Lung transplantation: Anesthetic management

INTRODUCTION — Over 4000 lung transplants are performed annually in the United States after increasing steadily for the past decade (figure 1). This topic will discuss anesthetic and pain management for lung transplantation, including unique aspects of this thoracic surgical procedure. General considerations for anesthetic management of open thoracic surgical procedures and one lung ventilation are discussed in other topics:

●(See "Anesthesia for open pulmonary resection".)

●(See "One lung ventilation: General principles" and "Lung isolation techniques".)

Preanesthetic consultation and preparations for lung transplantation are discussed in a separate topic. (See "Lung transplantation: Preanesthetic consultation and preparation".)

Guidelines for selection of recipients, specific surgical techniques, and postoperative medical and surgical management are discussed in separate topics:

●(See "Lung transplantation: An overview".)

●(See "Lung transplantation: General guidelines for recipient selection".)

●(See "Lung transplantation: Disease-based choice of procedure".)

●(See "Lung transplantation: Procedure and postoperative management".)

OVERVIEW OF SURGICAL TECHNIQUES — Anesthetic management is determined in part by whether the patient will have a single lung transplant, bilateral lung transplant, or heart-lung transplantation. This decision is made by the surgeon and lung transplantation team based on the patient's underlying disease [1]. (See "Lung transplantation: Disease-based choice of procedure" and "Heart-lung transplantation in adults".)

●Single lung transplantation – Single lung transplantation accounts for approximately 25 percent of adult lung transplant procedures (figure 1). Indications for single versus bilateral lung transplantation are discussed separately. (See "Lung transplantation: Procedure and postoperative management", section on 'Single lung transplantation' and "Lung transplantation: Disease-based choice of procedure".)

Single lung transplantation is accomplished with the patient in lateral position on the operating table (figure 2), via a standard posterolateral or anterolateral thoracotomy incision on the selected side. (See "Anesthesia for open pulmonary resection", section on 'Positioning' and "Patient positioning for surgery and anesthesia in adults", section on 'Lateral decubitus'.)

One lung ventilation (OLV) is necessary during resection of the lung that will be replaced, unless full cardiopulmonary bypass (CPB) support has been established (see "One lung ventilation: General principles" and "Lung isolation techniques"). Although no lung ventilation is necessary during full CPB, ventilation of the nonoperative lung is typically necessary when partial mechanical cardiorespiratory support with venoarterial (VA) or venovenous (VV) extracorporeal membrane oxygenation (ECMO) is employed, in order to oxygenate the residual pulmonary blood flow traversing that lung before it mixes with the ECMO blood flow. Furthermore, mechanical ventilation is typically continued to minimize nonoperative lung atelectasis. (See "Extracorporeal life support in adults in the intensive care unit: Overview".)

In patients receiving VA ECMO support via femoral cannulae (see 'Intraoperative venoarterial ECMO support' below), the location of this "mixing point" may be within the aortic arch. In such cases, blood flowing to the head and arms may not be fully oxygenated since it is primarily from the patient's own ventilated (and often diseased) nonoperative lung, even though the lower body receives fully oxygenated blood from the ECMO circuit. Thus, there is often a discrepancy in blood oxygenation for the upper versus the lower body (ie, a differential hypoxemia, also termed "north-south syndrome," or "harlequin syndrome"). Notably, north-south syndrome does not occur with VV ECMO since VV ECMO oxygenates venous blood before it enters the pulmonary circulation; thus, the mixing point occurs in the right atrium (RA) (see 'Intraoperative venovenous (VV) ECMO support' below). Counterintuitively, north-south syndrome is worse when cardiac function is better during VA ECMO since ejection of deoxygenated blood from the heart pushes the mixing point distally in the aorta. Options for treatment of this differential hypoxemia include [2]:

•Reducing native cardiac output through infusion of a beta blocking agent (if cardiac function is hyperdynamic).

•Placing an LV vent for cardiac decompression (if cardiogenic pulmonary edema is affecting alveolar gas exchange).

•Increasing VA ECMO flow to move the mixing point closer to the aortic valve. Increasing VA ECMO flow risks inducing cardiac distension and may cause pulmonary edema and worsen oxygenation [3].

•Dividing the arterial outflow cannula with a Y connector and providing oxygenated blood into the venous system prior to the pulmonary circulation (called veno-arterial-venous ECMO) can improve systemic oxygenation; however, this requires careful monitoring and adjustment of diverted arterial flows [4].

Even if CPB support is not planned, personnel and equipment for CPB support remain on standby for the duration of a lung transplantation procedure so that CPB can be initiated immediately to assist in the management of refractory hypoxemia, intractable hemodynamic instability, or severe bleeding due to difficulty with surgical dissection (see 'Use of cardiopulmonary bypass' below). For example, patients who initially tolerate OLV may experience severe right ventricular (RV) dysfunction and hemodynamic instability at the time of clamping of the pulmonary artery (PA) in preparation for lung resection. PA clamping significantly increases pulmonary artery pressure (PAP) since all cardiac output is suddenly diverted through the vasculature of a single lung. Some patients with pre-existing pulmonary hypertension do not tolerate PA clamping without mechanical cardiorespiratory support with ECMO or full CPB [5]. Furthermore, patients who initially tolerate PA clamping may require cardiorespiratory support later in the procedure (eg, when the left atrium is partially clamped to complete the pulmonary vein anastomoses or at the time of reperfusion of the newly transplanted lung. (See 'Mechanical cardiorespiratory support' below and "Lung transplantation: Procedure and postoperative management", section on 'Extracorporeal life support'.)

●Bilateral lung transplantation – Bilateral lung transplantation is performed in approximately 75 percent of adult patients (figure 1) and is required in those with generalized bronchiectasis (eg, cystic fibrosis) [6], chronic pulmonary infection, or significant pulmonary hypertension (figure 1). Patients with other indications also frequently receive bilateral lung transplants due to improved long-term outcomes in some patient groups. (See "Lung transplantation: Disease-based choice of procedure".)

During bilateral lung transplantation, the lungs are implanted separately but sequentially [7]. The standard approach is a bilateral sequential operation through a transverse thoracosternotomy (ie, clamshell) incision (figure 3) [7]. The patient is supine, and bilateral submammary incisions are made with transection of the sternum, allowing for complete visualization of the lungs and heart. An alternative bilateral antero-axillary thoracotomy approach that does not transect the sternum is preferred in some centers. Another surgical approach is via a classic sternotomy, but this incision does not provide ideal visualization. (See "Lung transplantation: Procedure and postoperative management", section on 'Bilateral lung transplantation'.)

