Intensive care unit management of lung transplant patients

Intraoperative issues

The type of surgical incision (clamshell incision vs. anterolateral thoracotomies vs. median sternotomy) for lung transplantation depends on several factors, including single or bilateral lung transplantation, CPB use, history of prior thoracic surgery in the recipient, and surgeon’s preference. Bilateral anterior thoracotomy (sternal sparing) performed for BLT has a lower rate of sternal infections and healing complications than the clamshell incision. During surgery, three anastomoses are made on each side. They include the bronchus, pulmonary artery, and cuff of the pulmonary veins to the left atrium from posterior to anterior. Bronchial artery anastomosis is usually not made. In addition, lymphatic and nerve-ending anastomoses are not made. About 30%–40% of patients require CPB support intraoperatively for hemodynamic instability, hypoxemia, and right ventricular failure after clamping the first or second pulmonary artery. CPB is also commonly needed in recipients with pulmonary hypertension or in situations where independent lung ventilation is impossible. The tubing, cannulas, membrane oxygenators, and pumps used in the CPB machine often trigger a systemic inflammatory response, and patients tend to be hypotensive from the resulting vasoplegia. Intraoperative extracorporeal membrane oxygenator (ECMO) machines have several advantages over CPB. They decrease the length of the circuit, thus decreasing the blood–air interface. There are fewer blood products that are transfused and a lower incidence of PGD. After the surgery, the double-lumen ETT used for independent lung ventilation is exchanged for a single-lumen ETT. The patient is transferred to the intensive care unit (ICU) after chest closure. The patient is then weaned off the ventilator and from EMCO in the ICU.

Lung transplant recipients who have pulmonary hypertension require special attention. During surgery, every effort is made to prevent a sudden rise in pulmonary pressure that may cause right ventricular failure. Intraoperative transesophageal echocardiography (TEE) helps monitor the right ventricular function very closely. Inhaled nitric oxide (iNO), inhaled prostacyclin, and intravenous milrinone are used to support right ventricular function intraoperatively and during the immediate postoperative period.

Immediate postoperative intensive care unit management

Weaning the patient off the mechanical ventilator and ECMO is performed by the ICU physician who collaborates with the thoracic surgeon. Stabilization of respiratory function and ventilator weaning are the initial goals when the patient arrives in the ICU from the operating room. Either pressure- or volume-targeted ventilation is used. The goal is to keep the airway pressures low to avoid barotrauma and gas leakage through the fresh bronchial anastomoses, prevent atelectasis, and at the same time avoid volutrauma to the newly implanted grafts. Lung-protective ventilation strategy with tidal volumes (V _T ) around 6 mL/kg of predicted body weight and low to moderate positive end-expiratory pressure (PEEP) should be used. High PEEP should be avoided. In patients who undergo SLT, it might be challenging to ventilate the graft, as the compliance of the native lung will be different. Care should be taken to avoid overinflation of the native emphysematous lung, as this might lead to hemodynamic compromise from auto-PEEP (intrinsic PEEP). Patients typically present with hypoxemia, hypercapnia, and hemodynamic instability.

