Method of operating a control device for controlling an infusion device

• US 9,849,241 B2
• Filed: 02/24/2014
• Issued: 12/26/2017
• Est. Priority Date: 04/24/2013
• Status: Active Grant

• Current Assignee: Fresenius KABI Deutschland GmbH (Fresenius SE & Co. KGaA)
• Original Assignee: Fresenius KABI Deutschland GmbH (Fresenius SE & Co. KGaA)
• Inventors: Becker, Michael
• Primary Examiner(s): Mendez, Manuel
• Application Number:
  US14/786,118
• Publication Number:
  US 20160074582A1
• Time in Patent Office: 1,401 Days
• Field of Search: 604 65- 67, 604151, 604131, 128DIG 12, 128DIG 13
• CPC Class Codes: A61M 2205/35 Communication
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61M 2230/10 Electroencephalographic signals
• CPC Class Codes: A61M 2230/43 Composition of exhalation
• CPC Class Codes: A61M 5/172 electrical or electronic A61M5/16804, A61M5/16831 take precedence
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: G16H 20/17 delivered via infusion or injection

Abstract

Method of operating a control device for controlling an infusion device A method of operating a control device (2) for controlling an infusion device (33) for administering a drug to a patient (P) comprises the steps of: providing a model (p) to predict a time-dependent drug concentration (Cplasma, Clung, Cbrain) in multiple compartments (A1-A5) of a patient (P); setting a target concentration value (CTbrain) to be achieved in at least one of the compartments (A1-A5) of the patient (P); determining a drug dosage (D1) to be administered to a first compartment (A1) of the multiple compartments (A1-A5) of the patient (P) using the model (p) such that the difference between the target concentration value (CTbrain) and a predicted steady-state drug concentration (Cplasma, Clung, Cbrain) in the at least one of the compartments (A1-A5) is smaller than a pre-defined threshold value (Ub-rain); providing a control signal (S1) indicative of the drug dosage (D1) to an infusion device (33) for administering the drug dosage (D1) to the patient (P); obtaining a measurement value (M1, M2) indicating a measured drug concentration in a second compartment (A2, A3) of the multiple compartments (A1-A5) at a measurement time (t1, t2); adjusting the model (p) such that the model (p) predicts a drug concentration (Clung, Cbrain) in the second compartment (A2, A3) at the measurement time (t1, t2) which at least approximately matches the measured drug concentration in the second compartment (A2, A3); and determining a new drug dosage (D2, D3) to be administered into the first compartment (A1) of the patient (P) using the model (p) such that the difference between the target concentration value (CT-brain) and a predicted steady-state drug concentration (Cplasma, Clung, Cbrain) in the at least one of the compartments (A1, A2, A3) is smaller than the predefined threshold value (Ubrain). In this way a method is provided which allows for an improved (personalized and predictive) control of a drug administration procedure, in particular when administering an anaesthetic drug such as Propofol and/or an analgesic drug such as Remifentanil within a procedure.

Claims

1. A method of operating a control device for controlling an infusion device for administering a drug to a patient, the method comprising the steps of:

(a) providing a model to predict a time-dependent drug concentration in multiple compartments of a patient;

(b) setting a target concentration value to be achieved in at least one of the compartments of the patient;

(c) determining a drug dosage to be administered to a first compartment of the multiple compartments of the patient using the model such that the difference between the target concentration value and a predicted steady-state drug concentration in the at least one of the compartments is smaller than a pre-defined threshold value;

(d) providing a control signal indicative of the drug dosage to an infusion device for administering the drug dosage to the patient;

(e) obtaining at least one measurement value indicating a measured drug concentration in at least a second compartment of the multiple compartments at one or more measurement times;

(f) adjusting the model such that the model predicts a drug concentration in at least the second compartment at one or more measurement times, which at least approximately matches the measured drug concentration in at least said second compartment; and

(g) determining a new drug dosage to be administered into the first compartment of the patient using the model such that the difference between the target concentration value and a predicted steady-state drug concentration in the at least one of the compartments is smaller than the pre-defined threshold value.

