Lung Transplantation

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69 Lung Transplantation

David Weill

Historical Perspective

Lung transplantation evolved from heart-lung transplantation as a method by which donor organs could be used more efficiently. Heart-lung transplantation was first performed in 1981 ¹ and was initially the procedure of choice for diseases that are now more commonly treated by transplant using either bilateral sequential lung transplantation or single-lung transplantation. The appeal of developing the isolated lung transplant technique was improvement in donor organ utilization. Specifically, by using each of the three thoracic organs available from a single donor (i.e., two lungs and a heart), donor organ utilization can be maximized while achieving acceptable outcomes.

The double-lung transplant procedure, originally accomplished by en bloc replacement using a tracheal anastomosis, was first performed in 1983 in Toronto. The bilateral procedure is now performed as a sequential transplant using bilateral bronchial anastomoses. The bilateral sequential technique, as compared with the en bloc tracheal anastomotic technique, has been associated with fewer airway anastomotic complications, likely as a result of the superior blood supply from retrograde pulmonary artery flow.

Single-lung transplantation was first described in 1986.² The advantage of the procedure is that it has allowed maximal donor utilization while being associated with good patient outcomes. The single-lung procedure has historically been accepted as the procedure of choice for common transplant indications such as emphysema and idiopathic pulmonary fibrosis and is currently performed as commonly as the bilateral procedure.³

Survival and Demographics

Worldwide, 1200 to 1400 patients receive a lung transplant each year. Despite the yearly increase in patients on the transplant waiting list (recently nearly 4000 patients), the number of transplant procedures performed each year has been relatively stable over the past several years (Figure 69-1).³ Significant discussion and research regarding methods to expand the donor pool are ongoing,⁴ but until strategies to increase lung donor procurement are actually employed, the number of transplants performed each year will likely remain stable.

Figure 69-1 Number of lung transplants reported by year.

(Adapted from the International Society for Heart and Lung Transplantation [http://ishlt.org/]).

Long-term survival after lung transplantation is limited by the development of the bronchiolitis obliterans syndrome (BOS), which is commonly referred to as chronic rejection. BOS, defined by declining spirometry below the best postoperative level achieved, is variable in time to onset but increases in frequency as duration post transplant lengthens. Unfortunately, the etiology of BOS remains elusive, but it likely involves both immune and nonimmune mechanisms, including frequent early acute rejection episodes, infection with cytomegalovirus (CMV), severe early postoperative lung injury, and donor factors. Largely because the mechanism of BOS is unknown, satisfactory treatment is currently unavailable.

Indications and Procedure Choice

Indications for lung transplant are listed in Table 69-1 according to the generally accepted procedure choice. Although there are many end-stage lung diseases that can potentially be amenable to lung transplantation, four diseases account for the vast majority of lung transplant recipients: emphysema (both cigarette-induced and due to alpha₁-antitrypsin deficiency), cystic fibrosis, primary pulmonary hypertension, and idiopathic pulmonary fibrosis.³ Contraindications to transplant include evidence of extrapulmonary disease such as significant kidney, liver, or cardiac disease; poor nutritional or rehabilitation status; recent or current malignancy; and a poor psychosocial profile.

TABLE 69-1 Lung Transplant by Procedure Type (in Order of Frequency)

Single-Lung Transplant	Double-Lung Transplant
Emphysema/chronic obstructive pulmonary disease (COPD)	Cystic fibrosis
Idiopathic pulmonary fibrosis	Emphysema/COPD
Alpha₁-antitrypsin deficiency	Alpha₁-antitrypsin deficiency
Re-transplant	Idiopathic pulmonary fibrosis
Primary pulmonary hypertension
Bronchiectasis

Generally the procedure of choice is the one that can be performed safely while utilizing the available donor organs most efficiently. Emphysema is the most common lung transplant indication and has consistently been associated with the best survival post transplant.³ While some controversy exists regarding the optimal procedure choice (single versus double) in this group of patients,⁵ most patients with emphysema who have undergone a lung transplant have received a single-lung transplant. Bilateral lung transplant has traditionally been reserved for suppurative lung diseases, such as cystic fibrosis, and other bronchiectatic disease where replacing as much infected lung tissue as possible is the primary goal. Patients with primary pulmonary hypertension generally receive a bilateral lung transplant because this prevents the potentially life-threatening situation that occurs when, in performing a unilateral transplant, nearly all cardiac output flows to the allograft, given its relatively lower vascular resistance compared to the native primary pulmonary hypertension lung. In the early transplant period when single lungs were transplanted for this indication, the result in most centers was profound unilateral pulmonary edema in the allograft.

