Traumatic brain injury (TBI) is the leading cause of death and disability among all trauma-related injuries globally.1 One-third to half of trauma-related deaths are primarily caused by TBI, affecting 15–20/100,000 individuals annually.1 Severe traumatic brain injury (sTBI) accounts for 8% of all TBI worldwide, with approximately 5.48 million people suffering from severe traumatic brain injury annually.1 Hyperglycaemia frequently occurs in the early stages following TBI and is associated with adverse outcomes, potentially through promoting oxidative stress pathways and inducing neuroinflammation.2 However, glucose is the main energy source for brain cells, and hypoglycaemia exacerbates critical neurocognitive dysfunction and exerts a strong dose-dependent effect on the mortality rate of critically ill patients.2 The optimal blood glucose target for patients with sTBI therefore remains largely unclear.2, 3 At the beginning of this century, intensified insulin therapy was reported to improve the prognosis of critically ill patients by maintaining blood glucose levels at 4.4–6.1 mmol/L.4 However, the 2009 NICE-SUGAR study suggested that intensified insulin therapy did not improve prognosis but increased the incidence of hypoglycemia.5 In 2018, a review of blood glucose control for TBI reached similar conclusions.2 The latest brain microdialysis research suggests that insulin indeed lowers blood glucose and that the intensified blood glucose control method is associated with brain energy crisis in TBI patients and the deterioration of their prognosis.6 Therefore, the current blood glucose control target for sTBI patients mainly adheres to the recommendations of the American Diabetes Association, which is to control blood glucose levels between 7.8 and 10 mmol/L.2, 5, 7

For critically ill patients, continuous intravenous insulin infusion is the most effective method for achieving glycaemic targets. Paper-based or electronic protocols can be used for glucose management, but there is still a lack of standardized insulin infusion plans worldwide, and the same applies to sTBI patients.7 Computer-based insulin infusion protocols have shown advantages by calculating insulin doses based on current glucose levels and trends, but such commercial options are expensive and complex to operate and have not been widely used.8 Many classical paper-based protocols have been designed, each with advantages and disadvantages. The four most common types are the Yale protocol, Leuven protocol, SPRINT protocol, and NICE-SUGAR protocol.5, 9, 10 The blood glucose targets of the first three protocols are low and require insulin loading, which can easily cause hypoglycemia,9, 10 although some studies suggest that the Yale protocol is associated with better outcomes in certain patient populations.9 The NICE-SUGAR protocol, or Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation, is designed to maintain normoglycaemia in critically ill patients through relatively loose glucose targets and lower monitoring frequency, potentially posing risks of hyperglycaemia (Supplementary Material 1). In contrast, the Yale protocol, emphasizing precision in blood glucose control, employs insulin loading to achieve lower glucose levels in critically ill individuals and has been associated with better outcomes in specific patient populations (Supplementary Material 2). However, during the acute phase of traumatic brain injury, certain nutritional support characteristics, such as high energy demands in the early stages of trauma, can increase resting energy consumption by 1–2 times the baseline prediction. Patients with sTBI may remain in a coma for a long time, and while their gastrointestinal tract is relatively intact, it may have reduced motility, requiring early and continuous enteral nutrition support.11 This requires early, adequate, and continuous insulin infusion and the development of an insulin infusion plan tailored to the characteristics of TBI. To our knowledge, this is the first study report to introduce a convenient and safe paper-based insulin infusion protocol that applies to sTBI patients, combining the advantages of the NICE-SUGAR and Yale protocols.