Automatic infusion system based on an adaptive patient model

• US 20050171503A1
• Filed: 03/24/2003
• Published: 08/04/2005
• Est. Priority Date: 03/22/2002
• Status: Active Grant

• Current Assignee: KU Leuven Research & Development
• Original Assignee: KU Leuven Research & Development
• Inventors: Aerts, Jean-Marie, Van Den Berghe, Greta, Berckmans, Daniel, De Smet, Frank, Pluymers, Bert, De Moor, Bart
• Granted Patent: US 7,491,187 B2
• Time in Patent Office: Days
• US Class Current: 604/504
• CPC Class Codes: A61M 2005/14208 with a programmable infusion control system, characterised by the infusion program
• CPC Class Codes: A61M 2205/6018 providing set-up signals for the apparatus configuration
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: A61M 5/142 Pressure infusion, e.g. using pumps
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00

Abstract

Present invention is a system of blood glucose monitoring and intensive insulin therapy in a ICU for strict maintenance of normoglycemia which reduces intensive care and hospital mortality and morbidity of critically ill adult patients. The findings of present study also reveal factors determining insulin doses needed to maintain normoglycemia as well as the impact of insulin dose versus blood glucose level on the observed outcome benefits have been established. The invention provides a control system that adapts the flow of the insulin infusion based on insulin requirement calculated by blood glucose levels and clinical parameters such as history of diabetes, Body Mass Index, blood glucose level on admission, reason of ICU admission, time in the ICU, type and severity of illness, caloric intake, obesity, drugs affecting insulin sensitivity). This automated insulin monitoring systems significantly reduces the workload and human resource management problems for intensive insulin therapy in patients in the ICU.

Claims

1. An apparatus comprising a sensor to produce a signal indicative of the glycemia levels in a person, a programmable actuator adapted to deliver a blood glucose regulator to said person and a control system adapted to regulate the administration level of said blood glucose regulator, wherein a model-based predictive controller based on a dynamic patient model predicts the future response of the process output to the control input as a function of time and compensates effects of external disturbance on a patient'"'"'s glycemia by adjusting the administration rate of the blood glucose regulator to achieve a status of normoglycemia in said person, which is a critically ill patient or a patient subjected to condition of changing insulin resistance.

2. The apparatus of claim 1, wherein the controller pro-actively compensates the future effect of known current or future disturbances by using the dynamic patient model in order to minimise the deviation from normoglycemia.

35. The apparatus of claim 1, wherein the control system furthermore comprises a continuous feedback of the process output to control.

36. The apparatus of claim 1, wherein the controller is a feedback controller based on a dynamic patient model.

37. The apparatus of claim 1, wherein the external disturbance is one selected from the group of disturbances consisting of:

change in kind of medication, dose of medication, means of administration of medication, and change in caloric intake.

38. The apparatus of claim 1, configured to maintain normoglycemia in a critically ill person under a condition of decreasing insulin resistance over time.

39. The apparatus of claim 1, wherein the controller comprises a PI(D).

40. The apparatus of claim 1, wherein said dynamic patient model is based on a low-order (N)ARX-model.

41. The apparatus of claim 1, wherein said dynamic patient model is based on a state-space model.

42. The apparatus of claim 1, wherein the control system comprises two main components:

1) the mathematical (adaptive) model of the patient for which in the initial phase an initial model is used based on the ‘

profile’

or ‘

constitution’

of the critically ill patient (factors that can influence the basal or mean blood glucose regulator requirements) and after the initial phase, the incoming closed-loop measurements are used to adapt the initial parameters of the said initial model such that it more closely approximates the dynamic behavior of the glycemia in that particular critically ill patient; and

2) the controller.

43. The apparatus of claim 42, wherein said profile of said critically ill patient comprises one or more of the following variables:

BMI, prior history of diabetes, on-admission parameters, reason for ICU admission.

44. The apparatus of claim 43, wherein said on-admission parameters are selected from the group consisting of:

APACHE-II on admission, on-admission glycemia, caloric intake on admission, concomitant medication on admission.

45. The apparatus of claim 43, wherein the on-admission parameters of the patients and the patient profile are classified into distinct classes each associated with their own parameter settings for the initial model.

46. The apparatus of claim 1, wherein prefiltered input and output variables (i.e. instrumental variables) are used to estimate the model parameters.

3-34. -34. (canceled)

47. A method for the treatment of a critically ill patient under a condition of insulin resistance or under a condition of increased glucose turnover, which comprises administering a blood glucose regulator an apparatus comprising

a sensor to produce a signal indicative of the glycemia levels in said patient;

a programmable actuator adapted to deliver a blood glucose regulator to said patient; and

a control system adapted to regulate the administration level of said blood glucose regulator,

wherein said apparatus comprises a model-based predictive controller based on an adaptive patient model which predicts the future response of the process output to the control input as a function of time and compensates effects of external disturbance on said patient'"'"'s glycemia by adjusting the administration rate of the blood glucose regulator to achieve a status of normoglycemia in said critically ill patient.

48. The method of claim 47, wherein the blood glucose regulator is selected from insulin, an insulin analogue, an active derivative of insulin or a monomeric human insulin analogue.

49. The method of claim 47, wherein the blood glucose regulator is selected from the group consisting of:

glucagon like peptide 1 (a GLP-1), a GLP-1 analog, GLP-1 derivatives and pharmaceutically acceptable salts thereof, somatostatin, gastric inhibitor polypeptide, glucose-dependent insulinotropic peptide, bombesin, calcitonin gene-related peptide, gastrin-releasing peptide, cholinergic agonists, isoproterenol, and bethanechol.

50. The method of claim 47, wherein hyperglycemia is reduced to stable normoglycemia in a critically ill patient without causing hypoglycemia in an initial phase of less than 24 hours and normoglycemia is maintained under changing conditions of said critically ill patient (e.g., decreasing insulin resistance, other route of feeding, change in medication) or complications of said critically ill patient (e.g., concomitant infection).

51. The method of claim 47, wherein said apparatus is configured to maintain blood glucose between 60 mg/dl and 130 mg/dl in said critically ill patient.

52. The method of claim 47, wherein said apparatus is configured to maintain blood glucose between 80 and 110 mg/dl in said critically ill patient.

53. A method for the treatment of a critically ill patient, to prevent or decrease the incidence of blood stream infection, to reduce morbidity and mortality in the critical care, to prevent or decrease the incidence of prolonged inflammation, to prevent or decrease the incidence of acute renal failure, to prevent or decrease the incidence of polyneuropathy, to prevent or decrease the incidence of immune-mediated destruction of the beta cells, to prevent or decrease the incidence of systemic inflammatory response syndrome (SIRS) to prevent or decrease the incidence of sepsis, to prevent or decrease the incidence of endoneural edema, to prevent or decrease the incidence of phrenic nerves or to decrease dialysis or hemofiltration, which comprises administering a blood glucose regulator using an apparatus comprising:

a sensor to produce a signal indicative of the glycemia levels in said patient;

a programmable actuator adapted to deliver a blood glucose regulator to said patient; and

a control system adapted to regulate the administration level of said blood glucose regulator;

wherein said apparatus comprises a model-based predictive controller based on an adaptive patient model which predicts the future response of the process output to the control input as a function of time and compensates effects of external disturbance on said patient'"'"'s glycemia by adjusting the administration rate of the blood glucose regulator to achieve a status of normoglycemia in said critically ill patient.