Candidate Selection

Because of the rigors of a major thoracic surgery such as lung replacement, an extensive evaluation process occurs in all potential lung transplant recipients. The majority of the preoperative testing is directed toward excluding significant extrapulmonary disease, particularly those diseases that would lessen the chances of survival in the immediate postoperative period or make tolerance of the commonly used postoperative immunosuppression difficult. Occult coronary artery disease or malignancies are commonly uncovered as the evaluation proceeds, particularly in those patients who have significant cigarette-smoking histories. Other important goals of the evaluation process are to determine the likelihood of compliance with the complicated postoperative medical regimen and the existence of a solid support system to help with medical care once the patient leaves the hospital.

Waiting List Considerations

Time on Waiting List

Waiting times for lung transplant recipients are highly unpredictable and vary considerably geographically. Waiting list priority is strictly according to time, or “seniority,” on the list. Currently there is no waiting list status system, although there likely will continue to be significant efforts to give priority to those on the waiting list who are more ill and who are most likely to do well post transplant. Unfortunately, devising such a system for lung allocation is problematic, primarily owing to the lack of compelling data correlating likelihood of waiting list mortality among the various disease groups with the highest probability of survival after transplantation. At most centers, as the numbers of patients referred for transplant increase and the length of the waiting list increases, waiting times continue to lengthen, and the mortality rate for patients on the waiting list will increase as well.

Care of Patients on Waiting List

Management of patients on the lung transplant waiting list involves close interaction with the referring physician. Treatment is directed toward the underlying disease process and is not generally affected by the patient’s waiting list status. However, clinical activities that may affect transplant outcome should form prominent aspects of the medical care plan. For instance, enrollment and participation in a cardiopulmonary rehabilitation program is of paramount importance so waiting patients can develop or maintain the best cardiovascular fitness possible. Furthermore, weight management is often an important issue, and regular exercise can help avoid excessive weight gain, which is associated with poor outcomes after transplantation. Conversely, in patients with cystic fibrosis, weight maintenance can be achieved by regular consultation with nutritional support personnel familiar with patients in whom specific dietary needs exist. Other considerations requiring the attention of the transplant team include substantial increases in corticosteroid use, which although never definitively linked to poor outcomes post transplant, remain a theoretical concern in terms of bronchial anastomotic and wound healing. As lung transplant waiting lists grow at most centers, regular outpatient clinic visits to monitor patients on the waiting list will likely become more important so that clinical issues that may affect transplant success can be detected and addressed.

An important development in donor lung allocation occurred in 2005 with the institution of the Lung Allocation Score (LAS). Traditionally, lungs had been allocated using a time-based system governed by how long a patient had been on the lung transplant waiting list. However, the new LAS system is based on two factors: (1) expected mortality on the waiting list for a given patient and (2) expected survival following lung transplant. These two factors are influenced by a number of clinical parameters that are measured by individual transplant centers and used to assign a score. The highest scores are assigned to patients with relatively high waiting list mortality (due to severity of illness) and an adequate or better chance of survival following lung transplantation. Familiarity with this system is particularly important for the ICU physician, who may encounter a patient with a high urgency score.

Donor Criteria

The expansion of lung transplantation as a therapy for end-stage lung disease is not limited by the number of potential recipients but rather by the availability of suitable donor organs. The standard, or “classic,” lung donor criteria are well known, if not closely followed, among lung transplant practitioners. Although some of these criteria certainly make good sense (i.e., a clear chest radiograph, no bronchoscopic evidence of aspiration), nearly all the others are controversial, often ignored, and not based on convincing research data.⁴ The standard or classic lung donor criteria are listed in Table 69-2. Whereas certain geographic regions in the United States, some countries in Europe, and Australia have adopted more aggressive donor management strategies that have resulted in more donor lungs, many areas with lung transplant programs have fewer than expected lung donors.

