Traditional ventilator management of acute respiratory distress syndrome (ARDS), emphasizing normalization of blood gases, promoted high rates of conventional barotrauma. Research revealed a broader range of ventilator-induced lung injury, physiologically and histopathologically indistinguishable from ARDS itself. It is now known that overdistention and cyclic inflation of injured lung can exacerbate lung injury and probably promote systemic inflammation, effects minimized by low tidal volumes/plateau pressures and by application of positive end-expiratory pressure. No compelling data suggest a safe interval for nonprotective ventilation in humans; historically defined "low" tidal volumes may remain excessive for certain patients. Protective ventilation, however, entails carbon dioxide accumulation ("permissive hypercapnia"). Despite extensive study, debate remains, even over whether consequent respiratory acidosis is harmful, tolerable with physiologic adaptation, or intrinsically adaptive. Its gross systemic effects seem generally tolerated by critically ill patients; however, subsets, including those with ischemic heart disease, left or right heart failure, pulmonary hypertension, or cranial injury, may be at higher risk. In controlled trials demonstrating mortality benefit from lung-protective ventilation, acidosis was more tightly controlled than in negative studies. Decreased acidosis-associated dyspnea probably explains reduced use of sedatives and paralytics noted in those trials. There may thus be disparate goals in ARDS management: rapid institution of a restrictive ventilatory strategy, and avoidance of significant acidosis. We review data pertaining to ARDS physiology, ventilator-induced lung injury, lung-protective ventilatory strategies, and the physiology of respiratory acidosis. Tracheal gas insufflation is considered as a means to reconcile the clinical goals of ventilatory reduction and control of acidosis.
AshbaughDG, BigelowDB, PettyTL, LevineBE. Acute respiratory distress in adults. Lancet1967;2(7511):319–323.
2.
BernardGR, ArtigasA, BrighamKL, CarletJ, FalkeK, HudsonL, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination. Am J Respir Crit Care Med1994;149(3 Pt 1):818–824.
3.
WareLB, MatthayMA. The acute respiratory distress syndrome. N Engl J Med2000;342(18):1334–1349.
4.
SandifordP, ProvinceMA, SchusterDP. Distribution or regional density and vascular permeability in the adult respiratory distress syndrome. Am J Respir Crit Care Med1995;151(3 Pt 1):737–742.
5.
GattinoniL, PesentiA, TorresinA, BaglioniS, RivoltaM, RossiF, et al. Adult respiratory distress syndrome profiles by computed tomography. J Thorac Imag1986;1(3):25–30.
PelosiP, CrottiS, BrauiL, GattinoniL.Computed tomography in adult respiratory distress syndrome: what has it taught us?Eur Respir J1996;9(5):1055–1062.
8.
GattinoniL, PesentiA, AvalliL, RossiF, BombinoM.Pressure-volume curve of total respiratory system in acute respiratory failure: computed tomographic scan study. Am Rev Respir Dis1987;136(3):730–736.
9.
GattinoniL, D'AndreaL, PelosiP, VitaleG, PesentiA, FumagalliR.Regional effects and mechanism of positive end expiratory pressure in early adult respiratory distress syndrome. JAMA1993;269(16):2122–2127.
10.
GattinoniL, PesentiA, BombinoM, BaglioniS, RivoltaM, RossiF, et al. Relationships between lung computed tomographic density, gas exchange, and PEEP in acute respiratory failure. Anesthesiology1988;69(6):824–832.
11.
GattinoniL, PelosiP, CrottiS, ValenzaF.Effects of positive end-expiratory pressure on regional distribution of tidal volume and recruitment in adult respiratory distress syndrome. Am J Respir Crit Care Med1995;151(6):1807–1814.
12.
SesslerCN. Mechanical ventilation of patients with acute lung injury. Crit Care Clin1998;14(4):707–729.
13.
MacnaughtonPD, EvansTW. Management of adult respiratory distress syndrome. Lancet1992;339(8791):469–472.
14.
TobinMJ. Mechanical ventilation. N Engl J Med1994;330(15):1056–1061.
15.
MacklinMT, MacklinCC. Malignant interstitial emphysema of the lungs and mediastinum as an important occult complication in many respiratory diseases and other conditions: an interpretation of the clinical literature in the light of laboratory experiment. Medicine1944;23:281–352.
16.
