Treatment of the obesity hypoventilation syndrome
- Thomas J Martin, MD
Thomas J Martin, MD
- Associate Professor of Clinical Medicine
- University of Virginia School of Medicine
- Assistant Professor of Medicine
- Edward Via Virginia College of Osteopathic Medicine
- Associate Professor of Medicine
- Virginia Tech-Carilion School of Medicine
Obesity hypoventilation syndrome (OHS) exists when an obese individual (body mass index [BMI] >30kg/m2) has awake alveolar hypoventilation (arterial carbon dioxide tension [PaCO2] >45 mmHg), which cannot be attributed to other conditions such as pulmonary disease, skeletal restriction, neuromuscular weakness, hypothyroidism, or pleural pathology [1-3].
Patients with OHS typically have a diminished respiratory drive, obesity-related respiratory impairment, and sleep-related breathing abnormalities . Obstructive sleep apnea (OSA) is particularly common among patients with OHS, occurring in 85 to 92 percent of patients who have OHS [5-7]. Conversely, OHS is less common among patients with OSA, occurring in 4 to 20 percent of patients with OSA [8-11].
The natural history and treatment of OHS are reviewed here. The clinical manifestations, diagnosis, and pathogenesis of OHS are discussed separately. (See "Clinical manifestations and diagnosis of obesity hypoventilation syndrome" and "Pathogenesis of obesity hypoventilation syndrome".)
Treatment is important because untreated obesity hypoventilation syndrome (OHS) can progress to acute, life-threatening cardiopulmonary compromise. In addition, untreated OHS is associated with a high mortality rate, a reduced quality of life, and numerous morbidities, including pulmonary hypertension, right heart failure, angina, and insulin resistance [4,12-14].
A prospective cohort study compared consecutively admitted patients with obesity-associated hypoventilation and severely obese patients without hypoventilation . It found that the patients with obesity-associated hypoventilation had a higher mortality rate 18 months after discharge (23 versus 9 percent) as well as increased rates of invasive mechanical ventilation during the admission and long-term care after discharge. Specific therapy was recommended during the admission for only 13 percent of the patients with obesity-associated hypoventilation.
- BICKELMANN AG, BURWELL CS, ROBIN ED, WHALEY RD. Extreme obesity associated with alveolar hypoventilation; a Pickwickian syndrome. Am J Med 1956; 21:811.
- Mokhlesi B, Kryger MH, Grunstein RR. Assessment and management of patients with obesity hypoventilation syndrome. Proc Am Thorac Soc 2008; 5:218.
- Chouri-Pontarollo N, Borel JC, Tamisier R, et al. Impaired objective daytime vigilance in obesity-hypoventilation syndrome: impact of noninvasive ventilation. Chest 2007; 131:148.
- Piper AJ, Grunstein RR. Obesity hypoventilation syndrome: mechanisms and management. Am J Respir Crit Care Med 2011; 183:292.
- Banerjee D, Yee BJ, Piper AJ, et al. Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure. Chest 2007; 131:1678.
- Kessler R, Chaouat A, Schinkewitch P, et al. The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases. Chest 2001; 120:369.
- Pérez de Llano LA, 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.
- 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.
- Laaban JP, 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.
- 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.
- Trakada GP, Steiropoulos P, Nena E, et al. Prevalence and clinical characteristics of obesity hypoventilation syndrome among individuals reporting sleep-related breathing symptoms in northern Greece. Sleep Breath 2010; 14:381.
- Fletcher EC, Shah A, Qian W, Miller CC 3rd. "Near miss" death in obstructive sleep apnea: a critical care syndrome. Crit Care Med 1991; 19:1158.
- Nowbar S, Burkart KM, Gonzales R, et al. Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med 2004; 116:1.
- Miller A, Granada M. In-hospital mortality in the Pickwickian syndrome. Am J Med 1974; 56:144.
- Randerath W, Verbraecken J, Andreas S, et al. Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep. Eur Respir J 2017; 49.
- Waldhorn RE. Nocturnal nasal intermittent positive pressure ventilation with bi-level positive airway pressure (BiPAP) in respiratory failure. Chest 1992; 101:516.
- Priou P, Hamel JF, Person C, et al. Long-term outcome of noninvasive positive pressure ventilation for obesity hypoventilation syndrome. Chest 2010; 138:84.
- Piper AJ, Wang D, Yee BJ, et al. Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax 2008; 63:395.
- Masa JF, Corral J, Caballero C, et al. Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea. Thorax 2016; 71:899.
- Hida W, Okabe S, Tatsumi K, et al. Nasal continuous positive airway pressure improves quality of life in obesity hypoventilation syndrome. Sleep Breath 2003; 7:3.
- Tsolaki V, Pastaka C, Kostikas K, et al. Noninvasive ventilation in chronic respiratory failure: effects on quality of life. Respiration 2011; 81:402.
- Heinemann F, Budweiser S, Dobroschke J, Pfeifer M. Non-invasive positive pressure ventilation improves lung volumes in the obesity hypoventilation syndrome. Respir Med 2007; 101:1229.