TABLE 69-2 Standard Lung Transplant Donor Criteria

Age <55 years

ABO blood group compatibility

Clear chest radiograph

PaO₂ > 300 mm Hg on fractional inspired oxygen of 1.0 and positive end-expiratory pressure = 5 cm H₂O

Less than 20-pack-year smoking history

Absence of chest trauma

No aspiration or sepsis

Gram stain shows sputum sample free of bacteria, fungus, and significant number of white blood cells

Postoperative Care

Early postoperative care of lung transplant recipients can be divided into four general categories: (1) hemodynamic management, (2) respiratory management, (3) initiation of an immunosuppression regimen, and (4) infectious disease prophylaxis. Although many basic critical care principles apply to the care of lung transplant recipients, certain special considerations apply.

Hemodynamic Management

Fluid Administration

In the early postoperative period, proper fluid management may be the most important aspect of lung transplant care. Because the lymphatic drainage is disrupted during surgery, the transplanted lung has a propensity toward pulmonary edema, and this tendency is exacerbated by several conditions. First, owing to the procurement and reimplantation process, lung allografts suffer lung injury that is characterized by a diffuse capillary leak. This process, commonly referred to as ischemia-reperfusion injury or the reimplantation response, is usually mild and treated easily with supportive measures. This type of injury is characterized by diffuse pulmonary infiltrates radiographically and varying degrees of oxygenation impairment. In cases of severe injury, the pulmonary edema may be profound and require more aggressive measures such as independent lung ventilation, inhaled nitric oxide, and in extreme cases, extracorporeal membrane oxygenation (ECMO). Second, because intraoperative and early postoperative hypotension occurs commonly, overexuberant resuscitation with crystalloid solutions sometimes occurs and worsens the pulmonary edema. In some circumstances, hypotension or decreased urine output has been treated with starch solutions that, because of the large molecules they contain, results in passage of even greater amounts of fluid through the dilated capillary channels.

Especially in the first 72 hours after surgery, judicious use of intravenous fluids should be exercised, and efforts should be made to minimize fluid administration while maintaining adequate urine output. Use of pulmonary artery catheters is standard in the early postoperative care of transplant recipients and helps guide fluid management. Low central venous pressures (0–5 mm Hg) are the objective. Also, careful attention to input and output measurements provides additional information regarding volume status and is a reminder to administer only essential fluids. Generally, if renal function allows, an appropriate goal is to keep the patient 1 L negative for the first 3 postoperative days. This is best achieved with liberal use of loop diuretics and limiting extra fluid infusions.

Hypotension is common after lung transplantation. Not only is the patient (by design) intravascularly volume depleted but he or she is also receiving medications that cause hypotension: paralytics, sedatives, and analgesics. As a result, during the early postoperative period, patients typically will have episodes of hypotension that need to be addressed. Another important consideration is the effect of positive-pressure ventilation on the hemodynamics of a recent lung transplant recipient, particularly in those receiving a single-lung transplant for emphysema, owing to discrepancies in native lung and allograft compliance characteristics. These discrepancies, coupled with many recipients who not only have preoperative right ventricular dysfunction but also in whom postoperative intravascular volume depletion is intentionally achieved, can result in overinflation of the native lung. The concept of native lung hyperinflation is covered in more detail later in Ventilator and Respiratory Management, but one must consider whether early postoperative hypotension is best treated with ventilator management strategies that address overdistention of the native lung.

During periods where hypotension is found to be the result of profound intravascular volume depletion, fluid resuscitation should ideally include solutions that have the greatest tendency to remain in the vascular space and not simply migrate through the dilated pulmonary capillary channels. Colloid solutions such as albumin and packed red blood cells (RBCs) are ideal in this setting, as is replacement with clotting factors, particularly in the patient who has postsurgical consumption of these factors. Generally, in hypotensive patients with hemoglobin less than 10 g, use of packed RBCs is the treatment of choice. If a patient has very little postoperative bleeding, albumin infusions provide a temporary solution to intravascular volume depletion and can be given in conjunction with a loop diuretic to achieve a more brisk diuresis by transiently increasing effective renal blood flow. This effect is likely short lived but nonetheless provides a temporary increase in oncotic pressure that may lessen the development of pulmonary edema.

