Permissive hypercapnia — role in protective lung ventilatory strategies

  • John G. Laffey
  • Donall O’Croinin
  • Paul McLoughlin
  • Brian P. Kavanagh


‘Permissive hypercapnia’ is an inherent element of accepted protective lung ventilation. However, there are no clinical data evaluating the efficacy of hypercapnia per se, independent of ventilator strategy. In the absence of such data, it is necessary to determine whether the potential exists for an active role for hypercapnia, distinct from the demonstrated benefits of reduced lung stretch. In this review, we consider four key issues. First, we consider the evidence that protective lung ventilatory strategies improve survival and we explore current paradigms regarding the mechanisms underlying these effects. Second, we examine whether hypercapnic acidosis may have effects that are additive to the effects of protective ventilation. Third, we consider whether direct elevation of CO2, in the absence of protective ventilation, is beneficial or deleterious. Fourth, we address the current evidence regarding the buffering of hypercapnic acidosis in ARDS. These perspectives reveal that the potential exists for hypercapnia to exert beneficial effects in the clinical context. Direct administration of CO2 is protective in multiple models of acute lung and systemic injury. Nevertheless, several specific concerns remain regarding the safety of hypercapnia. At present, protective ventilatory strategies that involve hypercapnia are clinically acceptable, provided the clinician is primarily targeting reduced tidal stretch. There are insufficient clinical data to suggest that hypercapnia per se should be independently induced, nor do outcome data exist to support the practice of buffering hypercapnic acidosis. Rapidly advancing basic scientific investigations should better delineate the advantages, disadvantages, and optimal use of hypercapnia in ARDS.


Hypercapnic acidosis Mechanical ventilation Acute lung injury ARDS Ventilation-induced lung injury Buffering 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Fihlo G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR (1998) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338:347–354PubMedGoogle Scholar
  2. 2.
    The Acute Respiratory Distress Syndrome Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342:1301–1308Google Scholar
  3. 3.
    Pinhu L, Whitehead T, Evans T, Griffiths M (2003) Ventilator-associated lung injury. Lancet 361:332–340PubMedGoogle Scholar
  4. 4.
    Boussarsar M, Thierry G, Jaber S, Roudot-Thoraval F, Lemaire F, Brochard L (2002) Relationship between ventilatory settings and barotrauma in the acute respiratory distress syndrome. Intensive Care Med 28:406–413PubMedGoogle Scholar
  5. 5.
    Maggiore SM, Jonson B, Richard JC, Jaber S, Lemaire F, Brochard L (2001) Alveolar derecruitment at decremental positive end-expiratory pressure levels in acute lung injury: comparison with the lower inflection point, oxygenation, and compliance. Am J Respir Crit Care Med 164:795–801PubMedGoogle Scholar
  6. 6.
    Dreyfuss D, Saumon G (1992) Barotrauma is volutrauma, but which volume is the one responsible? Intensive Care Med 18:139–141PubMedGoogle Scholar
  7. 7.
    Dreyfuss D, Saumon G (1998) Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 157:294–323PubMedGoogle Scholar
  8. 8.
    Dreyfuss D, Saumon G (1998) From ventilator-induced lung injury to multiple organ dysfunction? Intensive Care Med 24:102–104PubMedGoogle Scholar
  9. 9.
    Ricard JD, Dreyfuss D, Saumon G (2002) Ventilator-induced lung injury. Curr Opin Crit Care 8:12–20PubMedGoogle Scholar
  10. 10.
    Slutsky AS, Tremblay LN (1998) Multiple system organ failure. Is mechanical ventilation a contributing factor? Am J Respir Crit Care Med 157:1721–1725PubMedGoogle Scholar
  11. 11.
    Tremblay LN, Slutsky AS (1998) Ventilator-induced injury: from barotrauma to biotrauma. Proc Assoc Am Physicians 110:482–488PubMedGoogle Scholar
  12. 12.
    Ricard JD, Dreyfuss D (2001) Cytokines during ventilator-induced lung injury: a word of caution. Anesth Analg 93:251–252PubMedGoogle Scholar
  13. 13.
