One single dose of etomidate negatively influences adrenocortical performance for at least 24 h in children with meningococcal sepsis

Objective: To investigate the effect of one single bolus of etomidate used for intubation on adrenal function in children with meningococcal sepsis. Design: Retrospective study conducted between 1997 and 2004. Setting: University-affiliated paediatric intensive care unit (PICU). Patients and participants: Sixty children admitted to the PICU with meningococcal sepsis, not treated with steroids. Interventions: Adrenal hormone concentrations were determined as soon as possible after PICU admission, and after 12 h and 24 h. To assess disease severity, PRISM score and selected laboratory parameters were determined. Measurements and main results: On admission, before blood was drawn, 23 children had been intubated with etomidate, 8 without etomidate and 29 were not intubated. Children who were intubated had significantly higher disease severity parameters than those not intubated, whereas none of these parameters significantly differed between children intubated with or without etomidate. Children who received etomidate had significantly lower cortisol, higher ACTH and higher 11-deoxycortisol levels than those who did not receive etomidate. Arterial glucose levels were significantly lower in children who were intubated with etomidate than in non-intubated children. When children were intubated with etomidate, cortisol levels were 3.2 times lower for comparable 11-deoxycortisol levels. Eight children died, seven of whom had received etomidate. Within 24 h cortisol/ACTH and cortisol/11-deoxycortisol ratios increased significantly in children who received etomidate, but not in children who did not, resulting in comparable cortisol/ACTH ratios with sti

Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups (P=0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo (P=0.061 for intent-to-treat population). The primary reason for not completing treatment was > or =1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P<0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76+/-0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78+/-0.76 to 80 mm, P=0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm(3), respectively; P=0.16 to 0.72). CONCLUSIONS: Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae

Serum lipids and disease severity in children with severe meningococcal sepsis.

Contains fulltext : 48167.pdf (publisher's version ) (Closed access)OBJECTIVE: To evaluate the role of cholesterol and lipoproteins in children with severe meningococcal sepsis. DESIGN: Retrospective observational study. SETTING: A university-affiliated pediatric intensive care unit. PATIENTS: Fifty-seven patients admitted to the pediatric intensive care unit with meningococcal sepsis or septic shock. INTERVENTIONS: Total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) concentrations were measured in serum samples drawn within 6 hrs after admission to the pediatric intensive care unit and 12, 24, 48, 72 hrs, 7 days, and 1-3 months afterward. Standard deviation scores of these variables (sd scores) were calculated to correct for age-related differences. To assess disease severity, the Pediatric Risk of Mortality (PRISM) score, the Sepsis-related Organ Failure Assessment (SOFA) score, and the Disseminated Intravascular Coagulation (DIC) score were determined as well as selected laboratory variables. MEASUREMENTS AND MAIN RESULTS: Ten patients died. Total serum cholesterol on admission was very low in all patients. This hypocholesterolemia was caused by low HDL concentrations but in particular by low LDL cholesterol levels. Eight patients had undetectable LDL levels on admission. Total cholesterol levels were significantly lower in nonsurvivors than in survivors (0.97 vs. 1.60, p = .013), whereas levels of LDL and HDL did not significantly differ between both groups. Total cholesterol sd scores were similar between survivors and nonsurvivors. Within survivors, cholesterol sd score was significantly lower in patients with shock compared with those with sepsis. The total cholesterol, HDL, and LDL levels correlated with clinical variables of disease severity and with levels of cytokines. Total cholesterol, HDL, and LDL levels normalized rapidly in survivors and were completely normal 1-3 months after admission. CONCLUSIONS: Extremely low levels of total serum cholesterol, HDL, and LDL are found in the initial phase of children with severe meningococcal disease. Total cholesterol levels are significantly lower in nonsurvivors than in survivors, but not the sd score. Total cholesterol, HDL, and LDL levels on admission are inversely associated with disease severity. Hypocholesterolism is associated with hypocortisolism. The concentrations of total cholesterol and lipoproteins steadily increase after 24 hrs in survivors and are normalized 1-3 months after pediatric intensive care unit admission