Anesthesia for heart transplantation

INTRODUCTION — In the United States, 3817 heart transplants were performed in 2021 at transplant centers specializing in treating patients with end-stage heart failure [1]. Although the number of transplants has increased some during the past several years, a shortage of donor organs is always a major limiting factor.

This topic will discuss perioperative and anesthetic management of patients undergoing cardiac transplantation after a donor heart has been allocated. Indications, contraindications, donor selection, and processes for allocation of a donor heart are discussed in separate topics. (See "Heart transplantation in adults: Indications and contraindications" and "Heart transplantation in adults: Donor selection and organ allocation".)

PREANESTHETIC ASSESSMENT — An assessment of the patient's pre-surgery health status is necessary to plan perioperative anesthetic management for cardiac transplantation.

General considerations — General considerations for a candidate for cardiac transplantation include the underlying etiology of heart failure (more information can be found at the International Thoracic Organ Transplant Registry), documented priority status as an organ recipient, and assessment of comorbidities (table 1). Since patients may be on the transplant waitlist for many months prior to receiving a donor organ, it is critically important to identify any recent health status changes that might impact the decision to proceed with transplantation. Frailty related to age or chronic end-organ disease is identified, with confirmation of treatment as indicated (eg, physical rehabilitation, nutritional optimization) [2]. Identification of acute infection, new onset renal or liver insufficiency, stroke, active malignancy, or recent (within six months) tobacco use, alcohol use disorder, or other substance use may be contraindications to transplantation and warrant discussion with the cardiac surgeon and transplant team (table 2). (See "Heart transplantation in adults: Indications and contraindications".)

Other general considerations include the timing of surgery (ie, based upon availability of the donor organ), plans for immunosuppression, and the antibiotic regimen to be prescribed. Also, it is particularly important to note the presence of any type of cardiac implantable electronic device (CIED; pacemaker or implanted cardioverter-defibrillator [ICD]) or ventricular assist device (VAD), or the use of intravenous (IV) inotropic agent, or IV or inhaled pulmonary vasodilator therapy. The perioperative management plan for these devices and therapies must be discussed with the surgeon and transplant team.

Further discussion regarding preanesthetic consultation for any type of cardiac surgery is available in a separate topic. (See "Preoperative evaluation for anesthesia for cardiac surgery".)

Fasting status — Typically, time for preoperative preparation for cardiac transplantation is limited since the potential recipient is notified of a potential matched donor heart only after initial screening has occurred. In many cases, the time required to coordinate operating room availability for organ procurement and concurrent recipient preparation allows adequate notice for eight hours of fasting before surgery, particularly for solid foods like meat (table 3). However, this fasting interval is not always possible since organ ischemic time (ie, the time from cross-clamping of the blood supply to the donor organ until coronary reperfusion to the organ occurs after implantation into the recipient) should be minimized due to the negative impact on graft function if ischemic time is longer than five to six hours [3]. For patients who do not have adequate time for fasting, rapid sequence induction of anesthesia and tracheal intubation is employed with appropriate additional precautions against aspiration, as described separately. (See "Preoperative fasting in adults" and "Rapid sequence induction and intubation (RSII) for anesthesia".)

Planning for antibiotic prophylaxis and pretransplant immunosuppression — The goals of pretransplant immunosuppressive therapy is to prevent cardiac allograft rejection while minimizing drug toxicities and major sequelae of immune suppression (eg, infection). Immunosuppressive regimens for cardiac transplantation vary according to transplant center experience and recipient characteristics (eg, renal function, baseline risk of rejection, individual drug tolerability). Regimens vary among institutions, are tailored for each patient, and are ordered by the transplant team. Adherence to the prescribed immunosuppression prophylaxis regimen, including appropriate timing, is important for graft function. One example of a pretransplant immunosuppressive regimen includes the combination of IV basiliximab 20 mg given over 30 minutes, IV mycophenolate 1000 mg infused over two hours, and IV methylprednisolone 1000 mg given as a bolus prior to cardiopulmonary bypass (CPB). (See "Heart transplantation in adults: Induction and maintenance of immunosuppressive therapy".)

