Management of the Postoperative Lung Transplant Patient

Introduction¹

• Lung transplantation is the definitive treatment for end-stage pulmonary diseases.
• Survival of lung transplant recipients is currently 60% at 5 years.
• Characteristics of the donor, recipient, and the interaction between them affect posttransplantation outcomes (Table 1).

Postoperative Management^1,3-5

• The main goals of postoperative lung transplant management are summarized in Table 2.

Mechanical Ventilation

• Lung transplant recipients are at risk for ventilator-induced lung injury (VILI), thus, lung-protective mechanical ventilation should be used.
• In single lung transplant recipients with fibrotic disease, use tidal volumes of 4-6 ml/kg donor predicted body weight to reduce the risk of overdistension of the allograft.
• In single lung transplant patients with obstructive disease, maximize the expiratory time and target a lower positive end-expiratory pressure to reduce the risk of hyperinflation of the native lung.
• Early weaning and extubation, ideally within 3-5 days posttransplantation
• Early mobilization and chest physiotherapy to facilitate bronchial hygiene and prevent atelectasis
  • Cough assist devices are discouraged due to the risk of injury to the healing bronchial anastomosis.

Hemodynamics and Fluids

• A Swan-Ganz catheter is essential to accurately monitor and manage cardiac preload, systemic and pulmonary arterial pressures, vascular resistances, cardiac output, and mixed venous oxygen saturation (SvO₂)
• Hemodynamic management in the first 72 hours is shown in Figure 1.
  • Specific hemodynamic targets, in combination with lung-protective ventilation, are associated with decreased severity of PGD.⁷
• The initial goal is to maintain adequate end-organ perfusion with the lowest possible cardiac output to avoid exacerbating reperfusion injury-induced lung edema.
  • Monitor by measuring lactate, urine output, and SvO₂
• Slowly increase lung perfusion by increasing cardiac output gradually to its expected target, while closely monitoring graft function (gas exchange and lung compliance)
• Judicious fluid administration in the early postoperative period to avoid pulmonary edema, with a goal of euvolemia
• Monitor coagulation factors and point-of-care viscoelastic coagulation studies, and correct coagulopathy accordingly to minimize the risk of bleeding
• Venoarterial extracorporeal membrane oxygenation (ECMO) is used as rescue therapy for patients with refractory cardiogenic shock or pulmonary hypertension with marked pulmonary edema
• Atrial fibrillation occurs in 20-30% of patients postoperatively, is generally transitory, and has an unclear impact on patient outcome
  • Management includes maintaining adequate electrolytes and a rate-control strategy, with β-blockers as the first-line agent in hemodynamically stable patients
  • Electrical cardioversion is reserved for unstable patients and refractory atrial fibrillation
  • If it persists for longer than 48 hours, start anticoagulation
  • Avoid amiodarone due to the risk of inducing lung injury

Nutrition

• Formal swallowing assessment should be performed, and enteral feeding initiated as soon as it is safe to do so.
• Patients with cystic fibrosis should receive enteral feeds with elemental or semielemental feed formulations.
• Aspiration precautions should be implemented for all lung transplant recipients due to the incidence of dysphagia and recurrent laryngeal nerve injury, and high morbidity and mortality associated with pulmonary aspiration.

Immunosuppression

• Acute rejection affects more than half of lung transplant recipients within the first year
• Triple-drug maintenance immunosuppression therapy is the standard of care: a calcineurin inhibitor (tacrolimus or cyclosporine A), a cell-cycle inhibitor (mycophenolate or azathioprine), and a corticosteroid.
• Induction therapy with basiliximab, antithymocyte globulin, or alemtuzumab is likely associated with improved outcomes and is routinely used in about 50% of lung transplant centers.⁸
• In patients with renal disease, advanced age, or complicated transplant surgery, early basiliximab therapy should be considered to enable a delayed start of nephrotoxic calcineurin inhibitors.

