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.¹ 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.²

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).³ However, those recommendations did not address OLV because protective ventilation during OLV has not been investigated yet with adequately powered trials.^4,5 Clearly, it must be taken into account that mediastinal displacement, surgical manipulation and chest immobilization, external pressure on the dependent lung,⁶ 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.⁷

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.^8,9 Accordingly, the regional stress of the lungs is not well reproduced by gross measurements of lung mechanics.^10,11

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.^12,13 Also, tidal close-and-reopening of lung units, so-called atelectrauma,¹⁴ can occur in regions close to atelectasis. Importantly, barotrauma, volutrauma, and atelectrauma can have effects on both epithelial and endothelial cells,^15,16 and cause fragmentation of the fragile extracellular matrix.^17,18 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.^19,20 Furthermore, the damage of the extracellular matrix induced by mechanical ventilation might be exacerbated by fluid load,²¹ 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“.²² 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.²³ These effects are termed “biotrauma“.²⁴

In the alveolar-epithelial barrier, mechanical stress can disrupt endothelial cells and lead to capillary stress failure.^25,26 Also in the presence of structurally intact cells, disruption of adherence junctions (“tight junction”) can occur.²⁷ 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.²⁸ Those phenomena are more likely during overstretching, but have been described also during atelectrauma.^29,30 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,³¹ 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.³² Independently of the mechanism, alveolar edema interferes with surfactant function.³³ 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.³⁴

During OLV, presence of atelectasis favors the inhomogeneity of ventilation, which in turn can increase the forces applied to the lung parenchyma.⁹ 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.^35–37 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),³⁸ 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,³⁹ and aims at a minimal PEEP level to assure adequate gas exchange (oxygen saturation ≥ 88%–90%), low V_Tand low respiratory rate.⁴⁰

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.⁴¹ 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.⁴²

In isolated nonperfused mouse lungs, both an open-lung approach (V_T of 6 mL/kg, RM and PEEP of 14–16 cmH₂O) as well as a lung rest strategy (V_T of 6 mL/kg, PEEP of 8–10 cmH₂O, 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 cmH₂O).⁴³ 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.⁴³

In healthy mice, mechanical ventilation with a V_T of 8 mL/kg and PEEP of 4 cmH₂O 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.⁴⁴ In another investigation, even least-injurious ventilator settings were able to induce VILI in the absence of a previous pulmonary insult in mice.⁴⁵ Of note, the deleterious effects of mechanical ventilation in noninjured lungs are only partly dependent on its duration.⁴⁶ However, an experimental study demonstrated that large V_T had only minor (if any) deleterious effects on the lungs, despite prolonged mechanical ventilation.¹³ 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.⁴⁷

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.⁶¹ Mild hypercapnia can also improve hypercapnic pulmonary vasoconstriction,⁶² shift the oxyhemoglobin dissociation curve rightward, improve oxygenation,⁶³ 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.⁶⁴ 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.⁶⁵ Mechanical power represents the energy per unit of time that is delivered to the lungs, and depends directly on the respiratory rate.⁶⁶ 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.⁶⁷

Because respiratory acidosis may have also undesirable side effects, including increased intracranial pressure, pulmonary hypertension, myocardial depression, and decreased renal perfusion,^68–70 its use must be considered judiciously.

Positive End-Expiratory Pressure and Recruitment Maneuvers

During OLV, especially in the lateral decubitus position, the dependent lung can by compressed by the mediastinal and intraabdominal structures, as well as surgical manipulation, resulting in further reduction of FRC. PEEP has the potential to keep lung units open at the end of expiration preventing the formation of atelectasis and thereby increasing FRC above the closing capacity of the lungs. Also, appropriate levels of PEEP may result in ventilation within a linear part of the pressure-volume curve of the respiratory system, minimizing atelectrauma.⁴⁰ However, PEEP can lead also to hyperinflation, increasing the alveolar dead space, and compressing lung capillaries. This might result in an increased afterload of the right ventricle with cardiovascular depression, need for fluid loading, and inotropic support. Furthermore, PEEP in the ventilated lung can shift perfusion to the nonventilated lung, resulting in an increased intrapulmonary shunt. Special caution is needed when setting PEEP in patients with severe obstructive disease, because inspiratory flow limitation may result in dynamic hyperinflation because of auto-PEEP.

The appropriate level of PEEP has been a matter of intensive debate in the last decade, and higher levels of PEEP are frequently used. However, recent clinical trials failed to show that high PEEP could improve outcome. In nonobese patients, as well in obese patients submitted to abdominal surgery, a PEEP of 12 cmH₂O did not reduce the incidence of PPCs.^71,72 Besides using a fixed value, PEEP can be individualized according to different characteristics: (1) the best compliance by a decremental PEEP titration to reach the best compliance;⁷³ (2) the lowest driving pressure;⁷⁴ and (3) according to electrical impedance tomography (EIT).⁷⁵ The titrated PEEP may vary depending on the titration method used. PEEP titrated according to the compliance of the respiratory system in patients submitted to abdominal surgery did not reduce the occurrence of PPCs when compared with low PEEP.⁷⁶ In a small RCT, PEEP level titrated to the lowest driving pressure during OLV, as compared with a fixed level of PEEP of 5 cmH₂O, resulted in improved lung protection.⁷⁴ PEEP values determined with EIT effectively improved oxygenation and lung mechanics during OLV in elderly patients undergoing thoracoscopic surgery.⁷⁵ However, adequately powered studies on the effects of different PEEP levels on lung protection are missing.

The effects of a particular level of PEEP may vary when PEEP is used isolated or in combination with an RM.⁷⁷ Currently, high-quality evidence is lacking to recommend a routine RM for all patients and further research is required.³ An RM is a maneuver aimed at increasing the transpulmonary pressure in an attempt to revert alveolar collapse.⁷⁸ Different RMs have been described to achieve this aim in the ventilated, and also the nonventilated, lung. All RMs lead to a temporary increase of the airway pressure, usually with values of 40 cmH₂O or more, during 20 to 40 seconds. Most frequently, this is achieved by switching the mechanical ventilator to manual ventilation and using bag squeezing along with appropriate fresh gas flow and setting of the adjustable pressure-limiting valve, as shown schematically in Fig. 20.3. Albeit popular, this procedure is not standardized and may be less effective because loss of airway pressure may occur when resuming mechanical ventilation. The preferred approach is to conduct an RM under pressure-controlled ventilation (PCV), as shown illustratively in Fig. 20.3. If PEEP titration is necessary, changing for volume-controlled ventilation (VCV), followed by decremental PEEP steps of 2 to 3 cmH₂O to identify the value leading to maximal compliance of the respiratory system is likely adequate. Alternatively, the RM can be conducted under VCV by increasing V_T in increments of 4 mL/kg pbw under a constant high PEEP level of 12 cmH₂O. RMs that are conducted under tidal ventilation are usually known as “stepwise RM.” Importantly, during the stepwise RMs, the respiratory rate is reduced to 10/min at an inspiratory to expiratory ratio (I:E) of 1:1, and 1 minute is spent at each V_T or PEEP step to allow enough time for lung recruitment during inspiration (3 seconds).

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