Thoracic Anesthesia


Postoperative Management of Thoracic Surgical Patients


22. Routine Postoperative Care of the Thoracic Surgical Patient


Respiratory, Renal, and Cardiovascular Postoperative Complications

Alessia Pedoto
David Amar

Key Points

1. Respiratory complications occur in 12% to 26% patients and account for the majority of morbidity and mortality following thoracic surgery. Postoperative predicted DLCO (ppDLCO) may be used to identify high-risk patients preoperatively. Prolonged air leak is the most common respiratory complication following thoracic surgery.

2. Renal complications following thoracic procedures are uncommon and usually occur in the setting of sepsis. Use of NSAIDs, dehydration, and preexisting renal disease are all predisposing factors. Pharmacologic therapy is generally not effective, and prevention continues to be the desired strategy.

3. Supraventricular arrhythmias are common after lung resection and are typically transient, but increase morbidity and hospital length of stay. Diltiazem appears to be effective in preventing postoperative atrial fibrillation.

Clinical Vignette

A 72-year-old man with long-standing smoking history underwent a thoracotomy and right pneumonectomy for nonsmall cell lung cancer and was admitted to the surgical ICU postoperatively. He has diet controlled diabetes mellitus type II and hypertension. Preoperative medications include lovastatin and lisinopril.

Pneumonectomy is one of the surgical curative options for nonsmall cell lung cancer (NSCLC).1,2 It is usually considered for extensive tumors or for tumors located in specific anatomic areas, often as part of a multimodal approach combined with perioperative chemo3 and radiation treatment.4

Despite strict selection criteria, improved surgical and anesthetic techniques, and enhanced postoperative care, patients like the one described in the clinical vignette still suffer significant postoperative complications following lung resection surgery. There is considerable variability in the reported mortality rates after pneumonectomy (5%-6%) which depend on the case volume of the hospital, the age of the patient, the side of surgery4-7 and the use of induction chemotherapy.3 Old age, poor nutritional status, current smoking, and coronary artery disease8 are all well-known risks factors associated with an increased morbidity and mortality after lung resection. Respiratory complications are especially prevalent and a major contributor to morbidity in this patient population, who often exhibits preexisting pulmonary disease. The presence of COPD may increase the risk of developing bronchopleural fistulas and acute respiratory failure.8 Additionally, predicted postoperative DLCO (ppDLCO) is the strongest predictor of increased operative mortality and respiratory morbidity, independently from the presence of COPD9,10 (see Chapter 9). Unfortunately not all centers perform routine DLCO measurements, more so in the presence of normal spirometric measurements.

As a result of all the above, great effort should be tailored in preventing postoperative complications, since they are associated with an increase in ICU admission rates, hospital length of stay and mortality rates.8 This chapter focuses on important respiratory, renal, and cardiovascular complications following thoracic surgery.

POD1: The patient’s (from Clinical Vignette) oxygenation worsened and he was placed on 100% nonrebreather mask. His condition continued to deteriorate and was reintubated on the morning of POD2. His CXR showed diffuse pulmonary infiltrates on the left lung and normal postoperative changes in the right hemithorax.


Respiratory complications are common after pneumonectomy (especially right sided), and several risk factors have been suggested. They account for the majority of morbidity and mortality, despite an overall improvement in surgical and postoperative strategies.

Table 23-1 summarizes early complications after pneumonectomy, while Table 23-2 summarizes the common radiographic findings in these patients. Early respiratory complications are discussed here.

Table 23–1. Incidence of Common Early Complications after Pneumonectomy1,3,5,6,8,69,76



Table 23–2. Radiographic Characteristics of Respiratory Complications112



Postpneumonectomy pulmonary edema (PPPE) is characterized by a sudden onset of noncardiogenic pulmonary edema, which is fatal in more than 60% patients if not recognized. It occurs in 2% to 4% pneumonectomy cases, especially right-sided ones. The etiology is unknown and its clinical features are undistinguishable from the adult respiratory distress syndrome (ARDS).11 A high index of suspicion is necessary for the diagnosis and cardiac failure, pneumonia, sepsis as well as bronchopleural fistula all need to be excluded. Pulmonary infiltrates on chest x-ray and respiratory distress on clinical exam are common diagnostic features.11,12

The onset of PPPE is usually within the first two postoperative days and can present with oliguria in patients with normal preoperative renal function.11 Hypovolemia is usually present due to fluid restriction and possible sequestration of water into a “leaky” lung. Oliguria and pulmonary infiltrates on chest x-ray preceded the onset of dyspnea by an average of 23 hours in a small study.13 Other signs included tachycardia, lung rales, and hypoxemia, and sometimes the presence of subcutaneous emphysema on the operative side.12 Fever (>38°C) and leukocytosis can also be present. Hypoxemia is usually unresponsive to oxygen therapy or diuretics (including “renal dose” dopamine), and often requires endotracheal intubation within the first three days after surgery.13 The treatment is largely supportive and includes diuretics, oxygen, mechanical ventilation, and fluid restriction.

The pathophysiology of PPPE is unclear, with several proposed mechanisms. Volume overload remains a very controversial explanation. Some of the landmark literature originated from animal studies, with variable results on the development of edema. Not all the fluid overloaded animals developed PPPE, and the timing between the clinical manifestation and the diagnosis made at the autopsy remains unclear.12 In a series of 5 case reports,13 PPPE developed in patients who were both eu- and hypovolemic, suggesting more complicated mechanisms.

An increase in the alveolo-capillary membrane permeability has been demonstrated by Waller et al14 who measured the amount of radioisotopic tracer accumulation in lung tissue in patients who underwent pneumonectomy. The changes occurred within 5 hours of surgery. Proposed etiologic factors were neutrophil activation and an increase in pulmonary vascular resistance.14

Impaired lymphatic drainage has been suggested as another potential factor contributing to PPPE. Using a dog model, Little et al15 showed that disruption of the lymphatic drainage was associated with PPPE. However, several other animal and human studies have failed to demonstrate a link between the two. Furthermore, the lung has a significant lymphatic drainage reserve, and further compensation can occur via pleural drainage.11 It is therefore unlikely that lymphatic drainage impairment plays a major role in the development of PPPE.

One-lung ventilation (OLV) with high tidal volumes and hyperoxia has been linked to the damage of the alveolo-capillary membrane. Animal studies have shown that the production of reactive oxygen species associated with high peak airway pressure may cause injury of the alveolo-capillary membrane with an increase in pro-inflammatory cytokines, which may contribute to PPPE.11 In humans, the use of large tidal volume (VT) ventilation with increased peak inspiratory pressure (PIP >40 cm H2O) can be associated with an increase in pulmonary vascular resistance and subsequent pulmonary hypertension.11,16 An important lesson is learned form the ARDS data network on lung injury and high tidal volume.17 A protective lung strategy includes tidal volumes of 3 to 4 cc/kg with OLV, peak inspiratory pressure less than 35 cm H2O and plateau pressures less than 25 cm H2O, with the potential need to accept permissive hypercapnia.

The pneumonectomy empty space can lead to mediastinal shift and hyperinflation of the remaining lung with consequent severe pulmonary hypertension, leading to respiratory distress and death.11Stabilization of the mediastinum in the midline using intermittent clamping of a water sealed chest tube or use of a balanced drainage system helps prevent this complication12 (see Chapter 22).

A certain degree of right ventricular overload occurs after pneumonectomy, even in the absence of preoperative cardiac disease.11 Patients who develop acute lung injury postoperatively exhibit an increase in mean pulmonary arterial pressures and right ventricular dilatation, and this is usually associated with a poor prognosis.18 Although right ventricular dysfunction is unlikely to represent the main etiologic factor, it may contribute unfavorably to the course of PPPE.

Treatment for PPPE is mainly supportive, consisting of mechanical ventilation, fluid restriction and the use of diuretics. Steroid administration intraoperatively in the attempt to prevent PPPE remains controversial, with the majority of the trials done in the ICU setting in patients with ARDS. Cerfolio et al19 designed a safety study on the role of methylprednisolone administered prior to clamping the pulmonary artery in patients undergoing pneumonectomy, and looked at the rate of complications. The 37 subjects who were treated with corticosteroids had a reduced incidence of PPPE/ARDS when compared to historical controls. However, the study was small, not randomized, and the definition of PPPE was very broad, with no mention of the degree of hypoxia and the amount of infiltrates on chest radiography. There was also no follow up on the potential long-term effects of steroids, making potential clinical recommendations difficult.

Given the grave prognosis and the lack of targeted interventions, it is imperative that the thoracic anesthesiologist be familiar with this complication and that he or she make every effort to minimize its occurrence. Suggested perioperative strategies include minimization of intraoperative volume replacement, the use vasopressors to treat intraoperative hypotension (as opposed to fluid boluses), the use of protective lung ventilation strategies, the administration of supplemental oxygen therapy in the postoperative period to reduce pulmonary vascular resistance, and the use of balanced drainage systems after pneumonectomy.


