Thoracic Anesthesia

PART 2

Thoracic Anesthesia Practice


CHAPTERS


 

19
Anesthesia for Lung Transplantation

Wendy L. Pabich
Mihai V. Podgoreanu


Key Points

1. Preoperative respiratory assessment should include pulmonary function tests, ventilation/perfusion (V/Q) scans, and an arterial blood gas. The patient’s ability to tolerate one-lung ventilation can be determined by V/Q scan, and if both lungs are being transplanted the lung with less perfusion should be transplanted first.

2. Cardiac function should be assessed with particular attention paid to evaluation of right ventricular (RV) function. Elevated pulmonary arterial pressures can precipitate RV failure, and may greatly influence the decision to attempt transplantation with or without CPB.

3. The newly transplanted lung should be ventilated with as low a FiO2 as possible, ideally room air, to minimize damage by oxygen free radicals. Barotrauma to the new lung can be avoided by keeping inspiratory pressures less than 25 cm H2O and PEEP less than 10 cm H2O.

4. Hemodynamic instability or refractory hypoxemia may deem cardiopulmonary bypass necessary and typically occurs at one of three critical phases of the operation: (a) after pulmonary artery clamping during the first transplant; (b) after perfusing the first allograft but before starting the second lung; and, (c) after pulmonary artery clamping during the second transplant.



Case Vignette


The patient is a 45-year-old man who is listed for bilateral sequential lung transplantation due to idiopathic pulmonary fibrosis. He has undergone pulmonary rehabilitation and now continuously uses oxygen at the rate of 4 L/min. His PA pressures are 68/25. Recently his respiratory symptoms have worsened significantly and he has thus been moved to the active transplant list.

He has mild esophageal reflux disease and is otherwise well.

He takes famotidine and albuterol by mouth and is on an epoprostenol (Flolan) infusion.

Vital signs: 105/60, HR 95, SpO2 on 4 L/min oxygen 91%.

Laboratory values are normal.


BACKGROUND

Providing anesthesia for lung transplantation (LT) is considered by many to be the coup de maître of cardiothoracic anesthesia. Some say it involves the most complex manipulation of cardiothoracic physiology, particularly when cardiopulmonary bypass (CPB) is not used. Many anesthetic considerations for LT are in fact similar to those for other thoracic and cardiovascular procedures; however, this chapter highlights the unique clinical elements involved in perioperative management of LT recipients and the implications for their future anesthetic care. Because LT is performed infrequently in clinical practice, typically with little opportunity for preoperative preparation and consultation, a thorough understanding of end-stage lung disease pathophysiology and its specific pharmacological and technical implications is required to minimize associated major morbidity and mortality.

Indications for LT include 4 primary diagnostic groupings of end-stage pulmonary disease: (1) obstructive lung disease (chronic obstructive pulmonary disease [COPD], with or without alpha-1-antitrypsin deficiency, due to chronic bronchitis and/or emphysema, and bronchiectasis); (2) restrictive lung disease (idiopathic pulmonary fibrosis [IPF], sarcoidosis, obliterative bronchiolitis); (3) cystic fibrosis or immunodeficiency disorders (hypogammaglobulinemia); and (4) pulmonary vascular disease (idiopathic pulmonary arterial hypertension, Eisenmenger syndrome). In 2007, patients with IPF comprised the single largest group of adult LT recipients (27%), while emphysema was the most common diagnosis among LT recipients before 2007.1,2 Cystic fibrosis (CF) remains the principal indication for LT in pediatric patients older than 5 years, whereas in infants and preschool children the most common indications are idiopathic pulmonary arterial hypertension and congenital heart disease (seeFigures 19–1 to 19–4).3

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Figure 19–1. Pretransplant chest computed tomography of a patient with panlobular emphysema.

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Figure 19–2. Pretransplant chest computed tomography of a patient with cystic fibrosis. Note the cystic bronchiectasis with peribronchial wall thickening.

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Figure 19–3. Pretransplant chest radiograph of a patient with extensive bilateral pulmonary fibrosis. The patient underwent bilateral lung transplantation.

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Figure 19–4. Pretransplant chest radiograph of a patient with extensive pulmonary fibrosis, right greater than left. The underwent single right lung transplantation.

The 2005 implementation of the Lung Allocation Score (LAS) system, designed to assign a relative priority score to distribute cadaveric lungs to appropriate recipients, marks the most significant change in LT in the last decade. The LAS includes measures for urgency of need for transplant and posttransplant likelihood of survival, with higher scores representing higher urgency and a greater potential transplant benefit. Adoption of the LAS system has resulted in substantial reductions in both the number of active wait-listed lung candidates and median waiting time.2 Despite the fact that over time candidates with increasingly higher LAS scores have been receiving transplants, overall recipient survival has continued to improve by era (currently 79% at 1 year; 52% at 5 years), although this has largely been driven by improvements in 1-year survival. Recipient age has also increased consistently over time, most strikingly in patients older than 60 years (35% in 2008).1 The total number of pediatric LTs also appears to be increasing (93 procedures in 2007), the majority of which are being performed in adolescent patients (12-17 years old).

