Anesthesiology

Lung Transplant

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What the Anesthesiologist Should Know before the Operative Procedure

Lung transplants are complex and for many centers infrequent procedures. Prior to acceptance on a transplant list, recipients undergo thorough medical assessment. In order to individualize care, it is essential that the anesthesiologist have a detailed knowledge of their patient’s disease, associated comorbidities, and the planned procedure. Whether a “go-call” has been received or is imminent, efficient data review must be combined with standard preoperative assessment to provide best care.

Single lung transplants resemble pneumonectomy surgery, performed in lateral decubitus position through a thoracotomy incision. In contrast, double lung procedures are performed supine through a clamshell incision with arms raised above the head or through sequential lateral thoracotomy incisions based on surgeon preference.

Supine or lateral, double lung transplants always occur as sequential single lung procedures, only obliging circulatory support if the brief period between first diseased lung removal and donor implantation cannot be tolerated, such as when hilar clamping worsens preexisting pulmonary hypertension and precipitates acute right heart failure (e.g., primary pulmonary hypertension). Nonetheless, surgeon preference is the commonest indication for use of support devices during some or all double lung transplants at many institutions (e.g., cardiopulmonary bypass [CPB], intra-aortic balloon counterpulsation [IABP], venovenous extracorporeal membrane oxygenation [ECMO]).

An important role of the anesthesiologist is to help coordinate transplant events with other team members, including recipient arrival, preparation, operating room activation, surgery (timing vs. donor remoteness/harvest delays, etc.), and ICU bed availability. Transplant coordination requires not only good communication skills, but also a clear understanding of events surrounding both harvest and implant procedures, and the numerous responsibilities and roles of all the team members.

Communication with surgeon and transplant coordinator is also critical to clarify any variation in the anticipated procedure (e.g., lung transplant alone or combined with aortocoronary bypass, or heart/liver/kidney transplant), any plans for circulatory support, and individualized antibiotic and immune suppressive plans.

Sometimes recipient antibodies will require coordination of added interventions such as intravenous immunoglobulin or plasmapheresis therapy. Evidence of donor or recipient cytomegalovirus infection may also require perioperative antiviral therapy. The anesthesiologist should be involved at all stages with verification of ABO donor/recipient compatibility and lung size matching.

General indications for lung transplant

  • Pulmonary hypertension not controlled with medical therapy

  • Hypercapnia along with increasing need for intensive care

  • Forced expiratory volume (FEV) <20-39%, and diffusing capacity of the lung for carbon monoxide (DLCO) <20-39% in context with the patient’s specific disease etiology and the time course of pulmonary function decline

  • Refractory pneumothorax for bronchiectasis

  • Refractory hypercapnia or hypoxemia

  • Refractory pulmonary hypertension

  • Persistent heart failure, elevated right atrial pressure for pulmonary hypertension, or cardiac index (CI) <2 L/m2/min

  • Severe functional impairment

  • Patient not immunosuppressed with only moderate steroid use

End-stage lung disease in transplant candidates can be grouped into three main categories, including those with air space disease (obstructive or restrictive) and those with pulmonary vascular disease. Emphysema due to smoking or alpha 1 antitrypsin deficiency is the commonest obstructive disorder.

When obstructive disease is associated with severe pulmonary infection, such as with cystic fibrosis or bronchiectasis, double lung transplant is necessary to avoid contamination. Other lung conditions are eligible for single or double lung transplant; these include primary pulmonary hypertension and the restrictive diseases such as idiopathic pulmonary fibrosis and sarcoid.

A solid understanding of lung pathophysiology is central to the management of lung transplant patients. While diseased lungs become unimportant once they are removed, understanding their abnormalities prior to explant is key to the safe management of the lung transplant patient; particularly variable by presenting disease are the implications on the “bridging period” between first diseased lung explant and donor lung implant.

Emphysema, bronchiectasis, and cystic fibrosis are examples of obstructive pulmonary diseases. These patients are treated with bronchodilators, chest physiotherapy and rehabilitation, steroids, low flow oxygen, and antibiotics to combat recurrent infection.

Obstructive pulmonary disease is characterized by increased resistance to bronchial airflow, increased lung volumes and dilated airspaces, and can be associated with a large “barrel chest.” Obstructive lungs tend to lose their elastic recoil and/or become occupied by infectious material.

Pulmonary function tests (PFTs) reflect these changes through a decreased forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1), a decreased FEV1/FVC ratio, a decreased maxiumum mid-expiratory flow rate (MMFR), and sometimes an accompanying decrease in the DLCO. Air trapping is also reflected by an increased residual volume (RV), total lung capacity (TLC), and functional reserve capacity (FRC).

