Lung transplant is an effective method of treating patients with end-stage respiratory diseases, but problems such as the imbalance between the number of donor organs and the number of recipients needing organs still play a leading role. From a transplant point of view, a multiorgan donor is considered of greatest efficiency, so that all organs that can potentially be used should be transplanted. The combination of the vast geographical territory of Russia, the shortage of actual donors, and the relatively small number of transplant centers has led to the need to transport donor lungs by air over long distances. There were already precedents in the world for remote preservation of donor organs for transplant. In this study, we have described the unique experience of remote evaluation of donor lungs with their subsequent air transportation and transplantation, which is the first such description in Russia to our knowledge. The donor lungs for lung transplant were brought from medical institutions of the Samara region to Moscow. During remote evaluation, all information was transmitted to the transplant center by providing access to the automated information system “Organ Donation,” which was used at that time by the service and contained all information about a potential donor in real time. The 2 transplant candidates had end-stage cystic fibrosis and severe respiratory failure; both patients underwent organ implantation from donors located outside their regions. In conditions of shortages of donor organs, long-distance transportation is a reasonable, feasible, and safe procedure.

Key words : Organ donation, Remote assessment, Transplantology, Transportation of donor organs

Introduction

Lung transplantation is a well-established treatment method that improves the quality of life of patients with end-stage respiratory failure who have not res-ponded to other medical or surgical interventions.¹ Since the first lung transplant performed by James Hardy and colleagues at the University of Mississippi in 1963, more than 70 000 lung transplants have been performed worldwide.² According to the US Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients, the survival rate is 85% at 1 year after lung transplant, 68% at 3 years posttransplant, and 55% at 5 years posttransplant.³

Significant advances have been made in the field of lung transplantation over the past few decades. New technologies, such as EX-VIVO perfusion, along with a wider use of donors with cardiac death and expanded criteria for selection of donors, have opened up great prospects in the near future for solving the problem of donor shortages.⁴ Despite these achievements, morbidity and mortality in patients with end-stage respiratory damage remain high compared with other types of solid-organ transplant procedures. Lung transplant is an effective treatment for patients with end-stage respiratory disease, but there is still a general shortage of donors, and many transplant candidates cannot live to see a suitable donor available.

Presently, not all regions of the Russian Federation are covered by transplant care; 66 transplant centers operate in 36 regions, of which lung transplant is performed only in Moscow in 2 centers (N. V. Sklifosovsky Research Institute of Emergency Medicine and V. I. Shumakov National Research Center of Transplantology and Artificial Organs).⁵

Materials and Methods

The Samara region is a compactly located region in the Middle Volga with an area of 53 565 km². The region has a population of 3 142 683. Transport accessibility within the region is good; there are paved roads between cities, and the federal highway M5 “Ural” passes through the region. The region has 1 international airport (Kurumoch) located in the geographical center of the region between the cities of Samara and Tolyatti. Nine medical institutions in the region have a license for the preservation of donor organs. The donor potential of the region can be up to 40 lungs per year.^6,7

Proposals for the allocation of donor organs are sent from the region to transplant centers in other regions. Standard criteria are used to assess the suitability of donors for lung preservation: age up to 55 years, smoking of <20 packs/year, no significant chronic diseases in the anamnesis (malignancies, diabetes mellitus), no purulent tracheobronchitis, and ratio of Pao2₂ at 100% fraction of inspired oxygen [Fio2]-to-positive end-expiratory pressure [PEEP] of 5 mm Hg of <300 mm Hg. All information was transmitted to the transplant center by providing access to the automated information system “Organ Donation,” which at that time was used by the service and contained all information about a potential donor in real time, with fibrobronchoscopy data in the form of a video file and DICOM file of the lung radiography examination also uploaded to the specified system. Such a tool, created on the prototype of the UNOS information system (iTransplant), allows users to document all data transfer and make the process of offering a donor more transparent and objective. The lung donor risk index was calculated using the 2020 Zurich Lung Donor Risk Index system.

In general, management of potential donors is conducted by on-duty anesthesiologists-resuscitators, using the “rule 100.”⁸ Crystalloid replenishment was used to achieve euvolemia, 5% albumin was preferred for volume control, and resuscitation with hydroxyethyl starch was avoided. Both donors described in this report did not have a decrease in hemoglobin levels below 70 g/L; therefore, the use of blood products was not discussed. Target central venous pressure was 6 to 8 mm Hg and target mean arterial pressure >60 mm Hg. As pressor support, vasopressin (0.01-0.04 U/min), dopamine, norepinephrine, and epinephrine were titrated to achieve the minimum acceptable dose. Desmopressin was used to control polyuria, which developed on the background of brain death and secondary diabetes insipidus. The sodium level was controlled by gastric lavage with distilled water. Glucose levels were controlled by administration of insulin. As an antimicrobial prophylaxis, carbapenems (imipenem-cilastatin) were administered to potential donors at a daily dose of 2 g. The ventilation strategy involved reducing ventilation volumes to 6 mL/kg. Daily fibrobronchoscopy sanations were performed.

