Pathophysiologie und Diagnostik

Zusammenfassung

Künstliche Beatmung kann das Lungengewebe in Abhängigkeit von Beatmungseinstellungen (Druckamplitude, endexspiratorischer Druck, Frequenz) und Beatmungsdauer schädigen. Insbesondere in den inhomogen geschädigten Lungen von ARDS–Patienten führt alveoläre Überdehnung zum Volutrauma, zyklisches Öffnen und Schließen der Alveolen zum Atelektotrauma. Von besonderer Bedeutung ist wohl, dass diese Vorgänge auch zum Biotrauma, das heißt zu einer beatmungsinduzierten Überaktivierung der pulmonalen Entzündungsantwort führen können. Diese Probleme sind bei der derzeit empfohlenen Beatmung mit 6ml/kg idealisiertes Körpergewicht vermindert, aber nicht eliminiert. Eine Beatmungsoptimierung mit dem Ziel der Reduktion beatmungsassoziierter Lungenschäden kann in Zukunft hoffentlich erzielt werden durch die Überwachung atemmechanischer Messgrößen, wie Stress–Index und Slice–Methode, und durch die bettseitige Anwendung neuer echtzeitfähiger bildgebender Verfahren wie der elektrischen Impedanztomographie.

Summary

Mechanical ventilation may lead to lung injury depending on the ventilatory settings (e.g. pressure amplitudes, endexpiratory pressures, frequency) and the length of mechanical ventilation. Particularly in the inhomogeneously injured lungs of ARDS patients, alveolar overextension results in volutrauma, cyclic opening and closure of alveolar units in atelectrauma. Particularly important appears to be the fact that these processes may also cause biotrauma, i.e. the ventilator–induced hyperactivation of inflammatory responses in the lung. These side effects are reduced, but not eliminated with the currently recommended ventilation strategy with a tidal volume of 6ml/kg idealized body weight. It is our hope that in the future optimization of ventilator settings will be facilated by bedside monitoring of novel indices of respiratory mechanics such as the stress index or the Slice technique, and by innovative real–time imaging technologies such as electrical impedance tomography.

Schlüsselwörter:

Lungenprotektive Beatmung - beatmungsbedingte Lungenschädigung - Biotrauma - Monitoring

Keywords:

Lung protective ventilation - ventilator–induced lung injury - biotrauma - monitoring

Kernaussagen

• Beatmungsinduzierte Lungenschädigung ist bei der derzeit empfohlenen Beatmung mit 6ml/kg idealisiertes Körpergewicht vermindert, aber nicht eliminiert.

• Alveoläre Überdehnung kann zum Volutrauma, zyklisches Öffnen und Schließen der Alveolen zum Alektotrauma führen. Ein Biotrauma kann infolge beatmungsinduzierter Überaktivierung der pulmonären Entzündungsantwort entstehen.

• Überwachung von beatmeten Patienten ist z.Zt. nicht optimal.

• Beatmungseinstellungen müssen individuell anhand von Messgrößen unterschiedlicher Monitoringverfahren definiert werden.

• Zu den Standardverfahren zählen die Ermittlung von respiratorischen und atemmechanischen Messgrößen sowie klassische bildgebende Verfahren.

• Neue Methoden (z.B. EIT, Stress–Index– und Slice–Methode) könnten in der Zukunft bettseitig und kontinuierlich Informationen liefern, mit denen die Beatmungseinstellungen optimiert werden können.