Decreasing the respiratory rate, increasing the expiratory time, and decreasing the PEEP can help. If these measures do not help, brief disconnection from the ventilator circuit should be considered. If the situation continues, double-lumen tube placement and independent lung ventilation should be considered. Likewise, the compliance of the native fibrotic lung will be worse when compared with the new graft. This might risk the overinflation of the newly transplanted allograft. Mild pulmonary edema is a common finding in transplanted lungs because of the absence of lymphatic drainage. This usually clears up in the first few days. If end-organ perfusion is adequate, as indicated by adequate urine output and downtrending lactate, an increase in fluids to boost preload is avoided. ^, iNO is frequently used in patients with pulmonary hypertension and right ventricular failure in the operating room. However, the intraoperative use of iNO does not seem to decrease the incidence of PGD. ^, The patient is rapidly weaned from iNO in the ICU. As soon as clinical stability is achieved, weaning from the mechanical ventilator is started. The oxygen fraction is steadily decreased if tolerated. The majority of the patients can be weaned and extubated within the first 24 hours. ^, Early extubation minimizes the chance of pulmonary infections and lowers stress on the bronchial anastomoses. Patients can be extubated to noninvasive positive-pressure ventilation (NIPPV). This helps in the unloading of the respiratory muscles, decreasing respiratory rate and dyspnea and improving ventilation/perfusion mismatch. NIPPV can also be used in recipients who demonstrate phrenic nerve dysfunction. Patients requiring prolonged mechanical ventilation should be considered for early tracheostomy. In these patients, early tracheostomy would minimize sedation and help with physical therapy while providing easier access for secretion clearance. Patients who require reintubation can also be considered for tracheostomy. If patients cannot be extubated, the decision to perform a tracheostomy should be made by the end of the first week. Although lung transplant recipients who end up with a tracheostomy tend to be sicker, have a longer ICU stay, and require prolonged ventilation, there is no difference in their short- and long-term survival rates compared with recipients who do not have a tracheostomy. Tracheostomy in this population is an important option that enables weaning from the mechanical ventilator and is associated with better patient tolerance. Chest tube removal depends on the 24-hour drainage from each tube. Apical chest tubes are removed first, followed by the basilar tubes, provided their drainage is less than 150 mL/24-hour period. Vigorous airway clearance techniques to mobilize secretions are an essential component of the recovery process after extubation. The cough reflex is blunted in these patients because of denervated lungs and splinting of the chest because of the pain resulting from the incision and the presence of chest tubes. Airway clearance techniques include bronchodilators, incentive spirometry, the flutter valve, chest physiotherapy, and nebulized hypertonic saline.

Pain control is an essential component of postoperative ICU care. Adequate analgesia is critical to prevent splinting of the chest that would cause atelectasis. Fentanyl infusion and patient-controlled analgesia pumps are used once patients are more awake in the immediate postoperative period. Morphine is avoided, as the creatinine clearance tends to fluctuate with the initiation of calcineurin inhibitors, and there is a risk of accumulating toxic metabolites of morphine. During surgery, patients undergo stretching of thoracic joints, ribs, vertebrae, and muscles; manipulation of pleura and lungs; and chest tube placement. All of these cause considerable pain upon waking from anesthesia. Inadequate pain control prevents patients from coughing and expanding the graft, thus increasing pulmonary complications. Moreover, the transplanted lungs are denervated and lack cough reflex. Patients tend to splint from pain, and as a result, diaphragmatic excursions are decreased, causing retention of mucus that leads to atelectasis. Thoracic epidural analgesia is used for unilateral or bilateral thoracotomy. Epidural analgesia also reduces opiate requirements, thus decreasing sedation from opiates and enabling patients to participate more in mobilization and physical therapy. Oxycodone is started once patients are extubated and able to tolerate oral medications. Nonsteroidal antiinflammatory drugs are avoided for analgesia, as they tend to worsen renal function, especially in patients who are on tacrolimus or cyclosporine. More recently, thoracic paravertebral catheter and intercostal cryoanalgesia have been used for postoperative pain control from the clamshell incision and pain emanating from the chest tubes. In thoracic paravertebral catheter analgesia, four paravertebral catheters are placed, two at the T4 level for controlling pain from the clamshell incision and two at the T8 level for pain emanating from chest tubes. Intercostal cryoanalgesia is performed intraoperatively on intercostal nerves 3–9 bilaterally. Both modalities decrease the amount of opiate required in the postoperative period and aid with pulmonary rehabilitation. ^,

Immunosuppression

Immunosuppression is initiated in the operating room. The first dose of an induction agent, basiliximab, is administered on the day of surgery, just before the graft’s first perfusion. The second dose is repeated on the fourth postoperative day. The first dose of Solu-Medrol (methylprednisolone) (10 mg/kg) is also administered before the first graft’s perfusion. This is followed by 1 g of intravenous mycophenolate mofetil. Tacrolimus is initiated after the arrival of the patient in the ICU. This practice might vary slightly from one center to another.

