Adverse pulmonary event
Definition
Observation
Acute respiratory failure
Postoperative PaO2 <60 mmHg on room air, a PaO2/FIO2 ratio <300 mmHg, or arterial oxyhemoglobin saturation measured with pulse oximetry <90 % and requiring oxygen therapy [12]
It may present as mild, moderate, or severe form
Mild, adequate response to supplemental oxygen; moderate, inadequate response to supplemental oxygen requiring noninvasive or invasive mechanical ventilation; severe, acute respiratory distress syndrome [14]
Prolonged air leak
Air leak requiring >7 days of postoperative chest tube drainage [16]
After acute respiratory failure, possibly the most common pulmonary complication following thoracic surgery
Respiratory infection
Receiving antibiotics for a suspected respiratory infection and met one or more of the following criteria: new or changed sputum, new or changed lung opacities, fever, white blood cell count >12 × 109 L−1 [12]
Postoperative hemorrhage
Bleeding through the chest tubes requiring reoperation or three or more red blood cell packs [16]
Atelectasis
Lung opacification with a shift of the mediastinum, hilum, or hemidiaphragm toward the affected area and compensatory overinflation in the adjacent non-atelectatic lung [12]
Pneumothorax
Air in the pleural space with no vascular bed surrounding the visceral pleura [12]
As far as not related to the surgical procedure alone
Bronchospasm
Newly detected expiratory wheezing treated with bronchodilators [12]
In mechanically ventilated patients, increased airway pressure during positive-pressure ventilation or prolonged expiratory phase [16]
Pulmonary embolism
As documented by pulmonary arteriogram or autopsy or supported by a ventilation/perfusion radioisotope scans [16]
Aspiration pneumonitis
Acute lung injury after the inhalation of regurgitated gastric contents
Pleural effusion
Chest radiograph demonstrating blunting of the costophrenic angle, loss of sharp silhouette of the ipsilateral hemidiaphragm in upright position, evidence of displacement of adjacent anatomical structures, or (in supine position) a hazy opacity in one hemithorax with preserved vascular shadows
As far as not related explained by the preoperative patient condition alone
Acute pulmonary edema
Evidence of fluid accumulation in the alveoli as documented by lung imaging
Not explained by poor cardiac function
Purulent pleuritis
Receiving antibiotics for a suspected infection
As far as not related explained by the preoperative patient condition alone
4.4 Risk of Developing Postoperative Pulmonary Complications
Along the last 16 years, more than 50 risk factors for PPCs have been identified and discussed in the literature [9, 10, 17]. Factors related to development of PPCs can be seen also as “predictors” and addressed in terms of relative contribution to the odds of developing such complications. They may be combined by means of statistical models into scores that will ultimately reflect the probability of patients to develop PPCs.
The milestone of a structured presentation of factors related to the development of pulmonary adverse events in surgery patients has been established by the American College of Physicians (ACP) in the year 2006 [17]. Those are factors related to the patient’s preoperative condition, the surgical procedure itself, as well as the type of anesthesia delivered and have been expanded and improved in subsequent studies.
4.4.1 Risk Factors Related to the Patient’s Condition
4.4.1.1 Age
Advanced age has been recognized as a major risk for different adverse postoperative events [18] and represents the most frequent factor related to PPCs [17]. Aging may increase the vulnerability of organ systems to a major surgical stress, or decrease the capability of organ systems to respond to a combination of multiple minor stressors, which may ultimately compromise their ability to respond to such challenges [19]. Although such phenomenon, usually known as frailty, is not exclusive of the elderly patient, it is more often observed in higher age groups. In fact, advanced age seems to be only a surrogate of frailty, which is accompanied by an increased pro-inflammatory response in both nonsurgical [20] and surgical patients [21]. Nevertheless, age still properly stratifies the risk of PPCs.
4.4.1.2 Functional Dependence
Functional dependence reflects perhaps a relevant degree of disability of a patient, and as such it is closely related to age and frailty. It has been shown that this patient-related risk factor and its severity are associated with increased serum levels of pro-inflammatory markers [22]. Particularly, patients with advanced age frequently present frailty and some degree of disability with functional dependence, which further increases the risk for postoperative complications [23].
4.4.1.3 Classification of the American Society of Anesthesiologists (ASA)
The ASA classification for general risk evaluation is popular among anesthesiologists, even if considerable variability among assessors has been reported in different studies [24, 25]. As a score derived from the degree of impairment of several organ systems, the ASA classification is unspecific but has the advantage of integrating possible single factors that may have higher sensibility for PPCs [9]. However, when taken into account for computing risk of PPCs, the ASA classification may jeopardize the contribution of relevant risk factors. Thus, its use as part of risk assessment must be judiciously considered.
4.4.1.4 Smoking
It has been claimed that in lung cancer surgery, the odds of smoking as a risk factor for PPCs is increased [26]. However, the impact of smoking on the development of PPCs after thoracotomy [27], even in patients undergoing lung cancer resection, has been questioned [28]. Therefore, compared to other factors, smoking seems to play a less important role for PPCs.
