Obesity hypoventilation syndrome

Visasiri Tantrakul, MD
Division of Sleep Medicine
Department of Medicine
Ramathibodi Hospital
Mahidol University
Definition of OHS
• OHS is defined by the combination of obesity (BMI≥30 kg/m2),
SDB, and awake daytime hypercapnia (awake resting
PaCO2≥45 mmHg at sea level), after excluding other causes for
hypoventilation.
• OHS=most severe form of obesity-induced respiratory
compromise leading to increased rate of mortality, chronic
heart failure, pulmonary hypertension, and hospitalization with
acute-on-chronic hypercapnic respiratory failure.
• Prevalence of OHS in population is unknown, but the prevalence
of OHS is 8-20% in sleep center in patients referred for SDB
 Common causes of hypercapnia
other than OHS
• Chest wall restriction (eg. scoliosis)
• Severe interstitial lung disease
• Severe obstructive lung diseased (FEV1<1L or <35% predicted)
• CNS structural defects- tumor, CVA, brainstem or spinal cord lesion
• Neuromuscular disorders
• Severe hypothyroidism/myxedema
• Severe electrolyte abnormalities (hypophosphatemia and
hypocalcemia)
• Metabolic alkalosis caused by high doses of loop diuretics

Lee, et al. Crit Care Clin 2008

• Although, definition of OHS suggest diurnal pathology,
polysomnography or sleep respiratory polygraphy is required to
determine the pattern of SDB and hypoventilation.
• Obstructive vs non-obstructive to tailor treatment and establish
optimal PAP setting.
• 90% of OHS have co-existent OSA (AHI≥ 5 events/hour), with
nearly 70% having severe OSA.
• The remaining 10% of patients with OHS without OSA (AHI<5
events/hour)= non-obstructive, sleep-sleep dependent
hypoventilation.
Mechanisms implicated in OHS
• Decreased chest wall and lung compliance secondary to excess
adipose tissue
• Increased upper airway and total respiratory system resistance
• Respiratory muscle weaknesss
• Impaired central drive-decreased ventilatory response to
hypercapnic and hypoxia
• Coexistent obstructive sleep apnea
• Neurohormonal abnormalities-leptin resistance
 Research
Presentation
Correlation of BMI and Obesity
Hypoventilation Syndrome in
Thai Obstructive Sleep Apnea Patients

Gunthiga Laplertsakul1, Visasiri Tantrakul1, Somprasong Liamsombut1

1Division of Pulmonary and Critical Care Medicine, Ramathibodi hospital,

Faculty of Medicine, Mahidol University

 Study protocol
Baseline characteristics collection
- Personal history
- Underlying disease, STOP-BANG Overnight polysomnography with
Epworth sleepiness scale transcutenous CO2 monitoring
- Physical examination e.g. vital signs,
neck, waist circumference,
mallampati score, weight, height, BMI
Searching participants for Pulmonary function test and ERV
eligibility at OPD of
Ramathibbodi sleep center Arterial blood gas

Body composition analysis by

Definition of OHS in this study Inbody Fat analyzer 770
- Presence of daytime hypercapnia (PaCO2
> 45 mm Hg or > 6 kPa)
- Absence of other known causes of alveolar
hypoventilation
Does the risk of other metabolic comorbidities e.g. OHS increasing with BMI
in overweight Asian population?
 129 participants were
included in the study to
assess

normal Stage 0 (pure OSA) Stage I/II ORSH Stage III/IV OHS

N= 1 (0.9%) N= 90 (69.7%)
N= 18 (13.9%) N= 20 (15.5%)

Prevalence of OHS in sleep-breathing disorder = 15.5%

 Result
• Table 1 Demographic data

and baseline characteristics

Result
Result
 Result : Univariate analyasis
Variables Odds ratio p-value

- Neck circumference 1.11 0.02

- Epworth Sleepiness 1.10 0.04
Scale
- Lowest oxygen 0.93 <0.001
saturation during
sleep
- Average HR during 1.05 0.02
PSG
- Maximal HR during 1.01 0.03
PSG
- FVC predicted 0.95 0.006
- Arterial HCO3 2.26 <0.001
• Table 2- Hypoventilation in Obesity stages 0-IV: OSA severity

OSA severity Stage 0 (n, %) Stage I/II (n, %) Stage III/IV (n, %)

