AU743765B2 - Monitoring the occurence of apneic and hypopneic arousals - Google Patents

Description

S&F Ref: 288512AUD1

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT

ORIGINAL

Name and Address of Applicant: Actual Inventor(s): Address for Service: Invention Title: ResMed Limited 82 Waterloo Road North Ryde NSW 2113 Australia Gregory Alan Colla and John William Ernest Brydon Spruson Ferguson St Martins Tower 31 Market Street Sydney NSW 2000 Monitoring the Occurence of Apneic and Hypopneic Arousals *n The following statement is a full description of this invention, including the best method of performing it known to me/us:- 5845c Monitoring the Occurrence of Apneic and Hypopneic Arousals Field of the Invention This invention relates to methods and apparatus for the determination or monitoring of arousals that are indicative of an apneic or hypopneic episode. An "A/H episode", as used hereafter, is to be understood as including both obstructive apneas (lack of breathing) or hypopneas (reduction in breathing) occurring during sleep.

Background of the Invention People suffering from Obstructive Sleep Apnea (OSA) and related conditions experience many A/H episodes during sleep. The conventional treatment for OSA is the well known Continuous Positive Airway Pressure (CPAP) treatment. An A/H episode often has an associated arousal, which is a nervous system response to low blood oxygen level and/or high blood carbon dioxide level.

o.e 15 The condition of OSA normally is diagnosed by laboratory based polysomnography (PSG). PSG involves the measurement of sleep and respiratory variables including EEG, EOG, chin EMG, ECG, respiratory activity, nasal airflow, chest and abdominal movements, abdominal effort and oxygen saturation. The data gathered leads to a calculation of the Respiratory Disturbance Index (RDI) which is the average number of arousals per hour due to respiratory disturbance. PSG is uncomfortable for a patient due to the placement of numerous electrodes on the patient's head or face and the wearing of a mask or nasal prongs. PSG is an expensive procedure and has the inconvenience of requiring the patient to attend a sleep clinic for a whole night requiring continuous technician attendance.

In the clinic, cortical arousals can be detected by measuring and interpreting, either automatically or by eye, changes in the patient's EEG and EMG. Arousals are an important indicator of the amount and quality of sleep obtained by a patient and the degree of severity of the patient's apneas.

-2- To obtain a display of the EEG, electrodes must be attached to the patient's head and the signals from these electrodes passed through high gain amplifiers before subsequent display and recording. This is often inconvenient and time consuming; the s signals also can become distorted or disappear due to electrode dislodgement or other artefacts such as sweating. To detect an arousal, the EEG, once displayed, requires interpretation either visually by a skilled operator or automatically by a computer-based analysis system. Apart from the difficulties of attaining accurate EEG data, EEG apparatus also is relatively more expensive than much other biomedical apparatus.

EEG data on its own is not an accurate determination of the occurrence of A/H episodes an arousal can be due to other factors as noted.

Prior art disclosures that form background information to the present invention include R. Ferber, et al, "ASDA Standards of Practice Portable Recording in the Assessment of Obstructive Sleep Apnea", Sleep, 17(4): 378-392, 1994; L. Ferini- Strambi, et al, "Heart rate variability during sleep in snorers with and without obstructive sleep apnea, Chest, 102(4): 1023-7, Oct. 1992; and C. Guilleminault, et al, "A review of 50 children with obstructive sleep apnea syndrome", Lung, 159:275-287, 1981.

S •Summary of the Invention It is an object of the present invention to overcome or at least ameliorate one or more of the problems with the prior art. In one preferred form the invention seeks to provide a method and apparatus for monitoring the occurrence of arousals due to A/H episodes.

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o*oo e o oO [R:\LIBK]I01896.doc:jls -3- It has been determined that the coincident occurrence of change in the sympathetic physiological variable of sweating and another physiological variable is indicative of an arousal associated with an apneic or hypopneic episode.

