Computerization of the Yale insulin infusion protocol and potential insights into causes of hypoglycemia with intravenous insulin

Diabetes Technol Ther. 2013 Mar;15(3):246-52. doi: 10.1089/dia.2012.0277. Epub 2013 Jan 4.


Background: The management of critically ill hyperglycemic patients in the intensive care unit (ICU) has been fraught with recent controversy. Only one randomized trial has demonstrated a mortality benefit to intensive glycemic control, with all subsequent studies failing to confirm this benefit and revealing a markedly increased risk of severe hypoglycemia (SH) in intensively treated patients. In most of these trials, adherence to the protocols were neither tracked nor reported.

Methods: A retrospective analysis of all patients admitted to an ICU who were treated with an insulin infusion directed by the GlucoCare™ IGC System, an FDA-cleared insulin-dosing calculator (Yale 100-140 mg/dL protocol). Mean blood glucose (BG) levels, time to target range and incidence of SH (<40 mg/dL) and moderate hypoglycemia (MH) (40-69 mg/dL) were determined, and potential causes of hypoglycemic episodes were assessed.

Results: Mean post-target BG was approximately 123 mg/dL. Of >55,000 readings in 1,657 patients, overall incidence of SH was 0.01% of readings and 0.3% of patients. MH occurred in 1.1% of readings and 17.6% of patients. The top potential causes of MH were: (1) Protocol-directed recommendations including continuation of insulin with BG <100 mg/dL and decreases in the frequency of BG checks (63.7%), and (2) Staff non-adherence to protocol directives (15.3%).

Conclusions: The results of the GlucoCare-directed Yale 100-140 mg/dL protocol experience revealed an extremely low incidence of SH and an incidence of MH of 1.1%. The incidence of SH in this study was lower than the control group of the NICE-SUGAR study and are supportive of the new Society of Critical Care guidelines to target BG levels of 100-150 mg/dL in critically ill patients. Further refinements to the original protocol and emphasis on staff adherence to protocol directives could potentially further reduce these very low hypoglycemia rates.

MeSH terms

  • Algorithms
  • Blood Glucose / metabolism*
  • Critical Care / organization & administration
  • Critical Care / standards
  • Critical Illness
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / epidemiology
  • Drug Therapy, Computer-Assisted* / methods
  • Female
  • Glycated Hemoglobin A / metabolism*
  • Guideline Adherence / statistics & numerical data
  • Humans
  • Hypoglycemia / chemically induced*
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Incidence
  • Insulin / administration & dosage*
  • Insulin / adverse effects
  • Insulin Infusion Systems
  • Male
  • Patient Care Team / organization & administration*
  • Retrospective Studies
  • United States / epidemiology


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human