LawrenceRD. Respirator-induced pneumothorax and subcutaneous emphysema: experimental overinflation of cadaver lungs. J Forensic Sci1974;19(3):548–556.
17.
ZwillichCW, PiersonDJ, CreaghCE, SuttonFD, SchatzE, PettyTL. Complications of assisted ventilation: a prospective study of 354 consecutive episodes. Am J Med1974;57(2):161–170.
18.
de LatorreFJ, TomasaA, KlamburgJ, LeonC, SolerM, RiusJ.Incidence of pneumothorax and pneumomediastinum in patients with aspiration pneumonia requiring ventilatory support. Chest1977;72(2):141–144.
19.
PetersenGW, BaierH.Incidence of pulmonary barotrauma in a medical ICU. Crit Care Med1983;11(2):67–69.
20.
GammonRB, ShinMS, BuchalterSE. Pulmonary barotrauma in mechanical ventilation: patterns and risk factors. Chest1992;102(2):568–572.
21.
MariniJJ, CulverBH. Systemic gas embolism complicating mechanical ventilation in the adult respiratory distress syndrome. Ann Intern Med1989;110(9):699–703.
22.
MeadJ, TakishimaT, LeithD.Stress distribution in lungs: a model of pulmonary elasticity. J Appl Physiol1970;28(5):596–608.
23.
TeplitzC.The core pathobiology and integrated medical science of adult acute respiratory insufficiency. Surg Clin North Am1976;56(5):1091–1133.
24.
ParkerJC, HernandezLA, PeevyKJ. Mechanisms of ventilator-induced lung injury. Crit Care Med1993;21(1):131–143.
25.
DreyfussD, SaumonG.Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med1998;157(1):294–323.
26.
GreenfieldLJ, EbertPA, BensonDW. Effect of positive pressure ventilation on surface tension properties of lung extracts. Anesthesiology1964;25:312–316.
27.
BarschJ, BirbaraC, EggersGWNJ, et al. Positive pressure as a cause of respirator-induced lung injury (abstract). Ann Intern Med1970;72:810.
28.
WebbHH, TierneyDF. Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures: protection by positive end-expiratory pressure. Am Rev Respir Dis1974;110(5):556–565.
29.
DreyfussD, BassetG, SolerP, SaumonG.Intermittent positive-pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats. Am Rev Respir Dis1985;132(4):880–884.
30.
KolobowT, MorettiMP, FumagalliR, MascheroniD, PratoP, ChenV, JorisM.Severe impairment in lung function induced by high peak airway pressure during mechanical ventilation: an experimental study. Am Rev Respir Dis1987;135(2):312–315.
31.
ZapolWM, SniderMT, HillJD, FallatRJ, BartlettRH, EdmundsLH, et al. Extracorporeal membrane oxygenation in severe respiratory failure. A randomized prospective study. JAMA1979;242(20):2193–2196.
32.
GattinoniL, PesentiA, CaspaniML, PelizzolaA, MascheroniD, MarcolinR, et al. The role of total static lung compliance in the management of severe ARDS unresponsive to conventional treatment. Intensive Care Med1984;10(3):121–126.
33.
TsunoK, PratoP, KolobowT.Acute lung injury from mechanical ventilation at moderately high airway pressures. J Appl Physiol1990;69(3):956–961.
34.
PolakB, AdamsH.U.S. Naval Med Bull1932;30:165.
35.
DreyfussD, SolerP, BassetG, SaumonG.High inflation pressure pulmonary edema: respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis1988;137(5):1159–1164.
36.
DreyfussD, SaumonG.Barotrauma is volutrauma, but which volume is the one responsible?Intensive Care Med1992;18(3):139–141.
37.
HernandezLA, PeevyKJ, MoiseAA, ParkerJC. Chest wall restriction limits high airway pressure-induced lung injury in young rabbits. J Appl Physiol1989;66(5):2364–2368.
38.
CarltonDP, CummingsJJ, SheererRG, PoulainFR, BlandRD. Lung overexpansion increases pulmonary microvascular permeability in young lambs. J Appl Physiol1990;69(2):577–583.
39.
BowtonDL, KongDL. High tidal volume ventilation produces increased lung water in oleic acid-injured rabbit lungs. Crit Care Med1989;17(9):908–911.
DreyfussD, SolerP, SaumonG.Mechanical ventilation-induced pulmonary edema: interaction with previous lung alterations. Am J Respir Crit Care Med1995;151(5):1568–1575.
