Lung transplantation

Lung transplantation - the possibility of saving life for patients with respiratory failure, with a high risk of death, despite optimal medication. The most common indications are COPD (chronic obstructive pulmonary disease, COPD - chronic obstructive pulmonary disease), idiopathic pulmonary fibrosis, cystic fibrosis, a1-antitrypsin deficiency, primary pulmonary hypertension. Less common indications are interstitial lung diseases (eg, sarcoidosis), bronchiectasis, congenital heart disease.

Transplantation of one or both lungs is used with equal success in most lung diseases without cardiac involvement; the exception is chronic diffuse infections (eg, bronchiectasis), in which transplantation of both lungs is preferable. Transplantation of the heart-lung complex is indicated with Eisenmenger syndrome and any pulmonary diseases with severe irreversible ventricular dysfunction; corpulmonale (pulmonary heart) is not an indication for such a transplantation, as often the condition recurs after lung transplantation. Transplantation of one or two lungs is carried out equally often and at least 8 times more often than transplantation of the heart-lung complex.

Relative contraindications are age (65 years for lung transplantation, 60 for lung transplantation, 55 for heart-lung transplantation), active smoking, previous thoracic surgeries, and for some patients with cystic fibrosis and in some medical centers - pulmonary infections caused by resistant strains of Burkholderia cepacia, which significantly increases the risk of death.

Almost all lungs receive from donor corpses with brain death and a working heart. Rarely, if the bodies of the donor corpse are not suitable, the transplant uses the share of a living donor (usually when transplanting from parents to children). The donor may be a person younger than 65 years old who has never smoked and who has no active lung disease, as evidenced by oxygenation (Pa ₀₂ / Fi ₀₂ > 250-300 mm Hg), lung elongation (peak inspiratory pressure <30 cm H O at V _T 15 ml / kg and positive expiratory pressure = 5 cm H O) and a normal macroscopic picture with bronchoscopy. Donors and recipients should be anatomically fit in size (determined by radiographic examination) and / or physiologically (total pulmonary volume).

The timing of the transplantation should be determined by factors such as the degree of obstruction (FEV1, forced expiratory volume in 1 s, FEV - forced expiratory volume <25-30% of that in patients with COPD, insufficiency of a1-antitrypsin or cystic fibrosis); Pa <55 mm Hg. P. Ra with> 50 mm Hg. P. Pressure in the right atrium is greater than 10 mm Hg. Art. And peak systolic pressure> 50 mm Hg. Art. For patients with primary pulmonary hypertension; progression of clinical, radiographic and physiological symptoms of the disease.

Lung transplantation is still one of the least developed areas of modern transplantology. Successful implementation of lung transplantation depends on proper selection of the donor and recipient, early diagnosis of rejection crises, effectiveness of immunosuppression, correct anti-infective therapy in the postoperative period.

The development of the terminal stage of lung injury in the destruction of the pulmonary parenchyma or vasculature is one of the leading causes of disability and mortality in adult patients. Several variants of transplantation have been developed for the treatment of the terminal stage of lung diseases, each of which has certain theoretical and practical advantages. These include lung transplantation, heart-lung complex. The choice of a procedure for lung transplantation is based to a large extent on the consequences of leaving the native lung in place. For example, single pulmonary lung transplantation is not indicated in the presence of infection or severe bullous emphysema that are present in the contralateral lung. A cross infection would infect a healthy transplanted lung, and a pronounced bullous lesion in the native lung can lead to a large discrepancy between perfusion and ventilation and displacement of the mediastinum. In such cases, preference is given to transplantation of both lungs. Transplantation of a single lung is quite feasible without IR and is rarely complicated by bleeding. Another advantage of single lung transplantation is that this performed bronchial anastomosis heals with significantly fewer complications compared to a single tracheal anastomosis in the transplantation of a block of two lungs.

Transplantation of two lungs at once can lead to better functional results in the treatment of the terminal stage of pulmonary hypertension. When transplanting two lungs at once, it is mandatory to use IR with complete systemic heparinization and extensive mediastinal dissection - both these factors dramatically increase the risk of postoperative coagulopathy. Bilateral sequential lung transplantation, recently used in clinical practice, may be an alternative to the transplantation of a block of two lungs, since it combines the advantages of using bibronchial anastomosis and allows the IR to be abandoned.

When establishing the diagnosis of chronic pulmonary hypertension with right ventricular failure, the choice method is heart-lung transplantation. However, with the stored functional capabilities of the heart, an isolated lung transplant can be optimal for a patient with end-stage lung disease.

