lung transplant.ppt donor selection and management

lung transplant.ppt donor selection and management

1. JOURNAL PRESENTATION- Lung Donor Selection and Management: An Updated Review By- Dr. Payal Gawai

2. Lung Donor Selection and Management Lung transplantation ( LTx ) is a lifesaving treatment for end-stage lung disease patients with no other options. the first LTx in 1963, Advancements seen in: Surgical techniques Immunosuppression Post-transplant management Diagnostic testing improve short- and long-term outcomes.

3. Ideal donor lung criteria: Age <55 years ABO compatibility Clear chest radiograph PaO2 >300 mm Hg on FiO2 1.0 and PEEP 5 cm H2O Cigarette smoking history ≤20 pack-years No chest trauma No evidence of aspiration or sepsis No prior cardiopulmonary surgery Negative sputum gram stain No purulent secretions on bronchoscopy Extended criteria donors: Age ≥55 years PaO2 <300 mm Hg on FiO2 1.0 and PEEP 5 cm H2O Cigarette smoking history >20 pack-years Inhalation drug abuse Presence of infiltrations on chest X-ray or purulent secretions on bronchoscopy Donors with prior cardiothoracic procedures

4. Proper donor selection and management reduce early post-transplant complications and primary graft dysfunction (PGD). PGD, due to ischemia-reperfusion injury, within 30 days post- LTx . PGD leads to prolonged mechanical ventilation, longer ICU stays, and baseline lung allograft dysfunction. Risk factors for PGD – donor’s smoking history, clinical course at organ allocation, lung preservation mode, and recipient’s pulmonary hypertension.

5. Donor Age Standard donor age: ≤55 years for lung transplantation Extended criteria donor age: ≤65 years CF recipients with donors ≥55 years: inferior survival, longer ICU stays donors older than 50 years have increased the risk of death for recipients younger than 60 years compared to recipients older than 60 years. No significant differences in ventilatory support duration, ICU, or hospital stay Bronchial anastomotic complications: no difference, Five-year survival: 73.6% (older) vs. 73.1% (younger), Five-year CLAD-free survival: 51.5% (older) vs. 59.2% (younger),

6. studies shows: Increased survival and decreased bronchiolitis obliterans in opposite-gender transplants (M to F, F to M). ISHLT registry - Increased mortality in F to M transplants. F to F transplants:--Improved short- and long-term survival. Race matching: no change in one-year rejection rates Donors of African American origin: increased risk of death for recipients, regardless of recipient variables Recipient race: no difference in survival rate Donor Gender and Donor Race

7. Smoking History Donor smoking history raises concerns for: Obstructive pulmonary disease Undiscovered cancer/metastases Future malignancy risk To Minimize the risks it involves: In-depth chest imaging (X-rays, CT scans) Bronchoscopy examination Biopsy of suspicious areas during organ retrieval safe amount of cigarette smoke exposure for donors is Not defined Smoking history should not exclude donors Apical blebs from smoking can be resected during transplantation For donors with >20 pack-year history: Careful CT assessment for emphysematous changes or suspicious lesions Assessment of respiratory mechanics on the ventilator to guide for acceptance decisions

8. Oxygenation PaO2 Measurement: PaO2 on 100% FiO2 and PEEP of 5 used for quality assessment of donor lungs Standard donor criteria: PaO2 >300 mm Hg Research Findings: UNOS database study ( Zafar et al.): donor PaO2 did not affect graft survival, irrespective of transplant laterality Whitford et al.: no differences in time to extubation , incidence and severity of PGD, graft function, and 1-year survival between recipients with PF ratio <300 and >300 Atelectasis in high BMI donors contributes to lower PF ratio Lungs with lower PF ratio can be used via: Intraoperative lung recruitment (PEEP 25-30 cm H2O for 30 seconds) Ex vivo lung perfusion

9. Size Size Matching in Donor Assessment: predicted total lung capacity ( pTLC ) based on age ,sex and height of donor. pTLC Calculation: Males: pTLC = 7.99 × height (m) - 7.08 Females: pTLC = 6.60 × height (m) - 5.79 Acceptable donor pTLC : 75%-125% of recipient pTLC . Considerations and Techniques: pTLC ignores weight, race, and recipient's lung disease. 3D CT volumetry provides accurate lung volume measurement, aiding size matching. Using 3D-CT scans to measure the recipient's chest volume helps surgeons determine the correct size for lung grafts. This technology allows them to accurately calculate how much to reduce the grafts before transplantation, ensuring a better fit and potentially improving outcomes.Pediatric patients with small chests may need lobar/split-lung transplantation or wedge resections. Lung reduction using staplers can be performed for oversized donor lungs

10. Active Infection Donor Airway Samples: Positive sputum gram stain and cultures common. Identification of organisms, susceptibilities, and appropriate antimicrobial therapy is treatment Infection Management: Important for donors with infiltrates or consolidation on imaging. Positive donor gram stain does not predict post-transplant pneumonia, oxygenation, or mechanical ventilation duration. Study Findings: Newcastle group: poor early graft performance and reduced survival with positive donor BAL cultures. Recommendations: Frequent airway sampling. Targeted antimicrobial therapy against detected organisms for optimal transplant outcomes.

