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Control of Breathing

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Cardiopulmonary Monitoring

Abstract

The control of breathing is an area of active research with important implications for the management of critically ill. The regulation of carbon dioxide occurs through a negative feedback control system involving peripheral and central chemoreceptors as well as effectors via the diaphragm and respiratory muscles. The interactions of the various sensors is a topic that is still debated, but the existing literature largely supports a hyper-additive model. Although the control system regulates arterial blood gases and work of breathing, it responds to many different perturbations including activity and lung function. Clinical implications important for the intensivist are discussed including mechanisms of dyspnea, worsening of hypercapnia during supplemental oxygen, patient–ventilator dyssynchrony. A thorough understanding of control of breathing is helpful for the intensivist and could be critical to the success of individualized therapy or personalized medicine in the ICU.

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References

  • Akoumianaki E, Lyazidi A, Rey N, Matamis D, Perez-Martinez N, Giraud R, Mancebo J, Brochard L, Richard JM. Mechanical ventilation-induced reverse-triggered breaths: a frequently unrecognized form of neuromechanical coupling. Chest. 2013;143:927–38.

    Article  PubMed  Google Scholar 

  • Beall CM, Strohl KP, Blangero J, Williams-Blangero S, Almasy LA, Decker MJ, Worthman CM, Goldstein MC, Vargas E, Villena M, Soria R, Alarcon AM, Gonzales C. Ventilation and hypoxic ventilatory response of Tibetan and Aymara high altitude natives. Am J Phys Anthropol. 1997a;104:427–47.

    Article  CAS  PubMed  Google Scholar 

  • Beall CM, Strohl KP, Blangero J, Williams-Blangero S, Decker MJ, Brittenham GM, Goldstein MC. Quantitative genetic analysis of arterial oxygen saturation in Tibetan highlanders. Hum Biol. 1997b;69:597–604.

    CAS  PubMed  Google Scholar 

  • Beitler JR, Sands SA, Loring SH, Owens RL, Malhotra A, Spragg RG, Matthay MA, Thompson BT, Talmor D. Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria. Intensive Care Med. 2016;42:1427–36.

    Article  PubMed  PubMed Central  Google Scholar 

  • Berngard SC, Beitler JR, Malhotra A. Personalizing mechanical ventilation for acute respiratory distress syndrome. J Thorac Dis. 2016;8:E172–4.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dempsey JA. Exercise hyperpnea. Chairman’s introduction. Adv Exp Med Biol. 1995;393:133–6.

    Article  CAS  PubMed  Google Scholar 

  • Dempsey JA, Forster HV, Birnbaum ML, Reddan WG, Thoden J, Grover RF, Rankin J. Control of exercise hyperpnea under varying durations of exposure to moderate hypoxia. Respir Physiol. 1972;16:213–31.

    Article  CAS  PubMed  Google Scholar 

  • Dempsey JA, et al. Regulation of ventilation and respiratory muscle function in NREM sleep. Prog Clin Biol Res. 1990;345:145–54; discussion 154-145. available.

    CAS  PubMed  Google Scholar 

  • Dempsey JA, Veasey SC, Morgan BJ, O’Donnell CP. Pathophysiology of sleep apnea. Physiol Rev. 2010;90:47–112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duffin J, Mohan RM, Vasiliou P, Stephenson R, Mahamed S. A model of the chemoreflex control of breathing in humans: model parameters measurement. Respir Physiol. 2000;120:13–26.

    Article  CAS  PubMed  Google Scholar 

  • Dunn WF, Nelson SB, Hubmayr RD. Oxygen-induced hypercarbia in obstructive pulmonary disease. Am Rev Respir Dis. 1991;144:526–30.

    Article  CAS  PubMed  Google Scholar 

  • Esnault P, Cardinale M, Hraiech S, Goutorbe P, Baumstrack K, Prud’homme E, Bordes J, Forel JM, Meaudre E, Papazian L, Guervilly C. High respiratory drive and excessive respiratory efforts predict relapse of respiratory failure in critically ill patients with COVID-19. Am J Respir Crit Care Med. 2020;202:1173–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feldman JL. Neurobiology of breathing control. Where to look and what to look for. Adv Exp Med Biol. 1995;393:3–5.

    Article  CAS  PubMed  Google Scholar 

  • Feldman JL. Chapter 14--looking forward to breathing. Prog Brain Res. 2011;188:213–8.