Inefficient exhalation associated with obstructive lung disease (also known as breath “stacking” or “auto-PEEP”) can cause “dynamic hyperinflation.” Moderate or severe hypotension with the onset of positive pressure ventilation during anesthesia induction for lung transplant with obstructive lung disease may herald dynamic hyperinflation (due to impaired venous return); more serious complications such as tension pneumothorax and cardiac arrest can occur. Some forms of end-stage obstructive lung disease involving chronic bacterial infection (e.g., cystic fibrosis, bronchiectasis) require tailored perioperative antibiotic regimens.

Idiopathic pulmonary fibrosis and sarcoidosis are examples of restrictive pulmonary disease. These patients are commonly treated with steroids and/or cytotoxic agents, and sometimes present requiring supplemental oxygen at very high flow rates.

Restrictive disease is characterized by decreased lung compliance and volume, impaired diffusion, disturbance of gas exchange, and mild to moderate pulmonary hypertension; PFTs for these patients show decreased FEV1, FVC, and DLCO with a preserved FEV1/FVC ratio. Patients are usually diagnosed by lung biopsy with alveolar walls demonstrating diffuse fibrotic changes.

The small scarred lungs of restrictive disease are often associated with equivalently small chest cavities, often obliging some “trimming” such that donor lungs are sufficiently small to fit. In addition to staple wedge resections or even lobectomy to reduce the donor lung size, efforts to match lung to chest sometimes also include bilateral stay sutures externalized to the abdominal wall that temporarily retract the recipient diaphragm.

Sometimes residual lung-chest cavity mismatch causes hemodynamic instability from “pulmonary tamponade,” occasionally requiring reopening of the chest cavity. “Pulmonary tamponade” generally improves greatly with tracheal extubation and the transition from positive pressure ventilation to spontaneous breathing.

Restrictive lung disease sometimes has effects on the pulmonary vasculature that can cause pulmonary hypertension (mean pulmonary artery pressures exceeding 25 mm Hg) and associated right ventricular hypertrophy. In this setting the anesthesiologist must be particularly vigilant of the risk of periprocedural acute right heart decompensation and hemodynamic instability due to further restriction of an already limited pulmonary vascular tree, such as with right or left pulmonary artery clamping.

End-stage pulmonary vascular disease, such as with primary pulmonary hypertension, is diagnosed by right heart catherization, demonstrating severely elevated pulmonary arterial pressures, and lung biopsy demonstrating narrowed or occluded pulmonary vessels. Most abnormalities are seen in muscular small arteries, arterioles, and muscular veins. Although PFTs often identify a decreased DLCO, lung function is usually otherwise normal.

Treatment is focused on ameliorating pulmonary hypertension, often through the use of nonselective and selective pulmonary vasodilators by continuous infusion (e.g., epoprostanol sodium). Evidence of severely diseased pulmonary vasculature with borderline compensated right heart function and suprasystemic pulmonary artery pressures increases the risk of cardiac arrest with anesthesia induction and is also an absolute indication for the use of CPB support to achieve lung transplantation.

1. What is the urgency of the surgery?

What is the risk of delay in order to obtain additional preoperative information?

Lung transplant surgeries are emergent procedures, but timing their start is part art, part science, due to the challenge of combining urgent need to proceed (e.g., re-do thoracotomy) with retarding effects such as the all too common donor harvest delays. Nonetheless, once organ harvest has occurred procrastination is highly counterproductive. The desired reperfusion interval for lungs is less than 7 hours, although emerging reperfusion technologies such as “lung-in-a-box” are significantly extending harvest-to-implant periods, even allowing for improved donor-recipient (HLA) matching. Current lung matching is limited to donor/recipient ABO blood type compatibility.

The expectation of caregivers on the day of surgery should be the need to perform a highly efficient patient re-review only. Optimizing anesthesia preparedness for lung transplant procedures in this regard must be a programmatic goal, such that elements required of the preoperative assessment are all but complete long prior to the day of surgery.

2. Preoperative evaluation

Transplant candidates have widely varying functional status ranging from ambulatory individuals receiving home oxygen to decompensated critically ill patients requiring ventilatory support or even ECMO.

Patients listed for lung transplantation have already undergone an extensive preoperative workup and are usually medically optimized for surgery. It is extremely rare to delay a lung transplant after the “go” call has been issued. Rare cases would be new evidence of other organ dysfunction or serious infection.