    Edmonds JF, Berry E, Wyllie JH (1969) Release of prostaglandins caused by distension of the lungs. Br J Surg 56:622–623PubMedGoogle Scholar
  14. 14.
    Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS (1997) Injurious ventilatory strategies increase cytokines and c-fos mRNA expression in an isolated rat lung model. J Clin Invest 99:944–952PubMedGoogle Scholar
  15. 15.
    Murphy D, Cregg N, Tremblay L, Engelberts D, Laffey JG, Slutsky AS, Romaschin A, Kavanagh BP (2000) Adverse ventilator strategy causes pulmonary to systemic translocation of endotoxin. Am J Resp Crit Care Med 162:27–33PubMedGoogle Scholar
  16. 16.
    Nahum A, Hoyt J, Schmitz L, Moody J, Shapiro R, Marini JJ (1997) Effect of mechanical ventilation strategy on dissemination of intratracheally instilled Escherichia coli in dogs. Crit Care Med 25:1733–1743PubMedGoogle Scholar
  17. 17.
    Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS (1999) Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 282:54–61PubMedGoogle Scholar
  18. 18.
    Dreyfuss D, Ricard JD, Saumon G (2003) On the physiologic and clinical relevance of lung-borne cytokines during ventilator induced lung injury. Am J Respir Crit Care Med 167:1467–1471PubMedGoogle Scholar
  19. 19.
    Hickling KG, Walsh J, Henderson S, Jackson R (1994) Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study. Crit Care Med 22:1568–1578PubMedGoogle Scholar
  20. 20.
    Bidani A, Tzouanakis AE, Cardenas VJ Jr, Zwischenberger JB (1994) Permissive hypercapnia in acute respiratory failure. JAMA 272:957–962PubMedGoogle Scholar
  21. 21.
    Laffey JG, Kavanagh BP (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury (Letter). N Engl J Med 343:812PubMedGoogle Scholar
  22. 22.
    Eichacker PQ, Gerstenberger EP, Banks SM, Cui X, Natanson C (2002) Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 166:1510–1514PubMedGoogle Scholar
  23. 23.
    Ricard JD (2003) Are we really reducing tidal volume — and should we? Am J Resp Crit Care Med 167:1297–1298PubMedGoogle Scholar
  24. 24.
    Rubenfeld G, Caldwell E, Hudson L (2001) Publication of study results does not increase use of lung protective ventilation in patients with acute lung injury. Am J Resp Crit Care Med 163:A295Google Scholar
  25. 25.
    Weinert CR, Gross CR, Marinelli WA (2003) Impact of randomized trial results on acute lung injury ventilator therapy in teaching hospitals. Am J Respir Crit Care Med 167:1304–1309PubMedGoogle Scholar
  26. 26.
    Thompson BT, Hayden D, Matthay MA, Brower R, Parsons PE (2001) Clinicians' approaches to mechanical ventilation in acute lung injury and ARDS. Chest 120:1622–1627PubMedGoogle Scholar
  27. 27.
    Jorgensen EO, Holm S (1999) The course of circulatory and cerebral recovery after circulatory arrest: influence of prearrest, arrest and post-arrest factors. Resuscitation 42:173–182PubMedGoogle Scholar
  28. 28.
    Suljaga-Pechtel K, Goldberg E, Strickon P, Berger M, Skovron ML (1984) Cardiopulmonary resuscitation in a hospitalized population: prospective study of factors associated with outcome. Resuscitation 12:77–95PubMedGoogle Scholar
  29. 29.
    Balakrishnan I, Crook P, Morris R, Gillespie SH (2000) Early predictors of mortality in pneumococcal bacteraemia. J Infect 40:256–261PubMedGoogle Scholar
  30. 30.
    Mathur NB, Singh A, Sharma VK, Satyanarayana L (1996) Evaluation of risk factors for fatal neonatal sepsis. Indian Pediatr 33:817–822PubMedGoogle Scholar
  31. 31.
