Intensive Care Unit Insulin Delivery Algorithms: Why So Many? How to Choose?

Abstract

OBJECTIVE: Studies showing improved outcomes with tight glycemic control in the intensive care unit (ICU) have resulted in a substantial number of new insulin delivery algorithms being proposed. The present study highlights mechanisms used in the better-known approaches, examines what might be critical differences among them, and uses systems theory to characterize the conditions under which each can be expected to perform best. METHODS: Algorithm dose (DeltaI/DeltaG) and step (response to a persistent elevation in glucose) response curves were calculated for written instruction algorithms, developed at the Providence Heart and Vascular Institute (Portland [P] protocol), the University of Washington (UW), and Yale University (Y), together with similar curves for the Glucommander (GM) and proportional integral derivative (PID) computer algorithms. From the simulated curves, different mechanisms used to adjust insulin delivery were identified. RESULTS: All algorithms increased insulin delivery in response to persistent hyperglycemia, but the mechanism used altered the algorithm's sensitivity to glucose, or gain, in the GM, UW, and Y protocols, while leaving it unchanged for the P protocol and PID algorithm. CONCLUSIONS: The increase in insulin delivery in response to persistent hyperglycemia observed with all the algorithms can be expected to bring subjects who respond to insulin to targeted glucose ranges. However, because the PID and P protocols did not alter the insulin delivery response curves, these algorithms can be expected to take longer to achieve target glucose levels in individuals who are insulin resistant and/or are exposed to increased carbohydrate loads (e.g., glucose infusions). By contrast, the GM, UW, and Y algorithms can be expected to adapt to the insulin resistance such that the time to achieve target levels is unchanged if the time for insulin to act does not change. If the insulin resistance is accompanied by a longer time for insulin to act, the UW, Y, and GM algorithms may increase the risk of hypoglycemia. Under these conditions, the longer time required for the PID and P protocols to achieve a target glucose level may be a reasonable trade-off for no increase in the risk of hypoglycemia.

Figure 1.

(A) Insulin delivery rate (initial recommendation) for the UW (blue), P (green), and Y (red) protocols at varying initial glucose values. The P and UW protocols curve upward with increasing glucose level (solid curves show polynomial fits), whereas the Y protocol increases linearly (straight line fit). (B) Recommended change in infusion rate for each protocols, assuming that the subject begins therapy at 180 mg/dl but with a subsequent blood glucose reading the same or decreased. Dotted line corresponds to a starting rate of 2 IU/h.

Figure 2.

(A) Graphical representation of the different sliding scales used in the UW protocol. Solid curves indicate polynomial fits. (B) Algorithm gain (ΔI/ΔG) as glucose increases from 135 to 315 mg/dl along the Algorithm 3 curve (left bars, blue) and as glucose remains fixed at 195 mg/dl, but the curve changes from Algorithm 1 to Algorithm 4 (right bars).

Figure 3.

(A) Incremental changes in insulin used by the P protocol in response to the prevailing glucose. For glucose above target (dashed vertical line) the change is proportional to glucose (solid line, 0.01 IU/h per mg/dl with r² = 1) but double that when glucose is below target (solid circle, −0.5 IU/h for a drop or 25 mg/dl = 0.02 IU/h per mg/dl). (B) Adjustments in the increment based on the rate of change of glucose calculated for different glucose ranges (symbols). Within each range, the adjustment is approximately proportional to rate of change (0.03 IU/h per mg/dl per h with slope common to all lines and r² = 0.97) but with the target rate of change (X-intercept) increasing from 0 in the glucose range of 65 and 120 to 75 mg/dl per h in the range of 181 and 240 mg/dl.

Figure 4.

(A) Incremental changes in insulin for the Y protocol (data to left of split axis). Solid line indicates that the change is approximately proportional to glucose for values up to ∼150 mg/dl, but values higher than 150 mg/dl (open squares) produces the same incremental change (1Δ). Curves to the right of the split axis show adjustments made based on the rate of change of glucose (0.025Δ per mg/dl per h, with slope common to all glucose ranges). (B) Change in magnitude of the increment (Δ) based on current insulin delivery rate (symbols) with corresponding quadratic polynomial fit (solid curve).

Figure 5.

Recommended insulin delivery rates for the P, UW, and Y algorithms assuming a subject initiates therapy at 180 mg/dl and does not respond to insulin (analogous to a hyperglycemic clamp). Portland protocol is shifted back in time by 2 min and the Y protocol forward by 2 min to prevent overlap of symbols. All algorithms effect a continuous rise in delivery. The Y and P algorithms initiate therapy with a concomitant bolus. The P protocol continues with adjunctive boluses on each incremental step.

Figure 6.

(A) GM (blue) and PID (red) algorithm responses for a subject initiating therapy at 180 mg/dl with no subsequent change in glucose superimposed with curves for the written instruction algorithms shown in Figure 5 (shaded curves). (B) Glucommander glucose response curves superimposed with similar curves for the UW algorithm shown in Figure 2 together with PID curve.