Demand apnea control of central and obstructive sleep apnea

An apparatus and method for the control of both central and obstructive sleep apnea using electrical stimulation on a demand basis. Implantable sensors monitor the respiration cycle and determine the occurrence of apnea events. Central apnea is sensed by the passage of an escape interval of time without the sensing of an inspiratory event and a concurrent decrease in blood oxygen saturation. Obstructive sleep apnea is sensed as an abnormal pressure differential across the airway. The diaphragm is electrically stimulated upon sensing of central apnea. The musculature of the upper airway is electrically stimulated upon sensing of an occurrence of obstructive sleep apnea. Stimulation of the upper airway is provided whenever central apnea is sensed.

CROSS REFERENCE TO CO-PENDING APPLICATIONS 
U.S. patent application Ser. No. 07/610,854, filed Nov. 8, 1990, entitled 
"Muscle Tone"; U.S. patent application Ser. No. 07/610,851, filed Nov. 8, 
1990, entitled "Servo Muscle Control"; and U.S. patent application Ser. 
No. 07/617,158, filed Nov. 23, 1990, entitled "Multiple Stimulation 
Electrodes", are all assigned to the assignee of the present invention and 
incorporated herein by reference. 
BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates generally to implantable medical devices, and 
more particularly, relates to implantable medical devices for the 
treatment of apnea. 
2. Description of the Prior Art 
The medical characteristics of sleep apnea have been known for some time. 
There are two generally recognized forms of the disease. The first is 
central sleep apnea, which is associated with the failure of the body to 
automatically generate the neuro-muscular stimulation necessary to 
initiate and control a respiratory cycle at the proper time. Work 
associated with employing electrical stimulation to treat this condition 
is discussed in "Diaphragm Pacing: Present Status", by William W. L. 
Glenn, in Pace, Volume I, at pages 357-370 (July-September 1978). 
The second condition is known as obstructive sleep apnea. It is discussed 
at some length in "Obstructive Sleep Apnea: Diagnosis and Treatment", by 
Drs. Cook and Osguthorpe in Journal of South Carolina Medical Association, 
81 (12): 647-651 (December 1985). 
At present, a tracheostomy may be the treatment of choice for a number of 
patients when obstructive sleep apnea is severe. A less traumatic recent 
approach is continuous positive airway pressure (CPAP). This technique 
seeks to maintain upper airway patency with compressed air. More recently, 
some interest has been displayed in electrical stimulation of the muscle 
tissue along the upper airway during respiration. U.S. Pat. No. 4,830,008 
issued to Meer discusses a technique for electrical stimulation of the 
muscles of the upper airway in synchrony with the respiratory cycle. U.S. 
Pat. No. 4,506,666 issued to Durkan discusses such stimulation in 
conjunction with pressurized airflow supplied by a respirator. 
The electrical stimulation of the prior art techniques, however, are 
primarily concerned with causing contractile motion of the stimulated 
muscle. This means that the stimulation energy must necessarily be 
relatively large, and the effects of the stimulation are directly 
cognizable by the patient. 
More significant is that prior art systems tend to be directed toward 
treatment of either central or obstructive sleep apnea. There exists no 
effective means for treating both conditions which are found together in a 
sizable number of patients. 
SUMMARY OF THE INVENTION 
The present invention overcomes the disadvantages of the prior art systems 
by providing an apparatus and method for treating both central sleep apnea 
and obstructive sleep apnea in a coordinated fashion using a single 
hardware system. The treatment involves monitoring the respiratory 
activity of the patient and supplying appropriate stimulation as required. 
To monitor events of central sleep apnea, sensors are employed to detect 
indices of reduced or absent respiratory drive. For example, a pressure 
sensor implanted in the thorax can be used to detect respiratory effort. 
An oxygen sensor implanted in the circulatory system can be used to detect 
arterial oxygen saturation or mixed venous oxygen saturation, both 
measures decreasing during apnea. A sensing electrode implanted on the 
phrenic nerve can be used to detect central nervous system inspiratory 
drive to the respiratory muscles. 
