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.

Description

CROSS REFERENCE TO RELATED APPLICATION

The present application claims the priority of U.S. provisional application 60/291,873, filed May 18, 2001.

BACKGROUND OF THE INVENTION

The present invention is directed to a method and apparatus for controlling the administration of an hypnotic drug in “closed loop” fashion.

An hypnotic drug may comprise an anesthetic agent and the hypnotic state induced in a patient by the administration of such a drug in one of anesthetization. An hypnotic drug typically acts on the brain to produce a lessening or loss of consciousness in the patient. The extent to which the patient is anesthetized is often termed the “hypnotic level” or “depth of anesthesia.” In the present invention, the existing hypnotic level, or depth of anesthesia, in the patient is sensed and used to control the hypnotic drug administration to the patient in the manner of a closed loop, or feedback, regulator to achieve and maintain a desired level in the patient.

More particularly, the present invention employs the complexity of electroencephalographic (EEG) data obtained from the patient as a sensed indication of the hypnotic level of the patient for use in controlling hypnotic drug administration. The use of such an indication provides closed loop control of drug administration that is based on an accurate assessment of the hypnotic condition of the patient and one that is highly responsive to changes in that condition. Such an indication can be made rapidly responsive to changes in the hypnotic condition of the patient.

Hypnotic drugs, or anesthetic agents, are administered by inhalation or intravenously. When administration is by inhalation, the anesthetic agent comprises a volatile liquid that is vaporized in a vaporizer. The vaporized anesthetic agent is entrained in breathing gases for the patient. The concentration of the anesthetic agent supplied by the vaporizer is determined by the anesthesiologist by manipulating appropriate controls on the vaporizer. The concentration of anesthetic agent in the lungs of the patient may be measured by measuring the amount of anesthetic agent contained in the breathing gases exhaled by the patient at the end of the exhalation phase of the respiratory cycle, i.e. the end tidal concentration (ET_conc). Typical inhaled anesthetic agents are sevoflurane, enflurane, and desflurane, among others.

In a simple form, intravenous administration of an hypnotic drug may employ a syringe that injects the drug into a vein of the patient. For extended administration, a motor driven syringe or a motor driven infusion pump may be employed. A commonly used, intravenously administered, anesthetic agent is propofol.

In addition to hypnosis, high quality anesthesia must also consider loss of sensation (analgesia), muscle relaxation, suppression of the autonomous nervous system, and blockage of the neuro muscular function. This may require administration of a number of different drugs via the same or different routes. Further, different hypnotic drugs and/or different administration routes may be used at different stages of an anesthetization or a medical procedure. For example, hypnosis may be introduced by an intravenously administered drug and maintained by an inhaled drug.

In the process by which a drug, including a hypnotic drug, takes its effect in the body, two aspects are important: pharmacokinetics and pharmacodynamics. 24 26 also contains one or more computational elements, such as a microprocessor, that performs artifact detection and removal and determines the spectral entropy or other characterization of the amount of complexity or disorder in the EEG signal obtained from electrodes 20, as well as spectral power data derived from the EMG signal data obtained from the electrodes, thereby to provide EEG signal data.

The output of EEG complexity determination unit 26 comprises a diagnostic index or other value indicative of the complexity or disorder of the EEG signal data. As noted above, it is deemed preferable for reasons of reducing response times, particularly in sensing the emergence of the patient from the hypnotic state, to incorporate data from EMG signals in such a diagnostic index or value. It may also be advantageous to provide more than one index. For example, indices in which signal complexities have has been computed over different frequency ranges may be used. The output from EEG complexity determination unit is provided to a further input of control unit 16 as shown in FIG. 1 to complete a control loop in control 10.

In a simple embodiment of the invention shown in FIG. 1, control logic unit 16, may be seen as a comparator 28, as shown in FIG. 1A. Comparator 28 compares the reference signal generated by input device 16 18 with the feedback signal provided by EEG complexity determination unit 24 26 and provides an output signal corresponding to the difference between the two inputs. This output signal may be applied to control logic or signal processor 30, the output of which forms the output signal to anesthetic delivery unit 14 for use in controlling the amount of hypnotic drug delivered to patient 12 and hence his/her hypnotic level.