The recipient’s underlying disease process is the major determinant in selecting 1 of the 4 types of transplant procedures generally available: single-lung transplantation, bilateral lung transplantation, transplantation of lobes from living related donors, and combined procedures.

Single-Lung Transplantation

Patients whose transplanted lung will receive most of the ventilation and perfusion, as in the case of IPF or COPD, typically undergo single-lung transplantation (SLT). Single-lung transplantation extends the limited supply of donor organs to more patients and is characterized by a decreased need for CPB, but it provides less lung function as a buffer for late complications. The procedure, which involves a pneumonectomy of the native lung followed by implantation of the lung allograft is most often performed via a standard posterolateral thoracotomy. Typically, the lung that is more affected (see Figure 19–1) based on preoperative ventilation/perfusion (V/Q) scanning or the site contralateral to a previous thoracotomy is chosen for transplant. If both lungs are equally affected, some centers will preferentially transplant the left lung because it is technically easier to access the pulmonary veins and main stem bronchus on the left side.

Bilateral Lung Transplantation

Bilateral orthotopic lung transplantation (BOLT) is most often performed as two sequential SLTs. The principal indication for BOLT is suppurative lung disease that would result in contamination of the transplanted lung by the native lung (such as in CF or generalized bronchiectasis), although the proportion of BOLT has risen for each of the 4 major indications since 1994. The number of bilateral lung transplantations being performed has steadily increased in past decades, from a trivial percentage of total lung transplants in 1990 to more than two-thirds of the 2708 LTs performed in 2007.1 Bilateral sequential SLT procedures can be performed with or without CPB. The decision of whether or not to attempt the procedure without CPB depends upon disease severity, but emergent CPB may be required if the patient develops refractory hypoxemia during one-lung ventilation (OLV) or experiences hemodynamic instability during pulmonary artery clamping or surgical manipulation. The most commonly used surgical approach for this procedure is via a single clamshell incision (transverse thoracosternotomy), but sequential thoracotomies or median sternotomy may occasionally be used as well. A less invasive surgical approach involving limited bilateral thoracotomy guided by thoracoscopic visualization has yielded positive early results, does not preclude the use of CPB and may particularly benefit patients with impaired wound healing due to long-term glucocorticoid therapy.4

Double-lung transplantation (en bloc) using a tracheal anastomosis, although still performed, is falling out of favor because it requires CPB and because the tracheal anastomosis is more susceptible to postoperative complications than the bronchial anastomoses in BOLT.5

Living Donor Lung Transplantation

In some selected recipients, LT may be performed using lung tissue from 2 blood-group-compatible living donors. Use of CPB is optional for SLT unless significant pulmonary hypertension or severe hypoxemia is present. For a bilateral lobe transplant, the donor lobes are implanted in a manner similar to a bilateral sequential cadaveric LT, except that CPB is always used to avoid passing the entire cardiac output through a single donor lobe. Living donor-related lobar lung transplantation is only performed in specialized centers. Although it is thought to be more beneficial in the pediatric population, the numbers of these transplants have fallen dramatically in recent years.3 It should be reserved for patients who are judged unlikely to survive until cadaveric lungs become available. However, intubated patients and those undergoing retransplantation have a significantly high risk of mortality.6 There is an ongoing debate about the ethical issues concerning transplantation from living donors, particularly regarding the added risk of potential complications in the donor patients, although several reports suggest that donor morbidity has been minimal.7 Table 19–1 outlines the potential advantages and disadvantages of living donor LT.

Table 19–1. Potential Advantages and Disadvantages for Living Donor Lung Transplant

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Combined Procedures

Combined heart-lung transplantation is typically reserved for patients with idiopathic pulmonary arterial hypertension, unrepairable congenital heart disease (with Eisenmenger syndrome), or left ventricular failure (see Figure 19–5). It is performed much less frequently than other kinds of transplantation (only 86 procedures in 2007)1 and obviously requires use of CPB.

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Figure 19–5. Pretransplant chest radiograph of a patient with repaired congenital heart disease but with progressive heart failure. Note the cardiomegaly, prominent right heart border and enlarged pulmonary arteries consistent with known pulmonary arterial hypertension. A heart-lung transplant is planned due to the combination of cardiac and pulmonary disease.

