Care of the Transplant Patient
Steven D. Nathan, MD
The critical care management issues of organ transplant recipients is a growing area to which intensivists are increasingly being exposed, not only in the big academic institutions, but also in smaller community hospitals as more of these patients live longer and further from their "mother ships." Therefore it is becoming increasingly important for intensivists and pulmonologists to be familiar with the management nuances of these complicated patients. The management of organ transplant recipients was the topic of several discussions at the ACCP meeting. Debbie Levine, MD, from the University of Texas in San Antonio, addressed the intensive care unit (ICU) management of liver transplant candidates and recipients. Liver transplantation is the treatment of choice for various forms of end-stage liver disease, including viral liver disease, liver malignancies, acute liver failure, and certain metabolic derangements. What is also being seen in recent years is that sicker patients are undergoing transplantation. Sicker patients before transplant translates into sicker, more complicated patients after transplant. Frequently, these patients undergo transplantation when they have comorbidities and organ dysfunction. Dr. Levine alluded to the operating room experience being a "mere moment between 2 ICU stays" and that othotopic liver transplantation (OLTx) frequently involves extensive abdominal surgery on suboptimal surgical candidates.
For the patient with acute liver failure, there are several clinical consequences that extend into the posttransplant period. These include coagulation abnormalities, inadequate factor synthesis, fibrinolysis, and hypocalcemia. One needs to follow the coagulation abnormalities closely and aim for an international normalized ratio (INR) in the 1.5 to 2 range while keeping the platelet level above 50,000 and fibrinogen levels above 100 mg/dL. Sepsis is another major issue, with a high incidence of fungal infections in particular in patients with acute liver failure. After transplant, as with all forms of transplant, liver recipients are at continuous risk for infections. Neurological issues run the spectrum from encephalopathy to cerebral edema, which may require intracranial pressure monitoring.
Pulmonary problems after transplant include the need for prolonged mechanical ventilation. The cause is usually multifactorial with issues such as weakness, malnutrition, extensive upper abdominal surgery, pain, blood loss, marked vascular volume shifts, and sequelae of reperfusion injury all playing a role. In 1 report of OLTx recipients, 11% of 546 patients required ventilatory support beyond 24 hours.[1] Acute respiratory distress syndrome in this setting has been reported in 4% to 25% of cases and carries with it a mortality rate as high as 80%. Pulmonary edema has been reported in 14% to 88% of cases and can be the result of overhydration and/or cardiac dysfunction. Perioperative pleural effusions may also occur and are usually right-sided or bilateral. These may enlarge over the first week after OLTx and about 10% ultimately require drainage.
The diaphragm may also be affected. In one study, 79% of 48 OLTx patients had delayed or absent phrenic nerve conduction on electromyography.[2] This is mostly felt to be the result of crush injury by the subhepatic caval clamp. However in the context of liver transplantation, it is rarely associated with the need for prolonged mechanical ventilation. Drug-induced pulmonary dysfunction is seen mostly these days after the use of rapamycin, which has been reported to cause interstitial pneumonitis, bronchiolitis obliterans organizing pneumonia, and diffuse alveolar hemorrhage. However, the onset of these is usually insidious and is generally not a perioperative problem.
Venous thromboembolism is seen rarely in patients with cirrhosis despite these patients receiving autoanticoagulation drugs. In one series, venous thromboembolism was found in 0.5% of 113 patients with an elevated INR and in another series of patients undergoing autopsy portal vein thrombosis was seen in more than 50%.
Pulmonary vascular disorders of liver disease run the spectrum from hepatopulmonary syndrome (HPS) to portopulmonary hypertension (portoPH). The former is primarily a disease of vasodilatation and might be caused by various mediators not being cleared appropriately by the liver. On the other end of the spectrum, portoPH is felt to be caused by an excess of vasoconstrictors such as thromboxane and endothelin. HPS tends to be a progressive disease with worsening hypoxemia.[3] The 5-year survival of HPS is a dismal 20%. Transjugular intrahepatic portosystemic shunts do not affect the course of this disease, and the gold standard therapy is liver transplantation. The hypoxemia may take months to years to resolve after OLTx, but complete resolution will be seen in about 80% of patients.
PortoPH can occur with or without cirrhosis. Although it is usually associated with a high cardiac output, the prognosis is very poor and is worse than that of idiopathic pulmonary arterial hypertension or HIV-associated pulmonary hypertension. Patients will usually die of this before they succumb to their liver disease. The advent of effective therapies for pulmonary arterial hypertension has enabled patients with portoPH to be treated and to undergo successful transplant, whereas previously they would not have been regarded as appropriate candidates for OLTx. With regard to HPS and portoPH, liver transplantation allows the unique opportunity to reverse organ disease by transplanting another organ.
Dr. Wickii Vigneswaran, MD, Director of the Lung Transplant Program at the University of Chicago, addressed the perioperative care of the patient undergoing thoracic organ transplant. Dr. Vigneswaran underscored a few salient points to begin. Both heart and lungs are life-saving organs so we have "got to get it right." Both have limited ischemic times so no time can be wasted. Finally, the key to success is a multidisciplinary team approach.[4]
Donor preparation and procurement includes avoiding high filling pressures and barotrauma. Ongoing monitoring of the lung through serial arterial blood gas measurement, chest x-rays, and a surveillance bronchoscopy is also essential. Organ preservation includes cold pulmonary flush with a pulmonary vasodilator, retrograde flushing to ensure the removal of all emboli, and cold solution for transportation.