Postoperative pneumonia still represents a major cause of morbidity and mortality after lung resection. The incidence is variable (2%-40%), depending on the population studied, the extent of surgery, and the type and timing of perioperative antibiotic prophylaxis.20 Clinical diagnosis may be difficult, since hypoxia, fever, or an abnormal chest x-ray may be common findings in the postoperative period. Hypoventilation due to pain, as well as the inability to cough and clear secretions, is commonly associated with atelectasis and eventually postoperative pneumonia. Several independent risk factors have been proposed, such as COPD, FEV1 <70%, age >75, induction chemotherapy, type of surgical resection (lobectomy and bilobectomy versus pneumonectomy), intraoperative bronchial colonization and male gender.20,21 High tidal volumes and increased fluid administration are also contributing factors for pneumonia, as well as other postoperative respiratory complications such as ventilator induced lung injury and pulmonary embolism.22 Postoperative pneumonia is associated with higher rates of re-intubation and noninvasive ventilation modalities, prolonged length of stay in the hospital and in the ICU and overall higher mortality rates (19%). It commonly occurs during the first postoperative week, with a peak on postoperative day four.20,23 Lung resection is usually defined as a “clean–contaminated” procedure, due to the opening of the trachea and bronchi and migration of tracheobronchial contaminants, especially with bacterial strands that are resistant to common antibiotic prophylaxis.20 Several studies20,23 suggest that the most common causative micro-organisms are Haemophilus influenzae (41.7%), Streptococcus pneumoniae (25%), Enterobacteriaceae (8.7%), and Pseudomonas (25%) species. Despite recommended antibiotic prophylaxis, the incidence of postoperative pneumonia is still high, and no defined guidelines are available for noncardiac thoracic surgery.23 First and second generation cephalosporins are commonly used in the United States to prevent wound infection, empyema, and pneumonia. While they are extremely efficacious against the former, controversial results exist for the latter.23 In most of the cases the etiology for postoperative pneumonia favors gram negative microorganisms, which are susceptible to a broader coverage. Schussler et al24 studied 455 patients who underwent major lung resection and noted a decrease in postoperative pneumonia after changing the antibiotic regimen from a second generation cephalosporin (cephamandole) to high-dose amoxicillin-clavulanate. The study was reflective of a clinical practice change, and it was neither prospective nor randomized, making the conclusions difficult to apply in the United States, where first generation cephalosporins still remain the recommended antibiotic of choice, with vancomycin or clindamycin as an alternative for β-lactamase allergic patients.25 Current recommendations consist of a single dose antibiotic regimen at an appropriate dosage per body weight, with repeated administration intraoperatively if the wound is not closed after two half lives of the drug.25 Temperature control, supplemental oxygen, and avoidance of hyperglycemia are all additional maneuvers suggested to decrease the incidence of postoperative infections;25 however, their impact on postoperative pneumonia remains unclear.


Bronchopleural fistula (BPF) is defined as a communication between the bronchial lumen and the pleural space, and it can be confirmed via bronchoscopy, thoracotomy, or both.26 It occurs most commonly after right pneumonectomy, probably due to the length of the remaining bronchial stump (longer on the right side), especially if not covered with a flap.1,26 Its incidence is estimated to be from 0% to 9%, leading to a mortality rate of 16% to 23%. Local and systemic risks factors have been identified.26 Local risk factors include bronchial invasion by the tumor, length of the stump, integrity of blood supply, preoperative radiation, stump closure technique (manual suturing vs stapling) and extent of the resection. Extensive lymph node dissection has also been suggested as a cause for BPF formation.27 Systemic factors include patient age older than 70, male gender, diabetes, poor nutritional status, preoperative chemotherapy and underlying lung disease, COPD with low FEV1 and DLCO, and the presence of empyema.26 Common symptoms include cough, which may be productive and worsening when laying on the ipsilateral side of the fistula, or signs of infection if empyema is present. Conventional treatment consists of surgical repair with thoracoplasty and chest wall fenestration to allow drainage of the infected cavity and antibiotic irrigation.28 However, this procedure is associated with high morbidity and mortality rates, especially in the elderly and frail, with many of these patients being unable to have their thoracic fenestration closed. Minimally invasive bronchoscopic approaches have been investigated in an attempt to avoid a repeat thoracotomy.29 The studies published on this topic are mainly a summary of case reports, where the number of patients analyzed is still too small to allow any recommendations. Proposed procedures involve tracheo-endobronchial stent placement (mainly with metallic stents), fibrin glue occlusion, and scar tissue forming agents at the site of the fistula (Nd:YAG laser and sclerosing material). Fibrin glue use has been associated with 20% mortality, 35.6% rate of progression to surgical repair and 15.6% rate of chronic empyema. Better results seem to be achieved with synthetic glue, with a 67% resolution rate for the fistula and a survival rate of 83%. However, only 10% of the empyema seems to resolve with this technique.29 In the majority of cases, serial CT scans or bronchoscopic follow up are required, with repeated treatment being frequently necessary. Overall, prevention still remains the best treatment for BPF, focusing on modifying the potential risk factors when possible. Please refer to Chapter 18 for an in-depth discussion of the anesthetic management of patients undergoing bronchopleural fistula repair.


Acute lung injury (ALI) without an obvious etiology has been described after major lung resection in 1% to 3% cases.5,10 The incidence of ALI has significantly decreased in recent years, mainly due to an improvement in postoperative management and analgesic techniques. As a result, recent efforts have been directed toward understanding the pathophysiology and prevention of this serious complication.

According to the guidelines of the American-European Consensus Conference on ARDS, acute lung injury is defined as an acute onset of hypoxia with an abnormal PaO2/FiO2 ratio (usually <300) and radiographic infiltrates that are characteristic of pulmonary edema.30 ALI can occur either in the early (day 0-3) or late (day 3-10) postoperative period.31 The former is usually associated with PPPE, while the latter is associated with postoperative pneumonia or aspiration.

The strongest predictors for post-thoracotomy ALI seem to be related to patient characteristics (severe pulmonary disease, alcohol consumption) and perioperative medical care (extended resection, ventilator-induced lung injury and fluid overload).10,32 Recent focus has been directed toward one-lung ventilation strategies, with the goal of avoiding alveolar hyperinflation, alveolar stretching, and enhanced release of proinflammatory mediators. A retrospective study on 146 patients who underwent pneumonectomy showed that high tidal volumes and peak airway pressures during one-lung ventilation were associated with an increased incidence of postoperative ALI/ARDS.33 These findings were true both for healthy patients and those with decreased preoperative pulmonary compliance.34Several animal models have demonstrated an increased systemic inflammatory response in the lung when high tidal volumes and plateau airway pressures were used, leading to increased mortality.35

Overall, once post pneumonectomy ALI occurs, hospital length of stay is prolonged and in-hospital mortality increased.10,33 Treatment is mainly supportive, focusing on mechanical ventilation with low tidal volumes (4-6 cc/kg predicted body weight), plateau airway pressures less than 30 cm H2O, respiratory rates titrated to maintain pH between 7.3 and 7.45, and an appropriate FiO2 and PEEP to achieve adequate oxygenation (O2 saturations of 88%-95%).35 As a consequence of the low minute ventilation, moderate hypercapnia may occur. This is usually well tolerated unless metabolic acidosis is also present, which may require an increase in respiratory rate and the use bicarbonate infusion. Recruitment maneuvers should be done intermittently and held for 30 seconds, as they may cause significant concomitant hypotension, limiting peak airway pressures to 35 cm H2O. Prone positioning may be considered as a short-term rescue treatment in the ICU setting in case of persistent hypoxia despite high FiO2 (>60%) and plateau pressures (>30 cm H2O). In selected patients, oxygenation may improve. However, multiple studies have shown no effect on mortality, which still remains elevated.35 The physiologic mechanisms by which the prone position may improve oxygenation are still unclear. Alveolar recruitment, redistribution of ventilation toward areas that have better perfusion, and elimination of cardiac compression by the lungs are suggested hypotheses.35 Among the risks of prone positioning are dislodgment and occlusion of the endotracheal tube and pressure ulcers.35

Several randomized trials have shown a reduction in the duration of mechanical ventilation in patients who have been able to tolerate trials of spontaneous ventilation on a daily basis.35 Patients who breathed unassisted for 30 to 120 minutes a day were able to be extubated earlier than those on pressure support or assist control ventilation. Ventilation with a T-piece, continuous positive airway pressure or 7 cm H2O of pressure support may be used if patients meet certain criteria, such as PEEP less than 8 cm H2O and FiO2 less than 50%, hemodynamic stability and the ability to initiate respiratory efforts.35 Moreover, trials of spontaneous ventilation paired with light sedation or wakeup periods are associated with earlier extubation rates, shorter ICU and hospital stay and decreased mortality rates.36

Several pharmacological interventions have been studied in addition to the protective lung ventilation strategies discussed above. However, the results are not too promising. Nitric oxide, prostaglandins and prostacyclins, surfactants, lisophylline, ketoconazole, and immuno-nutrition with fish oil have all been used successfully in animal models but have not shown the same positive results in clinical studies.37 Novel strategies under investigation target the stimulation of proteins in the alveolar epithelium to enhance edema clearance, the proliferation of type 2 pneumocytes to repair damaged alveoli, and the use of anticytokine antibodies to target inflammatory mediators.37

