Disorders of ventilatory control
- Douglas C Johnson, MD
Douglas C Johnson, MD
- Associate Professor, Department of Medicine
- Tufts University School of Medicine
- Section Editor
- Scott Manaker, MD, PhD
Scott Manaker, MD, PhD
- Section Editor — Critical Care
- Professor of Medicine
- University of Pennsylvania School of Medicine
- Deputy Editors
- Helen Hollingsworth, MD
Helen Hollingsworth, MD
- Deputy Editor — Pulmonary, Critical Care, and Sleep Medicine
- Associate Professor of Medicine
- Boston University School of Medicine
- April F Eichler, MD, MPH
April F Eichler, MD, MPH
- Senior Deputy Editor — UpToDate
- Deputy Editor — Neurology and Sleep Medicine
- Assistant Professor of Neurology
- Harvard Medical School
The respiratory system is dependent upon a complex system of ventilatory control to ensure appropriate and adequate ventilation in order to supply oxygen, remove carbon dioxide, and maintain acid-base homeostasis. Respiratory centers in the brain integrate input from neural and chemical receptors and provide neuronal drive to the respiratory muscles, which maintain upper airway patency and drive the thoracic bellows to determine the level of ventilation.
The abnormalities of ventilatory control that result from a variety of disorders, including chronic obstructive pulmonary disease (COPD), asthma, Ondine's curse, carotid body resection, Cheyne-Stokes respiration, myxedema, starvation, and neuromuscular disease, will be reviewed here. In addition, the effects of several pharmacologic agents on ventilation and ventilatory control will be reviewed. The physiologic aspects of ventilatory control and the evaluation of patients with disorders of ventilation are discussed separately. (See "Control of ventilation".)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Development of hypercapnia is inconsistent among patients with chronic obstructive pulmonary disease (COPD) and similar degrees of airflow obstruction. COPD patients exhibiting the "blue bloater" profile of hypercapnia (CO2 retention, ie, elevated arterial carbon dioxide tension [PaCO2]) and hypoxemia have decreased respiratory drive compared with "pink puffers," who are eucapnic and have relatively normal oxygen levels [1,2].
The pattern of breathing in patients with chronic CO2 retention is characterized by a low tidal volume and high frequency, usually ≥22 breaths/minute. This respiratory pattern in combination with impaired matching of ventilation and perfusion leads to increased dead space ventilation and diminished alveolar ventilation, which contributes to CO2 retention .
Some hypercapnic, hypoxemic patients with COPD develop increased CO2 retention when O2 is administered. Such patients usually have both blunted hypercapnic and hypoxic drives . Other factors contributing to CO2 retention during O2 breathing include worsening of ventilation-perfusion distribution secondary to relief of compensatory pulmonary vasoconstriction , and unloading of CO2 due to the Haldane effect . (See "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure".)
- Lourenço RV, Miranda JM. Drive and performance of the ventilatory apparatus in chronic obstructive lung disease. N Engl J Med 1968; 279:53.
- Matthews AW, Howell JB. Assessment of responsiveness to carbon dioxide in patients with chronic airways obstruction by rate of isometric inspiratory pressure development. Clin Sci Mol Med 1976; 50:199.
- Javaheri S, Blum J, Kazemi H. Pattern of breathing and carbon dioxide retention in chronic obstructive lung disease. Am J Med 1981; 71:228.
- Bradley CA, Fleetham JA, Anthonisen NR. Ventilatory control in patients with hypoxemia due to obstructive lung disease. Am Rev Respir Dis 1979; 120:21.
- Lee J, Read J. Effect of oxygen breathing on distribution of pulmonary blood flow in chronic obstructive lung disease. Am Rev Respir Dis 1967; 96:1173.
- Lenfant C. Arterial-alveolar difference in PCO2 during air and oxygen breathing. J Appl Physiol 1966; 21:1356.
- Kikuchi Y, Okabe S, Tamura G, et al. Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma. N Engl J Med 1994; 330:1329.
- Rebuck AS, Read J. Patterns of ventilatory response to carbon dioxide during recovery from severe asthma. Clin Sci 1971; 41:13.
- Kazemi H, Kanarek DJ. Gas exchange in asthma. In: Status Asthmaticus, Weiss EB (Ed), United Park Press, Baltimore 1978. p.101.
- Severinghaus, JW, Mitchell, RA. Ondine's curse - failure of respiratory center automaticity while awake. Clin Res 1962; 10:122.
- Mellins RB, Balfour HH Jr, Turino GM, Winters RW. Failure of automatic control of ventilation (Ondine's curse). Report of an infant born with this syndrome and review of the literature. Medicine (Baltimore) 1970; 49:487.
