METHODS AND SYSTEMS FOR DETERMINING AN INTRAVENOUS INSULIN INFUSION RATE TO CORRECT HYPERGLYCEMIA OF A PATIENT, TO MAINTAIN EUGLYCEMIA OF A PATIENT, AND TO PREVENT HYPOGLYCEMIA OF A PATIENT

• US 20100137788A1
• Filed: 11/02/2007
• Published: 06/03/2010
• Est. Priority Date: 11/02/2006
• Status: Active Grant

• Current Assignee: Emory University, University of South Carolina
• Original Assignee: Emory University
• Inventors: Braithwaite, Susan S., Umpierrez, Guillermo E.
• Granted Patent: US 8,721,584 B2
• Time in Patent Office: Days
• US Class Current: 604/66
• CPC Class Codes: A61M 2005/14208 with a programmable infusion control system, characterised by the infusion program
• CPC Class Codes: A61M 2005/14296 Pharmacokinetic models
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: A61M 5/14244 adapted to be carried by the patient, e.g. portable on the body
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00

Abstract

Methods and systems for determining an intravenous infusion rate to correct hyperglycemia of a patient, to maintain euglycemia of a patient, and to prevent hypoglycemia are disclosed. In one aspect, a method for determining an intravenous insulin infusion rate to correct hyperglycemia of a patient includes estimating an insulin infusion maintenance rate to maintain euglycemia in a patient. Further, a relationship between a current blood glucose concentration of the patient and a target blood glucose concentration may be determined. An insulin infusion rate may be determined based on the estimated insulin infusion maintenance rate and based on the relationship between the current blood glucose concentration and the target blood glucose concentration. A glycemic response of the patient may be measured while using the determined insulin infusion rate. The insulin infusion maintenance rate is re-estimated based on the glycemic response of the patient at a previous insulin infusion rate.

Claims

1. A method for determining an intravenous insulin infusion rate to correct hyperglycemia of a patient, the method comprising:

(a) estimating an insulin infusion maintenance rate to maintain euglycemia in a patient;

(b) determining a relationship between a current blood glucose concentration of the patient and a target blood glucose concentration;

(c) determining an insulin infusion rate based on the estimated insulin infusion maintenance rate and based on the relationship between the current blood glucose concentration and the target blood glucose concentration;

(d) measuring a glycemic response of the patient while using the determined insulin infusion rate;

(e) re-estimating the insulin infusion maintenance rate based on the glycemic response of the patient at a previous insulin infusion rate; and

(f) repeatedly performing steps (b)-(e), wherein the estimated insulin infusion maintenance rate in step (e) during each n^th iteration is utilized to determine the insulin infusion rate in step (c) of each (n+1)^th iteration, n being an integer.

2. The method of claim 1 wherein estimating an insulin infusion maintenance rate includes estimating the insulin infusion maintenance rate using the following equation during hyperglycemia:

3. The method of claim 2 wherein ROD_previous is utilized only if the previous blood glucose concentration is above a predetermined target value with logarithmic transform in a case that blood glucose concentration increasing, wherein ROD_previous is zero if the previous blood glucose concentration is below the predetermined target value, wherein ROA_previous is utilized only if the previous blood glucose concentration is below the predetermined target value, and wherein ROA_previous is zero if the previous blood glucose concentration is at or above a predetermined target value.

4. The method of claim 2 comprising modifying ROD_previous utilizing the following equations:

ROD_{previous,revised}=ROD_previous,when ROD_previous≧

0,and

ROD_{previous,revised}=−

ln(|ROD_previous|+1),when ROD_previous<

0.

5. The method of claim 1 wherein determining an insulin infusion rate includes determining an insulin infusion rate for a next iteration based on the estimated insulin infusion maintenance rate from a previous iteration utilizes one of the following equations:

6. The method of claim 5 wherein ROD_ideal,next is zero if the current blood glucose concentration is below a predetermined target value.

7. The method of claim 5 wherein ROD_ideal,next is a function of a distance between the current blood glucose concentration and the target blood glucose concentration that approaches a maximum value by one of linearly and asymptotically as provided by the following equations, wherein linearly approaching the maximum value is defined by the following equation:

8. The method of claim 1 wherein determining an insulin infusion rate includes:

(a) assigning predetermined numeric values to equation parameters utilized to calculate the insulin infusion rate based on a condition of the patient; and

(b) calculating the insulin infusion rate based on the predetermined numeric values and an equation including the predetermined numeric values, wherein the equation is a function of the current blood glucose concentration and the insulin infusion maintenance rate.

9. The method of claim 8 wherein the condition of the patient is one of diabetic ketoacidosis and hyperglycemic hyperosmolar state, wherein the parameter values utilized for the condition of diabetic ketoacidosis and hyperglycemic hyperosmolar state differ from the parameter values utilized for other populations.

10. The method of claim 9 comprising receiving input regarding the condition of the patient.

11. The method of claim 1 comprising assigning user-definable default parameters and parameter values based on the condition of the patient.

12. The method of claim 11 comprising re-assigning the values of the parameters during treatment based on operator input.