    Friedman G, Berlot G, Kahn RJ, Vincent JL (1995) Combined measurements of blood lactate concentrations and gastric intramucosal pH in patients with severe sepsis. Crit Care Med 23:1184–1193PubMedGoogle Scholar
  32. 32.
    Anyaegbunam A, Fleischer A, Whitty J, Brustman L, Randolph G, Langer O (1991) Association between umbilical artery cord pH, five-minute Apgar scores and neonatal outcome. Gynecol Obstet Invest 32:220–223PubMedGoogle Scholar
  33. 33.
    Thorens JB, Jolliet P, Ritz M, Chevrolet JC (1996) Effects of rapid permissive hypercapnia on hemodynamics, gas exchange, and oxygen transport and consumption during mechanical ventilation for the acute respiratory distress syndrome. Intensive Care Med 22:182–191PubMedGoogle Scholar
  34. 34.
    Forsythe SM, Schmidt GA (2000) Sodium bicarbonate for the treatment of lactic acidosis. Chest 117:260–267PubMedGoogle Scholar
  35. 35.
    Potkin RT, Swenson ER (1992) Resuscitation from severe acute hypercapnia. Determinants of tolerance and survival. Chest 102:1742–1745PubMedGoogle Scholar
  36. 36.
    Tuxen DV, Williams TJ, Scheinkestel CD, Czarny D, Bowes G (1992) Use of a measurement of pulmonary hyperinflation to control the level of mechanical ventilation in patients with acute severe asthma. Am Rev Respir Dis 146:1136–1142PubMedGoogle Scholar
  37. 37.
    Feihl F, Perret C (1994) Permissive hypercapnia. How permissive should we be? Am J Respir Crit Care Med 150:1722–1737Google Scholar
  38. 38.
    Roupie E, Dambrosio M, Servillo G, Mentec H, el Atrous S, Beydon L, Brun-Buisson C, Lemaire F, Brochard L (1995) Titration of tidal volume and induced hypercapnia in acute respiratory distress syndrome. Am J Respir Crit Care Med 152:121–128PubMedGoogle Scholar
  39. 39.
    Kiely DG, Cargill RI, Lipworth BJ (1996) Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans. Chest 109:1215–1221PubMedGoogle Scholar
  40. 40.
    Slinger P, Blundell PE, Metcalf IR (1997) Management of massive grain aspiration. Anesthesiology 87:993–995PubMedGoogle Scholar
  41. 41.
    Goldstein B, Shannon DC, Todres ID (1990) Supercarbia in children: clinical course and outcome. Crit Care Med 18:166–168PubMedGoogle Scholar
  42. 42.
    Laffey JG, Kavanagh BP (1999) Carbon dioxide and the critically ill — too little of a good thing? (Hypothesis paper). Lancet 354:1283–1286PubMedGoogle Scholar
  43. 43.
    Kregenow DA, Rubenfeld G, Hudson L, Swenson ER (2003) Permissive hypercapnia reduces mortality with 12 ml/kg tidal volumes in acute lung injury. Am J Resp Crit Care Med 167:A616Google Scholar
  44. 44.
    Shibata K, Cregg N, Engelberts D, Takeuchi A, Fedorko L, Kavanagh BP (1998) Hypercapnic acidosis may attenuate acute lung injury by inhibition of endogenous xanthine oxidase. Am J Resp Crit Care Med 158:1578–1584PubMedGoogle Scholar
  45. 45.
    Laffey JG, Engelberts D, Kavanagh BP (2000) Buffering hypercapnic acidosis worsens acute lung injury. Am J Resp Crit Care Med 161:141–146PubMedGoogle Scholar
  46. 46.
    Laffey JG, Tanaka M, Engelberts D, Luo X, Yiang S, Tanswell TK, Post M, Lindsay T, Kavanagh BP (2000) Therapeutic hypercapnia reduces pulmonary and systemic injury following in vivo lung reperfusion. Am J Respir Crit Care Med 162:2287–2294PubMedGoogle Scholar
  47. 47.