4.4.1.5 Respiratory Symptoms
4.4.1.6 Peripheral Oxygen Saturation and Pulmonary Function Tests (PFTs)
Low peripheral oxygen saturation adds importantly to the risk of PPCs following different types of surgical interventions, including thoracic surgery [11]. Despite its almost intuitive rationale, this risk factor has been recognized only recently [9].
In the context of thoracic surgery, PFTs comprehend spirometry and diffusing capacity of the lung for carbon monoxide (DLCO). According to the American College of Chest Physicians, impairment of the forced expiratory volume in one second (FEV1) and DLCO are useful in stratifying the risk of disability and even mortality following lung resectional surgery [31]. In patients with lung cancer undergoing surgery, FEV1 represented the PFT parameter that was better associated with PPCs and better contributed to the risk evaluation [32]. The predictive value of PFTs holds useful regardless of the surgical approach, i.e., also for minimally invasive lobectomy [33].
4.4.1.7 Respiratory Infection Prior to Surgery
4.4.1.8 Preoperative Hypoalbuminemia, Weight Loss, and Body Mass Index (BMI)
These factors are closely related to the nutritional status. Low serum albumin concentrations seem to increase the risk of PPCs in the general population [17], possibly to increased incidence of anastomose leakage. In patients undergoing pneumonectomy, hypoalbuminemia was associated with bronchopleural fistula formation [35]. Also, weight loss exceeding 10 % in the past 6 months preceding surgery increases the risk of postoperative pneumonia [36]. Whereas a BMI <18.5 kg/m2 increases the risk of death after lobectomy for cancer [37], a BMI >18.5 kg/m2 increases the risk of PPCs after thoracotomy.
4.4.1.9 Preoperative Anemia
4.4.1.10 Chronic Obstructive and Other Pulmonary Diseases
Chronic obstructive pulmonary disease (COPD) is a comparatively high prevalent disease [39] that carries a considerable risk for patients to develop both non-pulmonary and pulmonary postoperative adverse events [40]. This disease has been incorporated into numerous scores for prediction of risk of PPCs [7, 41–47]. In thoracic surgery patients, COPD is a common comorbidity that underlies many of the indications for such interventions, for example, lung volume reduction surgery, bullectomy, and lung transplantation [48], as well as lung cancer resection and spontaneous pneumothorax surgery [49]. In addition, the degree of severity of COPD plays a relevant role for prognosis prediction, since it is associated with increased need for ICU admission following pulmonary resection [50]. Importantly, the attributable risk of COPD may be decreased upon pulmonary rehabilitation measures [29]. In the general population, chronic pulmonary diseases have been implicated in the need for postoperative reintubation [45].
4.4.1.11 Congestive Heart Failure (CHF)
4.4.1.12 Renal Disease
4.4.1.13 Liver Disease
4.4.1.14 Obstructive Sleep Apnea (OSA)
4.4.1.15 Current Alcohol Use
Alcohol impairs the immune response [56] and causes neurologic impairment, which may facilitate aspiration and the development of pneumonia postoperatively. Alcohol use has been identified as a risk factor for development of PPCs in the general surgical population [17], as is associated with higher risk of death following pneumonectomy [57].
4.4.1.16 Diabetes Mellitus
4.4.2 Procedure-Related and Intraoperative Risk Factors
Thoracic surgery, as compared to other types of surgical interventions, has been associated with relatively high risk for PPCs in different investigations [3, 17, 44]. This figure is explained by the fact that the intervention itself causes direct injury to the lungs, the airways, and also the respiratory muscles, likely interfering with the capability to ventilate, mobilize secretions, and cough. Also, the presence of atelectasis may impair the gas exchange and lead to hypoxemia. Certainly, the surgical approach contributes to determine the impact on the risk of PPCs.
4.4.2.1 Thoracotomy Versus Median Sternotomy
During thoracotomy, the intercostal muscles are likely more injured than during sternotomy, which could be associated with more severe pain and ventilatory impairment. In patients undergoing lung cancer resection, median sternotomy was associated with shorter length of hospital stay, but did not improve survival [59].
4.4.2.2 Video-Assisted Thoracoscopic Versus Open Thoracic Surgery
Laparoscopy compared to open surgery has been found to decrease mortality in the general surgical population [51]. A recent meta-analysis showed that in lung cancer patients with compromised lung function, lobectomy with video-assisted thoracoscopy (VATS) is associated with lower risk for pulmonary morbidity than open surgery [60]. In fact, compared to most open surgical approaches, VATS has been classified as low risk for postoperative ARDS [44].
4.4.2.3 Extent of Lung Resection
Extensive lung resection may be associated with a shift of the pulmonary perfusion to the remaining capillary bed, increasing the shear stress to those areas and consequent failure [61]. In patients undergoing thoracic surgery for lung cancer, the incidence of acute lung injury was more than three times higher after pneumonectomy than lobectomy or lesser resections [62].