- Mokhlesi B, Tulaimat A, Evans AT, et al. Impact of adherence with positive airway pressure therapy on hypercapnia in obstructive sleep apnea. J Clin Sleep Med 2006; 2:57.
- Sugerman HJ, Fairman RP, Sood RK, et al. Long-term effects of gastric surgery for treating respiratory insufficiency of obesity. Am J Clin Nutr 1992; 55:597S.
- Harman EM, Wynne JW, Block AJ. The effect of weight loss on sleep-disordered breathing and oxygen desaturation in morbidly obese men. Chest 1982; 82:291.
- Nguyen NT, Hinojosa MW, Smith BR, et al. Improvement of restrictive and obstructive pulmonary mechanics following laparoscopic bariatric surgery. Surg Endosc 2009; 23:808.
- Sugerman HJ. Surgery for morbid obesity. Surgery 1993; 114:865.
- Johnson W, DeMaria E. Surgical treatment of obesity. Curr Treat Options Gastroenterol 2006; 9:167.
- DeMaria EJ, Murr M, Byrne TK, et al. Validation of the obesity surgery mortality risk score in a multicenter study proves it stratifies mortality risk in patients undergoing gastric bypass for morbid obesity. Ann Surg 2007; 246:578.
- Longitudinal Assessment of Bariatric Surgery (LABS) Consortium, Flum DR, Belle SH, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med 2009; 361:445.
- Lecube A, Sampol G, Lloberes P, et al. Asymptomatic sleep-disordered breathing in premenopausal women awaiting bariatric surgery. Obes Surg 2010; 20:454.
- Sareli AE, Cantor CR, Williams NN, et al. Obstructive sleep apnea in patients undergoing bariatric surgery--a tertiary center experience. Obes Surg 2011; 21:316.
- Haines KL, Nelson LG, Gonzalez R, et al. Objective evidence that bariatric surgery improves obesity-related obstructive sleep apnea. Surgery 2007; 141:354.
- Lee YH, Johan A, Wong KK, et al. Prevalence and risk factors for obstructive sleep apnea in a multiethnic population of patients presenting for bariatric surgery in Singapore. Sleep Med 2009; 10:226.
- Saliman JA, Benditt JO, Flum DR, et al. Pulmonary function in the morbidly obese. Surg Obes Relat Dis 2008; 4:632.
- Hallowell PT, Stellato TA, Schuster M, et al. Potentially life-threatening sleep apnea is unrecognized without aggressive evaluation. Am J Surg 2007; 193:364.
- Berry RB, Chediak A, Brown LK, et al. Best clinical practices for the sleep center adjustment of noninvasive positive pressure ventilation (NPPV) in stable chronic alveolar hypoventilation syndromes. J Clin Sleep Med 2010; 6:491.
- Sugerman HJ, Baron PL, Fairman RP, et al. Hemodynamic dysfunction in obesity hypoventilation syndrome and the effects of treatment with surgically induced weight loss. Ann Surg 1988; 207:604.
- Gallagher SF, Haines KL, Osterlund LG, et al. Postoperative hypoxemia: common, undetected, and unsuspected after bariatric surgery. J Surg Res 2010; 159:622.
- Sugerman HJ, Fairman RP, Baron PL, Kwentus JA. Gastric surgery for respiratory insufficiency of obesity. Chest 1986; 90:81.
- Martí-Valeri C, Sabaté A, Masdevall C, Dalmau A. Improvement of associated respiratory problems in morbidly obese patients after open Roux-en-Y gastric bypass. Obes Surg 2007; 17:1102.
- Korenkov M, Shah S, Sauerland S, et al. Impact of laparoscopic adjustable gastric banding on obesity co-morbidities in the medium- and long-term. Obes Surg 2007; 17:679.
- Lettieri CJ, Eliasson AH, Greenburg DL. Persistence of obstructive sleep apnea after surgical weight loss. J Clin Sleep Med 2008; 4:333.
- Greenburg DL, Lettieri CJ, Eliasson AH. Effects of surgical weight loss on measures of obstructive sleep apnea: a meta-analysis. Am J Med 2009; 122:535.
- Grunstein RR, Stenlöf K, Hedner JA, et al. Two year reduction in sleep apnea symptoms and associated diabetes incidence after weight loss in severe obesity. Sleep 2007; 30:703.
- Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med 1980; 93:391.
- Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet 1981; 1:681.
- Goldstein RS, Ramcharan V, Bowes G, et al. Effect of supplemental nocturnal oxygen on gas exchange in patients with severe obstructive lung disease. N Engl J Med 1984; 310:425.
- Martinez FJ, Bermudez-Gomez M, Celli BR. Hypothyroidism. A reversible cause of diaphragmatic dysfunction. Chest 1989; 96:1059.
- Ladenson PW, Goldenheim PD, Ridgway EC. Prediction and reversal of blunted ventilatory responsiveness in patients with hypothyroidism. Am J Med 1988; 84:877.
- MASSUMI RA, WINNACKER JL. SEVERE DEPRESSION OF THE RESPIRATORY CENTER IN MYXEDEMA. Am J Med 1964; 36:876.
