PICKWIKIAN SYNDROME

PRAYUDI SANTOSO
Divisi Respirologi dan Penyakit Kritis Respiratori
Departemen Ilmu Penyakit Dalam
FK UNPAD/RSHS
BANDUNG 2018
 Curricullum Vitae
Dr. dr. Prayudi Santoso, SpPD-KP, M.Kes, FCCP, FINASIM
E-mail: prayudimartha@yahoo.com

Education :
MD Medical School, Padjadjaran University, Bandung, Indonesia
Internal Med Medical School, Padjadjaran University, Bandung, Indonesia
Pulmonology Consultant Collegiums of Internal Medicine, Indonesia
MSc Medical School, Padjadjaran University, Bandung Indonesia
PhD Medical School, Padjadjaran University, Bandung Indonesia

Occupation :
Staf of Respirology & Critical Care Division, Internal Medicine Department,
Faculty of Medicine Padjadjaran university/Hasan Sadikin General Hospital, Indonesia
Coordinator of MDR-TB Team Hasan Sadikin General Hospital Bandung, Indonesia

Organization :
Society of Internal Medicine West Java, - Indonesia
Society of Respirologi Indonesia (PERPARI)
Fellow American College of Chest Physcian (ACCP)
Member European Respiratory Society (ERS)
 Historical background

 Apnea- literally means “without breath”

 Pickwickian papers fat boy “Joe”
 Osler and later Burwell applied the name “Pickwickian
Syndrome” to patients with Obesity, Hypersomnolence and
signs of Chronic hypoventilation
Joe the “fat boy.”
(Detail from “Mr. Pickwick in Chase of His Hat.” Illustration by Robert Seymour. In: Dickens C. The
posthumous papers of the Pickwick Club. Published in serial form. London: Chapman and Hall; 1836.
Courtesy The Beinecke Rare Book & Manuscript Library, Yale University.)
 DIAGNOSTIC FEATURES OF OBESITYHYPOVENTILATION SYNDROME
Obesity
Body mass index ≥ 30 kg/m2
Chronic Hypoventilation
Awake daytime hypercapnia (sea-level arterial PCO2 ≥ 45 mm Hg)
Possible role of serum venous bicarbonate or calculated bicarbonate >27 mEq/L from
capillary blood gas
Sleep Breathing Disorder
Obstructive sleep apnea (apnea-hypopnea index [AHI] ≥ 5 events/hour)
Non-obstructive sleep hypoventilation (AHI <5 events/hour, PaCO2 above 55 mm Hg for
more than 10 minutes or an increase in the PaCO2 [or surrogate] above 10 mm Hg
[compared with awake supine PaCO2] to a value >50 mm Hg for >10 minutes during
sleep, or sustained hypoxemia with oxygen saturation ≤88% without obstructive
respiratory events)
Exclusion of Other Causes of Hypoventilation
Severe obstructive airways disease (e.g., chronic obstructive pulmonary disease)
Severe interstitial lung disease
Severe chest wall disorders (e.g., kyphoscoliosis)
Severe hypothyroidism
Neuromuscular disease
Congenital hypoventilation syndromes
Prevalence of obesity-hypoventilation syndrome in patients with obstructive sleep apnea (OSA), sorted by body mass index (BMI). In the U.K.
study,21 the mean BMI was nearly 40 kg/m2, and 38% of subjects had a BMI higher than 40 kg/m2. Similarly, in the U.S. study,19 the mean BMI was 43
kg/m2, and 60% of subjects had a BMI higher than 40 kg/m2. In contrast, the mean BMI in the French study18 was 34 kg/m2, and only 15% of subjects
had a BMI higher than 40 kg/m2. Italian data30 were provided by Professor Onofrio Resta (personal communication).
 CLINICAL FEATURES OF PATIENTS WITH OBESITY HYPOVENTILATION
SYNDROME*
Clinical Features Mean (Range)
Age (years) 52 (42–61)
Male (%) 60 (49–90)
Body mass index (kg/m2) 44 (35–56)
Neck circumference (cm) 46.5 (45–47)
pH 7.38 (7.34–7.40)
Arterial PCO2 (mm Hg) 53 (47–61)
Arterial PO2 (mm Hg) 56 (46–74)
Serum bicarbonate (mEq/L) 32 (31–33)
Hemoglobin (g/dL) 15
Apnea-hypopnea index 66 (20–100)
SpO2 nadir during sleep (%) 65 (59–76)
Percent sleep time SpO2 < 90% 50 (46–56)
FVC (% predicted) 68 (57–102)
FEV1 (% predicted) 64 (53–92)
FEV1/FVC 0.77 (0.74–0.88)
Medical Research Council dyspnea class 3 or 4 (%) 69
Epworth sleepiness scale score 14 (12–16)
*Features are based on aggregated sample of 757 patients from 15 studies.
 PHYSIOLOGIC DIFFERENCES BETWEEN EUCAPNIC MORBIDLY OBESE PATIENTS AND
THOSE WITH OBESITY-HYPOVENTILATION SYNDROME
Eucapnic Morbid Obesity-Hypoventilation
Obesity Syndrome
Waist:hip ratio ↑ ↑↑
FEV1/FVC Normal Normal/↓
Total lung capacity Normal Slight ↓
Functional residual capacity ↓ ↓
Vital capacity Normal or ↓ ↓↓
Expiratory reserve volume ↓ ↓↓
Work of breathing ↑ ↑↑
Hypercapnic/hypoxic ventilatory drive Normal ↓
Inspiratory muscle strength Normal ↓
FEV1, Forced expiratory volume in first second; FVC, forced vital capacity.
OHS: clinical features
 Symptoms similar to OSA
 Loud snoring, periods of choking in sleep, excessive sleepiness in daytime,
fatigue
 Dyspnea on exertion
 BMI >35 kg/m2
 May heave features of Right Heart Failure
 Rales, hepatomegaly, edema
 Hypercapnia – PaCO2>45 mm Hg during wakefulness
 Hypoxic – PaO2 <70 mm Hg but have normal alveolar-arterial gradient
if no associated heart or lung disease
 Elevated hematocrit
 EKG, ECHO – features of RVH, Pulmonary HTN
 PFT – restrictive ventilatory defect
 Often have coexisting OSA
Clinical features of the patient with obesity hypoventilation syndrome.