Since immunosuppression increases susceptibility to infection, it is critically important to ensure that the antibiotic prophylactic regimen is administered within the prescribed time to ensure that broad spectrum coverage is provided. Most regimens include a beta-lactam (choice guided by the institution's antibiogram) and vancomycin. If a patient has been treated with thymoglobulin preoperatively, some institutions might also include fluconazole or similar antifungal drugs. Typically, an intravenous (IV) first-generation cephalosporin such as cefazolin is administered (ie, 2 g for a patient <120 kg and 3 g for a patient ≥120 kg, with re-dosing after 3 hours), beginning 30 to 60 minutes before the anticipated time of surgical incision to ensure that tissue levels of antibiotic are adequate during incision. In addition, vancomycin 15 mg/kg (maximum 2 g) IV is administered beginning 60 to 120 minutes before surgical incision; this prolonged infusion time is necessary to avoid flushing, erythema, and hypotension (ie, "red man" syndrome) (see "Vancomycin hypersensitivity", section on 'Vancomycin infusion reaction') Vancomycin dosing is repeated every 12 hours. Patients with a penicillin allergy can receive ciprofloxacin 400 mg IV every eight hours along with vancomycin. (See "Prophylaxis of infections in solid organ transplantation", section on 'Peri-transplantation prophylaxis'.)

Perioperative management of cardiac implantable electronic devices — Most heart transplant recipients will have an ICD in place at the time of transplant surgery, and some are dependent on continuous pacemaker function to maintain hemodynamic stability. Ideally, a CIED (ie, pacemaker or ICD) is interrogated and reprogrammed immediately prior to transplant surgery, with the antitachycardia function turned off and pacemaker settings evaluated and programmed for optimal function during the prebypass period in an individual patient [4]. For example, in a patient with heart block or slow sinus rhythm, reprogramming to an asynchronous mode (eg, DOO) with heart rate set at 80 to 90 beats per minute may help to maintain hemodynamic stability prior to transplantation. (See "Perioperative management of patients with a pacemaker or implantable cardioverter-defibrillator".)

Management of pulmonary hypertension — Candidates for cardiac transplantation undergo right heart catheterization and determination of pulmonary vascular resistance (PVR) prior to being placed on the transplant waitlist, and at repeated intervals thereafter (algorithm 1).

Patients with elevated pulmonary artery systolic pressure >50 mmHg, and either elevated PVR >3 Wood units (320 dynes-sec-cm^-5) or elevated transpulmonary gradient of >15 mmHg, are at risk for acute right ventricular (RV) failure of the transplanted heart. If PVR decreases to ≤3 Wood units with systolic blood pressure ≥85 mmHg in response to pulmonary arterial vasodilator therapy administered in the cardiac catheterization laboratory or during hemodynamic monitoring in the intensive care unit, patients are considered to be acceptable candidates for cardiac transplantation and typically continue therapy with pulmonary vasodilator agents while waiting for a donor organ. If the PVR remains >3 Wood units with vasodilator testing, patients may undergo a two- to eight-week trial of medical therapy (eg, diuresis and milrinone +/- sildenafil) [5]. If PVR remains >3 Wood units, some patients may be treated with a trial of mechanical circulatory support (MCS), typically with a left ventricular assist device (LVAD) as a bridge-to-candidacy with repeated reassessments for changes in PVR [6]. On a case-by-case basis, some centers perform cardiac transplantation in patients with PVR up to 5 Wood units [7].

It is critically important that chronically administered pulmonary vasodilator therapies be continued during the prebypass period in patients with preoperative pulmonary hypertension, and such therapies will likely be necessary to achieve separation from CPB following cardiac transplantation. (See 'Weaning from CPB and early postoperative considerations' below.)

Some patients with irreversible severe pulmonary hypertension may be candidates for combined heart-lung transplantation. (See "Heart transplantation in adults: Indications and contraindications", section on 'Elevated pulmonary vascular resistance' and "Heart-lung transplantation in adults".)

Considerations for patients requiring mechanical circulatory support — Increasing numbers of patients presenting for cardiac transplantation have an MCS device in place as a bridge to transplantation (eg, left ventricular assist device [LVAD], right ventricular assist device [RVAD], intraaortic balloon pump [IABP], extracorporeal membrane oxygenation [ECMO], total artificial heart [TAH]) (figure 1) [8]. The impact of a patient's requirement for MCS on organ allocation priority is discussed separately. (See "Heart transplantation in adults: Donor selection and organ allocation", section on 'Allocation'.)

Intermediate or long-term devices — A short-term or long-term LVAD is often used as a bridge to transplantation if clinical status deteriorates in a patient awaiting cardiac transplantation. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device", section on 'Bridge to transplantation'.)