Absolute contraindications for lung transplantation are:

  • Malignancy in the last two years

  • Significant spinal or chest wall deformity

  • Advanced other organ dysfunction not amenable to treatment

  • Extrapulmonary infection such as HIV, hepatitis B or C

  • Medical noncompliance

  • Lack of consistent social support system for the patient

  • An untreatable or psychological condition that affects medical compliance

  • Recent (within 6 months) substance addiction

Relative contraindications for lung transplantations are

  • Age greater than 65 years

  • Critical or unstable clinical condition such as ECMO, shock, or mechanical ventilations

  • Patients with extremely poor rehabilitation potential

  • Patients with colonization of a highly resistant infectious organism

  • Patients with BMI greater than 30 kg/m2

  • Patients with severe osteoporosis

  • Patient with poorly controlled comorbitities such as diabetes

3. What are the implications of co-existing disease on perioperative care?

Comorbidities can often be anticipated with knowledge of the primary lung problem that prompted referral for transplant. Prevalent conditions include atherosclerotic heart disease, active respiratory infection, chronic steroid use, compensated right heart failure, gastroesophageal reflux, diabetes, and in selected cases liver and kidney disease.

As mentioned above, serious comorbidities may influence surgical planning, such as for coexisting coronary artery disease and the use of CPB or IABP. However, there is little room to delay surgery for risk reduction in the immediate pretransplant period, rather awareness of comorbities should be integrated into perioperative decision-making by the anesthesia team. If issues raised preoperatively are of significant concern, then consideration should be given to finding an alternate recipient for the available organ.

b. Cardiovascular system

Lung transplant procedures involving acute or unstable cardiovascular conditions are rare. Cardiac conditions that may influence or modify lung transplant surgery include the presence of a patent foramen ovale (PFO), impaired right heart function, vulnerability to supraventricular arrhythmias such as atrial fibrillation, and coronary artery disease.

A PFO may be diagnosed preoperatively or intraoperatively by transesophageal echocardiography (TEE). Added to cerebral air embolism precautions, are concerns that a PFO will increase considerably the risk of arterial oxygen desaturation due to acute right-to-left shunting of deoxygenated blood during events such as hilar clamping and explant of the first lung, also as a complication of the postoperative period. Prompt reporting of a PFO diagnosed during surgery by TEE is important since this may influence the surgeon to add PFO closure to the procedure, requiring CPB.

Right heart dysfunction in lung transplant candidates is common, and may influence the course of surgery by increasing the risk of acute right heart failure and requiring added hemodynamic support through any period of single lung perfusion.

Although undiagnosed coronary artery disease should be rare, combined aortocoronary bypass grafting and lung transplant is sometimes performed, generally either with CPB, or off-pump with IABP support.

If supraventricular arrhythmias are present or develop and render a patient hemodynamically unstable, cardioversion is an effective first intervention. Although lung transplant candidates are often at risk for supraventricular arrhythmias due to their pulmonary disease and anticipated intraoperative exposure to adrenergic agonist agents (e.g., epinephrine), preoperative management of these individuals does not generally involve any arrhythmia prophylaxis.

c. Pulmonary

Lung transplant patient’s primary presenting disease is pulmonary in origin. This is discussed in the initial section of this chapter. Disease processes can be classified into 3 main categories: (1) restrictive pulmonary disease, (2) pulmonary vascular disease, and (3) obstructive pulmonary disease.

d. Renal-GI:

Three main GI-renal concerns exist in preparation for lung transplant surgery, including the high prevalence of gastroesophageal reflux disease (GERD) in lung transplant candidates, esophageal disease as a contraindication to TEE, and standard considerations related to chronic kidney disease.

Chronic micro-aspiration related to GERD is implicated as a contributor to end stage lung disease in many patients, and some centers follow successful lung transplant with early Nissan fundoplication surgery if GERD exists. As a practical aspect of pretransplant preparation, the anesthesiologist should assess for any clinical evidence of GERD, continue related medications and consider standard preoperative treatment with oral sodium citrate. When appropriate, rapid sequence intubation should be performed and care during tracheal extubation be taken to minimize the risk of aspiration.

Use of TEE for monitoring and diagnosis during lung transplantation is common. Hence, it is important in the perioperative screening of these patients to access for absolute or relative contraindication to TEE. Of the standard contraindications to TEE, the presence of esophageal strictures or varicies (e.g., lung-liver transplant candidates) would be the most common concerns.

Except with candidates for combined lung-kidney transplant, obvious severe kidney disease would be uncommon in patients presenting for lung transplant surgery. However, chronic kidney disease (i.e., CKD, glomerular filtration rate less than 60ml/min) is often present with normal serum creatinine levels in patients over sixty. All the standard considerations related to CKD are applicable to lung transplant surgery, but notably acute kidney injury (AKI) complicates the postoperative course of many patients undergoing lung transplantation and therefore drug dosing in anticipation of some renal impairment during surgery may be prudent (e.g., muscle relaxants).

e. Neurologic:

Patients with severe neurologic disease would generally not be eligible for lung transplantation.

f. Endocrine:

