Management of One-Lung Ventilation: Protective Lung Ventilation

Introduction

One-lung ventilation (OLV) was first described in 1931, and the first pneumonectomy for cancer was performed in 1933. Although technology has evolved since then, OLV still poses a challenge for the anesthesiologist. For several decades, the impairment of gas exchange during OLV represented the focus of the attention. Accordingly, intraoperative mechanical ventilation settings were aimed at avoiding or reversing hypoxemia, as well as hypercapnia, without much concern about the potentially harmful effects of the mechanical stress on the lung parenchyma. Those settings included tidal volume (V _T ) of 10–12 mL/kg of the actual body weight (for a single lung), and zero positive end-expiratory pressure (PEEP). Since then, however, the concept of ventilator-induced lung injury (VILI) emerged and became the cornerstone of mechanical ventilation. The so-called “lung-protective ventilation” strategy, which is based on the use of low V _T with low distending pressures, gained much attention when a multicenter randomized trial showed that V _T of 6 mL/kg of the predicted body weight (pbw) led to lower mortality in patients with the acute respiratory distress syndrome (ARDS) when compared with V _T of 12 mL/kg pbw. It is worth noting that the lung-protective strategy was associated with lower oxygenation than the nonprotective strategy in that study. Furthermore, a meta-analysis showed that use of low V _T is associated with favorable outcomes also in patients without injured lungs.

The use of protective ventilation strategies is not limited to the intensive care unit setting and became widespread also among anesthesiologists to be applied in the operating room. A recent compilation of recommendations for intraoperative mechanical ventilation emphasized the role of low V _T and distending pressures, as well as of adequate PEEP levels, during general anesthesia, as a means to reduce the risk of postoperative pulmonary complications (PPCs). However, those recommendations did not address OLV because protective ventilation during OLV has not been investigated yet with adequately powered trials. ^, Clearly, it must be taken into account that mediastinal displacement, surgical manipulation and chest immobilization, external pressure on the dependent lung, and atelectasis formation increased during thoracic surgery as compared with the other types of surgeries. To date there is no convincing evidence that the data derived from patients with ARDS in the ICU can be translated to the thoracic surgical patients.

In this chapter, we will review the mechanisms of VILI, and explore the basic concepts of protective mechanical ventilation during OLV for thoracic surgery, with emphasis on the maintenance of adequate gas exchange, while avoiding injury that might increase the risk of PPCs.

Ventilator-Induced Lung Injury

During mechanical ventilation, atelectatic and overdistended lung regions may coexist, increasing vulnerability of lungs to the potentially detrimental effects of mechanical ventilation. ^, Accordingly, the regional stress of the lungs is not well reproduced by gross measurements of lung mechanics. ^,

Different mechanisms have been proposed for VILI, most of which are interrelated ( Fig. 20.1 ). Increased airway pressure ( barotrauma ) or the application of relatively high V _T ( volutrauma ) may generate excessively high stretch (strain) and transpulmonary pressures (stress), exceeding the elastic properties of the lung parenchyma above its resting volume and causing direct physical damage of the alveolar-capillary barrier and the cells attached. ^, Also, tidal close-and-reopening of lung units, so-called atelectrauma , can occur in regions close to atelectasis. Importantly, barotrauma, volutrauma, and atelectrauma can have effects on both epithelial and endothelial cells, ^, and cause fragmentation of the fragile extracellular matrix. ^, The mechanical damage of the extracellular matrix favors the formation of interstitial edema and activation of metalloproteinases, may not necessarily cause inflammation, however, these fragments of the extracellular matrix have the potential to activate inflammatory mediators. ^, Furthermore, the damage of the extracellular matrix induced by mechanical ventilation might be exacerbated by fluid load, which is not uncommon to be underestimated during general anesthesia.

In cells, especially those from the alveolar epithelium, mechanical stress can be transducted into chemical signals through different pathways, which elicit proinflammatory and profibrotic responses. This process is known as “ mechanotransduction ". Mechanotransduction can lead to cell apoptosis, and release of homing molecules that promote homing and remote activation of neutrophils and macrophages in lungs and peripheral organs. These effects are termed “ biotrauma ".