The increased age of acceptable LT recipients has resulted in a higher incidence of concurrent cardiac disease. In well-selected patients, LT may thus be performed simultaneously with valvular or coronary artery bypass graft surgery. The cardiac procedure is usually performed first regardless of whether CPB is planned for LT, and offers a survival benefit compared to LT alone.8

Combined lung/liver transplantation may be beneficial in some patients with coexisting severe lung and liver disease, which can be present in CF. This particular procedure provides a unique challenge to the anesthesiologist with regard to fluid management because the goal of such management in lung transplants typically involves restricting fluids to minimize pulmonary edema, whereas liver transplants are associated with massive transfusion and administration of fluids. The organs are typically transplanted in tandem, with the LT occurring first.

PREOPERATIVE EVALUATION AND PREPARATION

Most LT patients undergo an extensive evaluation to define their clinical condition and suitability for LT before being listed as potential transplant recipients. Preoperative workups should be easily accessible to the anesthesia team because surgery most often occurs at odd hours. Because LT candidates may experience long waits, it is important to assess any potential changes in baseline functional status since the patient’s last workup by the transplant service. Anesthetic evaluation should include such routine details as fasting status, previous response to anesthesia, cardiopulmonary assessment, and airway examination, followed by a discussion about anesthetic management and risks, including death and intraoperative recall and use of postoperative thoracic epidural analgesia.9

The preoperative respiratory assessment should at least include pulmonary function tests, V/Q scans, and an arterial blood gas measurement. The patient’s ability to tolerate OLV can be determined by V/Q scan. If both lungs are being transplanted, the more diseased lung (with less perfusion) should be transplanted first. The likelihood of requiring CPB increases if the non-operative lung has little perfusion or the room air partial pressure of oxygen (PaO2) is less than 45 mm Hg.

Cardiac function should be assessed with particular attention to evaluating right ventricular (RV) function. Preoperative tests should include an electrocardiogram, a 24-hour Holter monitor, a transthoracic echocardiogram, and left and right cardiac catheterization (to evaluate coronary disease, left and right ventricular function, and pulmonary circulation). Pulmonary arterial pressures (PAP) may be elevated in severe lung disease and can precipitate RV failure when they exceed two-thirds of systemic arterial pressures. This can greatly influence the decision to attempt transplantation with or without CPB. Mean pulmonary arterial (PA) pressures greater than 40 mm Hg and pulmonary vascular resistance greater than 5 Wood units predict an increased likelihood that CPB will be necessary.

Patients with severe pulmonary hypertension may develop right-to-left intracardiac shunting and should be evaluated for a history of embolic events. Understandably, particular care should be taken to avoid injecting any intravascular air in these patients. The presence of a patent foramen ovale or any other intracardiac shunts should be routinely assessed preoperatively by transthoracic echocardiogram in all LT candidates. Severe pulmonary hypertension can also cause vocal cord dysfunction due to impingement of the left recurrent laryngeal nerve by the enlarged pulmonary arteries, placing these patients at an increased risk for aspiration.

Patients with CF may have associated hepatic dysfunction; therefore, liver function tests should be obtained. Many CF patients also experience malabsorption of fat-soluble vitamins from the gastrointestinal tract. Consequently, preoperative coagulation studies should be obtained, and vitamin K should be administered as necessary. Furthermore, CF and bronchiectasis patients are likely to be resistant or allergic to antibiotics and may require preoperative desensitization.

The need for additional preoperative laboratory tests should be dictated by the individual patient’s disease. Preoperative hematocrit, white blood cell count, and chemistry panels should be obtained and corrected as necessary. Polycythemia may be present secondary to chronic hypoxemia, requiring special laboratory assessment. Blood group, histocompatibility antigens, and panel-reactive antibodies are routinely assessed to assist with donor matching, perioperative immunosuppression, additional preoperative treatments to reduce alloreactivity (plasmapheresis, intravenous immunoglobulin), and overall risk stratification.

Immunosuppressive induction and antibiotics may be started preoperatively, with the patient receiving the first doses orally. Preoperative sedation should be used cautiously because benzodiazepines and narcotics can exacerbate preexisting hypercarbia and hypoxia, particularly in patients with COPD. Conversely, preoperative anxiety and the accompanying catecholamine surge may worsen RV dysfunction in patients with pulmonary hypertension.5

In addition to the American Society of Anesthesiologists standard monitors, Table 19–2 lists suggested monitoring for LT to enable quick diagnosis and treatment of expected intraoperative hemodynamic and respiratory instability during one-lung ventilation (OLV) and pulmonary artery clamping.

