The current invention relates to a system for the differentiation between hypnotic and paralytic states of a patient undergoing medical anesthesia or sedation. It further relates to the use of electrophysiological signals to identify and differentiate such states. More particularly, it relates to use of physiological signals to distinguish between natural sleep, on the one hand, and anesthesia and sedation on the other. The invention further relates to the use of electroencephalographic signals, in concert with other physiological and electrophysiological signals, to identify and differentiate such states.
In current medical practice, patients are placed under general anesthesia during invasive surgery. In post-surgical and other medical situations, particularly in an intensive care unit (ICU), patients are sedated although not fully anesthetized. Commonly administered anesthetic and sedative drugs cause a patient to lose consciousness and/or sensation, or at least to have diminished consciousness and/or sensation. An anesthesia practitioner monitors the patient's state of awareness by means of clinical signs known empirically to provide useful and reliable information about the patient's state of awareness or unconsciousness.
Post surgery, and in other medically required circumstances, a patient is admitted to an ICU for close monitoring of condition and for relevant treatment. While in the ICU a patient is often sedated, sometimes heavily, sometimes lightly. It is important to maintain the ICU patient at an appropriate level of sedation. Drugs commonly used to manage patient sedation include hypnotics, anxiolytics, and analgesics. One drug used to manage patient sedation is PRECEDEX dexmedetomidine.
In all of the above situations, frequent assessment of the patient's state of anesthesia or sedation is crucial. The need for patient sedation monitoring also exists in office based surgery, ambulatory surgery, and recovery rooms.
With respect to induced full or partial hypnotic states, clinicians typically monitor the patient's state visually using one of several known scales that are based on patient characteristics. Sedation monitoring currently is accomplished by using one or more of ten subjective scoring systems. These scoring systems include, but are not limited to, Ramsey Sedation Scale, Riker Sedation Agitation Scale, Richmond Sedation Scale, Motor Activity Assessment Scale, Bion Scale, Glasgow Coma Scale, and others. When properly used, these scoring systems have proven to be an effective way to decrease mortality and morbidity in the ICU, and, particularly with ventilated patients, decrease the amount of sedative drugs used, shorten the stay in the ICU, decrease incidence of ICU psychosis, and improve patient comfort.
These scoring systems have a number of drawbacks in common, including:
Due to the inherent subjectivity of these tests, it is difficult to provide a predictable, accurate measurement of the patient's depth of sedation. This limitation underscores the need for an automatic sedation monitor that provides an objective measurement regardless of the clinician administering the test. Because clinicians are accustomed to measuring depth of sedation using the known, subjective tests, it is advantageous that the automatic sedation monitor, at least in one embodiment, be scaled to one of the more common and familiar sedation scales.
The most widely used anesthesia/sedation scale is the Ramsay Sedation Scale (RSS). This scale is simple and relatively straightforward for the clinician to apply, although imprecise and subjective for the reasons discussed above. The stages and indications of the RSS are shown in Table 1:
As the table indicates, the Ramsay Scale is divided roughly into “awake” states, stages 1 through 3, and “asleep” states, stages 4 through 6. “Asleep” in this context means either (i) normal sleep; or (ii) anesthetized or heavily sedated, i.e., a chemically induced “sleep.” One of the problems addressed by anesthesia/sedation monitor of the present invention is that of distinguishing between normal sleep and chemically induced sleep. The Ramsay Scale defines sleep at an RSS of 4, with a brisk response to external stimulus. The most common external stimulus used for this purpose is a glabellar tap, which provokes an eyeblink response (see below).
As noted, it is desirable to have an objective measurement of the level of anesthesia or sedation of a patient, possibly based on the RSS scale or another known sedation scale, so as not to have to rely on the subjective impressions of clinicians. Systems for measuring depth of anesthesia/sedation have been developed using EEG signals, generally in combination with other signals, to monitor anesthesia, sleep, and other states on the consciousness-unconsciousness continuum. Representative examples include, but are not limited to, Kaplan et al., U.S. Pat. No. 5,813,993, issued Sep. 29, 1998; Maynard, U.S. Pat. No. 5,816,247, issued Oct. 6, 1998; Kangas et al., U.S. Pat. No. 5,775,330, issued Jul. 7, 1998; John, U.S. Pat. No. 5,699,808, issued Dec. 23, 1997; John, U.S. Pat. No. 4,557,270, issued Dec. 10, 1985; John, U.S. Pat. No. 4,545,388, issued Oct. 8, 1985; Prichep, U.S. Pat. No. 5,083,571, issued Jan. 28, 1992; and John, U.S. Pat. No. 6,067,467 issued May 23, 2000.
