Review Article| Volume 30, ISSUE 3, P467-478, September 2009

The Pickwickian Syndrome—Obesity Hypoventilation Syndrome

  • Stephen W. Littleton
    Affiliations
    Sleep Medicine Fellowship Program, Section of Pulmonary and Critical Care Medicine, University of Chicago, 5841 South Maryland Avenue, MC 4000, Room W438, Chicago, IL 60637, USA
    Search for articles by this author
  • Babak Mokhlesi
    Correspondence
    Corresponding author. Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, 5841 South Maryland Avenue, MC 0999, Room L11B, Chicago, IL 60637.
    Affiliations
    Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, 5841 South Maryland Avenue, MC 0999, Room L11B, Chicago, IL 60637, USA
    Search for articles by this author

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Chest Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Lugaresi E.
        • Coccagna G.
        • Tassinari C.A.
        • et al.
        Particularités cliniques et polygraphiques du syndrome d'impatience des membres inférieurs.
        Rev Neurol. 1965; 115 ([in French]): 545
        • Gastaut H.
        • Tassinari C.A.
        • Duron B.
        Polygraphic study of the episodic diurnal and nocturnal (hypnic and respiratory) manifestations of the Pickwick syndrome.
        Brain Res. 1966; 1: 167-186
        • Lavie P.
        Who was the first to use the term Pickwickian in connection with sleepy patients? History of sleep apnoea syndrome.
        Sleep Med Rev. 2008; 12: 5-17
        • Auchincloss Jr., J.H.
        • Cook E.
        • Renzetti A.D.
        Clinical and physiological aspects of a case of obesity, polycythemia and alveolar hypoventilation.
        J Clin Invest. 1955; 34: 1537-1545
        • Burwell C.S.
        • Robin E.D.
        • Whaley R.D.
        • et al.
        Extreme obesity associated with alveolar hypoventilation: a Pickwickian syndrome.
        Am J Med. 1956; 21: 811-818
        • Dickens C.
        The posthumous papers of the Pickwick Club.
        The Macmillan Company, New York1904
        • Tauman R.
        • Gozal D.
        Obesity and obstructive sleep apnea in children.
        Paediatr Respir Rev. 2006; 7: 247-259
        • Mokhlesi B.
        • Kryger M.H.
        • Grunstein R.R.
        Assessment and management of patients with obesity hypoventilation syndrome.
        Proc Am Thorac Soc. 2008; 5: 218-225
        • Verin E.
        • Tardif C.
        • Pasquis P.
        Prevalence of daytime hypercapnia or hypoxia in patients with OSAS and normal lung function.
        Respir Med. 2001; 95: 693-696
        • Laaban J.P.
        • Chailleux E.
        Daytime hypercapnia in adult patients with obstructive sleep apnea syndrome in France, before initiating nocturnal nasal continuous positive airway pressure therapy.
        Chest. 2005; 127: 710-715
        • Kessler R.
        • Chaouat A.
        • Schinkewitch P.
        • et al.
        The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases.
        Chest. 2001; 120: 369-376
        • Resta O.
        • Foschino Barbaro M.P.
        • Bonfitto P.
        • et al.
        Hypercapnia in obstructive sleep apnoea syndrome.
        Neth J Med. 2000; 56: 215-222
        • Golpe R.
        • Jimenez A.
        • Carpizo R.
        Diurnal hypercapnia in patients with obstructive sleep apnea syndrome.
        Chest. 2002; 122 (author reply: 1101): 1100-1101
        • Akashiba T.
        • Akahoshi T.
        • Kawahara S.
        • et al.
        Clinical characteristics of obesity-hypoventilation syndrome in Japan: a multi-center study.
        Intern Med. 2006; 45: 1121-1125
        • Akashiba T.
        • Kawahara S.
        • Kosaka N.
        • et al.
        Determinants of chronic hypercapnia in Japanese men with obstructive sleep apnea syndrome.
        Chest. 2002; 121: 415-421
        • Leech J.A.
        • Onal E.
        • Baer P.
        • et al.
        Determinants of hypercapnia in occlusive sleep apnea syndrome.
        Chest. 1987; 92: 807-813
        • Mokhlesi B.
        • Tulaimat A.
        • Faibussowitsch I.
        • et al.
        Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea.
        Sleep Breath. 2007; 11: 117-124
        • Kawata N.
        • Tatsumi K.