Table 19–2. Suggested Intraoperative Monitors for Lung Transplant

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Large-caliber peripheral venous access should be obtained to treat intravascular volume losses as they occur. Care should be taken to ensure that access remains unobstructed with standard arm positioning for a clamshell incision; antecubital lines are prone to obstruction. Central line placement before anesthetic induction may prove difficult in patients unable to lie supine without sedation and/or worsening of baseline hypoxia. Strict asepsis should be respected with all line placement given the anticipated immunosuppression in these patients. Blood products should be cross-matched and available in the operating room. At our institution, placement of thoracic epidural catheters for postoperative analgesia is deferred until the patient arrives to the intensive care unit postoperatively.

Although the recipient is prepared for surgery as soon as a potential donor has been identified, induction of anesthesia is postponed until the donor lungs have been inspected and approved by the retrieval team and confirmed with the transplant coordinator.

INTRAOPERATIVE MANAGEMENT

Lung transplant candidates are usually critically ill with severe cardiopulmonary disease, yet the nature of the transplant operation is to induce further dysfunction with OLV, surgical manipulation, intravascular volume loss, sudden change in ventilatory function, severe acid-base abnormalities, and difficulties with oxygenation.10 Several periods are particularly critical in the intraoperative management of LT and will be discussed in greater detail below. These include induction of anesthesia, initiation of positive pressure ventilation, establishment and maintenance of OLV, pulmonary artery clamping and unclamping, and reperfusion of the pulmonary allograft. However, unanticipated problems often occur, and the anesthesiology team must be ready to react quickly and treat sudden changes in multiple physiological functions. Full cardiopulmonary bypass (CPB) support and a perfusion team are always on standby throughout the procedure.

Anesthetic Induction and Maintenance

Both denitrogenation and achievement of an amnestic end-tidal level of inhaled anesthetic are significantly slower in patients with end-stage lung disease due to increased V/Q mismatch and thus may prolong the period of vulnerability to recall at the beginning of the procedure.5

Rapid-sequence or modified rapid-sequence induction is usually indicated, as the procedure is typically urgent and patients may not have been fasting. Agents with minimal cardiac depressant effects are preferred, including etomidate and narcotics, but hypnotic agents, including ketamine, propofol, and midazolam, have also been used.11 Attention to hemodynamic changes with slow titration of induction agents is critical for a safe induction, but profound hypotension and ventricular depression can occur and is counteracted with small fluid boluses, inotropes, and pulmonary vasodilators.5 Patients with end-stage lung disease are in general at least moderately hypovolemic due to preoperative diuretics and increased insensible losses from the increased work of breathing. Although intraoperative fluid restriction is of paramount importance in the overall management of LT, as the resultant pulmonary edema can compromise allograft function,12 judicious preoperative fluid boluses may attenuate the hemodynamic effects of anesthetic induction and positive-pressure ventilation. In patients with severe pulmonary hypertension, induction should begin only with an available surgeon in the operating room and typically after femoral arterial cannulation to facilitate emergent CPB in the case of cardiac arrest.9

Once the position is verified via fiberoptic bronchoscopy, rapid airway control should be accomplished using either a double-lumen endotracheal tube (DLT) or a single-lumen tube with an endobronchial blocker, depending on institutional practices. A DLT is preferred at our institution because it facilitates better lung isolation, suctioning, application of continuous positive airway pressure (CPAP) to the non-ventilated lung, and permits independent lung ventilation. Further, a left-sided DLT is preferred because the position of the bronchial lumen should not interfere with surgical access to the left main stem bronchus. A single-lumen tube is sufficient in situations when use of CPB is planned electively.

Anesthesia can be maintained with an inhaled agent such as isoflurane, although, as stated above, end-stage lung disease may impact the uptake of inhaled agents. Total intravenous anesthesia may be more predictable, and it better preserves hypoxic pulmonary vasoconstriction that is otherwise blunted with inhaled anesthetics. Moreover, to avoid cardiac depression from volatile anesthetics, many centers rely on a narcotic-based “cardiac anesthetic,” which provides improved hemodynamic stability. One note of caution concerning narcotic-based techniques is that initiation of CPB, removal of the native lung, and reperfusion of the transplanted lung are all critical in the pharmacokinetic profiles of narcotics. All narcotics are subject to a decrease in plasma concentration when CPB is initiated. Fentanyl concentrations decrease the most due to binding to the CPB circuit. The lungs also provide a significant “first pass” effect on narcotics, with approximately 60% of sufentanil and 75% of fentanyl undergoing uptake.13 The implication of this pharmacokinetic profile is that when the native lung is removed, a significant dose of narcotic is also removed. Plasma levels of narcotics will further decrease upon reperfusion of the newly transplanted lung due to the same “first pass” effect. At a time of hemodynamic instability associated with allograft reperfusion, volatile agents may be below the minimum alveolar concentration required to produce amnesia, and a reduction in plasma concentration of narcotics may increase susceptibility to intraoperative awareness or recall. As such, narcotics should be redosed and used in combination with benzodiazepines, volatile agents (if tolerated), or propofol infusion for maintenance of anesthesia.5 Paralysis will be necessary throughout the procedure and long-acting neuromuscular blocking agents are ideal.