    Laffey JG, Jankov R, Engelberts D, Tanswell AK, Post M, Lindsay T, Mullen JB, Romaschin A, Stephens D, McKerlie C, Kavanagh BP (2003) Effects of therapeutic hypercapnia on mesenteric ischemia — reperfusion injury. Am J Respir Crit Care Med: 168:1383–1390Google Scholar
  48. 48.
    Henan D, Laffey JG, Hopkins N, Boylan JF, Mcloughlin P (2002) Therapeutic hypercapnia attenuates endotoxin induced acute lung injury (Abstract). Am J Resp Crit Care Med 165:A383Google Scholar
  49. 49.
    Broccard AF, Hotchkiss JR, Vannay C, Markert M, Sauty A, Feihl F, Schaller M (2001) Protective effects of hypercapnic acidosis on ventilator-induced lung injury. Am J Respir Crit Care Med 164:802–806PubMedGoogle Scholar
  50. 50.
    Sinclair SE, Kregenow DA, Lamm WJ, Starr IR, Chi EY, Hlastala MP (2002) Hypercapnic acidosis is protective in an in vivo model of ventilator-induced lung injury. Am J Respir Crit Care Med 166:403–408PubMedGoogle Scholar
  51. 51.
    Laffey JG, Engelberts D, Duggan M, Veldheuizen R, Lewis J, Kavanagh BP (2003) Carbon dioxide attenuates pulmonary impairment resulting from hyperventilation. Crit Care Med 31:2634–2640PubMedGoogle Scholar
  52. 52.
    Nomura F, Aoki M, Forbess JM, Mayer JE (1994) Effects of hypercarbic acidotic reperfusion on recovery of myocardial function after cardioplegic ischemia in neonatal lambs. Circulation 90:321–327Google Scholar
  53. 53.
    Kitakaze M, Takashima S, Funaya H, Minamino T, Node K, Shinozaki Y, Mori H, Hori M (1997) Temporary acidosis during reperfusion limits myocardial infarct size in dogs. Am J Physiol 272:H2071–H2078PubMedGoogle Scholar
  54. 54.
    Vannucci RC, Towfighi J, Heitjan DF, Brucklacher RM (1995) Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat. Pediatrics 95:868–874PubMedGoogle Scholar
  55. 55.
    Vannucci RC, Brucklacher RM, Vannucci SJ (1997) Effect of carbon dioxide on cerebral metabolism during hypoxia-ischemia in the immature rat. Pediatr Res 42:24–29PubMedGoogle Scholar
  56. 56.
    Barth A, Bauer R, Gedrange T, Walter B, Klinger W, Zwiener U (1998) Influence of hypoxia and hypoxia/hypercapnia upon brain and blood peroxidative and glutathione status in normal weight and growth- restricted newborn piglets. Exp Toxicol Pathol 50:402–410PubMedGoogle Scholar
  57. 57.
    Rehncrona S, Hauge HN, Siesjö BK (1989) Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: difference in effect by lactic acid and CO2. J Cereb Blood Flow Metab 9:65–70PubMedGoogle Scholar
  58. 58.
    Sweeney M, Beddy D, Honner V, Sinnott B, O'Regan RG, McLoughlin P (1998) Effects of changes in pH and CO2 on pulmonary arterial wall tension are not endothelium dependent. J Appl Physiol 85:2040–2046PubMedGoogle Scholar
  59. 59.
    Sweeney M, O'Regan RG, McLoughlin P (1999) Effects of changes in pH and PCO2 on wall tension in isolated rat intrapulmonary arteries. Exp Physiol 84:529–539PubMedGoogle Scholar
  60. 60.
    Ooi H, Cadogan E, Sweeney M, Howell K, O'Regan RG, McLoughlin P (2000) Chronic hypercapnia inhibits hypoxic pulmonary vascular remodeling. Am J Physiol Heart Circ Physiol 278:H331–H338PubMedGoogle Scholar
  61. 61.