- Mullan S, Hosobuchi Y. Respiratory hazards of high cervical percutaneous cordotomy. J Neurosurg 1968; 28:291.
- Marin-Sanabria EA, Kobayashi N, Miyake S, Kohmura E. Snoring associated with Ondine's curse in a patient with brainstem glioma. J Clin Neurosci 2006; 13:370.
- Lassman AB, Mayer SA. Paroxysmal apnea and vasomotor instability following medullary infarction. Arch Neurol 2005; 62:1286.
- Bogousslavsky J, Khurana R, Deruaz JP, et al. Respiratory failure and unilateral caudal brainstem infarction. Ann Neurol 1990; 28:668.
- Trang H, Dehan M, Beaufils F, et al. The French Congenital Central Hypoventilation Syndrome Registry: general data, phenotype, and genotype. Chest 2005; 127:72.
- Idiopathic congenital central hypoventilation syndrome: diagnosis and management. American Thoracic Society. Am J Respir Crit Care Med 1999; 160:368.
- Paton JY, Swaminathan S, Sargent CW, Keens TG. Hypoxic and hypercapnic ventilatory responses in awake children with congenital central hypoventilation syndrome. Am Rev Respir Dis 1989; 140:368.
- Shannon DC, Marsland DW, Gould JB, et al. Central hypoventilation during quiet sleep in two infants. Pediatrics 1976; 57:342.
- Shea SA, Andres LP, Shannon DC, et al. Respiratory sensations in subjects who lack a ventilatory response to CO2. Respir Physiol 1993; 93:203.
- Shea SA, Andres LP, Shannon DC, Banzett RB. Ventilatory responses to exercise in humans lacking ventilatory chemosensitivity. J Physiol 1993; 468:623.
- Gozal D, Marcus CL, Ward SL, Keens TG. Ventilatory responses to passive leg motion in children with congenital central hypoventilation syndrome. Am J Respir Crit Care Med 1996; 153:761.
- Shea SA. Life without ventilatory chemosensitivity. Respir Physiol 1997; 110:199.
- Gozal D, Simakajornboon N. Passive motion of the extremities modifies alveolar ventilation during sleep in patients with congenital central hypoventilation syndrome. Am J Respir Crit Care Med 2000; 162:1747.
- Ize-Ludlow D, Gray JA, Sperling MA, et al. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood. Pediatrics 2007; 120:e179.
- Katz ES, McGrath S, Marcus CL. Late-onset central hypoventilation with hypothalamic dysfunction: a distinct clinical syndrome. Pediatr Pulmonol 2000; 29:62.
- Carroll MS, Patwari PP, Weese-Mayer DE. Carbon dioxide chemoreception and hypoventilation syndromes with autonomic dysregulation. J Appl Physiol (1985) 2010; 108:979.
- Winter, B. Surgical treatment of asthma, chronic bronchitis and emphysema by bilateral carotid body resection. Respir Ther 1975; 5:18.
- Stulbarg MS, Winn WR, Kellett LE. Bilateral carotid body resection for the relief of dyspnea in severe chronic obstructive pulmonary disease. Physiologic and clinical observations in three patients. Chest 1989; 95:1123.
- Lugliani R, Whipp BJ, Seard C, Wasserman K. Effect of bilateral carotid-body resection on ventilatory control at rest and during exercise in man. N Engl J Med 1971; 285:1105.
- Cherniack NS, Longobardo GS. Cheyne-Stokes breathing. An instability in physiologic control. N Engl J Med 1973; 288:952.
- Dowell AR, Buckley CE 3rd, Cohen R, et al. Cheyne-Stokes respiration. A review of clinical manifestations and critique of physiological mechanisms. Arch Intern Med 1971; 127:712.
- Brown, HW, Plum, F. The neurologic basis of Cheyne-Stokes respiration. Am J Med 1961; 30:849.
- Javaheri S. A mechanism of central sleep apnea in patients with heart failure. N Engl J Med 1999; 341:949.
- Javaheri S, Parker TJ, Wexler L, et al. Occult sleep-disordered breathing in stable congestive heart failure. Ann Intern Med 1995; 122:487.
- Zwillich CW, Pierson DJ, Hofeldt FD, et al. Ventilatory control in myxedema and hypothyroidism. N Engl J Med 1975; 292:662.
- NORDQVIST P, DHUNER KG, STENBERG K, ORNDAHL G. Myxoedema coma and carbon dioxide-retention. Acta Med Scand 1960; 166:189.
