Perioperative Care of the Surgical Patient: Heart, Lung, and Mediastinum Procedures

This chapter consists of three major sections, each of which addresses different aspects of the perioperative management of cancer patients requiring thoracic surgery. Over the last decade, the field of thoracic surgery has advanced in many ways, for example, the rise of minimally invasive surgery, the introduction of immunotherapy drugs, and a growing trend toward standardization of care with enhanced recovery protocols. With these advancements, this chapter is designed to provide recommendations for anesthesiologists to refine their knowledge base of thoracic procedures.

Anesthetic Management for Thoracic Procedures in the Cancer Patient

Lung cancer remains the leading cause of cancer-related deaths in the United States. Recent cancer data have estimated a total of 239,320 new cases of lung cancer each year and 161,250 deaths resulting from lung cancer in the United States in 2010. The most common modifiable risk factors influencing the development of lung cancer include cigarette smoking, occupational exposure (i.e., asbestos, arsenic, beryllium silica, and diesel fumes), diet, and ionizing radiation. While there are several risk factors for lung cancer, cigarette smoking is linked to 90% of lung cancer deaths. ^, Public health campaigns and physician intervention remain the most effective strategies for promoting smoking cessation. In recent years, there has been a growing effort to encourage early screening among high-risk patients. In 2013, the National Lung Screening Trial (NLST) demonstrated a 20% reduction in mortality with low-dose computed tomographic (LDCT) screening, and the guidelines recommend annual LDCT for high-risk patients. ^, As more patients undergo screening, we expect higher detection rates and a growing need for surgical intervention.

Over the last decade, advances in surgical techniques, along with the development of newer immunotherapy agents, have both prolonged survival and improved postoperative outcomes. These advances have introduced new challenges in the perioperative management. In this chapter, we discuss the important elements of preoperative assessment with attention to diagnosis and emerging therapies used in the management of lung cancer. We provide recommendations for intraoperative management during open and minimally invasive thoracic surgeries. We conclude with a discussion on postoperative management to reduce morbidity and mortality after lung resection.

Oncologic Management of Lung Cancer

A clear understanding of the clinical features, staging, and treatment is important to optimize the perioperative care of the lung cancer patient. Lung cancer is classified into two major categories: non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC and SCLC account for 85% and 15% of all lung cancers, respectively. There are three major subtypes of NSCLC, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Among all lung cancers, adenocarcinoma remains the most common type of lung cancer, with an incidence of 40%.

With a confirmed diagnosis, medical oncologists utilize the TNM staging system ( Fig. 22.1 ) to devise a suitable treatment plan.

Fig. 22.1, American Joint Committee on Cancer: Lung Cancer Staging 7th ed.

It is paramount for anesthesiologists to become familiar with chemotherapy agents and emerging therapies that medical oncologists use in the management of NSCLC and SCLC.

Until recently, chemotherapy and surgery remained the mainstay of management. Platinum-based chemotherapy with carboplatin or cisplatin is the mainstay for NSCLC and SCLC. Platinum-based chemotherapy has been used in combination with other classes of chemotherapy agents to allow for a durable immune response against cancer cells. The disadvantage of many chemotherapeutic agents, however, is the failure to discriminate between normal and cancer cells, thus leading to major systemic toxicities ( Table 22.1 ).

Table 22.1

Chemotherapy for Non–small and Small Cell Lung Cancer

Chemotherapy	Drugs	Common Side Effects
Alkylating agent (platinum-based)	Carboplatin Cisplatin	Nausea, vomiting, anemia, neutropenia, neurotoxicity, nephrotoxicity
Taxanes	Paclitaxel Docetaxel	Ventricular dysfunction, arrhythmias, pneumonitis, peripheral neuropathies, fluid retention, cutaneous toxicity
Anthracyclines	Doxorubicin Adriamycin	Cardiotoxicity (pericarditis, left ventricular dysfunction, heart failure)
Vinca alkaloids	Vincristine Vinblastine Vinorelbine	Myelosuppression, peripheral neuropathy, myalgias, rare weakness

Cancer immunotherapy has emerged as a new therapy, and these drugs direct the immune system to exclusively target tumor cells, thereby minimizing the harmful effects of systemic chemotherapy. Immunotherapy for lung cancer encompasses a broad class of drugs, including:

Immune checkpoint inhibitors
Chimeric antigen receptor (CAR) -T cells
Monoclonal antibodies
Nonspecific immunotherapy
Cancer vaccines

Each class of drugs has a specific mechanism to harness the immune system against tumor cells and their mechanism of action, as detailed in Table 22.2 .