The role of corticosteroids in ALI/ARDS patients is still controversial in terms of morbidity and mortality, especially when high doses are used (30 mg/kg/d of methylprednisolone or equivalent).38 A meta-analysis of 5 cohort and 4 randomized controlled studies (a total of 648 subjects) favored the use of low dose methylprednisolone or equivalent (0.5-2.5 mg/kg/d) in the early stage of the disease, leading to a decreased mortality rate and improved morbidity.39 Similar results were found when more than a 7-day course was investigated, even though the sample size analyzed was small.38Corticosteroid treatment needs to be initiated prior to the onset of the end-stage fibrosis, usually occurring within two weeks of diagnosis, and weaning should be gradual to prevent rebound inflammation. In the early phase, the disease is characterized by an intense inflammatory response, both generalized and local, with an increase in cytokines and chemokines, alveolar membrane disruption, and fibrogenesis.38 An abnormal pathway in the proinflammatory response involving glucocorticoid receptors has been identified both in the systemic and pulmonary circulation, explaining a potential rationale for corticosteroid treatment.38 A high index of suspicion for side effects is needed when steroids are used for a prolonged time, since nosocomial infections in the absence of fever and prolonged neuromuscular weakness may be quite common in the ICU setting.38


Tracheostomy is usually performed in patients requiring prolonged mechanical ventilation or presenting with upper airway obstruction.40,41 Despite being a procedure that is widely performed in ICU patients, the indications, timing and choice of technique remain controversial.42 It seems that a consensus is reached only for mechanical ventilation longer than 3 weeks, as reported in a recent survey sent to several ICUs in France,40 even though another French study suggested 7 days as optimal.42 Some studies suggest an improved survival when tracheostomy is performed early, but the results are still controversial partly depending on patient risk factors such as age, neuromuscular status and COPD.42

Several advantages and disadvantages of tracheostomy were reported by the physicians responding to the aforementioned survey, the main advantage being easier weaning from the ventilator, better patient comfort and tracheal toileting, and the ability to take oral nutrition.

Among the complications of tracheostomy, tracheal injury and stomal infection were most commonly listed. See Table 23–3 for a summary of the indications, contraindications, and complications of tracheostomy. Tracheostomy can be performed surgically in the operating room, or percutaneously at the bedside in appropriate candidates. Percutaneous tracheostomy offers additional advantages, such as the fact that it is done at the bedside, eliminating the need for transport, which can be labor intensive and risky, especially if the patient is unstable. By eliminating the need for operating room time and personnel, the overall costs of the procedure are significantly decreased.43 In a survey of Dutch ICUs, the lack of operating room availability was listed in 9.1% cases as a reason for delaying tracheostomy, only preceded by the absence of a surgeon (11.4%).44,45 This caused a delay of 2 to 3 days from the time the decision of performing a tracheostomy was made. The procedure is relatively contraindicated in patients with adverse anatomical conditions such as short, fat neck, or obesity an enlarged thyroid gland, an inability to extend the neck, including either documented or suspected cervical spine fracture, previous cervical spine surgery or tracheostomy, coagulopathy, and anticoagulation therapy. Ben Nun et al46 reported a series of 157 patients who underwent percutaneous tracheostomy at the bedside, 58 of which had 1 or more relative contraindications. The incidence of short- and long-term complications for both percutaneous and surgical tracheostomy patients was similar, provided the procedure was performed by experienced personnel. The authors concluded that the only true contraindication for the percutaneous approach was the pediatric population because of the limited experience, agreeing with the majority of the experts in the field. A retrospective study conducted in Brazil showed similar results in terms of complications, when the procedure was performed by surgical residents supervised by a thoracic surgeon, and the patient population had no contraindications for the percutaneous approach.47

Table 23–3. Indications, Contraindications, and Complications of Tracheostomy41,43,44


POD 2: Intravenous loop diuretics were administered on POD 1 with a modest response but his creatinine rose to 3.1 mg/dL. The diuretics were discontinued later.


Acute renal failure (ARF) after lung resection is an uncommon complication and usually occurs as a result of infection or sepsis.48 Despite its low incidence (0.4%-1.0%),5,48,49 it is associated with a 60% to 90% mortality rate.45,48,50 Although the etiology is unclear, fluid restriction, sepsis, nephrotoxic agents, cardiogenic shock and tumor embolization have all been suggested as predisposing factors.51Kheterpal et al49 in an observational study conducted on 75,952 patients undergoing noncardiac and nonvascular surgery found that age, male gender, diabetes mellitus, either on oral medications or insulin, acute heart failure, ascites, hypertension, and renal insufficiency were all associated with an increased risk of postoperative renal injury. Interestingly enough, low urinary output was not associated with ARF. This is in contrast with common clinical practice where a “good” urinary output is indicative of preserved renal function and a guide for fluid management. In a small study, Golledge et al52 found that ARF significantly increased morbidity and mortality after thoracic surgery. Hospital length of stay was 50% longer and mortality 19% higher. They proposed similar risk factors to those described above. Systemic hypotension, which can occur with the use of epidural analgesia, was also suggested as another cause for ARF, especially if local anesthetics were used at high concentration or volume. In healthy subjects, thoracic epidural analgesia interferes with the renin-angiotensin-vasopressin system. Sharrock et al53 in a retrospective study of 150 patients undergoing total hip replacement showed that hypotensive epidural anesthesia did not increase the incidence of postoperative ARF even in patients with preoperative renal disease. In that study, mean arterial pressure was kept at about 40 to 55 mm Hg for an average of 95 minutes, and low dose epinephrine infusion was used to maintain cardiac output. Patients with renal disease were rehydrated during surgery more liberally than the controls, and maybe this contributed to prevent long-term renal disease. As reassuring as these results may be, it must be kept in mind that this model does not completely apply to the thoracic population. Thoracic epidural analgesia is commonly used intraoperatively, but with lower concentrations of local anesthetic and with the goal of keeping the hemodynamics as close as possible to baseline. Rehydration is not used liberally, and average blood loss is usually less than 500 mL.

Renal failure is classified as oliguric (<400cc/d) or nonoliguric (>600 cc/d), the latter being easier to treat and associated with a better prognosis.48,54 Other than supportive care, volume expansion and hemodialysis are the suggested treatments. However, volume expansion is poorly tolerated in the thoracic population, especially after pneumonectomy, due to the potential risk of pulmonary edema, and the use of diuretics can potentially cause harm, thus is not routinely recommended. Maintenance of tissue oxygenation, treatment of sepsis, nutritional support and some form of dialysis and filtration (continuous arteriovenous hemofiltration in case of volume overload, continuous arteriovenous hemodiafiltration for hyper-kalemia, acidosis, or progressive azotemia) have also been suggested.48

Nonsteroidal anti-inflammatory drugs (NSAIDs) are usually used as an adjunct to intravenous narcotics or epidural analgesia in the postoperative period, and may potentially cause ARF due to their nonspecific inhibition of cyclooxygenase enzymes.55 By decreasing prostaglandin production, NSAIDs decrease pain and inflammation, but may also cause hypertension, gastrointestinal hemorrhage and renal dysfunction. The analysis of the literature is inconclusive on the role of these medications on perioperative renal function. In patients without renal disease, NSAIDs may reduce creatinine clearance, as well as potassium and sodium elimination on postoperative day 1. However, no effect on urinary volume or need for hemodialysis has been described.55-57 Preexisting renal disease as well as dehydration (or fluid restriction) may play a role in the development of renal insufficiency related to NSAID use, especially in patients with chronic renal failure, where residual function is prostaglandin dependent. When NSAIDs and aminoglycosides are administered together, there is an additive increased risk of developing ARF, even in the presence of normal preoperative renal function.57 Cyclooxygenase (COX) inhibitors, especially COX2, represent a potentially safer alternative to non specific NSAIDs, especially in the presence of preexisting renal dysfunction. However, a review of the literature has produced inconsistent results to be able to provide recommendations.57 Moreover, these drugs are available only in the oral form in the United States, making their use difficult in the immediate postoperative period.

Several medications are still used for renal protection, however the data in the literature is extremely controversial in terms of whether they improve outcome (summary in Table 23–4).

Table 23–4. Possible Pharmacologic Treatment of Acute Renal Failure


Low dose dopamine (2-5 mcg/kg/min) has been extensively used to improve renal perfusion and prevent or treat ARF. At this dose, dopamine activates the dopaminergic receptors D1, D2, and D4, promoting renal vasodilatation with a subsequent increase in renal perfusion and diuresis. While D1 receptors promote renal vasodilatation, D2 and α-receptors cause vasoconstriction, decrease glomerular filtration rate and sodium excretion. Selective D1 receptor activation may potentially be protective against acute tubular necrosis (ATN). However, there is a poor correlation between infusion rates and achieved plasma levels. Patients receiving renal dose dopamine often have activation of α- and β-receptors, leading to unwanted tachycardia, for example.58 Despite the controversial results in the literature on the role of dopamine as a nephroprotective agent, several surveys in the ICU still confirm the popularity of this drug.59 Lauschke et al60 demonstrated that low dose dopamine neither prevents nor reverses ARF, and does not improve outcome. In critically ill patients, especially if older than 55 years of age, renal perfusion seems to deteriorate due to an increase in renal vascular resistance, which may be already increased at baseline and may be unaffected by dopamine infusion. A meta-analysis of 61 trials (3356 patients) using low-dose dopamine did not show any effect on mortality, need for renal replacement therapy and overall adverse events. Urinary output and creatinine clearance were increased during the first day of treatment, while serum creatinine levels were decreased. However, there was no clinical significance for patients with or at risk for ARF.59 Tachyarrhythmias were reported as the most common adverse event, followed by myocardial, limb or cutaneous ischemia.