    Lang JD Jr, Chumley P, Eiserich JP, Estevez A, Bamberg T, Adhami A, Crow J, Freeman BA (2000) Hypercapnia induces injury to alveolar epithelial cells via a nitric oxide-dependent pathway. Am J Physiol Lung Cell Mol Physiol 279:L994–L1002PubMedGoogle Scholar
  62. 62.
    Zhu S, Basiouny KF, Crow JP, Matalon S (2000) Carbon dioxide enhances nitration of surfactant protein A by activated alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 278:L1025–L1031PubMedGoogle Scholar
  63. 63.
    Kitakaze M, Weisfeldt ML, Marban E (1988) Acidosis during early reperfusion prevents myocardial stunning in perfused ferret hearts. J Clin Invest 82:920–927PubMedGoogle Scholar
  64. 64.
    Preckel B, Schlack W, Obal D, Barthel H, Ebel D, Grunert S, Thamer V (1998) Effect of acidotic blood reperfusion on reperfusion injury after coronary artery occlusion in the dog heart. J Cardiovasc Pharmacol 31:179–186PubMedGoogle Scholar
  65. 65.
    Bonventre JV, Cheung JY (1985) Effects of metabolic acidosis on viability of cells exposed to anoxia. Am J Physiol 249:C149–C159PubMedGoogle Scholar
  66. 66.
    Gores GJ, Nieminen AL, Wray BE, Herman B, Lemasters JJ (1989) Intracellular pH during “chemical hypoxia” in cultured rat hepatocytes. Protection by intracellular acidosis against the onset of cell death. J Clin Invest 83:386–396Google Scholar
  67. 67.
    Gores GJ, Nieminen AL, Fleishman KE, Dawson TL, Herman B, Lemasters JJ (1988) Extracellular acidosis delays onset of cell death in ATP-depleted hepatocytes. Am J Physiol 255:C315–C322PubMedGoogle Scholar
  68. 68.
    Xu L, Glassford AJ, Giaccia AJ, Giffard RG (1998) Acidosis reduces neuronal apoptosis. Neuroreport 9:875–879PubMedGoogle Scholar
  69. 69.
    Takeshita K, Suzuki Y, Nishio K, Takeuchi O, Toda K, Kudo H, Miyao N, Ishii M, Sato N, Naoki K, Aoki T, Suzuki K, Hiraoka R, Yamaguchi K (2003) Hypercapnic acidosis attenuates endotoxin-induced nuclear factor-κB activation. Am J Respir Cell Mol Biol 29:124–132PubMedGoogle Scholar
  70. 70.
    Weber T, Tschernich H, Sitzwohl C, Ullrich R, Germann P, Zimpfer M, Sladen RN, Huemer G (2000) 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 162:1361–1365PubMedGoogle Scholar
  71. 71.
    Prys-Roberts C, Kelman GR, Green-baum R, Robinson RH (1967) Circulatory influences of artificial ventilation during nitrous oxide anaesthesia in man. II. Results: the relative influence of mean intrathoracic pressure and arterial carbon dioxide tension. Br J Anaesth 39:533–548PubMedGoogle Scholar
  72. 72.
    Ebata T, Watanabe Y, Amaha K, Hosaka Y, Takagi S (1991) Haemo-dynamic changes during the apnoea test for diagnosis of brain death. Can J Anaesth 38:436–440PubMedGoogle Scholar
  73. 73.
    Vannucci RC, Towfighi J, Brucklacher RM, Vannucci SJ (2001) Effect of extreme hypercapnia on hypoxic-ischemic brain damage in the immature rat. Pediatr Res 49:799–803PubMedGoogle Scholar
  74. 74.
    Allen DB, Maguire JJ, Mahdavian M, Wicke C, Marcocci L, Scheuenstuhl H, Chang M, Le AX, Hopf HW, Hunt TK (1997) Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg. 132:991–996PubMedGoogle Scholar
  75. 75.
    Pedoto A, Caruso JE, Nandi J, Oler A, Hoffmann SP, Tassiopoulos AK, McGraw DJ, Camporesi EM, Hakim TS (1999) Acidosis stimulates nitric oxide production and lung damage in rats. Am J Respir Crit Care Med 159:397–402PubMedGoogle Scholar
  76. 76.
