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author:("Brits, piette")
1.  Etomidate and mortality in cirrhotic patients with septic shock 
Background
Clinical effects and outcomes of a single dose etomidate prior to intubation in the intensive care setting is controversial. The aim of this study is to evaluate the association of a single dose effect of etomidate prior to intubation on the mortality of septic cirrhotic patients and the impact of the subsequent use of low dose hydrocortisone.
Methods
This is a nested-cohort study within a randomized double blind placebo controlled study evaluating the use of low dose hydrocortisone in cirrhotic septic patients. Cirrhotic septic patients ≥ 18 years were included in the study. Patients who received etomidate prior to intubation were compared to those who did not receive etomidate for all cause 28-day mortality as a primary outcome.
Results
Sixty two intubated patients out of the 75 patients randomized in the initial trial were eligible for this study. Twenty three of the 62 intubated patients received etomidate dose prior to intubation. Etomidate use was not associated with all cause 28-day mortality or hospital mortality but was associated with significantly higher ICU mortality (91% vs. 64% for etomidate and controls groups, respectively; p = 0.02). Etomidate patients who received subsequent doses of hydrocortisone required lower doses of vasopressors and had more vasopressor-free days but no improvement in mortality.
Conclusions
In this group of septic cirrhotic patients with very high mortality, etomidate increased ICU mortality. Subsequent use of hydrocortisone appears to have no benefit beyond decreasing vasopressor requirements. The lowest mortality was observed in patients who did not receive etomidate but received hydrocortisone.
doi:10.1186/1472-6904-11-22
PMCID: PMC3295685  PMID: 22208901
2.  sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy 
Critical Care  2011;15(4):R203.
Introduction
Hyperglycemia 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).
Methods
A 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.
Results
Both 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.
Conclusions
These 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.
doi:10.1186/cc10420
PMCID: PMC3387645  PMID: 21871056

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