Prolonged recruitment manoeuvre improves lung function with less ultrastructural damage in experimental mild acute lung injury

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Abstract

The effects of prolonged recruitment manoeuvre (PRM) were compared with sustained inflation (SI) in paraquat-induced mild acute lung injury (ALI) in rats. Twenty-four hours after ALI induction, rats were anesthetized and mechanically ventilated with VT = 6 ml/kg and positive end-expiratory pressure (PEEP) = 5 cmH2O for 1 h. SI was performed with an instantaneous pressure increase of 40 cmH2O that was sustained for 40 s, while PRM was done by a step-wise increase in positive inspiratory pressure (PIP) of 15–20–25 cmH2O above a PEEP of 15 cm H2O (maximal PIP = 40 cmH2O), with interposed periods of PIP = 10 cmH2O above a PEEP = 15 cmH2O. Lung static elastance and the amount of alveolar collapse were more reduced with PRM than SI, yielding improved oxygenation. Additionally, tumour necrosis factor-α, interleukin-6, interferon-γ, and type III procollagen mRNA expressions in lung tissue and lung epithelial cell apoptosis decreased more in PRM. In conclusion, PRM improved lung function, with less damage to alveolar epithelium, resulting in reduced pulmonary injury.

Introduction

Cyclic opening and closing of atelectatic alveoli and distal small airways with tidal ventilation is a basic mechanism often leading to ventilator-induced lung injury (VILI) (Dreyfuss and Saumon, 1998). However, atelectatic lung units must be initially opened for PEEP to be effective (Lachmann, 1992). Therefore, lung recruitment manoeuvres (RMs) are used to open up collapsed lung, while PEEP counteracts alveolar derecruitment during low tidal volume ventilation (Crotti et al., 2001, Pelosi et al., 2001).

The response to RMs varies according to the nature, phase, and/or extent of the lung injury (Riva et al., 2008), pre-existing and post procedural patterns of tidal volume and PEEP, number of RMs performed (Richard et al., 2001), and characteristics of recruitment techniques (Borges et al., 2006). Definite guidelines for RM methodology have not been established. The most commonly used RM is the sustained inflation (SI), with rapid high recruitment pressure at 40 cmH2O applied for up to 60 s (Lapinsky et al., 1999, Rimensberger et al., 1999, Kloot et al., 2000, Grasso et al., 2009). SI has been shown to be effective in reducing lung atelectasis (Farias et al., 2005), improving oxygenation (Lapinsky et al., 1999) and respiratory mechanics (Farias et al., 2005, Riva et al., 2008), and preventing endotracheal suctioning-induced alveolar derecruitment (Maggiore et al., 2003). However, other studies have shown that SI might be less effective (Villagrá et al., 2002), short-lived (Brower et al., 2003, Oczenski et al., 2004), associated with circulatory side-effects (Oczenski et al., 2004, Odenstedt et al., 2005a), increased risk of baro/volutrauma (Boussarsar et al., 2002, Lim et al., 2003, Meade et al., 2008), and reduced net alveolar fluid clearance (Constantin et al., 2007), resulting in worsened oxygenation (Musch et al., 2004) and severe clinical consequences (Meade et al., 2008). Furthermore, in preterm lambs, a few sustained inflations, when forced immediately at birth, may have compromises the effect of subsequent surfactant rescue treatment (Björklund et al., 1997).

Several other types of RMs have been suggested to achieve lung volume expansion with less traumatic methods, such as: 1) prolonged lower pressure recruitment manoeuvre with PEEP elevation to 15 cmH2O and end-inspiratory pauses for 7 s twice per minute during 15 min (Odenstedt et al., 2005b), 2) incrementally increased PEEP limiting the maximum inspiratory pressure (Lim et al., 2001), and 3) pressure-controlled ventilation (PCV) applied with escalating PEEP and constant driving pressure (Villagrá et al., 2002, Fujino et al., 2001, Medoff et al., 2000). Nevertheless, during these RMs PEEP increased progressively achieving higher PEEP levels, which may have yielded lung parenchyma injury.