After the chest is opened, both native lungs are mobilized. The native lung with the worst function (as previously assessed by ventilation/perfusion scan) is replaced first, while OLV is used for the contralateral lung. Following a brief period of reperfusion of the first lung allograft, OLV switches to the opposite side and the second lung is implanted. With the respiratory support provided by unilateral lung ventilation during bilateral lung transplantation, some patients can avoid mechanical cardiorespiratory support throughout the surgical procedure. However, similar to single lung transplantation, problems with hypoxemia or hemodynamic instability during clamping of the PA on either side may necessitate ECMO or full CPB support. (See "Lung transplantation: Procedure and postoperative management", section on 'Extracorporeal life support'.)

INTRAOPERATIVE ANESTHETIC MANAGEMENT — We agree with international consensus recommendations that have been drafted for anesthetic and intensive care management of patients undergoing lung transplantation [8].

Monitoring — Invasive intravascular monitors and a transesophageal echocardiography (TEE) probe are employed during lung transplantation

Invasive intravascular monitors

●Intra-arterial catheter – An intra-arterial catheter is placed before induction of general anesthesia since patients scheduled for lung transplantation are susceptible to hypotension during induction due to intravascular volume depletion. Preoperative hypercapnia (partial pressure of carbon dioxide [PaCO₂] >55 mmHg) predicts development of hypotension with induction [9].

For patients with a radial artery catheter who have a clamshell incision, cephalad retraction of the chest wall during surgery can compress the subclavian artery against the first rib; in such cases the femoral arterial pressure can be 10 to 20 mmHg higher than the radial arterial pressure for the duration of the retraction. If radial arterial pressure readings are suspected to be inaccurate, intraoperative hypotension can be confirmed either by checking noninvasive blood pressure measurements using a cuff on the contralateral arm, or by placing a femoral arterial line.

●Large-bore central venous catheter – Since most patients require administration of intravenous (IV) vasopressors and inotropes, and may need extracorporeal membrane oxygenation (ECMO) or full cardiopulmonary bypass (CPB), a large-bore central venous catheter (CVC) is always inserted, typically after induction of general anesthesia. For most patients, we prefer a 9 Fr double-lumen introducer placed in the right internal jugular (IJ) vein. A subclavian CVC site is less desirable due to a higher risk of pneumothorax during insertion, and the catheter may become obstructed during retraction of the chest wall.

●Pulmonary artery catheter – A pulmonary artery catheter (PAC) is also inserted, typically after induction, in order to monitor pulmonary artery pressure (PAP) throughout the perioperative period [10]. The surgeon must be aware of the position of the PAC before transecting the pulmonary artery (PA) in order to avoid entrapment of the catheter tip. Using TEE (midesophageal ascending aorta short-axis view) to position the PAC tip within the main PA before its bifurcation aids in avoiding this complication.

Transesophageal echocardiography — TEE is routinely employed during single or bilateral lung transplantation for initial evaluation of cardiovascular anatomy and function and subsequent continuous intraoperative monitoring [11-17]. The etiology of systemic hypotension can be rapidly assessed and appropriately managed with vasopressor therapy (primarily) and/or volume administration during periods of hemodynamic instability.

●Intravascular volume assessment – Assessment of intravascular volume status and left ventricular (LV) filling is helpful to guide fluid therapy throughout the intraoperative period. Inadequate LV filling can be quickly assessed in the transgastric midpapillary short-axis view using qualitative visual assessment of LV cavity size. Also, quantitative measurements of the internal diameter or cross-sectional area of the LV at end-diastole can be made. These qualitative and/or quantitative assessments allow recognition of changes from baseline. (See "Intraoperative transesophageal echocardiography for noncardiac surgery", section on 'Assessment of left ventricular volume'.)

These assessments are particularly valuable during periods of hypotension. Although maintaining a restrictive fluid strategy is important for postoperative pulmonary graft function (see 'Fluid and transfusion management' below), this may lead to hypotension, particularly in hypovolemic patients. Other causes of inadequate LV filling can also be recognized using TEE, including acute right ventricular (RV) dysfunction or systemic vasodilation occurring after lung reperfusion, which can also cause dynamic LV outflow tract obstruction [10].

●Right ventricular function – RV function is assessed throughout the procedure [10,16,17]. Increased RV end-diastolic volume, decreased RV free-wall endocardial excursion and wall thickening, LV septal displacement, and decreased tricuspid annular plane systolic excursion are some of the most commonly observed signs of RV overload and dysfunction (movie 1) [18]. Details regarding a comprehensive TEE assessment of RV function are discussed elsewhere. (See "Echocardiographic assessment of the right heart".)

Development of severe RV dysfunction influences intraoperative decisions to initiate mechanical cardiorespiratory support (eg, ECMO or full CPB), particularly during PA clamping if hypoxemia and/or hemodynamic instability are refractory to inotropic agents and pulmonary vasodilators [10,19]. (See 'Mechanical cardiorespiratory support' below.)

●Left ventricular function – LV dysfunction may occur due to coronary air embolism following reperfusion of the transplanted lung if de-airing of the graft is incomplete. Most commonly, inferior regional wall motion abnormality and RV dysfunction occurs due to air embolism to the right coronary artery. (See "Intraoperative transesophageal echocardiography for noncardiac surgery", section on 'Regional LV systolic function'.)

Intraoperative TEE is also used to:

●Guide ECMO cannula placement – TEE is typically employed in patients requiring intraoperative ECMO (figure 4 and image 1) [19]. (See 'Intraoperative venovenous (VV) ECMO support' below and 'Intraoperative venoarterial ECMO support' below.)

TEE can be used to guide placement of a venous cannula into the right atrium (RA) without abutting the tricuspid valve or interatrial septum [16]. Successful guidewire cannulation for the arterial cannula is confirmed by visualization of a wire in the descending aorta, with proper final positioning of an arterial cannula in the descending aorta sometimes possible, depending on cannula length. Furthermore, poor venous return due to hypovolemia or complications caused by an ECMO cannula (eg, kinking, obstruction, perforation of the interatrial septum) can often be diagnosed with TEE [16]. (See "Extracorporeal life support in adults in the intensive care unit: The role of transesophageal echocardiography (TEE)".)

●Assess post-transplant pulmonary vein anastomoses – Post-transplant assessment of pulmonary vein (PV) anastomoses is important to rule out any restriction of blood flow through these vessels since this may lead to postoperative pulmonary edema, hypoxia, and lung graft failure [14,16,20-22]. PV flow may be restricted due to kinking, external compression, sutures, or thrombus in the PV [12,21,22]. Poor gas exchange and allograft engorgement suggest significant PV obstruction [22].

