HYPOVENTILATION
1. Physiology of hypoventilation
2. Can’t vs Won’t breathe
3. Common and emerging causes
4. Consequences: pulmonary hypertension, sodium
avid state/edema, neurocognitive dysfunction,
mortality
5. Permissive effects of sleep
6. Treatments: PAP, weight loss surgery, oxygen,
thyroid replacement, narcotic modification, phrenic
pacing
7. Cases
Hypoventilation
mechanisms
VE
PC02 =
PC02
VC02
VD/VT
0.863 x VC02
VE x (1- VD/VT)
Hypoventilation
mechanisms
PC02
80
b
aa
Increasing
VD/VT
VC02
a
40
PC02
P02
3.5
7
VE
Clinical Categories of
Hypoventilation
• Can’t breathe: dyspnea due to
mechanical restraint, weakness, or
excessive ventilation.
• Won’t breathe: no dyspnea. Depressed
drive due to congenital or acquired
controller error.
Can’t breathe
-Airway Obstruction
• COPD, asthma, cystic fibrosis
-Restrictive
• Obesity
• Kyphoscoliosis
-Weakness
• ALS/myopathies
Mechanical Restraint
Kyphoscoliosis
Angle > 90o
COPD Fev1 < 30%
Obesity + OSA
Ventilatory drive
High HCO3
+ low drive
High HCO3
Low Drive
Normal
JAP 100:1737
Permissive effects of sleep
COPD; N=54
20
15
Frequency
10
5
0
5
5-10 10-15 15-20 20-25 25-30 30-35
Rise in PC02 (mmHg)
O'Donoghue FJ, European Respiratory Journal 2003;21(6):977-984
Treatable Causes of Mechanical
Restraint
•
•
•
•
Upper airway obstruction - tracheostomy
Lower airway obstruction - bronchodilators
Obesity - surgery
Kyphoscoliosis - PAP
Consequences of
Hypercapnia/Hypoxemia
Renal:
•~30% reduction in GFR
•~30% reduction in sodium clearance
Cardiovascular:
•Increased sympathetic
•Pulmonary hypertension
Neurocognitive:
•Impairment
•Encephalopathy
Hypoxemia + Hypercapnia 
Pulmonary Hypertension
Post-Hospitalization Mortality
Nowbar S, Am J Med 2004; 116:1–7
Won’t breathe
• Exogenous: narcotics, sedatives.
• Endogenous: Leptin resistance1-5, alkalosis,
myxedema, adaptation, genetic6-10, structural.
1.Yee BJ Respiration 2006;73:209-12.
2.Shimura R Chest 2005;127:543-9.
3.Atwood CW Chest 2005;128:1079-81.
4.Phipps PR Thorax 2002;57:75-6.
5.O'Donnell CP Amer J of Resp & Crit Care Med 1999;159:1477-84.
6.Doherty LS Eur Resp J 2007;29:312-6
7.Weil JV Resp Phys & Neurobiol 2003;135:239-46.
8.Fagan KA High Alt Med & Biol 2001;2:165-71.
9.Kawakami Y Respiration 1982;43:101-7.
10.Leitch AG Clin Sci & Molec Med 1975;48:235-8.
In chronic disease, “won’t
breathe” may represent an
adaptation that can be reversed
with treatment
Change in PC02 (mmHg)
Voluntary Hyperventilaton
25
Won’t
20
15
10
5
Can’t
0
0
50
100
FeV1 % predicted
Leech JA, Chest 1987; 92:807–813
150
Two areas of rapid acceleration:
Obesity
Prescribed Narcotics
Weight Loss in Obesity
Small case series with improvement in gas
exchange (6-15mmHg)1,2 with surgical
weight loss
1Sugerman
HJ. Chest. 1986;90:81-6
2Sugerman HJ. American Journal of Clinical Nutrition. 1992;55:597S-601S
Deaths from prescribed
opiods
Substance Abuse and Mental Health Services Administration 2007
Opioid Deaths
Pharmacoepidemiology and Drug Safety,
2013; 22: 438–442
Narcotic Dosing Adjustments?
Hypoventilation dynamically worsens with
acute narcotic dosing
Hypoventilation worsens if sedative added to
narcotic
Hypoventilation is partially-corrected after 6
weeks of stable methadone dosing
Can’t + Won’t the leptin
story
Ventilation
Leptin resistance in OSAH
BMI
FEV1/FVC, %
PaCO2, mm Hg
AHI
Leptin, ng/mL
PCO2<45 (106)
PCO2>45 (79)
32.5 + 0.3
84.2 + 0.6
40.9 + 0.3
52.9 + 2.2
9.0 + 0.4
33.2 + 0.8
85.4 + 1.7
46.6 + 0.4
47.4 + 2.8
14.3 + 1.0
p
NS
NS
< 0.01
NS
< 0.01
Shimura R, Chest 2005;127:543-9
Leptin resistance in obesity
leptin CSF/serum ratio is fourfold
higher in lean individuals compared to obese subjects
Caro JF. . Lancet 1996; 348:159–161
Hypoventilation Diagnosis
.