Anatomico-physiological features of the respiratory system and pathophysiological changes in the terminal stage of parenchymal lung diseases. The terminal stage of lung parenchymal diseases is, in its etiology, restrictive, obstructive or infectious. Restrictive pulmonary diseases are characterized by interstitial fibrosis with loss of elasticity and extensibility of the lung. By nature, most fibrotic diseases are idiopathic (of unknown origin), but they can also be caused by inhalation damage or immune processes. Interstitial lung diseases affect the blood vessels with the subsequent manifestation of pulmonary hypertension. Diseases of this category are functionally manifested by a decrease in lung volume and diffusion capacity at a maintained airflow rate.

The most common cause of the terminal stage of obstructive lung disease is emphysema caused by smoking, but there are other causes, including asthma and some relatively rare congenital diseases. Among them, alpha1-antitrypsin deficiency associated with severe bullous emphysema. In obstructive diseases, the resistance of the respiratory tract is sharply increased, the rate of the expiratory flow is reduced and the residual volume is sharply increased, the ventilation-perfusion relations are violated.

The infectious etiology of the terminal stage of lung diseases is cystic fibrosis and bronchoectatic disease. Cystic fibrosis causes obturation of peripheral respiratory tract mucus, chronic bronchitis and bronchiectasis. In addition, the terminal stage of pulmonary vascular diseases may be a consequence of primary pulmonary hypertension, which is a relatively rare disease of unknown etiology and is manifested by increased LSS due to muscle hyperplasia of LA and fibrosis of small-diameter arterioles. Another reason for the deformation of the pulmonary arterial bed is EPS with Eisenmenger syndrome and diffuse arteriovenous malformations.

The main indications for transplantation at the terminal stage of any lung disease are progressive deterioration of tolerance, increased oxygen demand and delay of CO2. Other factors that predetermine transplantation are the emergence of the need for permanent infusion support and the manifestation of physical and social insolvency.

The operation depends on the rate of increase in functional disorders and the ability of the prostate to compensate for the progression of pulmonary hypertension. Given the limited availability of donor organs, special contraindications to lung transplantation include severe depletion, neuromuscular diseases or dependence on ventilation (since the strength of the respiratory muscles is extremely important for successful recovery); severe chest deformity or pleural disease (complication of surgical procedures and postoperative ventilation); progression of right ventricular failure or glucocorticoid dependence (because the healing of anastomosed airways is impeded by steroids).

[1], [2], [3], [4]

Lung transplantation: preoperative preparation

The study of preoperative lung function and right heart catheterization, the study of ventilation-perfusion ratios and arterial blood gas parameters are very useful for predicting possible difficulties that may occur during and after induction. For example, a decrease in the flow rate during exhalation and abnormal air retention in the lungs may increase hypoxemia and hypercapnia and lead to hemodynamic instability during mask ventilation and after intubation of the trachea. Elevated DLA can serve as an indicator of the need for IR, because right ventricular failure can develop almost suddenly at the onset of single-pulmonary ventilation or ligation of the pulmonary artery. Even in the absence of pulmonary hypertension, it is recommended to have an apparatus for venovenous bypass for these cases, since gas exchange is so compromised. Obviously, monitoring systemic and pulmonary blood pressure is vital for lung transplantation, although pronounced dyspnea may cause significant difficulties in the internal jugular vein catheterization prior to induction.

Transplantation of one lung

The procedure for transplantation of one lung includes pneumonectomy and implantation of a new lung, as well as the mobilization of the omentum on the vascular pedicle to move to the bronchi. If the natural lungs are damaged equally and there are no signs of pleural scarring, for the transplantation the left lung is selected for technical reasons: the right pulmonary veins of the recipient are less accessible than the left, the left bronchus is longer, besides the left half of the chest easier adapts to the donor lung more than recipient, size. Most surgeons prefer that during the removal the donor's lung is collapsed, bronchial blockers and double-lumen endobronchial tubes are used for this purpose.

For introductory anesthesia, a rapid intubation technique is used, preference is given to drugs that do not have cardiodepressant and histamine-like effects (eg, etomidate, vecuronium bromide). The use of dinitrogen oxide is avoided in patients with bullae or elevated LSS, as well as in cases where 100% oxygen is required to maintain an acceptable saturation of the arterial blood. To maintain anesthesia successfully used opioids in high doses, powerful IA in combination with long-acting muscle relaxants. With the onset of single-pulmonary ventilation, as a rule, there are sharp disruptions in gas exchange and hemodynamics. Methods for improving oxygenation in these conditions include the use of PEEP in dependent lung, CPAP or high-frequency ventilation in an independent lung when the pulmonary artery is cross-linked. If at that moment the DL increases sharply, right ventricular failure may develop.

Vasodilator and / or inotropic drugs can reduce the burden on the right heart, if they are ineffective, one-lung ventilation should continue. Similarly, if hemodynamic parameters or systemic arterial saturation worsen when the pulmonary artery is compressed before pneumonectomy, it may be necessary to use AIC.

