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Ventilatory Strategies For Arterial Hypoxaemia: A Peep Into ...

  1. 1. Page 1 of 15 Ventilatory Strategies For Arterial Hypoxaemia: A Peep Into The Future? The failure of aerobic tissue metabolism (tissue hypoxaemia) inevitably results in organ dysfunction, and consequently its detection and correction is an important focus for critical care physicians. Of the four causes of tissue hypoxaemia (Table 1), three were famously described by the Cambridge University physiologist Joseph Barcroft in August 1920, whilst the fourth, cytopathic hypoxia, has been described more recently1 . Barcroft’s categorisation is memorable because it describes sequentially the barriers to the transfer of oxygen from inspired gas to mitochondrium. This article addresses the management of the most proximate of these in patients requiring mechanical ventilation – the impairment of oxygen transfer from inhaled gas to red blood cell leading to arterial hypoxaemia. Arterial hypoxaemia Before we can devise a logical strategy for the management of arterial hypoxaemia we must first understand what causes it. Of the six possible causes of arterial hypoxaemia (Table 2) not all are either relevant, or amenable to clinical manipulation. For example, the clinician has little control over barometric pressure (unless working at high altitude with the option of moving the patient to sea level), and in mechanically ventilated patients neither a low fractional inspired oxygen concentration (FIO2) nor hypoventilation are likely to be relevant factors. Furthermore there is little evidence that obstruction to the diffusion of oxygen from alveolus to pulmonary capillary is ever a significant contributor in clinical practice. The term ‘shunt’ refers to blood returning to the left ventricle which has not been ‘arterialized’ by contact with a ventilated alveolus. Even under normal circumstances a small shunt arises from venous blood returning to the left ventricle from the bronchial veins, which drain the small arterial supply to the pulmonary parenchyma, and the Thebesian veins, which drain the left ventricular myocardium. A pathological shunt may be cardiac or pulmonary in origin. Intra-cardiac shunt is invariably associated with the failure of either the inter-atrial or inter-ventricular septum, and may be congenital or acquired. In most cases the presence of an intra-cardiac shunt as the cause for arterial hypoxaemia is obvious, either because the presence of a congenital lesion has previously
  2. 2. Ventilatory Strategies For Arterial Hypoxaemia Page 2 of 15 been identified, or because an acquired intra-cardiac shunt is suggested by the clinical circumstances. Very occasionally a previously ‘silent’ atrial septal defect or patent foramen ovale may suddenly cause arterial hypoxaemia even in the absence of pulmonary hypertension2 , and may be easily overlooked unless considered as a possible cause. Arterial hypoxaemia arising from an intra-cardiac shunt can only be reversed by correction of the anatomical defect. Intra-pulmonary shunt arises from blood that is diverted away from ventilated alveoli through arterio- venous anastamoses, or that supplies alveoli with no ventilation. However alveolar ventilation that is anything less than normal (low ratio of ventilation to perfusion, V/Q) also causes arterial hypoxaemia. Therefore arterial hypoxaemia arising from shunt (zero ventilation) can be seen as a special case of arterial hypoxaemia arising from alveoli with a reduced ratio of ventilation to perfusion (V/Q). Together these are the predominant contributors to arterial hypoxaemia, with a small additional contribution, in some cases, from venous desaturation. So the questions then arises, what are the causes of low V/Q and shunt, and what can we do about them? Low V/Q Hypoventilation of lung units may occur with proximal airway obstruction (Table 3), loss of the alveolar lumen by occupation of the air space by cellular material (consolidation) or fluid (alveolar flooding), or as a result of alveolar atelectasis. Obstruction of the proximal airway does not usually present a diagnostic problem, either because of a suggestive history (of aspiration) or because of the clinical context in which it has occurred (e.g. pulmonary haemorrhage in a patient with pulmonary-renal syndrome). It may occasionally occur unexpectedly as a sudden deterioration in oxygenation in a patient receiving mechanical ventilation, and in this case the most common cause is mucus plugging of a bronchus (Figure 1). In most cases, some form of physical intervention is required, either to directly relieve the obstruction by rigid or flexible bronchoscopy, or to isolate healthy lung by passage of a double-lumen endotracheal tube. Loss of alveolar airspace by the influx of inflammatory cells, fibrin and cellular debris resulting in pulmonary consolidation is not amenable to any form of physical intervention and depends on the resolution of the underlying condition. In contrast, alveolar flooding may respond to a variety of therapeutic manoeuvres. The passage of fluid from capillary to interstitium, and then from the interstitium
  3. 3. Ventilatory Strategies For Arterial Hypoxaemia Page 3 of 15 to alveolar lumen, is determined by the balance between the hydrostatic and colloid osmotic pressures in the three compartments (capillary, interstitium and alveolus), the reflection co-efficients of the interceding endothelium (capillary/interstitium interface) or epithelium (interstitial/alveolar interface), and the function of the drainage mechanisms (pneumocyte abluminal Na+ /K+ -ATPase and pulmonary lymphatics). Currently nothing can be done to alter the pulmonary capillary endothelial reflection co-efficient which falls as a result of the relaxation of inter-endothelial tight junctions mediated by inflammatory mediators. The alveolar epithelial reflection co-efficient has two components; the first being the inter-epithelial tight junctions (similar to the pulmonary capillary endothelium), the second arising from the effect of alveolar surfactant. As with the capillary endothelium, relaxation of inter-epithelial tight junctions is currently not amenable to intervention. Loss of alveolar surfactant occurs by a number of mechanisms which include the degradation of alveolar surfactant by plasma proteins that have leaked into the alveolar lumen and the loss of alveolar type II pneumocytes which synthesize surfactant. The administration of exogenous surfactant (either synthetic or of animal origin) has been shown to improve lung mechanics, oxygenation and outcome in neonates with hyaline membrane disease3 , but has yet to be shown to be of benefit in adults. Capillary fluid efflux may be reduced, or indeed reversed, by minimising the pulmonary capillary filtration pressure, which in disease may not equate to the pulmonary artery occlusion pressure because of the presence of significant pulmonary venous flow restriction, and in patients with ARDS the resultant reduction of extra-vascular lung water has been shown to be associated with a better outcome4 . Alveolar fluid reabsorption (but not interstitial fluid absorption5 ) may be promoted by positive end-expiratory pressure and results in improved oxygenation. Alveolar fluid reabsorption is promoted in animal models of pulmonary oedema by activation of the abluminal pneumocyte Na+ /K+ -ATPase by b-adrenoreceptor agonists6,7 , suggesting that these agents may be helpful in promoting the resolution of pulmonary oedema in patients8 . Interstitial fluid drainage through the pulmonary lymphatics may be encouraged by minimising central venous pressures. There is no evidence that manipulation of the plasma colloid oncotic pressure with either natural (human albumin solution, fresh frozen plasma) or synthetic products has any effect on reducing either alveolar or interstitial fluid. Atelectasis Atelectasis (alveolar collapse) in mechanically ventilated patients occurs as a consequence of (1) surfactant depletion/degradation, (2) gravitational compression from increased interstitial fluid in