Table 22.2

Immunotherapy for Lung Cancer

Immunotherapy	Mechanism of Action	Example of Drugs
Immune checkpoint inhibitors	Monoclonal antibodies target specific receptor-ligand pathways on T cells.	Nivolumab Durvalumab Pembrolizumab Atezolizumab
CAR-T cells	T cells are removed from the patient and genetically modified to express specific chimeric antigen receptors. Modified cells are cloned and given back to the patient to elicit an immune response.	PD-L1 CAR-T cells (currently under investigation) ^a
Monoclonal antibodies	Antibodies targeting specific antigens (growth factors).	Cetuximab (EGF) Bevacizumab (VEGF) Erlotinib (VEGF) Gefitinib (EGFR)
Nonspecific immunotherapies	No specific targets. Use of cytokines to boost immune system or slow angiogenesis.	IL-2 Interferon α & β
Cancer vaccines	Exposure to tumor antigens activates memory T cells and B cells.	CIMAvax Epidermal Growth Factor vaccine ^a

CAR-T cells , Chimeric antigen receptor T cells; EGF , epidermal growth factor; EGFR , EGF receptor; IL, interleukin; PD-L1, programmed-death ligand 1; VEGF , vascular epidermal growth factor.

^a No FDA approval.

Preoperative Evaluation

Thoracic surgical patients often present with complex medical histories and require comprehensive assessment to elicit pertinent medical history. Preoperative assessment of thoracic surgical patients should be divided into three major components: (a) an assessment of pulmonary function, (b) evaluation of comorbidities and major risk factors, and (c) the development of a strategy for optimization.

The preoperative assessment of pulmonary function should include a thorough physical examination along with pertinent tests and imaging to assess respiratory mechanics, gas exchange, and cardiopulmonary interaction. During the physical examination, an assessment of general appearance, muscle wasting, neck circumference, digit clubbing, cyanosis, respiratory rate and pattern, respiratory effort during conversation, and movement provide important information about the patient’s pulmonary status. Symptoms of cough (i.e., frequency), sputum production, dyspnea with and without activity, and recent pulmonary infections can reveal the severity of pulmonary disease.

Pulmonary function tests (PFTs) provide useful information regarding respiratory mechanics and gas exchange. Specific measurements from the PFT correlate with poor postoperative outcomes. The most valid test for postthoracotomy respiratory complications is the predicted postoperative FEV ₁ . The FEV ₁ is a measurement of the volume of air expelled from a person’s lung in 1 s. The predicted postoperative FEV ₁ (ppoFEV ₁ ) is calculated by determining the amount of functional lung remaining after lung resection. A simple approach to calculating the postoperative FEV ₁ is using the following formula : ppoFEV ₁ % = preoperative FEV ₁ % × (1 − % functional lung tissue removed/100). ppoFEV ₁ is used primarily for risk stratification. A ppoFEV ₁ value <40% has consistently been associated with an increased risk of respiratory complications. The diffusing capacity for carbon monoxide (Dlco) is another measurement from the PFTs that can predict postoperative outcomes. Dlco represents the gas exchange capacity across the alveolar-capillary membrane. Similar to FEV ₁ , the predicted postoperative Dlco can be calculated as: ppoDlco % = preoperative Dlco% × (1 − % functional lung tissue removed/100).

Brunelli et al. demonstrated that the assessment of Dlco and ppoDlco was predictive of postoperative morbidity and respiratory complications, even in the presence of normal airflow. ^, Of these parameters, a low Dlco is one of the strongest predictors of postoperative pulmonary complications, whereas FEV ₁ is not an independent predictor at all. Some investigators argue that the Dlco should be used regardless of the FEV ₁ .