Diabetes is a common endocrine disorder, particularly in cystic fibrosis patients with pancreatic insufficiency. Regular perioperative serum glucose monitoring and insulin therapy by intravenous infusion is a standard part of most lung transplant procedures. The stress of surgery, administration of steroid immunosuppression, and intravenous inotropic agents are all potent sources of hyperglycemia. While serum glucose levels >200 mg/dL are generally avoided, the proposed benefits of “tight” glucose control targets (80-110 mg/dL) have not been confirmed in most studies.

g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (eg. musculoskeletal in orthopedic procedures, hematologic in a cancer patient)

Of note in regard to patient factors influencing surgical decision making is selection of the first lung to be transplanted during a double lung transplant. In particular, presence of bullous disease, differential lung ventilation perfusion scan indicating poor perfusion of one lung and a previous history of lung resection are all factors that may contribute to deciding which lung is removed first. A general approach is employed aimed at minimizing injury to the implanted organ while optimizing patient management even at the cost of “mistreatment” of lung tissue that will subsequently be explanted.

4. What are the patient's medications and how should they be managed in the perioperative period?

Management of chronic medications in patients presenting for lung transplant is similar to that of medications for any operation. Standard medication optimization is part of the workup for lung transplant, and the timing from realization that a lung is available for transplant to surgery is generally too short to hold medications for any meaningful time period. Insulin dosing should be guided by serum glucose determinations. Care is taken ahead of time to avoid chronic medications that would be harmful if not held prior to surgery.

h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern?

Although chronic steroid therapy is common in lung transplant candidates, perioperative steroid stress dose is generally unnecessary due to the large intraoperative dose of steroids for immunosuppression.

i. What should be recommended with regard to continuation of medications taken chronically?

Although general principles for continuation and cessation of perioperative medications are also relevant to lung transplant surgery, their application is rarely necessary due to the urgency of the surgery and the optimization of chronic medications as part of the intense medical workup lung transplant candidates undergo.

j. How To modify care for patients with known allergies -

Specific immunosuppressant and antibiotic (particularly for cystic fibrosis and bronchiectasis patients) regimens that include consideration of known allergies are prespecified as part of the preparation for lung transplant surgery.

Known drug tolerance (e.g., sedative-hypnotic tolerance related to extended infusions during an intensive care episode for positive pressure ventilation) should alert the anesthesiologist to the added risk for awareness.

k. Latex allergy- If the patient has a sensitivity to latex (eg. rash from gloves, underwear, etc.) versus anaphylactic reaction, prepare the operating room with latex-free products.

Standard considerations for latex allergy including avoidance of all latex containing items are applicable.

l. Does the patient have any antibiotic allergies- [Tier 2- Common antibiotic allergies and alternative antibiotics]

See earlier text.

m. Does the patient have a history of allergy to anesthesia?

Standard considerations are relevant for lung transplant patients with allergies to anesthetic agents or a history that warrants precautions for specific conditions such as malignant hyperthermia, serum cholinesterase, or NADH methemoglobin reductase deficiency.

5. What laboratory tests should be obtained and has everything been reviewed?

A lung transplant, once the “go” call is received, is an emergent procedure. Most transplant candidates have undergone extensive evaluation as part of their preparation for lung transplant surgery, and therefore should not require added investigations as part of their immediate preparation for surgery. Standard investigations repeated on the day of surgery include a complete blood count, basic chemistry, coagulation panel, and a type and screen.

Standard lung transplant workup tests

  • Pulmonary:

  • Chest X-ray

  • Chest CT

  • Pulmonary function tests

  • Differential lung ventilation perfusion scan

Laboratory investigations

  • Complete blood count

  • Basic metabolic profile

  • Liver function tests

  • Coagulation panel

  • Type and screen

  • Seriologies

  • Histocompatibility antigens

  • Panreactive proteins

Cardiac

  • Transthoracic echocardiography

  • Right and left heart catherization

  • 24 hour Holter

Intraoperative Management: What are the options for anesthetic management and how to determine the best technique?

Single and double lung transplants are performed under general anesthesia (inhaled or total intravenous). Regional thoracic epidural analgesia should be discussed preoperatively as a mainstay of postoperative pain management for most patients.

a. Regional anesthesia

Regional anesthesia is not appropriate for the intraoperative management of lung transplant patients. Thoracic epidural analgesia is highly suitable for the postoperative period. Although sometimes there is sufficient time to allow for epidural catheter insertion preoperatively, this procedure usually occurs postoperatively after any impairment of coagulation is corrected

b. General Anesthesia

Benefits/drawbacks: General anesthesia is the only option for lung transplant surgery – this can be provided by inhaled anesthesia versus total intravenous anesthesia (TIVA).