11. Donor Malignancy Donors with Malignancy History: Obtain complete history: type, staging, diagnosis year, treatments, recurrence history. It helps us to predict transmission risk. Immunosuppression Post-Transplant accelerates tumor dissemination. Donors with active malignancy generally not recommended. Exceptions: extremely low-risk tumors (basal cell skin cancer, some squamous cell cancers, in situ cervix carcinomas, certain primary CNS tumors excluding high-risk types).

12. Donation After Circulatory Death (DCD) DCD vs. DBD Donors: Differ biologically, legally, and procedurally. Medically assisted circulatory death permitted in some countries (e.g., Belgium, Netherlands). Managed vs. Uncontrolled DCD: Managed DCD : intentional removal of cardiac and ventilatory support in a controlled setting. Uncontrolled DCD : higher risk of lung damage. Lung transplantation outcomes with DCD donors equivalent to those with DBD donors.

13. Donor Risk Criteria Ensuring Safety and Outcomes: Assess donors for HIV, HBV, HCV transmission risk. OPTN and PHS define risk criteria and policies for donor and recipient screening. Testing Protocols: All potential donors tested for HIV, HBV, HCV using NAT and serological tests, regardless of risk criteria. Risk Criteria Within 3 Months: Sex with a person known or suspected to have HIV, HBV, or HCV. Man who had sex with another man. Sex in exchange for money or drugs. Sex with a person who had sex for money or drugs. Drug injection for nonmedical reasons. Sex with a person who injected drugs for nonmedical reasons. Incarceration for ≥72 consecutive hours. Unknown medical or social history. Child born to a mother with HIV, HBV, or HCV. Child breastfed by a mother with HIV. Risk Assessment: the risk for undetected infection in donors with risk criteria present, when screened by NAT 30 days after the most recent risk behavior was less than 1 per million for HIV, HCV and HBV infection

14. Hepatitis B Donors HBcAb + Donors: used to increase available organs. It is Safe with hepatitis B vaccinated recipients. HBsAg + Donors: Rarely reported for lung transplantation. Study by Belga shows that HBsAg + Donors considered in urgent thoracic transplantation. Good short-term outcomes with antiviral therapy and HBIG .

15. Hepatitis C Donors Previously contraindicated due to 100% transmission risk. Current opioid crisis and second-generation DAAs(Direct acting antivirals ) enabled utilization of HCV+ organs. Study by Cypel et al: Compared outcomes of 22 HCV+ donors with 187 HCV- donors. Lungs from HCV+ donors placed on EVLP prior to transplant. 90% of HCV+ recipients developed viremia within a week, treated with 12-week DAA therapy. Significantly shorter waitlist time for HCV+ donor recipients. No significant differences in primary graft dysfunction, hospital stay, ICU stay, or acute rejection. Combination of physical viral clearance with germicidal light-based therapies using normothermic ex-vivo lung perfusion shows better results .

16. COVID-positive Donors RT-PCR Ct Values : Used alongside donor history and chest imaging for assessing organ suitability and transmissibility . Study Findings : Donors with Ct <35 : Declined for lung donation. Donors with Ct >35 : Further tested; those with positive LRT RT-PCR were declined. Recommendations for Deceased Donors: Pre-Transplant Symptom Assessment : Avoid donors with active clinical COVID-19 symptoms, irrespective of exposure history or negative PCR tests. Testing Requirements : Perform SARS-CoV-2 RNA testing using nasopharyngeal/ oropharyngeal swab, sputum/tracheal aspirate, bronchial wash, or BAL within 72 hours before organ donation. Deep Respiratory Specimen : Strongly recommend a deep respiratory specimen (bronchial wash, BAL, mini-BAL, or tracheal aspirate) for SARS-CoV-2 RNA testing for all lung donors. Thoracic CT Scan : for assessing donor risk and potential COVID-19 infection. Antigen Test : Not acceptable for donor evaluation. COVID-19 Vaccination : Vaccination status does not impact these recommendations.