Commercial ventures have developed practical systems for monitoring patient anesthesia/sedation state. Representative examples include a patient state analyzer (SEDLine) manufactured by Physiometrix, Inc., the analytical aspect of which is described in Ennen, et al., U.S. Pat. No. 6,317,627, issued Nov. 13, 2001, and incorporated herein by reference in its entirety, and a system manufactured by Aspect Medical Systems, Inc. The Physiometrix SEDLine analyzer is a sedation monitor that uses spectral and temporal measurements processed from the patient's EEG to estimate a level of hypnosis or sedation. It produces a measure called the patient state index (PSI). The Aspect Medical system incorporates technology described in a series of patents of which Chamoun, U.S. Pat. No. 5,010,891, issued Apr. 30, 1991, and Chamoun, et al., U.S. Pat. No. 5,458,117, issued Oct. 17, 1995, are representative examples. The methods therein described make substantial use of a calculation of bispectral (BIS) indices of consciousness and anesthesia.
The previously described scoring systems can be used in conjunction with an EEG-based anesthesia and sedation monitor to provide an objective measurement of sedation level estimate and to show trends in the patient's level of anesthesia and sedation.
Although commercially available monitors are frequently trained against the Observer's Assessment of Alertness and Sedation scale (OAAS), they cannot readily differentiate between natural sleep induced hypnosis and chemically induced hypnosis. Although a computed hypnotic state parameter may be accurate, a patient who is merely asleep will respond rapidly to a provocative stimulus, whereas a patient with the same computed level of drug induced hypnosis will not. (If this were not true, people would not wake up to their alarm clock and there would be many more wake-ups during surgical procedures.) For example, an index of 40 for the SEDLine analyzer and 50 for the BIS monitors would represent ideal sedation under most circumstances for drug induced sedation. However, these numbers are also commonly obtained from patients enjoying normal sleep.
For a patient that is merely asleep and not chemically sedated or only lightly sedated, the patient state index or the BIS index would likely rise after an external stimulus is applied, but the value of these indices as a predictor of a response assumes prior knowledge of the sedative drugs, if any, being administered to the patient. A desired characteristic of a sedation monitor would be to eliminate the need for such a-priori drug information. However, currently no automated system for scoring patients against a validated sedation scoring system exists that provides a clinician the ability to differentiate between arousable sleep and non-arousable, drug-induced hypnosis.
One of the most common external stimuli used to assess whether a patient is merely asleep or is chemically sedated or anesthetized is the glabellar tap. The glabellar tap is a primitive reflex reaction in which the eyes blink if an individual is tapped lightly directly between the eyebrows. This reflex is observed whether the eyes are open or closed. An automated indicator of response to a glabellar tap, or even better to a simulated glabellar tap, is highly desirable.
The glabellar tap monitoring system of the present invention involves the application of a specific provocative electrical stimulus to the patient and an electronic observation of the presence or absence of a blink reflex. Automation of this assessment requires the presentation of an electrical stimulus through an auxiliary circuit, usually referred to herein as the “glabellar stimulator,” and the monitoring of the patient's response to the stimulus, particularly the patient's eyeblink amplitude and the patient's eyeblink response latency. The stimulus is delivered as an objective, repeatable stimulus delivered electronically either automatically or upon the demand of the clinician, e.g., through the use of a push-button activator.