Therefore, the invention discloses an apparatus for monitoring the occurrence of arousals associated with apneic or hypopneic episodes, the apparatus comprising: sensor means for obtaining two or more signals each indicative of sympathetic nervous system activity from a patient, one said signal representative of skin conductance and or each other signal representative of other sympathetic nervous system variables; and means for 1o correlating said skin conductance signal and at least said other signal, a coincident change in said correlated signals being indicative of the occurrence of an arousal.

The correlation can be other than a correlation in the strict mathematical sense, including coincident visual inspection, logical ANDing, indicator voting or weighted sums relative to a threshold.

Preferably, the sensor means comprises electrodes attachable to a patient's body.

The signals derived from the electrodes can be signal-conditioned. Furthermore, the means for correlating includes data processor means. Each said signal can have an o 20 associated confidence level so that a weighting can be applied in the correlation.

o The changes in physiological states can include reduction in blood oxygen saturation, change in heart rate, change in skin conductance, change in skin temperature, and increase in blood pressure.

oo The invention further provides a method for monitoring the occurrence of arousals associated with apneic or hypopneic episodes, the method comprising the steps of: obtaining two or more signals, each indicative of sympathetic nervous system activity from a patient, one said signal representative of skin conductance and the or each other signal representative of other sympathetic nervous system variables; correlating the skin conductance signal and at least one said other signal; and determining whether there is a coincident change in said correlated signals as an indication of the occurrence of an arousal.

[R:\LIBKOI 896.doc:js Embodiments of the invention have the advantage of being non-invasive. This is of particular importance when diagnosis of conditions such as OSA must be undertaken on a baby or small child who may be disturbed by the conventional PSG apparatus.

One embodiment, relating to apparatus for the acquisition of data from which the diagnosis of apneic or hypopneic episodes, and thus the likelihood of the presence of conditions including OSA exist in a patient, can, in the first instance, substitute for a conventional sleep study and allow a candidate to collect data when in the home in a noninvasive manner. The data then can be analysed by a medical practitioner and a determination made of whether further detailed investigations need to be conducted.

Brief Description of the Drawings Fig. 1 is a schematic block diagram of diagnostic apparatus embodying the 15 invention; THE NEXT PAGE IS PAGE 6 *oooo *oo oooo* [R:\LIBKO I896.doc:jls -6- Fig. 2 is a schematic block diagram of a circuit for measuring skin conductance; Fig. 3 is a plot of skin conductance with time; Fig. 4 is a plot of skin conductance together with airflow rate, heart rate and SaO 2 and Fig. 5 is a plot of skin conductance measured periodically both before and during CPAP treatment is implemented.

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o4 20 Description of Preferred Embodiments The sequence of events leading to an arousal due to an apnea or hypopnea are as follows: 1. The patient's upper airway obstructs as they try to inspire, or the central nervous system drive to breathe is inhibited and the patient makes no effort to breathe.

2. The oxygen level in the patient's arterial blood begins to fall and the carbon dioxide level rises.

3. After some time, which may exceed a minute, blood gas sensitive receptors in the carotid and/or aortic arteries force an arousal causing the patient to partially wake and recommence breathing.

This sequence is associated with a number of physiological changes (apart from those of the EEG referred to above) some of which are driven by the sympathetic nervous system which can be monitored: 1. A fall in blood oxygen saturation (SaO 2 with subsequent post-apneic rise. SaO 2 can be measured by pulse oximetry.

2. A decrease in heart rate as the patient's hypercapnia increases, followed by an increase when they arouse and restart breathing. Heart rate can be measured by ECG techniques.

3. A change in skin conductance due to sweating, measured by application of an electrical potential to measure conductance/impedance.

4. Increase in blood pressure. Blood pressure can be measured by continuous sphygomomanometry.

5. Change in constriction of blood vessels in the skin leading to a change in skin temperature and a change in tissue volume, particularly that in the fingers. This can be measured by plethysmography.

