Peter Slinger MD, FRCP, Assoc. Prof., Dept. Anesthesia, University of Toronto
The objectives of this seminar are: 1) To update Anesthesiologists on the status of lung transplantation; 2) To examine recent and future advances in lung transplantation; 3) To highlight the lessons learned from lung transplantation that apply in general to anesthesia in patients with end-stage lung disease. The majority of recent advances in thoracic anesthesia have occurred because of experiences in lung transplantation.
Limits of Resectability:
Many patients thought to be inoperable a decade ago are now presenting for pulmonary resection for cancer1 because transplantation has expanded our understanding of lung mechanics and early post-operative pulmonary function2. Anesthesiologists need to revise their preoperative assessment and intraoperative management of these patients. Estimating predicted post-operative (ppo) pulmonary function for three aspects of respiration: lung mechanics, gas exchange and cardio-pulmonary interaction is the most useful method of stratifying these patients.
A ppoFEV1 <40% normal is associated with increased risk of respiratory complications3. Of available potential measures of lung mechanics, ppoFEV1 % is the most valid4. Patients with ppoFEV1 30-40% can be safely extubated in the operating room if gas exchange (the most valid estimate is ppoDLCO>40%)5 and cardio-pulmonary interaction (the most valid measure is exercise testing)6 are acceptable. Other useful measures of heart-lung interaction are stair climbing and the six-minute walk test.
Epidural analgesia is the only method of pain relief proven to decrease post-operative pulmonary complications7 and the recent trend to improved outcome in high-risk patients following pulmonary resection seems to be related to the use of epidural analgesia8. For maximal efficacy it is important to use the synergistic effect of a combination of local anesthetics and opioids provided by thoracic epidural analgesia9,10.
Airway Management
a) Lung isolation: Initial problems from the use of standard double lumen tubes (DLT’s) for lung isolation for transplantation included technical difficulty making the bronchial anastomosis with an in situ double-lumen endobronchial tube, problems dealing with copious thick secretions through the narrow lumens of a DLT and the need to change the DLT to a single-lumen tube for postoperative ventilation. These problems prompted many transplant teams to use combinations of bronchial blockers and single-lumen endotracheal tubes. However, all bronchial blockers are prone to intra-operative movement and mal-positioning11.
The advantage of a double-lumen tube in transplantation is that it allows direct continuous access to both lungs for suctioning, oxygenation and to examine the bronchial anastomoses. Several advances have allowed the continued use of DLTs for transplantation. The use of segmental bronchial lavage at induction via a single-lumen tube, prior to placement of the DLT facilitates clearing secretions. Improved double-lumen tube designs with shorter endobronchial segments12 and improved familiarity of anesthesiologists with fiberoscopic lobar anatomy13 has aided positioning of DLT’s. Right-sided DLT’s now can be used safely for left-sided surgery14. Because of the improved flow-resistance characteristics of modern DLT’s, it is not necessary to change these DLT’s to single-lumens immediately at the end of surgery when the upper airway may be more difficult15.
b) Management of difficult lower airways. Prior to transplantation, significant non-malignant bronchial stenoses were extremely rare. Anesthetic managment of bronchial stenosis and malacia is now a common procedure in transplant centres because it occurs in 10-20% of cases16. Principles of management for all these cases are: maintain spontaneous ventilation, no blind instrumentation of the airway and “Nolle Pontes Ignii Consumere” (don’t burn your bridges). The recent development of expandable metal stents placed by rigid bronchoscopy 17 is a major advance for those patients over previous laser excisions and will be useful for many other situations of tracheo-bronchial compression.
Cardiopulmonary Bypass (CPB). There was initially much argument over the necessity to avoid CPB, whenever possible, due to theoretical and anecdotal damage to the already ischemic endothelium of the donor lung. This prompted much investigation of methods to predict18,19 and avoid CPB during lung transplantation. A consensus seems to be emerging that CPB temporarily decreases postoperative gas exchange, increases intra-operative blood loss, and increases the duration of postoperative mechanical ventilation. However, there is no net decrease in short or long term mortality attributable to CPB21. Aprotinin has the potential to decrease fibrinolysis during CPB for lung transplantation22.