The fully automated version of this invention includes equipment necessary for the electronic measurement of the patient's eyeblink amplitude, eyeblink latency, and morphology (e.g., the system described in U.S. Pat. No. 6,317,627), equipment necessary for calculating a response value based upon these electronically measured parameters, and a display for communicating the response value to a clinician. The glabellar stimulator can be integrated with a known EEG monitoring systems, such as that described in U.S. Pat. No. 6,317,627, or can be a stand-alone system designed to operate functionally in combination with such an EEG monitoring system. In the EEG system disclosed in U.S. Pat. No. 6,317,627, a plurality of electrodes are mounted on the patient's forehead, with at least one electrode, preferably the ground electrode, located just above an anatomical point called “the Nasion,” The Nasion is the valley or recessed area (as seen in profile) that is just below the eyebrows, generally considered to be where the nose “starts”. In most patients the Nasion is at the same level as the tips of the upper eyelashes. The Nasion is a reference point that can be used to locate electrodes associated with an EEG monitoring system.
The electronic glabellar tap stimulating and measuring system of this invention automates the delivery of a precise electrical stimulus that is independent of patient contact impedance. The system accomplishes this task by delivering a predetermined amount of charge from the stimulus circuit. The stimulus magnitude is independent of contact impedance by virtue of an arrangement in which a charge control comparator increases the pulse duration for a given preset stimulus magnitude and a higher contact impedance, resulting in the desired total charge being transferred to the patient. The system provides a continuous pulse train of mono-phasic or multi-phasic pulses. The system may also be programmed to deliver a train-of-four or a double burst stimulation pattern for assessment of drug-induced paralysis.
The embodiment of the present invention disclosed herein is calibrated to the Ramsay Sedation Scale (RSS) because of the RSS system is very familiar to many practitioners. However, it is to be appreciated that the present invention can be calibrated to any of the known sedation scales, and that the present invention can be parameterized to a new sedation scale, either one specifically designed for use with the system of the present invention or one that has applicability beyond the present invention.
The stimulus circuitry used in connection with the present invention can be actively charge-balanced to produce an approximately zero net charge transfer, that is, a substantially charge neutral electrical stimulus pulse or pulse train, within the glabellar stimulator blanking period. This feature contributes to achieving a near zero offset at the amplifier input, thereby contributing to maximum attenuation of the stimulus pulse artifact. Zero net charge, however, does not mean zero net energy. The stimulus current, independent of its sign, provides “stimulus energy”, which means energy as sensed by the patient's peripheral nervous system, not the calculated net physical energy delivered by the pulse generator. The patient's response, although non-linear, is a monotonically increasing function of the “stimulus energy”. For the most part, the difference between the energy delivered by the stimulus pulse generator and the stimulus energy is accounted for by the I2R losses from the electrodes.
The circuitry of the current invention is designed to be integrated with an EEG amplifier where, within milliseconds of the stimulus, EEG and eyeblink signals are processed. The EEG and eyeblink signal acquisition can be temporarily disabled while the stimulus is being applied to avoid unwanted transient artifacts caused by the stimulus pulse. The circuitry is also capable of being programmed to create train-of-four and tetanus pulses for paralysis monitoring.
As noted above, the glabellar tap is a reflex wherein a person's eyes blink if the individual is tapped lightly between the eyebrows. It has been determined that an electrical stimulus of the correct amplitude and duration, and of the correct pulse shape, will provoke a pseudo-glabellar tap blink reflex that varies in a predictable way and that produces response parameters, i.e., presence and magnitude of eyeblink, that can be detected and measured to generate an objective determination of the patient's depth of sedation. The presence and magnitude of the eyeblink response can be measured using an analytical system of the type disclosed in U.S. Pat. No. 6,317,627, optionally with modifications to the software for improved performance. Other EEG based monitoring systems for detecting and measuring the presence and magnitude of eyeblink can be configured used in conjunction with the present invention.
In order for an eyeblink event to be identified and scored for the waveforms depicted in
Each or a selected combination of the derived parameters of eyeblink amplitude and latency will produce an output, which when compared to predetermined or adaptive thresholds, are used to estimate the Ramsey Sedation Score. The Ramsey Sedation Score or any equivalent processed value can be displayed as a dimensionless metric such as used in RSS or RASS, or probability score representative of the probability that the person is responsive or non-responsive.
