SAN DIEGO – An updated version of the Yale Insulin Infusion Protocol for intensive care unit management of hyperglycemia provided effective and safe targeted blood glucose control in compliance with national guidelines among 115 patients in Yale’s medical ICU.

Yale–New Haven (Conn.) Hospital has used a standardized intravenous insulin infusion protocol (IIP) in its medical ICU since 2003. The initial glucose target was 100-140 mg/dL, based on a 2001 study demonstrating the benefits of glycemic control in that range among critically ill patients (N. Engl. J. Med. 2001;345:1359-67). In 2005, the target was further lowered to 90-120 mg/dL. Both of those protocols were validated and published, and are used in many U.S. hospitals, said Dr. Shilpa Shetty, an academic hospitalist at Griffin Hospital, Derby, Conn., an affiliate of Yale–New Haven Hospital.

A change was prompted in 2009, when the Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study demonstrated significantly increased mortality among ICU patients undergoing intensive insulin therapy (N. Engl. J. Med. 2009;360:1283-97). Following that, the American Association of Clinical Endocrinologists and the American Diabetes Association issued a joint consensus statement endorsing a less stringent blood glucose target of 140-180 mg/dL in critically ill patients (Endocr. Prac 2009;15:353-69).

Subsequently, the Yale Protocol was revised yet again to a target blood glucose range of 120-160 mg/dL. That range was chosen because the AACE/ADA consensus statement had said that there might be additional benefit in keeping patients at the lower end of the recommended 140-180 mg/dL range, and with prior validated protocols the median blood glucose values always ended up at the upper end of the target range.

"We expected to stay at the lower end of the AACE/ADA target, which we did," Dr. Shetty said in an interview.

In the current study, clinical responses to the first 115 drips using the latest revised protocol were tracked for validation at Yale–New Haven Hospital. Minimal inservicing was required, since the nurses were already fully trained in the previous protocols. The protocol was triggered when a registered nurse identified a patient with two blood glucose values above 180 mg/dL.

The responsible physician then placed the order for the drip. Insulin was delivered via infusion pumps in 0.5 units/hour increments, with bolus and initial infusion rates determined by a formula based on the patient’s blood glucose value. While on the infusion, the protocol specifies that the patients’ blood glucose be checked hourly until glucose levels stabilize – defined as three consecutive values in target range – at which point the checks could be done less frequently.

Data were collected during September 2009 through January 2010. The 115 consecutive insulin infusions included 17 patients who were placed on the drip more than once. The patients had a mean age of 62 years, with a mean body mass index of 31.8 kg/m². About half (51%) were male, 65% were white, 17% black, 13% Hispanic, and 5% Asian. Two-thirds (64%) had a prior diagnosis of diabetes, and 44% had been using insulin at home prior to entering the ICU.

Admitting diagnoses included acute respiratory failure in 29%, sepsis in 25%, and bacterial pneumonia in 11%. Mean length of ICU stay was 19.5 days, and hospital stay, 36.4 days. The mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score – a well-validated severity of illness scoring system that predicts mortality with a 0-71 scale – was 24 (higher numbers mean worse prognosis). In NICE-SUGAR, the mean APACHE score was 21, compared with 9 for the 2001 study that led to the original Yale Protocol, Dr. Shetty noted.

Starting at a mean pre-infusion blood glucose of 306.1 mg/dL, the infusion brought the blood glucose down to a mean of 155.9 mg/dL once the target of less than 160 mg/dL was reached, in a mean of 8.3 hours. During the infusion, the mean nadir glucose value was 92.5 mg/dL. Patients spent a mean of 95 hours on the infusion, with a mean infusion dose of 3.9 units per hour. Once the target was achieved, the protocol maintained 42% of subsequent blood glucose values within the target 120-160 mg/dL, and 76% were less than 180 mg/dL, she reported.

Hypoglycemia was rare. Of a total 8,272 recorded blood glucose readings, just 0.3% were less than 70 mg/dL, and 0.02% were below 40 mg/dL. No deleterious effects attributable to low blood sugar were noted. These low rates of hypoglycemia were comparable to prior Yale ICU protocols. The proportion of patients experiencing blood glucose values of 40 mg/dL or less was just 1.7%, compared with a mean 2.1% in seven previous insulin infusion studies, she noted.

The new Yale protocol was "readily accepted and easily implemented by the medical ICU nursing staff, and can be easily implemented by hospitals that are currently utilizing one of the original Yale protocols," Dr. Shetty concluded.

Dr. Shetty stated that she has no conflicts of interest.

Revised Yale ICU Protocol Maintains Target Glycemia