- Robert C Hyzy, MD
Robert C Hyzy, MD
- Professor of Medicine
- University of Michigan Medical Center
- Jorge Hidalgo, MD
Jorge Hidalgo, MD
- Professor of Critical Care; Chief, Divison of Critical Care
- Karl Heusner Memorial Hospital/Belize Healthcare Partners
Mechanical ventilation was traditionally applied with the aim of normalizing blood gas values, particularly the arterial carbon dioxide tension (PaCO2). However, this is no longer the primary goal of mechanical ventilation. The emphasis is now on maintaining adequate gas exchange while minimizing the risks of mechanical ventilation. Acceptance of the hypercapnia and continuation of the ventilation strategy is called permissive hypercapnia . Permissive hypercapnia is supported by the observation that hypercapnia is well tolerated and may be advantageous to patients with pulmonary disease .
Examples of strategies to reduce the risk of mechanical ventilation include (1) low tidal volume ventilation to protect the lung from ventilator-associated lung injury in patients with acute lung injury and (2) reduction of the tidal volume, respiratory rate, or both to minimize intrinsic positive end-expiratory pressure (ie, auto-PEEP) in patients with obstructive lung disease, thereby protecting the lung from barotrauma.
Typical clinical situations in which permissive hypercapnia may be used are reviewed here, as well as the contraindications, technique, benefits, and potential harms. The use of permissive hypercapnia in patients with acute respiratory distress syndrome and asthma is reviewed separately. (See "Mechanical ventilation of adults in acute respiratory distress syndrome" and "Invasive mechanical ventilation in adults with acute exacerbations of asthma".)
Clinical scenarios in which permissive hypercapnia may be appropriate include acute respiratory distress syndrome (ARDS) managed with low tidal volume ventilation and obstructive lung disease (asthma and chronic obstructive pulmonary disease [COPD]) managed with a low tidal volume and/or a low respiratory rate to minimize intrinsic positive end-expiratory pressure (ie, auto-PEEP); :
●ARDS – Low tidal volume ventilation improves important clinical outcomes in patients with ARDS. The respiratory rate is routinely increased during low tidal volume ventilation in an effort to maintain adequate minute ventilation. However, the increased respiratory rate may be insufficient to compensate for the low tidal volumes and hypercapnia may develop. (See "Mechanical ventilation of adults in acute respiratory distress syndrome", section on 'Low tidal volume ventilation'.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Tuxen DV. Permissive hypercapnic ventilation. Am J Respir Crit Care Med 1994; 150:870.
- Core Topics in Mechanical Ventilation, Mackenzie I (Ed), Cambridge University Press, 2008. p.153.
- Feihl F, Perret C. Permissive hypercapnia. How permissive should we be? Am J Respir Crit Care Med 1994; 150:1722.
- Roberts BW, Karagiannis P, Coletta M, et al. Effects of PaCO2 derangements on clinical outcomes after cerebral injury: A systematic review. Resuscitation 2015; 91:32.
- Hagen EW, Sadek-Badawi M, Carlton DP, Palta M. Permissive hypercapnia and risk for brain injury and developmental impairment. Pediatrics 2008; 122:e583.
- Kavanagh BP, Laffey JG. Hypercapnia: permissive and therapeutic. Minerva Anestesiol 2006; 72:567.
- Bidani A, Tzouanakis AE, Cardenas VJ Jr, Zwischenberger JB. Permissive hypercapnia in acute respiratory failure. JAMA 1994; 272:957.
- Tobin MJ. Culmination of an era in research on the acute respiratory distress syndrome. N Engl J Med 2000; 342:1360.
- Laffey JG, Engelberts D, Kavanagh BP. Buffering hypercapnic acidosis worsens acute lung injury. Am J Respir Crit Care Med 2000; 161:141.
- Laffey JG, Tanaka M, Engelberts D, et al. Therapeutic hypercapnia reduces pulmonary and systemic injury following in vivo lung reperfusion. Am J Respir Crit Care Med 2000; 162:2287.
- Laffey JG, Kavanagh BP. Carbon dioxide and the critically ill--too little of a good thing? Lancet 1999; 354:1283.
- Kregenow DA, Rubenfeld GD, Hudson LD, Swenson ER. Hypercapnic acidosis and mortality in acute lung injury. Crit Care Med 2006; 34:1.
- Shapiro JI, Elkins N, Logan J, et al. Effects of sodium bicarbonate, disodium carbonate, and a sodium bicarbonate/carbonate mixture on the PCO2 of blood in a closed system. J Lab Clin Med 1995; 126:65.
- Nahas GG, Sutin KM, Fermon C, et al. Guidelines for the treatment of acidaemia with THAM. Drugs 1998; 55:191.
- http://www.ashp.org/menu/DrugShortages/DrugsNoLongerAvailable/Bulletin.aspx?id=687 (Accessed on June 13, 2016).
- Curley GF, Laffey JG, Kavanagh BP. CrossTalk proposal: there is added benefit to providing permissive hypercapnia in the treatment of ARDS. J Physiol 2013; 591:2763.
