Objective To determine whether inclusion of glutamine, selenium, or both in a standard isonitrogenous, isocaloric preparation of parenteral nutrition influenced new infections and mortality among critically ill patients. Design Randomised, double blinded, factorial, controlled trial. Setting Level 2 and 3 (or combined) critical care units in Scotland. All 22 units were invited, and 10 participated. Participants 502 adults in intensive care units and high dependency units for ≥48 hours, with gastrointestinal failure and requiring parenteral nutrition. Interventions Parenteral glutamine (20.2 g/day) or selenium (500 μg/day), or both, for up to seven days. Main outcome measures Primary outcomes were participants with new infections in the first 14 days and mortality. An intention to treat analysis and a prespecified analysis of patients who received ≥5 days of the trial intervention are presented. Secondary outcomes included critical care unit and acute hospital lengths of stay, days of antibiotic use, and modified SOFA (Sepsisrelated Organ Failure Assessment) score. Results Selenium supplementation did not significantly affect patients developing a new infection (126/251 v 139/251, odds ratio 0.81 (95% CI 0.57 to 1.15)), except for those who had received ≥5 days of supplementation (odds ratio 0.53 (0.30 to 0.93)). There was no overall effect of glutamine on new infections (134/250 v 131/ 252, odds ratio 1.07 (0.75 to 1.53)), even if patients received ≥5 days of supplementation (odds ratio 0.99 (0.56 to 1.75)). Six month mortality was not significantly different for selenium (107/251 v 114/251, odds ratio 0.89 (0.62 to 1.29)) or glutamine (115/250 v 106/252, 1.18 (0.82 to 1.70)). Length of stay, days of antibiotic use, and modified SOFA score were not significantly affected by selenium or glutamine supplementation. Conclusions The primary (intention to treat) analysis showed no effect on new infections or on mortality when parenteral nutrition was supplemented with glutamine or selenium. Patients who received parenteral nutrition supplemented with selenium for ≥5 days did show a reduction in new infections. This finding requires confirmation. Trial registration Current Controlled Trials ISRCTN87144826INTRODUCTION Infection and sepsis are major causes of increased mortality, morbidity, and resource use in intensive care units. They are associated with both illness and drug related impairment of the immune system, compounded by malnutrition often observed in patients admitted to critical care. 1The enteral feeding route is preferred for critically ill patients because of its reduced costs and risk of infective complications.2 Parenteral nutrition, however, has an important role because many intensive care patients have gastrointestinal dysfunction. 3Recent systematic reviews have suggested that parenteral administration of glutamine to critically ill patients reduces mortality (risk ratio 0.71 (95% confidence interval 0.55 to 0.92)) and new infections (risk ratio 0.76 (0.62 to 0.93)). 4 Selenium supplementati...

When given in an equimolar, rapid, intravenous infusion, HSD reduces intracranial pressure more effectively than mannitol.

BackgroundTraumatic brain injury is a major cause of death and severe disability worldwide with 1,000,000 hospital admissions per annum throughout the European Union.Therapeutic hypothermia to reduce intracranial hypertension may improve patient outcome but key issues are length of hypothermia treatment and speed of re-warming. A recent meta-analysis showed improved outcome when hypothermia was continued for between 48 hours and 5 days and patients were re-warmed slowly (1°C/4 hours). Previous experience with cooling also appears to be important if complications, which may outweigh the benefits of hypothermia, are to be avoided.Methods/designThis is a pragmatic, multi-centre randomised controlled trial examining the effects of hypothermia 32-35°C, titrated to reduce intracranial pressure <20 mmHg, on morbidity and mortality 6 months after traumatic brain injury. The study aims to recruit 1800 patients over 41 months. Enrolment started in April 2010.Participants are randomised to either standard care or standard care with titrated therapeutic hypothermia. Hypothermia is initiated with 20-30 ml/kg of intravenous, refrigerated 0.9% saline and maintained using each centre's usual cooling technique. There is a guideline for detection and treatment of shivering in the intervention group. Hypothermia is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to maintain intracranial pressure <20 mmHg. Intracranial hypertension is defined as an intracranial pressure >20 mmHg in accordance with the Brain Trauma Foundation Guidelines, 2007.DiscussionThe Eurotherm3235Trial is the most important clinical trial in critical care ever conceived by European intensive care medicine, because it was launched and funded by the European Society of Intensive Care Medicine and will be the largest non-commercial randomised controlled trial due to the substantial number of centres required to deliver the target number of patients. It represents a new and fundamental step for intensive care medicine in Europe. Recruitment will continue until January 2013 and interested clinicians from intensive care units worldwide can still join this important collaboration by contacting the Trial Coordinating Team via the trial website http://www.eurotherm3235trial.eu.Trial registrationCurrent Controlled Trials ISRCTN34555414