In alternative embodiments of the present invention, alternative physical and electrophysiological methods for detecting eyeblinks are utilized. One alternative utilizes a properly placed photoreflective sensor to detect eyeblinks. Although the photoreflective sensor is electrically isolated from stimulus pulse artifact and can detect both the presence of an eyeblink and the eyeblink latency, the accuracy of the photoreflective sensor's amplitude measurements may vary dependent on sensor placement. Other optical systems such as those used in headgear designed to detect drowsiness for certain task monitoring applications also can be used in conjunction with the present invention to detect eyeblinks.
The system of the instant invention replaces the stimulation of a mechanically applied glabellar tap with an electrical stimulus pulse. This pseudo-glabellar tap system uses, in one embodiment, a standard frontal (forehead) array of electrodes, e.g., conducting gel electrodes, to transmit electric pulses to appropriate locations on a patient's forehead. Preferably these locations are selected from known locations on the patient's forehead, e.g., the F8, Fp1, Fp2, F7, Afz, and Fpz locations, which are used to collect EEG input in the Physiometrix SEDLine system. However, it will be appreciated that other designations or locations can be used with various EEG monitoring systems.
Serial input output segment 16 sends converted signals to host instrument 18. As previously indicated, host instrument 18 can be configured per the system described in U.S. Pat. No. 6,317,627.
The stimulus pulses generated by the glabellar stimulator circuit of the present invention can approach 100 volts, and thus can be more than six orders of magnitude larger than the physiological responses being measured. For this reason, the system of the present invention preferably includes a system to attenuate this voltage by blocking the amplifiers' input during delivery of the stimulus (blanking period), by attenuating all signal inputs, and by minimizing the residual charge or charge transfer left on the second stage filter.
As illustrated in
During the shunt period the generation of the patient state index using previously transmitted signals can continue uninterrupted while the stimulus pulse is transmitted. The patient's response is analyzed after the shunt is reopened and incoming signals reach the preamplifier again. Blanking the amplifier in this manner makes it possible to detect eyeblinks within milliseconds of the stimulus.
The shunt by itself, however, may only attenuate the pulse voltage that reaches the preamplifier by a factor of approximately 100 to 1. For this reason, it may be necessary to provide additional protection from the pulse stimulus. Protective circuitry provided in patient module 18 can provide an additional 50 to 1 attenuation factor. As explained more fully below, approximately zero net charge transfer in the glabellar stimulator pulse train provides an additional attention factor of approximately 10-20 to 1, and common mode rejection of the residual pulse artifact that persists as an offset voltage can achieve an additional attenuation factor of approximately 10-20 to 1.
Referring to the circuit diagram of
During routine patient monitoring using the circuitry depicted in
The preamplifier blind period is not created by this H-bridge shunt but rather is created by the preamplifier input shunt 20 described above and illustrated in
Pulse polarity is determined by the set of opposing H-Bridge branches that are closed. In the embodiment of the present invention depicted in
The requisite pulse sequence logic is pre-programmed for a plurality of selectable pulse sequences. The stimulus pulse mode can be selected from a menu associated with host instrument 18. Host instrument 18 sends a command to a programmable logic array (PLA) 17 in the patient module, thereby setting its internal logic to initiate (upon command) the desired pulse sequence. The pulse-timing parameters are stored in the PLA 17. The stimulus pulse command can be initiated by depressing an external pushbutton 15, or by a timer in host instrument 18 that has been set by the user to check patient status at predetermined intervals.
The system of the present invention preferably is configured to monitor total charge in order to deliver the desired (relative, not absolute) stimulus energy. The net stimulus effect is independent of the sign and proportional to stimulus energy (in turn proportional to I2). In other words, the stimulus effect does not net out to zero while the system is driving the net stimulus pulse charge to zero.
The charge control comparator 34 depicted in
A triphasic pulse sequence with zero net charge can be produced in a similar fashion. Comparator 1 will trigger the pulse sequence logic 33 to invert the phase of a triphasic stimulus pulse when 25% of the programmed stimulus energy has been delivered. Comparator 3 will trigger the pulse sequence logic 33 to invert the phase of a triphasic stimulus pulse when 75% of the programmed stimulus energy has been delivered. This final phase reversed stimulus pulse then terminates when the output of the net charge integrator 35 returns to the reference value just prior to the stimulus pulse as shown at 45 in
For a given preset stimulus magnitude and higher contact impedance, the charge control comparator increases the pulse durations resulting in the same total charge being transferred to the patient. A voltage V1 at resistor 36 is set to ensure that the primary pulse magnitude at the transformer primary 32B times the turns ratio can produce a voltage of approximately 60 volts at the transformer secondary 32A. The transformer also provides for patient safety by providing isolation between active electronic circuitry and patient applied parts.