Different techniques of RMs have been proposed as an adjunct to mechanical ventilation and differences among them may be related to the following parameters: the level of recruiting pressure, the duration over which it is maintained, the pattern applied to accomplish recruitment, and the post-RM PEEP (Lapinsky et al., 1999, Rimensberger et al., 1999, Cakar et al., 2000, Kloot et al., 2000, Medoff et al., 2000, Fujino et al., 2001, Lim et al., 2001, Grasso et al., 2002, Villagrá et al., 2002, Marini, 2008). So far, however, the benefits and possible risks of RMs have not been clearly established.

Therefore, we hypothesized that using a prolonged recruitment manoeuvre (PRM), maintaining a fixed higher PEEP level and progressively increasing the positive inspiratory pressure, lung parenchyma stress and strain could be minimized, with less negative hemodynamic effects.

The aim of the present study was to compare the effects between a PRM, using pressure-controlled ventilation with a fixed PEEP level and a progressive increase in positive inspiratory pressure, and sustained inflation on arterial blood gases, lung mechanics and histology (light and electron microscopy), and mRNA expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, interferon (INF)-γ, transforming growth factor (TGF)-β1, TGF-β2, and type III procollagen (PCIII) in lung tissue in an experimental paraquat-induced mild ALI.

Section snippets

Methods

This study was approved by the Ethics Committee of the Carlos Chagas Filho Institute of Biophysics, Health Sciences Centre, and Federal University of Brazil. All animals received care in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the U.S. National Academy of Sciences.

Results

Mean arterial pressure was maintained stable (65–95 mmHg) during the RM and throughout the experiments.

PaO2 and pH were lower while PaCO2 was higher in ALI than in C, independent of ventilatory strategy (P < 0.05) (Table 1). In ALI, the percentage of increase of PaO2 from BASELINE to END was 13% (p = 0.01) and 44% (p < 0.001) after SI and PRM, respectively (Table 2). PaCO2 significantly decreased (21%, p = 0.007) and pH increased (p = 0.02) only in PRM group with no significant changes in SI (Table 1).

Discussion

In the present experimental model of mild ALI, a PRM, using pressure-controlled ventilation and progressively increased driving pressures with a fixed PEEP of 15 cmH2O, was compared to conventional rapid high pressure recruitment manoeuvre (SI) and showed an improvement in gas-exchange and Est,L, with less alveolar collapse, lung epithelial cell apoptosis, alveolar epithelial and endothelial cell damage, pulmonary inflammation, and PCIII mRNA expression in lung tissue.

ALI was induced by

Acknowledgements

The authors would like to express their gratitude to Mr. Andre Benedito da Silva for animal care, Mrs. Jaqueline Lima do Nascimento for her skilful technical assistance during the experiments, Mrs. Ana Lucia Neves da Silva for her help with microscopy, and Mrs. Moira Elizabeth Schöttler for assistance in editing the manuscript.

Supported by: Centres of Excellence Program (PRONEX-FAPERJ), Brazilian Council for Scientific and Technological Development (CNPq), Carlos Chagas Filho, Rio de Janeiro

References (59)

  • P. Chomczynski et al.

    Single-step method of RNA isolation by acid guanidium thiocyanate–phenol–chloroform extraction

    Anal. Biochem.

    (1987)
  • C.S. Garcia et al.

    What increases type III procollagen mRNA levels in lung tissue: stress induced by changes in force or amplitude?

    Respir. Physiol. Neurobiol.

    (2004)
  • S.P. Albert et al.

    The role of time and pressure on alveolar recruitment

    J. Appl. Physiol.

    (2009)
  • G.B. Allen et al.

    Choosing the frequency of deep inflation in mice: balancing recruitment against ventilator-induced lung injury

    Am. J. Physiol. Lung Cell. Mol. Physiol.

