LungTransplantation¶

Chapter 309 | Part 7: Disorders of the Respiratory System · Part 7 – Respiratory Disorders · Chapter 309

Key Clinical Points¶

The transition from LAS (2005) to CAS (2023) incorporates ethical considerations and access beyond just survival metrics.
Primary Graft Dysfunction (PGD) is a result of ischemia-reperfusion injury, not infection or rejection.
Severe PGD is defined by PaO2/FiO2 <100 at 72 hours post-transplant; it portends increased mortality and risk for CLAD.
B. cenocepacia colonization poses a high risk of bacteremia and early mortality post-transplant.
Nutritional status has a U-shaped relationship with outcomes, where BMI <18 or 30–35 increases risk.
Ex vivo lung perfusion (EVLP) can salvage up to 50% of potentially unsuitable donor lungs (e.g., DCD).
ECMO bridging to transplant offers survival rates equivalent to direct transplant in high-volume centers.
Frailty is an independent marker of poor outcome, distinct from 6-minute walk distance.
Donor management focuses on maintaining hemodynamic stability and avoiding hyperthermia/excessive oxygen.
Specific contraindications include active malignancy, certain Burkholderia species, and uncorrected organ dysfunction.

DEFINITION & CLASSIFICATION¶

• Definition (Harrison's 22e): Lung transplantation is a surgical procedure involving the replacement of one or both native lungs with donor lungs to treat end-stage lung disease. • Allocation Systems: ◦ LAS (Lung Allocation Score): Implemented in 2005; prioritizes based on survival metrics. ◦ CAS (Composite Allocation Score): Introduced in 2023; incorporates ethics, access, and efficiency beyond just survival.

EPIDEMIOLOGY¶

• Trends in Indications: ◦ IPF: Most common restrictive lung disease; increasingly frequent indication since LAS implementation. ◦ Pulmonary Vascular Disease: Less frequent due to medical advances, but remains an option for refractory cases. ◦ Cystic Fibrosis: Evaluation typically considered when FEV reaches ~30% predicted. • Wait-List Mortality: ◦ Under LAS: 10–12 deaths per 100 patient-years. ◦ CAS Goal: Improve equity and remove hard cutoffs in prioritization.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Primary Graft Dysfunction (PGD): ◦ Cause: Result of ischemia-reperfusion injury in the allograft. ◦ Distinction: Not related to infection or rejection. ◦ Clinical Presentation: Diffuse infiltrates on chest x-ray and poor pulmonary gas exchange. ◦ Severity Criteria: ◦ Mild PGD: PaO2/FiO2 <300. ◦ Severe PGD: PaO2/FiO2 <100 at 72 h post-transplant → increased mortality risk & risk factor for CLAD. • Donor Lung Pathophysiology: ◦ Brain death effects: Causes severe perturbations and neurogenic pulmonary edema. ◦ Stressors: Hemodynamic instability and neurogenic shock are major threats to allograft function.

CLINICAL FEATURES¶

• Functional Assessment: ◦ 6-minute walk distance: Inversely correlated with wait list and post-transplant mortality. ◦ Frailty: Independent marker of poor outcome. ◦ Assessment Tools: SPPB, Fried Frailty Phenotype (FFP), and Lung Transplant Frailty Scale (LT-FS) (the latter includes body composition/biomarkers). • Nutritional Status: ◦ U-shaped relationship: Risk increases in both underweight (BMI <18) and overweight (BMI 30–35) patients. ◦ Intervention: Nutritional consultation and enteral feeding for underweight patients. • Psychosocial Assessment: ◦ Multidisciplinary approach: Social work, psychiatry, and financial coordination. ◦ Focus areas: Anxiety, depression, substance abuse, and compliance with medical therapy.

DIFFERENTIAL DIAGNOSIS¶

• Infectious Considerations: ◦ Burkholderia cenocepacia: High risk of bacteremia, abscess, and early mortality. ◦ Other Burkholderia: B. dolosa and B. gladioli (similar risks); other species often have outcomes comparable to non-colonized patients. ◦ Mycobacteria: M. abscessus leads to chronic, refractory infections. ◦ Fungal: Assessment based on pathogenicity, resistance, and pre-transplant response. • Malignancy Considerations: ◦ Requirement: Period of remission before consideration. ◦ Variables: Duration depends on type, stage, and likelihood of recurrence.

DIAGNOSTIC APPROACH¶

Donor Evaluation (Table 309-2): • Criteria for ideal donor: ◦ Age <55 years. ◦ PaO2/FiO2 >300 on PEEP 5 cmH2O. ◦ Tobacco history <20 pack-years. ◦ Clear chest radiograph and negative sputum Gram stain.
Recipient Evaluation: • PFTs (e.g., FEV1 <25% predicted). • Functional assessment (6-minute walk distance). • Infectious workup (Burkholderia, Mycobacteria, etc.). • Nutritional and Psychosocial screening.
Post-Transplant Monitoring: • Assess for PGD at 72 hours post-transplant. • Criteria: PaO2/FiO2 <100 → Severe PGD; PaO2/FiO2 <300 → Mild PGD.

