CON: Routine intraoperative PLV has been shown to improve outcome in patients affected by ALI/ARDS
Andrew Maslow, MD
Rhode Island Hospital
Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) typically includes a mix of poorly functioning consolidated lung, bullae, and relatively normal lung, the latter of which is at risk for over-distention and injury during positive pressure ventilation (PPV), which traditionally involved high inflation pressures and tidal volumes (TV) to recruit atelectatic or diseased lung units. Concerns that high-volume, high-pressure (HVHP) ventilation could cause regional over-distention and injury of relatively normal lung has become an active topic of research and discussion.1 Ventilator-induced lung injury (VILI), which includes over-distention, endothelial dysfunction, protein-rich pulmonary edema, hemorrhage, and inflammation, can be reproduced experimentally within two days in a pig model of pneumonia,2 using relatively high TV (20 to 50 ml/kg) and airway pressures (up to 50 cmH2O). In normal lung, a transalveolar plateau pressure (PPL) of 35 cmH2O causes maximum distention.3 Based on these experimental data, protective lung ventilation (PLV) strategies, involving 'low airway pressures' (peak (PAW) ^le; 30-40 cmH2O; plateau or peak end-inspiratory (PInsp) ≤ 30-35 cm H2O) and low TV (≤ 6-8 ml/kg), liberal PEEP, and permissive hypercapnea, have been proposed for patients with or at risk for ALI/ARDS requiring PPV. The goals of PLV are to maintain lung volumes above and below the lower and upper inflection points (resp.) on the pulmonary pressure-volume curve to prevent alveolar collapse and over-distention.
Despite these concepts and published literature and opinion, debate continues regarding the outcome benefits of PLV for patients with or at risk for ARDS requiring prolonged mechanical ventilation. Even less data is available supporting the intraoperative application of PLV for relatively healthier lungs requiring PPV during the intraoperative period.
Elevation of cytokines (bio-trauma) has been proposed as a mechanism of VILI and a possible cause of non-pulmonary organ dysfunction and mortality. However, cytokine elevations have been extremely variable during different modes of PPV despite same experimental protocols and same research teams.4-7 Furthermore, these cytokine elevations are not consistently tied to outcome.8 In one experimental model of ARDS, high TV (40 > 15 > 7 cc/hg) was associated with lower TNFa and macrophage levels (Whitehead). In patients with relatively normal lungs undergoing major thoracic or abdominal surgeries, high and low TV (12-15 ml/kg vs 6 ml/kg) produced similar inflammatory responses.9
In prospective randomized studies examining the effect of PLV in ARDS,10-14 the conclusions have been mixed. Three studies have found either no difference in short (1-2 mos) or long (1-2 yrs) term clinical outcome between PLV and TPPV, or improved outcome during TPPV.10-12 Stewart et al randomized 120 patients at risk for ARDS to TPPV or PLV.10 TV (7 ml vs. 10 ml/kg), PAW (24 vs. 32-34 cmH2O), and PPL (22 vs. 26-28 cmH2O) were lower for the PLV group, who needed higher ventilator frequency and bicarbonate administration to maintain arterial pH > 7.0. In association with hypercapnea and acidosis, the PLV group had a higher incidence of renal dysfunction and renal failure requiring dialysis. Duration of ventilation, ICU and hospital stay, and mortality (approx. 50%) were not different between the groups. In a similar study of 116 patients with ARDS, 60-day mortality was greater for the PLV group (46.6 vs. 37.9%).11
Two randomized studies reported a benefit of PLV for patients with ARDS.13,14 Both were stopped after an interim analysis showed a benefit for PLV. Although the smaller study reported a lower 28 day mortality (11/29 (38%) vs 17/24 (71%)) with PLV, the authors did not account for nor explain the cause of death in five patients within 24 hours of randomization in the TPPV group.13 It suggests that pre-study variables, not accounted for by the global APACHE risk assessment score, contributes to outcome. Furthermore, the 71% mortality reported in the TPPV is higher than reported mortalities (20-60%)15 further raising the possibility of unaccounted for variables. In the larger of these studies, 861 patients were randomized to either TPPV or PLV.14 Unlike other studies, PaCO2 levels and pH were kept similar between the two groups. The incidence of barotrauma was not significantly different at 28 days. Although both groups had reductions of pulmonary cytokine levels (IL-6), the authors recorded fewer non-pulmonary organ failures for the PLV group. However, there was no information regarding treatment protocols of pulmonary and non-pulmonary organ dysfunctions. Non-pulmonary dysfunction may not have been well controlled for, or treated equally between the two groups, and may have contributed to differences in pulmonary failure and mortality. While the PLV group had a lower mortality (31% vs. 39.8%), the mortalities for both groups are equal to or lower than those reported elsewhere, raising concerns that mortality may be more related to non-pulmonary functions and not ventilatory strategy. No multivariate analyses were performed to assess the contribution of different variables on mortality, nor did the authors list the causes of death. In two investigations that actually listed the causes of death, pulmonary failure accounted for only 2.5% and 13% of deaths.10,13 Without detailed evaluation of the data by a multivariate analysis, it is premature to conclude that ventilation strategy was a predictor of outcome.