An additional benefit of PFTs is the ability to demonstrate the presence of reactive airway disease, which can improve with bronchodilators. The use of bronchodilators is warranted in patients with a favorable response to bronchodilators in PFTs. A cardiopulmonary exercise test (CPET) may be performed to assess oxygen uptake as well as cardiopulmonary reserve and is notably a better predictor of postoperative pulmonary complications than resting cardiac and pulmonary function tests alone. A maximum oxygen consumption (Vo _2max ) <10 mL/kg/min is associated with a postoperative mortality rate of 4% after thoracic surgery and a cutoff value of 20 mL/kg/min is strongly recommended for pneumonectomy.

Further investigation with special imaging studies is suggested for large pulmonary resections (bilobectomy and pneumonectomy). The use of a ventilation/perfusion lung scan (V/Q scan) provides detailed information about the distribution of perfusion to both lungs. The scan is achieved with the inhalation of radioactive xenon along with the injection of technetium-labeled macroaggregates, and the percentage of radioactivity taken up by each lung correlates with the contribution of that lung to overall function. FEV ₁ can also be determined from a V/Q scan and a predicted postoperative FEV ₁ value can be calculated from these.

Imaging plays an important role in the preoperative assessment of endobronchial invasion and the involvement of vascular structures. Chest radiography is typically performed as the initial imaging modality. This imaging modality provides an assessment of irregularities in the lung parenchyma, pleural effusions, and mediastinal shift. CT scans provide detailed information about the lung parenchyma (i.e., presence of bullae), the presence of airway compression, and/or endobronchial lesions. A review of multiple imaging modalities can assist in developing a concrete anesthetic plan.

A major component in the preoperative evaluation is preparing a risk-reduction strategy based on the patient’s comorbidities and risk factors to prevent postoperative complications. Beyond pulmonary evaluation, an assessment of cardiac history should be performed. Perioperative cardiovascular risk factors should be assessed and evaluated with further testing, if required. Patients with good functional capacity (>4 metabolic equivalents [METS]) do not require further testing. Patients with poor functional capacity (<4 METS) and/or a known history of ischemic heart disease or heart failure should undergo a pharmacologic stress test. The results of the stress test will determine whether coronary revascularization is necessary.

Other pathologic conditions associated with increased perioperative risks, that can be treated and optimized while awaiting surgery include anemia, malnutrition, frailty, chronic obstructive pulmonary disease, alcohol consumption, and active smoking. ^, Anemia and malnutrition are common among cancer patients, and the correction of these derangements can significantly improve clinical outcomes. The underlying causes of anemia should be investigated and appropriately treated. Oral iron supplementation and the use of erythropoietin may benefit specific populations but are not without risk. In most cases, immune-enhancing nutritional supplements may be sufficient to address anemia and malnutrition if initiated in advance. Additionally, preoperative smoking cessation and inspiratory muscle training are encouraged to optimize pulmonary function prior to surgery. A comprehensive review of modifiable and nonmodifiable risk factors should be performed to optimize perioperative planning.

Intraoperative Management

The intraoperative management of lung cancer patients continues to present a unique set of challenges for anesthesiologists. The use of protective ventilation strategies, analgesia, and judicious fluid management is essential to permit fast and functional recovery after surgery. In this section we discuss intraoperative management with special attention to airway management, ventilation strategies, analgesia, and fluid management.

Monitoring

Thoracic surgery requires the use of standard ASA monitors and adequate intravenous access prior to anesthesia induction. Large-bore intravenous access is required, and a central venous catheter (CVC) should be strongly considered in patients with poor peripheral access to ensure adequate fluid resuscitation. The use of invasive monitoring depends on the extent of lung resection and the presence of significant comorbidities. An arterial line is generally indicated for major anatomic lung resections (i.e., lobectomy, bilobectomy, and pneumonectomy). An arterial line is highly recommended in patients with a significant history of cardiac or pulmonary disease (i.e., history of myocardial ischemia or congestive heart failure), regardless of the extent of lung resection. An arterial line permits the measurement of dynamic indices to assess fluid responsiveness. In thoracic surgery, the interpretation of dynamic indices may alter with changes in intrathoracic pressure with an open chest and chest insufflation. Transesophageal echocardiography (TEE) is a valuable imaging modality that can be combined with dynamic indices from the arterial line to provide additional information on fluid status and ventricular function in patients with significant coronary artery disease and/or low ejection fractions.