Mild n (%) 12 (13%) 3 (17%) 3 (15%)

Moderate n (%) 20 (22%) 3 (17%) 3 (15%)

Severe n (%) 58 (65%) 12 (66%) 14 (70%)

Result: Spearman correlaton

• Poor correlation
of PaCO2 and BMI
(0.12)
Purpose of guidelines
• To improve early recognition of obesity hypoventilation
syndrome (OHS) and advise clinicians concerning the
management of OHS, with the goal of reducing variability in
clinical practice.
• The guideline should empower the clinicians to make
appropriate clinical decisions in the context of individual patient
value and preference, level of evidence, and panel discussion.
• Most OHS patients remained undiagnosed and untreated until
late in the course of disease when presenting with acute-on-
chronic hypercapnic respiratory failure, or in the case of
ambulatory care with pulmonary or sleep specialist.
• OHS is often misdiagnosed event in severe obesity admitted with
acute hypercapnic respiratory failure.
• Early recognition and effective treatment are important in
improving morbidity and mortality.
• 1. Should serum bicarbonate and/or spO2 rather than PaCO2 be used
to screen for OHS in obese adults with SDB?
Recommendation 1A:
For obese patients with SDB with high pretest probability of having OHS,
we suggest measuring PaCO2, rather than serum bicarbonate or SPO2 to
diagnose OHS
Recommendation 1B: For patients with low to moderate probability of
having OHS (<20%), we suggest using serum HCO3 to decide when to
measure PaCO2: <27 mmol/L, clinician may forego measuring PaCO2, as
the diagnosis of OHS is unlikely. (very low level of evidence)
≥27 mmol/L, clinician might need to measure PaCO2
to confirm or rule out diagnosis of OHS (very low level of evidence)
• Recommendation IC: We suggest that clinician avoid using SpO2
during wakefulness to decide when to measure PaCO2 patients
suspected of OHS until more data about usefulness of SpO2 in
this context become available (very low level evidence)
• Patients with high pre-test probability of OHS are usually severely
obese with typical sign and symptom of OHS and can be mildly
hypoxemic during wake and/or significantly hypoxemic during
sleep. This is usually with patients with OSA
Lee, et al. Crit Care Clin 2008
Should hospitalized adults suspected of
having OHS, in whom the diagnosis has
not yet been made, be discharged
from the hospital with or without PAP
treatment until the diagnosis of OHS is
either confirmed or ruled out?
• Hospitalized patients suspected of having OHS who develop and
acute-on-chronic hypercapnic respiratory failure have higher short-
term (1-2yr) mortality than ambulatory patients with OHS.

Marick PE, et al. Obes Sci Pract 2016; 40-47

• Retrospective study of tertiary-care teaching hospital identified
600 patients with unequivocal OHS.
• 43% were misdiagnosed with COPD or undiagnosed of OHS.
• Most common admission diagnosis were respiratory failure, heart
failure, and sepsis.
• 15% died during index hospitalization. Predictors= age,
creatinine, respiratory failure, sepsis, and admission to ICU
• Hospital survivors (mean F/U 3.2 years) had 19% mortality with
overall cumulative mortality of 31.3%. predictors= age,
creatinine, admission to ICU

Marick PE. Obes Sci Pract 2016;2:40-47

Whether prescribing empiric PAP at the
time of hospital discharge versus
awaiting outpatient workup (Sleep study
and PAP titration in the sleep
laboratory) reduces mortality remained
unknown

:no evidence from RCT

2-observational studies
• One observational study reported mortality of 23% at 18 months
in OHS patients discharged from hospital without PAP.
• Another observational study which all patients received NIV
reported 2-year mortality rate of 8% (10 y study with 94%
adherence)
- predictors of survival on NIV depends on PaO2, pH, wbc at
baseline
- predictors of survival at F/U= reduction of PaCO2 23%, and
Hb at follow-ups, independent of baseline and change of BMI

Nowbar, et al. Am J Med 2004;116:1-7

Budweiser S, et al. J Intern Med 2007;261:375-383
Nowbar, et al. Am J Med 2004;116:1-7
Individual data analyses
• 9/10 studies retrieved individual data analyses regarding:
- age, sex, BMI, baseline ABG (pH, PaCO2, PaO2), ABG on
discharge, PFT, discharge on PAP or no-PAP and all-cause mortality
at 3 months (related to recent hospitalization)
- 3 studies, entire cohort had hospitalized patients
- 6 studies had subgroup of hospitalized patients
- 1162 hospitalized patients with OHS or suspect survived
hospital and were discharged.
• Of these, 119 (10%) were discharge without PAP and 1,043(90%) on PAP.