42.
WooSW, Hedley-WhyteJ.Macrophage accumulation and pulmonary edema due to thoracotomy and lung overinflation. J Appl Physiol1972;33(1):1421.
43.
TsunoK, MiuraK, TakeyM, KolobowT, MoriokaT.Histopathologic pulmonary changes from mechanical changes at high peak airway pressures. Am Rev Respir Dis1991;143(5 Pt 1):1115–1120.
44.
KawanoT, MoriS, CybulskyM, BurgerR, BallinA, CutzE, BryanAC. Effect of granulocyte depletion in a ventilated surfactant-depleted lung. J Appl Physiol1987;62(1):27–33.
45.
MuscedereJG, MullenJBM, GanK, SlutskyAS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med1994;149(5):1327–1334.
46.
TremblayL, ValenzaF, RibeiroSP, LiJ, SlutskyAS. Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest1997;99(5):944–952.
47.
RanieriVM, SuterPM, TortorellaC, De TullioR, DayerJM, BrienzaA, et al. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA1999;282(1):54–61.
48.
von BethmannAN, BraschF, NüsingR, VogtK, VolkHD, MullerKM, et al. Hyperventilation induces release of cytokines from perfused mouse lung. Am J Respir Crit Care Med1997;157(1):263–272.
49.
NahumA, BurkeWC, RavenscraftSA, MarcyTW, AdamsAB, CrookePS, MariniJJ. Lung mechanics and gas-exchange during pressure-control ventilation in dogs: augmentation of CO₂ elimination by an intratracheal catheter. Am Rev Respir Dis1992;146(4):965–973.
50.
MontgomeryAB, StagerMA, CarricoCJ, HudsonLD. Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis1985;132(3):485–489.
51.
CorbridgeTC, WoodLDH, CrawfordGP, ChudobaMJ, YanosJ, SznajderJI. Adverse effects of large tidal volume and low PEEP in canine acid aspiration. Am Rev Respir Dis1990;142(2):311–315.
52.
GoldbergHS, MitznerW, BatraG.Effect of transpulmonary and vascular pressures on rate of pulmonary edema formation. J Appl Physiol1977;43(1):14–19.
53.
DreyfussD, SolerP, SaumonG.Overinflation pulmonary edema is not related to large volume swings but to the level of lung distension (abstract). Am Rev Respir Dis1989;139(4 Pt 2):A417.
SandharBK, NiblettDJ, ArgirasEP, DunnillMS, SykesMK. Effects of positive end-expiratory pressure on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome. Intensive Care Med1988;14(5):538–546.
56.
RoupieE, DambrosioM, ServilloG, MentecH, el AtrousS, BeydonL, et al. Titration of tidal volume and induced hypercapnia in acute respiratory distress syndrome. Am J Respir Crit Care Med1995;152(1):121–128.
57.
CarvalhoCRR, BarbasCSV, MedeirosDM, MagaldiRB, Lorenzi FilhoG, KairallaRA, et al. Temporal hemodynamic effects of permissive hypercapnia associated with ideal PEEP in ARDS. Am J Respir Crit Care Med1997;156(5):1458–1466.
58.
AmatoMB, BarbasCS, MedeirosDM, MagaldiRB, SchettinoGP, Lorenzi-FilhoG, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med1998;338(6):347–354.
59.
NiblettDJ, SandharBK, DunnillMS, SykesMK. Comparison of the effects of high frequency oscillation and controlled mechanical ventilation on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome. Br J Anaesth1989;62(6):628–636.
60.
High-frequency oscillatory ventilation compared with conventional mechanical ventilation in the treatment of respiratory failure in preterm infants. The HIFI Study Group. N Engl J Med1989;320(2):88–93.
61.
SlutskyAS. High frequency ventilation. Intensive Care Med1991;17(7):375–376.
62.
HighKM, SniderMT, RichardR, RussellGB, SteneJK, CampbellDB, et al. Clinical trials of an intravenous oxygenator in patients with adult respiratory distress syndrome. Anesthesiology1992;77(5):856–863.
63.
ConradSA, EggerstedtJM, MorrisVF, RomeroMD. Prolonged intracorporeal support of gas exchange with an intravenacaval oxygenator. Chest1993;103(1):158–161.
64.
GuinardN, BeloucifS, GatecelC, MateoJ, PayenD.Interest of a therapeutic optimization strategy in severe ARDS. Chest1997;111(4):1000–1007.