Fenoldopam, a selective postsynaptic D1 receptor agonist, has been used in critically ill patients with ARF as a nephroprotective agent at doses of 0.03 to 0.1 mg/kg/min. Fenoldopam increases blood flow to the renal cortex and to a greater extent to the outer medulla, and decreases oxygen demand in the thick ascending limb, the proximal convoluted tubule and the cortical collecting ducts by inhibiting sodium transport.61 In the early stage of ARF, fenoldopam seems to produce a more significant reduction in creatinine in the first 3 days of infusion when compared to low-dose dopamine,61 but does not affect the need for hemodialysis or mortality, except in patients with diabetes or after coronary artery bypass grafting.58 The absence of β-effects has been associated with less arrhythmias, making this drug safer than dopamine when higher doses are needed.45 Tachycardia may occur to compensate for rapid vasodilatation.

Loop diuretics such as furosemide or bumetanide can be used to convert oliguric to nonoliguric ARF, the latter having a better prognosis. However, several meta-analyses do not show a decrease in mortality in patients with ARF, despite a reduction in the oliguric period.62,63 The requirement for hemodialysis, the number of dialysis sessions, the number of patients remaining oliguric despite the treatment and the length of hospital stay is also unchanged. Moreover, at higher doses (1-3.4 g/d), there is an increase in temporary deafness and tinnitus,63 which may go undiagnosed if the patient is sedated and mechanically ventilated. Mehta et al64 studied 552 critically ill patients with ARF who received either boluses or continuous infusion of loop diuretics alone or in combination with thiazide diuretics. They found a 68% increase in mortality, 77% increase in the odds of non recovery of renal function and an overall increase in hospital length of stay. They postulated that the increase in urinary output may have contributed to underestimate the severity of renal dysfunction, delaying proper treatment.

Dexmedetomidine is a selective α2-agonist that has been shown, in a small study, to increase urinary output after thoracic procedures.50 Binding of the α2-receptors within the central nervous system causes a decrease in the sympathetic outflow and catecholamine level,65 which is thought to cause less renal vasoconstriction. In a prospective randomized study of 28 patients undergoing lung resection, the use of dexmedetomidine as an adjunct to postoperative epidural analgesia was associated with increased urinary output, a decrease in serum creatinine and an improved creatinine clearance during the first four postoperative days.50 Patients received a loading dose of 0.5 mcg/kg of medication over 20 minutes, followed by 0.4 mcg/kg/h continuous infusion for 24 hours. Proposed mechanisms were an improved glomerular function by decreasing circulating levels of norepinephrine, possibly a direct effect on the kidney (mainly seen in animal models) and an interference with the antidiuretic effect of arginine-vasopressin. Similar results were found in animal models of ARF from both ischemia-reperfusion injury66 and after intravenous contrast injection.67 In both cases, renal protection was more significant when the drug was started prior to the ischemic insult.

Sodium bicarbonate infusion has also been investigated as a possible protective strategy to prevent renal insufficiency. Medullary renal vasoconstriction with subsequent ischemia and oxidant/free radical injury are two proposed mechanisms leading to nephropathy. Bicarbonate infusion may reduce free radical production by increasing tubular pH.68 However, a single-blinded randomized study conducted on 353 patients with stable renal disease undergoing coronary angiography showed that the use of sodium bicarbonate was not superior to the use of normal saline solutions to prevent contrast induced nephropathy.68 Both estimated glomerular filtration rates and mortality at 30 days and 6 months were similar between the two groups.

POD3: The patient developed atrial fibrillation with rapid ventricular response. Vital signs: BP 80/40, HR 150, T 37.9, SpO2 90% on FiO2 60%. Medications included dopamine 3 mcg/kg/min, fentanyl 50 mcg/h and midazolam 1 mg/h.


Postoperative Arrhythmias

Supraventricular tachyarrhythmias affect about 18% to 20% patients undergoing noncardiac thoracic surgery.69 The most important risk factors are age 60 years and older70 and intrapericardial pneumonectomy.8 Other markers associated with these arrhythmias are an elevated white blood cell count on post operative day one71 and an elevated perioperative N-terminal-pro-B-type natriuretic peptide.72 The most common rhythm disturbance is atrial fibrillation (AF), followed by supraventricular tachycardia (SVT), atrial flutter and premature ventricular contractions (PVCs). They are usually diagnosed on the second postoperative day and respond to pharmacological cardioversion.70,73-75

Sustained ventricular tachyarrhythmias are quite rare after lung resection.69 A study conducted on 412 patients showed a 15% incidence of nonsustained ventricular tachycardia (≥3 beats) during the first 96 hours after major lung resection.76 None of the patients with nonsustained ventricular tachycardia had hemo-dynamic instability that required treatment at any time, and the only preoperative risk factor identified was the presence of a left bundle branch block. There was no association with age, other clinical factors, or core temperature upon arrival to PACU. On multivariate analysis, there was an independent association between nonsustained ventricular tachycardia and postoperative atrial fibrillation (POAF). Proposed mechanisms for this observation included vagal withdrawal or irritation, and/or a surge in sympathetic activity. These findings differ from the cardiac surgical literature, where the presence of postoperative ventricular tachycardia is often associated with poor outcome.69

POAF can manifest either as an isolated complication or be associated with respiratory or infectious disease.70 It is typically transient and reversible and seems to affect individuals with an electrophysiologic substrate for arrhythmias present before or as a result of surgery.77 Despite the good prognosis, patients with POAF after thoracic surgery have a reported risk of 1.7% to develop cerebrovascular accidents.69 This is mostly due to thromboembolism, which can occur within 24 to 48 hours from the onset of POAF. If sinus rhythm cannot be successfully restored within this time frame, anticoagulation should be considered, weighing the risk of postoperative bleeding.69

Several mechanisms have been proposed to explain POAF, but no consistent factors other than age have been proven. Aging per se has been associated with a remodeling of the atrial myocardium, with consequent changes in the sinoa-trial and atrioventricular nodal conduction, as well as an increased sensitivity to catecholamine activity, especially after surgical trauma in the area.69 By age 75, it appears that only 10% normal sinus nodal fibers are present.78 Moreover, in the elderly, triggering of the inflammatory response, with activation of the complement and several proinflammatory cytokines has been suggested as responsible for POAF.79 Amar et al71 showed that in patients older than 60 years of age a doubling in white blood cells (WBC) count on post operative day 1 was associated with a threefold increase in the odds of developing POAF. The peak surge in WBC count paralleled the time of onset of POAF. They suggested that β2-receptor activation could be responsible for this finding, probably secondary to an increase in catecholamine tone. An increase in sympathetic activity and high endogenous catecholamine levels have also been proposed in other studies.71 The use of thoracic epidural analgesia had disappointing results on preventing POAF.80 This may be due to the high individual variability of sympathetic blockade. Positive inotropic agents, such as dopamine, as well as anemia, fever, hypoglycemia, postoperative ischemia, and surgical complications represent other possible aggravating causes.77 Stretching or inflammation of the pulmonary veins, as well as hilar manipulation and mediastinal shift have also been suggested as other contributing mechanisms.73,81

With rapid POAF, patients may exhibit dyspnea, palpitations, dizziness, syncope, respiratory distress, and hypotension. As is true for any type of arrhythmia, pulmonary embolism or myocardial ischemia and electrolyte abnormalities need to be excluded or corrected.82 As part of the workup for new onset POAF, transthoracic echocardiography has been recommended by the American Heart Association guidelines to rule out any structural disease, if such information is not already available.83

Mortality seems to be increased in patients who develop arrhythmias, even though this is not the direct cause, except in the presence of heart failure or prolonged hypotension.74 Hospital length of stay and overall costs are increased, suggesting the importance of prevention when possible.70,84 In most cases, POAF resolves prior to hospital discharge and the great majority of these patients remain in sinus rhythm 6 weeks after surgery.79

Patients are considered at risk for postoperative supraventricular arrhythmias if they have two or more of the risk factors listed in Table 23–5, and if so, they may be started on pharmacological prophylaxis either preoperatively or in the immediate postoperative period.