Positioning for the procedure depends upon the type of operation performed and can determine the optimal choice for sites of invasive monitoring. Single-lung transplantation can be done either with the patient supine or in lateral decubitus. Bilateral lung transplantation is often performed with the patient in the supine position with the arms above the head for transsternal bilateral thoracotomy. Once the patient is positioned, airway access can become difficult and intravenous and arterial lines in the upper extremities can be easily occluded. Pressure points should be carefully checked and padded.

After intubation, a transesophageal echocardiography (TEE) probe should be inserted. This allows for direct assessment of dynamic changes in cardiac function (particularly in the right ventricle), preload optimization, evaluation for intracardiac shunts (eg, patent foramen ovale), intracardiac air/assisting with de-airing maneuvers, calculation of PA pressures, and postoperative assessment of vascular anastomotic sites for stenosis, torsion, or kinking. Continuous intraoperative TEE monitoring allows for early recognition of critical events and informs therapeutic interventions.14

Intraoperative normothermia should be aggressively maintained unless CPB is planned electively because hypothermia can worsen pulmonary hypertension and coagulopathy and delay extubation.

Mechanical Ventilation

Initiation of positive-pressure ventilation in patients with end-stage lung disease can be associated with many complications. High airway pressure in patients with restrictive lung disease and in those with COPD-associated blebs can lead directly to barotrauma (pneumothorax, pneumomediastinum, or air leakage through bronchial anastomoses) or indirectly to volutrauma (lung hyperinflation and circulatory collapse). The risk for these complications can be minimized by adequate selection of ventilator settings based on the patient’s preoperative values because most of these patients have adapted to levels outside the normal range. Tolerating such “permissive hypercapnia” reduces the adverse effects of mechanical ventilation, although it should be noted that hypercapnia can exacerbate pulmonary hypertension.9 Although the general benefits of limiting tidal volume and airway pressures have been proven in all thoracic surgical patients including LT patients, based on current evidence, there does not appear to be a clear advantage of one ventilation mode over another (ie, volume-controlled versus pressure-controlled ventilation).15

Patients who have severe airflow obstruction are also at increased risk of dynamic hyperinflation during positive pressure ventilation. This results in residual positive end-expiratory pressure (auto-PEEP) and can lead to severe hypotension and even cardiac arrest caused by lung overinflation that results in reduced venous return and direct compression of the heart. In such patients, ventilation settings should maximize expiratory time, avoid extrinsic PEEP, and even include periods of circuit disconnect/apnea if hypotension persists.9

Maneuvers to improve oxygenation during OLV include increased fraction of inspired oxygen (FiO2), titrating PEEP, intermittent reinflation, CPAP to the nonventilated lung, recruitment maneuvers, and fiberoptic-guided suctioning of secretions. Irreversible hypoxemia that develops during OLV can be managed by clamping the pulmonary artery to eliminate the shunt through the deflated, unventilated lung. Further refractory hypoxemia, hemodynamic instability, and/or compromised surgical access at this stage are indications for CPB, which will be discussed later.

Surgical dissection during OLV may be complicated by adhesions from previous thoracic surgery or vascular collaterals. The phrenic and vagus nerves must be safeguarded, and the recurrent laryngeal nerve must be avoided on the left side.

Pulmonary Artery Clamping

As discussed above, clamping of the pulmonary artery that supplies the nonventilated lung improves V/Q matching, oxygenation, and ABG values. The ensuing significant increase in PA pressures is usually well tolerated in patients with normal baseline values but may quickly precipitate RV dysfunction and failure in patients with pre-existing pulmonary hypertension. This results in a vicious cycle—due to ventricular interdependence, RV dilation leads to impaired left ventricular (LV) filling, LV failure, RV ischemia, and further dysfunction. Signs of RV dysfunction include elevated right atrial pressures and new or worsened tricuspid valve regurgitation associated with a dilated and hypocontractile RV on intraoperative TEE. Treatment involves judicious use of pulmonary vasodilators and inotropes. Vasodilators such as nitroglycerin, sodium nitroprusside, and nicardipine can be used to treat pulmonary hypertension, although care must be taken to avoid causing simultaneous systemic hypotension. Gas exchange and V/Q mismatch can generally be worsened by administration of vasodilators through blunting of hypoxic pulmonary vasoconstriction, although this is less of an issue in this setting, where the PA supplying the deflated lung is clamped. Inhaled nitric oxide (iNO) at concentrations up to 20 ppm is usually effective in decreasing the PAP and reducing the RV workload without negatively affecting the systemic circulation.