    Pedoto A, Nandi J, Oler A, Camporesi EM, Hakim TS, Levine RA (2001) Role of nitric oxide in acidosis-induced intestinal injury in anesthetized rats. J Lab Clin Med 138:270–276PubMedGoogle Scholar
  77. 77.
    Shams H, Peskar BA, Scheid P (1988) Acid infusion elicits thromboxane A2-mediated effects on respiration and pulmonary hemodynamics in the cat. Respir Physiol 71:169–183PubMedGoogle Scholar
  78. 78.
    Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271:C1424–C1437PubMedGoogle Scholar
  79. 79.
    Pryor WA, Squadrito GL (1995) The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide (see comments). Am J Physiol 268:L699–L722PubMedGoogle Scholar
  80. 80.
    Stamler JS (1994) Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell 78:931–936PubMedGoogle Scholar
  81. 81.
    Squadrito GL, Pryor WA (1998) Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide. Free Radic Biol Med 25:392–403PubMedGoogle Scholar
  82. 82.
    van der Vliet A, Eiserich JP, Shigenaga MK, Cross CE (1999) Reactive nitrogen species and tyrosine nitration in the respiratory tract: epiphenomena or a pathobiologic mechanism of disease? Am J Respir Crit Care Med 160:1–9PubMedGoogle Scholar
  83. 83.
    Denicola A, Freeman BA, Trujillo M, Radi R (1996) Peroxynitrite reaction with carbon dioxide/bicarbonate: kinetics and influence on peroxynitrite-mediated oxidations. Arch Biochem Biophys 333:49–58PubMedGoogle Scholar
  84. 84.
    Alvarez B, Ferrer-Sueta G, Freeman BA, Radi R (1999) Kinetics of peroxynitrite reaction with amino acids and human serum albumin. J Biol Chem 274:842–848PubMedGoogle Scholar
  85. 85.
    Tobin MJ (1994) Mechanical ventilation (review). N Engl J Med 330:1056–1061PubMedGoogle Scholar
  86. 86.
    Kollef MH, Schuster DP (1995) The acute respiratory distress syndrome (review). N Engl J Med 332:27–37PubMedGoogle Scholar
  87. 87.
    Levy MM (1998) An evidence-based evaluation of the use of sodium bicarbonate during cardiopulmonary resuscitation. Crit Care Clin 14:457–483PubMedGoogle Scholar
  88. 88.
    Grillo JA, Gonzalez ER (1993) Changes in the pharmacotherapy of CPR. Heart Lung 22:548–553PubMedGoogle Scholar
  89. 89.
    Sun JH, Filley GF, Hord K, Kindig NB, Bartle EJ (1987) Carbicarb: an effective substitute for NaHCO3 for the treatment of acidosis. Surgery 102:835–839PubMedGoogle Scholar
  90. 90.
    Goldsmith DJ, Forni LG, Hilton PJ (1997) Bicarbonate therapy and intracellular acidosis. Clin Sci 93:593–598PubMedGoogle Scholar
  91. 91.
    Abu Romeh S, Tannen RL (1986) Amelioration of hypoxia-induced lactic acidosis by superimposed hypercapnea or hydrochloride acid infusion. Am J Physiol 250:F702–F709PubMedGoogle Scholar
  92. 92.
    Arieff AI, Leach W, Park R, Lazarowitz VC (1982) Systemic effects of NaHCO3 in experimental lactic acidosis in dogs. Am J Physiol 242:F586–F591PubMedGoogle Scholar
  93. 93.
    Graf H, Leach W, Arieff AI (1985) Evidence for a detrimental effect of bicarbonate therapy in hypoxic lactic acidosis. Science 227:754–756PubMedGoogle Scholar
  94. 94.
    Graf H, Leach W, Arieff AI (1985) Metabolic effects of sodium bicarbonate in hypoxic lactic acidosis in dogs. Am J Physiol 249:F630–F635PubMedGoogle Scholar
  95. 95.