Table 23–5. Proposed Risk Factors for Supraventricular Tachyarrhythmias69,70,74,77


Several regimens are available to prevent or treat atrial tachyarrhythmias. β-blockers have gained popularity as preventive medications due to their cardio-protective effects. The rationale for their use as prophylaxis is to counteract the effects of the sympathetic predominance that occurs after surgery, which may enhance patient susceptibility to dysrhythmias. β-blockers inhibit intracellular calcium influx via second messenger systems and have a membrane stabilizing effect.85 When used in the thoracic population, the respiratory side effects need to be taken into consideration as they may worsen pulmonary function in the postoperative period. Pulmonary edema has been described as a potential side effect after lung resection,86 as well as hypotension and bradycardia. Moreover, in patients on chronic β-blockers, withdrawal may lead to rebound tachycardia.87 The β-blocker length of stay study (BLOS) analyzed the effects of β-blockers administered after cardiac surgery as prophylactic agents in both naive patients and in those already taking β-blockers preoperatively. The goal was to prevent POAF, and possibly decrease the length of stay in the hospital and ICU. Despite a small decrease in the incidence of POAF in those patients already on β-blockers, an increased length of stay was observed in the very same group.88 This was attributed to the development of adverse cardiac and pulmonary effects. Recently, the Perioperative Ischemic Evaluation (POISE) trial showed that aggressive β-blockade can reduce postoperative myocardial infarction and even POAF, but at the cost of an increase in mortality related to cerebrovascular events in patients who had hypotension and decreased cerebral perfusion.89 These findings have been consistent with other trials using lower doses of β-blockers, and question the safety of this strategy.90

Sotalol is a class III antiarrhythmic with significant activity as a nonselective β-blocker and a potassium channel blocker. Potassium current blockade results in prolongation of both the action potential and the QT interval, which can predispose to ventricular dysrhythmias such as Torsades de Pointes.87 This can occur at both therapeutic and toxic dosages.85 Because of the renal excretion, its use is contraindicated in patients with a creatinine clearance less than 46 mL/min. As with other β-blockers, sotalol is effective in decreasing POAF, but does not reduce hospital length of stay or postoperative morbidity. Several studies have reported significant bradycardia that led to discontinuation of therapy.77 Unfortunately, most of the literature on this medication comes from the cardiac surgical population rather than the thoracic one.82

The calcium channel blockers verapamil and diltiazem have been used for both prophylaxis and treatment of POAF. They directly block the L-type calcium channel, decreasing calcium entry in the cell. This causes a slowing of the sinoatrial automaticity and atrio-ventricular nodal conduction.85 In addition, this class of drugs may reduce pulmonary vascular resistance and right ventricular pressure, making this an attractive option after major lung resection, where a potential increase in pulmonary arterial pressures may be present.86 Hypotension, more frequent with verapamil, is one of the major side effects and one of the most common reasons to stop the medication. In the cardiac population, calcium channel blockers seem to cause a 40% decrease of postoperative myocardial infarction rates and 45% reduction of ischemia.86 Amar et al78 demonstrated that diltiazem is superior to digoxin when used to prevent supraventricular dysrhythmias, specifically POAF, in patients after intrapericardial or standard pneumonectomy. However, both drugs had equal effect on ventricular dysrhythmias, echocardiographic changes in right ventricular function and hospital length of stay. In the largest study to prevent POAF in thoracic surgical patients, diltiazem was shown to be safe and effective in reducing the rate of POAF by almost 50%.84

Prophylactic digitalization to prevent POAF is not a common practice nowadays, since there are no proven benefits and potential associated side effects.91 At the present time, digoxin is not recommended in the postoperative period to prevent POAF.91 In patients with chronic atrial fibrillation, digoxin does not seem to be able to restore normal sinus rhythm, and as a single agent it does not adequately control the ventricular response unless very high doses are used.91 For this purpose, it is usually combined with β-blockers or calcium channel blockers92 and it works better in cases of chronic atrial fibrillation and heart failure with systolic dysfunction.91 Digitalis toxicity and the difficulty in assessing proper plasma levels are the main limiting factors for its use.74 Moreover, several studies had demonstrated a superior effect of calcium channel blockers in preventing POAF, with less potential side effects.78 Digoxin should be avoided in patients with renal insufficiency, electrolyte disturbances (hypokalemia, hypomagnesemia, and hypercalcemia), acute coronary syndromes and thyroid disorders. The main mechanism of action is by enhancing vagal activity, mainly on the atrioventricular node, thus decreasing ventricular response during atrial arrhythmias.87 The sympathetic response is also inhibited in a way unrelated to the increase in cardiac output. Digoxin binds the sodium-potassium ATPase channel, mainly on the myocardium, blocking its transport.92 This promotes an increase in intracellular calcium, which increases cardiac contractility.

Amiodarone is a multiple sodium-potassium-calcium channel blocker and a β-adrenergic inhibitor often used to maintain sinus rhythm after electrical cardioversion in the general population. It works best as prophylactic agent when administered 1 week prior to surgery;93 however, the precise mechanism of action is unknown.94 The calcium-potassium channel blockade causes an increase in the duration of the action potential and the refractory period in the cardiac tissue. Hypotension and bradycardia can be significant, especially in patients with congestive heart failure and left ventricular dysfunction, as well as QT prolongation.81 Other side effects include hypo/hyperthyroidism, hepatic and neurotoxicity, and prolongation of warfarin half-life.94 Pulmonary toxicity is, however, the main concern of amiodarone therapy after lung resection.86 It can occur at lower dosages than the ones used in the general population, and can manifest as chronic interstitial pneumonitis, bronchiolitis obliterans, adult respiratory distress syndrome (ARDS) or a solitary lung mass.81 In a very small prospective randomized study, Van Mieghem et al95 examined the role of amiodarone prophylaxis on POAF after lung resection, comparing it to verapamil. No difference was observed between the two drugs in the interim analysis. However, the study had to be stopped prematurely due to an increased incidence of ARDS in the amiodarone group (7.4% in the patients who had a right pneumonectomy vs 1.6% for other types of lung resections). Mortality rates were also higher in the patients who received amiodarone. This occurred despite using standard intravenous regimens and having therapeutic plasma concentrations. Two mechanisms were proposed: an indirect one, by increasing inflammatory mediators, and a direct one, by causing direct damage to the cells and subsequent fibrosis. Independently from the etiology, they recommended to avoid amiodarone after lung resection. By surgically decreasing the amount of lung parenchyma available, standard doses of amiodarone can account for higher pulmonary concentrations of the drug, which may reach toxic levels. Later studies, when amiodarone was used for a short-time period, did not confirm an increased incidence of respiratory toxicity.69 Overall, the efficacy of amiodarone in preventing POAF does not seem to be different from diltiazem.69 The main indication for amiodarone as a treatment agent is for patients with POAF and pre-excitation conduction abnormalities, such as Wolf-Parkinson-White syndrome.83

Magnesium is indicated if hypomagnesemia exists. A randomized controlled study conducted in 200 patients to undergo cardiopulmonary bypass surgery showed a decreased incidence of POAF when magnesium sulfate was administered as a prophylactic drug.96 However, several trials in the cardiac surgical population have given conflicting results on the benefits of magnesium and POAF prophylaxis, with the only agreement to maintain magnesium levels within normal values.87 Except in patients with acute renal failure, magnesium has a relatively safe profile.

Statins, 3-hydroxy-3-methylglutaratyl coenzyme-A reductase inhibitors, have been shown to suppress electrical remodeling and prevent POAF in animal models.81 They are powerful lipid lowering drugs, highly effective in preventing coronary artery disease. Studies conducted in hypercholesterolemic patients on statins undergoing coronary artery bypass grafting (CAGB) showed a decrease in postoperative major cardiac events.97 When started 1 week prior to on pump CABG, they decreased the incidence of POAF, as well as hospital length stay.77,98 This effect was potentiated if patients were also taking β-blockers.98 One possible explanation seems to be related to their anti-inflammatory mechanism, and observational studies conducted in patients undergoing major lung resection have observed an increase in C-reactive protein and interleukin 6 in the postoperative period.99 Preoperative use of statins was associated with a threefold decrease in the probability of developing POAF.100

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been suggested to reduce the incidence of POAF, with the greatest effect on patients with heart failure and systolic left ventricular dysfunction, but not in patients with systemic hypertension.101 They may also have a role in maintaining sinus rhythm after electrical cardioversion. Inhibition of the reninangiotensin-aldosterone system seems to attenuate left atrial dilatation and fibrosis, and to contribute to slowing conduction in animal studies, all factors that can trigger and maintain re-entry circuits. These effects seem to be potentiated when β-blockers are used in conjunction in patients with chronic heart failure.77 So far, the majority of the literature has focused on outcome in patients with chronic atrial fibrillation. When POAF is investigated, the results are controversial with both positive77 and negative102 findings.

