how can obstructive sleep apnea be evaluated beyond anatomy? david p. white, md professor of...
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How can Obstructive Sleep Apnea be Evaluated Beyond
Anatomy?
David P. White, MD
Professor of Medicine
Harvard Medical School
Chief Medical Officer:
Philips Respironics
Obstructive Sleep Apnea Phenotypic Traits
• Anatomy.• Pharyngeal dilator muscle control
asleep.• Arousal Threshold.• Loop Gain/Control of breathing.
Hyoid Bone
Mandible
Maxilla
Nasal Passage
Trachea
Epiglottis
Tongue(Genioglossus)
Soft Palate
Choanae
Richard SchwabClinics in Chest Medicine, 1998
Pcrit measurement
60s
10
2
Pmask
+0.5
-0.5
Flow
Pcrit measurement
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0.5
0 1 2 3 4 5 6 7 8
Mask pressure (cm H2O)
Flo
w
Pcrit
Sforza and KreigerAm J Respir Crit Care Med, 1999
Pharyngeal Anatomy in Obstructive Sleep Apnea
Anatomy alone, at least as measured by Pcrit, explains little of the variability
in apnea severity (as measured by RDI).
Obstructive Sleep Apnea Phenotypic Traits
• Anatomy.• Pharyngeal dilator muscle control
asleep.• Arousal Threshold.• Loop gain/ control of breathing.
Arousal andObstructive Sleep Apnea
What is required for the pharyngeal dilator muscles to open the upper airway during sleep?
• The muscles must be recruitable and effective.
• The individual must stay asleep long enough for the muscles to be recruited.
Berry et al – AJRCCM, 1997
Gleeson et al – 1990Am Rev Respir Dis
Guilleminault et al – Chest, 1993
Arousal andObstructive Sleep Apnea
Combined individual variability in:• Respiratory arousal threshold.• Upper airway muscle responsiveness
and effectiveness.
May explain much of the variability in the severity of obstructive sleep apnea.
Obstructive Sleep Apnea Phenotypic Traits
• Anatomy.• Pharyngeal dilator muscle control
asleep.• Arousal threshold.• Loop gain/ Control of breathing.
Ventilatory Instability
and
Upper Airway Obstruction
RUA
Ventilatory Motor Output
Nadir of motor output
Obstruction
Baseline
Chemical Feedback Loop
PCO2 Circulatory Delay
VE (R)
PCO2
PC02
Ve
Ventilatory disturbance
VE (D)
Plant
Controller
Ve
Loop Gain
• A measure of the susceptibility to periodic breathing.
Ventilatory Response
Ventilatory DisturbanceLoop Gain =
Loop Gain = 0.5
Disturbance Response
Ventilatory Response
Ventilatory Disturbance
Loop Gain =
LG = 0.5
Loop Gain = 0.5
Disturbance
Response
Ventilatory Response
Ventilatory Disturbance
Loop Gain =
LG = 0.5
Loop Gain = 0.5
Disturbance
Response
Ventilatory Response
Ventilatory DisturbanceLoop Gain =
LG = 0.5
Loop Gain 1
Disturbance
Response
Ventilatory Response
Ventilatory Disturbance
Loop Gain =
Disturbance
Response
LG = 0.5
LG = 1
Loop Gain 1
Disturbance
Response
Ventilatory Response
Ventilatory Disturbance
Loop Gain =
Disturbance
Response
LG = 0.5
LG = 1
• Proportional Assist Ventilator (PAV) delivers pressure in proportion to the patients effort.
• Thus we can increase the Ventilation Response for a given Ventilatory Disturbance.
Loop Gain Measurement
Ventilatory Response
Ventilatory DisturbanceLoop Gain =
Proportional Assist Ventilation
PAV amplifies the underlying loop gain and can induce periodic breathing.
LG = 0.5
LG = 0.2
PAV amplification
0.5
0.0
-0.5
Flo
w-p
av
9
20
15
10
cmH
20
Mas
k
4
-1.0
-0.5
0.0
lite
rV
t-p
av
2
0 50 100 150 200 250 300 350 400 450 500s
50% assist
VTAF 1.65
VTAFs
60% assist
VTAF 2.08
1.0
0.5
0.0
-0.5
Flo
w-p
av
9
20
15
10
cmH
20
Mas
k
4
-1.0
-0.5
0.0
lite
rV
t-p
av
2
900 950 1000 1050 1100 1150 1200 1250 1300 1350s
75% assist
VTAF 2.44
80%
1.0
0.5
0.0
-0.5
Flo
w-p
av
9
20
15
10
cmH
20
Mas
k
4
-1.0
-0.5
0.0
lite
rV
t-p
av
2
1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800s
80%75%
VTAF 2.44
1.0
0.5
0.0
-0.5
Flo
w-p
av
9
20
15
10
cmH
20
Mas
k
4
-1.0
-0.5
0.0
lite
rV
t-p
av
2
1800 1825 1850 1875 1900 1925 1950 1975 2000 2025 2050 2075 2100 2125 2150 2175 2200 2225 2250s
80%85%
60%
Loop gain vs. AHI
0
20
40
60
80
100
0.1 0.3 0.5 0.7
Loop gain
AH
I (e
pis
od
es/
ho
ur) r = 0.36
p = 0.076
Pcrit measurement
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0.5
0 1 2 3 4 5 6 7 8
Mask pressure (cm H2O)
Flo
w
Pcrit
Baseline info
N Age BMI
Low risk
(Pcrit < -1) 7 47.4 2.7 34.3 3.2
Borderline risk
(Pcrit -1 to +1) 9 44.9 3.2 31.9 2.5
High risk
(Pcrit > +1) 7 42.7 3.8 34.2 4.0
Negative Pcrit Group
0
20
40
60
80
100
0.1 0.3 0.5 0.7
Loop gain
AH
I (e
pis
od
es/
ho
ur)
r = -0.31p = 0.45
Atmospheric Pcrit Group
0
20
40
60
80
100
0.1 0.3 0.5 0.7
Loop gain
AH
I (e
pis
od
es/
ho
ur)
r = 0.88p = 0.0016
Positive Pcrit Group
0
20
40
60
80
100
0.1 0.3 0.5 0.7
Loop gain
AH
I (e
pis
od
es/
ho
ur) r = 0.19
p = 0.66
Loop Gain
• Can probably be determined fairly easily during NREM sleep.
• Will likely turn out to be an important cause of OSA is a subset (20-25%) of patients.
• As loop gain can be manipulated with drugs, oxygen etc, novel therapies may emerge for these patients if they can be identified.
Obstructive Sleep Apnea Phenotypic Traits
• Anatomy.• Pharyngeal dilator muscle control
asleep.• Arousal Threshold.• Loop Gain/Control of breathing.