        • Terada J.
        • et al.
        Daytime hypercapnia in obstructive sleep apnea syndrome.
        Chest. 2007; 132: 1832-1838
        • Sturm R.
        Increases in morbid obesity in the USA: 2000–2005.
        Public Health. 2007; 121: 492-496
        • Lee W.
        • Nagubadi S.
        • Kryger M.H.
        • et al.
        Epidemiology of obstructive sleep apnea: a population-based perspective.
        Exp Rev Resp Med. 2008; 2: 349-364
      1. (Available at:) (Accessed January 24, 2009)
        • Laaban J.P.
        • Orvoen-Frija E.
        • Cassuto D.
        • et al.
        Mechanisms of diurnal hypercapnia in sleep apnea syndromes associated with morbid obesity.
        Presse Med. 1996; 25: 12-16
        • Flegal K.M.
        • Graubard B.I.
        • Williamson D.F.
        • et al.
        Excess deaths associated with underweight, overweight, and obesity.
        JAMA. 2005; 293: 1861-1867
        • Young T.
        • Finn L.
        • Peppard P.E.
        • et al.
        Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort.
        Sleep. 2008; 31: 1071-1078
        • Hida W.
        Quality of life in obesity hypoventilation syndrome.
        Sleep Breath. 2003; 7: 1-2
        • Budweiser S.
        • Hitzl A.P.
        • Jorres R.A.
        • et al.
        Health-related quality of life and long-term prognosis in chronic hypercapnic respiratory failure: a prospective survival analysis.
        Respir Res. 2007; 8: 92-101
        • Berg G.
        • Delaive K.
        • Manfreda J.
        • et al.
        The use of health-care resources in obesity-hypoventilation syndrome.
        Chest. 2001; 120: 377-383
        • Nowbar S.
        • Burkart K.M.
        • Gonzales R.
        • et al.
        Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome.
        Am J Med. 2004; 116: 1-7
        • Budweiser S.
        • Riedl S.G.
        • Jorres R.A.
        • et al.
        Mortality and prognostic factors in patients with obesity-hypoventilation syndrome undergoing noninvasive ventilation.
        J Intern Med. 2007; 261: 375-383
        • Campos-Rodriguez F.
        • Pena-Grinan N.
        • Reyes-Nunez N.
        • et al.
        Mortality in obstructive sleep apnea-hypopnea patients treated with positive airway pressure.
        Chest. 2005; 128: 624-633
        • Lin C.C.
        • Wu K.M.
        • Chou C.S.
        • et al.
        Oral airway resistance during wakefulness in eucapnic and hypercapnic sleep apnea syndrome.
        Respir Physiol Neurobiol. 2004; 139: 215-224
        • Kawano K.
        • Usui N.
        • Kanazawa H.
        • et al.
        Changes in nasal and oral respiratory resistance before and after uvulopalatopharyngoplasty.
        Acta Otolaryngol Suppl. 1996; 523: 236-238
        • Sampson M.G.
        • Grassino K.
        Neuromechanical properties in obese patients during carbon dioxide rebreathing.
        Am J Med. 1983; 75: 81-90
        • Cattapan S.E.
        • Laghi F.
        • Tobin M.J.
        Can diaphragmatic contractility be assessed by airway twitch pressure in mechanically ventilated patients?.
        Thorax. 2003; 58: 58-62
        • Laffey J.
        • Kavanagh B.
        Permissive hypercapnia.
        in: Tobin M.J. Principles and practice of mechanical ventilation. McGraw Hill, New York2006: 373-392
        • Sharp J.T.
        • Henry J.P.
        • Sweany S.K.
        • et al.
        The total work of breathing in normal and obese men.
        J Clin Invest. 1964; 43: 728-739
        • Han F.
        • Chen E.
        • Wei H.
        • et al.
        Treatment effects on carbon dioxide retention in patients with obstructive sleep apnea-hypopnea syndrome.
        Chest. 2001; 119: 1814-1819
        • Berthon-Jones M.
        • Sullivan C.E.
        Time course of change in ventilatory response to CO2 with long-term CPAP therapy for obstructive sleep apnea.
        Am Rev Respir Dis. 1987; 135: 144-147
        • Lin C.C.
        Effect of nasal CPAP on ventilatory drive in normocapnic and hypercapnic patients with obstructive sleep apnoea syndrome.
        Eur Respir J. 1994; 7: 2005-2010
        • Rapoport D.M.