Low pressure and low volume (LPLV) ventilation causes atelectasis, reductions in functional residual capacity (FRC), hypercapnea, and acidosis, the latter altering renal and cerebral blood flow, and cardiopulmonary and vascular functions. Whether this may be offset by increasing the respiratory rate (RR) and application of PEEP is not clear. Despite increasing RR to maintain similar minute ventilation (MV), hypercapnea and acidosis still occur,10-13 suggesting PLV is associated with a greater amount of dead space ventilation and is not as efficient at excreting CO2.The distribution of lung pathology, PPV and the effects of PEEP are not easily predicted and not always beneficially matched.16 Approximately 1/3 of patients may have no benefit or even a detriment with the application of PEEP. 17,18 Different etiologies of ARDS (primary pulmonary vs. secondary causes of pulmonary dysfunction) are associated with varying benefits with different modes of ventilation, arguing against the blanket application of one ventilatory strategy. 17,18
In a meta-analysis, use of higher TV (10-12 ml/kg) was found to be associated with similar outcome compared to LVLP ventilation as long as PPL were kept <31 cmH2O.19 There is no consensus as to what constitutes the best mode PLV.19,20 This clinical conclusion is supported by animal data using an ex-vivo model of rabbit lung.21 Ventilator settings were varied between high and low mean PAW (13 vs 22 cmH2O) and small and large TV (6 vs. 18 ml/kg).22 Lower pressure/high TV ventilation was associated with significantly less hemorrhage and lung weight gain than other modes of ventilation, supporting the concept that high TV may be more beneficial when associated with acceptable airway pressures.
Furthermore, a recorded PPL or PInsp during general anesthesia and surgery likely overestimates the true trans-alveolar pressure since the assumption that the intrapleural pressure equals zero may not be valid, due to the effects of anesthetic agents and extra-parenchymal factors affecting total pulmonary compliance. Adjusting ventilation based on PAW, PPL, or PInsp can result in hypoventilation, acidosis, and atelectasis.
Application of PLV during one-lung ventilation for thoracotomy has not proven beneficial.9,23,24 Instead, a reduction in TV and increase in RR, increases auto-PEEP, increases ventilatory dead space, and reduces CO2 excretion and systemic oxygenation.9,23,24 Likewise, in cardiac surgery, PLV has not resulted in superior hemodynamics, earlier extubation, nor reduced hospital stay.25
The application of low volume/low pressure ventilation, liberal PEEP, and permissive hypercapnea, all of which are components of PLV, has not been shown to convincingly improve outcome for patients with ARDS and even less so for healthier lungs subjected to PPV for relatively brief periods during surgery. The assumption that PAW, PInsp, and PPL are accurate substitutes for transalveolar pressure could lead to harmful hypoventilation, acidosis, and atelectasis, which would not be predictably offset by increasing the RR or application of PEEP. Different ventilator settings likely have different benefits at appropriate times; however, the blanket application of PLV to all patients at risk for ALI is not supported. Ventilatory settings should be individualized for each patient and in concert with the surgical procedure.
- Dreyfuss D, Saumon G: Ventilator-induced lung injury: Lesson from experimental studies. Is J Respir Crit Care Med 1998; 157:294-323.
- Goldstein I, Bughalo MT, Marquette CH, Lenaour G, Lu Q, Rouby JJ: Mechanical ventilation-induced air-space enlargement during experimental pneumonia in piglets. Am J Respir Crit Care Med 2001; 163:958-964.