For recipient preparation, it is important not to discontinue any therapy and to correct any anticoagulant therapy. Prospective cross-matching of the allograft is generally recommended for a panel-reactive antibody titer more than 10%. Such a recipient might also be treated with plasmaphoresis and/or intravenous immunoglobulin G.
A double lumen tube is inserted for lung recipients, preferably a left-sided tube to avoid occluding the right upper lobe. Cardiopulmonary bypass is necessary for patients with significant pulmonary hypertension and right ventricular dysfunction. Structures to avoid include the phrenic nerve, and it is also important to guard against venous or arterial anastamotic stenoses. Attention should be paid to hemostasis, preservation of the blood supply to the bronchial stump, and prevention of excess fluid accumulation. At the end of surgery the endotracheal tube should be changed and a bronchoscopic inspection of the anastamosis should be performed, with clearance of secretions and blood.
Postoperative care includes careful monitoring of the allograft. Primary graft dysfunction is the most common cause of early mortality. Filling pressures should be kept in the normal to low range. Among other factors, the lack of lymphatic drainage may predispose the patient to edema. Ventilator support should include low tidal volumes and low positive end-expiratory pressure (PEEP). PEEP should be avoided for patients with chronic obstructive pulmonary disease who receive a single lung to avoid dynamic hyperinflation of the native lung. Early extubation should be the goal where possible, but not in the operating room because patients might still manifest primary graft dysfunction. If the patient is still intubated for more than 48 hours, then a bronchoscopy prior to extubation is prudent. Early tracheostomy for failed extubation is advised because this will help with early mobilization and rehabilitation.
Postoperative care actually begins before the surgery in terms of education, discharge planning, nutrition, pulmonary rehabilitation, and patient/family education. This also allows for expectations to be managed. A multidisciplinary approach is the key, and collaborative team meetings are essential to ensuring that all team members are "on the same page."
Tim Whelan, MD, from the University of Minnesota, spoke about the medical ICU management of lung transplant recipients. He focused on common problems that might affect these patients and might result in them going to and being treated in a community ICU. The first condition addressed was that of bronchiolitis obliterans syndrome because this is responsible for most deaths beyond the first year. This physiologic entity is characterized by progressive airflow obstruction. Other conditions such as infection, acute rejection, disease recurrence, and airway complications need to be excluded.
Chronic renal disease is also a major long-term problem. This usually results from chronic calcineurin therapy. At 10 years posttransplant, about 50% of patients have a creatinine level more than 2.5, and at 5 years 3.2% of patients are on chronic hemodialysis.
For patients with acute respiratory failure, the differential diagnosis includes infection, acute rejection, congestive heart failure, volume overload, thromboembolic disease, and inflammatory lung disease (eg, rapamycin toxicity). Cytomegalovirus infection is seen in 13% to 75% of lung transplant recipients. It is often diagnosed in conjunction with another problem and clinicians need to be aware of ganciclovir-resistant strains (6% to 10% of cases). Other infections that might occur include community respiratory viruses and fungal infections, especially Aspergillus sp and Candida sp.
A high index of suspicion should always be maintained for venous thromboembolism and pulmonary emboli, which have a reported incidence of 6% to 8.6%
In addition, drug-drug interactions should always be considered, especially with the calcineurin inhibitors because these drugs may result in untoward side effects. Dr. Whelan ended with a sobering quotation that "lung transplant recipients can have as many diseases as they damn well please."
Kevin Chan, MD, from the University of Michigan, discussed ICU outcomes after hematopoietic stem cell transplantation (HSCT). There are about 16,000 HSCT procedures in the United States each year. Indications include hematologic malignancies, certain solid tumors, and some immune-mediated diseases. Prior to HSCT, patients receive some combination of ablative chemotherapy with or without radiation therapy. Pulmonary complications are seen in about 50% to 60% of patients. ICU admission is required in 30% to 40% and respiratory failure occurs in 10% to 25% of cases. The pulmonary problems that may be encountered include infections, acute graft host disease, diffuse alveolar hemorrhage, idiopathic pneumonitis, congestive heart failure, and bronchiolitis obliterans. In all, pulmonary complications account for 30% to 45% of deaths after HSCT.
Dr.Chan provided a historic perspective and through a series of temporarily sequential articles demonstrated a slow improvement in outcomes through the years in these patients. In one of the more recent papers, Soubani and associates[5] reported that 11% of patients who underwent HSCT were admitted to the medical ICU, 61% were discharged from the ICU, and 41% were discharged home. Predictors of a poor outcome include high Acute Physiology and Chronic Health Evaluation scores, high lactate levels, positive blood cultures, need for pressors or mechanical ventilation, bilirubin level, and multiple organ system failure. It is important to discuss the patient's prognosis with both the patient and the patient's family to manage expectations, especially if the patient requires ICU admission.[6]