Vascular access: The potential for major blood loss, hemodynamic instability and requirement for numerous continuous drug infusions obliges multiple sites of intravenous access for lung transplant surgery. One or two large bore (18/16 gauge) peripheral venous catheters plus a central line are essential. A vascular approach ipsilateral to the (first) operative lung for subclavian or internal jugular central venous puncture when lung transplant involves thoracotomy using ultrasound visualization is preferred; this strategy minimizes risk for concerns such as unrecognized bullous lung disease and the potential for tension pneumothorax in the nonoperative lung. “Down-side” tension pneumothorax can be lethal when it manifests intraoperatively.

Radial arterial catheter placement for beat-to-beat blood pressure monitoring and arterial blood gas assessment is essential.

Monitoring: In addition to standard ASA monitors lung transplant procedures almost always involve intra-arterial, pulmonary artery and central venous catheters, TEE, and a urinary bladder catheter monitoring. Additional monitoring that is variably employed include continuous cardiac output, pulmonary artery venous oximetry, bispectral index, and cerebral oximetry monitoring.

Positioning: For double lung transplants the positioning (varying by surgeon and institution) is either a clamshell incision requiring supine positioning with arms overhead or sequential thoracotomies requiring right and left lateral decubitus positions. For single lung transplants the incision is a thoracotomy and requires lateral decubitus positioning. Attention to nerve pressure points includes the brachial plexus in the axilla, radial nerve at the humerus, and ulnar nerve at the elbow.

Ventilator management before lung transplant: Prior to transplant issues such as dynamic hyperinflation, high airway pressure related to restrictive lung disease, hypoxia, and hypercarbia.

Ventilator management after lung transplant: Goals in management of the newly transplanted lung include avoidance of atelectasis, use of the lowest oxygen level acceptable, and avoidance of barotrauma. Specific targets for application of positive end expiratory pressure and peak inspiratory pressure to the newly transplanted lung are often prespecificied by surgeons.

Temperature management: Given the many factors with significant potential to render a patient hypothermic during lung transplant surgery it is prudent to employ all available tools to maintain normothermia, even if use of cardiopulmonary bypass is anticipated. In this regard, fluid warmers, elevated room temperature and external warming/forced hot air devices should be employed.

Airway management: Lung transplant surgery requires lung isolation, usually with a double lumen endotracheal (ET) tube. A right-sided double lumen tube placed with fiber optic bronchoscope guidance is used for left single lung transplant, but otherwise a left-sided tube is preferable. At the end of surgery to facilitate bronchoscopy, the double lumen tube is exchanged for a single lumen ET tube to transfer to the ICU. Exchange catheters may be helpful to facilitate changing of ET tubes.

c. Monitored Anesthesia Care

MAC is not applicable for lung transplant surgery.

6. What is the author's preferred method of anesthesia technique and why?

Anesthesia Management:

A standard anesthetic strategy for “routine” lung transplant patients (i.e., those without issues that require specific attention such as severe pulmonary hypertension) involves limiting line placement to peripheral intravenous and arterial lines prior to induction. One or two small intravenous boluses of midazolam (e.g., 0.25-0.5mg) during this period provide sedation, but more importantly allows the patient’s response (e.g., tolerant vs. somnolent) to influence dosing for anesthesia induction. Hypnosis is achieved with modest doses of intravenous fentanyl (2-3ug/kg) and propofol as required, followed by muscle relaxation (e.g., succinylcholine 1-1.5mg/kg or vecuronium 0.1mg/kg), and bronchoscopically confirmed double lumen endotracheal tube placement. Anesthetic maintenance is initially achieved using inhaled volatile agent at levels sufficient only to place an internal jugular central venous catheter, and pulmonary artery catheter flotation at this point allows for direct assessment of pulmonary artery pressures, which may influence subsequent management. Volatile agent is then replaced with surgical levels of TIVA, including propofol by infusion (eg. 100-150ug/kg/min) and incremental boluses of opioid (e.g., fentanyl 5-8ug/kg) and muscle relaxant. Inhaled nitric oxide is also added (20ppm) from the start of surgery, particulary in the presence of pulmonary hypertension.

Hemodynamic instability during anesthesia induction:

For selected patients where the risk of instability or even cardiac arrest during anesthesia induction is high (e.g., severe pulmonary hypertension) consideration of central line and pulmonary artery catheter placement awake, and even femoral arterial and venous access prior to anesthesia induction to facilitate emergent cardiopulmonary bypass may be prudent. Access is challenging with such patients who often have extreme dyspnea and are uncomfortable in Trendelenberg position or even mildly reclined to engorge their central veins, however such positioning is rarely necessary due to the high likelihood of right heart dyfunction and elevated central venous pressures that usually accompany these circumstances.

