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Pickwickian Syndrome

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Synonyms: Obesity-Hypoventilation Syndrome (OHS), Pickwick Syndrome

"The object that presented itself to the eyes of the astonished clerk, was a boy - a wonderfully fat boy - habited as a serving lad, standing upright on the mat, with his eyes closed as if in sleep."1

The term Pickwickian Syndrome was first coined by Dr C.S. Burwood and colleagues who described the case of a businessman, weighing in at over 260 pounds with a height of 5ft 5 inches.2 The classic triad of features is extreme obesity, somnolence, daytime hypercapnoea and obstructive apnoea.3

Pathophysiology

Controversy surrounds the pathophysiology. Only a small proportion of morbidly obese patients suffer from the condition, so factors other than obesity must be at work. Some authors believe that the basic problem relates to the way the ventilatory drive reacts to hypoxia and hypercapnoea.4 Others consider that fat distribution, hormones and upper airway size are involved.

Upper airways' obstruction is certainly known to play a prominent role. It may be associated with rapid eye movement (REM) atonia, increased fat distribution around the neck and upward displacement of the diaphragm by abdominal fat.5 Experiments with mouse models suggest that deficiency of or resistance to leptin (a substance which reduces the surface tension of lung tissue) may be involved, leading to alterations in central respiratory drive and reduced ventilatory responsiveness, permitting development of carbon dioxide retention. Changes in neuromodulators resulting from the effects of hypoxia may further exacerbate the problem by depressing arousal from sleep in the face of abnormal breathing.3

Differentiation has been made between people suffering from sleep apnoea and Pickwickian syndrome in which hypoventilation is also evident whilst they are awake.6 Most patients with the syndrome also have sleep apnoea but some patients do not, suggesting that it is the obesity per se which is causing chronic hypoventilation.7

Epidemiology

There are no figures available for incidence or prevalence, mainly because the condition has been poorly defined in the past and often confused with obstructive sleep apnoea. It has been estimated that approximately 10-20% of patients with obstructive sleep apnoea have OHS.4 Risk factors mirror that for obesity and the condition is commoner in females. Tonsillar hypertrophy is an aggravating factor in children. The peak ages of presentation are 5-7 years and adolescence.5

Presentation4,5

History

Symptoms suggestive of the diagnosis may include features of sleep apnoea (witnessed apnoea, snoring enuresis, nightmares, sleep-walking), chronic mouth breathing, daytime sleepiness, hyperactivity in children, morning headaches, decreased exercise tolerance, poor school performance, poor memory and poor concentration.

A drug history should be taken to exclude alcohol excess, sedating antihistamines and central nervous system depressants, all of which can aggravate the condition.

  • The typical patient will be clinically obese, with marked fat deposition around the chin and abdomen. Thoracic kyphosis is often a feature. Leg oedema may be present.
  • The head, ears, nose and throat should be examined to exclude facial dysmorphologies or ENT abnormalities that may cause upper airways' obstruction such as macroglossia, micrognathia, retrognathia or high-arched palate. The tonsils should be examined to exclude hypertrophy and the nasal passages to exclude polyps, cysts or swollen nasal turbinates.
  • Examination of the chest may reveal signs of cor pulmonare (loud second heart sound, displaced cardiac impulse). Acquired pes excavatum may result from overuse of the respiratory muscles overcoming extrathoracic obstruction.
Diagnosis

Pickwickian syndrome cannot be diagnosed on history and examination alone but requires the demonstration of daytime hypercapnoea.7

Diagnostic criteria for Pickwickian syndrome

  • Body Mass Index À≥30 kg/m2
  • Daytime PaCO2>45 mmHg
  • Associated sleep-related breathing disorder (sleep apnoea-hypopnoea syndrome or sleep-hypoventilation or both)
  • Absence of other known causes of hypoventilation