    Article  PubMed  Google Scholar 

  • Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 does not lead to a “typical” acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;201:1299–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heinrich EC, Djokic MA, Gilbertson D, DeYoung PN, Bosompra NO, Wu L, Anza-Ramirez C, Orr JE, Powell FL, Malhotra A, Simonson TS. Cognitive function and mood at high altitude following acclimatization and use of supplemental oxygen and adaptive servoventilation sleep treatments. PLoS One. 2019;14:e0217089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hibbert K, Rice M, Malhotra A. Obesity and ARDS. Chest. 2012;142:785–90.

    Article  PubMed  PubMed Central  Google Scholar 

  • Horner RL. Motor control of the pharyngeal musculature and implications for the pathogenesis of obstructive sleep apnea. Sleep. 1996;19:827–53.

    Article  CAS  PubMed  Google Scholar 

  • Horner RL. Impact of brainstem sleep mechanisms on pharyngeal motor control. Respir Physiol. 2000;119:113–21.

    Article  CAS  PubMed  Google Scholar 

  • Horner RL. The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea. Respir Res. 2001;2:286–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horner RL. Pathophysiology of obstructive sleep apnea. J Cardiopulm Rehabil Prev. 2008;28:289–98.

    Article  PubMed  Google Scholar 

  • Horner RL, Innes JA, Murphy K, Guz A. Evidence for reflex upper airway dilator muscle activation by sudden negative airway pressure in man. J Physiol (Lond). 1991;436:15–29.

    Article  CAS  Google Scholar 

  • Kikuchi Y, Okabe S, Tamura G, Hida W, Homma M, Shirato K, Takishima T. Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma. N Engl J Med. 1994;330:1329–34.

    Article  CAS  PubMed  Google Scholar 

  • Malhotra A, Schwartz DR, Ayas N, Stanchina M, White DP. Treatment of oxygen-induced hypercapnia. Lancet. 2001;357:884–5.

    Article  CAS  PubMed  Google Scholar 

  • Manning HL, Schwartzstein RM. Pathophysiology of dyspnea. N Engl J Med. 1995;333:1547–53.

    Article  CAS  PubMed  Google Scholar 

  • Mascheroni D, Kolobow T, Fumagalli R, Moretti MP, Chen V, Buckhold D. Acute respiratory failure following pharmacologically induced hyperventilation: an experimental animal study. Intensive Care Med. 1988;15:8–14.

    Article  CAS  PubMed  Google Scholar 

  • Mathew OP. Maintenance of upper airway patency. J Pediatr. 1985;106:863–9.

    Article  CAS  PubMed  Google Scholar 

  • Mathew OP, Abu-Osba YK, Thach BT. Influence of upper airway pressure changes on genioglossus and muscle respiratory activity. J Appl Physiol. 1982a;52:438.

    Article  CAS  PubMed  Google Scholar 

  • Mathew OP, Abu-Osba YK, Thach BT. Genioglossus muscle response to upper airway pressure changes: afferent pathways. J Appl Physiol. 1982b;52:445.

    Article  CAS  PubMed  Google Scholar 

  • Mead J, Takishima T, Leith D. Stress distribution in lungs: a model of pulmonary elasticity. J Appl Physiol. 1970;28:596–608.

    Article  CAS  PubMed  Google Scholar 

  • Meza S, Younes M. Ventilatory stability during sleep studied with proportional assist ventilation (PAV). Sleep. 1996;19:S164–6.

    Article  CAS  PubMed  Google Scholar 

  • Meza S, Mendez M, Ostrowski M, Younes M. Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects. J Appl Physiol (1985). 1998a;85:1929–40.

    Article  CAS  Google Scholar 

  • Meza S, Giannouli E, Younes M. Control of breathing during sleep assessed by proportional assist ventilation. J Appl Physiol (1985). 1998b;84:3–12.

    Article  CAS  Google Scholar 

  • Moosavi SH, Banzett RB, Butler JP. Time course of air hunger mirrors the biphasic ventilatory response to hypoxia. J Appl Physiol (1985). 2004;97:2098–103.

    Article  CAS  Google Scholar 

  • Moss M, Ulysse CA, Angus DC, National Heart L, Blood Institute PCTN. Early neuromuscular blockade in the acute respiratory distress syndrome. Reply. N Engl J Med. 2019;381:787–8.

    PubMed  Google Scholar 

  • Orr JE, Heinrich EC, Djokic M, Gilbertson D, Deyoung PN, Anza-Ramirez C, Villafuerte FC, Powell FL, Malhotra A, Simonson T. Adaptive servoventilation as treatment for central sleep apnea due to high-altitude periodic breathing in nonacclimatized healthy individuals. High Alt Med Biol. 2018;19:178–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guerin C, Prat G, Morange S, Roch A, Investigators AS. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363:1107–16.