Ventilator and Respiratory Management

Initial care of early postoperative lung transplant recipients is directed toward ventilatory stability. Selection of a ventilator mode is generally dictated by the patient’s level of consciousness in the early postoperative period. For example, patients who are deeply sedated and/or under the influence of paralytic agents will obviously require full control of ventilation. The assist-control mode meets this requirement and is generally the preferred ventilatory modality in the immediate postoperative period. However, because an effort is made at many programs to extubate patients soon after surgery, use of less sedation and avoidance of paralytic agents are being employed. In such patients, less ventilatory control is required; patients usually do well with intermittent mandatory ventilation until early extubation is achieved. In patients with poor early graft function—for example, those with primary graft failure—ventilatory strategies that limit barotrauma are most efficacious and usually include pressure-control modalities. Certainly, with pressure-control ventilation, the use of sedation and paralytics is warranted, recognizing the potential deleterious neuromuscular effects of the latter when used in combination with high doses of corticosteroids and, in some instances, aminoglycoside antibiotics.

Native lung hyperinflation is more common when acute lung injury is present in the allograft, because the compliance discrepancy between the native lung and the allograft is even more pronounced. In this rare circumstance, independent lung ventilation using a double-lumen endotracheal tube can be initiated and can provide a means to ventilate the native lung and allograft according to the compliance characteristics of each.⁸ Independent lung ventilation outside of the operating room setting is associated with difficulties, particularly relating to endotracheal tube malpositioning and subsequent acute lobar or total lung collapse. Prevention and recognition of tube dislodgment requires constant surveillance, generally endoscopically, and is difficult unless personnel skilled with endoscopic endotracheal tube management skills are available on a continuous basis. Under these circumstances, diligent nursing care is required, including the administration of appropriate sedation and/or paralytic agents as well as the avoidance of routine repositioning of the patient.

Extubation

The extubation criteria in a lung transplant recipient are similar to those for other types of ventilated patients, particularly postsurgical patients. The patient should certainly be free of any lingering effects of the anesthetic and able to meet standard extubation criteria.⁹ As more experience with lung transplant management has developed, the decision to extubate is being made sooner, and some centers are even trying to extubate patients in the operating suite soon after surgery.¹⁰ Other programs, however, are reluctant to extubate this quickly because of concerns about delayed ischemia-reperfusion injury that would compromise allograft function or uncertainty about whether anesthetic medications have been completely cleared. Regardless, the dogma about leaving patients ventilated for a predetermined amount of time is now being challenged.

Chest Tube Management

Lung transplant recipients generally have two chest tubes per transplanted lung after surgery. A posterior tube is positioned to drain surgical bleeding, while the anterior tube evacuates air from the pleural space. The anterior tube is usually the first tube to be removed, given that in the absence of a bronchial anastomosis dehiscence, prolonged air leaks into the chest tube are uncommon. In fact, much of what is often mistakenly regarded as an air leak coming from the thorax is often air being introduced via the skin incision at the chest tube site. The posterior tube is removed when total 24-hour drainage from it is less than 150 mL. In a bilateral lung transplant, one should be cognizant that there is communication between the two hemithoraces because the pleural space has been opened. Because of this, chest tubes in bilateral transplants should be removed one tube per side at a time, with the anterior tubes being removed first followed by the posterior tubes.

Bronchoscopy After Lung Transplantation

The initial bronchoscopy after lung transplantation typically occurs in the operating room. The goal of the procedure is to assess the bronchial anastomoses and clear retained blood and sputum from the airway. Once the patient returns to the ICU, there is generally no need to bronchoscope the patient again in the first 24 postoperative hours unless complications develop. For instance, acute ventilatory insufficiency should prompt a bronchoscopic examination of the transplanted lung or lungs to make certain that acute mucus plugging of the airways is not accounting for the ventilatory insufficiency. Because of blood in the airway from the operation and caused by retained secretions from the native lung in single-lung recipients, mucus plugging is not rare. Serious complications from bronchoscopy early after surgery are rare. Transient oxygen desaturation during bronchoscopy is common but not generally harmful to the patient.

Immunosuppressive Regimens

Commonly Used Agents

Different transplant centers use different immunosuppressive regimens. However, general comments can be made about the more commonly used medications. Some programs use an induction strategy that involves the early administration of antibody, either directed directly at the lymphocyte (“lymphocyte-depleting”) or against interleukin receptor sites.¹¹ Most antibodies delivered are monoclonal and are better tolerated than the polyclonal antibodies used in the earlier transplant era. Regardless of which induction agent is preferred, a primary advantage of this strategy involves the early avoidance of nephrotoxic immunosuppressive agents (such as calcineurin inhibitors like cyclosporine or tacrolimus), while still providing adequate immunosuppression. This benefit is particularly important during the immediate postoperative period when renal insufficiency is common owing to purposeful intravascular volume depletion, use of nephrotoxic antibiotics and antiviral agents, and the effects of cardiopulmonary bypass (if used).

