Brintha Naidu

sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy

IntroductionHyperglycemia represents an independent prognostic factor in critically ill non-diabetic patients but not in those with diabetes. In this context, there is an ongoing debate on the benefit of an intensive insulin therapy, particularly in diabetic patients. We tested the hypothesis that expression of the receptor for advanced glycation end-products (RAGE), an important signal transduction receptor that elicits long-lasting nuclear factor kappa B (NF-κB) activation, may underlie this difference. RAGE expression is regulated by multiple ligands, including high mobility group box-1 (HMGB-1), and is reflected by its released soluble form (sRAGE).MethodsA predesigned analysis was conducted of prospectively collected samples from 76 hyperglycemic critically ill patients (33 type-2 diabetes, 43 non-diabetes) aged ≥18 years with blood glucose of > 6.1 mmol/L enrolled in a randomized controlled trial comparing intensive insulin therapy with conventional insulin therapy. sRAGE and its ligand HMGB-1 together with IL-6, and soluble thrombomodulin (as markers of inflammation and endothelial cell injury, respectively) were evaluated in ICU, at Days 1, 3, 5 and 7. Plasma samples from 18 healthy subjects were used as controls.ResultsBoth diabetic and non-diabetic hyperglycemic patients showed increased plasma sRAGE, HMGB-1 and soluble thrombomodulin levels at the time of admission to ICU. Plasma IL-6 concentration was only increased in non-diabetic patients. Plasma levels of sRAGE were higher in diabetic compared with non-diabetic patients. Intensive insulin therapy resulted in a significant decrease of sRAGE and thrombomodulin at Day 7, in diabetic but not in non-diabetic patients. Circulating sRAGE levels correlated positively with IL-6 and soluble thrombomodulin levels and inversely with HMGB-1. Multivariate regression analysis demonstrated that sRAGE remains independently correlated with HMGB-1 only in diabetic patients. Neither sRAGE nor any inflammatory markers are associated with mortality.ConclusionsThese findings support the hypothesis that sRAGE release, time-course and response to intensive insulin therapy differ between hyperglycemic diabetic and non-diabetic critically ill patients. Whether this difference underlies the dissimilarity in clinical outcome of hyperglycemia in these two conditions warrants further studies.

A multifaceted approach to improve hand hygiene practices in the adult intensive care unit of a tertiary-care center

A multidisciplinary team was formed to improve hand hygiene (HH) practices in a tertiary-care ICU. At baseline, an audit revealed that the overall HH compliance was 64% and was significantly lower at night than during the day shift. After implementing a stepwise multifaceted approach that included education, workplace reminders, active feedback and later universal contact precautions, the HH compliance improved significantly to >80%, and the improvement was sustained over several months. This improvement was noted during the day and night and affected different healthcare workers as well as visitors.

Computerized physician order entry of a sedation protocol is not associated with improved sedation practice or outcomes in critically ill patients.

BackgroundComputerized Physician Order Entry (CPOE) analgesia-sedation protocols may improve sedation practice and patients’ outcomes. We aimed to evaluate the impact of the introduction of CPOE protocol.MethodsThis was a prospective, observational cohort study of adult patients receiving mechanical ventilation, requiring intravenous infusion of analgesics and/or sedatives, and expected to stay in the intensive care unit (ICU) ≥24xa0h. As a quality improvement project, the study had three phases: phase 1, no protocol, July 1st to September 30th, 2010; phase 2, post implementation of CPOE protocol, October 1st to December 31st, 2010; and phase 3, revised (age, kidney and liver function adjusted) CPOE protocol, August 1st to October 31st, 2011. Multivariate analyses were performed to determine the independent predictors of mortality.ResultsTwo hundred seventy nine patients were included (no protocolu2009=u200991, CPOE protocolu2009=u200997, revised CPOE protocolu2009=u200991). Implementation of CPOE protocol was associated with increase of the average daily dose of fentanyl (3720u2009±u20093286 vs. 2647u2009±u20092212 mcg/day; pu2009=u20090.009) and decrease of hospital length of stay (40u2009±u200937 vs. 63u2009±u200985xa0days, pu2009=u20090.02). The revised CPOE protocol was associated with, compared to the CPOE protocol, a decrease of the average daily dose of fentanyl (2208u2009±u20092115 vs. 3720u2009±u20093286 mcg/day, pu2009=u20090.0002) and lorazepam (0u2009±u20090 vs. 0.06u2009±u20090.26xa0mg/day, pu2009=u20090.04), sedation-related complications during ICU stay (3.3xa0% vs. 29.9xa0%, p <0.0001), and ICU mortality (18xa0% vs. 39xa0%, pu2009=u20090.001). The impact of the revised CPOE protocol was more evident on patients aged >70xa0years or with severe kidney or liver impairment. Both the original CPOE protocol and the revised CPOE protocol were not independent predictors of ICU (adjusted odds ratio [aOR]u2009=u20091.85, confidence interval [CI]u2009=u20090.90–3.78; pu2009=u20090.09; aORu2009=u20090.70, CIu2009=u20090.32–1.53, pu2009=u20090.37; respectively) or hospital mortality (aORu2009=u20091.12, CIu2009=u20090.57–2.21, pu2009=u20090.74; aORu2009=u20090.80, CIu2009=u20090.40–1.59, pu2009=u20090.52; respectively).ConclusionsThe implementation of a CPOE analgesia-sedation protocol was not associated with improved sedation practices or patients’ outcome but with unpredicted increases of an analgesic dose. However, the revised CPOE protocol (age, kidney and liver function adjusted) was associated with improved sedation practices. This study highlights the importance of carefully evaluating the impact of changes in practice to detect unanticipated outcomes.