Differential diagnosis5
Investigations4,5,7
  • Arterial blood gases - these are needed to confirm daytime hypercapnoea and hypoxaemia.
  • Nocturnal oximetry should be carried out to determine whether sleep apnoea is also present (about one-fifth of sleep apnoeic patients will have Pickwickian syndrome). Formal polysomnography may be required in borderline cases.
  • Chest X-ray - may show chest wall deformities, or signs of cardiomegaly or congestive failure.
  • Echocardiogram - may show right ventricular hypertrophy.
  • ECG - arrhythmias and right bundle branch block have been recorded.
  • Pulmonary function tests:
    • Flow volume loop - expiratory volume as measured by spirometry is plotted in a continuous curve against flow rate - may show a 'sawtooth' pattern associated with upper airways' obstruction.8
    • Forced vital capacity and expiratory reserve volume may be reduced and airways' resistance increased.
  • Overnight polysomnography may confirm hypoventilation, hypoxia and hypercapnoea during sleep, especially in children and adolescents.
  • Full blood count and thyroid function should be performed to exclude anaemia and myxoedema.
Management4,7
  • A return to normal body weight is the mainstay of treatment. Unfortunately, although they may lose weight initially, many patients are non-compliant with dietary restriction in the long term. They are furthermore restricted from increasing their physical activity due to pulmonary symptoms. Barometric surgery may be required in severe cases. Continuous positive airways' pressure (CPAP) is helpful and may need to be supplemented by oxygen.
  • The inability of these patients to increase their ventilatory capacity should be borne in mind during their management (e.g. when they are subjected to hospital procedures which may lead to hyercapnoea).9
  • Tracheostomy may be needed in severe cases, although this has to a large extent been supplanted by CPAP.
  • Respiratory stimulants such as acetazolamide should work in theory but insufficient data has been obtained from clinical trials to recommend this therapy at present.
Complications
  • Chronic hypoventilation may be associated with congestive heart failure, cor pulmonale and angina. Future research is likely to focus on the links between the syndrome and cardiovascular morbidity.10 Early epidemiological data suggests a link with coronary artery disease and stroke.11
  • Conditions associated with obesity may include arterial hypertension, diabetes mellitus, hypothyroidism, osteoarthritis, hepatic dysfunction, hyperlipidemia, asthma and pulmonary hypertension.
Prognosis4

Prognosis is improved by early recognition, weight loss and CPAP. Two prospective studies reported no in-hospital deaths. Retrospective studies however reported considerable mortality (23% in one study) in OHS patients who refused long-term CPAP.


Document references
  1. Dickens C; The Pickwick Papers 1837
  2. BICKELMANN AG, BURWELL CS, ROBIN ED, et al; Extreme obesity associated with alveolar hypoventilation; a Pickwickian syndrome. Am J Med. 1956 Nov;21(5):811-8.
  3. Piper AJ, Grunstein RR; Current perspectives on the obesity hypoventilation syndrome. Curr Opin Pulm Med. 2007 Nov;13(6):490-6. [abstract]
  4. Mokhlesi B, Kryger MH, Grunstein RR; Assessment and management of patients with obesity hypoventilation syndrome. Proc Am Thorac Soc. 2008 Feb 15;5(2):218-25. [abstract]
  5. Cataletto M, Hertz G; Obesity-Hypoventilation Syndrome and Pulmonary Consequences of Obesity, eMedicine,updated November 2008.
  6. Pack AI; Advances in sleep-disordered breathing. Am J Respir Crit Care Med. 2006 Jan 1;173(1):7-15. Epub 2005 Nov 10. [abstract]
  7. Poulain M, Doucet M, Major GC, et al; The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies. CMAJ. 2006 Apr 25;174(9):1293-9. [abstract]
  8. Flow volume loops; Anaesthesia UK 2006
  9. Nelson JA, Loredo JS, Acosta JA; The Obesity-Hypoventilation Syndrome and Respiratory Failure in the Acute Trauma Patient. J Emerg Med. 2008 Aug 30. [abstract]
  10. 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 Feb;12(1):5-17. Epub 2007 Nov 26. [abstract]
  11. Marchiafava PL, Kusmic C, Longoni B, et al; Cell physiology of the pineal body. Arch Ital Biol. 1997 Mar;135(2):183-94. [abstract]

Internet and further reading Acknowledgements EMIS is grateful to Dr Laurence Knott for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2009.
Document ID: 4072
Document Version: 21
Document Reference: bgp26005
Last Updated: 26 Mar 2009
Planned Review: 26 Mar 2011

The authors and editors of this article are employed to create accurate and up to date content reflecting reliable research evidence, guidance and best clinical practice. They are free from any commercial conflicts of interest. Find out more about updating.

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