Flow from all four PVs should be examined with both color-flow and pulsed-wave Doppler (image 2). Flow should appear laminar (nonturbulent), with peak velocity <100 cm/second (movie 2). However, velocities may be transiently higher after single lung implantation when blood flow is disproportionately diverted through the new lung allograft due to its lower pulmonary vascular resistance (PVR).

●Assess post-transplant pulmonary artery anastomoses – Post-transplant assessment of both pulmonary artery (PA) anastomoses is also important to rule out stenosis [21]. The TEE midesophageal ascending aorta short axis view is best for visualizing the main PA and right PA. The left PA may be difficult to visualize by TEE due to proximity to the left main bronchus.

Two-dimensional assessment of each PA anastomosis should note a diameter that is ≥75 percent of the ipsilateral native PA [12,21]. Doppler assessment of each PA anastomosis is also necessary to rule out turbulent flow or a significant gradient across the anastomosis indicating possible stenosis.

Induction and intubation

Induction of general anesthesia — If a rapid sequence induction and intubation (RSII) is planned because of insufficient fasting time, induction agents and doses are selected based in part on the potential for hemodynamic instability. Even if ventricular function is normal, patients with severe pulmonary hypertension or poor lung compliance requiring high ventilation pressures are sensitive to the sudden reductions in preload that may occur during anesthetic induction [5]. For this reason, we typically choose etomidate 0.2 to 0.3 mg/kg to minimize likelihood of hemodynamic instability during anesthetic induction with planned RSII. (See "Lung transplantation: Preanesthetic consultation and preparation", section on 'Determination of fasting status' and "Rapid sequence induction and intubation (RSII) for anesthesia" and "General anesthesia: Intravenous induction agents", section on 'Etomidate'.)

In patients without aspiration risk factors, a combination of anesthetic and adjuvant agents may be used to achieve a slower induction. For example, a low dose of a short-acting benzodiazepine (eg, midazolam 1 to 4 mg) plus a moderate dose of synthetic opioid (eg, fentanyl 2 to 4 mcg/kg or sufentanil 0.2 to 0.5 mcg/kg) plus a reduced dose of the selected sedative-hypnotic induction agent (eg, propofol 0.5 to 1 mg/kg or ketamine 0.5 to 2 mg/kg or etomidate 0.2 mg/kg) may be administered. Propofol is the most commonly selected sedative-hypnotic anesthetic induction agent for lung transplant recipients since adrenal suppression during subsequent postoperative care is not a risk as it may be with etomidate [5,13]. (See "General anesthesia: Intravenous induction agents".)

A variety of vasoactive agents should be readily available (table 1), since hemodynamic instability may occur during or immediately after induction, even in patients with normal ventricular function.

Lung isolation — Lung isolation is usually with double-lumen endotracheal tube (DLT) placement [13]. During single lung transplantation, a left-sided DLT is selected for right pneumonectomy (figure 5), while a right-sided DLT is selected for left pneumonectomy (figure 6). For bilateral lung transplantation, a left-sided DLT is usually selected due to ease of use. In this case, the bronchial cuff of the left-sided DLT is positioned as far proximally as possible to allow room for the anastomosis. The cuff remains inflated in the left mainstem bronchus during the left bronchial anastomosis to avoid a large air-leak into the surgical field. (See "Lung isolation techniques", section on 'Double-lumen endobronchial tubes' and "Lung isolation techniques", section on 'Left pneumonectomy or bronchial surgery'.)

A bronchial blocker placed through a single-lumen tube may be selected (rather than a DLT) if the patient has anticipated or actual difficulty with intubation. However, bronchial blockers are vulnerable to dislodgement during manipulation of the mainstem bronchus. Also, in rare cases, a bronchial blocker or its guidewire has become entrapped in the surgical staple line along the left bronchial stump during lung resection surgery [23]. (See "Lung isolation techniques", section on 'Bronchial blockers'.)

Maintenance of anesthesia — We typically use the potent volatile inhalation agent sevoflurane for maintenance of general anesthesia, and we administer a nondepolarizing neuromuscular blocking agent. We also administer bolus doses of an IV opioid (eg, fentanyl, sufentanil), while some centers employ an infusion of sufentanil, remifentanil, or ketamine infusion. However, regional variations in techniques to maintain anesthesia during lung transplantation are common. For example, many European transplant centers avoid inhalation anesthetic agents and use a total IV anesthetic technique instead [13]. (See "Maintenance of general anesthesia: Overview".)

Ventilation before transplantation — Transitioning from spontaneous breathing to positive pressure ventilation during induction and subsequently transitioning to one lung ventilation (OLV) at the time of lung resection is often challenging in a patient with severe lung disease.

●Two lung ventilation after intubation – After intubation, low tidal volume (TV) ventilation is initiated at approximately 6 mL/kg (predicted body weight) during two lung ventilation. The respiratory rate is adjusted to maintain the end-tidal carbon dioxide (ETCO₂) and PaCO₂ near baseline. Although guidelines for low TV ventilation in patients with acute respiratory distress syndrome are clearly established (table 2), adjustments are often needed to achieve adequate ventilation and oxygenation during the operative period. (See "One lung ventilation: General principles", section on 'Lung-protective ventilation strategies'.)

●Changing to one lung ventilation – Prior to initiating OLV, patients are ventilated with an FiO₂ of 100 percent to minimize subsequent desaturation and promote absorption atelectasis in the non-ventilated lung, thereby decreasing shunt. After switching to OLV, the TV is typically decreased to approximately 4 to 5 mL/kg. The fraction of inspired oxygen (FiO₂) is adjusted, aiming for a pulse oxygen saturation (SpO₂) of 89 to 95 percent. However, oxygenation of the native single lung is frequently very poor so that titration of FiO₂ below 100 percent is not possible.

During either two lung or one lung ventilation, lung transplant patients are at risk for barotrauma caused by elevated ventilation pressures, with the potential consequences of tension pneumothorax when the chest is closed or a large air leak after the chest is open. Maintaining small TV with pressure-controlled ventilation reduces risk of barotrauma. However, providing a minute ventilation that is too low will worsen hypercarbia, which may worsen pulmonary hypertension and RV dysfunction. Even small increases in ETCO₂ may produce a measurable rise in PVR [24]. Additional details of OLV and an approach to the management of hypoxemia are provided separately. (See "One lung ventilation: General principles" and "Lung isolation techniques".)