Inhaled versus TIVA:

Many anesthesiologists prefer TIVA over inhaled general anesthesia for lung transplant due to its reliability - TIVA provides reliable agent delivery throughout a procedure compared to the potential for precarious vapor delivery with air leaks, shunts, periods of hypoventilation and sometimes the need to acutely shift to more versatile (intensive care) ventilators incompatible with volatile agent devices. In addition, air leaks can be significant, and may produce unnecessary inhaled anesthetic exposure of operating room personnel (and somnolence!), particularly of the surgeon.

Risk of Awareness:

Prior history of some lung transplant patients includes extensive periods of sedation for mechanical ventilation that may have produced extreme tolerance to sedatives and hypnotics. Such a background may increase the risk for intraoperative awareness with certain anesthetic regimens (e.g. benzodiazepine/opioid). Management of these patients should include use of anesthetics that are not subject concern in such patients, including propofol by infusion or inhaled volatile agents, and particular attention to monitoring (e.g., bispectral index, end-tidal volatile agent).

Muscle Relaxation:

Muscle relaxant selection and dosing should be considerate of the priority given to prompt tracheal extubation following lung transplant surgery and the potential for delayed agent clearance with AKI, a common complication of this procedure. Use of longer acting muscle relaxants such as pancuronium is easily avoided and may improve postoperative patient management.

Accurate blood pressure determination:

Radial artery blood pressure inaccuracies related to arm positioning, and high vasoconstrictor infusion rates during some periods of the surgery usually make femoral arterial blood pressure monitoring for lung transplant preferable if this is available.

Hemodynamic instability with pulmonary artery clamping:

Left or right pulmonary artery clamping eliminates pulmonary vasculature, and the resultant increase in vascular resistance can precipitate acute right heart failure. Clues to anticipate this complication include moderate or severe pre-existing pulmonary hypertension, TEE-identified right ventricular hypertrophy, and hemodynamic instability preceding clamping. Trial clamping prior to recipient lung explant and anticipatory institution of inotropic infusions can be useful in avoiding catastrophic cardiac arrest, but sometimes this concern warrants use of cardiopulmonary bypass.

Hemodynamic Instability during cardiac manipulation:

Mediastinal manipulation by the surgeon as a part of recipient lung explant, hilar preparation and donor lung implant are unavoidable. Yet these interventions often precipitate hemodynamic instability, sometimes sufficient alone to warrant a change of plan to employ circulatory support. However, interventions to attenuate these effects, combined with good communication can generally avoid unplanned circulatory support. Interventions include judicious boluses of fluid and vasopressors, vaspressor infusions, patient positioning (e.g., Trendelenberg) and occasional “breather breaks” where the surgeon briefly ceases activities at convenient moments to allow for recuperative or catch up periods. Epinephrine is a common vasoactive drug of choice due to its minimal pulmonary vasoconstrictive effects and bronchodilating effects.

Acute SVC syndrome and cerebral perfusion pressure:

As part of lung transplant procedures surgeons are obliged to manipulate the superior vena cava (SVC), often for prolonged periods, particularly with handling of the mediastinum in preparation for and during implant of a right lung. SVC manipulation often causes hypotension due to preload reduction, but superior caval obstruction also uniquely produces elevations of central venous pressure with mean values that commonly exceed 40-50mmHg. Such “acute SVC syndrome” causes cerebral engorgement but also severely compromises cerebral perfusion pressure in the setting of hypotension, normally reflected by mean arterial minus central venous pressure. This occurrence is important to relay to the surgeon and compute into any estimate of adequate cerebral perfusion pressure as part of resuscitative efforts. Importantly, central venous pressure monitoring solely from a femoral vein does not allow for recognition of this phenomenon.

a. Antibiotics, immune supression and other standard drug interventions:

Agents administered prior to lung transplant are individualized and determined ahead of time by a multidisciplinary transplant team and can differ from SCIP guidelines. Standard antibiotics include intravenous doses of vancomycin and ceftazidime. Specific agents are selected by sensitivity testing for patients with septic lung disease.

Immune suppression strategies are individualized but generally include intravenous tacrolimus and basiliximab prior to surgery, and azathioprine and methylprednisolone intraoperatively. Other agent such as intravenous immunoglobulin and mycophenolate mofetil may be requested for some patients. Other interventions include low dose heparin prior to lung implant, and intravenous mannitol and/or furosemide just prior to lung reperfusion.

b. What do I need to know about the surgical technique to optimize my anesthetic care?

Lung transplant surgery involves management of both diseased and newly harvested/implanted lungs, in addition to considerable hemodynamic instability due to manipulation of the heart and other major vascular structures. Of particular note, the newly implanted lung is an extremely vulnerable tissue since even after successful reperfusion it is recovering from an acute ischemic injury during transport, does not possess a functioning lymphatic or bronchial arterial system, and between first and second lung implant the initial lung will be subjected to twice normal blood flows. It is therefore not surprising that a surgical priority exists (shared by the anesthesiologist) to protect the new lung tissue as much as possible from any propensity to develop edema.