In the alveolar-epithelial barrier, mechanical stress can disrupt endothelial cells and lead to capillary stress failure. ^, Also in the presence of structurally intact cells, disruption of adherence junctions (“tight junction”) can occur. Together, those mechanisms increase the epithelial permeability of inflammatory factors and the formation of edema. On the alveolar side of the barrier, the permeability of the alveolar epithelium can also increase with mechanical stress. Those phenomena are more likely during overstretching, but have been described also during atelectrauma. ^, Besides the increased permeability during ventilation with high V _T , there is also a risk that excessive stretch impairs the Na, K-adenosine triphosphatase activity, further contributing to edema formation. Ventilation with low V _T reduces this risk of excessive stretch, but on the other hand, it favors hypoxia, and may impair fluid clearance. Independently of the mechanism, alveolar edema interferes with surfactant function. In addition to those phenomena, translocation of pathogens and proinflammatory mediators is more likely to occur when the alveolar-capillary barrier loses integrity, which may result in damage of distal organs.

During OLV, presence of atelectasis favors the inhomogeneity of ventilation, which in turn can increase the forces applied to the lung parenchyma. Those forces increase the likelihood that one or more of the mechanisms mentioned earlier takes place, and VILI can result even in previously noninjured lungs.

Mechanical ventilation settings may affect the risk of VILI and subsequent development of PPCs, which increase morbidity and result in a longer duration of in-hospital stay and even increased risk of death. Therefore protective mechanical ventilation settings should be known in detail by anesthesiologists performing OLV ( Table 20.1 ).

Protective One-Lung Ventilation

As shown in Fig. 20.2 , there are at least two possible mechanical ventilation strategies to reduce the risk of VILI, namely, the so-called open-lung approach and the lung rest strategy (permissive atelectasis). The open-lung approach is based on alveolar recruitment maneuvers (RM) (open the lungs), high levels of PEEP (keep the lungs open), and the use of low V _T . The lung rest strategy is based on the concept that atelectatic-collapsed lung regions, when not subjected to repetitive opening and closing, are protected from inflammation, and aims at a minimal PEEP level to assure adequate gas exchange (oxygen saturation ≥ 88%–90%), low V _T and low respiratory rate.

In a porcine model of experimental pneumonia, both exogenous surfactant administration and ventilation according to the open-lung approach attenuated bacterial growth and systemic translocation by minimizing alveolar collapse and atelectasis formation. In a similar model of experimental pneumonia in mechanically ventilated pigs, bacterial translocation was lowest with individually tailored PEEP levels, whereas low and high PEEP promoted bacterial translocation.

In isolated nonperfused mouse lungs, both an open-lung approach (V _T of 6 mL/kg, RM and PEEP of 14–16 cmH ₂ O) as well as a lung rest strategy (V _T of 6 mL/kg, PEEP of 8–10 cmH ₂ O, no RM) were associated with reduced pulmonary inflammatory response and improved respiratory mechanics compared with injurious mechanical ventilation (V _T of 20 mL/kg, PEEP of 0 cmH ₂ O). Interestingly, the lung rest strategy was associated with less apoptosis but more ultrastructural cell damage, most likely because of increased activation of mitogen-activated protein kinase pathways as compared with the open-lung strategy.

In healthy mice, mechanical ventilation with a V _T of 8 mL/kg and PEEP of 4 cmH ₂ O induced a reversible increase in plasma and lung tissue cytokines, as well as increased leukocyte infiltration, but the integrity of the lung tissue was preserved. In another investigation, even least-injurious ventilator settings were able to induce VILI in the absence of a previous pulmonary insult in mice. Of note, the deleterious effects of mechanical ventilation in noninjured lungs are only partly dependent on its duration. However, an experimental study demonstrated that large V _T had only minor (if any) deleterious effects on the lungs, despite prolonged mechanical ventilation. Possibly, this finding is explained by the lack of a previous inflammatory insult, as surgery, for example. In fact, it is the systemic inflammation that may prime the lungs to injury by mechanical ventilation.

