Closed loop drug administration method and apparatus using EEG complexity for control purposes

• US RE41,291 E1
• Filed: 09/21/2005
• Issued: 04/27/2010
• Est. Priority Date: 05/18/2001
• Status: Expired due to Term

• Current Assignee: GE Healthcare Finland OY (GE Healthcare Technologies, Inc.)
• Original Assignee: GE Healthcare Finland OY (GE Healthcare Technologies, Inc.)
• Inventors: Viertio-Oja, Hanna E., Cohen-Laroque, Emmanuel-S
• Primary Examiner(s): Basichas; Alfred
• Application Number:
  US11/232,411
• Time in Patent Office: 1,679 Days
• Field of Search: 600/544, 600/545, 600/546
• US Class Current: 600/544
• CPC Class Codes: A61B 2505/05 Surgical care
• CPC Class Codes: A61B 5/0476 Electroencephalography devices for psychotechnics A61B5/16
• CPC Class Codes: A61B 5/048 Detecting the frequency distribution of signals analysing frequency spectra in general G01R23/00
• CPC Class Codes: A61B 5/0488 Electromyography
• CPC Class Codes: A61B 5/1106 to assess neuromuscular blockade, e.g. to estimate depth of anaesthesia
• CPC Class Codes: A61B 5/4821 Determining level or depth of anaesthesia A61B5/1106 takes precedence
• CPC Class Codes: A61B 5/6814 Head
• CPC Class Codes: A61M 16/01 specially adapted for anaesthetising A61M16/104, A61M16/18 take precedence
• CPC Class Codes: A61M 16/18 Vaporising devices for anaesthetic preparations
• CPC Class Codes: A61M 2016/1035 the anaesthetic agent concentration
• CPC Class Codes: A61M 2202/0241 Anaesthetics; Analgesics
• CPC Class Codes: A61M 2230/04 Heartbeat characteristics, e.g. ECG, blood pressure modulation
• CPC Class Codes: A61M 2230/10 Electroencephalographic signals
• CPC Class Codes: A61M 2230/205 partial oxygen pressure (P-O2)
• CPC Class Codes: A61M 2230/30 Blood pressure A61M2230/04 takes precedence
• CPC Class Codes: A61M 2230/437 the anaesthetic agent concentration
• CPC Class Codes: A61M 2230/60 Muscle strain, i.e. measured on the user
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00

Abstract

A closed loop method and apparatus for controlling the administration of an hypnotic drug to a patient. Electroencephalographic (EEG) signal data is obtained from the patient. At least one measure of the complexity of the EEG signal data is derived from the data. The complexity measure may comprise the entropy of the EEG signal data. The EEG signal data complexity measure is used as the feedback signal in a control loop for an anesthetic delivery unit to control hypnotic drug administration to the patient in a manner that provides the desired hypnotic level in the patient. An EEG signal complexity measure obtained from the cerebral activity of the patient can be advantageously used in conjunction with a measure of patient electromyographic (EMG) activity to improve the response time of hypnotic level determination and of the feedback control of drug administration. A pharmacological transfer function may be used, along with pharmacokinetic and pharmacodynamic models.

Claims

1. A method for administering an hypnotic drug to a patient to establish a desired hypnotic level in the patient, said method comprising the steps of:

(a) establishing a reference signal corresponding to the desired hypnotic level to be provided established in the patient from the administration of the hypnotic drug;

(b) administering the hypnotic drug to the patient;

(c) obtaining EEG signal data resulting from cerebral activity of the patient and obtaining EMG signals resulting from muscle activity of the patient;

(d) deriving at least one measure of the complexity characteristics of the EEG signal data;

(e) deriving a measure of patient EMG activity;

(f) determining the hypnotic level existing in the patient from the complexity characteristics of the EEG signal data combined with the derived measure of patient EMG activity and providing a feedback signal corresponding to the hypnotic level existing in the patient;

(f)(g) comparing the feedback signal corresponding to the hypnotic level existing in the patient as a result of the administration of the hypnotic drug to the reference signal corresponding to the desired hypnotic level to be established in the patient from the administration of the drug to produce a control signal, indicative of the difference between the desired hypnotic level and the existing hypnotic level; and

(g)(h) controlling the administrationamount of the hypnotic drug administered to the patient in accordance with the comparison of step (f)control signal so that the hypnotic level of the patient is established and maintained at that corresponding to the reference signal.