13. The method of claim 1 wherein at least steps (a), (b), (d), (e), and (f) are automated.

24. The system of claim 11 wherein at least functions (i), (ii), (iv), (v), and (vi) are automated.

14. A method for determining an intravenous insulin infusion rate to maintain euglycemia of a patient, the method comprising:

(a) estimating an insulin infusion maintenance rate to maintain euglycemia in a patient;

(b) determining a relationship between a current blood glucose concentration of the patient and a target blood glucose concentration;

(c) determining an insulin infusion rate based on the estimated insulin infusion maintenance rate and based on the relationship between the current blood glucose concentration and the target blood glucose concentration;

(d) measuring a glycemic response of the patient to an insulin infusion given to the patient using the determined insulin infusion rate;

(e) determining a next insulin infusion maintenance rate by one of re-estimating the insulin infusion maintenance rate based on the glycemic response of the patient at a previous insulin infusion rate, carrying forward a previous insulin infusion maintenance rate unchanged to become the next insulin infusion maintenance rate, or based on criteria for risk of hypoglycemia setting the next insulin infusion maintenance rate to be a percentage less than the previous insulin infusion maintenance rate; and

(f) repeatedly performing steps (b)-(e), wherein in repeating steps (b)-(e) the next insulin infusion maintenance rate in step (e) during each n^th iteration is utilized to calculate the insulin infusion rate in step (c) of each (n+1)^th iteration, n being an integer.

15. The method of claim 14 wherein determining an insulin infusion rate includes determining the insulin infusion rate by using one of the following equations:

16. The method of claim 14 wherein at least steps (a), (b), (d), (e), and (f) are automated.

17. A method for determining an intravenous insulin infusion rate to prevent hypoglycemia, the method comprising:

(a) determining that a blood glucose concentration of a patient is within a euglycemic range; and

(b) in response to determining that the blood glucose concentration of the patient is within the euglycemic range, calculating an insulin infusion rate based on an exponential function associating a blood glucose concentration to an insulin infusion rate.

18. The method of claim 17 comprising calculating an insulin infusion rate using one of the following equations:

19. A system for determining an intravenous insulin infusion rate to correct hyperglycemia of a patient, the system comprising:

(a) a measurement receiver configured to receive a glycemic measurement of a patient; and

(b) an insulin infusion rate calculator configured to;

(i) estimate an insulin infusion maintenance rate to maintain euglycemia in the patient;

(ii) determine a relationship between a current blood glucose concentration of the patient and a target blood glucose concentration;

(iii) determine an insulin infusion rate based on the estimated insulin infusion maintenance rate and based on the relationship between the current blood glucose concentration and the target blood glucose concentration;

(iv) measure a glycemic response of the patient while using the determined insulin infusion rate;

(v) re-estimate the insulin infusion maintenance rate based on the glycemic response of the patient at a previous insulin infusion rate; and

(vi) repeatedly perform steps (ii)-(v), wherein the estimated insulin infusion maintenance rate in step (v) during each n^th iteration is utilized to determine the insulin infusion rate in step (iii) of each (n+1)^th iteration, n being an integer.

20. The system of claim 19 wherein the insulin infusion rate calculator is configured to identify a curve within a plurality of curves that provides an insulin infusion rate as a function of blood glucose concentration, wherein the curves are each associated with different patient maintenance rates.

21. The system of claim 20 wherein the insulin infusion rate calculator is configured to receive input regarding the patient condition of the patient, and configured to enter predetermined parameter values, based on a condition of the patient, that will identify a family of functions for a next insulin infusion rate for the patient such that the functions differ within the family according to the insulin infusion maintenance rate, wherein the members of a family of functions are the same with respect to target blood glucose concentrations (BG_{upper target}, BG_{true target}, and BG_{lower target}), BG_{critical high}, IR_@BG70, ROD_{@BGcritical high}, and ROD_{ideal,next,max}.

22. The system of claim 21 wherein one of the families is associated with diabetic ketoacidosis, and wherein one of the families is associated with hyperglycemic hyperosmolar state.

23. The system of claim 19 wherein the insulin infusion rate calculator is configured to estimate an insulin infusion maintenance rate includes estimating the insulin infusion maintenance rate using the following equation during hyperglycemia:

25. A system for determining an intravenous insulin infusion rate to maintain euglycemia of a patient, the system comprising:

(a) a measurement receiver configured to receive a glycemic measurement of a patient; and

(b) an insulin infusion rate calculator configured to;

(i) estimate an insulin infusion maintenance rate to maintain euglycemia in the patient;

(ii) determine a relationship between a current blood glucose concentration of the patient and a target blood glucose concentration;

(iii) determine an insulin infusion rate based on the estimated insulin infusion maintenance rate;

(iii) measure a glycemic response of the patient to an insulin infusion given to the patient using the determined insulin infusion rate;

(iv) re-estimate the insulin infusion maintenance rate based on the glycemic response of the patient; and

(v) repeatedly perform functions (ii)-(iv), wherein the estimated insulin infusion maintenance rate in function (iv) during each n^th iteration is utilized to calculate the insulin infusion rate in function (ii) of each (n+1)^th iteration, n being an integer.