The hypnotic level existing in patient 12, as ascertained by EEG complexity determination unit 26, is driven toward that corresponding to the input signal from input device 18 by the action of the control loop in control 10 in the well known manner of a closed loop or feedback regulator. The polarity of the reference and feedback inputs to comparator 26 28 are shown in FIG. 1A to graphically connote this control action. Specifically, the closed loop control apparatus incorporating control unit 16 acts in a manner to drive the difference between the reference signal from input unit 18 and the feedback signal from EEG complexity determination unit 26, and hence the output signal from control unit 16, to zero. For example, and starting at a zero input signal difference and output signal condition, if the hypnotic level of the patient elevates, or moves towards consciousness, the complexity of the EEG signal data will increase, as will the input signal from complexity determination unit 26 to the positive input of comparator 28. This will produce a positive output from control unit 16 to anesthetic delivery unit 14, which may be taken as a symbolic indication that a greater quantity of hypnotic drug should be administered to patient 12 by anesthetic delivery unit 14 to restore the hypnotic level to a lower value. The greater amount of drug so delivered will decrease the hypnotic level in the patient and cause it to move toward that established by the reference signal from input device 18. The decrease in the hypnotic level also causes the input signal from complexity determination unit to decrease to restore the input signal difference to zero. The converse is true if the hypnotic level of the patient moves towards a greater state of unconsciousness. That is, as patient 12 moves to a greater degree of unconsciousness, the output signal from EEG complexity determination unit 24 26 will decrease. When compared to the reference signal from input device 16 18, this will cause the output signal from comparator 26 28 to assume a symbolic negative value, indicative of a reduction in the amount of hypnotic drug to be supplied to patient 12 from anesthetic delivery unit 14 thereby allowing the level of unconsciousness of the patient to rise back to the desired value.

As shown in FIG. 3, to improve the administration of the hypnotic drug and to enhance patient safety, additional physiological data may be obtained from patient 12 for use in the operation of the closed loop control. For example, it is known that many, if not most of the drugs used in anesthesia, affect, sometimes severely, the cardiovascular status of the patient. Propofol is known to induce a drop of systemic blood pressure in patients, whereas desflurane can induce a significant increase in heart rate. This may have a significant impact on patients particularly sensitive to such changes of vital function such as elderly patients, critically ill patients, and diabetic patients. To this end, cardiovascular parameters, such as heart rate, blood pressure, blood oxygen saturation, and cardiac output, can be obtained by appropriate instrumentation 32 and supplied as a feedback signal to control unit 16a. Desired, or reference, values for these parameters may be inputted by an appropriate input device 18a, along with or separate from an hypnotic level reference values, to alter the output of control unit 16a to anesthetic delivery unit 14 so that the administration of the hypnotic drug to patient 12 is carried out in a manner to preserve these vital functions. The cardiovascular parameters may be used to alter the input signals provided to control unit 16a or a separate control loop responsive to desired and actual cardiovascular data may be provided inside of or outside of the control loop employing the EEG signal data complexity to, for example, limit the delivery rate of a drug or provide a specific combination of intravenous and volatile drugs.

Also as shown in FIG. 3, anesthetic delivery unit 14 may comprise an intravenous infusion pump 14a and a vaporizer 14b, for intravenously administered and inhaled hypnotic drugs, respectively. Pump 14a and vaporizer 14b may be controlled in coordinated fashion by control unit 16a.

As further shown in FIG. 3, when an inhaled hypnotic drug is administered to patient 12, as by use of vaporizer 14b, the end tidal drug concentration (ET_conc) exhaled by patient 10 12 may be measured by sensor 34 and supplied as a feedback signal to control unit 16a to provide a feedback control that ensures that the amount of hypnotic drug received by the patient corresponds to that commanded by the input to vaporizer 14b from control unit 16a. The concentration of hypnotic drug in the end tidal breathing gases of the patient corresponds to the concentration in the lungs of the patient and, therefore to that in the breathing gases provided to patient 12 by vaporizer 14b and is thus useful as a feedback signal.

FIG. 4 shows a modification of the control unit for the closed loop control apparatus shown in FIG. 1. As noted above, the pharmacology resulting from the administration of a drug depends to a considerable extent on the pharmacodynamic and pharmacokinetic properties of the drug. This is particularly true of a hypnotic drug that is not delivered directly into the effect-site. That is, an intravenously supplied hypnotic drug, such as propofol, is delivered to the venous blood of the patient whereas its effect occurs in the brain. For an inhaled drug that is delivered to the respiratory tract of the patient, somewhat more information is available as the concentration of the gas in the lung, which can be measured, is in steady state proportional to the concentration in arterial blood. Therefore, less pharmacokinetic modeling is required as the blood compartment concentration can be obtained from measurements.

