You are in: eMedicine Specialties > Emergency Medicine > PULMONARY Transplants, LungArticle Last Updated: Jul 17, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 8
  Author: Catherine Y Park, MD, Staff Physician, Department of Emergency Medicine, University of Southern California, Los Angeles County Coauthor(s): Allison J Richard, MD, Assistant Professor of Clinical Emergency Medicine, Keck School of Medicine, University of Southern California; Consulting Staff, Department of Emergency Medicine, LAC-USC Medical Center Editors: Mark S Slabinski, MD, FACEP, FAAEM, Vice President, EMP Medical Group; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Paul Blackburn, DO, FACOEP, FACEP, Program Director, Department of Emergency Medicine, Maricopa Medical Center; Assistant Professor, Department of Surgery, University of Arizona; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Barry E Brenner, MD, PhD, FACEP, Program Director, Professor, Department of Emergency Medicine, Professor, Internal Medicine, University Hospitals, Case Western Reserve School of Medicine Author and Editor Disclosure Synonyms and related keywords: lung transplantation, lung transplant, lung transplant complications, obstructive pulmonary disease, pulmonary hypertension, cystic fibrosis, idiopathic pulmonary fibrosis, Eisenmenger syndrome, single-lung transplantation, bilateral sequential transplantation, combined heart-lung transplantation, lobar transplantation INTRODUCTIONSection 2 of 8
  Background Since the time of the first successful single-lung transplantation in 1983, the number of lung transplant centers as well as organ recipients has continued to rise. This trend coupled with ongoing advances in transplant medicine has led to a growing patient subset that provides a unique challenge to the emergency physician. Pathophysiology Currently, the most common indication for lung transplantation is chronic obstructive pulmonary disease, but other common indications include pulmonary hypertension, cystic fibrosis, idiopathic pulmonary fibrosis, and Eisenmenger syndrome. Four different surgical techniques are used: single-lung transplantation, bilateral sequential transplantation, combined heart-lung transplantation, and lobar transplantation, with the overwhelming majority of organs procured from deceased donors. The indications for each of these techniques are evolving and are individual to the underlying disease processes. Medical complications seen in this patient population are variable and most importantly may be a result of surgical complications, graft rejection, or immunosuppression, either a direct pharmacologic toxicity or an infectious etiology. Frequency At the close of 2007, approximately 2,500 patients were awaiting lung or combined heart-lung transplantation, with transplantation programs available at nearly 70 hospitals nationwide. The mean waiting time for lung transplantation is nearly 14 months, and, in 2007, nearly 1500 patients received a donor organ. Age There is no defined lower limit of age for lung transplantation, and it is largely limited by the availabilities of suitable-sized donors. Because of the increasingly poor survival with advancing age, the following limits have been recommended: 55 years for heart-lung transplantation, 60 years for bilateral-lung transplantation, and 65 years for single-lung transplantation. Morbidity/mortality In 2007, survival rates were approximately 84% at 1 year and 44% at 5 years post transplantation for a single lung, and 83% and 50% at 1 and 5 years respectively for a double lung transplant. SURGICAL COMPLICATIONSSection 3 of 8
Acute surgical complications Surgical complications following lung transplantation can be further divided into acute and chronic complications. Many of the acute complications occur while the patient is still in the inpatient postoperative setting. Reperfusion edema, a type of noncardiogenic pulmonary edema, is seen in more than 95% of transplanted lungs. Reperfusion edema typically presents as hypoxemia and reduced lung compliance that begins within 24 hours postoperatively and is characterized by diffuse infiltrates on the chest radiograph. The symptoms peak by postoperative day 4-5, and they generally resolve by postoperative day 10. Other acute complications include hemothorax, pleural effusions, chylothorax (a result of perioperative injury to the thoracic duct), and pneumothorax. The ED physician should be aware of these complications, as patients are often discharged with conservative management only for these conditions. Other acute surgical complications include full or partial dehiscence of the bronchial anastomosis. Bronchial dehiscence results from ischemia of the anastomotic site and is seen in 2-3% of lung