During either two lung or one lung ventilation, the target for plateau inspiratory pressure should be <30 cm H₂O [10,13]. Positive end-expiratory pressure (PEEP) is usually set at 5 to 10 cm H₂O. Notably, higher PEEP levels may decrease preload and cause hypotension in an anesthetized, vasodilated patient undergoing lung transplantation. Prolonging the expiratory time (eg, inspiratory to expiratory [I:E] ratio) to a ratio of 1:3 or 1:4 for patients with chronic obstructive pulmonary disease (COPD; or other pulmonary conditions that impair expiratory flow rate) helps reduce air trapping by allowing sufficient exhalation time, although a high inspiratory flow (needed to shorten inspiratory time) may increase peak inspiratory pressures. Inadequate time for exhalation leads to breath-stacking with increased intrathoracic pressure and decreased venous return, which can lead to profound hypotension. Hypotension due to such dynamic hyperinflation (also termed auto-PEEP, intrinsic-PEEP, or gas-trapping) is treated by disconnecting the ventilator and allowing the patient to exhale fully. (See "Invasive mechanical ventilation in acute respiratory failure complicating chronic obstructive pulmonary disease", section on 'Ventilator settings' and "Dynamic hyperinflation in patients with COPD".)

Antibiotic prophylaxis and immunosuppression — Since immunosuppression places lung transplant recipients at high risk for opportunistic bacterial infections, broad-spectrum antibiotic prophylaxis is initiated prior to surgical incision. Examples are given in the table (table 3). (See "Bacterial infections following lung transplantation", section on 'Routine perioperative prophylaxis' and "Antimicrobial prophylaxis for prevention of surgical site infection in adults".)

Adherence to the prescribed plan for immunosuppression is critical to prevent allograft rejection and preserve lung function. A bolus of methylprednisolone (500 to 1000 mg) is administered in the intraoperative period immediately prior to reperfusion of each graft when the PA clamp is released. Additional induction immunosuppression therapy may be administered during the intraoperative or early postoperative period according to institutional protocol. These agents can be classified into two groups: monoclonal antibody preparations (eg, basiliximab) and polyclonal agents (eg, anti-lymphocyte and anti-thymocyte globulins). One example of an early initiation regimen includes basiliximab 20 mg administered as an IV infusion over 30 minutes and IV mycophenolate 1000 mg infused over two hours in the operating room (OR), with both agents initiated at the beginning of the operation. (See "Lung transplantation: Procedure and postoperative management", section on 'Initiation of immunosuppression' and "Induction immunosuppression following lung transplantation".)

Mechanical cardiorespiratory support — In approximately 20 to 40 percent of patients, either ECMO or full CPB is necessary to complete lung transplantation, although use varies widely among centers [13,19,25-30]. Patients who will most likely need ECMO or CPB include those with severe primary pulmonary hypertension with a transpulmonary pressure gradient >20 mmHg, pulmonary fibrosis, or RV dysfunction with hypertrophy or dilation [5,25-27,29]. We and many other centers favor use of ECMO rather than CPB when possible, based on observational studies indicating that ECMO support is associated with lower rates of primary graft dysfunction (PGD), need for dialysis, tracheostomy, or blood transfusion, and shorter intubation time and hospital stay [25-31].

Intraoperative venovenous (VV) ECMO support — Management of patients who require venovenous (VV) ECMO support in the preoperative period before lung transplantation is discussed separately. (See "Lung transplantation: Preanesthetic consultation and preparation", section on 'Preoperative extracorporeal membrane oxygenation'.)

If VV ECMO was initiated in the preoperative period and is being maintained when the patient enters the OR, the ECMO circuit monitor is positioned within view of the anesthesiologist for assessment of device function, flow, and pump speed. Dual-stage cannulae for VV ECMO that were placed via the right IJ vein depend on maintaining an appropriate position in order to function properly (figure 7). Desaturation while on VV ECMO may indicate malposition of the cannula or other causes of inadequate ECMO flow. Excess cannula rotation or retraction can cause the outflow port to become misaligned with the tricuspid valve, leading to ineffective flow of oxygenated blood into the RV. Thus, caution is necessary to avoid excessive manipulation of the cannula during head positioning for endotracheal intubation or central line placement in the left IJ or left subclavian vein. Furthermore, PAC placement may be challenging due to obstruction from VV ECMO cannulae. TEE guidance is used to assist PAC placement. (See "Extracorporeal life support in adults in the intensive care unit: The role of transesophageal echocardiography (TEE)", section on 'Monitoring during ECMO support'.)

In some cases, the surgeon may insert a bicaval dual-lumen cannula via the right IJ vein during the preoperative period as access for ECMO support [32,33]. In other cases, the surgeon may plan intraoperative insertion of a dual-lumen VV ECMO cannula, so the anesthesiologist must avoid placement of a standard CVC in the right IJ. In such cases, alternative sites for placement of the CVC include left IJ or left subclavian vein.

The anesthesiology team typically provides assistance with insertion of cannulae for initiation of ECMO support via TEE imaging, particularly if a dual-lumen cannula is used (figure 7). This dual-lumen cannula is highly dependent on positioning for adequate function. Also, any migration of this catheter may result in systemic hypoxemia if the outflow port is no longer positioned to provide adequate flow across the tricuspid valve. (See "Extracorporeal life support in adults in the intensive care unit: The role of transesophageal echocardiography (TEE)", section on 'Central cannulation'.)

If urgent intraoperative initiation of VV ECMO becomes necessary to treat refractory hypoxia during transition to OLV, clamping of the PA, partial clamping of the left atrium during PV anastomosis, or during reperfusion of the newly transplanted lung, this can be accomplished using femoral vein to femoral vein VV ECMO [17]. (See "Extracorporeal life support in adults in the intensive care unit: The role of transesophageal echocardiography (TEE)", section on 'Peripheral cannulation'.)

Intraoperative venoarterial ECMO support — Venoarterial (VA) is usually preferred for intraoperative cardiopulmonary support, rather than CPB [5]. If peripheral VA ECMO is needed during the intraoperative period due to anticipated or actual hemodynamic instability, the anesthesiology team typically provides assistance with TEE imaging during insertion of cannulae for initiation of ECMO support. Femoral vein to a femoral artery or to the right subclavian artery or central VA ECMO (RA to ascending aorta) can be established electively [17,34,35], or as an emergency if hemodynamic compromise occurs during lung transplant without full CPB support (figure 8) [17,19,25,26]. Although peripheral VA ECMO is associated with increased rates of groin vascular complications, it is the preferred technique when ECMO support is likely to be continued postoperatively [36]. An additional cannula is often used to provide oxygenated blood to the cannulated leg to avoid distal ischemia from obstructed blood flow (figure 8). (See "Extracorporeal life support in adults in the intensive care unit: The role of transesophageal echocardiography (TEE)", section on 'Cannula insertion and initiation'.)

