9/26/2018 HOW TO OPTIMIZE MY PATIENT FOR LUNG TRANSPLANT: GUIDE TO REFERRAL, EVALUATION AND SELECTION. Learning Objectives.

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1 HOW TO OPTIMIZE MY PATIENT FOR LUNG TRANSPLANT: GUIDE TO REFERRAL, EVALUATION AND SELECTION Disclosure I have no relevant financial relationships with any companies related to the content of this course. Aida Venado, MD MAS Assistant Professor University of California, San Francisco Aida.Venado@ucsf.edu Learning Objectives At the end of this session, the learner will be better able to: 1. refer patients for lung transplantation early enough 2. optimize patients to improve their chance of being listed 3. work collaboratively with transplant center to urgently evaluate hospitalized patients Outline Why select patients for lung transplant? Determining lung transplant candidacy Optimizing your patient for lung transplant Undergoing lung transplant 1

2 Why select patients for lung transplant? There is a shortage of suitable donor lungs. Complications lead to Early Post transplant Mortality Among recipients of lungs in the US: In 2016, 2345 lung transplants were performed in the US. Though, 2692 candidates were added to the transplant list that year. 6 month mortality: 6.6% 1 year mortality: 10.8% We need to identify and optimize patients at high risk of severe early complications. The goal is to select candidates that are likely to have survival benefit from transplant. Valapour M, Lehr CJ, Skeans MA, et al. Am J Transplant Jan;18 Suppl 1: Hook LJ, Lederer DJ. Expert Rev. Respir. Med. 6(1), (2012) Valapour M, Lehr CJ, Skeans MA, et al. Am J Transplant Jan;18 Suppl 1: Hook LJ, Lederer DJ. Expert Rev. Respir. Med. 6(1), (2012) Determining Lung Transplant Candidacy Evaluation of Lung Transplant Candidacy Referral Evaluation Selection Transplant Sick enough to need transplant? Well enough to have a successful transplant? Referring Provider Transplant Center 2

3 Is the patient likely to have a successful lung transplant? High (>80%) likelihood of surviving at least 90 days post transplant High (>80%) likelihood of surviving 5 years post transplant provided there is adequate graft function Absolute Contraindications 1. Recent malignancy 2. Untreatable organ dysfunction 3. Coronary artery disease not amenable to revascularization 4. Acute medical instability 5. Poorly controlled infection with resistant microbes 6. BMI 35 kg/m 2 7. Severely limited functional status with poor rehabilitation potential 8. Medical non adherence 9. Substance abuse or dependence Relative Contraindications 1. Age > 65 years + other relative contraindications 2. Age > 75 years 3. Mechanical ventilation or extracorporeal life support 4. Prior chest surgery 5. Infection with Burkholderia cenocepacia or gladioli, Mycobacterium abscessus 6. Infection with HIV, hepatitis B, hepatitis C 7. BMI with central obesity 8. Severe malnutrition Concern About Prior Chest Procedures Pleurodesis, chest tube insertion, lung volume reduction surgery Associated with bleeding, primary graft dysfunction and renal dysfunction Increased risk of phrenic nerve damage, chylothorax, re exploration 3

4 Selection of Lung Transplant Candidates Physiology Body Composition Psychosocial Readiness Prognosis Bilateral / single lung transplant Timing of transplant Organ function Comorbidities Malignancy Frailty Deconditioning Malnutrition Obesity Motivation Mental readiness Medical compliance Substance abuse Caregiver support Financial resources The decision to add patients to the wait list is discussed in multidisciplinary meeting. My patient has a contraindication. Does that mean he/she cannot get a lung transplant? Not necessarily. Some potential barriers are modifiable or can be managed in transplant centers with expertise. The evaluation purpose is to overcome barriers. Refer early & work collaboratively! The Evaluation is to Overcome Barriers The Evaluation is to Overcome Barriers Physiology Coronary artery disease Stent placement & clopidogrel Combined CABG & lung transplant Low LV ejection fraction Afterload reduction, ACE inhibitor, beta blocker Low renal function (24 h Cr clearance <60 ml/min) Optimal blood pressure control Optimal blood glucose control Avoid nephrotoxic medications Psychosocial Readiness Mental readiness for transplant Medical compliance Abstinence of substance abuse Learning disabilities Commitment of primary and secondary caregivers Financial resources Fundraising Suspicion of cirrhosis Liver biopsy Social worker, financial counselor, mental health provider 4

5 Optimizing Your Patient for Lung Transplant 1. Recognize trajectory of lung disease & refer early 2. Provide enough oxygen 3. Improve frailty 4. Improve body composition 5. Age appropriate cancer screening Optimizing Your Patient for Lung Transplant 1. Recognize trajectory of lung disease & refer early 2. Provide enough oxygen 3. Improve frailty 4. Improve body composition 5. Age appropriate cancer screening When should I refer my patient for lung transplant? Early preparing for transplant takes time!! A good reference to start: Is my patient sick enough to need lung transplant? High (>50%) risk of dying in 2 years from lung disease Depends on the diagnosis 5