●Implanted left ventricular assist device – Insertion of an LVAD can improve secondary organ function and nutritional status prior to transplantation as well as reduce pulmonary hypertension, thereby improving post-transplant survival. Examples include the HeartMate 3 (picture 1) centrifugal pump implanted via sternotomy [9], or the HeartWare LVAD (HVAD) centrifugal pump, which may be implanted via sternotomy or by less invasive techniques (partial sternotomy plus left mini-thoracotomy) (figure 2) [10,11]. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device", section on 'Ventricular assist devices' and "Treatment of advanced heart failure with a durable mechanical circulatory support device".)

Considerations in patients with an LVAD in place include:

•Previous sternotomy – Patients with previous sternotomy are at risk for injury to the cardiac chambers, great vessels, or LVAD cannulae during redo sternotomy. Anesthetic preparation includes ensuring that cross-matched blood products are immediately available in the operating room prior to sternotomy. Six units of packed red blood cells (RBCs) and six units of fresh frozen plasma (FFP) should be available for the transplantation procedure, with two units of RBCs pre-checked and available in the operating room in case emergency transfusion is needed during sternotomy. Also, an earlier "in-room" time is typically arranged to allow adequate time for a potentially difficult redo sternotomy and explantation of the LVAD.

•Anticoagulation status – Patients with an LVAD will typically arrive for preoperative preparation on short notice and be at therapeutic levels of anticoagulation with warfarin, which is chronically administered during LVAD support to prevent thromboembolic events [8]. The preoperative international normalized ratio is assessed and vitamin K 2 to 5 mg IV as well as two to four units of FFP should be administered, since approximately six hours is required for vitamin K to antagonize the effects of warfarin [8,12]. An alternative to use of FFP is administration of an unactivated 4 factor prothrombin complex concentrate (PCC), such as Kcentra 25 units per kg. This product contains high concentrations of the vitamin K-dependent clotting factors depleted by warfarin (factors II, VII, IX, X, protein C, and protein S) and may reduce overall blood product utilization [13-15]. However, PCC is not available in all centers and is avoided by some clinicians due to concerns regarding prothrombotic risk [16]. (See "Perioperative management of patients receiving anticoagulants", section on 'Urgent/emergency invasive procedure'.)

Importantly, pharmacologic reversal of chronic anticoagulation with vitamin K, FFP, or a PCC product is always delayed until the transplant team receives confirmation that the donor organ is of good quality and cardiac transplantation will definitely proceed.

●Total artificial heart – The total artificial heart (TAH) device is used as a bridge to transplantation for patients with severe biventricular failure (figure 3) [17] in Europe, Canada, and the United States. The TAH is implanted via sternotomy with complete excision of both ventricles and preservation of the back walls of the atria. Each artificial ventricle has mechanical inflow and outflow tilting disc valves that replace the native atrioventricular (AV) and semilunar valves. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device", section on 'Artificial hearts'.)

Considerations in patients with a TAH in place include:

•Previous sternotomy – Previous sternotomy places the patient at risk for injury to the great vessels during redo sternotomy. Similar to considerations for an LVAD implanted via sternotomy (see above), preparations are necessary to ensure that appropriate cross-matched blood products are available.

•Caution with placement of a central venous catheter – During insertion of a central venous catheter (CVC) in a patient with a TAH, neither the guidewire nor catheter should be introduced to a depth that could interfere with the artificial inflow valve on the right side of the TAH, since this may cause valve dysfunction resulting in device malfunction and death [18]. Placement of the CVC in the left internal jugular or left subclavian vein rather than the right internal jugular or right subclavian vein results in a greater distance between the skin insertion site and the inflow valve, thereby reducing risk for wire or catheter contact with the valve. We monitor CVC placement with transesophageal echocardiography (TEE) to ensure that the catheter is positioned above the innominate vein. Some centers arrange for insertion of the CVC under fluoroscopic guidance.

If a pulmonary artery catheter (PAC) is desired for separation from CPB, it can be placed preoperatively, positioned with its tip in the CVC introducer sheath, and secured within the sterile external PAC sleeve for eventual intracardiac placement into the cardiac allograft after removal of the TAH and implantation of the graft.  