Stepwise events in lung transplantation involve diseased lung removal, bronchial anastomosis (and functional testing with gentle hand ventilation using room air), followed by pulmonary vein then artery anastomoses. During the surgery other priorities include meticulous hemostasis and preservation of phrenic, recurrent laryngeal and vagus nerves. Due to the inadequacy of bronchial artery perfusion, some surgeons buttress their bronchial anastomoses with a wrap of omentum, an intercostal muscle pedicle or pericardial fat to improve vascularity.

Beyond bronchial anastomosis test ventilation, with reperfusion of the newly transplanted ventilation should start using small tidal volumes with low peak pressures (preferably pressure-limited mode). The new lung is vulnerable to stretch and high oxygen partial pressure. Goals for management should be 5-8cm H20 PEEP, peak airway pressures < 30cm H20, and an inspired oxygen concentration as close to room air as possible while avoiding hypoxemia, ideally <0.5.

Use of ECMO or CPB may be decided preoperatively or intraoperatively. Some centers use CPB for all cases while others reserve it for those who would could not otherwise tolerate the procedure. Veno-venous ECMO is an option to treat postoperative allograft dysfunction which delivers oxygenated blood to newly transplanted lungs without subjecting them to high inspired oxygen concentrations that can also be used as a bridge to re-transplantation in the unfortunate circumstance of severe acute rejection.

c. What Can I do intraoperatively to assist the surgeon and optimize patient care?

There are few surgeries where the anesthesiologist is more involved, or can have more influence on patient outcome. Lung transplant surgery success depends on superb surgical technique and speed but also on collaboration between surgeon and anesthesiologist to assure appropriate surgery timing, administration of antibiotic and immune suppression agents, steps to attenuate hemodynamic perturbations, approaches to minimize any potential for barotrauma or edema accumulation in the new lung, and provision of anesthesia that will not delay recovery when postoperative tracheal extubation is appropriate.

d.What are the most common intraoperative complications and how can they be avoided/treated?

Equally urgent and common as intraoperative complications during lung transplantation are difficulty in matching ventilation with surgical goals, and the almost continuous hemodynamic instability during mediastinal handling, especially if circulatory support is not used. Ventilatory challenges relate separately to the diseased and newly transplanted lungs. In general terms, a diseased lung can be “abused” to achieve adequate respiratory parameter as long as it will be removed (not necessarily true during single lung procedures), but a newly transplanted lung must be protected using all tools available. As outlined above, hemodynamic instability is critical to understand in the context of surgery, particularly the differentiation of hypovolemia from temporary mediastinal handling by the surgeon – the former being preferentially managed through logical fluid replacement, the latter through patient positioning and vasopressors, sometimes requiring the surgeon cease activities temporarily, adapt or adjust. The importance of recognizing the impact of SVC obstruction with hypotension on cerebral perfusion pressure must be appreciated.

Cardiac Complications:

Even young patients without any history of cardiac compromise often require continuation and slow postoperative wean of vasoactive agents started during surgery. Patients with preoperative right ventricular dysfunction particularly benefit from inhaled nitric oxide (20ppm), which is also weaned prior to tracheal extubation after surgery. Anastomosis of the pulmonary veins occasionally produces stenosis that impair left atrial filling, although these can often be recognized during the post-implant TEE.

Pulmonary Complications:

As outlined above, a critical aspect of lung transplant surgery involves post-reperfusion ventilator management. Beyond standard initial steps such as verifying ET tube placement, ET tube suctioning and evaluation for bronchospasm, adjustment of ventilator settings should adhere to goals to maintain PEEP levels 5-8 cm H2O, inspired oxygen levels below 50% and peak inspiratory pressures less than 30cm H2O. In difficult circumstances, sometime intensive care ventilators are more versatile than their operating room cousins. If all respiratory manipulation fails to sufficiently improve the situation, veno-venous ECMO can deliver oxygenated blood to the newly transplanted lung while avoiding further lung damage. Occasionally, a postoperative chest X-ray will indicate a lobar torsion - should this occur it is a surgical emergency to reduce the torsion and hopefully save the affected lobe.

a. Neurologic:

The most common neurologic complication in lung transplantation is stroke whether embolic in origin or due to hypoperfusion.

b. If the patient is intubated, are there any special criteria for extubation?

At the end of surgery after the dual lumen ET tube is exchanged for a single lumen ET tube, lung transplant patients are transported intubated to the ICU for several hours of observation. A single lumen ET tube with internal diameter 7.5-8 mm permits bronchoscopy and bronchial toilet prior to tracheal extubation, which can occur once the patient is hemodynamically stable, awake, and pain control is initiated.

c. Postoperative management

What analgesic modalities can I implement?

