Refresher Course : Are lung-protective ventilation strategies worth the effort ?

Nonphysiological ventilation in healthy lungs induces acute lung injury (ALI). Protective lung ventilation in patients with ALI improves outcome. Protective lung ventilation in noninjured lungs and in the absence of a primary pulmonary insult may initiate ventilation-induced lung injury (VILI), as evidenced by inflammatory markers. VILI has important implications that are remote to the lungs and may be associated with significant morbidity and mortality. Volatile anaesthetics can have a lungprotective effect. Excess fluids may contribute to perioperative lung injury. Anaesthesiologists manage a heterogeneous group of patients in the perioperative period, from patients with healthy lungs and patients with at-risk lungs through to patients with established ALI. More patients are at risk for ALI during surgery than previously thought. Appropriate perioperative management may prevent or ameliorate this lung injury. Although evidence is lacking from randomised controlled trials, applying protective ventilatory strategies seems to be a reasonable approach, based on the current understanding of mechanical ventilation and lung injury. © SASA South Afr J Anaesth Analg 2013;19(1):42-50 Refresher Course: Are lung-protective ventilation strategies worth the effort? 43 2013;19(1) South Afr J Anaesth Analg Refresher Course: Are lung-protective ventilation strategies worth the effort? two groups. However, it was not powered to do this. Better oxygenation was demonstrated in the lower tidal volume group during and immediately after one-lung ventilation, but not after 18 hours. In a study that considered conventional versus protective ventilation in critically ill patients without lung injury, de Olivera et al randomised patients to ventilation with either 10-12 ml/kg or 6-8 ml/kg of predicted body weight.7 In both groups, a PEEP of 5 was applied and the fraction of inspired oxygen (FiO2) titrated to keep oxygen saturation > 90%. At 12 hours post ventilation, inflammatory markers in bronchoalveolar lavage fluid [tumour necrosis factoralpha (TNFα) and IL-8] were significantly higher in the larger tidal volume group. Choi et al compared 12 ml/kg without PEEP vs. 6 ml/kg with 10 cm PEEP and showed procoagulant changes in lavage fluid of the larger tidal volume group after five hours of mechanical ventilation.8 A recent randomised control trial of 150 critically ill patients without ALI compared the tidal volumes of 10 ml/kg vs. 6 ml/kg of predicted body weight.9 The conventional tidal volumes were associated with a sustained plasma increase in inflammatory cytokines. Of importance is recent work that suggests that noninjurous or so-called protective ventilatory settings can induce lung injury in previously healthy lungs. An animal study that used a very elegant murine “one-hit” VILI model showed that even least injurious lung settings induced biochemical and histological changes that were consistent with lung injury.10 Work with rodents who underwent mechanical ventilation showed significant gene expression, including genes involved in immunity and inflammation, after only 90 minutes of protective ventilation.11 Whether this has an impact on clinical outcome is presently unknown. ALI is the most common cause of postoperative respiratory failure and is associated with markedly decreased postoperative survival.12 A prospective controlled case study by Fernandez-Perez et al that examined intraoperative ventilator settings and ALI after elective surgery in over 4 000 patients showed a 3% incidence of ALI in high-risk elective surgeries. Patients with ALI had significantly lower postoperative survival and increased length of hospital stay compared with controls. Interestingly in this study, intraoperative peak airway pressure, but not tidal volume, PEEP or FiO2 was associated with ALI. A retrospective cohort study that specifically assessed for intraoperative risk factors for ARDS in critically ill patients found that for patients who received fluid resuscitation > 20 ml/kg/hour, the odds of developing ARDS were three times greater than if < 10 ml/kg/hour was given [odds ratio 3.1, 95% confidence interval (CI) = 1.0-9.9, p-value = 0.05]. 13 Vt/IBW (ml/kg) and number of blood products were not associated with ARDS in this study. It is of interest that the majority of patients were ventilated with a Vt/IBW of 8-10 ml/kg and an intraoperative PEEP of 0. Ventilator-induced lung injury The phenomenon of VILI is well recognised and can be particularly significant in surgical specialties that require large transfusions, cardiopulmonary bypass and associated lung ischaemia-reperfusion injury (IRI). The deleterious effects of mechanical ventilation may be mediated by localised inflammation and the systemic release of inflammatory cytokines (biotrauma). Mechanical stretch from cyclical alveolar opening and closing sets up an inflammatory response in the alveolar epithelial cells and the vascular