- Crystal GJ. Carbon Dioxide and the Heart: Physiology and Clinical Implications. Anesth Analg 2015; 121:610.
- Broccard AF. Respiratory acidosis and acute respiratory distress syndrome: time to trade in a bull market? Crit Care Med 2006; 34:229.
- Mariani G, Cifuentes J, Carlo WA. Randomized trial of permissive hypercapnia in preterm infants. Pediatrics 1999; 104:1082.
- Broccard AF, Hotchkiss JR, Vannay C, et al. Protective effects of hypercapnic acidosis on ventilator-induced lung injury. Am J Respir Crit Care Med 2001; 164:802.
- Sinclair SE, Kregenow DA, Lamm WJ, et al. Hypercapnic acidosis is protective in an in vivo model of ventilator-induced lung injury. Am J Respir Crit Care Med 2002; 166:403.
- Laffey JG, O'Croinin D, McLoughlin P, Kavanagh BP. Permissive hypercapnia--role in protective lung ventilatory strategies. Intensive Care Med 2004; 30:347.
- Peltekova V, Engelberts D, Otulakowski G, et al. Hypercapnic acidosis in ventilator-induced lung injury. Intensive Care Med 2010; 36:869.
- Takeshita K, Suzuki Y, Nishio K, et al. Hypercapnic acidosis attenuates endotoxin-induced nuclear factor-[kappa]B activation. Am J Respir Cell Mol Biol 2003; 29:124.
- Laffey JG, Honan D, Hopkins N, et al. Hypercapnic acidosis attenuates endotoxin-induced acute lung injury. Am J Respir Crit Care Med 2004; 169:46.
- Bidani A, Wang CZ, Saggi SJ, Heming TA. Evidence for pH sensitivity of tumor necrosis factor-alpha release by alveolar macrophages. Lung 1998; 176:111.
- Serrano CV Jr, Fraticelli A, Paniccia R, et al. pH dependence of neutrophil-endothelial cell adhesion and adhesion molecule expression. Am J Physiol 1996; 271:C962.
- Shibata K, Cregg N, Engelberts D, et al. Hypercapnic acidosis may attenuate acute lung injury by inhibition of endogenous xanthine oxidase. Am J Respir Crit Care Med 1998; 158:1578.
- Coakley RJ, Taggart C, Greene C, et al. Ambient pCO2 modulates intracellular pH, intracellular oxidant generation, and interleukin-8 secretion in human neutrophils. J Leukoc Biol 2002; 71:603.
- Adding LC, Agvald P, Persson MG, Gustafsson LE. Regulation of pulmonary nitric oxide by carbon dioxide is intrinsic to the lung. Acta Physiol Scand 1999; 167:167.
- De Smet HR, Bersten AD, Barr HA, Doyle IR. Hypercapnic acidosis modulates inflammation, lung mechanics, and edema in the isolated perfused lung. J Crit Care 2007; 22:305.
- Schwartges I, Schwarte LA, Fournell A, et al. Hypercapnia induces a concentration-dependent increase in gastric mucosal oxygenation in dogs. Intensive Care Med 2008; 34:1898.
- Morisaki H, Yajima S, Watanabe Y, et al. Hypercapnic acidosis minimizes endotoxin-induced gut mucosal injury in rabbits. Intensive Care Med 2009; 35:129.
- Brofman JD, Leff AR, Munoz NM, et al. Sympathetic secretory response to hypercapnic acidosis in swine. J Appl Physiol (1985) 1990; 69:710.
- Hoka S, Arimura H, Bosnjak ZJ, Kampine JP. Regional venous outflow, blood volume, and sympathetic nerve activity during hypercapnia and hypoxic hypercapnia. Can J Physiol Pharmacol 1992; 70:1032.
- Carvalho CR, Barbas CS, Medeiros DM, et al. Temporal hemodynamic effects of permissive hypercapnia associated with ideal PEEP in ARDS. Am J Respir Crit Care Med 1997; 156:1458.
- Weber T, Tschernich H, Sitzwohl C, et al. Tromethamine buffer modifies the depressant effect of permissive hypercapnia on myocardial contractility in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2000; 162:1361.
- Foëx P, Fordham RM. Intrinsic myocardial recovery from the negative inotropic effects of acute hypercapnia. Cardiovasc Res 1972; 6:257.
- Tang WC, Weil MH, Gazmuri RJ, et al. Reversible impairment of myocardial contractility due to hypercarbic acidosis in the isolated perfused rat heart. Crit Care Med 1991; 19:218.
- Walley KR, Lewis TH, Wood LD. Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs. Circ Res 1990; 67:628.
- Orchard CH, Kentish JC. Effects of changes of pH on the contractile function of cardiac muscle. Am J Physiol 1990; 258:C967.
- Hata K, Goto Y, Kawaguchi O, et al. Hypercapnic acidosis increases oxygen cost of contractility in the dog left ventricle. Am J Physiol 1994; 266:H730.
- Nahurn, A, Marini, JJ. Alternatives to conventional mechanical ventilation in acute respiratory failure. Curr Pulmonol 1994; 15:157.