Right Ventricular Dysfunction. In the majority of cases, the underlying etiology of the hemodynamic decompensation leading to the necessity for CPB during transplantation is right ventricular dysfunction. Various combinations of vasoactive agents have been tried to increase right ventricular (RV) contractility and decrease RV afterload in this situation23. The most consistently useful pharmacologic methods seem to include an alpha-adrenergic agent such as Norepinephrine to support the RV. These seem to be able to augment cardiac output in the face of sudden increases in RV afterload without further increasing pulmonary vascular resistance24.This is combined with the most selective pulmonary vasodilator available, which at present is Nitric Oxide.
Disease Specific Anesthetic Advances:
Emphysema: Patients with severe emphysema or alpha1-antitrypsin deficiency form a large portion of the transplant population. Disease specific anesthetic implications for those COPD patients are:
i) Dynamic Hyperinflation (DHI). Any positive pressure ventilation, even manual bag/mask ventilation prior to intubation, can cause a sudden cardiovascular collapse in these patients due to DHI which is caused by the increased expiratory airflow resistance and the development of “auto-PEEP25. Treatment includes thorough pre-oxygenation prior to induction, invasive monitoring, immediate availability of inotropes/vasopressors, and the use of prolonged expiratory times (inspiratory: expiratory ratio <1: 4) with apneic periods as required. ii) Carbon Dioxide (CO2) Retention: CO2 -retention is no longer considered an absolute contraindication to lung resection26. PaCO2 levels among moderate-severe COPD patients do not correlate directly with lung mechanics27. Administration of supplemental oxygen causes an increase in PaCO2 in CO2-retainers not by a decrease of respiratory drive but due to an increase in physiological dead space, decreased matching of ventilation/perfusion and possibly decreased CO2-transport28. iii) Intra-operative Hypercarbia. It is frequently impossible to adequately eliminate CO2 intraoperatively in these patients29. Experience has shown that acidosis has adverse hemodynamic effects by increasing PVR, but hypercarbia alone is not deleterious. Severe levels of hypercarbia can be tolerated if hypoxemia and acidosis are avoided30. iv) Oxygenation. Oxygenation during one-lung ventilation (OLV) is much less a problem with emphysematous patients than other transplant recipients. It has been noted that patients with poorer lung mechanics tend to have better oxygenation during OLV31. This is probably related to the development of auto-PEEP during OLV in these patients32. These patients benefit from pressure-controlled OLV33. Cystic Fibrosis (CF): Problems encountered initially in transplantation for these patients included the inability to deal with thick bronchial secretions and to adequately ventilate these patients. CF patients, because they have both increased inspiratory and expiratory flow resistances, may benefit from slow inspiratory phase ventilation with a high airway pressure34. Due to the severely decreased lung compliance this method of ventilation causes little hemodynamic compromise in this subgroup of patients if air trapping is avoided. Other Diseases: Lessons from other severe end-stage lung diseases have been learned such as the postoperative hemodynamic instability of primary pulmonary hypertensives, the poor tolerance of pulmonary fibrotic patients for OLV and the risk of pneumothoraces in patients with lymphangiomyomatosis35,36,37. Lessons in Progress: Transesophageal Echocardiography (TEE). There is at present no consensus about the usefulness of TEE during lung transplantation. Approximately half of North American centres use TEE routinely during lung transplantation and the remaining centres use it as required. TEE is very useful to assess venous anastomoses but it is extremely difficult to assess left-sided pulmonary arterial anastomoses38. There is often a significant pressure gradient across the arterial anastomoses39 and TEE may be useful to assess left ventricular filling. In patients with severe pulmonary hypertension, TEE may detect abnormalities not seen at angiography or with transthoracic echocardiography such as pulmonary artery thrombi and septal defects40. The argument against routine TEE is that RV function is the most important intraoperative problem and this can be assessed directly during the critical periods32. Nitric Oxide (NO). Anecdotal evidence suggests that NO is useful to decrease PA pressures and aid the failing RV during transplantation20. The routine use of NO is currently the subject of a prospective study. Decreased endogenous production of NO both before and after transplantation may be a marker for poor postoperative outcome41. Donor Selection. The scarcity of donors and the improvements in lung preservation have lead transplant teams to begin accepting lungs that would not have been used 10 years ago. With these borderline lungs it is now obvious that donor age and ischemia time are two factors that correlate with poor outcome42. Acceptable ischemia time is now a more complicated topic than was initially thought and varies on a case by case basis, outcomes are poor if the donor is over 60yr. age and the ischemia time exceeds 8 hr.. Summary: Anesthetic management for lung transplantation continues to evolve. The major recent stimulus for progress in thoracic anesthesia has come from the need to provide care for lung transplantation patients. 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