17. Exposure to COVID-19 : Donors exposed to confirmed/suspected COVID-19 within the past 10 days can be considered if: Asymptomatic. More than 7 days post-exposure. At least one negative SARS-CoV-2 PCR from a lower respiratory sample within 24 hours of transplant. CT chest shows no pulmonary infection. Recipient is at high risk of death without the transplant. Prior COVID-19 : Donors with prior confirmed COVID-19 can be considered if: Clinical resolution of symptoms. More than 21 days since symptom onset. Immunocompetent without significant pulmonary disease. At least one negative RT-PCR. CT chest negative for pulmonary infection/chronic lung injury. Strongly recommend a lower respiratory sample for SARS-CoV-2 testing for all lung donors

18. . Donor Management Optimization of Brain-Dead Donor Lung- Utilization Rate : Less than 13% of brain-dead donors are used for lung transplantation. Management Strategies : Fluid Balance : Restrictive fluid balance linked to higher lung procurement rates. Aggressive volume repletion supports kidney function but may impair lung procurement. Ventilation : High PEEP (>10 cm H2O) or alveolar recruitment maneuvers (PEEP >16-20 cm H2O) can prevent lung injury but may impact hemodynamic status of donor .

19. Intensive Treatment Protocol : Protective Ventilation : Use lung-protective strategies. Recruitment Maneuvers : Employ methods to improve lung function. High PEEP : Utilize to prevent lung injury. Fluid Management : Restrict fluids, use diuretics, target reduced extravascular lung water (EVLW). Cardiac Output Monitoring : Guide fluid and catecholamine administration. Steroids : Administer after -brain death diagnosis. Outcome :Increased lung donor utilization, more than doubling lung graft retrieval and transplantation rates. Goals of management of donors includes- Optimize cardiac filling pressures. Maintain adequate arterial pressure for organ perfusion. Ensure patent airway. Implement lung protective ventilation strategies. Maintain metabolic homeostasis.

20. Monitoring Monitoring and Management of Donor : Hemodynamic Monitoring : Arterial and Central Venous Lines : Essential for tracking hemodynamic status. Pulmonary Artery (PA) Catheter : Preferred in donors with low mean arterial pressure (MAP <60 mm Hg) and appropriate central venous pressure (CVP 6-10 mm Hg). Regular Testing : Arterial Blood Gases : Monitor regularly for respiratory and metabolic status. Chest Radiographs CT Scan of Thorax End-Tidal Carbon Dioxide Monitoring : Bronchoscopies : for direct lung assessment. Lung Compliance : Track lung compliance; a decline in compliance alongside abnormal test results can indicate lung pathology.

21. Ventilatory and Airway Management Protective Lung Ventilation and Management During Donor Care: Ventilation Strategies : Tidal Volumes : Limit to 6-8 ml/kg ideal body weight (IBW). Driving Pressures : Keep low. PEEP : Use 8-10 cm H2O. Peak Airway Pressures : Avoid >35 mm Hg to prevent barotrauma / volutrauma . Endotracheal Suctioning : Perform regularly. Regular Monitoring : Arterial Blood Gases : Check for hypoxemia and acidosis; correct as needed. PO2 Levels : Limit to <500 mm Hg to reduce risk of bronchiolitis obliterans . Endotracheal Tube Cuff : Ensure proper inflation to prevent aspiration. Bronchoscopy : Examine airways for lesions, inflammation, or mucopurulence ; assess for aspiration and collect airway samples for infection . Ventilation-Perfusion Mismatch : Avoid hypervolemia , use antimicrobial therapy, diuretics, and recruitment maneuvers to decrease hypoxemia. Prone Positioning and Airway Clearance : Improve lung compliance.. Intraoperative Maneuvers : Deflation Test : Routine during lung procurement to assess compliance. Dynamic Compliance ( Cdyn ) : PIP - positive end-expiratory pressure/tidal volume; a strong predictor of short-term graft performance according to Benazzo and colleagues.

22. Role of Prone Ventilation Duration and Benefits : Prone Ventilation : 12-16 hours improves oxygenation and increases lung utilization in brain-dead donors with hypoxemia and atelectasis . Mechanisms :-Enhanced V/Q matching. Improved drainage of secretions. Long-term reduction in atelectasis . Safe prone positioning needs skilled personnel to manage tubes and catheters. OPO agencies should collaborate with hospitals/healthcare providers to train staff and educate families on the importance of prone positioning. Swine Model ( cDCD ) : Prone ventilation improved alveolar air distribution, reduced edema and cell inflammation, and decreased cell death during warm ischemia time (WIT). Better lung function and quality observed during ex vivo lung perfusion (EVLP) compared to the supine position. Prone positioning after death declaration may enhance lung utilization in cDCD Donors :