Information from these sensors can be evaluated in a decision algorithm to 
determine if central apnea is present. For example, lack of respiratory 
effort and/or phrenic nerve activity, and decreasing blood oxygen 
saturation are indicative of central apnea. Each of the sensors can be 
used individually as well. For example, lack of respiratory effort or 
phrenic nerve activity for a specified period of time since the last 
respiratory effort could indicate central apnea. Similarly, falling blood 
oxygen saturation could also indicate central apnea. 
It should be noted however, that no single sensor is as reliable as a 
combination of sensors in detecting central apnea. The decision must be 
made whether to incur the added complexity and cost associated with 
multiple sensors to provide improved accuracy of apnea detection. 
In response to a detected situation of central apnea, the implantable pulse 
generator provides stimulation pulses to electrically stimulate 
contraction of the diaphragm to artificially initiate inspiration. 
An easy, but less accurate way to monitor events of central sleep apnea is 
to employ sensors to determine the time of occurrence of inspiratory and 
expiratory activity. An escape interval clock is used to measure the time 
between such activity. Whenever initiation of inspiratory activity is 
delayed beyond a predetermined time, it is assumed that a central sleep 
apnea event has occurred. 
An obstructive sleep apnea event is identified by an abnormally high 
pressure differential across the upper airway during inspiration. As a 
result, the implantable pulse generator provides a train of stimulation 
pulses to the muscles of the upper airway to cause contraction of muscles 
which can separate (or open) the walls of the airway, and thereby remove 
the obstruction. Because the basic respiratory timing is interrupted 
during a central sleep apnea event, stimulation of the upper airway is 
always provided for respiratory cycles for which diaphragm pacing is 
employed.

DETAILED PREFERRED EMBODIMENTS 
FIG. 1 is a schematic diagram of the respiratory system of patient 10 
during inspiration. As a result of contraction of diaphragm 18, which 
increases the volume of thorax 16, a partial vacuum is created causing air 
to enter upper airway 12 and proceed in the direction of arrow 14. During 
an event of central sleep apnea, the neurological system of patient 10 
fails to automatically stimulate contraction of diaphragm 18 at the 
appropriate time for inspiration. This condition may be sensed by 
monitoring the EMG of diaphragm 18, pressure difference between the thorax 
16 and the ambient, airflow within upper airway 12, or other indication of 
inspiration at a time appropriate for inspiration. 
FIG. 2 is a schematic diagram of the respiratory system of patient 10 
during an obstructive apnea event. During inspiration, upper airway 12 
tends to collapse producing the obstruction to air flow at point 21. The 
above referenced literature describes in detail the physiological 
processes associated with the collapse of upper airway 12. 
FIG. 3 is a graphical representation for pressure 24 measured within upper 
airway 12 during respiration as a function of time 26. Curve 28 shows the 
pressure for normal functioning of the respiratory system. Time 35 
represents the end of the expiration portion of the cycle. Inspiration 
occurs from time 35 through time 36. Curve 32 shows the pressure 
measurements for the patient during central sleep apnea. The delay from 
time 37 to time 36 may be sufficient to detect central sleep apnea. Note 
that because respiration is a partially voluntary function, the rate may 
vary substantially providing a low confidence in detection solely by this 
means. Because curve 32 is produced by artificial stimulation of diaphragm 
18 at point 36, it results in a somewhat larger amplitude without the flat 
plateau at the desired pressure. This is caused by the less even 
contraction of diaphragm 18. 
Curves 38 and 40 represent the monitored pressure during inspiration with 
and without central sleep apnea, respectively. Detection of obstructive 
sleep apnea along curve 38 can occur as soon as time 37. 
FIG. 4 is a schematic diagram of patient 10 showing implantation of an 
electrical stimulation system for the treatment of both central and 
obstructive sleep apnea. Implantable pulse generator 20 is placed 
subcutaneously at a convenient position. Diaphragm 18 is electrically 
stimulated via electrode 56 coupled to lead 54. 
Patency of upper airway 12 is monitored by pressure sensor 42 and pressure 
sensor 48 coupled to implantable pulse generator 20 via cables 44 and 46, 
respectively. Stimulation of the musculature of upper airway 12 is 
accomplished via lead 52 coupled to electrode 50. All other referenced 
elements are as previously described. 
FIG. 5 is a plan view of a chronically implantable pressure transducer 60 
similar to that implanted as pressure sensors 42 and 48 (see also FIG. 4). 