After restoration of the blood supply of the donor lung, the ischemia period ends, but until the normal ventilation of the transplant systemic arterial saturation is usually reduced. At this stage, a bronchoscopy procedure may be required to remove secret or blood from the respiratory tract to restore the filling of the graft with air. As soon as the bronchial anastomosis is performed, the omentum moves on the chest on an intact vascular pedicle, which is wrapped in bronchial anastomosis. After the chest is closed, the endobronchial tube is replaced with a standard endotracheal tube.

Transplantation of both lungs

Transplantation of both lungs is most often used in patients with primary pulmonary hypertension or cystic fibrosis. The operation of transplantation of the block of two lungs is performed in the supine position, and, since both lungs are replaced simultaneously, the use of AIC is mandatory. Cardioplegic cardiac arrest is used to perform anastomosis of the left atrial stump containing all four pulmonary venous apertures. The respiratory tract is interrupted at the level of the trachea, therefore the standard endotracheal tube is used. As the systemic arterial blood supply of the trachea is compromised, it is wrapped with a vascularized omentum. Extensive retrocardial dissection often leads to denervation of the heart; in addition, it is difficult to control the occurrence of postoperative bleeding. Two-sided sequential single-lung transplantation was introduced for surgical treatment of the same contingent of patients who underwent transplantation of a block of two lungs, but it eliminates the need for IC and tracheal anastomosis. A relative disadvantage of this operation is that with consecutive implantation the time of ischemia of the second lung transplant is significantly prolonged.

Procedure of lung transplantation

A cold crystalloid preservative solution containing prostaglandins is injected through the pulmonary arteries into the lungs. The donor organs are cooled by ice-salt solution in situ or by means of a pulmonary-cardiac shunt, then they are removed. A preventive course of antibiotic therapy is prescribed.

Transplantation of one lung requires posterolateral thoracotomy. The own lung is removed, anastomoses are formed with the corresponding stumps of the bronchi, pulmonary arteries, pulmonary veins of the donor lung. Bronchial anastomosis to achieve adequate healing requires intussusception (insertion of one end into the other) or wrapping with an omentum or pericardium. The advantage is the simpler technique of the operation, the absence of the need for using an artificial circulation device and systemic anticoagulants (usually), the exact size and suitability of the contralateral lung from the same donor for another recipient. Disadvantages include the possibility of a discrepancy between ventilation / perfusion between own and transplanted lungs and the possibility of poor healing of a single bronchial anastomosis.

Transplantation of both lungs requires sternotomy or anterior transverse thoracotomy; The procedure is similar to two consecutive transplantations of one lung. The main advantage is the complete removal of all damaged tissues. The disadvantage is poor healing of tracheal anastomosis.

Transplantation of the heart-lung complex requires medial sternotomy with a pulmonary-cardiac shunt. Aortic, right atrial and tracheal anastomoses are formed, tracheal anastomosis is formed immediately above the bifurcation site. The main advantages are improved function of the transplant and more reliable healing of tracheal anastomosis, as coronary-bronchial collaterals are within the heart-lung complex. The drawbacks are the long operation and the need for the use of an artificial circulation device, an accurate selection of the size, the use of three donor organs for one patient.

Prior to reperfusion of the transplanted lung, recipients are often prescribed methylprednisolone intravenously. The usual course of immunosuppressive therapy includes calcineurin (cyclosporin or tacrolimus) inhibitors, purine metabolism inhibitors (azathioprine or mycophenolate mofetil) and methylprednisolone. During the first two weeks after transplantation, antitimocyte globulin or OKTZ is prophylactically prescribed. Glucocorticoids can be abolished for normal healing of bronchial anastomosis; they are replaced by higher doses of other drugs (eg, cyclosporine, azathioprine). Immunosuppressive therapy lasts indefinitely.

Rejection develops in most patients, despite immunosuppressive therapy. Symptoms and objective signs are similar in hyperosteroids, acute and chronic forms and include fever, dyspnea, cough, a decrease in Sa0 ₂, the appearance of interstitial infiltrates on the radiograph, a decrease in FEV by more than 10-15%. Hyperosteal rejection should be distinguished from early graft dysfunction, the cause of which is ischemic injury during the transplant procedure. The diagnosis is confirmed by bronchoscopic transbronchial biopsy, in which perivascular lymphocytic infiltration of small vessels is detected. Usually, intravenous glucocorticoids are effective. Treatment of recurrent or resistant cases is carried out in different ways and includes high doses of glucocorticoids, cyclosporin aerosol, antitumocyte globulin and SCC.