  4. 4. Ventilatory Strategies For Arterial Hypoxaemia Page 4 of 15 overlying lung9,10 , (3) absorption of oxygen from alveoli with long time constants11,12 (4) reversal of the normal ventilation gradient13 and (5) low tidal volumes. For the sake of clarity atelectasis can be described as taking two forms depending on its behaviour during the respiratory cycle; type A, in which the alveolus is collapsed at end-expiration but opens during inspiration (i.e. tidal recruitment), and type B, which is collapsed at both end-expiration and end-inspiration but may be recruited if sufficient pressure is used (Figure 2). The factors determining the proportion of type A and type B atelectasis in any given patient are currently unknown, but may include amongst other things patient morphology and aetiology of the lung disease. The extent to which type A atelectasis contributes to alveolar hypoventilation will depend on the frequency distribution of the ‘opening times’ of these alveoli over the inspiratory cycle, which is likely to vary depending on local factors (such as the position of the alveolus in the antero-posterior axis of the chest, Figure 3). Nevertheless there is evidence that tidal recruitment of collapsed alveoli (type A atelectasis) contributes to ventilator-associated lung injury 14,15 and may have a role in the genesis of multiple organ failure16,17 . Although the factors tending to precipitate atelectasis may be addressed (Table 4), direct intervention involves the application of positive end-expiratory pressure (PEEP) and, possibly volume recruitment manoeuvres and sighs. PEEP The effect of PEEP in improving oxygenation was originally described in the mid to late 1960’s18,19 , and PEEP has remained an important component of the ventilatory strategies for improving oxygenation. However, the question of how much PEEP to use has never been conclusively settled, and is now an issue of renewed interest because of recent evidence suggesting reduced mortality in patients ventilated with lower tidal volumes and airway pressures20,21 . One of the earliest suggested techniques for determining optimum PEEP was to examine the relationship between PEEP and oxygen delivery22 , as increasing levels of PEEP were noted to have opposite effects on arterial haemoglobin saturation on the one hand, and cardiac output on the other. Suter’s ‘best PEEP’ was therefore defined as the level of PEEP that was associated with the maximum oxygen delivery. Subsequent work, originally suggested in the 1980’s23-25 , focused on examination of lung mechanics for determining optimum PEEP. This method depends on examination of a plot of lung volume change from functional residual capacity against inflating pressure under conditions of zero flow (Figure 4). This can be seen to have a sigmoidal shape in which the slope of the line at any point represents total thoraco-pulmonary
  5. 5. Ventilatory Strategies For Arterial Hypoxaemia Page 5 of 15 compliance, and has three distinct segments; an initial segment of low but increasing compliance, a straight middle section where compliance is constant, and an upper section where compliance falls as total lung capacity is approached. If, as was originally thought, the initial low-compliance section of this curve is due to alveolar recruitment being completed at the lower inflection point (LIP), optimum PEEP would lie at a pressure just above the LIP. Setting PEEP in this way has been shown to be associated with a significant reduction in mortality in patients with ARDS20 , and has been shown to reduce the production of inflammatory cytokines by the lung26 , but the practical limitations of this technique in a non-research setting have prevented its widespread adoption27,28 . More recently investigators have questioned the validity of selecting PEEP based on the LIP of the inflation pressure/volume curve29,30 . Firstly, PEEP has its effect in the expiratory limb of the pressure/volume loop which is normally quite different from the inspiratory limb (Figure 5). The difference between the two limbs is partly ascribed to the effect of Laplace’s law which predicts that considerably more pressure is required to open collapsed alveoli than is needed to keep these recruited alveoli open, a phenomenon that has been convincingly demonstrated in an animal model31 and patients with ARDS30 . Secondly, mathematical modelling predicts that alveolar recruitment continues above the LIP32 , and this has now been demonstrated