Use of cardiopulmonary bypass — CPB is sometimes established electively prior to starting lung resection in patients with severe pulmonary hypertension, particularly if there is concern regarding RV function. As in typical CPB for cardiac surgery (figure 9), venous cannulation may be accomplished with a single dual-stage venous cannula placed via the appendage of the RA with the distal tip of the cannula positioned in the inferior vena cava or with bicaval separate cannulation of the superior vena cava and the inferior vena cava. Aortic cross clamping and cardiac arrest with cardioplegia are not necessary to perform lung transplantation on CPB unless concomitant intracardiac procedures or major atrial reconstruction are planned. (See "Initiation of cardiopulmonary bypass", section on 'Venous cannulation'.)

Anticoagulation

●No mechanical cardiorespiratory support – Anticoagulation during lung transplant without full CPB support is managed with 5000 units of IV heparin administered prior to vascular occlusion. Heparin is typically redosed prior to a second lung transplant on the contralateral side. The decision to reverse heparin with protamine is made by assessing the degree of ongoing bleeding and considering the potential adverse effects of protamine administration including an increase in PVR. Since the heparin dose is low, protamine reversal is often omitted.

●Extracorporeal membrane oxygenation – Either VV ECMO or VA ECMO requires some level of anticoagulation, although less than the systemic dose required for full CPB. Typically, a single dose of IV heparin 5000 units is administered to initiate either VV ECMO or VA ECMO. Subsequently, the activated clotting time (ACT) is maintained within a range (eg, 180 to 210 seconds) by administering additional doses of heparin or using a heparin infusion [19]. (See "Clinical use of coagulation tests", section on 'Monitoring heparins'.)

If VV ECMO was initiated during the preoperative period, the anticoagulation strategy may vary according to patient-specific and institution-specific factors. For example, a lower ACT target may have been selected for patients with any hemorrhagic complication (eg, epistaxis, cannulation site hematoma, intracranial hemorrhage, gastrointestinal bleeding). At our institution, anticoagulation in the intensive care unit (ICU) is maintained with a continuous infusion of IV heparin, titrated to an ACT of 180 to 210 seconds. Some institutions maintain activated partial thromboplastin time (aPTT) at 45 to 80 seconds, rather than monitoring ACT to manage anticoagulation in the ICU [37].

We turn off this heparin infusion just before patient transport to the OR, so that bleeding will be minimized during the initial dissection phase of the transplantation procedure. During the intraoperative period, small bolus doses of IV heparin (eg 2500 to 5000 units) are administered to achieve the intraoperative target ACT value (eg, 180 to 210 seconds) before beginning lung resection, and this value is maintained throughout the procedure while the patient remains on ECMO.

●Cardiopulmonary bypass – Full systemic anticoagulation is required for patients undergoing CPB. Typically, IV heparin 300 to 400 units/kg is administered, then the ACT is maintained at ≥400 to 480 seconds to prevent clot formation in the CPB circuit. (See "Blood management and anticoagulation for cardiopulmonary bypass", section on 'Heparin administration and monitoring'.)

Fluid and transfusion management — We use a restrictive fluid management strategy during lung transplantation, similar to other open thoracotomy procedures. Intraoperative administration of large fluid volumes is associated with increased lung interstitial fluid and other extravascular lung water; these may lead to pulmonary edema, prolonged postoperative ventilation, and increased risk of PGD [38-40] (see 'Primary graft dysfunction after reperfusion' below). We use crystalloid solution for maintenance fluid, but a colloid (eg, albumin 5%) is administered for volume resuscitation. (See "Anesthesia for open pulmonary resection", section on 'Fluid and hemodynamic management'.)

The volume of transfused red blood cells (RBCs) is a risk factor for PGD and mortality after lung transplantation, particularly when massive transfusion (>10 to 15 units) is required. [40-43]. Also, a higher ratio of fresh frozen plasma (FFP) to RBCs (>1:2) during massive transfusion is associated with more severe PGD [44]. In one study, transfusion of >15 units of RBCs was associated with increased mortality risk (hazard ratio [HR] 1.36, CI 1.14-1.6) in patients undergoing lung transplantation [43]. Use of recombinant human activated factor VIIa did not increase mortality risk in this study, but it is unclear whether its use decreases transfusion requirements in this setting.

Hemodynamic management — Hypotension is common during lung transplantation, particularly during clamping of the PA, side clamping (ie, partial clamping) of the left atrium to complete the PV anastomoses, and/or reperfusion of the lung. Preemptive treatment with vasopressors, inotropes, or pulmonary vasodilators may prevent the need for emergency mechanical cardiorespiratory support (table 1).

We use norepinephrine as the first-line vasopressor agent to treat hypotension, as do many other centers (table 1) [13]. If hypotension persists (eg, due to vasoplegic syndrome) [45], we add or substitute vasopressin to further increase systemic vascular resistance (SVR). Vasopressin has little effect on PVR [46] and no beta-agonistic effect, which may contribute to its association with reduced atrial fibrillation and other associated adverse outcomes when used to treat postoperative shock [47].

In patients with severe RV dysfunction or failure, we typically add or substitute epinephrine, dobutamine, or milrinone [10]. (See "Anesthesia for noncardiac surgery in patients with pulmonary hypertension or right heart failure", section on 'Vasopressors and inotropes' and "Intraoperative problems after cardiopulmonary bypass", section on 'Right ventricular dysfunction'.)

For patients with refractory pulmonary hypertension and RV dysfunction, an inhaled pulmonary vasodilator such as inhaled nitric oxide (iNO) may be added to achieve selective pulmonary vasodilation [5,13,48]. An alternative agent to reduce PVR is inhaled prostanoid (ie, epoprostenol) administered off-label via jet nebulizer [49-51]. However, optimal timing of initiation of pulmonary vasodilator therapy and efficacy of such therapy with respect to outcomes are unclear [52,53]. Therapy is frequently initiated at maximal dose to treat refractory pulmonary hypertension, with little opportunity for intraoperative weaning. Inability to wean off iNO at the end of the procedure is a risk factor for development of PGD [54]. (See 'Primary graft dysfunction after reperfusion' below and "Anesthesia for noncardiac surgery in patients with pulmonary hypertension or right heart failure", section on 'Chronic targeted therapy for pulmonary hypertension: Patient selection' and "Intraoperative problems after cardiopulmonary bypass", section on 'Right ventricular dysfunction'.)