•Anticoagulation status – Similar to patients with an LVAD, patients with a TAH will typically arrive for preoperative preparation on short notice and have therapeutic levels of anticoagulation with warfarin, as described above. Typically, these patients are also receiving antiplatelet agents (eg, high-dose aspirin and dipyridamole) [19]. Anesthetic preparation includes ensuring that six units of cross-matched RBCs and six units of FFP are immediately available, with two units of RBCs checked and in the operating room prior to sternotomy. In addition, one to two platelet apheresis units (ie, one apheresis unit harvested from a single donor that is equivalent to four to six pooled platelet units) should be available for transfusion if needed after CPB in a patient receiving antiplatelet agents. Assessment with thromboelastography is useful for guiding transfusion of these products during the intraoperative period. (See "Intraoperative transfusion and administration of clotting factors", section on 'Point-of-care tests'.)

•Anemia – Anemia is common in patients with a TAH, and centers typically maintain a low hemoglobin transfusion threshold of 6 g/dL to minimize the risk of alloimmunization due to transfusion [19]. Targeted hemoglobin levels during the cardiac transplantation procedure vary among transplant centers. At the author's institution, we maintain hemoglobin at 7 g/dL prebypass, 7 to 9 g/dL during bypass, and 8 g/dL postbypass. We transfuse to a slightly higher hemoglobin target of 9 g/dL immediately prior to the termination of bypass to allow for early postbypass administration of FFP and platelets to achieve hemostasis while maintaining adequate hemoglobin levels. Overall, the risk of alloimmunization at this juncture is low, as patients will have been treated with steroids and will be fully immunosuppressed in the days following the procedure.

Short-term devices — A short-term circulatory assist device may be inserted as a temporary bridge to urgent transplantation in a patient with cardiogenic shock, acute decompensated heart failure, or cardiopulmonary arrest. These temporary support devices are approved for up to 14 days. Patients supported with such devices (eg, intraaortic balloon pump [IABP], percutaneous ventricular assist device [PVAD], or extracorporeal membrane oxygenation [ECMO]) are given high priority for cardiac transplantation if associated criteria are met [20,21]. (See "Short-term mechanical circulatory assist devices", section on 'Implications of short-term mechanical circulatory support on the new UNOS heart transplant allocation policy' and "Heart transplantation in adults: Donor selection and organ allocation", section on 'Donor allocation system'.)

Patients with short-term devices are typically receiving anticoagulant agents to avoid thromboembolic complications. Bleeding from access-sites, gastrointestinal tract, and nasopharynx occurs commonly. Thus, TEE probe placement must be performed with care, and use of a nasopharyngeal temperature probe or nasal airway is avoided when coagulation abnormalities are present or if anticoagulation status is uncertain.

●Intraaortic balloon pump – An IABP provides hemodynamic support to patients in heart failure through sequential inflation and deflation to provide counterpulsation with a helium-containing balloon within the descending aorta. Use of IABPs has increased at some centers because these devices provide adequate circulatory support in selected patients, have a very low risk of drive-line infection, and their removal is not associated with the significant bleeding that may occur with removal of an LVAD. (See "Short-term mechanical circulatory assist devices", section on 'IABP' and "Intraaortic balloon pump counterpulsation".)

Considerations in patients with an IABP in place include:

•Complications – IABP malposition or displacement can cause a stroke if migration occurs proximally, or kidney injury if migration occurs distally. Access site hemorrhage, thrombocytopenia, and anemia are other potential complications. (See "Intraaortic balloon pump counterpulsation", section on 'Complications'.)

•Ability to ambulate – As a bridge-to-heart transplant, insertion of the IABP catheter through the subclavian artery rather than the femoral artery allows the patient to ambulate and undergo rehabilitation therapy while waiting for a donor organ [22-24].

•Anticoagulation status – Most, but not all, patients with an IABP are treated with IV unfractionated heparin guided by monitoring of the activated partial thromboplastin time (aPTT), although the optimal anticoagulation strategy is unclear [22,23,25,26]. Anticoagulation status is determined and abnormalities are appropriately treated shortly before surgery. Typically, heparin is discontinued when the patient is called to the preoperative holding area immediately prior to surgery. Some centers employ warfarin as anticoagulation in patients with subclavian placement of an IABP or similar devices. These patients can be managed as described above. (See 'Intermediate or long-term devices' above.)

●Percutaneous left ventricular assist device – PVADs include the Impella and the TandemHeart (figure 4 and figure 5). (See "Short-term mechanical circulatory assist devices", section on 'Non-IABP percutaneous circulatory devices'.)