Obesity Hypoventilation Syndrome:A Review of Epidemiology, Pathophysiology, and Perioperative Considerations Anesthes. 2012;117(1):188-205.
doi:10.1097/ALN.0b013e31825add60
Control and pattern of breathing in
obesity
 Obese patients often adapt a “rapid and shallow” breathing pattern
 Resting respiratory rate can be 40% higher in obese patients
 Ventilatory drive can be reduced in patients with OHS
 Diminished response to rising CO2
 Leptin resistance?
Beuther, et al 2006
Pathogenesis of OHS

 Upper airway obstruction during sleep (OSA) leads to increased CO2

 Eucapnic OSA patients are able to normalize their CO2 levels between
these events, patients with OHS are not
 Rise in bicarbonate levels further blunts ventilatory response to rise in
CO2
 Increased work of breathing due to restrictive effects of obesity
 Ventilation / perfusion mismatch
 Respiratory muscle impairment
 Patients with OHS lack the usual increased ventilatory drive seen in
patients with obesity
 Leptin resistance (leptin normally stimulates ventilation)
 Figure 1

The American Journal of Medicine 2005 118, 948-956DOI: (10.1016/j.amjmed.2005.03.042)

Mechanisms by which obesity and OSA result in chronic hypercapnia. HCO 3−= serum bicarbonate; OSA = obstructive sleep apnea.

Obesity Hypoventilation Syndrome:A Review of Epidemiology, Pathophysiology, and Perioperative Considerations Anesthes. 2012;117(1):188-205.
doi:10.1097/ALN.0b013e31825add60
Interapnea/hypopnea hyperventilation and carbon dioxide (CO 2) excretion. In the first cycle, the interevent hyperpnea is sufficient to
excrete the carbon dioxide accumulated during hypopnea. In the second cycle, much more carbon dioxide is accumulated during
apnea than is excreted after the event. Multiple cycles of excessive carbon dioxide accumulation during the apneic period lead to
hypercapnia. (Adapted from reference 35with permission.)

Obesity Hypoventilation Syndrome:A Review of Epidemiology, Pathophysiology, and Perioperative Considerations Anesthes. 2012;117(1):188-205.
doi:10.1097/ALN.0b013e31825add60
OHS and sleep study

 Oxygen desaturation during sleep

 Occur for longer periods than in patients who have OSA alone
 Most patients have associated OSA
 AHI severity is not associated with likelihood of coexisting OHS but
severe oxygen desaturation is associated with coexisting OHS
Treatment of OHS

 Nocturnal positive airway pressure

 BIPAP or CPAP +/- O2 (if necessary)
 Goal of eliminating obstructive events at night (if present) and improving
alveolar ventilation
 Follow up daytime blood gases should be done to see that hypoventilation
has improved
 Daytime supplemental oxygen
 Interventions directed at weight loss
 Dietary, pharmacologic, bariatric surgery
Treatment

 Weight loss and exercise

 CPAP (continuous positive airway pressure)
 Significantly improves sleepiness
 Improvements in quality of life
 Improvements in cognitive function
 Improves systemic blood pressure
 Indications for CPAP
 AHI>15 (moderate OSA)
 AHI 5-15 with excessive sleepiness, impaired cognitive function, mood disorders,
insomnia, cardiovascular disease or stroke
CPAP
(continuous positive airway pressure)
 Utilizes pressure to provide a pneumatic splint to maintain airway
patency
 More than 100 different mask options to customize treatment to an
individual patient
Prognosis of OHS

 Patients who are not treated with NIV have a higher mortality
 18 months 23%
 7 years 46%
 Untreated patients have increased levels of daytime sleepiness and
reduced quality of life
Survival curves for patients with untreated obesity hypoventilation syndrome (OHS) and morbidly obese patients with eucapnia as
reported by Nowbar et al. , 5 compared with patients with OHS treated with positive airway pressure therapy.76NPPV = noninvasive
positive pressure ventilation. (Reprinted with permission of the American Thoracic Society. Copyright © 2012 American Thoraci c
Society. Mokhlesi B, Kryger MH, Grunstein RR, 2008, Assessment and Management of Patients with Obesity Hypoventilation
Syndrome, Proceedings of the American Thoracic Society, 5:218–25, Official Journal of the American Thoracic Society7.)

Obesity Hypoventilation Syndrome:A Review of Epidemiology, Pathophysiology, and Perioperative Considerations Anesthes. 2012;117(1):188-205.
doi:10.1097/ALN.0b013e31825add60
Obesity Hypoventilation Syndrome:A Review of Epidemiology, Pathophysiology, and Perioperative Considerations Anesthes. 2012;117(1):188-205.
Obesity Hypoventilation Syndrome

 Sleep-related breathing disorder

 Hypersomnolence, fatigue
 Morning headache
 Hypoventilation:
PaCO2>45 mmHg
 Polycythemia
 Cor pulmonale