6. A reduction in breathing sounds as the apnea occurs followed by a snore or snort when the apnea is broken.

Taken separately, each of the above changes is only ambiguously related to an arousal after an obstructive event. Each also is subject to artefacts in the signal which are a function of how it is measured. However, by combining several of the above measurements, a much more artefact-free and specific diagnostic indicator of an arousal due to an A/H episode can be obtained.

15 Fig. 1 shows a plurality of sensors 1 0 1-10n from which signals of the type described above are obtained from the patient. The sensors typically will comprise a sensing portion to detect physiological functions such as blood oxygen saturation, heart rate, skin conductance, blood pressure, skin temperature and audible noises, coupled owith amplifying/buffering devices to derive an electrical signal.

The electrical signals each are passed to a corresponding preprocessing section 121-12 n The conditioning typically can include averaging, thresholding linearisation and differentiation for those signals which exhibit a marked change. Each of the n signals has a characteristic pattern or range of patterns associated with apneic and hypopneic events. Each matching pattern serves as an indicator for an apneic or hypopneic event. A characteristic pattern for each signal is as follows.

1. The blood oxygen saturation signal (SaO 2 is low-pass filtered, resulting in a baseline value. Signal values which differ from the baseline by a predetermined threshold, typically are positive indicators.

-8- 2. The heart rate signal is low-pass filtered to remove high frequency components, including the sinus rhythm. This signal is then differentiated, so that changes in the heart rate are evident. A fall in the heart rate followed by a marked increase in heart rate is an indicator. When the difference between the slowest and fastest heart-rate is greater than a specified minimum, typically beats per minute, the indicator scores positively.

3. The skin conductance is low-pass filtered, resulting in a baseline value, then is high-pass filtered to accentuate changes. When the conductance increases above a specific ratio of the baseline, typically 100%, the indicator scores positively.

4. The blood pressure signal (both systolic and diastolic) is low-pass .".filtered to produce a baseline value. The elevation of the blood pressure by more than a predetermined threshold, typically 25%, results in a positive indicator.

5. The skin temperature is low-pass filtered to produce a baseline value.

If the skin temperature falls below a specific threshold from the baseline, typically between 0.5 and 1.0°C, the indicator is positive.

6. Breathing sounds are band-pass filtered, typically between 30 and 300 Hz. The energy from this signal is estimated by squaring or rectifying the i 20 filtered signal, and is used as a measure of snore intensity. A significant fall in the snore intensity, typically by 6 dB, followed by a sharp increase, is a positive indicator.

The conditioned signals 141-14n, together with a quality signal 161-16 n giving a measure of the quality (confidence) of the signal, are passed to a multi-input processing device 18. The multiple input signals are processed algorithmically, with ones of the signals 14 having the higher quality factor being given more weight.

-9- The detection of an isolated matching pattern does not signify an apneic or hypopneic event. However, the coincidence of two or more of these indicators increases the confidence of event detection. Various algorithms can be used: 1. Indicator ANDing, whereby each of the indicators must be positive to indicate an arousal.

2. Indicator voting, whereby most of the indicators must be positive to indicate an arousal.

3. Weighted sum, whereby each of the indicators has a predetermined weight. The products of each indicator and its weight are accumulated. The sum indicates an arousal if the sum is above a predetermined threshold.

The processing device 18 thus makes a determination of whether an arousal associated with an A/H episode has occurred, and further determines the percentage !ili chance that this 'diagnosis' is correct, and yet further provides a determination of the duration of the A/H episode that preceded the arousal. These determined functions are logged to a memory device 20 for subsequent analysis, for example by plotting with time and observing coincidences, and also can be indicated on a display device 22 in real time.

From this information an index of arousals can be compiled, typically as arousals per hour, providing an alternative indicator to ROI, as previously discussed, to serve as a useful indicator of sleep quality.