transplantation patients. Bronchial dehiscence may present as pneumomediastinum, pneumothorax, or subcutaneous emphysema. Symptoms include tachypnea, shortness of breath, and secondary infections, such as mediastinitis, cause fevers and leukocytosis. Symptoms range from asymptomatic to fulminant respiratory failure and death depending on the severity of the dehiscence. Diagnosis is made by CT scan, or preferably, by bronchoscopy. Partial dehiscence less than 4 mm is generally managed conservatively, while larger injuries or complete dehiscence requires immediate surgical correction. Patients who present with suspected dehiscence should be admitted for further observation and evaluation. Delayed surgical complications Delayed airway complications are commonly seen postoperatively, and they typically present several weeks to months post transplantation. These complications include stenosis of the anastomotic site, formation of granulation tissue, or bronchomalacia. Pleural space problems may also occur and include such problems as bronchopleural fistulas, loculated pleural effusions, and hemothorax or fibrothorax. Presenting complaints include dyspnea with exertion, cough, or shortness of breath, and evaluation of the patient may reveal focal wheezing, recurrent lower respiratory tract infection, or diminished pulmonary function tests. Treatment options include dilatation via rigid bronchoscopy or balloon, debridement with laser or cryotherapy, and stent placement, and recently, brachytherapy has been suggested as a potential treatment modality. Surgical decortication has been suggested for treatment of pleural space complications. Other considerations Like any other postoperative patient, lung transplant recipients are at risk for pulmonary embolus. Recent postmortem studies have shown a high risk for pulmonary embolus and other thromboembolic events. Patients are at greatest risk in the first 30 days posttransplantation, although complications may still occur at any time postoperatively. Recent studies suggest that this high incidence of thromboembolic complications is due to a hypercoagulable state, which is of an unclear etiology. ED evaluation The ED evaluation should be flexible and tailored toward the patient's presentation and clinical suspicion for the underlying etiology. In general, the initial workup for surgical complications should include a CBC, chemistry panel, medication levels, a chest radiograph, and possibly a chest CT, especially if pulmonary embolus or bronchial dehiscence is suspected. Chest CT is also useful in evaluating new or changed pleural space diseases. A type and crossmatch may also be indicated. Further diagnostic testing and intervention should be performed with consultation with the transplant surgeon or pulmonologist. For example, pleural changes, such as thickening, calcifications, or effusions, may be seen up to 1 year postoperatively, and if unchanged from prior studies, they may not require any further emergent evaluation. Another example is chest CT evidence of dehiscence or stenosis, which requires bronchoscopy to guide treatment. GRAFT REJECTIONSection 4 of 8
Graft rejection may be divided into subcategories: hyperacute, acute, and chronic rejection. Hyperacute graft rejection Hyperacute, or primary graft failure, occurs within 72 hours postoperatively, making it an entity not typically seen by the emergency physician. Primary graft failure results from ischemia-reperfusion injury and presents similarly to acute respiratory distress syndrome. Early mortality may reach up to 60%, and patients who survive to hospital discharge additionally have a protracted course of recovery with significant impairments in pulmonary function. Acute graft rejection Acute graft rejection is characterized by a host T-cell response toward the transplanted organ. The incidence of acute graft rejection is highest in the first 3 months, with rare cases occurring 1 year post transplantation. The diagnosis of acute rejection is made based on both clinical and histologic criteria. Clinical features are nonspecific and include dyspnea, fever, leukocytosis, nonproductive cough, hypoxemia, or malaise. Chest radiography may show new opacifications or pleural effusions, but findings are often absent after the first month. The clinical course is variable and depends on the severity of rejection; mild cases of rejection may even be asymptomatic. Diagnosis of acute graft rejection can be confirmed with bronchoscopic lung biopsy, which reveals perivascular lymphocytic infiltrates. Treatment for acute graft rejection is high-dose parenteral steroids (methylprednisolone 0.5-1 g/d IV) and should be started in consultation with a pulmonologist. Chronic graft rejection Chronic graft