Ventilation after lung transplantation

Single lung transplantation

General considerations for lung-protective ventilation — After removal of the PA clamp and reperfusion of the transplanted lung, reinflation is accomplished with three to five manual recruitment breaths (eg, sequential inflations/deflations with 30 cm H₂O for 15 seconds each). A lung-protective ventilation strategy is employed, with low tidal volumes ≤6 mL/kg (based on the donor predicted body weight) to maintain low airway pressures after two lung ventilation has been reestablished [17,55,56]. Notably, peak inspiratory pressures will be lower before chest closure than after the chest is closed. PEEP is typically set at low levels (5 to 10 cm H₂O) and adjusted based on oxygenation. PEEP is used with extreme caution (eg, ≤5 cm H₂O) in patients with COPD who undergo single lung transplantation to avoid overinflation of the more compliant native lung. Respiratory rate is adjusted to maintain adequate minute ventilation. (See 'Ventilation before transplantation' above and "Lung transplantation: Procedure and postoperative management", section on 'Ventilatory support and weaning'.)

A high inspired oxygen concentration (FiO₂ >40 percent) is avoided during reperfusion of the transplanted lung since this is associated with PGD [17,41,57]. Typically, the lowest FiO₂ that maintains arterial partial pressure of oxygen (PaO₂) >70 mmHg and noninvasive pulse oximetry measurement of oxygenation (SpO₂) at 92 percent are targets that avoid reperfusion injury [17,55].

Notably, there are no standards for an ideal ventilation mode in all patients during the immediate post-transplantation period, or for maximum peak airway pressure, use of PEEP, or FiO₂ [58].

Avoid hyperinflation of the native lung — Native lung hyperinflation is a phenomenon specific to single lung transplantation performed for severe emphysema, where gas trapping within the native lung can cause mediastinal shift and compression of the transplanted lung with resulting impaired gas exchange and hemodynamic compromise [59]. Persistent native lung hyperinflation prolongs time on the ventilator in the postoperative period [59].

In the OR, the flow-volume loop or expiratory flow curve on the anesthesia ventilator monitor is examined for ongoing expiratory flow at the start of inspiratory flow (ie, flow rate does not return to zero). This alerts the clinician to possible breath-stacking (also called auto-PEEP or intrinsic-PEEP) and hyperinflation. If present, a biphasic capnography tracing indicates differences in exhalation rate and CO₂ release between the native and transplanted lung (figure 10) [60,61]. This phenomenon can be managed by using differential lung ventilation via the DLT during the intraoperative period. In the OR, a second portable ventilator is attached to the DLT lumen directed to the remaining native lung, and asynchronous ventilator settings for the patient’s disease are employed (eg, prolonged expiratory time to avoid breath-stacking, lower TV) [62].

Bilateral lung transplantation

After transplantation of the first lung — After a period of reperfusion (eg, 15 to 30 minutes), OLV of the transplanted lung is established prior to resection of the second lung. Recruitment breaths and lung-protective ventilation are managed as described for single lung transplantation (see 'Single lung transplantation' above). Low TV for single lung ventilation (4 mL/kg), PEEP of 5 to 10 cm H₂O, and the lowest possible FiO₂ that maintains PaO₂ >70 mmHg and SpO₂ at 92 percent are employed [55].

After transplantation of the second lung — After reperfusion and lung volume recruitment of the second transplanted lung, two lung ventilation is resumed with low TV ventilation (4 to 6 mL/kg), PEEP of 5 to 10 cm H₂O and the lowest FiO₂ that maintains SpO₂ at 92 percent. If higher (>50 percent) FiO₂ is required, oxygenation may be improved by additional recruitment maneuvers, small increases in PEEP, administration of bronchodilators, or airway suctioning.

Pressure-controlled ventilation may be selected for some patients, rather than volume control ventilation. In one study of patients undergoing sequential bilateral lung transplantation, an intraoperative ventilation strategy using pressure control ventilation (set at 16 cm H₂O) with higher PEEP (at 10 cm H₂O) plus recruitment maneuvers was compared with a strategy using volume control ventilation (TV 4 mL/kg ideal body weight) with lower PEEP (at 5 cm H₂O) [63]. At 24 postoperative hours, patients in pressure control group with higher PEEP had shorter times to extubation and similar oxygenation parameters. (See "Mechanical ventilation during anesthesia in adults", section on 'Modes of intraoperative mechanical ventilation' and "Modes of mechanical ventilation", section on 'Volume-limited versus pressure-limited'.)

Primary graft dysfunction after reperfusion — PGD may occur shortly after reperfusion of the transplanted lung and should be suspected in patients with refractory hypoxemia (low PaO₂/FiO₂ ratio) after inflation and reperfusion of the allograft(s) and exclusion of other sources of poor oxygenation (eg, occlusion of a pulmonary venous anastomosis, pulmonary thromboembolism, mucous plugging, cardiogenic pulmonary edema, aspiration, pneumonia, or antibody-mediated rejection of the donor lung) [56]. The risk of PGD may be increased due to various donor, recipient, and operative risk factors (figure 11).

The severity of PGD is graded based on the PaO₂/FiO₂ ratio and the presence or absence of diffuse opacities on the chest radiograph (table 4) [64]. (See "Primary lung graft dysfunction", section on 'Clinical manifestations' and "Primary lung graft dysfunction", section on 'Diagnostic evaluation'.)

For patients with refractory hypoxemia despite optimal intravascular volume status and fine-tuning of ventilator settings, a trial of iNO is initiated (typically at 10 to 20 parts per million [ppm]) [65]. For patients with PaO₂/FiO₂ <100, we start iNO at 20 ppm and wean this dose according to improvements in oxygenation. This is accomplished by weaning iNO from 20 ppm to 5 ppm in decrements of 5 ppm per one to two hours as tolerated. Once the dose reaches 5 ppm, weaning is accomplished in 1 ppm per hour decrements until iNO is discontinued. Signs that weaning is progressing too quickly include an increasing oxygen requirement or signs of RV failure (increasing central venous pressure, increasing pulmonary artery pressures and decreasing cardiac output or blood pressure). An alternative agent used in some institutions is inhaled epoprostenol administered at 0.01 to 0.05 mcg/kg/minute via jet nebulizer, with dose adjustments based on efficacy and tolerability of side effects (eg, hypotension, nausea and vomiting). (See "Primary lung graft dysfunction", section on 'Treatment'.)

ECMO may be necessary in patients with severe refractory hypoxia and/or hypercapnia and consequent RV failure [10]. VV ECMO is usually preferred in those who not require hemodynamic support since lower levels of anticoagulation are needed compared with VA ECMO, with lower risk of complications such as bleeding or stroke [19,66,67]. However, patients with pulmonary arterial hypertension or severe PGD may require VA ECMO to provide the most effective offloading and protection of the transplanted lungs. (See 'Mechanical cardiorespiratory support' above.)