2. The method according to claim 1 wherein step (d) is further defined as measuring an entropy of the EEG signal data.

3. The method according to claim 2 wherein step (d) is further defined as measuring the spectral entropy of the EEG signal data.

4. The method according to claim 2 wherein step (d) is further defined as measuring the approximate entropy of the EEG signal data.

5. The method according to claim 1 wherein step (d) is further defined as employing a Lempel-Ziv complexity measure.

6. The method according to claim 1 wherein step (d) is further defined as carrying out a fractal spectrum analysis to measure the complexity characteristics of the EEG signal data.

7. The method according to claim 1 further defined as deriving a plurality of EEG signal data complexity characteristics measures for use in determining the hypnotic level of the patient and controlling the administration of the hypnotic drug to the patient .

8. The method according to claim 1 wherein step (c) is further defined as obtaining EEG signals resulting from the cerebral activity of the patient for use in the derivation of the measure of step (d).

9. The method according to claim 8 wherein step (c) is further defined as obtaining EMG signals resulting from the muscle activity of the patient and the method further includes the step of deriving a measure of patient EMG activity for use with the derived measure of EEG signal complexity in controlling the administration of the hypnotic drug to the patient.

10. The method according to claim 9 1 wherein the step of deriving the measure of patient EMG activity is further defined as deriving the measure from a frequency domain power spectrum of the EMG signals.

11. The method according to claim 8 1 wherein step (c) is further defined as obtaining EMG signals resulting from the muscle activity of the patient and step (d) further includes the step of deriving a measure of the complexity characteristics of EEG signal data over a frequency spectrum incorporating the EEG signals and EMG signals for use with the a derived measure of the EEG signal data complexity in controlling the administration of the hypnotic drug to the patient characteristics.

12. The method according to claim 1 further including the steps of establishing desired cardiovascular characteristics for the patient;

obtaining cardiovascular data from the patient;

comparing the cardiovascular data of the patient to desired cardiovascular characteristics; and

further controlling the administration of the hypnotic drug in accordance with the comparison of cardiovascular characteristics and data.

13. The method according to claim 1 further including the step of establishing a transfer function between the pharmacological effects of the hypnotic drug in the patient and the administration of the drug to the patient for use in controlling the hypnotic drug administration.

14. The method according to claim 1 further including the step of employing a pharmacokinetic model in controlling the administration of the hypnotic drug to the patient.

15. The method according to claim 1 further including the step of employing a pharmacodynamic model in controlling administration of the hypnotic drug to the patient.

16. The method according to claim 15 further including the step of employing a pharmacokinetic model in controlling the administration of the hypnotic drug to the patient.

17. The method according to claim 13 further including the step of employing a pharmacokinetic model in establishing the transfer function for use in controlling the administration of the hypnotic drug to the patient.

18. The method according to claim 13 further including the step of employing a pharmacodynamic model in establishing the transfer function for use in controlling administration of the hypnotic drug to the patient.

19. The method according to claim 17 further including the step of employing a pharmacodynamic model in establishing the transfer function for use in controlling administration of the hypnotic drug to the patient.

20. The method according to claim 1 further including the steps of measuring amounts of volatile hypnotic drugs drug in the exhaled breathing gases in of the patient and controlling the administration of the hypnotic drugs drug in accordance with the volatile drug measurement.