- Skatrud J, Iber C, Ewart R, et al. Disordered breathing during sleep in hypothyroidism. Am Rev Respir Dis 1981; 124:325.
- Scrima L, Broudy M, Nay KN, Cohn MA. Increased severity of obstructive sleep apnea after bedtime alcohol ingestion: diagnostic potential and proposed mechanism of action. Sleep 1982; 5:318.
- Krol RC, Knuth SL, Bartlett D Jr. Selective reduction of genioglossal muscle activity by alcohol in normal human subjects. Am Rev Respir Dis 1984; 129:247.
- Sahn SA, Lakshminarayan S, Pierson DJ, Weil JV. Effect of ethanol on the ventilatory responses to oxygen and carbon dioxide in man. Clin Sci Mol Med 1975; 49:33.
- Dolly FR, Block AJ. Effect of flurazepam on sleep-disordered breathing and nocturnal oxygen desaturation in asymptomatic subjects. Am J Med 1982; 73:239.
- Geddes DM, Rudolf M, Saunders KB. Effect of nitrazepam and flurazepam on the ventilatory response to carbon dioxide. Thorax 1976; 31:548.
- Weil JV, McCullough RE, Kline JS, Sodal IE. Diminished ventilatory response to hypoxia and hypercapnia after morphine in normal man. N Engl J Med 1975; 292:1103.
- Simmons FB, Hill MW. Hypersomnia caused by upper airway obstructions: a new syndrome in otolaryngology. Ann Otol Rhinol Laryngol 1974; 83:670.
- Wijesinghe M, Williams M, Perrin K, et al. The effect of supplemental oxygen on hypercapnia in subjects with obesity-associated hypoventilation: a randomized, crossover, clinical study. Chest 2011; 139:1018.
- Hollier CA, Harmer AR, Maxwell LJ, et al. Moderate concentrations of supplemental oxygen worsen hypercapnia in obesity hypoventilation syndrome: a randomised crossover study. Thorax 2014; 69:346.
- Sutton FD Jr, Zwillich CW, Creagh CE, et al. Progesterone for outpatient treatment of Pickwickian syndrome. Ann Intern Med 1975; 83:476.
- Lyons HA, Huang CT. Therapeutic use of progesterone in alveolar hypoventilation associated with obesity. Am J Med 1968; 44:881.
- Rapoport DM, Garay SM, Epstein H, Goldring RM. Hypercapnia in the obstructive sleep apnea syndrome. A reevaluation of the "Pickwickian syndrome". Chest 1986; 89:627.
- Raurich JM, Rialp G, Ibáñez J, et al. Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO₂ response and acetazolamide treatment effects. Respir Care 2010; 55:1442.
- Powers MA. Obesity hypoventilation syndrome: bicarbonate concentration and acetazolamide. Respir Care 2010; 55:1504.
- Jones JB, Wilhoit SC, Findley LJ, Suratt PM. Oxyhemoglobin saturation during sleep in subjects with and without the obesity-hypoventilation syndrome. Chest 1985; 88:9.
- Orr WC, Imes NK, Martin RJ. Progesterone therapy in obese patients with sleep apnea. Arch Intern Med 1979; 139:109.
- Strohl KP, Hensley MJ, Saunders NA, et al. Progesterone administration and progressive sleep apneas. JAMA 1981; 245:1230.
- Cook WR, Benich JJ, Wooten SA. Indices of severity of obstructive sleep apnea syndrome do not change during medroxyprogesterone acetate therapy. Chest 1989; 96:262.
- Anttalainen U, Saaresranta T, Vahlberg T, Polo O. Short-term medroxyprogesterone acetate in postmenopausal women with sleep-disordered breathing: a placebo-controlled, randomized, double-blind, parallel-group study. Menopause 2014; 21:361.
- SHARP JT, HENRY JP, SWEANY SK, et al. THE TOTAL WORK OF BREATHING IN NORMAL AND OBESE MEN. J Clin Invest 1964; 43:728.
- Vasilakis C, Jick H, del Mar Melero-Montes M. Risk of idiopathic venous thromboembolism in users of progestagens alone. Lancet 1999; 354:1610.
- Douketis JD, Julian JA, 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.
- Conway WA, Victor LD, Magilligan DJ Jr, et al. Adverse effects of tracheostomy for sleep apnea. JAMA 1981; 246:347.
- Borel JC, Burel B, Tamisier R, et al. Comorbidities and mortality in hypercapnic obese under domiciliary noninvasive ventilation. PLoS One 2013; 8:e52006.
- Castro-Añón O, Pérez de Llano LA, De la Fuente Sánchez S, et al. Obesity-hypoventilation syndrome: increased risk of death over sleep apnea syndrome. PLoS One 2015; 10:e0117808.
- Berg G, Delaive K, Manfreda J, et al. The use of health-care resources in obesity-hypoventilation syndrome. Chest 2001; 120:377.
- Jennum P, Kjellberg J. Health, social and economical consequences of sleep-disordered breathing: a controlled national study. Thorax 2011; 66:560.