    Article  CAS  PubMed  Google Scholar 

  • Plataki M, Sands SA, Malhotra A. Clinical consequences of altered chemoreflex control. Respir Physiol Neurobiol. 2013;189:354–63.

    Article  PubMed  PubMed Central  Google Scholar 

  • Robinson TD, Freiberg DB, Regnis JA, Young IH. The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161:1524–9.

    Article  CAS  PubMed  Google Scholar 

  • Simonson TS, Yang Y, Huff CD, Yun H, Qin G, Witherspoon DJ, Bai Z, Lorenzo FR, Xing J, Jorde LB, Prchal JT, Ge R. Genetic evidence for high-altitude adaptation in Tibet. Science. 2010;329:72–5.

    Article  CAS  PubMed  Google Scholar 

  • Simonson T, Baker T, Banzett R, Bishop T, Dempsey J, Feldman J, Guyenet P, Hodson E, Mitchell G, Moya EA, Nokes B, Orr J, Owens R, Poulin M, Rawlings J, Schmickl C, Watters J, Younes M, Malhotra A. Silent hypoxemia in COVID-19. J Physiol (Lond). 2021:599(4);1057–65.

    Google Scholar 

  • Skatrud JB, Dempsey JA. Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation. J Appl Physiol. 1983;55:813–22.

    Article  CAS  PubMed  Google Scholar 

  • Skatrud JB, et al. A sleep-induced apneic threshold. Prog Clin Biol Res. 1990;345:191–9; discussion 199–200. available.

    CAS  PubMed  Google Scholar 

  • Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL. Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science. 1991;254:726–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song D, Navalsky BE, Guan W, Ingersoll C, Wang T, Loro E, Eeles L, Matchett KB, Percy MJ, Walsby-Tickle J, McCullagh JSO, Medina RJ, Khurana TS, Bigham AW, Lappin TR, Lee FS. Tibetan PHD2, an allele with loss-of-function properties. Proc Natl Acad Sci U S A. 2020;117:12230–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swenson ER. Hypoxia and its acid-base consequences: from mountains to malignancy. Adv Exp Med Biol. 2016;903:301–23.

    Article  CAS  PubMed  Google Scholar 

  • Tobert D, Simon PM, Stroetz RW, Hubmayr RD. The determinants of respiratory rate during mechanical ventilation. Am J Respir Crit Care Med. 1997;155:485–92.

    Article  CAS  PubMed  Google Scholar 

  • Tobin MJ. Basing respiratory management of COVID-19 on physiological principles. Am J Respir Crit Care Med. 2020;201:1319–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tobin MJ, Laghi F, Jubran A. Why COVID-19 silent hypoxemia is baffling to physicians. Am J Respir Crit Care Med. 2020;202:356–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Younes M. The physiologic basis of central apnea and periodic breathing. Curr Pulmonol. 1989;10:265–326.

    Google Scholar 

  • Younes M. Proportional assist ventilation. In: Mancebo J, Net A, Brochard L, editors. Update in intensive care and emergency medicine. New York: Springer; 2002. p. 39–73.

    Google Scholar 

  • Younes M, Ostrowski M, Thompson W, Leslie C, Shewchuk W. Chemical control stability in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2001;163:1181–90.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Section of Physiology, Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, USA

    Esteban A. Moya, Tatum S. Simonson & Frank L. Powell

  2. University of California San Diego, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, La Jolla, CA, USA

    Robert L. Owens

  3. UC San Diego, Department of Medicine, La Jolla, CA, USA

    Atul Malhotra

Authors
  1. Esteban A. Moya
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  2. Tatum S. Simonson
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  3. Frank L. Powell
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  4. Robert L. Owens
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  5. Atul Malhotra
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Corresponding author

Correspondence to Atul Malhotra .

Editor information

Editors and Affiliations

  1. Royal Victoria Hospital (McGill University Health Centre), Departments of Critical Care and Physiology McGill University, Montreal, QC, Canada

    Sheldon Magder

  2. UC San Diego, Department of Medicine, La Jolla, CA, USA

    Atul Malhotra

  3. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA

    Kathryn A. Hibbert

  4. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA

    Charles Corey Hardin

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Moya, E.A., Simonson, T.S., Powell, F.L., Owens, R.L., Malhotra, A. (2021). Control of Breathing. In: Magder, S., Malhotra, A., Hibbert, K.A., Hardin, C.C. (eds) Cardiopulmonary Monitoring. Springer, Cham. https://doi.org/10.1007/978-3-030-73387-2_15

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  • DOI: https://doi.org/10.1007/978-3-030-73387-2_15

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  • Online ISBN: 978-3-030-73387-2

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