The Augmented Versus Routine Approach to Giving Energy Trial: A Randomised Controlled Trial

Brief Summary

Detailed Description

Each year around 130,000 Australians are admitted to ICU at a daily cost of approximately $4000 per patient. Their care consumes close to 3 billion dollars per year. These critically ill patients are the sickest in the hospital. They require substantial resources and multiple interventions. Some die and many of those who survive have delayed and compromised functional recovery which can persist for months or years. Nutrition therapy is an essential standard of care for all ICU patients who are mechanically ventilated and remain in ICU for more than a few days. Enteral nutrition (via a nasogastric tube) is usually initiated within 24 hours of ICU admission with a formula containing 1 kcal/ml and prescribed at an approximate rate of 1 ml/kg/hour. However, standard enteral nutrition practice typically results in the delivery of only \~60% of the full-recommended calorie requirement. Although prescribed calories can reliably be delivered using the intravenous route, the enteral route is preferred for a number of reasons and is recommended by all nutrition guidelines as first-line therapy. In particular, enteral nutrition is more physiological, less costly and associated with fewer infective complications. Delivery of nutrient into the gut also has beneficial effects on subsequent gut function and may reduce ongoing sepsis which can be fuelled by the movement of gut flora through a permeable mucosa that has not been exposed to nutrient. Intravenous nutrition is accordingly, generally used only when enteral feeding is impossible, or persistently limited. Although supplementing enteral with intravenous nutrition can increase calorie delivery, this has not been shown to have a therapeutic benefit and may worsen important clinical outcomes. This may be because adverse effects associated with intravenous nutrition counteract the benefits of increased calorie delivery. Previous trials support the concept that optimising nutrition in the critically ill will improve outcome, however, the evidence is limited, inclusive and generally of low quality. It is extraordinary that there is not better (Level I) evidence to inform nutrition management in critically ill patients given the frequency of the intervention, the biologic rationale, the high mortality following ICU admission, the frequency of muscle wasting and the poor functional outcomes in survivors. This is especially true given the low cost of enteral nutrition (\~$23/day). The investigators recently completed pilot study clearly achieved all the key criteria which, for a pharmaceutical product, would lead to a phase III trial, namely: 1. feasibility; 2. safety; 3. separation; 4. excellent recruitment rate; 5. successful blinding; 6. a signal for benefit. A definitive study must now be done to establish whether 90-day survival and functional outcomes following critical illness may be improved by increased calorie delivery.

Primary Outcomes

Secondary Outcomes

• Time from randomisation until death(Day 180)
• Mortality(Day 180)
• Cause-specific mortality(Day 90)
• Number of days alive and not in ICU(Day 28)
• Number of days alive and not in hospital(Day 28)
• Quality of life assessment(Day 180)
• Functional outcomes for patients 65 years and over living independently(Day 180)
• Ventilator free days(Day 28)
• Vasopressor free days(Day 28)
• Proportion of patients receiving any renal replacement therapy(Day 28)
• Renal replacement therapy free days(Day 28)
• Functional outcomes for patients under 65 years in the work force(Day 180)
• Functional outcomes for patients under 65 years and not in the work force and patients 65 years and over living dependently(Day 180)
• Proportion of patients receiving vasopressor support(Day 28)
• Proportion of patients with positive blood cultures(Day 28)
• Proportion of patients requiring intravenous antimicrobials(Day 28)