Literatur

• 1 The Acute Respiratory Distress Syndrome Network. . 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. 2000;  342 1301-1308
• 2 Gajic O, Dara SI, Mendez JL. et al. . Ventilator–associated lung injury in patients without acute lung injury at the onset of mechanical ventilation.  Crit Care Med. 2004;  32 1817-1824
• 3 Hager DN, Krishnan JA, Hayden DL, Brower RG.. Tidal volume reduction in patients with acute lung injury when plateau pressures are not high.  Am J Respir Crit Care Med. 2005;  172 1241-1245
• 4 Checkley W, Brower R, Korpak A, Thompson BT.. Effects of a Clinical Trial on Mechanical Ventilation Practices in Patients with Acute Lung Injury. Am J Respir Crit Care Med (in press)
• 5 Gattinoni L, Carlesso E, Cadringher P. et al. . Physical and biological triggers of ventilator–induced lung injury and its prevention.  Eur Respir J Suppl. 2003;  47
• 6 Victorino JA, Borges JB, Okamoto VN. et al. . Imbalances in regional lung ventilation: a validation study on electrical impedance tomography.  Am J Respir Crit Care Med. 2004;  169 791-800
• 7 Uhlig S.. Ventilation–induced lung injury and mechanotransduction: Stretching it too far?.  Am J Physiol Lung Cell Mol Physiol. 2002;  282
• 8 Hubmayr RD.. Perspective on lung injury and recruitment. A skeptical look at the opening and collapse story.  Am J Respir Crit Care Med. 2002;  165 1647-1653
• 9 Dreyfuss D, Saumon G.. Ventilator–induced lung injury. Lessons from experimental studies.  Am J Respir Crit Care Med. 1998;  157 294-323
• 10 Boussarsar M, Thierry G, Jaber S. et al. . Relationship between ventilatory settings and barotrauma in the acute respiratory distress syndrome.  Intensive Care Med. 2002;  28 406-413
• 11 Brower RG, Lanken PN, MacIntyre N. et al. . Higher versus lower positive end–expiratory pressures in patients with the acute respiratory distress syndrome.  N Engl J Med. 2004;  351 327-336
• 12 Conrad SA, Zhang S, Arnold TC. et al. . Protective effects of low respiratory frequency in experimental ventilator–associated lung injury.  Crit Care Med. 2005;  33 835-840
• 13 Gajic O, Lee J, Doerr CH. et al. . Ventilator–induced cell wounding and repair in the intact lung.  Am J Respir Crit Care Med. 2003;  167 1057-1063
• 14 Uhlig S, Uhlig U.. Pharmacological interventions in ventilator–induced lung injury.  Trends Pharmacol Sci. 2004;  25 592-600
• 15 Uhlig S, Uhlig U.. Molecular mechanisms of pro–inflammatory responses in overventilated lungs.  Recent Res Devel Resp Critical Care Med. 2001;  1 49-58
• 16 Stamme C, Brasch F, von Bethmann A, Uhlig S.. Effect of surfactant on ventilation–induced mediator release in isolated perfused mouse lungs.  Pulm Pharmacol Therap. 2002;  15 455-461
• 17 Uhlig U, Drömann D, Goldmann T. et al. .Pulmonary responses to overventilation in late multiple organ failure. Anesthesiology (in press)
• 18 Meier T, Lange A, Papenberg H. et al. .Pulmonary cytokine responses during mechanical ventilation of non–injured lungs with and without end–expiratory pressure. Anesth Analg (in press)
• 19 Stüber F, Wrigge H, Schroeder S. et al. . Kinetic and reversibility of mechanical ventilation associated pulmonary and systemic inflammatory response in patients with acute lung injury.  Inten Care Med. 2002;  28 834-841
• 20 Ranieri VM, Suter PM, Tortorella C. et al. . Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome.  A randomized controlled trial. JAMA. 1999;  282 54-61
• 21 Zhang H, Downey GP, Suter PM. et al. . Conventional mechanical ventilation is associated with bronchoalveolar lavage–induced activation of polymorphonuclear leukocytes: a possible mechanism to explain the systemic consequences of ventilator–induced lung injury in patients with ARDS.  Anesthesiology. 2002;  97 1426-1433
• 22 Dolinay T, Kaminski N, Felgendreher M. et al. . Gene expression profiling of target genes in ventilator–induced lung injury.  Physiol Genomics. 2006;  26 68-75