Distal end 62 of chronically implantable pressure transducer 60 contains a 
semiconductor sensing element properly packaged for chronic implantation. 
Lead body 64 optionally contains pressure reference lumen 66, which is 
coupled to pressure vent 68. Electrical connector 70 couples to 
implantable pulse generator 20. For additional construction details, the 
reader may consult U.S. Pat. No. 4,407,296 issued to Anderson incorporated 
herein by reference. 
FIG. 6 is a block diagram of implantable pulse generator 20 employing the 
present invention. The pressure measurements of upper airway 12 from 
pressure sensors 42 and 48 (see also FIG. 4) are provided by cables 44 and 
46, respectively, to differential amplifier 72. The output of differential 
amplifier 72, which is more positive than negative, is rectified by 
half-wave rectifier 73 to eliminate the negative-going portion of the 
signal. This ensures that the resulting signal reflects pressure 
measurements of only the inspiratory portion of the respiration cycle. 
The inspiration pressure signal is integrated by low pass filter 74 over a 
period which is less than the normal respiration cycle. Integration or 
filtering in this manner eliminates high frequency pressure spikes. 
Circuit 76 monitors the inspiration signal in relationship to a first and 
lower threshold I. This first threshold is sufficient to determine only 
whether or not inspiration is in progress. The point is to make a 
determination of it and when inspiration begins. Circuit 76 provides a 
high binary output during inspiration, and a low binary output at all 
other times. 
The output of circuit 76 is supplied to "or" gate 92 to provide a reset 
signal to escape timer 82 whenever inspiration begins. Escape timer 82 
uses the output of oscillator 80 to determine the interval during which 
inspiration is anticipated. Should escape timer 82 finish counting the 
interval before "or" gate 92 provides a reset, the output of escape timer 
82 provides a signal to "and" gate 84. If threshold I has not been reached 
at that time, "and" gate 84 provides an output to one-shot 94 for the 
generation of electrical stimulation of diaphragm 18 (see also FIG. 4). 
The duration of electrical stimulation of diaphragm 18 is controlled by the 
output of one-shot 94. The electrical stimulation pulse train is generated 
by stimulation generator 98. The generated pulse train is amplified by 
output amplifier 104 and supplied to electrode 56 via lead 54 (see also 
FIG. 4). 
The outputs of circuit 76 and "and" gate 84 are supplied to "or" gate 86. 
Thus "or" gate 86 provides an output whenever naturally initiated 
inspiration is sensed by circuit 76 or electrically stimulated by the 
output of "and" gate 84. This output is provided to "and" gate 88. 
Circuit 78 monitors the inspiration signal and compares it to a higher 
threshold II. This threshold is set to distinguish between the normal 
increase in pressure of upper airway 12 associated with inspiration and 
the abnormal increase in pressure of upper airway 12 associated with 
obstructive sleep apnea. Such an abnormal pressure measurement causes 
circuit 78 to provide a binary high to "and" gate 88, which is "anded" 
with the inspiration signal from "or" gate 86. The output of "and" gate 88 
is provided to one-shot 90 which provides a timed output to delay 96. 
Proper timing of the electrical stimulation of upper airway 12 is ensured 
by the output of delay 96. The pulse train is generated by stimulation 
generator 100 and amplified by output amplifier 102. The stimulation pulse 
train is supplied to electrode 50 via lead 52 (see also FIG. 4). 
FIG. 7 is a graphical representation of various key signals within 
implantable pulse generator 20. Curve 108 is the half-wave rectified 
output of low pass filter 74 (see also FIG. 6). Pulse 110 represents the 
pressure measurement for normal inspiration. Pulse 112 represents the 
pressure measurement for inspiration during an obstructive event during 
sleep. The absence of a pulse at time 106 represents a central sleep apnea 
event. 
Curve 114 represents the output of circuit 76. Pulses 116 and 118 indicate 
detection of naturally occurring inspiration. No such detection is made at 
time 106. Curve 121 shows the output of escape timer 82. Pulses 122, 124, 
and 126 indicate the times before which inspiration should have occurred 
or a central sleep apnea event is assumed. Therefore, time 106 is assumed 
to be a central sleep apnea event. 