21. The method according to claim 13 further including the steps of measuring amounts of volatile hypnotic drugs drug in the exhaled breathing gases in of the patient and as employing the measurement in establishing the transfer function for use in controlling the administration of the hypnotic drug.

22. The method according to claim 13 further including the steps of obtaining cardiovascular data from the patient and as employing the cardiovascular data in establishing the transfer function for use in controlling the administration of the hypnotic drug.

23. The method according to claim 1 further including the step of providing information relating to one or more of the patient, the hypnotic drug, a medical procedure, and a physician for use in controlling the administration of the hypnotic drug to the patient.

24. The method according to claim 1 further including the step of storing information relating to one or more of the patient, the hypnotic drug, a medical procedure, and a physician for use in controlling the administration of the hypnotic drug to the patient.

25. The method according to claim 24 wherein the stored information includes information relating to a previous anesthetization of the patient.

26. The method according to claim 23 further including the step of storing information relating to one or more of the patient, the hypnotic drug, a medical procedure, and a physician and as employing the stored information for use in controlling the administration of the hypnotic drug to the patient.

27. The method according to claim 1 including the steps of generating information in the course of an anesthetization and employing the generated information in controlling the administration of the hypnotic drug to the patient.

28. Apparatus for administering an hypnotic drug to a patient to establish a desired hypnotic level in the patient, said apparatus comprising:

(a) means for establishing a reference signal corresponding to a the desired hypnotic level for to be established in the patient from the administration of the hypnotic drug;

(b) an anesthetic delivery unit for administering the hypnotic drug to the patient;

(c) a sensor means for obtaining EEG signal data resulting from the cerebral activity of the patient and for obtaining an EMG signal resulting from muscle activity of the patient;

(d) means coupled to said sensor means for deriving at least one measure of the complexity characteristics of the EEG signal data and for deriving a measure of EMG activity from the EMG signal, for determining the hypnotic level existing in the patient from the complexity characteristics of the EEG signal data combined with the derived measure of EMG activity, and for providing a feedback signal corresponding to same the hypnotic level existing in the patient; and

(e) a control unit including a comparator having inputs coupled to said elements (a) and (c) (d) and an output coupled to element (b), said comparator comparing the signals feedback signal corresponding to the hypnotic level existing in the patient as a result of the administration of the hypnotic drug and the reference signal corresponding to the desired hypnotic level to be established in the patient from the administration of the drug and providing an output signal to the anesthetic delivery unit, indicative of the difference between the reference and feedback signals, for controlling the anesthetic delivery unit and the administration amount of the hypnotic drug administered to the patient by the anesthetic delivery unit in accordance with the comparison output signal so that the hypnotic level of the patient is established and maintained at that corresponding to the reference signal.

29. The apparatus according to claim 28 wherein element (d) is further defined as means for measuring an entropy of the EEG signal data to determine the hypnotic level existing in the patient derive at least one measure of the complexity characteristics of the EEG signal data.

30. The apparatus according to claim 29 wherein element (d) is further defined as means for measuring the spectral entropy of the EEG signal data.

31. The apparatus according to claim 29 wherein element (d) is further defined as means for measuring the approximate entropy of the EEG signal data.

32. The apparatus according to claim 28 wherein element (d) is further defined as means employing a Lempel-Ziv complexity measure to determine the hypnotic level existing in the patient derive at least one measure of the complexity characteristics of the EEG signal data.

33. The apparatus according to claim 28 wherein element (d) is further defined as means for carrying out a fractal spectrum analysis to measure the complexity characteristics of the EEG signal data to determine the hypnotic level existing in the patient .

34. The apparatus according to claim 28 wherein element (d) is further defined as deriving a plurality of EEG signal data complexity characteristics measures for determining the hypnotic level existing in the patient to derive at least one measure of the complexity characteristics of the EEG signal data.

35. The apparatus according to claim 28 wherein element (c) is further defined as a sensor for obtaining EEG signals resulting from the cerebral activity of the patient and element (d) is further defined as using EEG signals in providing the signal corresponding to the hypnotic level existing in the patient.