Biatrial pacing and electrical cardioversion: Atrial pacing has been used as an alternative to pharmacological prophylaxis for POAF. There is a lot of controversy among the different pacing modalities and sites, current, rates and concurrent use of medications, with the majority of the studies conducted in the cardiac population after coronary surgery.77 At the present time, the only recommended modality to prevent POAF is biatrial pacing.103 Despite a 15% reduction in the incidence of POAF,103 several technical difficulties can be encountered with this modality. Loss of sensing, diaphragmatic pacing and left ventricular pacing are some of them.104 Most of the patients are paced at a rate of 80 to 90 or higher, depending on their intrinsic heart rate, and for a period of 3 to 5 days.104

Electrical cardioversion is used to treat atrial fibrillation in case of hemodynamic instability, and is successful in 67% to 94% cases.81 Biphasic waveforms are more successful than monophasic, using a current around 100 to 200 J and in a synchronized mode. Higher energy can be used for patients with high body mass index, prolonged atrial fibrillation or left atrial enlargement. Bradycardia (more common in patients on antiarrhythmics prior to cardioversion), ventricular tachyarrhythmias (in case of shock applied during repolarization), hypotension, pulmonary edema (probably due to myocardial stunning) and embolism are all potential complications. Electrolytes should be checked and normalized before cardioversion. In case of digitalis toxicity and hypokalemia, cardioversion should be avoided due to the high incidence of ventricular fibrillation. In this setting, low currents and prophylactic lidocaine should be used. Since bradycardia can be profound up to the point of asystole, pacing capabilities should be readily available.81

Myocardial Ischemia

The postoperative period is one where significant physiologic changes such as decreases in pulmonary function, hypoxia, fluid shifts, electrolyte imbalances, right ventricular dysfunction, and fluctuations in pain occur. Myocardial ischemia can accompany these changes and is present as an electrocardiographic finding in 3.8% lung resection patients, while infarction can occur in 0.2% to 0.9% cases.3,5,6 The incidence increases in patients with preoperative coronary artery disease and abnormal exercise testing. The highest risk is during the first 3 postoperative days, when a high degree of monitoring is suggested. The overall mortality ranges between 32% and 70%.82

It is estimated that 30% patients undergoing noncardiac surgery each year either have or are at risk for coronary artery disease.105 Ideally, these patients should be identified preoperatively, so that appropriate preventive interventions can be delivered throughout the perioperative period. In this respect, beta blockade should be instituted around the time of surgery in patients with three or more risk factors for coronary ischemia or in those on chronic beta blocker therapy.106 The risk of acute coronary syndrome is aggravated by the increased platelet adhesiveness and decreased fibrinolysis seen in the postoperative period. Furthermore, retrospective studies have shown that discontinuation of aspirin places patients at risk for myocardial infarction and stroke.107,108 It is therefore recommended that aspirin therapy be continued throughout surgery in those patients who were taking aspirin preoperatively, except in very selected cases.109

Cardiac stents, especially drug eluting stents, represent a significant problem due to the prolonged need of anticoagulation. Stopping dual antiplatelet therapy (aspirin and clopidogrel) is associated with the risk of stent thrombosis, which may be significantly high, while continuing it leads to an increased risk of intra- and postoperative bleeding and precludes the possibility of using regional anesthetic techniques.107 Duration of antiplatelet therapy is usually based on the type of stent: 4 to 6 weeks for bare metal stents, and 12 to 24 months for drug eluting ones. Patients with drug eluting stents are at higher risk of stent thrombosis, especially if the stent is long, at a bifurcation, if the revascularization is incomplete, or the patient has history of diabetes or heart failure.108 A nonrandomized observational prospective study conducted in noncardiac surgery patients who had cardiac stents placed within a year from surgery109 found that 44.7% patients suffered from cardiac complications postoperatively and 4.7% died. Dual antiplatelet therapy was stopped on average 3 days prior to surgery and substituted with intravenous unfractionated heparin or subcutaneous enoxaparin. Most of the complications occurred within the first 35 days from the stent placement and were cardiac in nature. Bleeding was not a significant variable. The recommendations for continuation of aspirin therapy mentioned above are especially important in this patient population. Clopidogrel should also be continued throughout surgery, or restarted as soon as possible after surgery if bleeding risk is high. In case stents are placed before surgery, bare metal stents are preferred due to their lower risk of thrombosis and the shorter duration of dual antiplatelet therapy. Of note, substitution of antiplatelet agents by an antithrombin such as heparin does not afford real protection against the risk of coronary or stent thrombosis.109

Heart Failure

Congestive heart failure can occur after major lung resection as a result of right- or left-sided dysfunction. Right heart failure can be secondary to changes either in contractility or afterload. Most of the studies that looked at changes in right ventricular function after lung resection were small, and found minor and transient differences when compared to the preoperative period. An increase in right ventricular end–diastolic volume was observed as a reversible finding during the first 2 postoperative days.82 Moreover, pulmonary arterial pressures and pulmonary vascular resistance were mildly increased during the early postoperative period in another study done on 15 patients.110 While postoperative changes in pulmonary arterial pressures, central venous pressures and pulmonary vascular resistance seem to be subtle at rest, they may become significant during exercise. Changes in right ventricular function are usually able to compensate for the former, but they may fail for the latter, leading to pulmonary hypertension.82 Other possible causes of right ventricular failure, although rare, include pulmonary embolism and cardiac herniation (see below).

Left ventricular failure is usually a consequence of right heart dysfunction, either by decreasing left ventricular preload or by interatrial septal shifts.82 Acute ischemia and valvular disease may also be contributing factors.

Cardiac herniation, a rare complication after pneumonectomy, may be responsible for both right and left heart failure. It occurs more commonly after intrapericardial pneumonectomy—right more often than left—and leads to a 50% mortality rate.82 Herniation can be secondary to an incomplete closure of the pericardium or the breakdown of a pericardial patch.111 One main contributing factor includes an increase in intrathoracic pressure, such as with coughing. Changes in position, with the operative side being dependent, positive pressure ventilation, rapid lung re-expansion or suction on the chest tube are also other possible causes. Symptoms depend on the side of the herniation. Right-sided cases present with superior vena cava syndrome due to kinking of the superior vena cava and decreased right ventricular filling, leading to hypotension, tachycardia and shock. Left-sided cases present with arrhythmias and myocardial ischemia leads to infarction, hypotension and ventricular fibrillation if untreated. This is due to less cardiac rotation, with myocardial compression from the pericardium. Clinical presentation and electrocardiographic findings are fairly nonspecific in suggesting the diagnosis, stressing the role of chest radiography and a high index of suspicion. Treatment is surgical, with repositioning of the heart and placement of a patch. In order to minimize hemodynamic instability, the patient should be kept on the lateral decubitus, with the operative side up.111


In the last few decades, a significant improvement in the surgical and anesthetic techniques has made pneumonectomy and major lung resection safer. The introduction of epidural analgesia, short acting anesthetics and minimally invasive surgical techniques have all contributed to decrease the incidence of postoperative complications. Fast track strategies and careful selection of patients undergoing lung resection procedures have also played an important role in postoperative and long-term outcome improvements. Better utilization of step down and acute postoperative care units have decreased the rate of ICU admissions, saving costs. Since the average age of patients requiring lung resection is increasing, anesthesiologists and surgeons will be facing more complex cases, due to the presence of multiple comorbidities. Careful preoperative workup, customizing the type of surgery as well as planning for in hospital and post discharge rehabilitation options will prove to be essential for decreasing complications and improving overall care for thoracic surgical patients.


1. Alexiou C, Beggs D, Rogers ML, Beggs L, Asopa S, Salama FD. Pneumonectomy for non-small cell lung cancer: predictors of operative mortality and survival. Eur J Cardiothorac Surg. 2001;20(3):476-480.

2. Graham E. Indications for total pneumonectomy. Chest. 1944;10(2):87-94.

3. Martin J, Ginsberg RJ, Abolhoda A, et al. Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy. Ann Thorac Surg. 2001;72(4):1149-1154.

4. Van Schil PE. Surgery: therapeutic indications. Cancer Radiother. 2007;11(1-2):47-52.

5. Boffa DJ, Allen MS, Grab JD, Gaissert HA, Harpole DH, Wright CD. Data from The Society of Thoracic Surgeons General Thoracic Surgery database: the surgical management of primary lung tumors.J Thorac Cardiovasc Surg. 2008;135(2):247-254.

6. Allen MS, Darling GE, Pechet TT, et al. Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg. 2006;81(3):1013-1019; discussion 1019-1020.

7. Strand TE, Rostad H, Damhuis RA, Norstein J. Risk factors for 30-day mortality after resection of lung cancer and prediction of their magnitude. Thorax. 2007;62(11):991-997.

8. Dancewicz M, Kowalewski J, Peplinski J. Factors associated with perioperative complications after pneumonectomy for primary carcinoma of the lung. Interact Cardiovasc Thorac Surg. 2006;5(2):97-100.

9. Ferguson MK, Vigneswaran WT. Diffusing capacity predicts morbidity after lung resection in patients without obstructive lung disease. Ann Thorac Surg. 2008;85(4):1158-1164; discussion 1155-1164.

10. Alam N, Park BJ, Wilton A, et al. Incidence and risk factors for lung injury after lung cancer resection. Ann Thorac Surg. 2007;84(4):1085-1091; discussion 1091.

11. Alvarez J. Post pneumonectomy pulmonary edema. In: Slinger, P, (ed). Progress in Thoracic Anesthesia, SCA Monograph. Lippincott Williams & Wilkins, Baltimore. Chapter 9. 2004:187-219.

12. Alvarez JM, Panda RK, Newman MA, Slinger P, Deslauriers J, Ferguson M. Postpneumonectomy pulmonary edema. J Cardiothorac Vasc Anesth. 2003;17(3):388-395.