65.
DarioliR, PerretC.Mechanical controlled hypoventilation in status asthmaticus. Am Rev Respir Dis1984;129(3):385–387.
66.
HicklingKG, HendersonSJ, JacksonR.Low mortality associated with low pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med1990;16(6):372–377.
67.
RahnH, ReevesRB, HowellBJ. Hydrogen ion regulation, temperature, and evolution. Am Rev Respir Dis1975;112(2):165–172.
68.
RahnH.Why are pH of 7.4 and Pco₂ of 40 normal values for man?Bull Eur Pysiopathol Respir1976;12(1):5–13.
JerusalemE, StarlingEH. On the significance of carbon dioxide for the heart beat. J Physiol (Lond)1910;40:279–294.
77.
TangWC, WeilMH, GazmuriRJ, BiseraJ, RackowEC. Reversible impairment of myocardial contractility due to hypercarbic acidosis in the isolated perfused rat heart. Crit Care Med1991;19(2):218–224.
78.
LowJM, GinT, LeeTW, FungK.Effect of respiratory acidosis and alkalosis on plasma catecholamine concentrations in anaesthetized man. Clin Sci (Colch)1993;84(1):69–72.
79.
BrofmanJD, LeffAR, MunozNM, KirchhoffC, WhiteSR. Sympathetic secretory response to hypercapnic acidosis in swine. J Appl Physiol1990;69(2):710–717.
80.
WalleyKR, LewisTH, WoodLDH. Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs. Cire Res1990;67(3):628–635.
81.
WexelsJC, MjosOD. Effects of carbon dioxide and pH on myocardial function in dogs with acute left ventricular failure. Crit Care Med1987;15(12):1116–1120.
82.
MatalonS, NesarajahMS, KrasneyJA, FahriLE. Effects of acute hypercapnia on the central and peripheral circulation of conscious sheep. J Appl Physiol1983;54(3):803–808.
83.
RotheCF, FlanaganAD, Maass-MorenoR.Reflex control of vascular capacitance during hypoxia, hypercapnia or hypoxic hypercapnia. Can J Physiol Pharmacol1990;68(3):384–391.
84.
SteinhartCR, PermuttS, GurtnerGH, TraystmanRJ. B-Adrenergic activity and cardiovascular response to severe respiratory acidosis. Am J Physiol1983;244(1):H46–H54.
85.
CardenasVJJr, ZwischenbergerJB, TaoW, NguyenPD, SchroederT, TraberLD, et al. Correction of blood pH attenuates changes in hemodynamics and organ blood flow during permissive hypercapnia. Crit Care Med1996;24(5):827–834.
86.
ThorensJ-B, JollietP, RitzM, ChevroletJ-C. 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 Med1996;22(3):182–191.
87.
HundE.Myopathy in critically ill patients. Crit Care Med1999;27(11):2544–2547.
88.
KupferY, NambaT, KaldawiE, TesslerS.Prolonged weakness after long-term infusion of vecuronium bromide. Ann Internal Med1992;117(6):484–486.
89.
ChadDA, LacomisD.Critically ill patients with newly acquired weakness: the clinicopatholological spectrum. Ann Neurol1994;35(3):257–259.
90.
WatlingSM, DastaJF. Prolonged paralysis in intensive care unit patients after the use of neuromuscular blocking agents: a review of the literature. Crit Care Med1994;22(5):884–893.
91.
PokorskiM, LahiriS.Relative peripheral and central chemosensory responses to metabolic alkalosis. Am J Physiol1983;245(6):R873–R880.
92.
LassenNA. Brain extracellular pH: the main factor controlling cerebral blood flow. Scand J Clin Lab Invest1968;22(4):247–251.
93.
MuizelaarJP, MarmarouA, WardJD, KontosHA, ChoiSC, BeckerDP, et al. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized trial. J Neurosurg1991;75(5):731–739.
94.
Prys-RobertsC, SmithWDA, NunnJF. Accidental severe hypercapnia during anaesthesia: a case report and review of some physiological effects. Br J Anaesth1967;39(3):257–267.
95.
PotkinRT, SwensonER. Resuscitation from severe acute hyercapnia: determinants of tolerance and survival. Chest1992;102(6):1742–1745.
96.
GoldsteinB, ShannonDC, TodresID. Supercarbia in children: clinical course and outcome. Crit Care Med1990;18(2):166–168.