in animal models of ARDS33 and in patients with ALI34,35 or ARDS30 . Taken together these two observations suggest that PEEP should be set after fully recruiting all available alveoli (i.e. both type A and type B atelectasis, see above) with a volume recruitment manoeuvre (VRM), as originally proposed by Lachman36 , followed by examination of the deflation limb of the pressure/volume curve to identify the critical closing volume30,37 . In practical terms this technique would still appear to require the construction of a volume/pressure curve, albeit during deflation rather than inflation, and in one study in patients with ALI no discrete critical closing pressure could be detected35 . An alternative technique suggested by mathematical modelling would be to select optimal PEEP during down-titration from total lung capacity by selecting the PEEP value associated with the maximum compliance38 , which in clinical practice is considerably easier to perform. Details of the optimum techniques for performing a VRM remain unspecified, even though VRM has been recommended in the management of ARDS39 . In this context VRM would primarily being used to safely aerate as much lung as possible (to total available lung capacity) in order to set optimum PEEP. Improvements in oxygenation and compliance achieved by a VRM will depend on the ratio of recruitable atelectasis (types A and B) to un-recruitable consolidation that is responsible for
  6. 6. Ventilatory Strategies For Arterial Hypoxaemia Page 6 of 15 the arterial hypoxaemia in that patient, at that time. There is evidence from both animal models of acute lung injury40 and patients with ARDS41,42 that this may differ, depending on the mechanism of injury, and that some patients may be ‘unresponsive’ to VRM. Another important issue that needs to be addressed is the frequency with which a VRM and PEEP titration should be performed. Significant alveolar collapse occurs in patients with ALI simply by the loss of PEEP34 , and further alveolar collapse is caused by endotracheal suction43,44 . In patients with severe arterial hypoxaemia it would therefore seem prudent to avoid the loss of PEEP at any time by using closed suction circuits and self-sealing nebuliser ports, and to perform a VRM after endotracheal suction. Even in the absence of nursing intervention the benefits accrued by a VRM fade over time, with some investigators reporting a return to baseline oxygenation in as little as five minutes45 . One contributing factor in the rapid loss of benefit following a VRM is an inappropriately low PEEP setting42 , but another contributing factor may be a high fractional inspired oxygen concentration (FIO2). Absorption atelectasis was described by Nunn46 and accounts for the increase in pulmonary shunt that occurs in patients breathing high concentrations of oxygen11,12 . In anaesthetised subjects the effects of a VRM lasted at least 40 minutes in those breathing 40% oxygen, but only 5 minutes in those breathing 100% oxygen47 . This data suggests that the interval between VRM’s should be inversely proportional to the FIO2, and that advantage should be taken of any improvement in oxygenation following a VRM by immediate reduction in the FIO2. Other strategies Prolonging the ratio of inspiratory to expiratory time results in an increase in the mean intra-pulmonary pressure, which is the principle determinant of the alveolar gas-exchange surface, and therefore oxygenation. But despite initially promising results48-50 , comparison of ‘inverse-ratio’ ventilation with conventional ventilation with equivalent values of PEEP has failed to demonstrate an indiscriminate oxygenation advantage51-53 . However in any given individual inverse ratio ventilation may improve oxygenation, and thereby allow a reduction in FIO2. Improved oxygenation in ventilated patients turned prone was originally advocated in 197454 , and has been shown to cause rapid and sustained improvements in oxygenation in some patients with ARDS55,56 . In a recent prospective study in patients with ARDS prone ventilation did not improve survival57 , but this
