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

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.

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.