MANAGEMENT & TREATMENT¶

Surgical Approach Selection: • Right/Left Thoracotomy: No CPB required; preferred for single-lung. • Transverse Thoracosternotomy (Clamshell): Increased exposure; used for bilateral or to avoid CPB. • Median Sternotomy: Standard for bilateral; fewer wound complications; allows complex cardiac procedures.
Procurement Operation: • Pre-incision: Bronchoscopy, airway definition, and secretion evacuation. • Preparation: Systemic heparinization; Prostacyclin 15 min prior to explant. • Execution: Heart arrested first → Pulmonoplegia instilled → Topical iced-saline in pleural spaces → Explant.
Recipient Operation: • Step 1: Hilar structure isolation and division. • Step 2: Bronchial anastomosis (first) → check with saline insufflation. • Step 3: Connect pulmonary artery and left atrial cuff. • Step 4: Reperfusion → Lung-protective ventilation → Transition to normal ventilation.
Induction of Immunosuppression: • Induction agents: IL-2 receptor/CD25 antagonist, antithymocyte globulin, or anti-CD52 monoclonal antibodies. • Post-induction: Systemic corticosteroids and purine modulators. • Maintenance: Three-drug regimen (calcineurin inhibitor, purine modulator, corticosteroids).
Perioperative Support: • Monitoring: Arterial pressure, pulse oximetry, ECG, temperature, urine output. • Equipment: Double-lumen tubes for non-CPB; avoid air entrainment in ECMO circuit.
Advanced Technologies: • ECMO: Used for bridging; survival rates equal to direct transplant in high-volume centers. • EVLP: Assessment of marginal donors → can salvage up to 50% of unsuitable lungs.
Infection Management: • Early (1 month): Gram-negative bacilli, CMV (prophylaxis standard). • Late (10 days–2 months): Fungal infections (Amphotericin B or azoles). • Pneumocystis: Prevented by trimethoprim-sulfamethoxazole.

COMPLICATIONS & PROGNOSIS¶

• Primary Graft Dysfunction (PGD): ◦ Incidence of severe PGD: ~10–15%. ◦ Impact: Severe PGD at 72h → increased mortality and risk for CLAD. • Infection Risks: ◦ Factors: Continuous environmental contact, reduced lymphatic function, and impaired mucociliary clearance. ◦ Timing: Highest incidence coincides with peak immunosuppression. • Nutritional/Psychosocial Outcomes: ◦ U-shaped relationship for nutrition; requirement of strong support systems for post-transplant care.

SPECIAL POPULATIONS¶

• Donor Management (Specific Protocols): ◦ Goal: Maintain hemodynamic stability and preserve lung function. ◦ Fluids: CVP maintained between 5–8 mmHg; avoid crystalloid boluses. ◦ Medications: Vasopressin for DI; Prostacyclin for pulmonary flush. ◦ Avoidance: Hyperthermia (arrhythmias/acidosis), excessive oxygen (free radical injury). • Donor Contraindications (Table 309-1): ◦ Absolute: Chronic lung disease, active malignancy, severe asthma history, HIV. ◦ Relative: Older age, thoracic trauma, pulmonary hypertension, hypoxemia. • Wait-List Management:  Pulmonary Vascular Disease: Maintain RV function; continue pulmonary vasodilators until transplant.  Renal/Metabolic: Optimize diabetes management (especially in CF patients with pancreatic dysfunction).  Respiratory: Continue oxygen and physical exercise; use steroids for acute exacerbations (taper quickly).

KEY PEARLS & HIGH-YIELD POINTS¶

• PGD eq Infection: PGD is an ischemia-reperfusion injury, not a result of infection or rejection. • B. cenocepacia: High risk for mortality; specific concern in post-transplant period. • EVLP Utility: Can salvage up to 50% of unsuitable donor lungs. • Nutritional U-Curve: Both underweight and overweight (BMI 30–35) are risks. • ECMO Bridge: Survival is equivalent to direct transplant in high-volume centers.

Reference Tables¶

TABLE 309-1 Contraindications to Lung Transplantation Surgical considerations Age Functional status¶

Harrison's 22e, p.2283

	ABSOLUTE CONTRAINDICATIONS	RELATIVE CONTRAINDICATIONS
Surgical considerations	Anatomic abnormalities not amenable to transplant procedure
Functional status	Immobility, inability to participate in physical therapy/rehabilitation	Limited functional status as defined by 6-minute walk distance
	Untreatable, irreversible organ dysfunction
	Active malignancy or malignancy with insufficient remission period
	Active bacterial bloodstream infection
	Uncontrolled viral infection (HIV, hepatitis)
Nutritional		BMI <18 or >30–35
	Untreatable, irreversible psychiatric disorder with potential to impact transplant outcome
	Active substance abuse
	Other circumstances that would impede ability to participate in and comply with posttransplant care

TABLE 309-2 Characteristics of the Ideal Lung Donor Donor age ABO compatibility Chest radiograph Pa o :Fi o Tobacco…¶

Harrison's 22e, p.2285

Donor age	<55 years
Chest radiograph	Clear
Tobacco history	<20 pack-years
Evidence of aspiration	Absent
Sputum Gram stain	Negative