rejection, like acute graft rejection, is also characterized by both histologic and clinical parameters. Clinically, the symptoms of chronic rejection are nonspecific and variable in severity. In mild chronic rejection, the patient may present with a nonproductive cough and dyspnea on exertion, and it can progress to dyspnea at rest, productive cough, pseudomonas colonization, and chest radiographic findings of bronchiectasis and air trapping. Histologic changes involve either the vasculature or the airways. Chronic vascular rejection is caused by atherosclerosis of the pulmonary vasculature, while chronic airway rejection is caused by bronchiolitis obliterans. Bronchiolitis obliterans occurs more frequently and is the main source of morbidity and mortality in lung transplant patients. Histologically, bronchiolitis obliterans is a dense irreversible scarring of the terminal and respiratory bronchioles, which partially or totally obliterates the lumen of the airway causing a progressive decline in pulmonary function. Because of the poor sensitivity of transbronchial lung biopsy, perhaps as low as 15-17%, the diagnosis of chronic graft rejection is largely clinical. Chronic graft rejection is thus defined as an unexplained drop in the FEV1 to a level of 80% or less of the patient's posttransplantation peak value. Other markers, such as interleukin 12 (IL-12) levels in bronchoalveolar lavage fluid and levels of exhaled nitric oxide, are currently under investigation as potential markers. Chronic rejection rarely occurs within the first 3 months after transplantation, but its prevalence increases with time. No specific treatment exists for chronic graft rejection, and efforts are aimed toward immunosuppression and primary prevention. ED evaluation The presenting symptoms of allograft rejection are nonspecific and may present similarly to pulmonary infections. The two etiologies must be differentiated in order to guide treatment. The ED physician should obtain a chest radiograph, drug levels, CBC, and chemistries and should consider admission for further diagnostic evaluation. Further confirmatory tests may need to be performed for suspected allograft rejection such as pulmonary function tests or bronchoscopy in order to obtain bronchoalveolar lavage fluid or transbronchial lung biopsies. Depending on the severity of the patient's presentation, these tests may be performed in the in-patient setting or during close outpatient follow-up. Disposition should be discussed with the pulmonologist or transplant team. IMMUNOSUPPRESSION-RELATED COMPLICATIONSSection 5 of 8
Although the first lung transplantation was performed in 1963, the first successful heart-lung transplantation was not performed until 1981. The success of this procedure after nearly 20 years can largely be attributed to the advent of cyclosporine as an immunosuppressive agent. Cyclosporine and the other immune modulators work by preventing host reactivity to the foreign allograft. Since the first successful transplant, immunosuppression has now become a mainstay of transplant medicine. However, the optimal regimen is still controversial. While successful transplantation would not be possible without use of these medications, they themselves pose a risk secondary to both direct toxicity as well as infectious complications. The current goal of immunosuppression is to find the optimal combination of drugs that maintains efficacy but minimizes the toxicity presented by each agent. Direct drug toxicity Immunosuppression regimens consist of two phases: induction and maintenance. The induction phase involves the first week immediately post transplantation, while the maintenance phase refers to the long-term immunosuppression required to prevent rejection of the allograft. Induction regimens typically involve a calcineurin inhibitor, either cyclosporine or tacrolimus, which blocks production of interleukin 2, causing a decline in T-cell proliferation. This is may be coupled with an antilymphocyte antibody preparation, such as OKT3, which binds to the T-cell receptor complex, or daclizumab and basiliximab, which bind to the T-cell interleukin 2 receptor. Long-term maintenance regimens generally consist of a combination of cyclosporine or tacrolimus, a cell-cycle inhibitor such as azathioprine or mycophenolate mofetil, and a glucocorticoid. Recent studies show promise for inhaled cyclosporine as an effective means for delivering high concentrations to the allograft, leading to reduction of chronicrejection. Detailed information on each of these medications is available elsewhere on this Web site; however, the most common side of effects of these medications are listed here. Evaluation of direct drug toxicity will be guided by the patient's regimen.
