Timing Of Nutrition In emergenCy laparotomy (TONIC) – A randomised trial comparing early parenteral nutrition vs standard nutritional care in adults undergoing emergency laparotomy.

Research Question Following Emergency Laparotomy, does early nutritional support with parenteral nutrition reduce complication frequency and severity compared to standard nutritional strategies? Background Emergency laparotomy refers to major surgery to treat intra-abdominal pathology such as intestinal obstruction, perforation, and infection. This is performed for around 21,000 people each year in England and Wales. It is associated with complication rates of up to 47%, & a 90 day mortality rate of 9.6%. Outcomes have not improved from these levels over several years. Malnutrition is a key driver of poor outcomes in surgery, affecting >30% of patients admitted. Following surgery, patients may have gastrointestinal dysfunction and be unable to eat or drink, meaning nutrition must be delivered through a parenteral route. Management of nutrition is highly variable in the emergency setting. No high quality definitive randomised trial has assessed the impact of early nutrition in a purely emergency general surgery population. Aims and objectives To conduct a randomised controlled trial to assess the impact of early parenteral nutrition (PN) on complication frequency and severity following emergency laparotomy. Methods Overview: A pragmatic randomised controlled trial. Inclusion criteria: Adult patients undergoing any National Emergency Laparotomy Audit (NELA) eligible procedure. No abdominal surgery in preceding 30 days. Intervention/Comparator: early PN within 48 hours of surgery, or ‘standard care’ in line with NICE CG32 which recommends PN should be started when a patient has gone 5 days without eating and drinking normally. Participants will be randomised prior to surgery to allow preparation of PN prescriptions and access to feeding lines (which can be placed in theatre if needed). Outcomes: The primary outcome is complication severity & frequency measured by the Comprehensive Complication Index (CCI). Participants will be followed up at discharge (primary timepoint), 30, & 90 days post-surgery where complications, functional assessments, and PROMS (EQ-5D-5L, Quality of Recovery-15, Gastrointestinal Recovery PROM (PRO-diGI)) will be captured. Pilot: An internal pilot will be conducted across 5 sites to assess feasibility according to defined stop-go criteria. Sample size: Based on a 6 point reduction in the CCI, allowing for up to 5% attrition and 90% power, a sample size of 449 participants in each arm is required (total 898). Analysis: CCI will be analysed on an intention to treat basis using linear regression with bootstrapped confidence intervals with arm and stratification factors as covariates. Health economic models will be developed to assess cost effectiveness at 90-days and to a year. Registration & governance: The study will be entered into a clinical trial registry. Ethical approvals will be secured prior to study commencement. An external steering committee and data monitoring committee will be established. Timelines for delivery 48 month project duration: 12m setup; 27m recruitment (first 6m are internal pilot); 3m follow-up; 6m close-out, analysis and write-up. Anticipated impact and dissemination If this study demonstrates benefit from early PN, it will lead to an implementable change in emergency surgery. We will share findings with policy makers & specialty associations, and through peer reviewed publication & conference presentation.