Airway Management

Airway management for thoracic surgery requires substantial planning prior to anesthesia induction. A thorough history and physical examination may predict the degree of difficulty in airway management. A history of head and neck cancer is common in lung cancer patients. Prior head and neck surgery and radiation can distort the airway anatomy, posing a challenge for airway management. The presence of a tracheostomy or a preexisting stoma may preclude the use of specific airway devices.

Double-lumen tubes are the preferred airway devices for one-lung ventilation (OLV) for thoracic surgery. Left- and right-sided double-lumen tubes are available but left-sided double-lumen tubes are preferred because the right upper lobe orifice remains unobstructed. Right-sided lumen tubes offer the advantage of an additional orifice to ventilate the right upper lobe but they can inadvertently obstruct the right upper lumen if not directly positioned. Anatomic variations of the right upper lobe bronchus contribute to the difficult positioning of a right-sided double-lumen tube. While the use of double-lumen tubes is common, there are clinical circumstances that prevent their use. Double-lumen tubes are relatively contraindicated in the following conditions :

A difficult airway
Preexisting stoma from tracheostomy
Tracheal narrowing
Distorted anatomy from an obstructing lesion in the airway
Limited mouth opening

Bronchial blockers are an alternative to the double lumen and should be considered in the clinical circumstances above. Bronchial blockers are used with a single-lumen tube and can be inserted on the inside or outside of the endotracheal tube depending on the size of the endotracheal tube. Bronchial blockers offer distinct advantages in the following clinical cases:

Pediatric patients (small airway)
Difficult airways (i.e., head and neck radiation, cervical spine injury)
A long surgical duration (i.e., esophagectomy) with the potential risk of postoperative ventilation, minimizing the loss of airway from an airway exchange
Patients unable to tolerate prolonged apnea (i.e., a ventilated ICU patient)

The disadvantages are the difficult placement, risk of displacement, slow collapse of the isolated lung, and inability to suction the operative lung. Both airway devices have advantages and disadvantages. The ultimate choice of a double-lumen tube compared to a bronchial blocker will depend on multiple factors, and the use of specific airway devices should be discussed with the surgeon prior to induction of anesthesia.

Induction and Maintenance

The choice of anesthetic drugs for induction and maintenance should decrease the stress response to surgery and allow for fast recovery times. The use of volatiles over an intravenous anesthetic in thoracic surgery is a contentious issue. Inflammatory markers are known to increase in the ventilated lung after the initiation of OLV but the evidence on whether the choice of volatile or intravenous agents contributes to inflammation during thoracic surgery remains unclear. Schilling et al. demonstrated the comparative effect of sevoflurane, desflurane, or propofol on patients undergoing OLV and found that patients receiving either desflurane or sevoflurane experienced lower levels of inflammatory markers in bronchoalveolar lavage (BAL) samples compared to those receiving propofol. ^, The use of desflurane and sevoflurane suppresses the local alveolar but not the systemic inflammatory response to OLV. Based on these findings, there is no clear advantage from a clinical standpoint, and the use of intravenous versus inhalation agents should be made at the discretion of the anesthesiologist.

Pain Management

Pain after thoracic surgery is one of the most severe types of postoperative pain. Inadequate pain relief can lead to immobility, ineffective breathing, and poor clearing of secretions, resulting in an increased incidence of postoperative atelectasis, pneumonia, and pulmonary embolism. Effective analgesia improves respiratory mechanics and increases the success of extubation after surgery. The use of regional anesthesia and opioid and non-opioid pharmacologic agents provides a diverse range of options for pain control. Epidural analgesia has long been established as the gold standard for pain management during thoracic surgery, and an epidural confers a variety of benefits. A major advantage of thoracic epidural analgesia (TEA) is the reduction of systemic opioids during surgery, which decreases the risk of opioid-induced respiratory depression. Respiratory depression suppresses the cough reflex and increases the risk of pulmonary infections due to retention of secretions. The risk of respiratory depression is low in the presence of an epidural catheter. Epidural analgesia provides effective pain relief and increases patient participation in controlled cough techniques. Potential complications of TEA include the development of a hematoma or abscess and should be carefully monitored during the postoperative period.