- Slutsky AS: Consensus on mechanical ventilation. Intensive Care Med 1994; 20:64-79, 150-162.
- Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS: Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest 1997; 99:944-952.
- Richard JD, Dreyfuss D, Saumon G: Production of inflammatory cytokines in ventilator-induced lung injury: A reappraisal. Am J Respir Crit Care Med 2001; 163:1176-1180.
- von Bethmann AN, Brasch F, Nusing R, Vogt K, Volk HD, Muller K , Wendel A, Uhlig S: Hyperventilation induces release of cytokines from perfused mouse lung. Am J Respir Crit Care Med 1998; 157:263-272.
- Uhlig U, Fehrenbach H, Lachmann RA, Goldmann T, Lachmann B, Vollmer E, Uhlig S: Phosphoinositide 3-OH kinase inhibition prevents ventilation-induced lung cell activation. Am J Respir Crit Care Med 2004; 169:201-208.
- 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. JAMA 1999; 282:54-61.
- Wrigge H, Uhlig U, Zinserling J, Behrends-Callsen E, Ottersbach G, Fischer M, Uhlig S, Putensen C: The effects of different ventilatory settings on pulmonary and systemic inflammatory responses during major surgery. Anesth Analg 2004; 98:775-781.
- Stewart TE, Meade MO, Cook DJ, Granton JT, Hodder RV, Lapinsky SE, Mazer CD, McLean RF, Rogovein TS, Schouten BD, Todd TRJ, Slutsky AS for the Pressure- and Volume-Limited Ventilation Strategy Group: Evaluation of a ventilation strategy to prevent barotraumas in patients at high risk for acute respiratory distress syndrome. N Eng J Med 1998; 338:355-361.
- Brochard L, Roudot-Thoraval F, Roupie E, Delclaux C, Chastre J, Fernandez-Mondejar E, Clementi E, Mancero J, Factor P, Matamis D, Ranieri M, Blanch L, Rodi G, Mentec H, Dreyfuss D, Ferrer M, Brun-buisson C, Todin M, Lemaire for the Multicenter Trial Group on Tidal volume Reduction in ARDS. Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. Am J Respir Crit Care Med 1998; 158:1831-1838.
- Brower RG, Shanholtz CB, Fessler HE, Shade DM, While Jr P, Wiener CM, Teeter JG, Dodd-o JM, Almog Y, Piantadosi S: Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 1999; 27:1492-1498.
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- Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volume as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301-8.
- Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000;342;1334-1349.
- Rouby JJ, Lu Q, Goldstein I: Selecting the right level of positive end-expiratory pressure in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2002; 165:1182-1186.
- Puybasset L, Chuzel P, Chao N, Slutsky AS, Coriat P, Rouby JJ: A computed tomography scan assessment of regional lung volume in acute lung injury. Am J Respir Crit Care Med 1998; 158:1644-1655.
- 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.
- Petrucci N, Iacovelli W: Ventilation with smaller tidal volumes: A quantitative systematic review of randomized controlled trials. Anesth Analg 2004; 99: 193-200.
- Rappaport SH, Shiner R, Yoshihara G, Wright J, Chang P, Abraham E: Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure. Crit Care Med 1994; 22:22-32.
- Broccard AF, Hotchkiss JR, Suzuki S, Olson D, Marini JJ: Effects of mean airway pressure and tidal excursion on lung injury induced by mechanical ventilation in an isolated perfused rabbit lung model. Crit Care Med 1999; 27:1533-1541.
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- Szegedi LL, Barvais Y, Sokolow Y, Yernault JC, d'Hollander AA: Intrinsic positive end-expiratory pressure during one-lung ventilation of patients with pulmonary hyperinflation. Influence of low respiratory rate with unchanged minute volume. Br J Anaesth 2002; 88:56-60.
- Katz JA, Laverne RG, Fairley B, Thomas AN: Pulmonary oxygen exchange during endobronchial anesthesia: Effect of tidal volume and PEEP. Anesthesiology 1982; 56:164-171.
- Chaney MA, Nikolov MP, Blakeman BP, Bakhos M: Protective ventilation attenuates postoperative pulmonary dysfunction in patients undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2000; 14:514-518.