36. The apparatus according to claim 35 wherein element (c) is further defined as a sensor for obtaining EMG signals resulting from the muscle activity of the patient and element (d) is further defined as deriving a measure of EMG activity from the EMG signals and using same with a measure derived from EEG signal complexity to provide the signal corresponding to the hypnotic level in the patient.

37. The apparatus according to claim 36 28 wherein element (d) is further defined as means for obtaining a frequency domain power spectrum of the EMG signals signal to derive the measure of EMG activity in the patient.

38. The apparatus according to claim 35 37 wherein element (c) is further defined as a sensor for obtaining EMG signals resulting from the muscle activity of the patient and element (d) is further defined as means for deriving the complexity characteristics of the EEG signal data over a frequency spectrum incorporating the EEG signals signal data and EMG signals signal for use with a derived measure of EEG signal data complexity characteristics to determine the hypnotic level of the patient.

39. The apparatus according to claim 28 further including means for providing a signal corresponding to desired cardiovascular characteristics for the patient;

means for obtaining cardiovascular signal data from the patient;

means for comparing the cardiovascular signal data of the patient to the desired cardiovascular characteristics signal; and

means for controlling the anesthetic delivery unit and the administration of the hypnotic drug in accordance with the comparison of the cardiovascular characteristics signal and cardiovascular signal data.

40. The apparatus according to claim 28 further including means in said control unit for establishing a transfer function between the pharmacological effects in the patient and the administration of the hypnotic drug to the patient for use in controlling said anesthetic delivery unit.

41. The apparatus according to claim 28 further including pharmacokinetic model means in said control unit for use in controlling operation of said anesthetic delivery unit.

42. The apparatus according to claim 28 further including pharmacodynamic model means in said control unit for use in controlling operation of said anesthetic delivery unit.

43. The apparatus according to claim 42 further including pharmacokinetic model means in said control unit for use in controlling the operation of said anesthetic delivery unit.

44. The apparatus according to claim 40 further including pharmacokinetic model means for use with said transfer function establishing means in controlling the operation of said anesthetic delivery unit.

45. The apparatus according to claim 40 further including pharmacodynamic model means in said control unit for use with said transfer function establishing means in controlling the operation of said anesthetic delivery unit.

46. The apparatus according to claim 44 further including pharmacodynamic model means in said control unit for use with said transfer function establishing means in controlling the operation of said anesthetic delivery unit.

47. The apparatus according to claim 28 further including means for measuring amounts of volatile hypnotic drugs drug in the exhaled breathing gases in of the patient and coupled to said control unit for use in controlling the anesthetic delivery unit.

48. The apparatus according to claim 40 further including means for measuring amounts of volatile hypnotic drugs drug in the exhaled breathing gases to of the patient, said means being coupled to said transfer function establishing means for use in establishing the transfer function.

49. The apparatus according to claim 40 further including means for obtaining cardiovascular data from the patient, said means being coupled to said transfer function establishing means for use in establishing the transfer function.

50. The apparatus according to claim 28 further including means for providing information relating to one or more of the patient, the hypnotic drug, a medical procedure, and a physician for use in controlling the administration of the hypnotic drug to the patient.

51. The apparatus according to claim 50 28 further including storage means for storing information relating to one or more of the patient, the hypnotic drug, a medical procedure, and a physician for use in controlling the administration of the hypnotic drug to the patient.

52. The apparatus according to claim 51 wherein the storage means stores information relating to a previous anesthetization of the patient.

53. The apparatus according to claim 50 further including storage means for storing information relating to one or more of the patient, the hypnotic drug, a medical procedure, and a physician for use in controlling the administration of the hypnotic drug to the patient.

54. The apparatus according to claim 28 including means for generating information in the course of an anesthetization and for employing the generated information in controlling the administration of the hypnotic drug to the patient.