19. Transplants

Epidemiology

As of the end of 2011, over 23,000 lung transplants have been performed in the United States.

Limiting factor is the availability of organs.

Compared to other organ transplants, long-term survival is worse than that of liver and kidney, but better than small bowel.

Key Pathophysiology

Early mortality can be divided into

30 day mortality: 10 to 15%, related to the transplant procedure and immediate postoperative complications

1 year mortality: 30%; leading cause is infection from high-dose immunosuppression

Recipients with certain preoperative diagnoses carry greater risks for specific complications

CF patients are at higher risk of infection due to preoperative presence of infection.

Complex congenital heart disease at higher risk for bleeding

Severe PHTN with single lung transplant at higher risk of severe ischemia-reperfusion injury and may require prolonged mechanical ventilation

Recipients of older grafts with longer ischemia times at risk of early and late graft dysfunction

Pulmonary denervation

Bronchial hyper-responsiveness

Decreased inhalation cough response (despite intact laryngeal cough response)

Denervation has been shown to have little effect on resting minute volume, tidal volume, respiratory rate, and breathing pattern.

Gas exchange

Hypoxic pulmonary vasoconstriction seems to remain intact in transplanted lungs.

Stunning of type 2 pneumocytes leads to decreased surfactant production immediately following transplantation, leading to increased risk of atelectasis.

Loss of lymphatic drainage in the transplanted lung leads to increased risk of pulmonary edema.

8 weeks after successful transplantation, these factors tend to normalize.

The pulmonary reimplantation response (PRR)/ischemia-reperfusion injury

Non-cardiogenic pulmonary edema in the immediate postoperative period, after ruling out rejection, infection, and cardiogenic causes

Ischemic vascular injury of the allograft results in increased permeability and interstitial and alveolar edema

Clinically results in hypoxemia with radiographic infiltrates

May also be associated with hypotension and decreased cardiac output

Some studies report at least mild injury in up to 57% of recipients.

Associated with prolonged ischemia time

Differential Diagnosis

30 day mortality

Graft failure (30%)

Primary graft failure: most commonly attributed to ischemia-reperfusion injury; can lead to diffuse alveolar damage and death

Nonspecific graft failure: diagnosis of exclusion when failure is either multifactorial in nature or not subject to postmortem confirmation

Infection (23.5%)

Cardiovascular (11.5%)

Acute rejection (5%)

Any occurrence associated with higher mortality rate, length of hospitalization, and compromised recovery

1 year mortality

Infection (38.7%)

Graft failure (17.5%)

Lymphoma (3.3%): both infections and lymphoma are considered to be side effects of high-dose immunosuppression, required due to the high rate of rejection of lung grafts when compared with other organs

Management and Treatment

Early postoperative care focuses on weaning from ventilator support, fluid management, immunosuppression, detection of early rejection, and prevention/treatment of infection

Generally, standard ventilation strategies suffice

Lung isolation is rarely indicated

Positive End Expiratory Pressure (PEEP) is usually indicated, except in the case of single lung transplant for COPD (leads to overinflation of the more compliant, grafted lung)

Pulmonary HTN—lability in hemodynamics and oxygenation are to be expected; these patients may benefit from prolonged mechanical ventilation

PRR—prolonged mechanical support and longer ICU stays

Judicious fluid and hemodynamic management—graft is prone to edema due to increased vascular permeability and loss of lymphatic drainage; vasopressor and inotropic support is preferred over fluid resuscitation

Treatment for PRR follows conventional paradigms for acute lung injury

Outcomes

PRR: no effect on 1 and 3 year survival

Double lung transplant half life is 4.9 to 7.9 years

Single lung transplant half life is 3.7 to 5.9 years

Most limiting factor to long-term survival is the occurrence of obliterative bronchiolitis and its clinical correlate, bronchiolitis obliterans syndrome, which portends chronic rejection

Chronic morbidity associated with immunosuppression

Calcineurin inhibitors: renal disease, hypertension, neurotoxicity

Steroids: osteoporosis, adrenal suppression, weight gain

Heart Transplantation

Common Causes to Remember

Epidemiology

Heart transplantation has been in clinical use for the past 40 years, although early attempts resulted in high mortality due to lack of effective immunosuppression.