After transplantation, the main immunosuppressive drugs include a combination of calcineurin inhibitors (tacrolimus or cyclosporine), antimetabolites (mycophenolate mofetil or azathioprine), and steroids. Calcineurin inhibitors are the cornerstone of the regimen. We default all patients to tacrolimus, mycophenolate mofetil, and prednisone. The dose of tacrolimus is gradually titrated to a tacrolimus trough level of 10–14 ng/mL by the end of the first postoperative week while closely monitoring serum creatinine levels. Mycophenolate mofetil is administered at a dose of 1 g twice daily while cautiously monitoring for cytopenias.

Antimicrobials

Broad-spectrum antibiotics that would cover gram-positive and gram-negative organisms are initiated before making skin incisions on the recipient. Typical antibiotics include a combination of vancomycin and cefepime—donor bronchus culture and prior cultures from recipient sputum guide the types and duration of the antibiotics. Trimethoprim-sulfamethoxazole, prophylaxis against Pneumocystis jiroveci, is started and given three times a week. Antifungal prophylaxis depends on pretransplant risk factors for Aspergillus . Recipients with cystic fibrosis and cavitary disease are thought to have a high risk and are prophylaxed with oral voriconazole or posaconazole or isavuconazole and inhaled amphotericin. Patients who are at low risk for aspergillosis are prophylaxed with itraconazole. The oral prophylaxis is continued for 6 months. Cytomegalovirus (CMV) prophylaxis depends on the CMV serologic status (IgG) of the donor and recipient before the transplantation. If the donor is positive and the recipient is negative (D+/R−, CMV mismatch), the recipient is prophylaxed with daily valganciclovir for a year or longer. If the donor is CMV negative and the recipient is CMV positive (D−/R+) or if the donor and recipient are CMV positive (D+/R+) (intermediate-risk group), the recipient is prophylaxed with Valcyte for 9–12 months. If the donor and recipient are CMV negative (D−/R−, low-risk group), the recipient is prophylaxed with acyclovir, which is effective against all herpesviruses other than CMV.

General measures

Patients tend to get constipated from immobilization and opiate analgesics used in the immediate postoperative period. This is prevented by instituting scheduled laxatives. Constipation and ileus also interfere with the absorption of immunosuppressive medications. Hence, great care is taken to avoid constipation and the slowing of gut motility. This is especially true in patients with cystic fibrosis who might require more aggressive measures that include osmotic laxatives in addition to stimulant laxatives. On a similar note, electrolyte imbalance could make constipation and ileus worse. Magnesium, calcium, potassium, and creatinine levels need to be monitored closely. Hypomagnesemia results from tacrolimus, proton pump inhibitors, and diuretics in the initial postoperative period. Intracellular levels of magnesium might be lower despite normal serum levels. This should be aggressively corrected to minimize neurotoxicity and cardiac dysrhythmias. Magnesium is a vital cofactor in muscle function and gastrointestinal motility. The incidence of venous thromboembolism in lung transplant recipients is much higher than in other populations. It is thought to be between 8% and 29%. As a result, deep vein thrombosis prophylaxis is enforced as soon as possible with low-molecular-weight heparin.

Lung transplant recipients have a high risk of gastroesophageal reflux from underlying esophageal dysmotility and recent thoracic surgery. Measures to control acid reflux and aspiration include keeping the head of the bed elevated at a 30-degree angle or more and using a proton pump inhibitor. Early and aggressive physical therapy is crucial in the success of lung transplantation to avoid critical care illness neuromyopathy. Once patients are extubated, they are mobilized to sit in a chair twice a day. If patients can achieve adequate analgesia, walking with assistance is encouraged.