In an idealized case, the charge delivery efficiency of the stimulator is 100%. The very short switching times and low RON for the H-Bridge and the low primary resistance for T1 with optimized ET constant ensure optimum efficiency. The voltage drop on C1 is a reflection of the total charge transferred.
Table II identifies and describes applicable circuit states:
Basic stimulus pulse performance requirements related to circuit design of the pulse generator are addressed as follows:
The pulse generation circuit can be constructed such that it is capable of generating a plurality of pulse types beyond the glabellar stimulation pulses of the current invention. For example, the pulse generation circuit can be constructed to transmit a series of provocative stimuli separated by variable intervals of short duration. Specific appropriate pulse shapes and durations can be preprogrammed into the system as shown in
The system of the current invention is capable of generating the bi- and tri-phasic stimulation pulses shown in
The Physiometrix SEDLine preamplifier has a high level of immunity to environmental, physiological, and procedural interference, in part by virtue of filtering. (A description of the preamplifier and related circuitry appears in U.S. Pat. No. 6,430,437.) The Physiometrix SEDLine filtering configuration is a multistage filter comprising part of the SEDLine's anti-aliasing system.
As with the Physiometrix SEDLine system, the input stage for physiological monitoring systems in general has single or multi-stage filters. However, different designs of the input stage may require correspondingly different pulse morphology to achieve comparable results in a different filter configuration.
When small electrophysiological signals such as EEG, EMG and EOG are being monitored concurrently using the same leads as the stimulus, the effective net charge transfer should be as close to zero as possible in order to minimize contamination of the incoming signals by the stimulus pulse. A stimulus pulse several orders of magnitude larger than the physiological signals being monitored gives rise to a significant residual offset in a preamplifier stage proportional to the net charge divided by the filter capacitance of that stage. As spelled out more fully below, the use of the pulse morphologies shown in
With reference to
In addition to the basic shape configuration, two overall parameters of the charge transfer pulse amplitude and shape are important in the downstream functioning of the pseudo-glabellar tap electrical stimulation system. The first is the stimulus pulse net charge. The net charge parameter is the integral over time of the (signed) value of the current flow, positive and negative, that the system delivers. In order to minimize effects on downstream electronics, the pulse parameters are manipulated so that the Net Charge is as close to zero as is practicable. Zeroing out the net charge produces the electrical equivalent of a glabellar tap while minimizing the residual stimulus pulse artifact due to the net charge at the preamplifier.
The second important parameter is the stimulus pulse total charge. The total charge represents the integral of the absolute value of the stimulus current. Use of the word “Total” refers to the integrated value of the current of either sign, that is, the total charge in and out, that flows through the patient. The voltage change V1 ΔA) measured at 38 in
The physiological stimulus level is a function of the pulse amplitude and duration. It is not entirely a function of, or proportional to, the stimulus pulse total energy, which is proportional to the time integral of the square of the current, but rather is a function of the integral of the absolute value of the current over time. It has been found that the magnitude of the pseudo-glabellar tap response is a monotonically increasing function of the total charge parameter, as defined above.
The stimulus circuitry is connected in series with the patient signal ground lead, preferably located just above the Nasion. In the case of use of the Pysiometrix SEDLine system and the Physiometrix frontal array, the ground lead located just above the Nasion delivers the full stimulus current, while the remaining applied electrodes (5) each return approximately 20% of the delivered stimulus current. This configuration ensures proper focus of the stimulus for the pseudo-glabellar tap just above the Nasion.
Pulse current and duration can be controlled separately. (See
Eyeblinks arising from the glabellar reflex will occur within a window of 50 to 1000 milliseconds after the stimulus pulse. The properties of the stimulus pulse (as described above) and the EEG, EOG, and EMG signal acquisition process (as described below) produces a reliable measurement of eyeblink response.