6 My patient with Interstitial Lung Disease Caveat: Correct ILD Diagnosis is Key! Referral At the time of diagnosis FVC < 80% of predicted DLCO < 40% of predicted Requirement for supplemental oxygen Failing medical therapy Listing FVC decline 10% in 6 months DLCO decline 15% in 6 months Desaturation < 88% 6 MWT < 250 m > 50 m decline in 6 MWT in 6 months Pulmonary hypertension Hospitalization Ryerson CJ et al Predicting survival across interstitial lung disease: the ILD-GAP model Chest 2014 My patient with Chronic Obstructive Pulmonary Disease Referral Progressive disease despite maximal therapy FEV1 < 25% predicted Simultaneous referral for LVRS is OK BODE index 5 6 PaCO2 > 50 mmhg PaO2 < 60 mmhg Listing BODE index 7 FEV1 < 15% 20% of predicted 3 severe exacerbations in 1 year 1 severe exacerbation with acute hypercapnia Moderate to severe pulmonary hypertension Prognosis in COPD Points on BODE Index B Body Mass Index >21 21 O Airflow Obstruction (FEV1 % of predicted) D MMRC Dyspnea scale E Exercise capacity (6 min walk distance, m) Points 4 year Survival (without transplant) % % % % Survival benefit from transplant only in COPD patients with BODE 7. 6

7 My patient with Cystic Fibrosis My patient with Pulmonary Hypertension Referral FEV1 30% predicted Rapidly declining FEV1 + Non tuberculous mycobacteria infection Burkholderia cepacia complex infection Diabetes PAP > 35 mmhg on echo Frequent exacerbations Requiring non invasive ventilation Increasing antibiotic resistance Worsening nutrition Pneumothorax Listing Chronic respiratory failure with: Hypoxia (PaO 2 < 60 mmhg) Hypercapnia (PaCO 2 > 50 mmhg) Long term non invasive ventilation Pulmonary hypertension Rapid lung function decline WHO functional class IV (symptoms at rest and severe with any activity) Referral NYHA Class III (comfortable at rest, symptoms with activity) NYHA Class IV (symptoms at rest, worse with any activity) Rapidly progressive disease Use of any parenteral therapy regardless of symptoms Pulmonary Veno occlusive Disease Listing NYHA Class III or IV despite 3 months of combination therapy Cardiac index < 2 L/min/m 2 Mean right atrial pressure > 15 mm Hg 6 MWT < 350 m Significant hemoptysis Pericardial effusion Progressive right heart failure: Renal insufficiency Hyperbilirubinemia Recurrent ascites Elevated brain natriuretic peptide Severe hemoptysis Optimizing Your Patient for Lung Transplant 1. Recognize trajectory and refer early 2. Provide enough oxygen 3. Improve frailty 4. Improve body composition (goal BMI > ) 5. Age appropriate cancer screening Pulmonary Hypertension is associated with Waitlist Mortality Mean PAP 25 mmhg Mean PAP 5 mmhg IPF CF COPD Hayes D Jr. Ann Thorac Surg Jan;101(1): Hayes D Jr. AJRCCM Oct 15;190(8): Hayes D Jr. COPD. 2016;13(1):

8 Provide Enough Oxygen Maintain SpO 2 >88% at all times (>90% if PH present). Reassess oxygen requirements and update prescription as needed. Diagnose and treat obstructive sleep apnea. Obtain echocardiogram if diffusion capacity declines. Refer to PH specialist (cardiology / pulmonology). Lacasse Y. Am J Resp Crit Care Med May 15;197(10): Hardinge M. Thorax. 2015;70:i1 i43 McLaughlin VV. J Am Coll Cardiol Apr 28;53(17): Farber HW. J Heart Lung Transplant Aug;37(8): LM Dowman. Respirology Jul;22(5): Optimizing Your Patient for Lung Transplant 1. Recognize trajectory and refer early 2. Provide enough oxygen 3. Improve frailty 4. Improve body composition 5. Age appropriate cancer screening Frailty is a State of Risk Frailty in Lung Transplant Candidates Not Frail Frail Is common: 10% by the Short Physical Performance Battery (SPPB) 28% by the Fried Frailty Phenotype (FFP) Is associated with death and delisting Is associated with 1 and 4 year post transplant mortality. Fried, LP. J Gerontol A Biol Sci Med Sci Singer JP. Annals of the American Thoracic Society. 2016;13(8): Singer JP, et al. American journal of respiratory and critical care medicine. 2015;192(11): Singer, JP. American Journal of Transplantation. In press 8