Upon ICU arrival, attention is paid to assuring the patient’s coagulation function is normal to facilitate prompt insertion of a thoracic epidural for post-operative pain control. Pain control by thoracic epidural is ideal since thoughtfully designed infusion solutions (e.g., combined bupivacaine 0.125%/hydromorphone 10ug/ml) can provide good analgesia with minimal respiratory depression or vasodilation-related hypotension.

What level bed acuity is appropriate? (Example: floor, telemetry, step-down, or ICU and justification):

All lung transplant patients start their postoperative recovery in an intensive care setting.

What are common postoperative complications, and ways to prevent and treat them? (Example: postop delirium, postop DVT/PE, reoperation for bleeding, functional decline, increased mortality)

a. Allograft dysfunction: Long term allograft dysfunction can lead to bronchiolitis obliterans and graft failure. Acute allograft dysfunction, related to acute rejection and/or ischemia-reperfusion injury, occurs in 10-25% of patients and causes the majority of early complications (including 50-90% of early deaths). It can be prevented through a variety of measures. Meticulous attention to immune suppressive measures and lung protection strategies, as outlined above are supplemented by transplant team interventions based on presumed contributing factors.

b. Acute kidney injury: Numerous perioperative factors contribute renal insult, and combine to make acute declines in creatinine clearance very common following lung transplant surgery. Up to 8% of patients following lung transplant surgery will require dialysis following surgery. Strategies aimed at renoprotection primarily involve avoidance of unnecessary renal insults.

c. Postoperative hemorrhage: Uncorrected coagulopathy and/or unaddressed surgical bleeding can contribute to ongoing bleeding and the need to return to the operating room for clot evacuation. Some surgeons believe postoperative bleeding is reduced if CPB is avoided. Re-operation portends poor prognosis, and postoperative management must include appropriate coagulation testing an transfusion therapy.

d. GERD: Reflux is common following lung transplant surgery. Procedure-related vagal nerve effects may be a contributing factor. Care should be taken in initiating oral nutrition in these patients and should not be initiated until the patient has passed a thorough swallow evaluation.

What's the Evidence?

Castillo, M.. "Anesthetic management for lung transplantation". Curr Opin Anaesthesiol. vol. 24. pp. 32-36.

Orens, J.B., Boehler, A., de Perrot, M., Estenne, M., Glanville, A.R., Keshavjee, S., Kotloff, R., Morton, J., Studer, S.M., Van Raemdonck, D., Waddel, T., Snell, G.I.. "A review of lung transplant donor acceptability criteria". JHeart Lung Transplant. vol. 22. 2003. pp. 22-1183.

Jackson, A., Cropper, J., Pye, R., Junius, F., Malouf, M., Glanville, A.. "Use of extracorporeal membrane oxygenation as a bridge to primary lung transplant: 3 consecutive, successful cases and a review of the literature". JHeart Lung Transplant. vol. 27. 2008. pp. 27-348.

Ritchie, M., Waggoner, A.D., Davila-Roman, V.G., Barzilai, B., Trulock, E.P., Eisenberg, P.R.. "Echocardiographic characterization of the improvement in right ventricular function in patients with severe pulmonary hypertension after single-lung transplantation". JAm Coll Cardiol. vol. 22. 1993. pp. 22-1170.

Rocca, G.D., Coccia, C., Pugliese, F., Antonini, M., Pompei, L., Ruberto, F., Venuta, F., Ricci, C., Gasparetto, A.. "Intraoperative inhaled nitric oxide during anesthesia for lung transplant". Transplant Proc. vol. 29. 1997. pp. 29-3362.

Canales, M., Youssef, P., Spong, R., Ishani, A., Savik, K., Hertz, M., Ibrahim, H.N.. "Predictors of Chronic Kidney Disease in Long-Term Survivors of Lung and Heart-Lung Transplantation". Am J Transplant. 2006.

Westerlind, A., Nilsson, F., Ricksten, S.E.. "The use of continuous positive airway pressure by face mask and thoracic epidural analgesia after lung transplantation". JCardiothorac Vasc Anesth. vol. 13. 1999. pp. 13-249.

Robertson, A.G., Krishnan, A., Ward, C., Pearson, J.P., Small, T., Lordan, J., Corris, P.A., Dark, J.H., Karat, D., Shenfine, J., Griffin, S.M.. "Anti-reflux surgery in lung transplant recipients: Outcomes and effects on quality of life". Eur Respir J.

Studer, S.M., Levy, R.D., McNeil, K., Orens, J.B.. "Lung transplant outcomes: a review of survival, graft function, physiology, health-related quality of life and cost-effectiveness". Eur Respir J. vol. 24. 2004. pp. 24-674.

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