13. Alvarez JM, Bairstow BM, Tang C, Newman MA. Post-lung resection pulmonary edema: a case for aggressive management. J Cardiothorac Vasc Anesth. 1998;12(2):199-205.

14. Waller DA, Keavey P, Woodfine L, Dark JH. Pulmonary endothelial permeability changes after major lung resection. Ann Thor Surg. 1996;61(5):1435-1440.

15. Little AG, Langmuir VK, Singer AH, Skinner DB. Hemodynamic pulmonary edema in dog lungs after contralateral pneumonectomy and mediastinal lymphatic interruption. Lung. 1984;162(3):139-145.

16. Van Der Werff YD, Van Der Houwen HK, Heijmans PJ, et al. Postpneumonectomy pulmonary edema. A retrospective analysis of incidence and possible risk factors. Chest. 1997;111(5):1278-1284.

17. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-1308.

18. Amar D, Burt ME, Roistacher N, Reinsel RA, Ginsberg RJ, Wilson RS. Value of perioperative Doppler echocardiography in patients undergoing major lung resection. Ann Thorac Surg. 1996;61(2):516-520.

19. Cerfolio RJ, Bryant AS, Thurber JS, Bass CS, Lell WA, Bartolucci AA. Intraoperative solumedrol helps prevent postpneumonectomy pulmonary edema. Ann Thorac Surg. 2003;76(4):1029-1033; discussion 1025-1033.

20. Schussler O, Alifano M, Dermine H, et al. Postoperative pneumonia after major lung resection. Am J Respir Crit Care Med. 2006;173(10):1161-1169.

21. Shiono S, Yoshida J, Nishimura M, et al. Risk factors of postoperative respiratory infections in lung cancer surgery. J Thorac Oncol. 2007;2(1):34-38.

22. Fernandez-Perez ER, Keegan MT, Brown DR, Hubmayr RD, Gajic O. Intraoperative tidal volume as a risk factor for respiratory failure after pneumonectomy. Anesthesiology. 2006;105(1):14-18.

23. Radu DM, Jaureguy F, Seguin A, et al. Postoperative pneumonia after major pulmonary resections: an unsolved problem in thoracic surgery. Ann Thorac Surg. 2007;84(5):1669-1673.

24. Schussler O, Dermine H, Alifano M, et al. Should we change antibiotic prophylaxis for lung surgery? postoperative pneumonia is the critical issue. Ann Thorac Surg. 2008;86(6):1727-1733.

25. Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis. 2004;38(12):1706-1715.

26. Deschamps C, Bernard A, Nichols FC, III, et al. Empyema and bronchopleural fistula after pneumonectomy: factors affecting incidence. Ann Thorac Surg. 2001;72(1):243-247; discussion 248.

27. Darling GE, Abdurahman A, Yi QL, et al. Risk of a right pneumonectomy: role of bronchopleural fistula. Ann Thorac Surg. 2005;79(2):433-437.

28. Ng T, Ryder BA, Maziak DE, Shamji FM. Treatment of postpneumonectomy empyema with debridement followed by continuous antibiotic irrigation. J Am Coll Surg. 2008;206(3):1178-1183.

29. West D, Togo A, Kirk A. Are bronchoscopic approaches to post-pneumonectomy bronchopleural fistula an effective alternative to repeat thoracotomy? Interact Cardiovasc Thorac Surg. 2007;6:547-550.

30. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(3 Pt 1):818-824.

31. Slinger PD. Acute lung injury after pulmonary resection: more pieces of the puzzle. Anesth Analg. 2003;97(6):1555-1557.

32. Licker M, Fauconnet P, Villiger Y, Tschopp JM. Acute lung injury and outcomes after thoracic surgery. Curr Opin Anaesthesiol. 2009;22(1):61-67.

33. Jeon K, Yoon JW, Suh GY, et al. Risk factors for post-pneumonectomy acute lung injury/acute respiratory distress syndrome in primary lung cancer patients. Anaesth Intensive Care. 2009;37(1):14-19.

34. Schilling T, Kozian A, Huth C, et al. The pulmonary immune effects of mechanical ventilation in patients undergoing thoracic surgery. Anesth Analg. 2005;101(4):957-965, table of contents.

35. Girard TD, Bernard GR. Mechanical ventilation in ARDS: a state-of-the-art review. Chest. 2007;131(3):921-929.

36. Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;371(9607):126-134.

37. Jain R, DalNogare A. Pharmacological therapy for acute respiratory distress syndrome. Mayo Clin Proc. 2006;81(2):205-212.

38. Meduri GU, Marik PE, Chrousos GP, et al. Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature. Intensive Care Med. 2008;34(1):61-69.

39. Tang BM, Craig JC, Eslick GD, Seppelt I, McLean AS. Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med. 2009;37(5):1594-1603.

40. Blot F, Melot C. Indications, timing, and techniques of tracheostomy in 152 French ICUs. Chest. 2005;127(4):1347-1352.

41. Pratt L. Tracheotomy: historical review. Laryngoscope. 2008;118:1597-1606.

42. Clec’h C, Alberti C, Vincent F, et al. Tracheostomy does not improve the outcome of patients requiring prolonged mechanical ventilation: a propensity study. Crit Care Med. 2007;35(1):132-138.

43. De Leyn P, Bedert L, Delcroix M, et al. Tracheotomy: clinical review and guidelines. Eur J Cardiothorac Surg. 2007;32(3):412-421.

44. Veelo D, Dongelmans D, Phoa K, Spronk P, Schultz M. Tracheostomy: current practice on timing, correction of coagulation disorders and peri-operative management—a postal survey in the Netherlands. Acta Anesthesiol Scand 2007;51:1231-1236.

45. Sear JW. Kidney dysfunction in the postoperative period. Br J Anaesth. 2005;95(1):20-32.

46. Ben Nun A, Altman E, Best LA. Extended indications for percutaneous tracheostomy. Ann Thorac Surg. 2005;80(4):1276-1279.

47. Perfeito J, Sterse da Mata C, Forte V, Carnaghi M, Tamura N, Leao L. Tracheostomy in the ICU: is it worthwhile? J Brasileiro de Pneumologia. 2007;33(6):687-690.

48. Urschel JD, Antkowiak JG, Takita H. Acute renal failure following pulmonary surgery. J Cardiovasc Surg (Torino). 1994;35(3):215-218.

49. Kheterpal S, Tremper KK, Heung M, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology. 2009;110(3):505-515.

50. Frumento RJ, Logginidou HG, Wahlander S, Wagener G, Playford HR, Sladen RN. Dexmedetomidine infusion is associated with enhanced renal function after thoracic surgery. J Clin Anesth. 2006;18(6):422-426.

51. Karzai W, Schmidt J, Jung A, Kroger R, Clausner G, Presselt N. Delayed emergence and acute renal failure after pneumonectomy: tumor emboli complicating postoperative course. J Cardiothorac Vasc Anesth. 2009;23(2);219-222.

52. Golledge J, Goldstraw P. Renal impairment after thoracotomy: incidence, risk factors, and significance. Ann Thorac Surg. 1994;58(2):524-528.

53. Sharrock NE, Beksac B, Flynn E, Go G, Della Valle AG. Hypotensive epidural anaesthesia in patients with preoperative renal dysfunction undergoing total hip replacement. Br J Anaesth. 2006;96(2):207-212.

54. Lameire N, Vanholder R, Van Biesen W. Loop diuretics for patients with acute renal failure: helpful or harmful? JAMA. 2002;288(20):2599-2601.

55. Bainbridge D, Cheng DC, Martin JE, Novick R. NSAID-analgesia, pain control and morbidity in cardiothoracic surgery. Can J Anaesth. 2006;53(1):46-59.

56. Lee A, Cooper MG, Craig JC, Knight JF, Keneally JP. The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on postoperative renal function: a meta-analysis. Anaesth Intensive Care. 1999;27(6):574-580.

57. McCrory CR, Lindahl SG. Cyclooxygenase inhibition for postoperative analgesia. Anesth Analg. 2002;95(1):169-176.

58. Tumlin JA, Finkel KW, Murray PT, Samuels J, Cotsonis G, Shaw AD. Fenoldopam mesylate in early acute tubular necrosis: a randomized, double-blind, placebo-controlled clinical trial. Am J Kidney Dis. 2005;46(1):26-34.

59. Friedrich JO, Adhikari N, Herridge MS, Beyene J. Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Ann Intern Med. 2005;142(7):510-524.

60. Lauschke A, Teichgraber UK, Frei U, Eckardt KU. “Low-dose” dopamine worsens renal perfusion in patients with acute renal failure. Kidney Int. 2006;69(9):1669-1674.

61. Brienza N, Malcangi V, Dalfino L, et al. A comparison between fenoldopam and low-dose dopamine in early renal dysfunction of critically ill patients. Crit Care Med. 2006;34(3):707-714.

62. Sampath S, Moran JL, Graham PL, Rockliff S, Bersten AD, Abrams KR. The efficacy of loop diuretics in acute renal failure: assessment using Bayesian evidence synthesis techniques. Crit Care Med. 2007;35(11):2516-2524.