    Benjamin E, Oropello JM, Abalos AM, Hannon EM, Wang JK, Fischer E, Iberti TJ (1994) Effects of acid-base correction on hemodynamics, oxygen dynamics, and resuscitability in severe canine hemorrhagic shock. Crit Care Med 22:1616–1623PubMedGoogle Scholar
  96. 96.
    Rhee KH, Toro LO, McDonald GG, Nunnally RL, Levin DL (1993) Car-bicarb, sodium bicarbonate, and sodium chloride in hypoxic lactic acidosis. Effect on arterial blood gases, lactate concentrations, hemodynamic variables, and myocardial intracellular pH. Chest 104:913–918PubMedGoogle Scholar
  97. 97.
    Fraley DS, Adler S, Bruns FJ, Zett B (1980) Stimulation of lactate production by administration of bicarbonate in a patient with a solid neoplasm and lactic acidosis. N Engl J Med 303:1100–1102PubMedGoogle Scholar
  98. 98.
    Okuda Y, Adrogue HJ, Field JB, Nohara H, Yamashita K (1996) Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endocrinol Metab 81:314–320PubMedGoogle Scholar
  99. 99.
    Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, Kaufman F, Quayle K, Roback M, Malley R, Kuppermann N (2001) Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med 344:264–269PubMedGoogle Scholar
  100. 100.
    Rotstein OD (2000) Novel strategies for immunomodulation after trauma: revisiting hypertonic saline as a resuscitation strategy for hemorrhagic shock. J Trauma 49:580–583PubMedGoogle Scholar
  101. 101.
    Shields CJ, Sookhai S, Winter DC, Dowdall JF, Kingston G, Parfrey N, Wang JH, Kirwan WO, Redmond HP (2001) Attenuation of pancreatitis-induced pulmonary injury by aerosolized hypertonic saline. Surg Infect (Larchmt) 2:215–224Google Scholar
  102. 102.
    Pascual JL, Khwaja KA, Ferri LE, Giannias B, Evans DC, Razek T, Michel RP, Christou NV (2003) Hypertonic saline resuscitation attenuates neutrophil lung sequestration and transmigration by diminishing leuko-cyte-endothelial interactions in a two-hit model of hemorrhagic shock and infection. J Trauma 54:121–130; discussion 130–132PubMedGoogle Scholar
  103. 103.
    Rizoli SB, Kapus A, Parodo J, Fan J, Rotstein OD (1999) Hypertonic immunomodulation is reversible and accompanied by changes in CD11b expression. J Surg Res 83:130–135PubMedGoogle Scholar
  104. 104.
    Cooper DJ, Walley KR, Wiggs BR, Russell JA (1990) Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study. Ann Intern Med 112:492–498Google Scholar
  105. 105.
    Cooper DJ, Herbertson MJ, Werner HA, Walley KR (1993) Bicarbonate does not increase left ventricular contractility duringL-lactic acidemia in pigs. Am Rev Respir Dis 148:317–322PubMedGoogle Scholar
  106. 106.
    Nahas GG, Sutin KM, Fermon C, Streat S, Wiklund L, Wahlander S, Yellin P, Brasch H, Kanchuger M, Capan L, Manne J, Helwig H, Gaab M, Pfenninger E, Wetterberg T, Holmdahl M, Turndorf H (1998) Guidelines for the treatment of acidaemia with THAM. Drugs 55:191–224PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • John G. Laffey
    • 1
  • Donall O’Croinin
    • 2
  • Paul McLoughlin
    • 3
  • Brian P. Kavanagh
    • 4
  1. 1.Department of AnaesthesiaUniversity College Hospital Galway and Clinical Sciences InstituteNational University of IrelandIreland
  2. 2.Department of PhysiologyUniversity college DublinIreland
  3. 3.Department of PhysiologyUniversity college DublinIreland
  4. 4.Department of Critical Care Medicinehospital for Sick ChildrenTorontoCanada

Personalised recommendations