Basal-bolus vs sliding-scale insulin for surgical patients: The RABBIT 2 Surgery trial
Does better glucose control in surgical patients affect outcomes in patients undergoing general surgery? To find out, we performed a prospective, multicenter, randomized, open-label trial in general surgery patients not in the ICU.18 We recruited and randomized 211 patients with type 2 diabetes who were on diet therapy or oral hypoglycemic agents or insulin in low doses (< 0.4 U/kg/day).
Oral drugs were discontinued on admission, and patients were randomized to receive either a basal-bolus regimen of glargine plus glulisine or regular insulin on a sliding scale. The basal-bolus group got 0.5 U/kg/day, half of it as glargine once daily and half as glulisine before meals. The total daily dose was reduced to 0.3 U/kg/day in patients age 70 and older or who had a serum creatinine level of 2.0 mg/dL or higher.
The goal was to maintain fasting and pre-meal glucose concentrations between 100 and 140 mg/dL. The total daily dose was raised by 10% (mostly in the glargine dose) if the blood glucose level was in the range of 141 to 180 mg/dL, and by 20% if the glucose level was higher than 181 mg/dL. The dose was decreased by 10% for glucose levels between 70 and 99 mg/dL, was decreased by 20% if the glucose level was between 40 and 69, and was held if the glucose level was lower than 40 mg/dL. If a patient was not able to eat, insulin glulisine was held until meals were resumed.
The sliding-scale group received regular insulin four times a day for blood glucose levels higher than 140 mg/dL.
The primary outcomes measured were the difference between groups in mean daily blood glucose concentration and a composite of hospital complications including postoperative wound infection, pneumonia, respiratory failure, acute renal failure, and bacteremia. Secondary outcomes were differences between groups in mean fasting and pre-meal blood glucose, number of hypoglycemic episodes (blood glucose < 70 mg/dL), hyperglycemic episodes (blood glucose > 200 mg/dL), length of hospital stay, need for intensive care, and rate of complications including wound infection, pneumonia, acute renal failure, and death.
Blood glucose levels were significantly lower in the basal-bolus group through the first 7 days after randomization, as measured before breakfast, lunch, and dinner, and at bedtime, and then they converged.
More patients in the sliding-scale group had hospital complications, 26 vs 9, P = .003. On the other hand, more patients in the basal-bolus group had episodes of hypoglycemia: 24 (23%) vs 5 (4.7%) had episodes of less than 70 mg/dL (P < .001), 12 (12%) vs 2 (1.9%) had episodes of less than 60 mg/dL (P = .005), and 4 (3.8%) vs 0 had episodes of less than 40 mg/dL (P = .057). The mean total daily dose of insulin was 33.4 units in the basal-bolus group and 12.3 units in the sliding-scale group.
WHAT HAVE WE LEARNED?
Don’t use a sliding-scale regimen as a single agent in patients with diabetes. Glycemic control is better with a basal-bolus regimen than with a sliding-scale regimen, and a basal-bolus insulin regimen is preferred for most patients with hyperglycemia.
The old human insulins (ie, regular and NPH) are still good and improve glycemic control as well as the new basal insulin analogues (detemir and aspart) do.
Improved control may reduce the rate of hospital complications, according to preliminary evidence. More studies are under way.
One size does not fit all. Those who are elderly or who have impaired renal function should receive lower doses of insulin, eg, 0.3 U/kg/day instead of 0.5 U/kg/day. Those who are on insulin should have their dose decreased when they are admitted to the hospital. Perhaps lean patients with type 2 diabetes should also have a lower dose.
Most hospitalized patients with diabetes and elevated blood glucose values (or hyperglycemia) should receive subcutaneous insulin treatment with a basal-bolus regimen or a multidose combination of NPH plus regular insulin. Selected patients with severe insulin resistance and persistent hyperglycemia despite subcutaneous insulin may benefit from continuous intravenous insulin infusion.
Patients treated with insulin at home should continue to receive insulin therapy in the hospital. However, the insulin dosage should be reduced by about 25% to allow for lower food intake.
QUESTIONS FOR FURTHER STUDY
Should we modify the standard basal-bolus regimen?
In a typical basal-bolus regimen, patients get 50% of their total daily insulin dose in the form of a basal injection and 50% in the form of rapid-acting boluses before meals. However, for a variety of reasons, hospitalized patients do not eat very much. Thus, a 50-50 basal-bolus regimen may not be ideal for patients with poor oral intake.
In the Basal-PLUS trial, currently under way, we are comparing the safety and efficacy of a daily dose of basal insulin (glargine) plus correction doses of a rapid-acting insulin analogue (glulisine) on a sliding scale and a standard basal-bolus regimen in medical and surgical patients.
Does one glycemic target fit all patients?
Falciglia et al19 found an association between hyperglycemia and death in patients with unstable angina, arrhythmias, stroke, pneumonia, gastrointestinal bleeding, respiratory failure, sepsis, acute renal failure, and congestive heart failure. However, they found no such association in patients with chronic obstructive pulmonary disease, liver failure, diabetic ketoacidosis, gastrointestinal neoplasm, musculoskeletal disease, peripheral vascular disease with bypass, hip fracture, amputation due to peripheral vascular disease, or prostate surgery. Should patients in this second group be treated with a less-intensive insulin regimen?
What is the best regimen after hospital discharge?
We are conducting a prospective clinical trial to assess the impact of insulin after hospital discharge. Our current practice when a patient is discharged from the hospital is as follows:
- If the admission hemoglobin A1c level is less than 7%, we restart the previous outpatient treatment regimen of oral antidiabetic agents, or insulin, or both.
- If the admission hemoglobin A1c is between 7% and 9%, we restart the outpatient oral agents and continue glargine once daily at 50% to 80% of the hospital dose.
- If the hemoglobin A1c level is higher than 9%, we discharge the patient on a basal-bolus regimen at the same dosage as in the hospital. As an alternative, we could restart the oral agents and add glargine once daily at 80% of the hospital dose.