Although epidural catheter placement remains the gold standard for pain control in lung surgery, the use of peripheral nerve blocks is gaining increasing popularity for pain management, including paravertebral nerve blocks, serratus anterior plane (SAP) block, erector spinae plane (ESP) block, midtransverse process to pleura (MTP) block, and intercostal (ICB) nerve blocks. The benefit of peripheral nerve blocks is the ability to perform a unilateral block with minimal risk of bleeding. Of these nerve blocks, paravertebral nerve blocks have been well studied in the literature. When pain was compared between paraverterbral block (PVB) and TEA at rest and during coughing, results showed that there was a significant difference in favor of PVB up to 72 h after thoracotomy. Studies have consistently demonstrated that paravertebral nerve blocks are an effective alternative to epidural analgesia for postthoracotomy pain but with a more beneficial side effect profile. ^, A 2016 systematic review confirmed that PVB had a better minor complication profile than thoracic epidural including hypotension (8 studies, 445 participants; relative risk [RR], 0.16; 95% confidence interval [CI], 0.07–0.38, P < 0.0001), nausea and vomiting (6 studies, 345 participants; RR, 0.48; 95% CI, 0.30–0.75; P = 0.001), pruritus (5 studies, 249 participants; RR, 0.29; 95% CI, 0.14–0.59; P = 0.0005), and urinary retention (5 studies, 258 participants; RR, 0.22; 95% CI, 0.1–0.46, P < 0.0001). Paravertebral nerve blocks have also been described in pain management for minimally invasive thoracic surgery. However, serratus nerve blocks and erector spinae nerve blocks are emerging as suitable alternatives for minimally invasive thoracic surgery because these blocks are safe and easier to perform with distinct landmarks. Few studies on the use of ultrasound-guided serratus nerve blocks have demonstrated a significant reduction in intraoperative opioid consumption and emergence time compared to general anesthesia alone in patients who underwent video-assisted thoracic surgery (VATS) lobectomy. The literature on erector spinae blocks in thoracic surgery is limited, and more research is needed. Intercostal nerve blocks are not frequently performed in the preoperative setting but are easily performed by surgeons under direct visualization for thoracotomy and minimally invasive surgery in patients with major contraindications for neuraxial anesthesia. Finally, these newer fascial blocks can be reserved for use as a rescue block in the event of a conversion of a minimally invasive surgery to an open thoracotomy until an epidural can be placed safely in the postoperative period.

Besides the use of regional anesthesia, non-opioid adjuvants are favored to further minimize the use of opioids. The addition of dexmedetomidine and ketamine infusions enhances analgesia. Dexmedetomidine has been shown to reduce opioid consumption in patients after minimally invasive and open thoracic surgery. Lee et al. showed that pain scores, opioid consumption, the incidence of postoperative nausea and vomiting as well as emergence agitation were significantly reduced with the addition of a dexmedetomidine infusion during VATS. A recent randomized controlled study confirmed that the use of dexmedetomidine in conjunction with a thoracic epidural amplified its effect after open thoracotomy with a reduction in pain scores and total analgesic dose. Intravenous acetaminophen and ketorolac are routinely administered to reduce the use of opioids provided no renal and liver abnormalities are present. In summary, the management of pain in thoracic surgical patients requires a multifaceted approach with the concomitant use of opioids, nonopioid adjuvants, and regional anesthesia to ensure optimal pain control.