Antimicrobial Therapy

• Infections are the most frequent postoperative complications, affecting up to 42% of lung transplant recipients within 3 months.
• Up to 25% of postoperative deaths are infection-related.
• Pneumonia is the most common type of bacterial infection after transplantation.
  • Pseudomonas aeruginosa is the most common offending organism, followed by Staphylococcus aureus.
• Early empiric prophylaxis with broad-spectrum antibiotics is employed in the immediate (72 hours) postoperative period while awaiting the final results of donor and recipient bronchoalveolar lavage cultures.
  • Optimal duration is unknown, with reported regimens of 48 hours to 7 days.
• Prophylaxis against cytomegalovirus and pneumocystis jirovecii is standard, while antifungal prophylaxis is patient- and center-specific.

Pain and Sedation

• Multimodal analgesia and thoracic epidural analgesia (TEA) are recommended for postoperative pain control. TEA is associated with decreased intensive care unit length of stay and decreased length of mechanical ventilation
• Myofascial plane blocks, including the erector spinae plane and serratus anterior plane blocks, are easy to perform, safe, and have shown promising results, providing satisfactory analgesia after lung transplantation.¹⁰
• The use of paravertebral catheters has been described, but supporting evidence remains lacking.
• Deep sedation and use of benzodiazepines should be avoided, and daily sedation pauses should be employed to mitigate the risk of delirium and prolonged mechanical ventilation, both of which are associated with increased mortality.

Postoperative Complications^1-3

• PGD is a form of ischemia-reperfusion injury, clinically similar to acute respiratory distress syndrome, that affects 20-30% of graft recipients and occurs within the first 72 hours posttransplantation.
  • Defined as bilateral lung infiltrates on chest X-ray and a PaO₂:FiO₂ ratio less than 300
  • Donor-specific risk factors: significant smoking history, alcohol use, age less than 18 or more than 64 years, undersized lungs, traumatic brain injury, and lung contusion
  • Recipient-specific risk factors: history of sarcoidosis, idiopathic pulmonary fibrosis, and pulmonary hypertension; BMI greater than 25, left ventricular diastolic dysfunction, preformed autoantibodies, and history of pleurodesis
  • Intraoperative risk factors: use of cardiopulmonary bypass, prolonged ischemic time (>8 hours), FiO₂ >40% during reperfusion, large volume blood transfusion (more than 1L), delayed chest closure, and single lung transplant¹
  • Repeated bronchoscopies may be necessary to exclude anastomotic airway complications.
  • Rescue treatments for severe PGD (PaO₂:FiO₂ less than 150): prone positioning, administration of neuromuscular blockade, and inhaled nitric oxide (NO).
  • ECMO support should be considered in patients with very severe graft dysfunction (PaO₂:FiO₂ less than 100), or respiratory acidosis with high ventilator pressure requirements.
  • Data from several case series support the use of ECMO for refractory PGD to prevent additional VILI and oxygen toxicity.
  • The best ECMO configuration is controversial. Venoarterial ECMO provides both respiratory and hemodynamic support and reduces pulmonary blood flow; veno-venous ECMO provides respiratory support, reduces mechanical stress to the graft, but does not reduce pulmonary perfusion nearly as much.⁷
• Other respiratory complications are listed in Table 3
• Neurologic complications affect over half of all lung transplant recipients
  • Delirium affects approximately 40% of patients. Preventative strategies include adequate pain control, avoidance of benzodiazepines, and early mobilization
  • Hyperammonemic encephalopathy is a rare but serious complication, occurring in 1-4% of patients, that can progress to cerebral edema, coma, and brain death
    • Plasma ammonia concentration is monitored for at least two weeks posttransplant.
    • Ammonia levels greater than 100 µmol/L should be treated immediately with hemodialysis and antimicrobial therapy (moxifloxacin and doxycycline) to target the ureaplasma species.
  • Others include stroke, immunosuppressant-induced encephalopathy, critical illness myopathy, central nervous system infections, posterior reversible encephalopathy syndrome, and recurrent laryngeal nerve injury.
• Other complications are listed in Table 3.