• 7 studies (n=955), NIV was prescribed on hospital discharge, the remaining 2 studies used
either CPAP or NIV on discharge. Unavailable data on PAP setting.

• Those without PAP were older (73 vs 64 y, p<0.001), had higher baseline PaCO2 (78.4 vs 62.2
mmHg, p<0.001), more female (14% vs 5%, p<0.001)

• At 3 months, 20 of 119 (16.8%) patients in no-PAP had died vs 24 out of 1043 (2.3%)patients
with PAP, p<0.0001. Adjusted 0.16;95%CI, 0.08-0.33; p<0.0001(age, sex, baseline PaCO2)

• Estimated risk difference: 136 fewer deaths per 1000 patients (95%CI 105-152 fewer
death/1000)
• Subgroup analyses on 328 patients with available data on ABG
at baseline and discharge (no-PAP n=100 vs PAP n=228) with
similar baseline characteristics, and ABG
• Mortality at 3-month, higher in no-PAP vs PAP on discharge:
9/100 died (9%, 95%CI: 4.2-16.4%) vs 10 /228 (4.4%; 95%CI 2.1-
7.9%), p=0.085. adjusted OR 0.48; 95%CI 0.19-1.24, estimated risk
difference = 44 fewer death per 1000 (95%CI 72 fewer-19more)
Key limitation
• No RCT data, only observational studies with heterogeneity on
inclusion/exclusion criteria, no relevant detail on PAP
prescription decision, no relevant outcomes.
• High risk of bias, level of certainty on reported outcomes= LOW
• Despite the limitation of available evidence, the panel agreed
that desirable effects of PAP outweigh its trivial, undesirable
effects. (mortality at 3 months after discharge) with large
difference between the 2 groups.
• Lacking data on cost-effectiveness, regional variation on cost
and availability of PAP, pay-out-of-pocket???
• In certain situations, patients discharged on NIV may be able to
be switched to CPAP after the sleep study. More cost-saving.
• Majority of patients from the studies (92%) were discharged on
NIV, as opposed to CPAP without undergoing sleep studies and
PAP titration, as such, the panel was uncertain whether OHS will
be as responsive to CPAP or not (OHS phenotype without severe
OSA)
• Therefore, NIV should be considered the treatment of choice
until further evaluation is performed with subsequent sleep
studies.
ATS recommendation
• We suggest that hospitalized patients suspected of having OHS
be started on NIV therapy before being discharged from the
hospital and continued on NIV therapy until they undergo
outpatient workup and titration of PAP therapy in the sleep
laboratory, ideally during the first 3 months after hospital
discharge (conditional recommendation, very low level of
certainty in the evidence)
Remarks
• When discharging patients on NIV, clinicians may choose to
discharge them on the same NIV setting that were used during
hospitalization.
• No empiric setting recommendation on NIV setting.
• In setting where NIV is not available because of limited
resources, discharging patients on auto-PAP is preferable to no
PAP.
• Ultimately, discharging patients from the hospital on NIV or auto-
PAP therapy should not be a substitute for arranging an out-
patient sleep study to appropriately titrate PAP therapy.
Future research
• Well-designed RCT to assess whether patients should be
discharged on PAP (NIV or CPAP) or not.
• Future trial should assess the impact of PAP on discharge on
Patient-centered outcomes: readmission rate, health care
utilization, quality of life, resolution of symptoms, and cost-
effectiveness.
• Research on optimal timing of sleep study after a hospitalization
for acute-on-chronic hypercapnic respiratory failure.
• And ROLE of auto-titrating NIV devices vs in-laboratory PAP
titration.
CPAP= fixed rate
BPAP: volume assured, 5-6ml/kg, IPAP 18-
22 cmH2O
EPAP 8-12 cmH2O, BUR 12-15 /min
CPAP failure predictors