• 23 Hamanaka K, Jian MY, Weber DS. et al. . TRPV4 initiates the acute calcium–dependent permeability increase during ventilator–induced lung injury in isolated mouse lungs.  Am J Physiol Lung Cell Mol Physiol. 2007;  293
• 24 Bhattacharya S, Sen N, Yiming MT. et al. . High tidal volume ventilation induces proinflammatory signaling in rat lung endothelium.  Am J Respir Cell Mol Biol. 2003;  28 218-224
• 25 Held HD, Boettcher S, Hamann L, Uhlig S.. Ventilation–induced chemokine and cytokine release is associated with activation of NFkB and is blocked by steroids.  Am J Respir Crit Care Med. 2001;  163 711-716
• 26 Li LF, Yu L, Quinn DA.. Ventilation–induced neutrophil infiltration depends on c–Jun N–terminal kinase.  Am J Respir Crit Care Med. 2003;  169 518-524
• 27 Belperio JA, Keane MP, Burdick MD. et al. . Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator–induced lung injury.  J Clin Invest. 2002;  110 1703-1716
• 28 Wilson MR, Goddard ME, O'Dea KP. et al. . Differential roles of p55 and p75 tumor necrosis factor receptors on stretch–induced pulmonary edema in mice.  Am J Physiol Lung Cell Mol. 2007;  293
• 29 Kim JH, Suk MH, Yoon DW. et al. . Inhibition of matrix metalloproteinase–9 prevents neutrophilic inflammation in ventilator–induced lung injury.  Am J Physiol Lung Cell Mol Physiol. 2006;  291
• 30 Chapman KE, Sinclair SE, Zhuang D. et al. . Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells.  Am J Physiol Lung Cell Mol Physiol. 2005;  289
• 31 Imai Y, Parodo J, Kajikawa O. et al. . Injurious mechanical ventilation and end–organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome.  JAMA. 2003;  289 2104-2112
• 32 Herrera MT, Toledo C, Valladares F. et al. . Positive end–expiratory pressure modulates local and systemic inflammatory responses in a sepsis–induced lung injury model.  Intensive Care Med. 2003;  29 1345-1353
• 33 Ranieri VM, Giunta F, Suter PM, Slutsky AS.. Mechanical ventilation as a mediator of multisystem organ failure in acute respiratory distress syndrome (letter).  JAMA. 2000;  284 43-44
• 34 Harris RS.. Pressure–volume curves of the respiratory system.  Respir Care. 2005;  50 78-98
• 35 Blanch L, López–Aguilar J, Villagrá A.. Bedside evaluation of pressure–volume curves in patients with acute respiratory distress syndrome.  Curr Opin Crit Care. 2007;  13 332-337
• 36 Hickling KG.. Reinterpreting the pressure–volume curve in patients with acute respiratory distress syndrome.  Curr Opin Crit Care. 2002;  8 32-38
• 37 DiRocco JD, Carney DE, Nieman GF.. Correlation between alveolar recruitment/derecruitment and inflection points on the pressure–volume curve.  Intensive Care Med. 2007;  33 1204-1211
• 38 Grasso S, Terragni P, Mascia L. et al. . Airway pressure–time curve profile (stress index) detects tidal recruitment/hyperinflation in experimental acute lung injury.  Crit Care Med. 2004;  32 1018-1027
• 39 Terragni PP, Rosboch GL, Lisi A. et al. . How respiratory system mechanics may help in minimising ventilator–induced lung injury in ARDS patients.  Eur Respir J. 2003;  42
• 40 Grasso S, Stripoli T, De M Michele. et al. . ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end–expiratory pressure.  Am J Respir Crit Care Med. 2007;  176 761-767
• 41 Mols G, Brandes I, Kessler V. et al. . Volume–dependent compliance in ARDS: proposal of a new diagnostic concept.  Intensive Care Med. 1999;  25 1084-1091
• 42 Hermle G, Mols G, Zügel A. et al. . Intratidal compliance–volume curve as an alternative basis to adjust positive end–expiratory pressure: a study in isolated perfused rabbit lungs.  Crit Care Med. 2002;  30 1589-1597
• 43 Kirchner EA, Mols G, Hermle G. et al. . Reduced activation of immunomodulatory transcription factors during positive end–expiratory pressure adjustment based on volume–dependent compliance in isolated perfused rabbit lungs.  Br J Anaesth. 2005;  94 530-535