Tidal Volume

OLV with high V _T has been shown to induce lung overdistension (volutrauma), promoting VILI. ^, In patients undergoing abdominal surgery, an intraoperative ventilation strategy with low V _T and PEEP improved postoperative lung function and even outcome. OLV with a V _T of 10 mL/kg pbw compared with 5 mL/kg pbw resulted in a higher inflammatory response in a small randomized control trial (RCT). In another RCT, OLV with a V _T of 6 mL/kg pbw as compared with 10 mL/kg pbw resulted in a lower incidence of postoperative lung dysfunction. A metaanalysis of randomized trials on low versus high V _T during OLV in patients undergoing thoracic surgery showed a lower incidence of pulmonary infiltrations and ARDS, but the incidence of PPCs did not differ between both strategies. A retrospective analysis suggested that the use of low protective V _T during OLV may be not sufficient to improve clinical outcomes if not accompanied by appropriate levels of PEEP. In the thoracic surgical patients, Blank et al. analyzed the data (medical records and the Society of Thoracic Surgery database) for postthoracic procedure complications of 1019 patients. Associations between ventilator parameters and clinical outcomes were examined by multivariate linear regression. They found that a V t of 8 to 9 mL/kg pbw was associated with fewer PPCs. In the large proportion of the patients, the large V _T during OLV was inversely propositional to the incidence of respiratory complications.

The estimation of pbw is crucial when setting the mechanical ventilator for OLV. The use of pbw is based on the assumption that volutrauma might be minimized by delivering a volume appropriate to the patient’s lung capacity. Lung capacity and respiratory system compliance are more closely related to height than weight. pbw for male and female patients can be calculated by the following formulas:

• Male:pbw = 50 + 0.91 (centimeters of height – 152.4)

• Female: pbw = 45.5 + 0.91 (centimeters of height – 152.4)

It has been suggested that the forced vital capacity (FVC) is a more reliable predictor of appropriate V _T for thoracic surgery than pbw, and that FVC values below 3.5 L are associated with reduced compliance of the respiratory system. Accordingly, V _T equal to functional residual capacity (FRC)/8, as measured preoperatively, could be used to guide the selection of V _T during OLV.

Although adequately powered trials are still missing for a strong recommendation of low protective V _T during OLV, values should not exceed 6 mL/kg pbw in most cases. ^,

Respiratory Rate

Low respiratory rates combined with low V _T during OLV likely result in hypercapnia. When deliberately conducted, this approach is usually termed permissive hypercapnia, and aims at minimizing VILI. Mild hypercapnia can also improve hypercapnic pulmonary vasoconstriction, shift the oxyhemoglobin dissociation curve rightward, improve oxygenation, thus enhancing oxygen delivery to tissue and, potentially improving wound healing and reducing infectious complications. Besides that, moderate respiratory acidosis resulting in arterial pH of approximately 7.25 can decrease the proinflammatory response during OLV. Recently, a comprehensive appraisal of the mechanisms of VILI suggested that the mechanical power transferred from the ventilator to the lung is associated with lung damage. Mechanical power represents the energy per unit of time that is delivered to the lungs, and depends directly on the respiratory rate. In each breath delivered by the mechanical ventilator, a certain amount of energy is transferred to the patient’s respiratory system, which is mainly used to overcome resistance of the airways and to expand the thorax wall. It has been hypothesized that the extent of lung injury depends on the total amount of “mechanical power” delivered by the ventilator per unit of time. Mechanical power is a single variable which combines volume, pressures, flow, and respiratory rate. Accordingly, lower respiratory rates might contribute to reduce the mechanical power and minimize VILI during OLV. Especially in patients with obstructive lung diseases who show expiratory flow limitation, low respiratory rates should be preferred, to avoid formation of auto-PEEP.

Because respiratory acidosis may have also undesirable side effects, including increased intracranial pressure, pulmonary hypertension, myocardial depression, and decreased renal perfusion, its use must be considered judiciously.