In the embodiment of the invention schematically shown in FIG. 4, a transfer function generator 50 may be used to improve the drug administration by control 10. Transfer function generator 50 establishes a desired relationship between the measured hypnotic level in patient 12, as characterized by the degree of complexity in the EEG signal data, and the rate or other characteristics of drug administration by anesthetic delivery unit 14. It also establishes a relationship between EEG signal data complexity and the clinical endpoints of hypnosis levels. In establishing the transfer function, a pharmacokinetic model 52 and pharmacodynamic model 54 for the drug may be employed. These models typically comprise algorithms describing the interaction between the hypnotic drug and a patient stored in, and employed by, a computer. The output of transfer function generator 50 is provided to control logic 30a in control unit 16b for use in its operation in the provision of an output signal to anesthetic delivery unit 14. For this purpose, control unit 16b, in addition to a comparative function, may comprise other control or computational elements, such as microprocessors, in control logic 30a. Control logic 30a may provide data, such as the state of its regulation, regulatory routines, or the various signal magnitudes in control unit 16b to models 52 and 54. In cases where a volatile hypnotic drug has been administered to the patient either alone or in addition to an intravenous drug, its concentration, as determined by the end tidal fraction ET_conc, may be provided to control unit 16b and to pharmacokinetic model 54 52 to permit less complicated pharmacokinetic modeling. Cardiovascular parameter data may also be provided to one or more of the models to improve the operation of the models and control 10 and patient safety.

Pharmacokinetic model 52 allows the hypnotic drug to be administered in such a way that its relative concentration in a given compartment, i.e. the brain, can be maintained generally stable, or constant at that which produces the desired hypnotic level. This stability brings a major advantage for both the patient and the anesthesiologist since once an efficient level of drug effect has been reached, the drug level, and hence the hypnotic level will remain constant, thereby to avoid changes in the patient condition, such as regaining consciousness. However, since an hypnotic drug's real effect cannot be fully predicted for a given patient due to pharmacogenetics and because of the variability among individuals of pharmacokinetics models, the use of pharmacodynamic model 54, in addition to pharmacokinetic model 52 and the determination of EEG signal data complexity by unit 26 allows for both the determination of the appropriate effect-site concentration, i.e. the concentration to achieve a given hypnotic level and hence EEG signal data complexity level, as well as a steady state drug level. Where needed for both the models, the “effect” of the hypnotic drug can be measured by evaluating the complexity of the EEG signal data, particularly that originating from the cerebral portion of the EEG signal data.

Also, as shown in FIG. 4, a programmed data source 56 can be provided in control unit 16b for use in operation of control 10. In addition to the input relating to the hypnotic level, source 56 may be used to generate and input data specific to a given anesthetization, including the patient's anthropometrics, such as weight, age, height, sex, body mass index, and the like. The data may also include information identifying the drug that is being administered to the patient. Other data that may be entered at source 56 include information pertaining to the duration of the procedure, the intensity of the surgery, minimum and maximum drug administration levels and/or rates, upper and lower hypnosis level limits and cardiovascular parameters, and the like. Such data could also include information regarding the pattern of surgical intensity likely to be encountered by the patient according to the type of surgery and/or the technique to be employed by the surgeon, and the idiosyncrasies of the surgical practice of a given surgeon. Information of this and other types can be inputted on an individual basis by an anesthesiologist or stored and retrieved from a database of preset surgical information. Such information may also be provided to models 52 and 54, via control logic 30a for use in their operation.

Programmed data in source 56 may also include timing data. This data may be used by control unit 16b to establish a stable, set complexity level for the EEG data signal, and hence hypnotic level in patient 12, for a predetermined period of time. Or, the programmed data may be such that the anesthesiologist could operate program data source 58 56 so that control 10 is operated in a manner to wake the patient after a preset time as for example, by setting up a “wake-up after ten minutes” routine in source 56. Responsive to inputs provided from data source 56, control logic 30a would then establish the required drug administration rates and timing for anesthetic delivery unit 14 to patient 12 to obtain this effect and timing. An analogous procedure could be carried out with respect to the administration of the hypnotic drug to induce unconsciousness, i.e. loss of consciousness in patient 12 at a point in time in the future. Such features are advantageous for cost savings in terms of operating room usage times, amounts of drug used, and the like.

The transfer function generator 50, as well as models 52, 54, may be supplied with information from a database storage device 58. Such a storage device will typically retain reusable data, such as standard data or stored patient data inputted to the storage device or inputted, or developed by control 10. This will enable patient data obtained during a prior anesthetization to be reused should the patient require a subsequent anesthetization with the same drug. If desired, transfer function generator 58 50 may also store information of the type described above in connection with source 56, such as patient type, nature of the surgery, surgical intensity, patterns, drug interaction, etc.

Also, control 10 can record a time series of measured and computed patient information to compute, after enough data is recorded, a patient's specific profile that, thereafter, can be used to predict the behavior of the patient for any particular change of drug delivery rate, as by use of models 52 and 54.

It will be appreciated that, for safety reasons, the control will include appropriate means to allow the anesthesiologist to manually control the delivery of the hypnotic agent, by operation of an input device, by direct intervention at the anesthetic delivery unit, or in same other effective manner.

It is recognized that other equivalents, alternatives, and modifications aside from those expressly stated, are possible and within the scope of the appended claims.

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 administration amount 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.