  7. 7. Ventilatory Strategies For Arterial Hypoxaemia Page 7 of 15 study has been criticised on a number of grounds58,59 , in particular that the technique was applied ‘too little, too late’. Other studies have suggested that early prone ventilation may be of benefit60 . Inhaled nitric oxide has been shown to significantly improve oxygenation and reduce pulmonary hypertension in some adults with ARDS61 , but in randomised controlled trials in adults these effects have not translated into a reduction in mortality62-65 . None of the studies were powered to examine mortality as a primary outcome and a recent meta-analysis66 has concluded that the full potential of inhaled nitric oxide in the treatment of ARDS is yet to be established. References 1. Fink MP: Bench-to-bedside review: Cytopathic hypoxia. Crit Care 2002; 6: 491-9 2. Mackenzie IM, Banning A, Dyar O: Pharmacologic exposure of an occult atrial septal defect. Crit Care Med 2001; 29: 1832-4 3. Jobe AH: Pulmonary surfactant therapy. N Engl J Med 1993; 328: 861-8 4. Humphrey H, Hall J, Sznajder I, Silverstein M, Wood L: Improved survival in ARDS patients associated with a reduction in pulmonary capillary wedge pressure. Chest 1990; 97: 1176-80 5. Hopewell PC, Murray JF: Effects of continuous positive-pressure ventilation in experimental pulmonary edema. J Appl Physiol 1976; 40: 568-74 6. Berthiaume Y, Staub NC, Matthay MA: Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep. Journal of Clinical Investigation 1987; 79: 335-43 7. Charron PD, Fawley JP, Maron MB: Effect of epinephrine on alveolar liquid clearance in the rat. Journal of Applied Physiology 1999; 87: 611-8 8. Barker PM: Transalveolar Na+ absorption. A strategy to counter alveolar flooding? American Journal of Respiratory and Critical Care Medicine 1994; 152: 302-3 9. Gattinoni L, Pesenti A, Bombino M: Relationships between lung computed tomographic density, gas exchange, and PEEP in acute respiratory failure. Anesthesiology 1988; 69: 824-32 10. Pelosi P, D'Andrea L, Vitale G, Pesenti A, Gattinoni L: Vertical gradient of regional lung inflation in adult respiratory distress syndrome. American Journal of Respiratory and Critical Care Medicine 1994; 149: 8-13 11. Suter PM, Fairley HB, Schlobohm RM: Shunt, lung volume and perfusion during short periods of ventilation with oxygen. Anesthesiology 1975; 43: 617-27 12. Santos C, Ferrer M, Roca J, Torres A, Hernandez C, Rodriguez-Roisin R: Pulmonary gas exchange response to oxygen breathing in acute lung injury. Am J Respir Crit Care Med 2000; 161: 26-31 13. Froese AB, Bryan AC: Effects of anesthesia and paralysis on diaphragmatic mechanics in man. Anesthesiology 1974; 41: 242-54 14. Webb HH, Tierney DF: Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis 1974; 110: 556-65 15. Muscedere JG, Mullen JB, Gan K, Slutsky AS: Tidal ventilation at low airway pressures can augment lung injury. American Journal of Respiratory and Critical Care Medicine 1994; 149: 1327-34 16. dos Santos CC, Slutsky AS: Mechanotransduction, ventilator-induced lung injury and multiple organ dysfunction syndrome. Intensive Care Med 2000; 26: 638-42. 17. Ranieri VM, Giunta F, Suter PM, Slutsky AS: Mechanical ventilation as a mediator of multisystem organ failure in acute respiratory distress syndrome. Journal of the American Medical Association 2000; 284: 43-4 18. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE: Acute respiratory distress in adults. Lancet 1967; 2: 319-23
  8. 8. Ventilatory Strategies For Arterial Hypoxaemia Page 8 of 15 19. Kumar A, Falke KJ, Geffin B, Aldridge B: Continuous positive pressure ventilation in acute respiratory failure. N Engl J Med 1970; 283: 1430-6 20. Amato MBP, Barbas CSV, Medeiros DM, Magaldi RB, Schettino DdPP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CRR: Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. New England Journal of Medicine 1998; 338: 347-354 21. 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. New England Journal of Medicine 2000; 342: 1301-8 22. Suter PM, Fairley B, Isenberg MD: Optimum end-expiratory airway pressure in patients with acute pulmonary failure. N Engl J Med 1975; 292: 284-9 23. Matamis D, Lemaire F, Harf A, Brun-Buisson C, Ansquar JC, Atlan G: Total respiratory pressure-volume curves in the adult respiratory distress syndrome. Chest 1984; 86: 58-66 24. Gattinoni L, Pesenti A, Avalli L, Rossi F, Bombino M: Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study. Am Rev Respir Dis 1987; 136: 730-6 25. Murray JF, Matthay MA, Luce JM, Flick MR: An expanded definition of the adult respiratory distress syndrome. American Review of Respiratory Disease 1988; 138: 720-3 26. Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS: Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. Jama 1999; 282: 54-61. 27. Hudson LD: Protective ventilation for patients with acute respiratory distress syndrome. N Engl J Med 1998; 338: 385-7 28. Lemaire F: ARDS and PV curves: the inseparable duet? Intensive Care Med 2000; 26: 1-2 29. Pelosi P, Gattinoni L: Respiratory mechanics in ARDS: a siren for physicians? Intensive Care Med 2000; 26: 653-6 30. Crotti S, Mascheroni D, Caironi P, Pelosi P, Ronzoni G, Mondino M, Marini JJ, Gattinoni L: Recruitment and derecruitment during acute respiratory failure: a clinical study. American Journal of Respiratory and Critical Care Medicine 2001; 164: 131-140 31. Sjostrand UH, Lichtwarck-Aschoff M, Nielsen JB, Markstrom A, Larsson A, Svensson BA, Wegenius GA, Nordgren KA: Different ventilatory approaches to keep the lung open. Intensive Care Med 1995; 21: 310-8 32. Hickling KG: The pressure-volume curve is greatly modified by recruitment. A mathematical model of ARDS lungs. Am J Respir Crit Care Med 1998; 158: 194-202 33. Pelosi P, Goldner M, McKibben A, Adams A, Eccher G, Caironi P, Losappio S, Gattinoni L, Marini JJ: Recruitment and derecruitment during acute respiratory failure: an experimental study. Am J Respir Crit Care Med 2001; 164: 122-30 34. Jonson B, Richard JC, Straus C, Mancebo J, Lemaire F, Brochard L: Pressure-volume curves and compliance in acute lung injury: evidence of recruitment above the lower inflection point. Am J Respir Crit Care Med 1999; 159: 1172-8 35. Maggiore SM, Jonson B, Richard JC, Jaber S, Lemaire F, Brochard L: 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 2001; 164: 795-801 36. Lachmann B: Open up the lung and keep it open. Intensive Care Med 1992; 18: 319-21 37. Rimensberger PC, Cox PN, Frndova H, Bryan AC: The open lung during small tidal volume ventilation: concepts of recruitment and "optimal" positive end-expiratory pressure. Crit Care Med 1999; 27: 1946-52. 38. Hickling KG: Best compliance during a decremental, but not incremental, positive end-expiratory pressure trial is related to open-lung positive end-expiratory pressure: a mathematical model of acute respiratory distress syndrome lungs. Am J Respir Crit Care Med 2001; 163: 69-78 39. Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L, Lamy M, Marini JJ, Matthay MA, Pinsky M, Spragg R, Suter P, Committee tC: The American-European Consensus Conference on ARDS, part 2. American Journal of Respiratory and Critical Care Medicine 1998; 157: 1332-47 40. Kloot TE, Blanch L, Melynne Youngblood A, Weinert C, Adams AB, Marini JJ, Shapiro RS, Nahum A: Recruitment maneuvers in three experimental models of acute lung injury. Effect on lung volume and gas exchange. Am J Respir Crit Care Med 2000; 161: 1485-94
  9. 9. Ventilatory Strategies For Arterial Hypoxaemia Page 9 of 15 41. Gattinoni L, Pelosi P, Suter PM, Pedoto A, Vercesi P, Lissoni A: Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease. Different syndromes? Am J Respir Crit Care Med 1998; 158: 3-11 42. Lim CM, Jung H, Koh Y, Lee JS, Shim TS, Lee SD, Kim WS, Kim DS, Kim WD: Effect of alveolar recruitment maneuver in early acute respiratory distress syndrome according to antiderecruitment strategy, etiological category of diffuse lung injury, and body position of the patient. Crit Care Med 2003; 31: 411-8 43. Dyhr T, Bonde J, Larsson A: Lung recruitment manoeuvres are effective in regaining lung volume and oxygenation after open endotracheal suctioning in acute respiratory distress syndrome. Crit Care 2003; 7: 55- 62 44. Maggiore SM, Lellouche F, Pigeot J, Taille S, Deye N, Durrmeyer X, Richard JC, Mancebo J, Lemaire F, Brochard L: Prevention of endotracheal suctioning-induced alveolar derecruitment in acute lung injury. Am J Respir Crit Care Med 2003; 167: 1215-24 45. Cakar