9 Frailty is Modifiable Optimizing Your Patient for Lung Transplant Enroll in pulmonary rehabilitation Exercise daily 1. Recognize trajectory and refer early 2. Provide enough oxygen 3. Improve frailty 4. Improve body composition 5. Age appropriate cancer screening Maddocks, M et al. Physical frailty and pulmonary rehabilitation in COPD: a prospective cohort study. Thorax Underweight and Obesity are associated with Death after Lung Transplant Improve Body Composition Goal Body Mass Index kg/m 2 (Caveat: BMI is a poor measure of adiposity, which is associated with post transplant mortality.) Refer to nutritionist Supplements, tube feedings Weight loss Wean off prednisone as much as possible ( 20 mg daily) Control hyperglycemia Hook LJ, Lederer DJ. Expert Rev. Respir. Med. 6(1), (2012) Singer JP. Am J Respir Crit Care Med Nov 1;190(9): Singer JP. Am J Respir Crit Care Med Nov 1;190(9):

10 Optimizing Your Patient for Lung Transplant Case: Optimization works 63 yo M respiratory therapist with OSA & familial IPF 1. Recognize trajectory and refer early 2. Provide enough oxygen 3. Improve frailty 4. Improve body composition 5. Age appropriate cancer screening 2009: lung biopsy. Mean PA 17 mmhg 2010: too early for transplant pulmonary rehabilitation & loose weight September 2015: Listed. O 2 at rest 5 LPM, exertion 8 LPM. Mean PA 29 mmhg May 2016: admitted from clinic. O 2 at rest 13 LPM, exertion 20 LPM 1 month wait in the hospital: O 2 at rest 15 LPM HFNC, ambulation 15 LPM NRB Walking 2 3 times daily Bilateral lung transplant on ECMO. Mean PA 41 mmhg Discharged 9 days post transplant Case: Struggling to transplant Case: Struggling to transplant 58 yo M gardener with diabetes who developed SOB 6 months later hospitalized for hypoxic respiratory failure Oxygen 80%, 30 LPM by HFNC Transferred to our ICU for transplant evaluation BMI 34, deconditioned No significant other, no children/relatives Not had colonoscopy Day 12 intubation and mechanical ventilation Day 14 Tracheostomy, heart catheterization (PA mean 51 mmhg) Day 17 CT colonography Day 20 listed for transplant Day 22 VA ECMO Day 24 Bilateral lung transplant 90 min lysis of adhesions Poor cardiac contractility VA ECMO post op Day 25 re exploration for left hemothorax, chest open Day 26 re exploration, chest closure, ECMO decannulation Day 35 re exploration for left chest wall hematoma 10

11 Case: Struggling to transplant Case: ECMO bridge to transplant Complications: Profound weakness Oropharyngeal dysphagia Required tube feedings Discharged 56 days post transplant to skilled nursing facility Required physical therapy Caregiver friends thankful for son surviving lung transplant Being on the Wait List Wait to be matched with a donor based on: Undergoing Lung Transplant Lung Allocation Score (ranges 0 100) LAS = Blood type Antibody profile Chest size Probability of living 1 year post transplant Benefit 2 X Probability of living 1 year in the waitlist Urgency Egan TM. Am J Transplant. 2006;6(5 Pt 2):

12 Early Post transplant Recovery Intraoperative and/or postoperative ECMO support Early extubation (~24 hours) Rehabilitation After Transplant Physical Therapy Ambulation 2 3 times daily Muscle strengthening Pain control with intercostal nerve cryoablation, low dose fentanyl and/or oxycodone, epidural analgesia. Daily bronchoscopy to clear secretions Nutrition Swallowing assessment Calorie count Tube feedings Gastric and bowel motility Aspiration precautions Lung Recipients are on Life long Immunosuppression Medications after Transplant The Good Prevent Rejection Infection The Bad Complications Malignancy Immunosuppression Prednisone Tacrolimus Mycophenolate Mofetil Treatment of Metabolic Complications Hyperglycemia Hyperkalemia Hypomagnesemia Hypertension Osteoporosis prophylaxis Peptic ulcer prophylaxis Metabolic and Systemic Infection Prophylaxis Pneumocystis jirovecii Aspergillus Pseudomonas Cytomegalovirus Treatment of pre transplant conditions Benign Prostate Hypertrophy Latent tuberculosis Raynaud s phenomenon Epilepsy 12

13 Staying Healthy after Transplant requires Diligence Learn more 1. Prevent infections 2. Daily exercise 3. Adequate nutrition 4. Strict adherence to medications 5. Follow up with transplant team 6. Follow up with primary care provider Avery RK, Michaels MG; and the AST Infectious Diseases Community of Practice. Am J Transplant. 2013;13(s4): Adegunsoye A, Strek ME, Garrity E, Guzy R, Bag R. Chest Jul;152(1): American Society of Transplantation. AST guidelines for nontransplant physicians caring for heart and/or lung transplant recipients. transplant physicians. Accessed September 4, Thank you Aida.Venado@ucsf.edu 13