Right heart failure can be treated with inotropes such as epinephrine (0.02-0.1 mcg/kg/min), dopamine (2-10 mcg/kg/min), norepinephrine (0.05-0.2 mcg/kg/min), milrinone (0.375-0.5 mcg/kg/min), or a combination of agents. Fluid loading should be used cautiously because RV function may deteriorate rapidly. Initiation of CPB should be considered after adequate heparinization if the patient remains hemodynamically labile despite pharmacologic intervention.

Pulmonary Artery Unclamping and Reperfusion

Once the native lung is extracted and the donor lung implanted, three anastomoses are performed in their posterior-anterior anatomic sequence: bronchus, pulmonary artery, and pulmonary veins-left atrium. The ischemic period ends when the vascular clamps are removed, but arterial oxygenation will not improve until ventilation is resumed. The pulmonary artery should not be unclamped until ventilation of the newly transplanted lung is possible, as perfusion of the unventilated lung would cause profound hypoxia. The newly transplanted lung should be ventilated with as low an FiO2 as possible (ideally room air) to minimize damage by oxygen free radicals. Barotrauma to the new lung can be avoided by keeping inspiratory pressures below 25 cm H2O and PEEP below 10 cm H2O. In SLT recipients, it may be beneficial to ventilate the lungs independently, and the appropriate ventilators should be made available. If oxygenation is marginal, an alveolar recruitment maneuver can be performed. This procedure has been shown to effectively increase arterial oxygenation, promote lung homogeneity, and minimize shear forces. The recruitment strategy typically consists of pressure-controlled ventilation; an increase in inspiratory time to 50%; and a sequential increase in positive inspiratory pressure/PEEP to 40/20, held for 10 breaths, and returned to baseline, which usually includes a PEEP of 8 cm H2O. However, the hemodynamic effects of recruitment maneuvers can be significant and may be minimized if more selective lobar recruitment maneuvers are performed.15

Reperfusion injury results in increased alveolar-arterial gradients, poor lung compliance, and pulmonary edema. It may appear within minutes to hours after reperfusion. Limiting lung volumes and PEEP can lessen the risk of reperfusion injury and primary graft dysfunction (PGD). Methylprednisolone (500 mg) is administered at the time of each lung reperfusion to help prevent acute allograft rejection.

Although unclamping the pulmonary artery should decrease pulmonary vascular resistance and lessen RV afterload, RV dysfunction can persist if allograft perfusion is suboptimal. Moreover, unclamping can result in air emboli that can travel to the coronary circulation, pointing to the importance of thoroughly de-airing the pulmonary artery and left atrium upon completion of the pulmonary vein anastomoses. The right coronary artery is most likely to be affected due to its anterior location in the supine patient, leading to an increased likelihood of RV ischemia. Although these changes are usually transient, increased vasopressor and inotropic support may be necessary.

Intraoperative TEE is essential at this stage to assess ventricular function, assist with de-airing maneuvers, and thoroughly evaluate all pulmonary vascular anastomoses to identify any hemodynamically significant obstructions that require immediate repair. Unrecognized anastomotic stenoses or kinks could precipitate pulmonary venous congestion, elevated PAP, and further right heart dysfunction, as well as allograft dysfunction. Similarly, intraoperative bronchoscopy is performed at the end of the procedure to inspect the bronchial anastomotic sites for stenoses and areas of limited focal necrosis. The bronchial anastomosis has been the most vulnerable site for complications, primarily due to the disruption in bronchial blood supply to the donor lung such that the donor bronchus is dependent upon retrograde bronchial blood flow through the pulmonary circulation.

Cardiopulmonary Bypass

Although CPB is obligatory in pediatric recipients, patients with severe pulmonary vascular disease, and in bilateral living lobar LT and combined heart-lung transplant, the need for CPB in other patient categories has generally been difficult to predict preoperatively and varies with recipient disease (Table 19–3). Though rarely indicated in recipients with obstructive lung disease, several series have reported the use of CPB in 17% to 41% of patients with restrictive lung disease.16-18 In the case of SLT, preoperative pulmonary function tests and resting oxygenation have poor discriminatory capability, but preoperative hemodynamic profiles may be helpful. In particular, patients with severe pulmonary hypertension are more likely to require CPB. As discussed, pulmonary vascular resistance always increases with clamping of the pulmonary artery; a more severe increase is seen in patients with restrictive versus obstructive disease, but the need for CPB is ultimately determined by the degree of change in cardiac index. In patients with restrictive disease, CPB has usually been necessary if the reduction in cardiac index exceeded 1 to 1.5 L/min/m2.16,17

Table 19–3. Indications for Extracorporeal Assistance During Lung Transplantation