N, der Kloot TV, Youngblood M, Adams A, Nahum A: Oxygenation response to a recruitment maneuver during supine and prone positions in an oleic acid-induced lung injury model. Am J Respir Crit Care Med 2000; 161: 1949-56 46. Nunn JF, Coleman AJ, Sachithanandan T, Bergman NA, Laws JW: Hypoxaemia and Atelectasis Produced by Forced Expiration. Br J Anaesth 1965; 37: 3-12 47. Rothen HU, Sporre B, Engberg G, Wegenius G, Hogman M, Hedenstierna G: Influence of gas composition on recurrence of atelectasis after a reexpansion maneuver during general anesthesia. Anesthesiology 1995; 82: 832-42 48. Tharratt RS, Allen RP, Albertson TE: Pressure controlled inverse ratio ventilation in severe adult respiratory failure. Chest 1988; 94: 755-62 49. Abraham E, Yoshihara G: Cardiorespiratory effects of pressure controlled inverse ratio ventilation in severe respiratory failure. Chest 1989; 96: 1356-9 50. Andersen JB: Ventilatory strategy in catastrophic lung disease. Inversed ratio ventilation (IRV) and combined high frequency ventilation (CHFV). Acta Anaesthesiol Scand Suppl 1989; 90: 145-8 51. Mancebo J, Vallverdu I, Bak E, Dominguez G, Subirana M, Benito S, Net A: Volume-controlled ventilation and pressure-controlled inverse ratio ventilation: a comparison of their effects in ARDS patients. Monaldi Arch Chest Dis 1994; 49: 201-7 52. Gonzalez Zambrano L, San Roman E, Gallesio AO, Prados AF, Principe GJ: [Evaluation of hemodynamic and respiratory variables in patients with acute respiratory distress syndrome in two ventilatory modes]. Medicina (B Aires) 1997; 57: 391-6 53. Huang CC, Shih MJ, Tsai YH, Chang YC, Tsao TC, Hsu KH: Effects of inverse ratio ventilation versus positive end-expiratory pressure on gas exchange and gastric intramucosal PCO(2) and pH under constant mean airway pressure in acute respiratory distress syndrome. Anesthesiology 2001; 95: 1182-8 54. Bryan AC: Comments of a devils advocate. American Review of Respiratory Disease 1974; 110: 143S-4S 55. Pappert D, Rossaint R, Slama K, Gruning T, Falke K: Influence of positioning on ventilation-perfusion relationships in severe adult respiratory distress syndrome. Chest 1994; 106: 1511-6 56. Fridrich P, Krafft P, Hochleuthner H, Mauritz W: The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome. Anesthesia and Analgesia 1996; 83: 1206-11 57. Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, Malacrida R, Latini R, for the Prone- Supine Study Group: Effect of prone positioning on the survival of patients with acute respiratory failure. New England Journal of Medicine 2001; 345: 568-73 58. Slutsky AS: The acute respiratory distress syndrome, mechanical ventilation, and the prone position. New England Journal of Medicine 2001; 345: 610-2 59. Zilstra JG, Ligtenberg JJM, van der Werf TS, Thorburn K, Kerr SJ, Baines PB, Malhotra A, Ayas N, Kacmarek R: Prone positioning of patients with acute respiratory failure. New England Journal of Medicine 2002; 346: 295-7 60. Beuret P, Carton M-J, Nourdine K, Kaaki M, Tramoni G, Ducreux J-C: Prone position as prevention of lung injury in comatose patients: a prospective, randomized, controlled study. Intensive Care Medicine 2002; 28: 564-9 61. Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM: Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med 1993; 328: 399-405
  10. 10. Ventilatory Strategies For Arterial Hypoxaemia Page 10 of 15 62. Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K, Hyers TM, Papadakos P, and the Inhaled Nitric Oxide in ARDS Study Group: Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Critical Care Medicine 1998; 26: 15-23 63. Michael JR, Barton RG, Saffle JR, Mone M, Markewitz BA, Hillier K, Elstad MR, Campbell EJ, Troyer BE, Whatley RE, Liou TG, Samuelson WM, Carveth HJ, Hinson DM, Morris SE, Davis BL, Day RW: Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS. Am J Respir Crit Care Med 1998; 157: 1372-80 64. Troncy E, Collet JP, Shapiro S, Guimond JG, Blair L, Ducruet T, Francoeur M, Charbonneau M, Blaise G: Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study. Am J Respir Crit Care Med 1998; 157: 1483-8 65. Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C: Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide. Intensive Care Med 1999; 25: 911-9 66. Sokol J, Jacobs SE, Bohn D: Inhaled nitric oxide for acute hypoxaemic respiratory failure in children and adults, The Cochrane Library. Oxford, Update Software, 2003 Tables Table 1 Barcroft’s classification of ‘anoxaemia’ (1 to 3), or the causes of the failure of aerobic cellular metabolism, with the addition of cytopathic hypoxia. 1) Anoxic – partial pressure of oxygen in arterial blood reduced (may also be called arterial hypoxaemia) 2) Anaemic – Arterial oxygen content reduced, either by an absolute (anaemia) or functional (carboxyhaemoglobin, methaemoglobin) deficit of haemoglobin. 3) Stagnant – Failure of arterial blood flow to tissues, either globally (cardiac failure, haemorrhage), or locally (arterio-venous shunt, thrombo-embolism). 4) Cytopathic – Inability of tissue to utilise supplied oxygen (e.g. cyanide poisoning). Table 2 Causes of arterial hypoxaemia 1) Low partial pressure of inspired oxygen: barometric pressure and FIO2 2) Hypoventilation 3) Diffusion barrier 4) Shunt 5) Low V/Q a. Proximal airway obstruction (Table 3) b. Loss of alveolar lumen with cellular material (consolidation) or fluid c. Atelectasis 6) Venous desaturation
  11. 11. Ventilatory Strategies For Arterial Hypoxaemia Page 11 of 15 Table 3 Causes of proximal airway obstruction leading to alveolar hypoventilation 1) Plugging of airway a) Mucous plug b) Blood c) Inhaled foreign body d) Shed airway epithelium e) Froth 2) Compression from outside the airway a) Enlarged lymph nodes b) Haematoma 3) Lesions arising from the airway wall a) Mucosal oedema 4) Other a) Airway transection and displacement Table 4 Causes of alveolar hypoventilation and their immediate treatment Cause of low V/Q Immediate solution to improve oxygenation Proximal airway obstruction Mechanical relief Occupation of alveolar air space, cellular None Occupation of alveolar air space, liquid: - ↑ capillary filtration pressure - low plasma oncotic pressure - Ø endothelial reflection coefficient - Ø lymphatic drainage - Ø endothelial reflection coefficient - loss of surfactant - Ø alveolar fluid reabsorption Reduce pulmonary venous hypertension Æ diuretics, arterial vasodilators (to reduce left- ventricular end-diastolic pressure) and pulmonary venodilators None None Reduce CVP Æ diuretics & venodilators None Replacement therapy? b-adrenoreceptor agonists, PEEP Atelectasis - loss of surfactant - compression - absorption - reversed ventilation gradient Recruitment & PEEP, ± sigh? Replacement therapy? Minimise alveolar & interstitial oedema, prone Minimise FIO2 Spontaneous ventilation, prone
  12. 12. Ventilatory Strategies For Arterial Hypoxaemia Page 12 of 15 Figures Figure 1 Collapse of the left lung due to mucus plugging of a bronchus. Figure 2 Left: Computerised tomography of the chest in a patient with the Acute Respiratory Distress Syndrome. Right: Diagram illustrating three distinct lung regions9 —A, normally aerated and ventilated lung; B, atelectatic lung, and C, consolidated lung. Atelectatic lung (B) divides into two sub-regions—B1, tidally recruited lung (type A atelectasis), and B2, recruitable lung (type B atelectasis).
  13. 13. Ventilatory Strategies For Arterial Hypoxaemia Page 13 of 15 Figure 3 Theoretical frequency distibution of alveolar (Type A)opening times during the inspiratory cycle
  14. 14. Ventilatory Strategies For Arterial Hypoxaemia Page 14 of 15 Figure 4 Diagram of the static inflation pressure/volume curve. Three distinct segments are recognized during inflation; an initial phase of low compliance terminating at the lower inflection point (sometimes called Pflex), a segment of higher compliance which is constant and which ends at the upper inflection point, and a final segment of diminishing compliance starting at the upper inflection point and ending at total lung capacity.
  15. 15. Ventilatory Strategies For Arterial Hypoxaemia Page 15 of 15 Figure 5 Diagram of the static inflation (blue) and deflation (green) pressure/volume curve. Inflation and deflation traces are distinct, a phenomenon termed ‘hysteresis’, which is explained by the effects of alveolar recruitment and the visco-elastic properties of the lung.