        • Garay S.M.
        • Epstein H.
        • et al.
        Hypercapnia in the obstructive sleep apnea syndrome. A reevaluation of the “Pickwickian syndrome.”.
        Chest. 1986; 89: 627-635
        • Zwillich C.W.
        • Sutton F.D.
        • Pierson D.J.
        • et al.
        Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome.
        Am J Med. 1975; 59: 343-348
        • Kalra S.P.
        Central leptin insufficiency syndrome: an interactive etiology for obesity, metabolic and neural diseases and for designing new therapeutic interventions.
        Peptides. 2008; 29: 127-138
        • Tankersley C.
        • Kleeberger S.
        • Russ B.
        • et al.
        Modified control of breathing in genetically obese (ob/ob) mice.
        J Appl Physiol. 1996; 81: 716-723
        • Tankersley C.G.
        • O'Donnell C.
        • Daood M.J.
        • et al.
        Leptin attenuates respiratory complications associated with the obese phenotype.
        J Appl Physiol. 1998; 85: 2261-2269
        • Considine R.V.
        • Sinha M.K.
        • Heiman M.L.
        • et al.
        Serum immunoreactive-leptin concentrations in normal-weight and obese humans.
        N Engl J Med. 1996; 334: 292-295
        • Ip M.S.
        • Lam K.S.
        • Ho C.
        • et al.
        Serum leptin and vascular risk factors in obstructive sleep apnea.
        Chest. 2000; 118: 580-586
        • Barcelo A.
        • Barbe F.
        • Llompart E.
        • et al.
        Neuropeptide Y and leptin in patients with obstructive sleep apnea syndrome: role of obesity.
        Am J Respir Crit Care Med. 2005; 171: 183-187
        • Shimura R.
        • Tatsumi K.
        • Nakamura A.
        • et al.
        Fat accumulation, leptin, and hypercapnia in obstructive sleep apnea-hypopnea syndrome.
        Chest. 2005; 127: 543-549
        • Makinodan K.
        • Yoshikawa M.
        • Fukuoka A.
        • et al.
        Effect of serum leptin levels on hypercapnic ventilatory response in obstructive sleep apnea.
        Respiration. 2008; 75: 257-264
        • Perez de Llano L.A.
        • Golpe R.
        • Ortiz Piquer M.
        • et al.
        Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome.
        Chest. 2005; 128: 587-594
        • Mokhlesi B.
        • Tulaimat A.
        • Evans A.T.
        • et al.
        Impact of adherence with positive airway pressure therapy on hypercapnia in obstructive sleep apnea.
        J Clin Sleep Med. 2006; 2: 57-62
        • Berger K.I.
        • Ayappa I.
        • Chatr-Amontri B.
        • et al.
        Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep.
        Chest. 2001; 120: 1231-1238
        • Rapoport D.M.
        • Sorkin B.
        • Garay S.M.
        • et al.
        Reversal of the “Pickwickian syndrome” by long-term use of nocturnal nasal-airway pressure.
        N Engl J Med. 1982; 307: 931-933
        • Masa J.F.
        • Celli B.R.
        • Riesco J.A.
        • et al.
        The obesity hypoventilation syndrome can be treated with noninvasive mechanical ventilation.
        Chest. 2001; 119: 1102-1107
        • Leech J.A.
        • Onal E.
        • Lopata M.
        Nasal CPAP continues to improve sleep-disordered breathing and daytime oxygenation over long-term follow-up of occlusive sleep apnea syndrome.
        Chest. 1992; 102: 1651-1655
        • Norman R.G.
        • Goldring R.M.
        • Clain J.M.
        • et al.
        Transition from acute to chronic hypercapnia in patients with periodic breathing: predictions from a computer model.
        J Appl Physiol. 2006; 100: 1733-1741
        • Ayappa I.
        • Berger K.I.
        • Norman R.G.
        • et al.
        Hypercapnia and ventilatory periodicity in obstructive sleep apnea syndrome.
        Am J Respir Crit Care Med. 2002; 166: 1112-1115
        • Schafer H.
        • Ewig S.
        • Hasper E.
        • et al.
        Failure of CPAP therapy in obstructive sleep apnoea syndrome: predictive factors and treatment with bilevel-positive airway pressure.
        Respir Med. 1998; 92: 208-215
        • Banerjee D.
        • Yee B.J.