As shown in
These measurements are compared to preset thresholds arrived at empirically. The eyeblink response to the pseudo-glabellar stimulator is measured and scored to determine equivalent RSS value in the range of levels 3 through 6. Combining the derived equivalent RSS value with, in the PSI from the patient state analyzer helps to differentiate between natural sleep and drug sedation.
The system of the present invention can be constructed utilizing an EEG-based eyeblink detector embodiment substantially similar to that described in U.S. Pat. No. 6,317,627, incorporated herein by reference. The function of eyeblink detection according to Ennen, et al. is described at Col. 9, line 26, through Col. 10, line 7. Eyeblink measurement parameters include amplitude and latency. These measurements are compared to preset thresholds that are arrived at empirically.
The system of Ennen, et al. can be modified to provide improved eyeblink discrimination. The eyeblink signal can be optimized in the presence of background EEG, EMG, and noise by summing the contra-lateral bipolar electrode pairs, for example, (Fp2-F8)+(Fp1-F7). Changes in the eyeblink signal profile that are a function of where the eyes are pointing are minimized by summing the contra-lateral bipolar electrode pairs, for example: (Fp2-F8)+(Fp1-F7).
The bipolar measurements (Fp2-F8)+(Fp1-F7) provide additional reduction in residual common mode energy when the stimulus is presented between the ground and reference leads. The signal represented by (Fp2-F8)+(Fp1-F7) is analyzed as described above. The eyeblink detector as described in U.S. Pat. No. 6,317,627 utilizes the sum of the contra-lateral bipolar electrode pairs referred to above.
Because most clinicians are skilled in and comfortable with the Ramsay Sedation Scale and its application, the embodiment of the present invention discussed herein converts the eyeblink parameter output to an RSS number. This scale is calibrated by clinical benchmarking. The method of measurement of eyeblink amplitude and latency are discussed above. These two parameters establish a bivariate function of sedation level. Using any of a number of techniques, including but not limited to the discriminant function technique referenced in U.S. Pat. No. 6,317,627, these values can be combined into a single discriminant score that is a monotonic function of sedation level. This in turn can be scaled, preferably by a monotonic function, to a Ramsay Sedation Scale value. Alternatively either the single parameter or the raw amplitude and latency values are tabulated, compiled in a database of eyeblink and latency measurements, and then compared statistically with clinician estimates of RSS. The resulting collection of clinical data in comparison to measured parameters enables the establishment of a functional relationship between either the raw parameters or a discriminant score and the RSS. By comparing the means, or the weighted combination of the means, of amplitude and latency measurements at clinically estimated RSS scores, an RSS equivalent scale is provided.
The eyeblink response to these singular or consecutive stimuli will be measured and scored to determine equivalent RSS from levels 3 through 6. The automated measurement of the RSS state will be accomplished concurrently with computation of the patient state index. The value of the computed RSS score, when displayed with the Patient State Index or BIS index, will enable an estimation of whether the index indicates natural sleep or drug induced hypnotic state. A change, especially an increase in the patient state index a few seconds after a provocative stimulus, provides an indication of patient responsiveness that can also be used to differentiate natural sleep from drug-induced hypnosis.
The numeric processed value of the response to the glabellar stimulator of the present invention can be displayed as a stand-alone trend or as a complementary independent indication of patient responsiveness to other processed hypnotic terms (such as PSI, BIS, State or Response Entropy) or unprocessed physiological parameters such as ETCO2, Blood Pressure or Heart Rate. The Ramsay Sedation Score, or any equivalent processed value, can be displayed as a dimensionless metric such as used in RSS or RASS, or probability score representative of the probability that the person is responsive or non-responsive.
Although the system of the present invention has been disclosed and described herein in the context of certain preferred embodiments, it will be appreciated by those of ordinary skill in the art that various modifications to and equivalents of the system can be made without departing from the intended spirit and scope of the present invention. The following claims are intended to encompass such modifications and equivalents.
This application claims priority from U.S. Provisional Patent Application No. 60/604,799, filed Aug. 26, 2004.
Number | Date | Country | |
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60604799 | Aug 2004 | US |