Ventilation Strategies

Pulmonary complications have been a leading cause of significant morbidity and mortality after thoracic surgery. Pulmonary complications include atelectasis, pneumonia, empyema, pulmonary embolism, bronchopleural fistulas, and acute respiratory failure. Many of these complications have declined with the use of antibiotic prophylaxis, improvements in analgesia, implementation of protective ventilation strategies, and postoperative chest physiotherapy. Among pulmonary complications, acute lung injury (ALI) remains high, with an incidence reported as 2%–7% in large cohort studies. The mortality associated with lung injury is reported to be as high as 50%. The causes of ALI are often multifactorial, with surgical trauma, ventilator-induced injury, and fluid overload identified as contributing factors.

Mechanical ventilation is consistently recognized as an important risk factor for perioperative ALI. Lung overinflation, hypoxia/hyperoxia with oxidative stress, and reperfusion injuries from mechanical ventilation increase the release of proinflammatory mediators contributing to alveolar injury. The use of protective ventilation is paramount to reducing the risk of complications after thoracic surgery. The use of lower tidal volumes, recruitment maneuvers, and the application of peak-end expiratory pressure (PEEP) have been widely recognized as core elements in protective ventilation for two-lung ventilation. It has long been established that protective lung strategies reduce pulmonary complications in nonthoracic surgery. Research on protective lung strategies for OLV has lagged, but significant advances have been made over the last decade.

The basic principles of protective ventilation strategies are to minimize barotrauma, atelectrauma, and biotrauma related to OLV. Licker et al. evaluated the impact of a protective lung strategy protocol using a combination of tidal volumes <8 mL/kg predicted body weight, inspiratory plateau pressures <35 cmH ₂ O, PEEP 4–10 cmH ₂ O, and the use of recruitment maneuvers on clinical outcomes. This study revealed a lower incidence of ALI in the protective ventilation group than in the conventional ventilation group (0.9% vs. 3.7%, P < 0.01). These findings provide a foundation for further research on OLV. Blank et al. demonstrated that the concomitant use of low tidal volumes and sufficient PEEP to prevent overdistension, atelectasis and decruitment protected the lung from iatrogenic injury. Within this study, the authors also explored the relationship between driving pressure and respiratory outcome.

Driving pressure is a surrogate for dynamic lung strain and can be defined as the difference between the plateau pressure of the airways at end-inspiration (P _PLAT,rs ) and PEEP. ^, Alternatively, driving pressure is calculated as ΔP = V _T /compliance of the respiratory system or lung. Blank et al. demonstrated that for every unit increase in driving pressure (∼ 1 cmH ₂ O), there was a 3.4% increase in the risk of major morbidity. The incidence of postoperative pulmonary complications was reported to be 5.5% in driving pressure-guided ventilation compared to 12.2% in patients with conventional protective ventilation during thoracic surgery. These research findings will change the current recommendations for protective lung ventilation and encourage anesthesiologists to use driving pressure-guided ventilation.

Special attention should be given to ventilator settings for specific patient populations. Cancer patients with prior exposure to bleomycin have a risk of lung injury during OLV. A higher Fio ₂ is often required to prevent hypoxemia during OLV, and anesthesiologists may need to tolerate a lower oxygen saturation with a lower Fio ₂ in patients on bleomycin. Patients with restrictive lung disease may require the addition of PEEP to reduce atelectasis and pulmonary shunting during OLV. In contrast, chronic obstructive pulmonary disease (COPD) may develop auto-PEEP during OLV, increasing the risk of hyperinflation and increased shunt. The presence of bulla within lung parenchyma may require the avoidance of nitrous oxide, ventilation at lower pressures and tidal volumes, increased expiratory time, and permissive hypercapnia. Permissive hypercapnia is generally well-tolerated and anesthesiologists should refrain from adjusting ventilator settings to normalize end-tidal CO ₂ . Wei et al. demonstrated that therapeutic hypercapnia during OLV not only improves respiratory function but also mitigates the OLV-related local and systemic inflammation in patients undergoing lung resection. Hypercapnia may not be safe in specific patient populations. Hypercarbia increases tachycardia, contractility, and systolic blood pressure, and decreases systemic vascular resistance, which could be detrimental to patients with a significant cardiac history. Therefore, a protective lung strategy during OLV should be carefully performed to minimize complications in patients with significant comorbidities.

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