The Use of Prophylactic Insulin in Surgical Patients without Diabetes

OBJECTIVE: Determine the feasibility and proof-of-concept of using prophylactic insulin (glucose-insulin-potassium [GIK]) to improve outcomes in non-diabetic (NoDM) surgical patients. SUMMARY BACKGROUND DATA: Perioperative hyperglycemia increases the risk of morbidity/mortality and insulin is used to treat it. Prevention of hyperglycemia with prophylactic insulin may be better than using treatment insulin alone, but feasibility issues need to be addressed before developing a full-scale randomized controlled trial (RCT). METHODS: A pilot RCT of GIK vs placebo among NoDM undergoing major abdominopelvic surgery. Feasibility (willingness to randomize, treatment completion) and clinical outcomes (glycemic control, neutrophil:lymphocyte ratio [NLR], and morbidity/mortality) were measured through 30 days. RESULTS: Of 248 eligible patients, 103 randomized (mean age 56, 54% female) to GIK (n=50) or placebo (n=53). Treatment was completed in 97% without episodes of severe hypoglycemia. Perioperative euglycemia (<125 mg/dL) was more common in the GIK arm (42%) vs control (27%) (P<.01). Hyperglycemia (BG >140 mg/dL) was less common in the GIK arm (37% vs. 48%, P<0.05), as was the use of treatment insulin (26% vs. 45%, aRR 0.6 [95% CI 0.4, 0.9]). The rise in NLR from pre-operative to post-operative day 1 was lower in the GIK group vs placebo (Delta 0.5, 95% CI -6.23 to 3.32). Fewer complications were noted in the GIK arm (12%) vs. control (21%) (aRR 0.5 [95% CI 0.2, 1.5]), albeit wide confidence intervals. CONCLUSION: Prophylactic insulin improves glycemic outcomes and may improve clinical outcomes, possibly in part through anti-inflammatory mechanisms. A full-scale RCT focused on morbidity/mortality endpoints is feasible and would address an important evidence gap.