low endocan level observed in ICU patients who developed ARDS is likely to be reliable.

Identification of a 14 kDa endocan fragment generated by cathepsin G, a novel circulating biomarker in patients with sepsis.

Severe septic syndrome, which is the most prevalent and lethal cause of acute respiratory distress syndrome, remains one of the most frequent causes of admission and death in intensive care units (ICU). Inflammatory phenomenon leading to severe sepsis are multiple and not yet completely understood. The main target damage during severe sepsis is the endothelium. Endocan, specifically secreted by activated-pulmonary vascular endothelial cells, is thought to play a key role in the control of the lung inflammatory reaction. A recent clinical investigation found that a low plasma endocan level was predictive of respiratory failure. In this study, the hypothesis that low levels of endocan may result from proteolysis was tested. We demonstrate that cathepsin G (CG), neutrophil elastase (NE), and to a lesser extent proteinase 3 (PR3), degrade endocan. Interestingly, a novel endocan peptide fragment of 14 kDa, named p14, was identified, resulting from the specific cleavage of endocan by CG, corresponding to the N-terminal 111-116 amino acids of the endocan polypeptide. An immunoassay specific for p14 endocan fragment was then developed, and revealed increased plasma levels of p14 in 20 out of 55 severe septic patients, ranging from 0.52 to 10.40 ng/mL versus undetectable p14 in plasma from 32 control subjects (p=0.0011). No correlations were found between p14 and endocan blood levels in severe septic patients. Taken together, the p14 endocan fragment represents a novel interesting biomarker which could participate to the pathogenesis of sepsis.