endothelial cells. Hyperinflation causes the nuclear translocation of nuclear factor-kappa B (NF-kB) (a key regulator of the expression of multiple genes involved in inflammatory response), and upregulation of other proinflammatory cytokines. Polymorphonuclear leukocyte recruitment and activation appear to be a key component of the mechanical stretch-induced inflammatory response. The balance between apoptosis and necrosis is unfavourably altered by both ischaemia-reperfusion and mechanical stretch.14 Biotrauma not only aggravates ongoing lung injury, but also has important systemic consequences because of the spillover of these inflammatory mediators into the systemic circulation, inducing remote organ dysfunction. A study that examined the novel mechanisms of remote organ injury resulting from VILI showed that mechanical ventilation can lead to epithelial cell apoptosis in the kidney and the small intestine, with accompanying biochemical evidence of organ dysfunction.15 Alveolar stretch-induced adhesion molecules were found in the lung and the liver and kidneys of mice who underwent injurious mechanical ventilation. In addition, cytokine and chemokine expression in pulmonary, hepatic and renal tissue after mechanical ventilation was accompanied by enhanced recruitment of granulocytes to these organs.16 These studies go some way in explaining the remote organ dysfunction that is noted with ALI and ARDS and the role that optimising ventilatory strategies play in ameliorating this. This leads to the question: are lung-protective strategies in ARDS17 applicable to the perioperative environment, specifically in patients with healthy lungs? A recent paper that examined this question highlighted the lack of randomised, controlled trials that focus on best intraoperative tidal volume, PEEP and use of intraoperative lung recruitment.18 While outcome studies are lacking, based on what is known about the effects of mechanical ventilation, it is reasonable to aim for protective ventilatory strategies in perioperative practice. Perioperative surgical environmental factors There are multiple factors in the surgical environment which can contribute to lung injury. The most obvious is the Refresher Course: Are lung-protective ventilation strategies worth the effort? 44 2013;19(1) South Afr J Anaesth Analg surgical approach. Site of operation is an important predictor of pulmonary complications, with upper abdominal and thoracic incisions being the most important19 (any surgery that approaches the diaphragm). A decrease in respiratory complications has been documented when major cavity procedures are carried out with minimally invasive versus open techniques.20,21 Atelectasis occurs frequently following open surgical procedures and in up to 90% of patients who undergo general anaesthesia.22 It is a pathological state that can contribute to or attenuate lung injury. Thus, anaesthesiologists must be aware of techniques to avoid or treat it.23 While open to debate, retrospective24,25 and prospective26 studies have shown that appropriate thoracic epidural analgesia reduces the incidence of respiratory complications (atelectasis, pneumonia and respiratory failure) after major abdominal and thoracic surgery. The benefits of epidural analgesia seem to be in direct proportion to the severity of the underlying lung disease in the patients. Patients with chronic obstructive pulmonary disease seem to derive the most benefit from epidural analgesia.27 Reviews that compared paravertebral block (PVB) with epidural analgesia in patients undergoing thoracic surgery showed equivalent analgesia efficacy, but a better sideeffect profile and lower complication rate with PVB.28,29 In the postoperative period, aggressive physiotherapy with continuous positive airway pressure in patients who develop early desaturation after major abdominal surgery leads to lower rates of major respiratory complications.30 One-lung ventilation Anaesthesiologists are faced with a heterogeneous patient group, in terms of underlying pathology and surgical procedure that requires one-lung ventilation. Both the patient’s pathology and the surgical procedure can predispose to, or cause ALI. ALI has been described since one-lung ventilation (OLV) was first employed in thoracic surgery. The most publicised report is a compilation of 10 pneumonectomy cases published in 198431 which focused on the role of intravenous overhydration as a cause of postpneumonectomy pulmonary oedema. Considerable work has subsequently followed, and understanding the risk factors, mechanisms of injury and management strategies for (what is now termed) post-thoracotomy ALI has greatly advanced. A thorough retrospective study of 806 pneumonectomies found a 2.5% incidence of post-pneumonectomy pulmonary oedema, with 100% mortality in affected patients.32 There was no difference in perioperative fluid balance between post-pneumonectomy ALI cases (24-hour fluid balance 10 ml/kg) versus matched pneumonectomy controls (13 ml/kg). Authors used rig