In another embodiment the signals obtained from the sensors can be directly stored in the memory device 20 in a time sequence for subsequent correlative processing by the processing device 18, or by a processor independent of the data acquisition module. This embodiment can serve as a data acquisition device for home usage, with the correlative processing occurring at a medical practitioner's surgery (for example) at a later time.

Particular embodiments now will be described, relating to clinical measurements performed on three patients, and for which the physiological variables measured include skin conductance and heart rate (particularly cardiac rate, both of which are sympathetic variables).

Heart rate is measured by a conventional technique, namely three lead ECG.

It is preferred that the electrodes are located at the patient's body's extremities to avoid apprehension and reduce the likelihood of unwanted artifacts due to gross body movement.

The skin conductance measurement similarly is performed at the body's extremities, in one case being on the sole of a foot where sweat glands are concentrated. An alternate site is the forehead. Skin conductance is to be understood as the reciprocal of skin resistance, which is affected by sweating. In the complex number domain, conductance is the real part of skin admittance. As follows, skin also exhibits a reactive property (essentially a capacitance), the reciprocal of which is the susceptance.

Fig. 2 shows a schematic block diagram of a skin conductance measurement system 30 representing one form of a sensor 10 and preprocessing section 12. An oscillator 32 applies a 1 kHz signal of approximately 0.6 Vpp signal between two electrodes placed apart on the sole of the patient's foot, thereby applying an excitation S•i *to the patient's skin 34. The current passing through the electrodes is dependent upon the conductance and susceptance of the skin and interconnecting tissue.

S 20 A sense resistor 36 converts the current to a signal voltage cS, which is *amplified by an amplifier 38. A demodulator circuit 40,42 removes the effects of the skin susceptance due to the skin's capacitance) from the amplified signal CS, so that the resulting signal, SCL, is proportional to the skin conductance (level). The baseline of the SCL is removed by a high pass filter 44 and amplified (not shown) so that responses to arousals are accentuated and more easily monitored. The resultant signal, SCR, is indicative of the skin conductance response.

Fig. 3 shows a time window of one half an hour during a sleep study performed on a patient known to be a sufferer of Obstructive Sleep Apnea. The upper -11trace represents the skin conductance SCL, and the lower trace the skin conductance response SCR. The sensed response at approximately t 267.5 minutes corresponded with an apneic arousal otherwise determined by PSG. Skin conductance thus is a reliable partial indicator of an arousal associated with an A/H episode.

Fig. 4 shows an excerpt from a sleep study conducted on a different patient showing a relevant 30 minute window. The patient is a known sufferer of OSA. The uppermost trace is heart rate filtered over one minute to remove sinus rhythm. The units are beats per minute, and the measurement is made with a pulse oximeter. The second trace (in descending order) is blood oxygen saturation (SaO 2 also measured with a pulse oximeter. The scale is 0-100%. The third trace is the SCR phase reference signal and the fourth trace the SCL base reference signal as measures of skin conductance. The units of conductance are relative only. The lowermost trace is of respiratory airflow measured with nasal cannulae and a pressure transducer.

Fig. 4 shows a continuous decrease in nasal airflow until approximately t 11 minutes corresponding to a hypopneic event. At this point nasal airflow increased with the taking of a sudden deep breath. The SaO 2 trace shows a corresponding fall of approximately which, because of heavy filtering, appears after the resumption of normal breathing, although in fact was coincident with the sudden deep breath. The chain of events was shallow breathing (hyponea), followed by a fall in SaG 2 followed by a resumption of normal breathing. Associated with the arousal causing the resumption of normal breathing is tachycardia, with the heart rate increasing by about bpm. The arousal is coincident in time with the sudden increase in skin conductance and heart rate. Thus these two quantities can be utilised in concert as an indicator of arousals associated with A/H episodes.

Interestingly, at approximately t 20 minutes, there is a sudden interruption in respiratory airflow as a result of the patient sighing, however there is no corresponding indicator in either skin conductance or heart rate to suggest that the cessation of flow was due to an apnea.