Awake PaCO2
40
35
50
Sleep PaCO2
50
45
55
Change in PaCO2
10
10
5
Benefits-removes false positive classifications
Challenges-instrumentation reliability
no
no
yes
Hypoventilation in Children
Pediatric Respiratory Rules
Reminders
Pediatric Respiratory Rules
CPAP Effective ~99%
CPAP Effective ~99%
Bilevel modes
• Support and control modes
• Fixed-Pressure
• Adjustable-Assured volume
• Adjustable-EPAP
CPAP Effective ~99%
Sleep study not required:
• Neuromuscular disease
• COPD in support mode
CPAP Effective ~99%
Sleep study not required:
• Neuromuscular disease
• COPD in support mode
• Adaptation that can be reversed with
treatment [6 week]
• Sleep is permissive
Hypoventilation in OHS/OSA
n=54 BMI 44+ 9
75
PC02 (mmHg)
70
65
60
55
50
45
40
Baseline
Bilevel PAP
de Llano LAP, Chest 2005;128:587 - 594
PAP in restrictive disease
75
P02
60
PC02
45
YEARS
0
1
2
3
4
5
Simonds AK Thorax 1995;50:604-609
PAP in restrictive disease
level III evidence
• Improvement in hypoventilation (PC02)
Ellis E. Chest 1988;94:811-815.
Hill NS. American Review of Respiratory Disease. 1992;145:365-371.
Piper AJ. European Respiratory Journal. 1996;9(7):1515-1522.
• Improvement in muscle power
Ellis E. Chest 1988;94:811-815.
Piper AJ. European Respiratory Journal. 1996;9(7):1515-1522.
• Improvement in sleepiness
Guilleminault C. Journal of Neurology, Neurosurgery & Psychiatry.
1998;65(2):225-232.
• Improvement in mortality
Pinto AC. Journal of the Neurological Sciences 1995;1129:19-26.
Raphael JC. Lancet 1994; 343:1600-4.
Case #1
32 year-old female with previous thyroidectomy admitted with
somnolence and hypercapnia.
Hypoventilation PCO2 128, PO2 115, pH 7.13, HCO3 45
Weight 506 lbs with massive edema
PSG: Hypoventilation and sleep apnea (AHI 25). Oxygen saturation
baseline 88%; nadir 63% and tcPC02 baseline 56mmHg and zenith
86mmHg
Delta HC03 meq/L; PC02 mmHg; TSH mU/L
Low Drive State
Reversible Hypoventilation
in Hypothyroidism
120
100
80
60
TSH
40
20
0
20
40
60
-20 0
Months
PC02 128 mmHg
Case #2
36-year-old thin male with a longstanding history of
wheezing. He has been noncompliant with medical
therapy for asthma and presents with dyspnea and severe
right heart failure with peripheral edema worsening over
two weeks.
Hypoventilation: Awake Pa02 50 mmHg PC02 63mmHg
Spirometry: FeV1 1.2 L
Echo: Pulmonary hypertension 60 mmHg + right atrial
pressure with dilated right ventricle, atrium and tricuspid
insufficiency
PSG: AHI 16 Sp02 nadir 79%; PtC02 90 asleep; initiated
on bilevel PAP 18/6 with PC02 80-90 mmHg. No clinical
improvement.
Bilateral vocal cord paralysis
Inspiratory flow < 1 L/sec
Awake PaC02 (mmHg)
120
100
80
60
40
20
0
Tracheostomy
Bilateral Vocal Cord Paralysis
•
Multisystem atrophy
•
Shy-Drager
•
Machado-Joseph
Iranzo A. Neurology 2004;63(5):930-2.
Blumin JH. Archives of Otolaryngology -- Head & Neck Surgery 2002;128(12):1404-7.
Iranzo A. Lancet 2000;356(9238):1329-30.
Wu YR. Journal of the Formosan Medical Association 1996;95(10):804-6.
Sadaoka. Sleep 1996;19(6):479-84.
Isozaki E. Clinical Neurology 1996;36(4):529-33.
McBrien F. Journal of Laryngology & Otology 1996;110(7):681-2.
Case #3
46 y/o female with pulmonary hypertension
[60+RA] and increasing peripheral edema
occurring over 3 years referred for
intermittent hypoxemia:
•normal chest xray
•negative pulmonary angiogram
•ECHO: no PFO
•FeV1/VC
2.3/2.6
VC 80%pred
Hypoxemia during day 78% when
bicycling; extreme fatigue, persistent
edema
•PCO2 55-65
•O2 sat 93%--30% with breath hold
Adult presenting with Congenital Central
Hypoventilation
Phox 2b mutation with 25 alanine
repeats
4 adults 17-55 y/o with hypoventilation with
phox B alanine repeats presenting with
•pulmonary hypertension
•hypoxemia during anesthesia
•respiratory failure during daytime
•respiratory failure during sleep
Trochet, 2008 AJRCCM
Chromosome 4p12
•Hirshprung’s
•Neuroblastoma
•Autonomic abnormalities
•Sildenafil
•BPAP at night
•Oxygen daytime
•FeedbackSpO2 during exercise
Non-PAP Therapy
Stimulants for Hypoventilation
• Progesterone- modestly lowers PCO21;
improves hypoventilation2 but not OSA3
• Acetazolamide- may worsen OSA, less effective
than progesterone in hypoventilation1
• Thyroid replacement in myxedema
1Skatrud
JB. Progress in Clinical & Biological Research. 136:87-95, 1983
2Hudgel DW. American Journal of Respiratory and Crit Care Medicine158:691-9, 1998
3Cook W. Chest 1989;96(2):262-6
Phrenic Pacing
HYPOVENTILATION SYNDROMES
1. Physiology of hypoventilation
2. Can’t vs Won’t breathe
3. Common and emerging causes
4. Consequences: pulmonary hypertension, sodium
avid state/edema, neurocognitive dysfunction,
mortality
5. Permissive effects of sleep
6. Treatments: PAP, weight loss surgery, oxygen,
thyroid replacement, narcotic modification, phrenic
pacing
7. Cases