Treatment failure defined as

1. Daytime PaCO2 >45 mmHg and/or
2. Oxygen desaturation < 90% for >30%
of the night time oximetry
Predictors= PaCO2 at 1-month(OR
1.4;95%CI 1.03-1.98) and mean night-time
SpO2 during first night of optimal CPAP
(OR 0.6; 95%CI 0.34-0.93);p=0.027
• Persistent elevated PaCO2>45 mmHg at 1 month (p=0.058)
CPAP 65.5% (95%CI 45.7%-82.1%)
- Bilevel PAP 39.1% (95%CI 19.7%-61.5%)
• Persistent elevated PaCO2>45 mmHg at 3 month (p=0.218)
-CPAP 53.6% (95%CI 33.9%-72.5%)
- Bilevel PAP 37.0% (95%CI 19.4%-57.6%)

• The only significant predictor of persistent ventilatory failure after 3 months

was PaCO2 at presentation, PaCO2>62mmHg= 8-fold, non significant trend
towards increasing age, and lower absolute FEV1, and lower baseline
respiratory disturbance index on PSG
Recommendations for Adjustment of
IPAP, EPAP, and PS:
1. IPAP and/or EPAP should be increased as described in AASM Clinical Guidelines

for the Manual Titration of Positive Airway Pressure in Patients with Obstructive

Sleep Apnea until the obstructive respiratory events are eliminated.

2. The pressure support (PS) should be increased every 5 minutes if the tidal

volume is low (< 6 to 8 mL/kg)

3. The PS should be increased if the arterial PCO2 remains 10 mm Hg or more

above the PCO2 goal at the current settings for 10 minutes or more.

An acceptable goal for PCO2 is a value less than or equal to the awake PCO2.

4. The PS may be increased if respiratory muscle rest has not been achieved by NPPV

treatment at the current settings for 10 minutes of more.

5. The PS may be increased if the SpO2 remains below 90% for 5 minutes or more and

tidal volume is low (< 6 to 8 mL/kg).

Journal of Clinical Sleep Medicine, Vol. 6,

Recommendations for Use and Adjustment of
the Backup Rate/Respiratory Rate:
1. A backup rate (i.e., ST mode) should be used in all patients with central hypoventilation,

those with a significant number of central apneas or an inappropriately low respiratory rate, and those who

unreliably trigger IPAP/EPAP cycles due to muscle weakness.

2. The ST mode may be used if adequate ventilation or adequate respiratory muscle rest is not achieved with the

maximum (or maximum tolerated) PS in the spontaneous mode.

3. The starting backup rate should be equal to or slightly less than the spontaneous sleeping respiratory rate

(minimum of 10 bpm).

4. The backup rate should be increased in 1 to 2 bpm increments every 10 minutes if the desired goal of the

backup rate has not been attained.

5. The IPAP time (inspiratory time) should be set based on the respiratory rate to provide an inspiratory time

(IPAP time) between 30% and 40% of the cycle time (60/respiratory rate in breaths per minute).

6. If the spontaneous timed mode is not successful at meeting titration goals then the timed mode can be tried.

Journal of Clinical Sleep Medicine, Vol. 6,

Recommendations Concerning
Supplemental Oxygen:
1. Supplemental oxygen may be added in patients with an awake
SpO2
< 88% or when the PS and respiratory rate have been optimized
but
the SpO2 remains < 90% for 5 minutes or more.
2. The minimum starting supplemental oxygen rate should be
1 LPM and increased in increments of 1 LPM about every 5
minutes
until an adequate SpO2 is attained (> 90%)

Journal of Clinical Sleep Medicine, Vol. 6,

NIPPV flow, pressure, leak, and
volume in BPAP S/T mode

• A=?

• B=?

• C=?
• In stepwise multiple linear regression model, the magnitude of
change in PaCO2 was associated only with PAP use (=1-.5
mmHg per average hour of nightly PAP use (95%CI-2.5,-
0.5,p=0.007) and baseline PaCO2 (β=-0.87, 95%CI, -1.2, -0.5),
p<0.001
• The change in PaO2 was related only to baseline PaO2 (β=-0.89;
95%CI-1.2, -0.57),p<0.001)
• The change in HCO3- (β=-0.77; 95%CI -1.1, -0.5); p<0.001
• Mild =PaCO2 46-50 mmHg
• Moderate = PaCO2 51-55 mmHg
• Severe PaCO2 ≥ 56 mmHg