Brain death is determined according to the adopted legislation, with a standard assessment of neurological status by a neurologist, an apnea oxygenation test, and a waiting period of 6 hours before death is determined. Permission for withdrawal is issued by the chief physician of the health care facility where the potential donor is located, as well as by a forensic medical expert. At the time of removal, medical organizations are not informed, in accordance with the procedure established by the legislation of the Russian Federation, that a potential donor during his lifetime or other persons declared their disagreement to the removal of his organs and tissues after death for transplantation. The gratuitous allocation of organs to Moscow from the region is agreed in writing by the regional transplant program director.

The technique for performing a virtual cross-match for lung transplant is to determine the compatibility of the recipient and the potential donor organ by analyzing blood serum virtually, using flow cytometry with multiplexing (Luminex).

Lung procurement was performed by a visiting team of surgeons from the hospital where lung transplant was performed, which arrived by air. The distance from the Samara airport (Kurumoch) was 75 and 110 km to the medical institutions; transpor-tation involved sanitary transport. Both donor cases were multiorgan donors, and the heart, liver, and kidneys were also preserved.

The standard surgical technique of removing the bi-pulmonary complex in a single block was used. Before antegrade perfusion, 500 pg of prostaglandin E dissolved in 10 mL of saline was injected bolus-wise into the pulmonary trunk. The lung block was packed in a standard triple bag system. Donor organs in the triple bag system were transported in a conventional transport refrigerator (marked with the IATA LHO).

Case Report

Case 1 patient information
Patient 1 was 30 years old and admitted on an emergency basis because of the appearance of donor lungs. Patient 1 had cough with discharge of viscous sputum of gray-green color of about 50 mL per day and shortness of breath with minimal physical exertion (4 points on the Medical Research Council Scale for Muscle Strength).

At the age of 1.5 years, a sweat test was used to establish the diagnosis of cystic fibrosis, which was a mixed pulmonary-intestinal form. At the age of 14 years, the patient presented with Pseudomonas aeruginosa infection, and, since 2010, she has required oxygen therapy regimen with a flow of 1 to 2 L/minute. Since 2013, the underlying disease has worsened, with incidences up to 6 times a year, and oxygen saturation at rest has decreased to 70%. In 2016, a suitable donor was identified in a hospital in Samara.

Case 1 physical examination and diagnosis
Upon admission, patient 1 presented with severe condition because of acute respiratory failure against the background of chronic respiratory failure and exhaustion. Examination revealed that oxygen saturation at rest without oxygen support was 89% to 90%, which decreased to 70% with minimal physical activity. During auscultation of the lungs, dry wheezing of various degrees in the basal parts of the lungs was demonstrated. Patient 1 had height of 1.70 m, weight of 50 kg, body mass index (in kilograms divided by height in meters squared) of 17.3, chest circumference of 78.5 cm, exhalation of 76 cm, blood pressure of 90/60 mm Hg, and heart rate of 130 beats/minute.

Patient 1 was diagnosed with cystic fibrosis (mixed pulmonary-intestinal form, severe course), exacerba-tion of chronic purulent-obstructive bronchitis, diffuse bronchiectasis, and diffuse hyper-pneumosclerosis. Complications included acute respiratory failure on the background of chronic respiratory failure of the third degree of hypoxemic type and secondary first-degree pulmonary hypertension.

Case 1 donor examination
The donor was a 39-year-old woman, diagnosed with brain death as a result of traumatic brain injury. The donor had height of 165 cm and chest circumference of 88 cm, corresponding to the recipient. The shape of the chest was barrel-shaped, and no pathology was observed during chest radiography. Examination showed ventilator breathing rate of 14 breaths/min, maximum inspiratory pressure of 16, PEEP of 5 mm Hg, Fio₂ of 30%, arterial oxygen saturation of 100%, Pao₂/Fio₂ of 4.6, mode intermittent positive pressure ventilation, heart rate of 90 beats/min, blood pressure of 100/60 mm Hg, central venous pressure of 0 cm of water, and hemoglobin level of 92 g/L. During fiberoptic bronchoscopy, no pathology of the trachea, right and left main, lobar and segmental bronchi mucosa was detected. The donor was recognized as acceptable for donation.