The output of output amplifier 104 is represented by curve 128. An 
electrical stimulation pulse train consisting of pulses 130a-130n is 
generated beginning at time 106 in response to the assumption that a 
central sleep apnea event has occurred. 
The output of circuit 78 is represented by curve 132. Because pulse 112 is 
in excess of threshold II (see also FIG. 6), pulse 134 is provided. Curve 
136 represents the output of output amplifier 102. It consists of a 
stimulation pulse train of pulses 138a-138n generated in response to pulse 
134. 
FIG. 8 is a schematic diagram of patient 10 having implanted a multiple 
sensor stimulation system. Sensor 158 is a standard neurological sensor 
coupled to the phrenic nerve. It transfers an electrical indication of 
neurological inspiratory drive to implantable pulse generator 120 via lead 
150. 
Sensor 152 is implanted within the cardiovascular system (e.g. right 
ventricle) of patient 10. It is coupled to implantable pulse generator 120 
via lead 15 and is used to measure decreases in oxygen level of the blood 
which are indicative of an apnea event. Such measurements may be made on 
either the arterial or venous side of the cardiovascular system. Use of 
the arterial side is somewhat more difficult to access because of the 
pressure, but will ordinarily provide the more pronounced signal. The 
venous side yields a signal which tends to be integrated by the 
cardiovascular system to compensate for differences in oxygen content over 
a given normal respiratory cycle. 
All remaining referenced elements are as previously discussed. 
FIG. 9 is a graphical representation of the amplitude of reflected light 
within the blood of patient 10 wherein normal respiration is present. The 
reflected response is centered about the red wavelengths. 
FIG. 10 is a graphical representation of the response of a reflectance 
oximeter within the blood of patient 10 during an apnea event. Note that 
the response is skewed toward the blue wavelengths. 
FIG. 11 is a plan view of an oxygen sensor 200 implantable within the 
cardiovascular system of patient 10. Oxygen sensor 200 operates on the 
principle of reflectance oximetry as discussed in more detail below. 
Distal tip 210 is implanted transvenously into the right ventricle using 
standard techniques. It is held in place by tines 212. 
Oximeter 216 emits light and measures the reflected response via an 
artificial sapphire window. Lead body 218 extends to connector 220 having 
terminal pin connectors 222, 224 and 226. Anchoring sleeve 228 provides 
for suturing of the proximal end without damage to the insulating sheath 
of lead body 218. Additional detail with regard to oxygen sensor 200 may 
be obtained from U.S. Pat. No. 4,813,421 issued to Baudino et al, 
incorporated herein by reference. 
FIG. 12 is a block diagram of implantable pulse generator 120 as used in a 
multiple sensor stimulation system. In this particular example, and not to 
be deemed limiting of the present invention, two sensors (i.e. pressure 
and blood oxygen) are used. Distal tip 210 of oxygen sensor 200 contains 
the sensing element as explained above. This sensing element functions as 
a reflectance oximeter which emits light from light emitting diode 312 
into the blood and senses the reflected response by photo sensitive 
element 316. Diode 314 permits oxygen sensor 200 to function with only the 
three conductors 364, 366, and 368. 
Power to light emitting diode 312 is supplied from current driver 310 and 
voltage driver 306, as coupled by line 362. Timing of this drive is 
provided by timing circuit 308 via lines 334 and 336. These timing signals 
are synchronized to the pressure sensing circuitry by delay logic 302 
coupled to timing circuit 308 by line 338. 
Current mirror 318 receives the return signal via conductor 368. The 
infrared signal is channeled to sample and hold circuit 332 by line 346. 
The control signal is similarly transferred to sample and hold circuit 330 
by line 346. The output of each is gated in turn to division network 328 
via lines 344 and 348 under control of timing signals received via lines 
340 and 342. 
Division network 328 compares the two signals to look for the color shift 
from red to blue (see also FIGS. 9 and 10) which signals an apnea event. 
The output is coupled via line 350 to "and" gate 88. In this manner, 
stimulation generator 100 is not triggered unless both oxygen and pressure 
sensors detect a probable apnea event. All other referenced elements are 
as previously described. 
Having thus described the preferred embodiments of the present invention, 
those of skill in the art will be readily able to apply the teachings 
found herein to yet other embodiments within the scope of the claims 
hereto attached.