97.
LaffeyJG, KavanaghBP. Carbon dioxide and the critically ill-too little of a good thing?Lancet1999;354(9186):1283–1286.
98.
YamaguchiK, TakasugiT, FujitaH, MoriM, OyamadaY, SuzukiK, et al. Endothelial modulation of pH-dependent pressor response in isolated perfused rabbit lungs. Am J Physiol1996;270(1 Pt 2):H252–H258.
99.
TaskerRC, PetersMJ. Combined lung injury, meningitis, and cerebral edema: how permissive can hypercapnia be?Intensive Care Med1998;24(6):616–619.
100.
StewartTE, MeadeMO, CookDJ, GrantonJT, HodderRV, LapinskySE, et al. Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group. N Engl J Med1998;338(6):355–361.
101.
The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med2000;342(18):1301–1308.
102.
BrochardL, Roudot-ThoravalF, RoupieE, DelclauxC, ChastreJ, Fernandez-MondejarE, et al. Tidal volume reduction for prevention of ventilator-induced acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. Am J Respir Crit Care Med1998;158(6):1831–1838.
103.
TobinMJ. Culmination of an era in research on the acute respiratory distress syndrome. N Engl J Med2000;342(18):1360–1361.
104.
PesentiA.Target blood gases during ARDS ventilatory management. Intensive Care Med1990;16(6):349–351.
105.
LessardMR, GuérotE, LorinoH, LemaireF, BrochardL.Effects of pressure-controlled with different I:E ratios versus volume-controlled ventilation on respiratory mechanics, gas exchange, and hemodynamics in patients with adult respiratory distress syndrome. Anesthesiology1994;80(5):983–991.
HirvelaER. Advances in the management of acute respiratory distress syndrome: protective ventilation. Arch Surg2000;135(2):126–135.
108.
KalletRH, JasmerRM, LuceJM, LinLH, MarksJD. The treatment of acidosis in acute lung injury with tris-hydroxymethyl aminomethane (THAM). Am J Respir Crit Care Med2000;161(4 Pt 1):1149–1153.
109.
AdroguéHJ, MadiasNE. Management of life-threatening acid-base disorders. First of two parts. N Engl J Med1998;338(2):26–34.
110.
KindigNB, FilleyGF. Intravenous bicarbonate may cause transient intracellular acidosis. Chest1983;83(4):712–715.
111.
ShapiroI, WhalenM, KuceraR, KindigN, FilleyG, ChanL.Brain pH reponses to sodium bicarbonate and Carbicarb during systemic acidosis. Am J Physiol1989;256(5 Pt 2):H1316–H1321.
112.
BleichHL, SchwartzWB. Tris buffer (THAM): an appraisal of its physiologic effects and clinical usefulness. N Engl J Med1966;274:782–787.
113.
LongSE, MenonAS, KatoH, GoldsteinRS, SlutskyAS. Constant oxygen insufflation (COI) in a ventilatory failure model. Am Rev Respir Dis1988;138(3):630–635.
114.
HurewitzAN, BergofskyEH, VomeroE.Airway insufflation: increasing flow rates progressively reduce dead space in respiratory failure. Am Rev Respir Dis1991;144(6):1229–1233.
115.
RavenscraftSA, BurkeWC, NahumA, AdamsAB, NakosG, MarcyTW, MariniJJ. Tracheal gas insufflation augments CO₂ clearance during mechanical ventilation. Am Rev Respir Dis1993;148(2):345–351.
116.
KalfonP, RaoGSU, GallartL, PuybassetL, CoriatP, RoubyJ-J. Permissive hypercapnia with and without expiratory washout in patients with severe acute respiratory distress syndrome. Anesthesiology1997;87(1):6–17; discussion 25A–26A.
117.
RichecoeurJ, LuQ, VieiraSR, PuybassetL, KalfonP, CoriatP, RoubyJJ. Expiratory washout versus optimization of mechanical ventilation during permissive hypercapnia in patients with severe acute respiratory distress syndrome. Am J Respir Crit Care Med1999;160(1):77–85.
118.
BarnettCC, MooreFA, MooreEE, PartrickDA, GoodmanJ, BurchJM, HaenelJB. Tracheal gas insufflation is a useful adjunct in permissive hypercapnic management of acute respiratory distress syndrome. Am J Surg1996;172(5):518–521; discussion 521–522.