23. Fluid Management Euvolemia : important for maintaining donor organ function. Challenges : Brain-dead donors may experience vascular tone loss, increased capillary permeability, and intravascular volume depletion. Sympathetic Surge : Causes neurogenic hypertension followed by hypotension. Fluid Management : Crystalloid Solutions : Use 0.9% sodium chloride or Ringer's lactate for fluid replenishment and maintenance in cases of reduced preload. Hypernatremia : Treat with dextrose-containing fluids or hypotonic solutions (e.g., 0.45% sodium chloride). Metabolic Acidosis : Sodium bicarbonate may be used to correct acidosis. Euvolemia vs. Pulmonary Edema : Careful balance is needed to avoid pulmonary edema. Monitoring : PA Catheter : Consider for accurate measurement of filling pressures, vascular pressures, and cardiac activity. Avoid sudden intravascular volume overloads, which may impair right ventricular function and lead to renal dysfunction.

24. Inotrope and Vasopressor Use Persistent Hypotension : Around 90% of brain-dead donors experience persistent hypotension despite fluid resuscitation, requiring vasopressors . First-Line Medications : Vasopressin: Receptors : V1 and V2 receptor agonist. Dosage : Use the lowest effective dose. Benefits : Linked to improved donor heart function and enhanced organ recovery. Dopamine: Use : Alternative first-line medication, particularly for inotropic support. Dosage : Low-dose (4 mg/kg/min) may reduce post-transplant dialysis needs. Evidence : Prospective randomized-controlled trial indicates reduced need for dialysis in renal and heart transplant recipients. Other Medications : Epinephrine and Norepinephrine : Function : Achieve hemodynamic targets. Concerns : Can downregulate beta-receptors, potentially reducing post-transplant contractility. Safety : Norepinephrine deemed safe in recent studies, but high doses (>0.2 mg/kg/min) may increase cardiac damage risk. Monitoring and Assessment : Echocardiograms : Evaluate cardiac function, especially in donors on vasopressors .

25. Hormone Replacement Therapy Hormonal Changes Post-Brain Death : Drop in Hormones : Abrupt fall in cortisol , insulin, antidiuretic hormone (ADH), and thyroxine levels. Impact : Necessitates hormonal therapy for effective organ perfusion and function. Corticosteroid Therapy : High-Dose Corticosteroids : Dosage : 15 mg/kg methylprednisolone . Benefits : Reduces systemic inflammatory response, pro-inflammatory cytokines, lung injury; improves oxygenation and lung procurement rate. Lower-Dose Corticosteroids : Dosage : 300 mg hydrocortisone. Benefits : Improves oxygenation and hemodynamic stability; less hyperglycemia compared to high doses of methylprednisolone . Diabetes Insipidus (DI ) : Affects 80% of donors due to ADH drop and reduced sympathetic vascular tone. Risks : Hypotension, hemoconcentration , hypernatremia . Monitoring : Polyuria : Urine output >3 ml/kg/hour or >3 liters/day. Serum Osmolality : High Urine Osmolality : Low Hypernatremia : Serum Na+ >145 mmol /liter. Treatment : Vasopressin or desmopressin (for normotensive donors) can enhance organ procurement.

26. Antibiotics and Intraoperative Assessment Antibiotic Selection : Basis : Choose antibiotics based on Bronchoalveolar Lavage Fluid (BALF) microbiology, including culture and drug sensitivity testing. Intraoperative Assessment : Spinal Reflexes : Present in some brain-dead donors (DBD); muscle relaxants may be required to inhibit somatic responses to surgical stimulation. Liver Procurement : In Situ Separation : May impact the duration of the donor operation. Fluid Management : Be prepared for significant fluid changes and possible blood transfusions in case of major bleeding. Ventilation : Tidal Volume : Maintain at 6 to 8 ml/kg as part of a lung-protective ventilation strategy. Hemodynamic and Metabolic Goals : Pre-Retrieval : Ensure these goals are met before donor lung retrieval.