Emergence and timing of extubation — At the conclusion of surgery, the DLT is exchanged for a single-lumen endotracheal tube. If airway management was challenging initially, an airway exchange catheter is used, particularly if ventilation and oxygenation are compromised at the conclusion of surgery. However, caution is advised to avoid airway trauma during insertion of an airway exchange catheter [68]. A flexible tip catheter may help to avoid this complication.

We do not routinely extubate patients in the OR because risk for reintubation may be higher compared with later extubation in the ICU, and benefits are uncertain [5,69-71]. However, some centers have developed protocols to facilitate extubation in the OR at the end of the procedure in selected patients [69-72]. Candidates for such early extubation include patients with low intraoperative transfusion requirements [70], minimal or absent episodes of intraoperative hemodynamic instability, no need for ECMO [69,70], and those with previously established epidural analgesia [69-72].

For patients on VV ECMO who have adequate oxygenation following lung transplantation, removal of ECMO cannula is often accomplished at the end of the operation.

Ideally, patients are weaned and extubated within 24 hours of surgery to reduce stress on bronchial anastomoses and decrease risk for pulmonary infection [19]. Splinting and rapid shallow breathing due to pain predispose to development of atelectasis. In particular, pulmonary mechanics are impaired after a clamshell incision, with marked reductions in postoperative forced expiratory volume (FEV₁) and vital capacity [73]. In addition, patients with a denervated lung have decreased cough reflex and decreased ability to clear secretions. For these reasons, some patients may need support with controlled postoperative mechanical ventilation for one to two days after lung transplantation surgery to allow time to achieve optimal pain control and pulmonary mechanics [74].

POSTOPERATIVE ANALGESIA — Providing effective postoperative analgesia after lung transplantation is critical to facilitate recovery, although no consensus exists regarding an optimal approach. Similar to other operations requiring thoracotomy, continuous thoracic epidural analgesia (TEA) or paravertebral block (PVB) are the most commonly employed techniques to control pain [17]. (See "Anesthesia for open pulmonary resection", section on 'Post-thoracotomy pain management'.)

Challenges in pain control — Pain after lung transplantation, particularly if performed via a clamshell incision or a large thoracotomy incision, may be severe. TEA or PVB for postoperative analgesia may be less effective compared with other procedures (see "Anesthesia for open pulmonary resection", section on 'Thoracic epidural analgesia' and "Anesthesia for open pulmonary resection", section on 'Paravertebral block') [73,75]. Furthermore, if a TEA catheter or bilateral PVB catheters are placed in the preoperative period, intraoperative administration of local anesthetic may result in a sympathectomy with vasodilation and hypotension, causing difficulty in maintaining a restrictive fluid management strategy (see "Overview of neuraxial anesthesia", section on 'Cardiovascular' and 'Fluid and transfusion management' above). For this reason, initiation of a local anesthetic infusion is generally deferred until the surgical procedure has been completed. Local anesthetics may be added to the continuous infusion for the TEA or PVB catheter in the intensive care unit (ICU), after the patient is no longer receiving general anesthetic agents, thereby avoiding the risk of additive or synergistic effects that may cause hypotension.

Optimal pain control is also challenging because administration of local anesthetic agents via an epidural catheter may result in a sympathectomy that can lead to hemodynamic instability in a fluid-restricted patient (see "Overview of neuraxial anesthesia", section on 'Cardiovascular'), although this may be less likely with unilateral paravertebral block (see "Thoracic paravertebral block procedure guide"). Furthermore, systemic administration of intravenous (IV) opioid agents, typically via patient-controlled analgesia (PCA), may result in hypotension, as well as oversedation and hypercarbia (see "Use of opioids for postoperative pain control", section on 'Opioid side effects and complications'). In addition, use of nonsteroidal anti-inflammatory drugs (NSAIDs) is typically avoided due to concern for increasing the risk of acute kidney injury in a fluid-restricted patient. (See "Nonopioid pharmacotherapy for acute pain in adults", section on 'Nonsteroidal anti-inflammatory drugs'.)

Neuraxial and regional techniques

Thoracic epidural analgesia — We typically place a TEA catheter in the postoperative (rather than the preoperative) period because of concerns regarding development of an epidural hematoma if intraoperative systemic anticoagulation is necessary for cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO). Patients are individually assessed by our acute pain service for epidural placement within 24 to 48 hours of transplantation. Institution-specific and patient-specific considerations determine whether timing is before or after tracheal extubation [74,76]. (See "Anesthesia for open pulmonary resection", section on 'Thoracic epidural analgesia'.)

In a retrospective review of more than 150 patients, preoperative placement of a TEA catheter was associated with significantly decreased postoperative opioid use and duration of controlled mechanical ventilation, compared with postoperative catheter placement [74]. However, earlier placement was not associated with reduced length of stay in the ICU or hospital. In another retrospective review of more than 100 patients, preoperative TEA catheter placement resulted in slightly better postoperative pain scores but no differences in pulmonary complications compared with postoperative placement [77].

Paravertebral block — Compared with TEA, catheter-based PVB with administration of a continuous infusion of local anesthetic agents to provide analgesia after thoracotomy or clamshell incision provides comparable analgesia and may be associated with fewer adverse side effects, particularly with unilateral PVB [17,78-83]. (See "Anesthesia for open pulmonary resection", section on 'Choice of technique' and "Anesthesia for open pulmonary resection", section on 'Paravertebral block' and "Thoracic paravertebral block procedure guide".)

A PVB catheter may be placed by either the anesthesiologist [84] or the surgeon [85]. Direct placement by the surgeon at the conclusion of the procedure has the advantage of appropriate timing after reversal of anticoagulation, thereby minimizing risk for hematoma. An advantage for PVB catheter placement after single lung transplantation is that unilateral catheter placement preserves function of the contralateral intercostal muscles and nerves [85,86].

Serratus anterior plane block — Case reports have described successful pain control using bilateral serratus anterior plane block catheters inserted after bilateral lung transplantation [17,87,88].

Systemic analgesics — A short-acting opioid (typically fentanyl) is administered to provide analgesia before leaving the operating room (OR), and a fentanyl infusion is initiated on arrival to the ICU as part of a sedation regimen while the patient remains intubated. In preparation for extubation, nurse-administered hydromorphone boluses are administered as needed, with a transition to hydromorphone PCA after extubation. Nonopioid analgesics are often added to reduce opioid requirements. (See "Nonopioid pharmacotherapy for acute pain in adults" and "Use of opioids for postoperative pain control".)