63. Ho KM, Sheridan DJ. Meta-analysis of frusemide to prevent or treat acute renal failure. BMJ. 2006;333(7565):420.

64. Mehta RL, Pascual MT, Soroko S, Chertow GM. Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA. 2002;288(20):2547-2553.

65. Chrysostomou C, Schmitt CG. Dexmedetomidine: sedation, analgesia and beyond. Expert Opin Drug Metab Toxicol. 2008;4(5):619-627.

66. Sun P, Ma D, Hossain M, Sanders RD, Maze M. Dexmedetomidine provides renoprotection against renal ischaemia-reperfusion injury in mice. Anesthesiology. 2008;109:A420.

67. Billings FTt, Chen SW, Kim M, et al. Alpha-2-adrenergic agonists protect against radiocontrast-induced nephropathy in mice. Am J Physiol Renal Physiol. 2008;295(3):F741-F748.

68. Brar SS, Shen AY, Jorgensen MB, et al. Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: a randomized trial. JAMA. 2008;300(9):1038-1046.

69. Amar D. Prevention and management of perioperative arrhythmias in the thoracic surgical population. Anesthesiol Clin. 2008;26(2):325-335, vii.

70. Roselli EE, Murthy SC, Rice TW, et al. Atrial fibrillation complicating lung cancer resection. J Thorac Cardiovasc Surg. 2005;130(2):438-444.

71. Amar D, Goenka A, Zhang H, Park B, Thaler HT. Leukocytosis and increased risk of atrial fibrillation after general thoracic surgery. Ann Thorac Surg. 2006;82(3):1057-1061.

72. Cardinale D, Colombo A, Sandri MT, et al. Increased perioperative N-terminal pro-B-type natriuretic peptide levels predict atrial fibrillation after thoracic surgery for lung cancer. Circulation. 2007;115(11):1339-1344.

73. Vaporciyan AA, Correa AM, Rice DC, et al. Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients. J Thorac Cardiovasc Surg. 2004;127(3):779-786.

74. Foroulis CN, Kotoulas C, Lachanas H, Lazopoulos G, Konstantinou M, Lioulias AG. Factors associated with cardiac rhythm disturbances in the early post-pneumonectomy period: a study on 259 pneumonectomies. Eur J Cardiothorac Surg. 2003;23(3):384-389.

75. Bobbio A, Caporale D, Internullo E, et al. Postoperative outcome of patients undergoing lung resection presenting with new-onset atrial fibrillation managed by amiodarone or diltiazem. Eur J Cardiothorac Surg. 2007;31(1):70-74.

76. Amar D, Zhang H, Roistacher N. The incidence and outcome of ventricular arrhythmias after noncardiac thoracic surgery. Anesth Analg. 2002;95(3):537-543, table of contents.

77. Mayson SE, Greenspon AJ, Adams S, et al. The changing face of postoperative atrial fibrillation prevention: a review of current medical therapy. Cardiol Rev. 2007;15(5):231-241.

78. Amar D, Roistacher N, Burt ME, et al. Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy. Ann Thorac Surg. 1997;63(5):1374-1381; discussion 1372-1381.

79. Amar D. Post-thoracotomy atrial fibrillation. Cur Opin Anesthesiol. 2007;20(1):43.

80. Ahn HJ, Sim WS, Shim YM, Kim JA. Thoracic epidural anesthesia does not improve the incidence of arrhythmias after transthoracic esophagectomy. Eur J Cardiothorac Surg. 2005;28(1):19-21.

81. Crawford TC, Oral H. Cardiac arrhythmias: management of atrial fibrillation in the critically ill patient. Crit Care Clin. 2007;23(4):855-872, vii.

82. Karamichalis JM, Putnam JB, Jr, Lambright ES. Cardiovascular complications after lung surgery. Thorac Surg Clin. 2006;16(3):253-260.

83. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114(7):e257-e354.

84. Amar D, Roistacher N, Rusch VW, et al. Effects of diltiazem prophylaxis on the incidence and clinical outcome of atrial arrhythmias after thoracic surgery. J Thorac Cardiovasc Surg. 2000;120(4):790-798.

85. DeWitt CR, Waksman JC. Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. Toxicol Rev. 2004;23(4):223-238.

86. Sedrakyan A, Treasure T, Browne J, Krumholz H, Sharpin C, van der Meulen J. Pharmacologic prophylaxis for postoperative atrial tachyarrhythmia in general thoracic surgery: evidence from randomized clinical trials. J Thorac Cardiovasc Surg. 2005;129(5):997-1005.

87. Bradley D, Creswell LL, Hogue CW, Jr, Epstein AE, Prystowsky EN, Daoud EG. Pharmacologic prophylaxis: American College of Chest Physicians guidelines for the prevention and management of Postoperative atrial fibrillation after cardiac surgery. Chest. 2005;128(2 Suppl):39S-47S.

88. Connolly SJ, Cybulsky I, Lamy A, et al. Double-blind, placebo-controlled, randomized trial of prophylactic metoprolol for reduction of hospital length of stay after heart surgery: the beta-Blocker Length Of Stay (BLOS) study. Am Heart J. 2003;145(2):226-232.

89. Devereaux PJ, Yang H, Yusuf S, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839-1847.

90. Fleisher LA, Poldermans D. Perioperative beta blockade: where do we go from here? Lancet. 2008;371(9627):1813-1814.

91. Tamargo J, Delpon E, Caballero R. The safety of digoxin as a pharmacological treatment of atrial fibrillation. Expert Opin Drug Saf. 2006;5(3):453-467.

92. Gheorghiade M, Adams KF, Jr, Colucci WS. Digoxin in the management of cardiovascular disorders. Circulation. 2004;109(24):2959-2964.

93. Mitchell LB, Exner DV, Wyse DG, et al. Prophylactic oral amiodarone for the prevention of arrhythmias that begin early after revascularization, valve replacement, or repair: PAPABEAR: a randomized controlled trial. JAMA. 2005;294(24):3093-3100.

94. Zimetbaum P. Amiodarone for atrial fibrillation. N Engl J Med. 2007;356(9):935-941.

95. Van Mieghem W, Coolen L, Malysse I, et al. Amiodarone and the development of ARDS after lung surgery. Chest. 1994;105(6):1642-1645.

96. Toraman F, Karabulut EH, Alhan HC, et al. Magnesium infusion dramatically decreases the incidence of atrial fibrillation after coronary artery bypass grafting. Ann Thorac Surg. 2001;72(4):1256-1261; discussion 1252-1261.

97. Thielmann M, Neuhauser M, Marr A, et al. Lipid-lowering effect of preoperative statin therapy on postoperative major adverse cardiac events after coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2007;134(5):1143-1149.

98. Patti G, Chello M, Candura D, et al. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia after cardiac surgery) study. Circulation. 2006;114(14):1455-1461.

99. Amar D, Zhang H, Park B, Heerdt PM, Fleisher M, Thaler HT. Inflammation and outcome after general thoracic surgery. Eur J Cardiothorac Surg. 2007;32(3):431-434.

100. Amar D, Zhang H, Heerdt PM, Park B, Fleisher M, Thaler HT. Statin use is associated with a reduction in atrial fibrillation after noncardiac thoracic surgery independent of C-reactive protein. Chest. 2005;128(5):3421-3427.

101. Healey JS, Baranchuk A, Crystal E, et al. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol. 2005;45(11):1832-1839.

102. Coleman CI, Makanji S, Kluger J, White CM. Effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on the frequency of post-cardiothoracic surgery atrial fibrillation. Ann Pharmacother. 2007;41(3):433-437.

103. Maisel WH, Epstein AE. The role of cardiac pacing: American College of Chest Physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery. Chest. 2005;128(2 Suppl):36S-38S.

104. Dunning J, Treasure T, Versteegh M, Nashef SA. Guidelines on the prevention and management of de novo atrial fibrillation after cardiac and thoracic surgery. Eur J Cardiothorac Surg. 2006;30(6):852-872.

105. Hassan SA, Hlatky MA, Boothroyd DB, et al. Outcomes of noncardiac surgery after coronary bypass surgery or coronary angioplasty in the Bypass Angioplasty Revascularization Investigation (BARI). Am J Med. 2001;110(4):260-266.

106. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. J Am Coll Cardiol. 2007;50(17):1707-1732.

107. Collet JP, Himbet F, Steg PG. Myocardial infarction after aspirin cessation in stable coronary artery disease patients. Int J Cardiol. 2000;76(2-3):257-258.

108. Collet JP, Montalescot G, Blanchet B, et al. Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes. Circulation. 2004;110(16):2361-2367.

109. Chassot PG, Delabays A, Spahn DR. Perioperative antiplatelet therapy: the case for continuing therapy in patients at risk of myocardial infarction. Br J Anaesth. 2007;99(3):316-328.

110. Reed CE, Spinale FG, Crawford FA, Jr. Effect of pulmonary resection on right ventricular function. Ann Thorac Surg. 1992;53(4):578-582.

111. Slinger P. Update on anesthetic management for pneumonectomy. Curr Opin Anaesthesiol. 2009;22(1):31-37.

112. Chae EJ, Seo JB, Kim SY, et al. Radiographic and CT findings of thoracic complications after pneumonectomy. Radiographics. 2006;26(5):1449-1468.