• 44 Tusman G, Suarez–Sipmann F, Böhm SH. et al. . Monitoring dead space during recruitment and PEEP titration in an experimental model.  Intensive Care Med. 2006;  32 1863-1671
• 45 Maisch S, Reissmann H, Fuellekrug B. et al. . Compliance and dead space fraction indicate an optimal level of positive end–expiratory pressure after recruitment in anesthetized patients.  Anesth Analg. 2008;  106 175-181
• 46 Nuckton TJ, Alonso JA, Kallet RH. et al. . Pulmonary deadspace fraction as a risk factor for death in the acute respiratory distress syndrome.  N Eng J Med. 2002;  346 1281-1286
• 47 Wrigge H, Sydow M, Zinserling J. et al. . Determination of functional residual capacity (FRC) by multibreath nitrogen washout in a lung model and in mechanically ventilated patients. Accuracy depends on continuous dynamic compensation for changes of gas sampling delay time.  Intensive Care Med. 1998;  24 487-493
• 48 Neumann P, Zinserling J, Haase C. et al. . Evaluation of respiratory inductive plethysmography in controlled ventilation: measurement of tidal volume and PEEP–induced changes of end–expiratory lung volume.  Chest. 1998;  113 443-451
• 49 van Genderingen HR, van Vught AJ, Jansen JR.. Estimation of regional lung volume changes by electrical impedance pressures tomography during a pressure–volume maneuver.  Intensive Care Med. 2003;  29 233-240
• 50 Wolf GK, Arnold JH.. Noninvasive assessment of lung volume: respiratory inductance plethysmography and electrical impedance tomography.  Crit Care Med. 2005;  33
• 51 Gattinoni L, Caironi P, Cressoni M. et al. . Lung recruitment in patients with the acute respiratory distress syndrome.  N Engl J Med. 2006;  354 1775-1786
• 52 Caironi P, Langer T, Gattinoni L.. Acute lung injury/acute respiratory distress syndrome pathophysiology: what we have learned from computed tomography scanning.  Curr Opin Crit Care. 2008;  14 64-69
• 53 Vieira SR, Puybasset L, Richecoeur J. et al. . A lung computed tomographic assessment of positive end–expiratory pressure–induced lung overdistension.  Am J Respir Crit Care Med. 1998;  158 1571-1577
• 54 Terragni PP, Rosboch G, Tealdi A. et al. . Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome.  Am J Respir Crit Care Med. 2007;  175 160-6
• 55 Frerichs I, Hahn G, Hellige G.. Thoracic electrical impedance tomographic measurements during volume controlled ventilation–effects of tidal volume and positive end–expiratory pressure.  IEEE Trans Med Imaging. 1999;  18 764-773
• 56 Frerichs I, Dargaville PA, van Genderingen H. et al. . Lung volume recruitment after surfactant administration modifies spatial distribution of ventilation.  Am J Respir Crit Care Med. 2006;  174 772-779
• 57 Lindgren S, Odenstedt H, Erlandsson K. et al. . Bronchoscopic suctioning may cause lung collapse: a lung model and clinical evaluation.  Acta Anaesthesiol Scand. 2008;  52 209-218
• 58 Frerichs I, Dargaville PA, Dudykevych T, Rimensberger PC.. Electrical impedance tomography: a method for monitoring regional lung aeration and tidal volume distribution?.  Intensive Care Med. 2003;  29 2312-2316
• 59 Caironi P, Gattinoni L.. How to monitor lung recruitment in patients with acute lung injury.  Curr Opin Crit Care. 2007;  13 338-343
• 60 Gattinoni L, Vagginelli F, Carlesso E. et al. . Prone–Supine Study Group. Decrease in PaCO2 with prone position is predictive of improved outcome in acute respiratory distress syndrome.  Crit Care Med. 2003;  31 2727-33
• 61 Borges JB, Okamoto VN, Matos GFJ. et al. . Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome.  Am J Respir Crit Care Med. 2006;  174 268-278
• 62 Dembinski R, Max M, Bensberg R. et al. . High–frequency oscillatory ventilation in experimental lung injury: effects on gas exchange.  Intensive Care Med. 2002;  28 768-74
• 63 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;  162 209-15