INFECTION IN THE IMMUNOSUPPRESSED PATIENTSection 6 of 8
Emergency physicians are often faced with the challenge of evaluating the febrile immunosuppressed patient. The emergency physician must be aware of the increased risk of opportunistic infections, the attenuation of the inflammatory response, which may mask the severity of the infectious process; and the fulminant course that these infections may take in an immunosuppressed patient. Although the etiology of infection is unpredictable, certain types of infections are seen more frequently depending on the length of time between the transplant and presentation to the emergency department. Infection in the first month post transplantation Infections occurring during the first month post transplantation are generally bacterial and nosocomial in origin. These infections are related to the surgical wound, vascular access catheters, urinary tract infections, and pneumonia are also common. Patients are given prophylactic antibiotics routinely immediately post transplantation, decreasing the rate of nosocomial infections. The causative organisms of these postoperative infections are otherwise identical to those seen in the nonimmunosuppressed postoperative patient, and their evaluation and treatment is also unchanged. Infection from 1-6 months post transplantation During this period, the level of immunosuppression reaches its peak, and accordingly, opportunistic infections and viruses pose significant hazards. Opportunistic infections from Pneumocystis jiroveci, and Legionella, Listeria, Aspergillus, or Candida species are more commonly seen, although cases of pulmonary or disseminated Cryptococcus species, Coccidioides immitis, and tuberculosis have also been reported. During the first 6 months, viral infections also become more significant, and common etiologies include cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes viruses, hepatitis B, and hepatitis C. Infection with CMV is of particular interest in post–lung transplantation patients. CMV infection occurs in approximately 58-69% of recipient-positive, donor-negative and recipient-positive, donor positive transplants, and is secondary only to bacterial pneumonia in post–lung transplantation infections. The most severe infections are usually primary infections in seronegative recipients. Secondary CMV infection occurs with reactivation of latent disease, which is unmasked with immunosuppression, or it may represent a new infection with a different strain of CMV. CMV most commonly causes pneumonitis, but it may also present as retinitis, hepatitis, colitis, or gastroenteritis. Clinical presentation of CMV pneumonitis is nonspecific and may include shortness of breath, low-grade fevers, decrease in pulmonary function, and cough. The chest radiographic appearance is similarly nonspecific and may show perihilar infiltrates, interstitial edema, focal consolidation, or pleural effusions. The clinical presentation is similar to that of acute graft rejection. The early diagnosis and treatment of CMV infection is imperative, as studies link early CMV infection with the future development of bronchiolitis obliterans and chronic graft rejection. The treatment of CMV infection is intravenous ganciclovir. Many transplant centers routinely administer ganciclovir for CMV prophylaxis; however, concern exists over rising resistance rates. Infections after 6 months post transplantation After the 6-month window, patients without evidence of rejection can be maintained on low doses of immunosuppressants. These patients have similar rates and types of infections seen in the general population and opportunistic infections are rare. However, patients with evidence of allograft rejection must be maintained on higher doses of immunosuppressants, rendering them more susceptible to aggressive and opportunistic infections. These high-risk patients are often placed on lifelong prophylactic medications, such as trimethoprim-sulfamethoxazole or antifungals. Viral infections are also persistent in this time period. Chronic EBV infection is also linked to the development of lymphoma and other posttransplantation lymphoproliferative diseases. ED evaluation The ED physician should have a conservative approach to posttransplantation patients presenting to the ED with infections or fevers. A high degree of suspicion must be kept for opportunistic infections; fulminant infections masked by immunosuppressant medications; and noninfectious complications, such as allograft rejection. The evaluation should be tailored to the degree of the patient's immunosuppression and potential infectious organisms, which may correlate to the time post transplantation. Non–transplant-related febrile illnesses should also be considered, such as appendicitis, pyelonephritis, or viral syndromes. Workup may include a CBC with differential, chest radiography, sputum, blood cultures, and/or urine cultures and urinalysis. Patients that are ill-appearing or with a high degree of immunosuppression should be started on broad-spectrum antibiotics. Patients that fail to respond to broad-spectrum antibiotics should also be evaluated for less common etiologies such as viral or fungal infections. Evaluation may include serum CMV or other suspected viral titers, bronchoscopy for bronchoalveolar lavage or tissue evaluation, and/or fungal cultures. Patients in the first 6 months post transplantation have a high degree of immunosuppression and will likely require admission to the hospital. However, well-appearing patients that are greater than 6 months post transplantation and who have had an uncomplicated medical course may potentially be discharged home. Because of the complexity of these cases and the potential for morbidity, the evaluation, treatment, and disposition of lung-transplant recipients should be discussed with a pulmonologist or with the transplant team. CONCLUSIONSection 7 of 8
Lung transplant recipients may present to the ED with presentations ranging from the mundane to life-threatening illnesses. A high level of suspicion must be maintained, especially in the severely immunosuppressed. Treatment and evaluation should be guided by clinical presentation, and early consultation with the pulmonologist or transplant team is recommended. REFERENCESSection 8 of 8
Article Last Updated: Jul 17, 2008 |