Most lung transplant programs use a three-drug immunosuppressive regimen. Corticosteroids are a central part of the early strategy, particularly during the period when adequate blood levels of the other immunosuppressive agents are not yet achieved. Because of the large corticosteroid doses used immediately after surgery, a variety of side effects can be expected. For example, fluid retention, systemic hypertension, and poor glucose control should be anticipated. Acute changes in mental status can also occur and clinically present as delirium or psychosis. Many of these effects can be eliminated by administrating the corticosteroids in a tapering fashion that aims to reduce the dosage as quickly as it is safe to do so.

Calcineurin inhibitors, such as tacrolimus and cyclosporine-based medications, comprise the second part of the three-drug strategy. These medications are typically administered intravenously early in the postoperative period for a number of reasons. First, lung transplant recipients are generally unable to take oral medications in the first 24 hours after surgery. Second, intravenous absorption is more predictable and avoids the rapid absorption seen early after oral administration, which is highly desirable in lung recipients in whom one would like to avoid nephrotoxic effects that could impede good urine output. Finally, because intravenous delivery is highly amenable to dose titration, turning off the intravenous drip in response to reduced urine output can quickly reestablish adequate urine output and helps achieve the goal of relative intravascular volume depletion that is critical in the early postoperative period. In the first 48 hours after surgery, a cyclosporine level equal to or less than 100 ng/mL and a tacrolimus level no greater than 5 is desirable. Once urine output is adequate and renal function is stable, drug dosage can be increased to achieve more therapeutic medication blood levels.

The third part of the immunosuppressive regimen involves the use of either azathioprine or mycophenolate mofetil. Azathioprine is generally well tolerated and is usually associated with mild, reversible side effects such as leukopenia, anemia, thrombocytopenia, and liver function test abnormalities. Mycophenolate mofetil, a newer agent, can also cause leukopenia and anemia. In some circumstances, the drug can lead to nausea, vomiting, and abdominal pain, all of which can be ameliorated by reducing the dose or temporarily stopping the drug. Monitoring of mycophenolic acid blood levels is being performed in some solid organ recipients,^12,¹³ but the precise target levels in lung transplantation are unknown.

Infectious Disease Prophylaxis

Infections after lung transplant are common and occur because of baseline immunosuppression, transmission from the donor, and ICU-related instrumentation (e.g., chest tubes, central venous catheters, endotracheal tubes). The antibiotic prophylactic regimen is directed toward preventing pneumonia, surgical site infections, and central line–related infections. Usually this goal is achieved through prophylactic use of late-generation cephalosporins and vancomycin. Because of their colonization with Pseudomonas species, patients with cystic fibrosis receive a third prophylactic antibiotic with good gram-negative coverage, such as an aminoglycoside.

Infection with CMV after transplant can lead to deleterious acute and chronic effects. Acutely, patients are at risk to develop CMV pneumonia which, in many instances, leads to severe morbidity and mortality. CMV syndrome, caused by CMV replication in the bloodstream, is heralded by the onset of malaise, fever, nausea, and vomiting. Furthermore, many believe that CMV infection (even asymptomatic) can lead to more long-term sequelae such as chronic allograft dysfunction (BOS).¹⁴

To prevent both the acute and chronic consequences of CMV infection, many programs have adopted an aggressive CMV prophylactic protocol. The more aggressive protocols include combination therapy using both ganciclovir and CMV hyperimmune globulin.¹⁵ The duration of therapy is dependent on CMV serology status of the donor and the recipient and is outlined in Table 69-3. Other less aggressive strategies are also used and, although less expensive and associated with less treatment-associated toxicity, likely lead to an increased incidence of CMV-related diseases.

TABLE 69-3 CMV Prophylaxis Protocol

	Recipient Positive	Recipient Negative
Donor Positive	6 wk GCV* (2 wk IV and 4 wk PO)	12 wk GCV* (6 wk IV, PO)
CMV-IG 3 doses (1 dose every 2 wk)	CMV-IG^† 7 doses in 6 wk
Donor Negative	No prophylaxis used

CMV IG, cytomegalovirus hyperimmune globulin; GCV, ganciclovir; IV, intravenous; PO, per os (oral).