4.4.2.4 Duration of Surgery
The duration of surgery has been shown to increase the risk of PPCs in different studies [3, 17, 44, 51]. Particularly, interventions lasting more than 2 h in the general surgical population [3, 11], or requiring more than 2 h of anesthetic time for pneumonectomy [63], have been independently associated with an increased probability of developing adverse pulmonary events.
4.4.2.5 Volatile Versus Intravenous Anesthetics
The anesthesia regimen has the potential to modulate the incidence of PPCs, given that certain anesthetics promote organ protection. In rats [64], but also in patients [65], volatile agents compared to intravenous anesthetics reduced lung injury and/or inflammation. However, up to this date, no randomized controlled trial demonstrated an advantage of volatile anesthetics in terms of outcome.
4.4.2.6 Muscle Paralysis
The use of neuromuscular blocking agents (NMBAs) for intubation of the trachea with devices that enable lung separation is almost mandatory, since such devices are comparatively larger than conventional endotracheal tubes and optimal conditions more difficult to obtain. Also, NMBAs are used to achieve optimal thoracic surgical conditions. In the general surgical population, intermediate-acting NMBAs have been implicated in an increased incidence of PPCs, especially if reversal of muscle paralysis is not appropriately performed [66].
4.4.2.7 Restrictive Versus Liberal Fluid Strategy
Liberal fluid strategies have been shown to increase the risk for lung injury after thoracic procedures. Fluid overload, impairment of lung lymphatic outflow, and damage of the pulmonary endothelium have been implicated as possible causes for such complication [67]. A retrospective study in patients undergoing anatomic lung resections showed that infusion rates exceeding 6 mL/kg/h increased the risk of PPCs [68].
4.4.2.8 Transfusion of Blood and Blood Products
Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion-related death. This syndrome is related to the passive infusion of human leukocyte antigen and human neutrophil antigen, which may elicit an antibody-mediated [69] inflammatory response, but a non-antibody mediated due to aged cellular blood products has been also identified [70]. Neutrophils seem to play a key role in TRALI. Those cells are activated by different insults, for example, hypotension, mechanical ventilation, or ischemia-reperfusion, which are usually present in thoracic surgery and serve as a first hit. The transfusion of blood and blood products leads then to a second hit, with resulting inflammatory response.
4.4.2.9 Mechanical Ventilation
Mechanical stress inflicted by the ventilator to the lung parenchyma has the potential to cause harm. In patients undergoing esophagectomy, a protective ventilation with low tidal volume (5 mL/kg, predicted body weight – PBW) with positive end-expiratory pressure (PEEP) of 5 cmH2O was associated with less lung inflammation than a non-protective mechanical ventilation with high tidal volume (10 mL/kg PBW) with PEEP of 0 cmH2O [71]. In a retrospective study in lung cancer patients, intraoperative ventilation with lower plateau inspiratory pressure was associated with a decreased incidence of acute lung injury [62]. In addition, a recent meta-analysis showed that protective compared to non-protective ventilation reduced the incidence of postoperative lung injury following abdominal and thoracic surgery. Since the term “protective ventilation” is not well defined and mostly seen as a bundle of measures (low tidal volume, PEEP, recruitment maneuvers, low inspiratory oxygen fraction), it is not clear which of those elements are responsible for lung protection. Apparently, low tidal volumes play an important role in lung protection, whereas the relevance of PEEP has not been demonstrated [72].
4.5 Predictive Models of Postoperative Pulmonary Complications in Thoracic Surgery
Several predictive models of postoperative complications have been developed, but only a few of them are specific for the thoracic surgery population and pulmonary complications. Those scores usually are limited by one or more of the following factors: (1) use of preoperative variables only; (2) lack of clearness of the model’s development as listed in the STROBE guidelines and defined according by the “Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD)” statement [73]; (3) lack of external validation in independent studies; (4) lack of generalizability to other patient populations; and (5) lack of capability of predicting the outcome of individual patients, rather than groups. However, they still build the fundament for stratification of patients for testing interventions, allocation of resources, benchmarking, and also professional audits. Moreover, for the treating physician, they may be helpful to justify and obtain informed consent for certain procedures on a more objective risk/benefit analysis basis. Also, they might contribute to improve a patient’s condition depending whether potentially modifiable risk factors are involved in a poor prognosis. In this subsection, we will briefly describe a few relevant scoring systems for prediction of PPCs, with emphasis in the application in noncardiac thoracic surgery.
4.5.1 The Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM)
4.5.2 The Cardiopulmonary Risk Index (CPRI)
The CPRI combines cardiopulmonary variables into one single score ranging from 1 to 10, where 10 represents the worst value. In patients undergoing pneumonectomy, but not other types of thoracic surgery, a CPRI ≥4 was associated with increased incidence of PPCs [76].
4.5.3 The Expiratory Volume Age Diffusion (EVÁD) Capacity Score
The EVÁD score uses three main covariates to assess the risk of complications after lung resection, namely, age, spirometry, and diffusing capacity [77]. Compared to the CPRI and POSSUM scoring systems, EVÁD showed a better predictive value for PPCs after major lung resection.
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