SUMMARY AND RECOMMENDATIONS

●Surgical approaches (See 'Overview of surgical techniques' above.)

•Single lung transplantation is accomplished in lateral position via a standard posterolateral or anterolateral thoracotomy incision. One lung ventilation (OLV) of the nonoperative lung is required unless full cardiopulmonary bypass (CPB) support has been established. During OLV, some patients require partial mechanical cardiorespiratory support with venoarterial (VA) or venovenous (VV) extracorporeal membrane oxygenation (ECMO).

•Bilateral lung transplantation is accomplished as two separate but sequential transplants, typically in supine position via a transverse thoracosternotomy (ie, clamshell) incision. The native lung with the worst function is replaced first while OLV is used for the contralateral lung. Following a brief period of dual lung ventilation and reperfusion of the first lung allograft, OLV is switched to the opposite side for transplantation of the second lung. Problems with hypoxemia or hemodynamic instability may necessitate ECMO or full CPB support.

●Monitoring – Transesophageal echocardiography (TEE) is used to monitor intravascular volume status and left and right ventricular (RV) function, guide ECMO cannula placement, and assess post-transplant pulmonary artery (PA) and pulmonary vein (PV) anastomoses. (See 'Monitoring' above.)

●Anticoagulation – Anticoagulation is required for lung transplantation; heparin dosing depends on whether the procedure is performed off-pump (with or without VA or VV ECMO support) or with full CPB support. (See 'Anticoagulation' above.)

●Induction of general anesthesia – For patients with aspiration risk factors, we perform rapid sequence induction and intubation (RSII); in such patients, we suggest etomidate as the anesthetic induction agent especially if hemodynamic instability is anticipated (Grade 2C).

For patients without aspiration risk, we suggest a slower induction technique (eg, low doses of short-acting benzodiazepine, synthetic opioid, and anesthetic induction agent) (Grade 2C). (See 'Induction of general anesthesia' above.)

●Endotracheal tube management – A double-lumen endotracheal tube (DLT) is typically used to facilitate OLV. During single lung transplantation, a left-sided DLT is selected for right pneumonectomy (figure 5); a right-sided DLT is selected for left pneumonectomy (figure 6). For bilateral lung transplantation, a left-sided DLT is usually selected, with the bronchial cuff positioned as far proximally as possible to allow room for the anastomosis. (See 'Lung isolation' above.)

At the conclusion of surgery, the DLT is exchanged for a single-lumen endotracheal tube. Weaning and extubation should occur within 24 hours of surgery to reduce stress on bronchial anastomoses and decrease risk for pulmonary infection. (See 'Emergence and timing of extubation' above.)

●Pretransplantation ventilator settings – After intubation, lung-protective, low tidal volume (TV) ventilation is initiated at approximately 6 mL/kg for two lung ventilation, then decreased to approximately 4 to 5 mL/kg for OLV. Positive end-expiratory pressure (PEEP) is initially set at 5 to 10 cm H₂O with plateau inspiratory pressure target <25 to 30 cm H₂O. Respiratory rate is adjusted to maintain the end-tidal carbon dioxide (ETCO₂) and partial pressure of carbon dioxide (PaCO₂) near baseline. Fraction of inspired oxygen (FiO₂) is adjusted to maintain pulse oxygen saturation (SpO₂) at 89 to 95 percent. (See 'Ventilation before transplantation' above.)

●Intraoperative fluid and hemodynamic support – We use a restrictive fluid management strategy, similar to other open thoracotomy procedures. (See 'Fluid and transfusion management' above.)

Hypotension is common during lung transplant procedures, particularly during clamping of the PA, partial clamping of the left atrium to complete the PV anastomoses, and/or reperfusion of the lung. We suggest using norepinephrine as the first-line vasopressor agent (Grade 2C). If hypotension persists, we add or substitute vasopressin to further increase systemic vascular resistance (SVR) with little effect on pulmonary vascular resistance (PVR) (table 1). In patients with severe RV dysfunction or failure, we typically add or substitute epinephrine, dobutamine, or milrinone. (See 'Hemodynamic management' above.)

●Mechanical cardiorespiratory support – Refractory hypoxemia and/or hypotension necessitates ECMO (VV or VA) or CPB in approximately 20 to 40 percent of lung transplant recipients. We suggest using ECMO rather than CPB when possible (Grade 2C). ECMO is associated with lower rates of primary graft dysfunction (PGD), need for dialysis, tracheostomy, and blood transfusion, and shorter intubation time and hospital stay. However, full CPB is necessary for some patients (eg, those requiring an additional cardiac surgical procedure). (See 'Mechanical cardiorespiratory support' above.)

●Post-transplantation ventilator settings – After reperfusion and inflation of the transplanted lung(s), with lung recruitment breaths as needed, lung-protective ventilation is established with low TV (eg, 6 mL/kg) and other ventilator settings similar to pretransplantation settings. PEEP is typically set at low levels (5 to 10 cm H₂O). FiO₂ is set at the lowest level that maintains SpO₂ at 92 percent. If FiO₂ >50 percent is necessary, additional recruitment maneuvers, small increases in PEEP, bronchodilator administration, and/or airway suctioning are employed. (See 'Ventilation after lung transplantation' above.)

●Primary graft dysfunction after reperfusion – PGD should be suspected in patients with refractory hypoxemia (low PaO₂/FiO₂ ratio) after inflation and reperfusion of the allograft(s) and exclusion of other sources of poor oxygenation (eg, mucous plugging, cardiogenic pulmonary edema, occlusion of a pulmonary venous anastomosis, pulmonary thromboembolism).

We suggest a trial of inhaled nitric oxide (iNO) for patients with refractory hypoxemia after optimizing ventilator settings and intravascular volume status (Grade 2C), typically at 10 to 20 parts per million (ppm). We start iNO at 20 ppm if arterial oxygen tension (PaO₂)/FiO₂ is <100, and wean the dose as oxygenation improves. An alternative is inhaled epoprostenol administered via jet nebulizer at 0.01 to 0.05 mcg/kg per minute. (See 'Primary graft dysfunction after reperfusion' above.)

●Postoperative pain management – We place a thoracic epidural analgesia (TEA) catheter or unilateral or bilateral paravertebral block (PVB) catheters.

We suggest deferring initiation of local anesthetic infusion until completion of the surgical procedure (Grade 2C). Intraoperative administration may result in sympathectomy with vasodilation and hypotension. Additionally, administration of systemic opioids via patient-controlled analgesia (PCA) is typically required. (See 'Postoperative analgesia' above.)