The Use of Prophylactic Insulin in Surgical Patients Without Diabetes: A Pilot Randomized, Controlled Trial

Determine the feasibility and proof-of-concept of using prophylactic insulin [glucose-insulin-potassium (GIK)] to improve outcomes in nondiabetic (NoDM) surgical patients.

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).

A pilot RCT of GIK versus placebo among nondiabetic undergoing major abdominopelvic surgery. Feasibility (willingness to randomize, treatment completion) and clinical outcomes (glycemic control, neutrophil:lymphocyte ratio, and morbidity/mortality) were measured through 30 days.

Of 248 eligible patients, 103 were 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%) versus the control (27%) ( P <0.01). 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%, Absolute Risk Reduction (aRR) 0.6 [95% CI: 0.4, 0.9]). The rise in neutrophil:lymphocyte ratio from preoperative to postoperative day 1 was lower in the GIK group versus placebo (Delta 0.5, 95% CI: -6.23 to 3.32). Fewer complications were noted in the GIK arm (12%) versus control (21%) (aRR 0.5 [95% CI: 0.2, 1.5]), albeit with wide CIs.

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.