-12- The data indicates that the correlation of skin conductance with one or more other physiological variables (whether associated with the sympathetic nervous system or not) or any two or more sympathetic physiological variables (for example blood pressure and heart rate), is an accurate determinant of the occurrence of an arousal associated with an A/H episode. Further, it is believed that the correlation of two sympathetic physiological variables, not necessarily including skin conductance, and for example heart rate and blood pressure, also is an accurate determinant.

Fig. 5 shows a plot of the variance of skin conductance for the third patient during a sleep study in which between t 20:30 hours and t 1:15 hours no CPAP treatment was in place, and between t 1:15 hours and t 5:30 hours CPAP treatment was in place. The sampling points are at five minute epochs. The 10 and :centiles have been shown. The plot indicates the reduction in variance of skin conductance both before and after the commencement of CPAP treatment as an indication of the reduction in the number of arousals due to A/H episodes and thus the reliability of skin conductance as a partial indicator of A/H episodes.

S In summary, embodiments of the invention can serve to monitor the occurrence of apneic or hypopneic episodes, to diagnose the occurrence of A/H episodes resulting :in arousals, to acquire data from which the diagnosis of A/H episodes resulting from arousals can be made, to determine an index of sleep quality, and to monitor the 20 sympathetic nervous system.

Claims (8)

1. Apparatus for monitoring the occurrence of arousals associated with apneic or hypopneic episodes, the apparatus comprising: sensor means for obtaining two or more signals each indicative of sympathetic nervous system activity from a patient, one said signal representative of skin conductance and or each other signal representative of other sympathetic nervous system variables; and means for correlating said skin conductance signal and at least said other signal, a coincident change in said correlated signals being indicative of the occurrence of an arousal. i0

2. Apparatus as claimed in claim 1, wherein said means for correlating includes a data processor for receiving and analysing said signals.

3. Apparatus as claimed in claim 2, wherein said data processor analyses said signals by one or more of the operations of: mathematical correlation, logical ANDing, indicator voting, and weighted sums relative to a threshold.

4. Apparatus as claimed in any one of the preceding claims, further comprising a memory for storing a time sequence of said signals for analysis, and said 20 data processor calculating an index of sleep quality proportional to the number of arousals V•o° in a period of time. o Apparatus as claimed in any one of the preceding claims, further comprising an indicator coupled to said data processor means, the indicator giving a visual indication upon the occurrence of an arousal. o00o

6. Apparatus as claimed in any one of the preceding claims, wherein the or each said other signal representative of sympathetic nervous system activity is chosen from blood oxygen saturation, heart rate, skin temperature, and blood pressure. o

7. Apparatus as claimed in claim 6, further comprising sensor means for obtaining a signal representative of breathing sounds, said breathing sounds signal being Sprovided to said data processor for inclusion in the correlation analysis. [R:\LIBK]OI 896.dmjcjI -14-

8. A method for monitoring the occurrence of arousals associated with apneic or hypopneic episodes, the method comprising the steps of: obtaining two or more signals, each indicative of sympathetic nervous system activity from a patient, one said signal representative of skin conductance and the or each other signal representative of other sympathetic nervous system variables; correlating the skin conductance signal and at least one said other signal; and determining whether there is a coincident change in said correlated signals as an indication of the occurrence of an arousal.

9. A method as claimed in claim 8, wherein said step of correlating 0io includes one or more of the processes of mathematical correlation, logical ANDing, indicator voting, and a weighted sum relative to a threshold. A method as claimed in claim 7 or claim 8, comprising the further step of determining an index of sleep quality that is proportional to the number of arousals in a Is period of time. :11. A method as claimed in any one of claims 7-9, wherein the or each said other signal representative of nervous system activity is chosen from blood oxygen saturation, heart rate, skin temperature, and blood pressure. DATED this twelfth Day of October, 2001 ResMed Limited S"Patent Attorneys for the Applicant SPRUSON FERGUSON [R:\LIBKOI 896.doc:jls