- MASSUMI RA, WINNACKER JL. SEVERE DEPRESSION OF THE RESPIRATORY CENTER IN MYXEDEMA. Am J Med 1964; 36:876.
- Doekel RC Jr, Zwillich CW, Scoggin CH, et al. Clinical semi-starvation: depression of hypoxic ventilatory response. N Engl J Med 1976; 295:358.
- Coxson HO, Chan IH, Mayo JR, et al. Early emphysema in patients with anorexia nervosa. Am J Respir Crit Care Med 2004; 170:748.
- Johnson DC, Kazemi H. Central control of ventilation in neuromuscular disease. Clin Chest Med 1994; 15:607.
- Bégin R, Bureau MA, Lupien L, Lemieux B. Control and modulation of respiration in Steinert's myotonic dystrophy. Am Rev Respir Dis 1980; 121:281.
- Bégin R, Bureau MA, Lupien L, Lemieux B. Control of breathing in Duchenne's muscular dystrophy. Am J Med 1980; 69:227.
- Skatrud J, Iber C, McHugh W, et al. Determinants of hypoventilation during wakefulness and sleep in diaphragmatic paralysis. Am Rev Respir Dis 1980; 121:587.
- Axen K, Bishop M, Haas F. Respiratory load compensation in neuromuscular disorders. J Appl Physiol (1985) 1988; 64:2659.
- Liistro G, Aubert G, Rodenstein DO. Management of sleep apnoea syndrome. Eur Respir J 1995; 8:1751.
- Skatrud JB, Dempsey JA, Kaiser DG. Ventilatory response to medroxyprogesterone acetate in normal subjects: time course and mechanism. J Appl Physiol Respir Environ Exerc Physiol 1978; 44:939.
- Kryger M, McCullough RE, Collins D, et al. Treatment of excessive polycythemia of high altitude with respiratory stimulant drugs. Am Rev Respir Dis 1978; 117:455.
- 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.
- Al-Damluji S. The effect of ventilatory stimulation with medroxyprogesterone on exercise performance and the sensation of dyspnoea in hypercapnic chronic bronchitis. Br J Dis Chest 1986; 80:273.
- Igarashi T, Nishimura M, Kobayashi S, et al. Dependency on the rate of change in PaO2 of the ventilatory response to progressive hypoxia. Am J Respir Crit Care Med 1995; 151:1815.
- Pesek CA, Cooley R, Narkiewicz K, et al. Theophylline therapy for near-fatal Cheyne-Stokes respiration. A case report. Ann Intern Med 1999; 130:427.
- Kronenberg RS, Cain SM. Effects of acetazolamide and hypoxia on cerebrospinal fluid bicarbonate. J Appl Physiol 1968; 24:17.
- Swenson ER, Hughes JM. Effects of acute and chronic acetazolamide on resting ventilation and ventilatory responses in men. J Appl Physiol (1985) 1993; 74:230.
- Skatrud JB, Dempsey JA. Relative effectiveness of acetazolamide versus medroxyprogesterone acetate in correction of chronic carbon dioxide retention. Am Rev Respir Dis 1983; 127:405.
- Forwand SA, Landowne M, Follansbee JN, Hansen JE. Effect of acetazolamide on acute mountain sickness. N Engl J Med 1968; 279:839.
- Grissom CK, Roach RC, Sarnquist FH, Hackett PH. Acetazolamide in the treatment of acute mountain sickness: clinical efficacy and effect on gas exchange. Ann Intern Med 1992; 116:461.
- Richalet JP, Rivera M, Bouchet P, et al. Acetazolamide: a treatment for chronic mountain sickness. Am J Respir Crit Care Med 2005; 172:1427.
- Javaheri S. Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Am J Respir Crit Care Med 2006; 173:234.
- Fontana M, Emdin M, Giannoni A, et al. Effect of acetazolamide on chemosensitivity, Cheyne-Stokes respiration, and response to effort in patients with heart failure. Am J Cardiol 2011; 107:1675.
- Zakynthinos S, Katsaounou P, Karatza MH, et al. Antioxidants increase the ventilatory response to hyperoxic hypercapnia. Am J Respir Crit Care Med 2007; 175:62.
- CHRONIC OBSTRUCTIVE PULMONARY DISEASE
- ONDINE'S CURSE
- Congenital central hypoventilation syndrome
- Late-onset central hypoventilation syndrome
- Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD)
- CAROTID BODY RESECTION
- CHEYNE-STOKES RESPIRATION
- NEUROMUSCULAR DISEASE
- DRUGS AFFECTING VENTILATORY DRIVE
- Central nervous system depressants
- SUMMARY AND RECOMMENDATIONS