Case 1 transplant procedure
A bilateral lung transplant was performed using a clamshell approach with the use of central venoarterial extracorporeal membrane oxygenation (ECMO). Bronchial and vascular anastomoses were formed and the right lung was then reperfused; the reperfusion was satisfactory, the right lung was pink, and the anastomoses were stable. Duration of pharmaco-cold preservation of the right lung was 8 hours and 30 minutes. Left lung reperfusion then occurred, showing pink left lung, satisfactory reperfusion, and consistent anastomoses. With volumetric mechanical ventilation, the size of the lung grafts corresponded to the size of the recipient’s chest. Duration of pharmaco-cold preservation of the left lung was 10 hours and 50 minutes.

Case 1 postoperative period
The postoperative period was accompanied by reper-fusion pulmonary edema. To maintain normocapnia, patient 1 required central ECMO with a capacity of 4 L/min. To maintain stable hemodynamics, patient 1 received vasopressor support with norepinephrine and dobutamine. Blood-gas composition was monitored every 4 hours to correct the parameters of mechanical ventilation and central ECMO. Imme-diately after surgery, the patient received basic drug therapy with immunosuppression that included tacrolimus 2 mg at 2 times/day, methylprednisolone 125 mg at 3 times/day, and mycophenolic acid 1 g at 2 times/day. She also received antibacterial (meropenem 6 g intravenously, linezolid 600 mg intravenously 2 times/day), anticoagulant, and gastroprotective agents. After condition of patient 1 had stabilized, on day 2, a rethoracotomy was performed, the patient was disconnected from the central ECMO, and she was extubated and transferred to noninvasive ventilation of the lungs.

The fibrobronchoscopy showed endoscopic picture corresponding to interstitial pulmonary edema. Satisfactory conditions were shown of the donor bronchial mucosa and anastomosis of the right and left main bronchi.

In the early postoperative period, acute post-hemorrhagic anemia (hemoglobin 68 g/L) was associated with the volume of surgical intervention, which was stopped by blood transfusion. According to the control computed tomography scans of the chest, no pathology was detected (Figure 1); areas of anastomoses were bronchial and vascular, and areas of cannulations were in satisfactory condition. The tacro-limus concentration was satisfactory at 10.3 ng/mL.

Drains were removed on day 8. The patient was discharged on day 38 after bilateral lung transplant in a satisfactory condition, on independent breathing, and saturation of 98%. The development of prednisolone-induced arterial hypertension, stopped by antihypertensive drugs, was also noted.

At 4 years after lung transplant, obliterating bronchiolitis developed due to chronic rejection of the lung graft. At this time, the patient became dependent on oxygen, and there was a progression of hyper-capnic respiratory failure. Noninvasive mechanical ventilation was also performed sporadically. In January 2023, the patient was hospitalized with pronounced respiratory failure and a rise in body temperature. She was treated in the intensive care unit for 27 days, underwent massive antibacterial, infusion, and symptomatic therapy, and underwent tracheal intubation because of the ineffectiveness of noninvasive mechanical ventilation. Despite the ongoing therapy, the patient died from uncorrected hypercapnia.

Case 2 patient information
Patient 2 was 38 years old and admitted on an emergency basis due to the presence of donor lungs. The main complaints were shortness of breath at rest (4 points on the Medical Research Council Scale for Muscle Strength) and cough with a small amount of viscous purulent sputum.

Family history of patient 2 showed an older sister with a clinical picture of cystic fibrosis and death in infancy. From the anamnesis at age 2 months, a diagnosis of cystic fibrosis was made. During school years, he periodically presented with pneumonia, but the intestinal syndrome always prevailed over the pulmonary one. On August 15, 2017, a suitable donor was found in the Samara region, and patient 2 was urgently called for surgery.

Case 2 physical examination and diagnosis
At admission, patient 2 showed moderate condition due to chronic respiratory failure and clear consciousness. The chest was symmetrically involved in the act of breathing and barrel-shaped, and the frequency of respiratory movements was 26 breaths/min. The patient showed hard breathing and crepitation in the lower parts. Noninvasive mechanical ventilation was performed with an oxygen flow of 8 L/min and arterial oxygen saturation of 88%, which reduced to 75% with minimal physical activity. Patient 2 had height of 1.82 m, weight of 58 kg, BMI of 17.4, and chest circumference of 92 cm on inspiration and 91 cm on exhalation. Anthropometric data matched the donor.

Patient 2 was diagnosed with cystic fibrosis (severe course), diffuse bronchiectasis, and diffuse pneumosclerosis. Complications included third-degree respiratory failure.