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Unlike SLT, in the case of adult bilateral lung transplantation, the preoperative hemodynamic profile is a poor predictor of need for CPB.16,18 Rather, CPB is triggered by hemodynamic instability or refractory hypoxemia typically occurring at 1 of 3 critical phases of the operation: (1) after PA clamping during the first transplant; (2) after perfusing the first allograft but before starting the second lung; and (3) after PA clamping during the second transplant. In several series of patients without pulmonary vascular disease, CPB was instituted in 23% to 32% cases at one of these time points.16,18

Although elective use of CPB for BOLT in patients with COPD does not appear to have adverse effects on early graft function or clinical outcomes,19 these conclusions should not be extrapolated to SLT, to diseases other than COPD, or to different operative scenarios, such as emergent use of CPB.

POSTOPERATIVE MANAGEMENT

Early postoperative care focuses on ventilatory support, hemodynamic management, immunosuppression, detection of early rejection, and prevention or treatment of infection. If independent lung ventilation is not necessary, the DLT should be exchanged intraoperatively for a single-lumen endotracheal tube at the end of the procedure after suctioning the stomach to prevent any aspiration of gastric contents into the newly transplanted lung(s). The patient is transferred intubated to the intensive care unit where mechanical ventilation continues with minimal FiO2 and low-level PEEP. Exceptions are patients undergoing SLT for COPD or emphysema, where PEEP should not be used because it tends to overinflate the more compliant lung.20

With an overall incidence variously reported between 10% and 25%, postoperative respiratory failure resulting from PGD is responsible for more than half of early mortality following LT. Recipient, donor, and therapy-related risk factors for PGD include: recipient body mass index greater than 25 kg/m2 and female sex; primary or secondary pulmonary hypertension; idiopathic or secondary pulmonary fibrosis: donor age greater than 45 years and donor head trauma; SLT; increased ischemic time; intraoperative hemorrhage or cardiovascular complications; and use of CPB in patients with severe RV dysfunction.21-23 Ischemia-reperfusion injury is the main cause of PGD, with an incidence between 10% and 15%. To standardize the definition of PGD, a grading system has been proposed based on the PaO2/FiO2 ratio,24 which strongly correlates with poor early outcomes.25 Management of PGD is supportive, including independent lung ventilation and, in extremis, extracorporeal membrane oxygenation (ECMO). The role of inhaled nitric oxide (iNO) in improving hemodynamics and ventilation-perfusion matching and reducing the incidence of ischemia-reperfusion injury and pulmonary edema in LT remains controversial.26-28 The usual recommended concentration of iNO is 10 to 20 ppm. Methemoglobinemia is a potential side effect of iNO and occurs in about 6% of patients. Nebulized epoprostenol (prostacyclin) has been proposed as an alternative to iNO with comparable results.26,29

ECMO is reserved for severe, life-threatening primary graft failure (selected grade 3) in patients who do not respond to maximal conventional treatment and a trial of iNO.30-33 ECMO is a supportive measure to optimize gas exchange during lung function recovery while avoiding the detrimental effects of aggressive mechanical ventilation and persistent severe hypoxemia, and it has been associated with a survival rate of 42% in one series of patients with PGD.31 Available evidence suggests that ECMO should be initiated within 24 hours of onset of severe PGD and should not be prolonged given the substantial morbidities associated with its use: bleeding, renal failure, neurologic problems, hypotension, and sepsis.31 When the patient does not require hemodynamic support, veno-venous ECMO should be used instead of veno-arterial ECMO. Retransplantation for PGD is associated with very poor outcomes and is usually avoided.

Some degree of pulmonary edema almost invariably occurs after LT due to increased vascular permeability and severed lymphatic drainage. To minimize lung water, pulmonary capillary wedge pressure should be kept as low as possible; ie, it should be kept consistent with adequate urine output, oxygen delivery, and systemic blood pressure. Combinations of vasopressor, inotropic, and diuretic drugs should be used as needed to achieve this balance. In a retrospective study, elevated central venous pressure (>7 mm Hg) was positively correlated with duration of mechanical ventilation and higher rates of intensive care unit utilization, hospitalization, and 2-month mortality.34 It remains unclear, though, whether a strategy aimed at maintaining central venous pressure <7 mm Hg would improve outcomes in LT or whether a high central venous pressure was merely a marker of severity of illness. A recent study reported a positive association between volume of intraoperative colloid (predominantly gelatin) and early lung allograft dysfunction, independent of known confounders such as use of CPB, pulmonary artery, and central venous pressures.12 The optimal choice of fluid for volume replacement post-LT remains unknown. Our institution favors the use of blood products to achieve a target hemoglobin level of 10 mg/dL, supplemented with colloid instead of crystalloid solutions if further volume replacement is necessary.