2. The method according to claim 1, wherein the drug is an anaesthetic drug such as Propofol, an analgesic drug such as Fentanil or Remifentanil, or a muscle relaxant.

3. The method according to claim 1 wherein the model is a pharmacokinetic-pharmacodynamic model to predict a drug concentration as a function of time in multiple compartments of a patient.

4. The method according to claim 1, wherein the first compartment is a plasma compartment and the second compartment is a brain or lung compartment.

5. The method according to claim 1, wherein the first compartment is a plasma compartment, the second compartment is a lung compartment and a third compartment is the brain compartment.

6. The method according to claim 1, wherein steps (d) to (g) are iteratively repeated.

7. The method according to claim 1, wherein step (f) includes:

adjusting at least one transfer rate constant or volume of the model indicating a transfer rate between different compartments or a volume of a compartment.

8. The method according to claim 1, wherein the at least one measurement value is taken by a measurement device which is constituted to measure a drug concentration in the patient'"'"'s breath.

9. The method according to claim 1, wherein at least one measurement value is obtained by continuously measuring the drug concentration in the patient'"'"'s breath over a predetermined number of breathing cycles.

10. The method according to claim 1, wherein at least one measurement value is taken by a measurement device which is constituted to measure an EEG signal resulting in an EEG index value.

11. The method according to claim 1, wherein the measurement time of step (e) lies in a range after the administration of the drug dosage by the infusion device indicated by the control signal of step (d) reaches a steady state status in at least the first compartment or is completed.

12. The method according to claim 1, wherein the at least one measurement value at one or more measurement times according to step (e) is obtained before the drug concentration in at least the second compartment reaches a steady state status or is completed.

13. The method according to claim 1, comprising:

transforming the measurement value into a measured drug concentration in the second compartment at the measurement time using a transformation function.

14. The method according to claim 1, wherein in a further step (h) at least one measurement value is obtained indicating a measured drug concentration in the third compartment of the multiple compartments at one or more measurement times and at least one measurement value is obtained indicating a measured drug concentration in the second compartment of the multiple compartments at one or more measurement times, and a first value indicating a drug concentration in the second compartment is determined based on the measurement values indicating a measured drug concentration in the third compartment by using the model and a second value indicating a drug concentration in the second compartment is determined based on the measurement values indicating a measured drug concentration in the second compartment using a transformation function wherein, in a further step, in case there is a difference between the first value and the second value, the transformation function is adapted, so that the first value and the second value match or are within a defined range.

15. A control device for controlling an infusion device for administering a drug to a patient, the control device being constituted to:

(a) provide a model to predict a time-dependent drug concentration in multiple compartments of a patient;

(b) set a target concentration value to be achieved in at least one of the compartments of the patient;

(c) determine a drug dosage to be administered to a first compartment of the multiple compartments of the patient using the model such that the difference between the target concentration value and a predicted steady-state drug concentration in the at least one of the compartments is smaller than a pre-defined threshold value;

(d) provide, as an output, a control signal indicative of the drug dosage to an infusion device for administering the drug dosage to the patient;

(e) obtain, as an input, at least one measurement value indicating a measured drug concentration in a least a second compartment of the multiple compartments at a measurement time;

(f) adjust the model such that the model predicts a drug concentration in at least the second compartment at the one or more measurement time which at least approximately matches the measured drug concentration in at least the second compartment; and

(g) determine a new drug dosage to be administered into the first compartment of the patient using the model such that the difference between the target concentration value and a predicted steady-state drug concentration in the at least one of the compartments is smaller than the pre-defined threshold value.

16. The control device according to claim 15, wherein the control device is constituted to request, as an input prior to step (d), a user information before providing the control signal to the infusion device.