* Intravenous dose 5 mg/kg q 12 h adjusted for creatinine clearance.

^† 150 mg/kg within 72 h post transplant, then every 2 weeks for 4 doses, then 100 mg/kg every 4 weeks for 2 additional doses

Prophylactic use of antifungal agents is controversial and varies among centers.¹⁶ There are single-center studies that have demonstrated a reduction in invasive fungal disease after instituting a fungal prophylactic regimen.¹⁷ Programs that do use antifungal prophylaxis generally use medications in the azole class or aerosolized amphotericin.^18,¹⁹ While there have been no conclusive studies in lung transplant to support an antifungal prophylactic strategy, some lung transplant physicians use these agents primarily for their ability to raise blood levels of the calcineurin inhibitors, which ultimately results in significant cost savings because the calcineurin inhibitor dose can be reduced.²⁰ One concern with this strategy, however, is the potential to select for resistant fungal infections, particularly candidal species.

Intensive Care Unit Issues

In the early postoperative period while the patient is mechanically ventilated, the use of sedative medications and paralytics is common. However, in most cases, when early allograft function is adequate, the routine use of paralytic medications can be avoided. Avoidance of these drugs is desirable given that paralyzing agents have been associated with prolonged paralysis, which in lung transplant recipients can impair ability to wean from mechanical ventilation and to participate fully in the postoperative physical therapy regimen. The deleterious effects of paralytic agents can be exacerbated by concomitant use of high-dose corticosteroids and aminoglycoside antibiotics,²¹ both of which are commonly used in the early postoperative period in lung transplant recipients.

Strategies involving gastrointestinal prophylaxis and prophylaxis against deep vein thrombosis are similar to those employed in other thoracic surgical patients. Generally, gastrointestinal prophylaxis is achieved using H₂ blockers or a proton-pump inhibitor and is particularly important early postoperatively when the patient is exposed to high doses of corticosteroids. Most programs continue the gastrointestinal prophylactic measures indefinitely. Because of the risk of surgical bleeding, prophylaxis is initially achieved using antistasis devices to the lower extremities. As the risk of postoperative bleeding diminishes, standard prophylactic regimens for deep venous thrombosis using heparin-based drugs can be safely used until the patient is fully ambulatory.

Early Postoperative Complications

Hemodynamic Instability

As discussed earlier, the immediate hemodynamic goal in the lung transplant recipient is intravascular volume depletion. Although achieving the goal of reducing the tendency toward pulmonary edema, this strategy often results in hypotension. Furthermore, the combination of intravascular volume depletion, a poorly compliant right ventricle requiring higher filling pressures, the use of sedative and paralytic medications that cause hypotension, and positive pressure provided by the mechanical ventilator can result in exacerbation of blood pressure difficulties. Fortunately, the hypotension that occurs commonly under these circumstances can be readily reversed by a few different measures. For example, gentle volume resuscitation with colloids, such as albumin or red blood cell transfusion, can reestablish an adequate blood pressure, while not contributing significantly to pulmonary edema development. In some patients with known preoperative right ventricular dysfunction, such as that seen in primary or secondary pulmonary hypertensives, maintaining adequate right ventricular filling pressures using volume expansion is important in ensuring adequate cardiac performance even in the presence of normal systemic blood pressures. The hemodynamic effect of positive-pressure ventilation has been discussed previously. If the lung transplant recipient experiences problems with positive-pressure-related hypotension, removal from the mechanical ventilator is the treatment of choice. Not only does this remove the hemodynamic effects of positive-pressure ventilation but it also obviates the need for administration of sedative and paralytic medications, all of which have hypotensive side effects. Rarely is there a need for inotropic or cardiopressor support, except in instances of early postoperative hypothermia or profound hemorrhage.

Ventilatory Instability

Ventilatory instability in the early postoperative period requires similar evaluation as any postsurgical patient. Initial efforts to determine the etiology of ventilatory problems should be directed at diagnosing mechanical problems related to the mechanical ventilator and the endotracheal tube. For instance, acute onset of hypercarbia in the early postoperative setting should lead to investigation of the patency of the endotracheal tube specifically and the bronchial tree generally. Plugging of the airways, either with retained mucus or blood, is very common in this setting and can cause rapid ventilatory insufficiency. Development of this problem is suggested by acute increases in ventilatory pressure, but it is definitively diagnosed by bronchoscopic examination of the airways. Treatment involves removal of mucus or blood blocking the airway. Of course, improper patient-ventilator synchrony can cause a similar clinical scenario and may result from inadequate patient sedation.