Differential diagnosis of persistent postoperative hypotension following LT includes the usual culprits (intravascular volume depletion, blood loss, acute myocardial injury, dysrhythmias, and auto-PEEP), but a high index of suspicion should be maintained for tension pneumothorax, pneumopericardium, and pericardial tamponade, which have all been described in LT patients.35 Excessive postoperative bleeding is particularly troublesome in patients undergoing heart-lung transplant and is usually due to the aortopulmonary collaterals in the chest wall and adhesions from previous thoracic surgeries, as well as impaired liver function from longstanding congestion and poor RV function. Myocardial injury can result from intraoperative coronary artery air embolism, cardiac manipulation during the procedure, postoperative coronary artery embolism of small thrombi from the left atrial pulmonary venous anastomosis, or preexisting coronary artery disease. Atrial dysrhythmias (primarily flutter and fibrillation) are common postoperatively in LT recipients (40%) and respond to conventional treatments, but methods to prevent their occurrence have not been studied.36 Pulmonary embolism should also be included in the differential diagnosis because LT recipients, like other patients undergoing major surgery, are at increased thromboembolic risk.37

Following completion of a V/Q scan and a surveillance bronchoscopy in the early postoperative period, patients without any evidence of ventilatory or hemodynamic instability quickly progress toward weaning from mechanical ventilation. Exceptions are recipients with pulmonary hypertension, especially after SLT, in whom ventilation, sedation, and neuromuscular blockade are usually continued for 1 to 2 days because of their extremely labile oxygenation and hemodynamics during this period.

Weaning from mechanical ventilation can be hindered if the phrenic or recurrent laryngeal nerves have been injured during the procedure. The reported incidence of diaphragmatic paralysis following LT ranges from 3% to 30%, with even higher incidence following heart-lung transplantation (40%).38,39 A low threshold for tracheostomy is adopted in these patients to facilitate weaning from mechanical ventilation and usually results in longer duration of hospitalization but it is not associated with serious long-term sequelae.39

A thoracic epidural catheter for postoperative pain control is placed once the potential need for CPB and heparinization has passed and after appropriate coagulation status has been confirmed. At our institution, the catheter is placed while the patient is still intubated in lateral decubitus. Analgesia can be obtained using epidural narcotics with or without local anesthetics.

Extreme care must be taken throughout the postoperative period to avoid aspiration, which can be catastrophic in these patients. Since both gastroesophageal reflux and gastroparesis are common in LT recipients, early aggressive surgical treatment of reflux (fundoplication) is routinely performed at our institution and has been shown to prevent chronic allograft dysfunction.40

Immunosuppression in LT recipients is typically started preoperatively while induction doses of cyclosporine and/or azathioprine and boluses of methylprednisolone (500-1000 mg) are given intraoperatively prior to reperfusion of each graft. Immunosuppression is continued postoperatively usually using a 3-drug maintenance regimen consisting of cyclosporine or tacrolimus, azathioprine or mycophenolate mofetil, and prednisone. Transbronchial lung biopsies have a high sensitivity for detecting acute rejection or Cytomegalovirus (CMV) infection in LT recipients but are inconsistent in diagnosing chronic rejection.

Broad-spectrum antibiotics are routinely continued perioperatively in order to suppress any potential pathogens isolated from either donor or recipient. Absent specific culture results, empiric coverage with 1.5 g of cefuroxime taken 3 times daily is initiated until cultures become available. If fungal species are isolated in early specimens, empiric fluconazole (for Candida species) and either itraconazole or nebulized amphotericin B (for Aspergillus species) should be added to the regimen.

ANESTHESIA AFTER LUNG TRANSPLANTATION

Important physiologic changes occur following LT, some of them specific to the type of procedure or to the pretransplant lung pathology. General physiologic changes after LT include denervation of the transplanted lung associated with bronchial hyperresponsiveness; impaired cough reflex and mucociliary clearance, which increase the risk of aspiration and respiratory infections; and a constellation of gastroesophageal disorders including oropharyngeal dysphagia, gastroesophageal reflux, and gastroparesis. As discussed above, diaphragmatic paralysis may occur in up to 30% of transplant recipients, most commonly in those receiving heart-lung transplants. Implications for future anesthetics include the potential for cardiac denervation, increased infectious risk, immunosuppressant toxicity and medication interaction, as well as the potential for airway strictures, aspiration, and difficulty in clearing secretions (Table 19–4).

Table 19–4. Anesthetic Considerations for Nonthoracic Procedures after Lung Transplantation

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40. Cantu Er, Appel JZr, Hartwig MG, et al; J. Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease. Ann Thorac Surg. 2004;78(4):1142-1151; discussion.