        • Piper A.J.
        • et al.
        Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure.
        Chest. 2007; 131: 1678-1684
        • Piper A.J.
        • Wang D.
        • Yee B.J.
        • et al.
        Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation.
        Thorax. 2008; 63: 395-401
        • Kushida C.A.
        • Chediak A.
        • Berry R.B.
        • et al.
        Clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea.
        J Clin Sleep Med. 2008; 4: 157-171
        • Redolfi S.
        • Corda L.
        • La Piana G.
        • et al.
        Long-term noninvasive ventilation increases chemosensitivity and leptin in obesity-hypoventilation syndrome.
        Respir Med. 2007; 101: 1191-1195
        • de Lucas-Ramos P.
        • de Miguel-Diez J.
        • Santacruz-Siminiani A.
        • et al.
        Benefits at 1 year of nocturnal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome.
        Respir Med. 2004; 98: 961-967
        • Storre J.H.
        • Seuthe B.
        • Fiechter R.
        • et al.
        Average volume-assured pressure support in obesity hypoventilation: a randomized crossover trial.
        Chest. 2006; 130: 815-821
        • Piper A.J.
        • Sullivan C.E.
        Effects of short-term NIPPV in the treatment of patients with severe obstructive sleep apnea and hypercapnia.
        Chest. 1994; 105: 434-440
        • Hensley M.J.
        • Read D.J.
        Intermittent obstruction of the upper airway during sleep causing profound hypoxaemia. A neglected mechanism exacerbating chronic respiratory failure.
        Aust N Z J Med. 1976; 6: 481-486
        • Kim S.H.
        • Eisele D.W.
        • Smith P.L.
        • et al.
        Evaluation of patients with sleep apnea after tracheotomy.
        Arch Otolaryngol Head Neck Surg. 1998; 124: 996-1000
        • Heinemann F.
        • Budweiser S.
        • Dobroschke J.
        • et al.
        Non-invasive positive pressure ventilation improves lung volumes in the obesity hypoventilation syndrome.
        Respir Med. 2007; 101: 1229-1235
        • Sugerman H.J.
        • Fairman R.P.
        • Sood R.K.
        • et al.
        Long-term effects of gastric surgery for treating respiratory insufficiency of obesity.
        Am J Clin Nutr. 1992; 55: 597S-601S
        • Pillar G.
        • Peled R.
        • Lavie P.
        Recurrence of sleep apnea without concomitant weight increase 7.5 years after weight reduction surgery.
        Chest. 1994; 106: 1702-1704
        • Mokhlesi B.
        • Tulaimat A.
        Recent advances in obesity hypoventilation syndrome.
        Chest. 2007; 132: 1322-1336
        • Bayliss D.A.
        • Millhorn D.E.
        Central neural mechanisms of progesterone action: application to the respiratory system.
        J Appl Physiol. 1992; 73: 393-404
        • Sutton Jr., F.D.
        • Zwillich C.W.
        • Creagh C.E.
        • et al.
        Progesterone for outpatient treatment of Pickwickian syndrome.
        Ann Intern Med. 1975; 83: 476-479
        • Lyons H.A.
        • Huang C.T.
        Therapeutic use of progesterone in alveolar hypoventilation associated with obesity.
        Am J Med. 1968; 44: 881-888
        • Poulter N.R.
        • Chang C.L.
        • Farley T.M.
        • et al.
        Risk of cardiovascular diseases associated with oral progestagen preparations with therapeutic indications [letter].
        Lancet. 1999; 354: 1610
        • Douketis J.D.
        • Julian J.A.
        • Kearon C.
        • et al.
        Does the type of hormone replacement therapy influence the risk of deep vein thrombosis? A prospective case-control study.
        J Thromb Haemost. 2005; 3: 943-948
        • Swenson E.R.
        Carbonic anhydrase inhibitors and ventilation: a complex interplay of stimulation and suppression.
        Eur Respir J. 1998; 12: 1242-1247
        • Tojima H.
        • Kunitomo F.
        • Kimura H.
        • et al.
        Effects of acetazolamide in patients with the sleep apnoea syndrome.
        Thorax. 1988; 43: 113-119
        • Whyte K.F.
        • Gould G.A.
        • Airlie M.A.
        • et al.
        Role of protriptyline and acetazolamide in the sleep apnea/hypopnea syndrome.
        Sleep. 1988; 11: 463-472