Case 2 donor examination
Donor had blood type O (I Rh+), was 35 years old, male, and had brain death from hemorrhagic stroke. The donor had height of 190 cm, chest circumference of 89 cm, demonstrated full vesicular respiration with no wheezing, and had normal chest shape. The donor was intubated in the hospital and had ventilation duration of 51 hours, mode continuous mandatory ventilation, maximum inspiratory pressure 15FiO, Fio₂ of 30%, PEEP of 5 mm Hg, Pao₂/Fio₂ of 3,2, arterial oxygen saturation of 100%, breath rate of 12 breaths/min, heart rate of 90 beats/min, blood pressure of 100/70 mm Hg, central venous pressure of 5 mm of water column, chest radiography without pathology, and hemoglobin level of 95 g/L.

The fibrobronchoscopy of the donor showed the condition of the tracheal mucosa, right and left main, and lobar and segmental bronchi without pathology. The donor was recognized as acceptable for donation.

Case 2 transplant procedure
The organ for transplant was procured normally. Lung transplant was performed without ECMO. Retrograde perfusion of the left lung was performed first, with the right lung started several hours later. Duration of pharmaco-cold ischemia was 10 hours for the left lung and 12 hours and 45 minutes for the right lung.

Case 2 postoperative period
On day 2 posttransplant, patient 2 was extubated, transferred to noninvasive ventilation with an oxygen supply of 4 to 5 L/min, and then to independent breathing with minimal oxygen support. After transplant, the patient started basic drug therapy with immunosuppressive agents of tacrolimus 2 mg at 2 times/day, methylprednisolone 125 mg intra-venously 3 times/day, and mycophenolic acid 1 g at 2 times/day. He also received mucolytic (acetyl-cysteine 70 mg/kg/day), antibacterial (meropenem 6 g intravenously, linezolid 600 mg intravenously at 2 times/day), antiviral (ganciclovir 250 mg at 2 times/day), anticoagulant, gastroprotective, and inhalation agents.

On fibrobronchoscopy, the condition showed bilateral lung transplant, signs of ulcerative anas-tomosis of the left main bronchus, ischemia of the mucosa of the donor bronchi of both lungs (third degree), and purulent tracheobronchitis (third degree).

The postoperative period was complicated by the addition of opportunistic infections (cytomegalovirus infection, fungi of the genus Aspergillus); patient 2 received antiviral (ganciclovir 100 mg at 2 times/day, then Valcit 900 mg once per day) and antifungal (Eraxis 100 mg at 2 times/day, Mycamine 100 mg once per day) therapy. Computed tomography data showed development of bilateral polysegmental pneumonia, and the patient received correction of antibacterial therapy. Drains were removed on day 8.

The patient was discharged from the hospital on day 87 after bilateral lung transplant in a satisfactory condition, breathing independently without oxygen support, having oxygen saturation of 97% to 98%, and showing satisfactory tacrolimus concentration in the blood (11.7 ng/mL).

During follow-up of 7 years, the patient had no episodes of shortness of breath, no decrease in exercise tolerance, and oxygen saturation of 97%. In 2023, computed tomography scans showed signs of local fibrotic changes in the upper lobes of both lungs (Figure 2), and isolated bullae in the upper lobes of both lungs.

Discussion

In both cases, there were difficulties during the preflight inspection, as the airport security service and airline employees were not properly aware of the requirement of paragraph 60 of the Order of the Ministry of Transport of the Russian Federation dated July 25, 2007, No. 104 (“On approval of the Rules for conducting pre-flight and post-flight inspections”). However, after the necessary explanations, the problems with preflight control were resolved. A package of accompanying documents was attached to the donor organ: an employee’s identity document, a copy of the license for transporting human organs and/or tissues, a passport of the donor organ, an integral part of data on the donor’s examination for the presence of vector-borne infections, a declaration of the safety of the cargo being transported, and an act of acceptance and transfer of the donor organ or tissue.9 Taking into account the need to preserve the reference sample, we organized long-term storage of frozen samples of biological material from potential donors for the incubation period of pathogens of hemo-transmissive infections.¹⁰

We requested information about a potential donor in the database of individuals with contraindications to blood donation. The removed donor organ was accompanied by the following biological material: 2 blood samples (4 mL each) in tubes with preservative K2-EDTA, 1 blood sample (10 mL) in a tube without preservative, and a fragment of the spleen for reference testing for the presence of vector-borne infections and immunological typing.

Conclusions

In the context of shortages of donor organs, long-distance transportation is a reasonable, feasible, and safe procedure. The first cases presented here showed that the implementation of interregional cooperation while preserving donor lungs does not require special organizational and technical measures; it can be implemented with good administrative contact and competent resuscitation doctors in donor hospitals. The development of logistics on information and transport will undoubtedly contribute to the availability of donor organs to patients, which will save more lives.11 Existing algorithms for evaluation and conditioning of donor lungs seem to be effective and made it possible to provide patients with donor organs in the described cases.

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