Chronic rejection (after a year or more) occurs in less than 50% of patients; it takes the form of obliterating bronchiolitis or not so often, atherosclerosis. Acute rejection may increase the risk of chronic disease. In patients with bronchiolitis obliterans, cough, dyspnea, decreased FEV with physical or radiographic signs of the process in the respiratory tract or without them. For differential diagnosis, pneumonia should be avoided. Diagnosis is based on bronchoscopy and biopsy data. No treatment is particularly effective, but the appointment of glucocorticoids, antithymocytic globulin, OKTZ, cyclosporine inhalation and re-transplantation may be recommended.

The most frequent surgical complications are poor healing of tracheal or bronchial anastomoses. Less than 20% of the recipients of one lung develop bronchial stenosis, which leads to shortness of breath and airway obstruction; it can be treated by dilatation and installation of the wall. Other surgical complications include hoarseness and paralysis of the diaphragm, which are the result of a lesion of the recurrent laryngeal or diaphragmatic nerves; a violation of the motility of the gastrointestinal tract due to a lesion of the thoracic department of the vagus nerve; pneumothorax. In some patients, supraventricular arrhythmias develop, possibly due to a change in conduction in the sutures between the pulmonary vein and the atrium.

What is the prognosis of lung transplantation?

By the first year, the survival rate is 70% for patients with transplants from live donors and 77% for transplantation from donor corpses. In general, the survival rate after 5 years is 45%. The mortality rate is higher in patients with primary pulmonary hypertension, idiopathic pulmonary fibrosis or sarcoidosis and lower in patients with COPD or with a deficiency of a-antitrypsin. The death rate is higher for one lung transplant than for both lung transplants. The most common causes of death during the first month are primary transplant failure, ischemia and reperfusion disorders, infections (eg, pneumonia), excluding cytomegalovirus; the most common causes between the 1st month and the 1st year are infections, and after 1 year - bronchiolitis obliterans. Among the risk factors leading to death, a mismatch in infection with cytomegalovirus (donor positive, recipient negative), incompatibility with the HLA-antigen system (HLA-DR), diabetes, the former need for mechanical ventilation or inotropic support are highlighted. In rare cases, the disease recurs, more often this is observed in patients with interstitial lung diseases. The tolerability of exercise is somewhat limited due to the hyperventilator response. The survival rate after 1 year after a heart-lung transplantation is 60% for patients and a transplant.

Assessment of the patient's condition after lung transplantation

Postoperative treatment of patients after an isolated lung transplant includes intensive respiratory support and differential diagnosis between rejection and lung infection, using transbronchial biopsies performed with a flexible bronchoscope. Early respiratory failure may result from preservation or reperfusion injury and is characterized by a pronounced arterioalveolar gradient in oxygen, decreased pulmonary elasticity (low pulmonary compliance) and the presence of parenchymal infiltrates, despite the low cardiac filling pressure. In these cases, ventilator with PEEP is usually used, but, taking into account the features of anastomosing the newly reconstructed airways, the inhalation pressure is maintained at the minimum values. Fi02 is also maintained at the lowest values, allowing sufficient blood saturation.

In addition to surgical complications, including bleeding, hemo- and pneumothorax, early graft dysfunction, the need for prolonged ventilation, lung transplantation is extremely dangerous for infectious complications. The lung is unique among transplantable visceral organs, as it is directly exposed to the environment. Disorders of lymph drainage, insufficient function of the ciliary epithelium and the presence of a seam line across the airways - these and other factors increase the susceptibility of the transplanted lungs to infection. During the first postoperative month, bacteria are the most common cause of pneumonia. After this period, the most frequent are CMV pneumonitis. The frequency of episodes of acute rejection after lung transplantation is great, which for clinical reasons alone is very difficult to distinguish from infection. This difference is vital, since SCS used to treat rejection can worsen the course of pneumonia and stimulate the generalization of systemic sepsis. Bronchoalveolar lavage fluid or sputum samples obtained during bronchoscopy can be useful in diagnosing diseases of infectious etiology. A transbronchial biopsy or an open lung biopsy is necessary to establish a diagnosis of rejection.

Bleeding is a complication that occurs most often after the transplantation of two lungs with a single block, especially in patients with pleural lesions or Eisenmenger syndrome with extensive mediastinal vascular collaterals. Diaphragmatic, wandering and recurrent laryngeal nerves are highly endangered during lung transplantation, and their damage complicates the process of stopping mechanical ventilation and restoring adequate independent breathing. Primary healing usually occurs for most bronchial anastomoses; very rarely bronchial fistula lead to stenosis, which can be successfully treated with silicone stents and dilations. The inconsistency of tracheal anastomoses, on the contrary, often leads to fatal mediastinitis. After performing the heart-lung transplantation, the development of the obliterating bronchiolitis characterized by the destruction of small respiratory bronchioles is described.

[5], [6]