27. Assessment and Management of Lung Function in Donor Procurement: Oxygenation Measurement : Arterial Blood Gas (ABG) : Reliable for overall oxygenation but may not accurately reflect individual lung function. Pulmonary Vein Gas Measurement : Advantage : Provides precise evaluation of gas exchange for each lung lobe. Evidence : Differential pulmonary vein gases are better predictors of primary graft dysfunction compared to donor arterial blood gases. Recommendation : Include selective pulmonary vein gas measurements for a more accurate assessment of lung function. Intraoperative Bronchoscopy : Assess Anatomical Variants : E.g., bronchus suis (accessory bronchus). Identify Intra-luminal Issues : Growths, airway inflammation, bleeding, or excessive secretions. Arterial Blood Gas Analysis : Conditions : Perform with FiO2 at 100% and PEEP of 5 cm H2O

28. Paragonix LUNGguard DLPS(Donor lung preservation): FDA-approved device for preserving donor lungs during transportation and transplantation using cold storage solutions. Enabled safe transportation of donor lungs over ~7,705 km with total ischemia duration exceeding 13 hours. GUARDIAN-LUNG Study : Evaluate outcomes of lung transplant patients receiving lungs preserved and transported using the Paragonix LUNGguard DLPS

29. Extravascular Lung Water (EVLW) : EVLW - : Fluid build-up in the alveolar and interstitial space. Causes elevated lung weight, common in ischemia reperfusion injury (IRI), and may impair lung function. Larger lungs (corrected for body size) had worse early clinical outcomes in both EVLP and straight lung transplant patients. Recent Porcine Study : Evaluate real-time lung weight measurements during EVLP to assess lung injury and donor lung suitability . Findings : Increased Kfc (filtration coefficient ) values were linked to real-time lung weight gain, indicating fluid leakage and lung injury.

30. Donor Lung Weight Measurement Abnormal Lung Weight Gain : Abnormal lung weight gain at 40 minutes into EVLP can indicate the need for further assessment at 1 and 2 hours. Phases of Real-Time Lung Weight Gain : Initial Rewarming Phase Evaluation Phase Reconditioning Phase Normalized lung weight gain was greater during the evaluation phase than during the reconditioning phase. Highest lung weight gain was noted during evaluation when FiO2 was 1.0, indicating that increased tidal volume during recruitment leads to increased fluid leakage . Real-time lung weight measurements are useful for assessing lung injury and determining donor lung suitability during EVLP. Early Warning : Abnormal lung weight gain at 40 minutes can serve as an early warning sign. Guiding Interventions : Lung weight data can help guide therapeutic interventions, such as hemoconcentration . Inflation Strategy : Lungs are left inflated at 75-80% of total capacity and at an FiO2 of 50% to reduce primary graft dysfunction and is importanat to avoid barotrauma High-Altitude Transport : Atmospheric pressure drops during high-altitude flights can cause volume expansion of lung air, risking barotrauma .

31. Effect of Local Anaesthetics on Lung Ischemia Reperfusion Injury Lung Ischemia-Reperfusion Injury (LIRI): Involves pulmonary endothelial cells, alveolar epithelial cells, alveolar macrophages, neutrophils , mast cells, platelets, proinflammatory cytokines, and surfactant. Volatile Anesthetics : Isoflurane and sevoflurane shown to reduce LIRI in animal studies. Anti-inflammatory Effects Anti-apoptotic Effects: Protective effects on lung tissue. Neutrophil Recruitment: Sevoflurane inhibits polymorphonuclear neutrophil recruitment into the lung. Vascular Smooth Muscle Tone: Volatile anesthetics act as pulmonary vasodilators. Metabolism Suppression: Reduced ATP use and activation of potassium adenosine triphosphate channels.

32. Ex Vivo Lung Perfusion (EVLP) Ex Vivo Lung Perfusion (EVLP): Established tool for assessing and rehabilitating donor lungs outside the body before implantation. Used for marginal or high-risk donor lungs otherwise unsuitable for transplantation. First applied by Steen in a DCD donor; effectiveness led to global adoption. Testing Modalities on EVLP: Includes radiography, bronchoscopy , angioscopy , and lung ultrasound. CLUE Study: Lung ultrasound used to assess edema; B-lines percentage ( extravascular lung water) quantified. Ayyat et al Study: Assessed 45 lungs from 23 donors, finding lower CLUE values in suitable lungs compared to unsuitable ones. Development of portable and automated EVLP equipment, enhanced imaging, and improved immunologic or genetic assessments.

33. Interventional Cross-circulation Platform Cross-Circulation Method: Utilized for rehabilitating donor lungs by providing prolonged, systemically regulated normothermic extracorporeal organ support . Guenthart Study Model : Conducted in a swine model with donor lungs unsuitable for transplantation. Findings: Lungs maintained on cross-circulation support without decline in lung function or tissue integrity. Lungs were amenable to repeated therapeutic interventions. Evidence of cellular regeneration and improved function over 36 hours.

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35. JOURNAL Lung Donor Selection and Management: An Updated Review Shefali Mody 1 , Soham Nadkarni 1 , Shreyash Vats 1 , Akshay Kumar 2 , Sravanthi Nandavaram 3 , Suresh Keshavamurthy