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 (see Figures 19–1 to 19–4).³

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

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

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

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

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.

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

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.