Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study.

RATIONALE: Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. OBJECTIVES: To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. METHODS: Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. MEASUREMENTS AND MAIN RESULTS: 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. CONCLUSIONS: We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536.

Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study.

Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. To assess soluble receptor for advanced glycation end-products (sRAGE), a marker of lung epithelial injury, as a predictor of ARDS in a high-risk population, adult patients with at least one ARDS risk factor upon admission to participating intensive care units (ICUs) were enrolled in a multicentre, prospective study between June 2014 and January 2015. Plasma sRAGE and endogenous secretory RAGE (esRAGE) were measured at baseline (ICU admission) and 24 hours later (day one). Four AGER candidate single nucleotide polymorphisms (SNPs) were also assayed because of previous reports of functionality (rs1800625, rs1800624, rs3134940, and rs2070600). The primary outcome was ARDS development within seven days. Of 500 patients enrolled, 464 patients were analysed, and 59 developed ARDS by day seven. Higher baseline and day one plasma sRAGE, but not esRAGE, were independently associated with increased ARDS risk. AGER SNP rs2070600 (Ser/Ser) was associated with increased ARDS risk and higher plasma sRAGE in this cohort, although confirmatory studies are needed to assess the role of AGER SNPs in ARDS prediction. These findings suggest that among at-risk ICU patients, higher plasma sRAGE may identify those who are more likely to develop ARDS.

The analgesic effects of a bilateral sternal infusion of ropivacaine after cardiac surgery.

BACKGROUND AND OBJECTIVES: The aim of this study was to assess the effects of a continuous postoperative administration of local anesthetic through 2 catheters placed deeply under fascia at the lateral edges of the sternum, close to the emergence of the intercostal nerves. We focused on pain during mobilization, as this aspect is likely to interact with postoperative morbidity. METHODS: Forty adult patients scheduled for open heart surgery with sternotomy were included in this randomized, placebo-controlled, double-blind study. A continuous fixed-rate infusion of 4 mL/hr of 0.2% ropivacaine or normal saline was administered during the first 48 postoperative hrs. All patients received acetaminophen and self-administered morphine. The efficacy outcomes were as follows: pain score during standardized mobilization and at rest; morphine consumption; spirometry and arterial blood gases; postoperative rehabilitation criteria, and patient satisfaction. Total ropivacaine plasma level was monitored throughout the study. RESULTS: Pain scores were lower in the ropivacaine group during mobilization (P = 0.0004) and at rest (P = 0.0006), but the analgesic effects were mostly apparent during the second day after surgery, with a 41% overall reduction in movement-evoked pain levels. The bilateral sternal block also reduced morphine consumption. It improved the patients' satisfaction and rehabilitation, but no effects were noted on respiratory outcomes. No major adverse effect due to the treatment occurred, but the ropivacaine plasma level was greater than 4 mg/L in 1 patient. CONCLUSIONS: This technique may find a role within the framework of multimodal analgesia after sternotomy, although further confirmatory studies are needed.