    (2006)
  • A.L. Baptista et al.

    Structural features of epithelial remodeling in usual interstitial pneumonia histologic pattern

    Lung

    (2006)
  • J.T. Berg et al.

    High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma

    J. Appl. Physiol.

    (1997)
  • L.J. Björklund et al.

    Manual ventilation with a few large breaths at birth compromises the therapeutic effect of subsequent surfactant replacement in immature lambs

    Pediatr. Res.

    (1997)
  • J.B. Borges et al.

    Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome

    Am. J. Respir. Crit. Care Med.

    (2006)
  • M. Boussarsar et al.

    Relationship between ventilatory settings and barotrauma in the acute respiratory distress syndrome

    Intensive Care Med.

    (2002)
  • R.G. Brower et al.

    Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure

    Crit. Care Med.

    (2003)
  • N. Cakar et al.

    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)
  • D. Chiumello et al.

    Lung stress and strain during mechanical ventilation of the acute respiratory distress syndrome

    Am. J. Respir. Crit. Care Med.

    (2008)
  • J.M. Constantin et al.

    Response to recruitment maneuver influences net alveolar fluid clearance in acute respiratory distress syndrome

    Anesthesiology

    (2007)
  • S. Crotti et al.

    Recruitment and derecruitment during acute respiratory failure: a clinical study

    Am. J. Respir. Crit. Care Med.

    (2001)
  • M.E. de Carvalho et al.

    Effects of overinflation on procollagen type III expression in experimental acute lung injury

    Crit. Care

    (2007)
  • D. Dreyfuss et al.

    Ventilator-induced lung injury: lessons from experimental studies

    Am. J. Respir. Crit. Care Med.

    (1998)
  • T. Dyhr et al.

    Both lung recruitment maneuver and PEEP are needed to increase oxygenation and lung volume after cardiac surgery

    Acta Anaesthesiol. Scand.

    (2004)
  • J.P. Fabisiak et al.

    Paraquat-induced phosphatidylserine oxidation and apoptosis are independent of activation of PLA2

    Am. J. Physiol.

    (1998)
  • E. Fan et al.

    Recruitment maneuvers for acute lung injury. A systematic review

    Am. J. Respir. Crit. Care Med.

    (2008)
  • L.L. Farias et al.

    Positive end-expiratory pressure prevents lung mechanical stress caused by recruitment/derecruitment

    J. Appl. Physiol.

    (2005)
  • Y. Fujino et al.

    Repetitive high-pressure recruitment maneuvers required to maximally recruit lung in a sheep model of acute respiratory distress syndrome

    Crit. Care Med.

    (2001)
  • L. Gattinoni et al.

    Lung recruitment in patients with the acute respiratory distress syndrome

    N. Engl. J. Med.

    (2006)
  • L. Gattinoni et al.

    Physical and biological triggers of ventilator-induced lung injury and its prevention

    Eur. Respir. J.

    (2003)
  • S. Grasso et al.

    Effects of recruiting maneuvers in patients with acute respiratory distress syndrome ventilated with protective ventilatory strategy

    Anesthesiology

    (2002)
  • S. Grasso et al.

    Inhomogeneity of lung parenchyma during the “open lung” strategy: a computed tomography scan study

    Am. J. Respir. Crit. Care Med.

    (2009)
  • R.D. Hubmayr

    Perspective on lung injury and recruitment: A skeptical look at the opening and collapse story

    Am. J. Respir. Crit. Care Med.

    (2002)
  • Y. Imai 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)
  • S.G. Kallapur et al.

    IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide

    Am. J. Respir. Crit. Care Med.

    (2009)
  • T.E. Kloot et al.

    Recruitment maneuvers in three experimental models of acute lung injury. Effect on lung volume and gas exchange

    Am. J. Respir. Crit. Care Med.

    (2000)
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