- Viitanen A, Salmenperä M, Heinonen J. Right ventricular response to hypercarbia after cardiac surgery. Anesthesiology 1990; 73:393.
- Wexels JC, Mjøs OD. Effects of carbon dioxide and pH on myocardial function in dogs with acute left ventricular failure. Crit Care Med 1987; 15:1116.
- Pulley DD, Kirvassilis GV, Kelermenos N, et al. Regional and global myocardial circulatory and metabolic effects of isoflurane and halothane in patients with steal-prone coronary anatomy. Anesthesiology 1991; 75:756.
- Lassen NA. Brain extracellular pH: the main factor controlling cerebral blood flow. Scand J Clin Lab Invest 1968; 22:247.
- Kontos HA, Raper AJ, Patterson JL. Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels. Stroke 1977; 8:358.
- Eisele JH, Eger EI 2nd, Muallem M. Narcotic properties of carbon dioxide in the dog. Anesthesiology 1967; 28:856.
- SIEKER HO, HICKAM JB. Carbon dioxide intoxication: the clinical syndrome, its etiology and management with particular reference to the use of mechanical respirators. Medicine (Baltimore) 1956; 35:389.
- WESTLAKE EK, SIMPSON T, KAYE M. Carbon dioxide narcosis in emphysema. Q J Med 1955; 24:155.
- Meissner HH, Franklin C. Extreme hypercapnia in a fully alert patient. Chest 1992; 102:1298.
- Caroll GC, Rothenberg DM. Carbon dioxide narcosis. Pathological or "pathillogical"? Chest 1992; 102:986.
- Kacmarek R, Hickling KG. Permissive hypercapnia. Respir Care 1993; 38:373.
- Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988; 138:720.
- Loftus CM, Silvidi JA, Bernstein DD, Kosier T. Effects of hypercapnia on cerebral blood flow following prophylactic and delayed experimental superficial temporal artery-middle cerebral artery bypass. Surg Neurol 1989; 31:183.
- Feihl F, Eckert P, Brimioulle S, et al. Permissive hypercapnia impairs pulmonary gas exchange in the acute respiratory distress syndrome. Am J Respir Crit Care Med 2000; 162:209.
- Pfeiffer B, Hachenberg T, Wendt M, Marshall B. Mechanical ventilation with permissive hypercapnia increases intrapulmonary shunt in septic and nonseptic patients with acute respiratory distress syndrome. Crit Care Med 2002; 30:285.
- Hassett P, Laffey JG. Permissive hypercapnia: Balancing risks and benefits in the peripheral microcirculation. Crit Care Med 2007; 35:2229.
- Mancini M, Zavala E, Mancebo J, et al. Mechanisms of pulmonary gas exchange improvement during a protective ventilatory strategy in acute respiratory distress syndrome. Am J Respir Crit Care Med 2001; 164:1448.
- Doerr CH, Gajic O, Berrios JC, et al. Hypercapnic acidosis impairs plasma membrane wound resealing in ventilator-injured lungs. Am J Respir Crit Care Med 2005; 171:1371.
- Lang JD, Figueroa M, Sanders KD, et al. Hypercapnia via reduced rate and tidal volume contributes to lipopolysaccharide-induced lung injury. Am J Respir Crit Care Med 2005; 171:147.
- Moody W Jr. Effects of intracellular H+ on the electrical properties of excitable cells. Annu Rev Neurosci 1984; 7:257.
- Madshus IH. Regulation of intracellular pH in eukaryotic cells. Biochem J 1988; 250:1.
- Cohen Y, Chang LH, Litt L, et al. Stability of brain intracellular lactate and 31P-metabolite levels at reduced intracellular pH during prolonged hypercapnia in rats. J Cereb Blood Flow Metab 1990; 10:277.
- Gennari FJ, Cohen JJ. Intracellular acid-base physiology. In: Acid/Base, Cohen JJ, Kassirer JP (Eds), Little, Brown, Boston 1982. p.25.
- Siesjö BK, Folbergrová J, MacMillan V. The effect of hypercapnia upon intracellular pH in the brain, evaluated by the bicarbonate-carbonic acid method and from the creatine phosphokinase equilibrium. J Neurochem 1972; 19:2483.
- Siesjö BK. Quantification of pH regulation in hypercapnia and hypocapnia. Scand J Clin Lab Invest 1971; 28:113.
- Cingolani HE, Koretsune Y, Marban E. Recovery of contractility and pHi during respiratory acidosis in ferret hearts: role of Na(+)-H+ exchange. Am J Physiol 1990; 259:H843.
- Portman MA, Lassen NA, Cooper TG, et al. Intra- and extracellular pH of the brain in vivo studied by 31P-NMR during hyper- and hypocapnia. J Appl Physiol (1985) 1991; 71:2168.
- Barrere B, Meric P, Borredon J, et al. Cerebral intracellular pH regulation during hypercapnia in unanesthetized rats: a 31P nuclear magnetic resonance spectroscopy study. Brain Res 1990; 516:215.