how can obstructive sleep apnea be evaluated beyond anatomy? david p. white, md professor of...

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.