Problems with early allograft function lead to inadequate ventilation and oxygenation. These problems are usually temporary and are best managed through supportive measures. However, in the case of primary graft failure, oxygenation and ventilatory problems are more profound and require more complex management strategies. In the setting of a double-lung transplant, management should include the application of increased levels of PEEP and, if necessary, alterations of inspiratory-to-expiratory ratios. In single-lung recipients, one can selectively ventilate the native lung while other measures are taken to improve allograft performance. This strategy can be accomplished through the use of double-lumen endotracheal tubes, which allow independent lung ventilation.²² In cases of significant allograft dysfunction, positioning the patient on the side with the native lung “down” can lead to increased perfusion to that side (i.e., the side with less pulmonary edema) and can lead to improvements in oxygenation.

Extracorporeal Membrane Oxygenation

In instances in which none of the measures described results in hemodynamic and ventilatory stability, ECMO is an alternative treatment strategy.²³^–²⁵ Although associated with significant morbidity, ECMO can rapidly restore hemodynamic and ventilatory stability. Important morbidity as a result of this therapy includes bleeding complications secondary to the anticoagulation necessary to maintain the ECMO circuit. Bleeding can occur anywhere and is particularly evident at the cannula insertion site. However, intracranial hemorrhage is the most catastrophic complication and the most common cause of death associated with ECMO.²⁶ The preferred ECMO method in lung transplant recipients is generally the venoarterial route, although the venovenous route has been used as well.²⁷ Insertion of the ECMO cannulas is best performed at the femoral site, because local control of bleeding can be achieved. Although associated with good hemodynamic stability, central cannulization often results in poorly controlled bleeding.

Operative Complications

Postoperative bleeding issues are similar to those present in other thoracic surgical patients and are best handled by correction of coagulopathies and replacement of red blood cells. As in other thoracic patients, careful chest tube output monitoring is essential in detecting and ultimately treating excessive bleeding. Return to the operating room for exploration in the presence of excessive bleeding is not uncommon after lung transplantation. Bleeding complications are generally more common in patients in whom dissection to free the native lung is difficult, such as in cystic fibrosis patients or in patients with fibrotic lung diseases. There is also a tendency toward more bleeding in patients who have required cardiopulmonary bypass.²⁸

As improvements in surgical technique have developed, a decrease in airway, venous, and pulmonary artery anastomotic complications has occurred.²⁹ Although uncommon, anastomotic complications in the immediate postoperative period generally involve the vascular connections rather than the bronchial anastomosis. Complications with the bronchial anastomosis, such as dehiscence or stricture, usually occur later in the postoperative period. Conversely, problems with venous^30,³¹ or pulmonary artery anastomoses³² manifest immediately postoperatively and are life threatening, particularly if not detected promptly.

Pulmonary artery stricture, or narrowing, is fortunately very uncommon. When it does occur, problems with oxygenation are seen and usually occur in the absence of radiographic abnormalities. The diagnosis is initially one of exclusion, where more common causes of poor oxygenation are investigated first. Once no evidence of other causes of poor allograft function can be found, evaluation of the pulmonary artery anastomosis should occur and usually is best accomplished via pulmonary angiography. Pulmonary perfusion scanning can, in some instances, be helpful and is noninvasive. However, nonspecific alterations in allograft blood flow do not distinguish among the usual causes of postoperative allograft dysfunction. Pulmonary angiography, on the other hand, can anatomically demonstrate pulmonary artery narrowing and provides the means to measure pressure gradients across the pulmonary artery anastomosis.³³ If a significant gradient across the pulmonary artery anastomosis were to exist, the suspicion of a pulmonary artery stricture would be high enough to warrant surgical re-exploration.

Of the complications associated with vascular anastomoses, problems with the venous anastomosis are most common. Because of the technical challenges associated with establishing the venous anastomosis and the low-flow state of the venous system, the venous anastomosis is susceptible to kinking or clot formation. Both of these complications cause impedance of venous return and backflow of blood into the pulmonary vasculature. This results in immediate and profound pulmonary edema that is refractory to all supportive measures. A clinical scenario of this kind should prompt immediate investigation, ideally via visualization and Doppler measurement of the venous anastomosis using transesophageal echocardiography.^34,³⁵