The Impella is a miniaturized continuous-flow axial pump that is positioned in the ascending aorta with the tip crossing the aortic valve. The pump draws blood from the left ventricle with outflow into the ascending aorta to offload the ventricle. Several versions of the device are available that provide between 2.5 L/min (Impella 2.5) to 5.3 L/min (Impella 5.0) support and may be placed via percutaneous or cutdown access to the femoral or axillary artery. Particularly for the Impella 2.5, pulsatile blood flow on arterial line monitoring is anticipated, as only partial left ventricular (LV) support is provided.

The TandemHeart provides LV support by drawing blood from the left atrium (LA) and returning it to the femoral artery. The inflow cannula is placed into the femoral vein and crosses the interatrial septum via transseptal puncture to draw oxygenated blood from the LA. A centrifugal blood pump is external to the patient and secured to the patient's leg. The outflow cannula is placed percutaneously into the femoral artery.

Considerations in patients with a PVAD include:

•Hemolysis – Hemolysis is common with these devices; thus, patients frequently have anemia and thrombocytopenia. Appropriate blood products should be available for administration after CPB.

•Anticoagulation status – Both Impella and the TandemHeart require continuous anticoagulation with IV unfractionated heparin. The Impella device utilizes a heparin-containing purge solution to prevent device thrombosis, and additional IV heparin is administered to achieve a target activated clotting time (ACT) of 160 to 180 seconds or an aPTT of 60 to 80 seconds [25]. The TandemHeart manufacturer recommends a target ACT of 180 to 200 seconds or aPTT of 60 to 80 seconds maintained via the purge solution [25]. Heparin is discontinued immediately prior to surgery when the patient is called to the preoperative holding area.

●ECMO – Venoarterial ECMO can also be used as a bridge to transplantation, and its use is associated with increased post-transplant mortality compared with use of a continuous-flow LVAD [27]. (See "Short-term mechanical circulatory assist devices", section on 'Extracorporeal membrane oxygenation' and "Extracorporeal life support in adults in the intensive care unit: Overview".)

Considerations in patients on ECMO include:

•Compromised pulmonary status – Patients are frequently intubated and may have compromised pulmonary status (eg, pulmonary edema or pulmonary hemorrhage due to inadequate LV decompression, or ventilator-associated pneumonia), which may be contraindications to transplantation. Discussion with the cardiac surgeon and transplant team is warranted.

•Anticoagulation status – Anticoagulation with IV unfractionated heparin to a target ACT 180 to 210 seconds is typical, unless systemic hemorrhage has occurred. Heparin is discontinued immediately prior to surgery when the patient is called to the preoperative holding area.

•Thrombocytopenia – Thrombocytopenia is common due to platelet consumption, often necessitating administration of platelets after cardiopulmonary bypass (CPB).

SURGICAL TECHNIQUES — Heart transplant is performed using a step wise approach:

●Suitability of the donor heart is confirmed at time of procurement. The donor heart may be allocated from a deceased donor (eg, donation after brain death [DBD] or donation after cardiac death [DCD]).

•Donation after brain death (DBD) – Cold ischemic time begins at the time of donor aortic cross-clamp during procurement and infusion of cold preservation solution.

•Donation after cardiac death (DCD) – This process is more complex in that life support is withdrawn in the operating room and organ procurement occurs following declaration of death after circulatory arrest. A warm ischemic period begins variably after withdrawal of life support when hemodynamic instability sets in (hypoxia and hypotension), referred to as the "agonal phase," and may last 30 minutes or more [28]. The agonal phase is followed by a predetermined "stand-off time," after declaration of circulatory arrest for verification (5 to 15 minutes). Then skin incision and rapid sternotomy are performed. The heart is reperfused by establishing cardiopulmonary bypass (CPB), which is the end of warm ischemic time, sinus rhythm is established, and the heart is evaluated for adequate function. Typically, organ procurement then proceeds as for DBD. However, a donor may be excluded if duration of warm ischemic time is >60 minutes (eg, due to a prolonged agonal phase), or if donor function is inadequate following reperfusion. Short-term outcomes of for heart transplantation after DCD have been promising [28,29].

●Median sternotomy is performed, and the heart and great vessels are exposed

●CPB is established.

●The recipient heart (or artificial heart) is removed with attention to providing appropriate tissue for reconstruction (bicaval or biatrial approach). Preexisting cardiac implantable electronic device (CIED) wires are transected during removal of the native heart. The pulse generator and remaining attached leads are typically removed after sternal closure at the end of the surgical procedure. Occasionally the pulse generator and wire remnants cannot easily be removed and are left in place for removal at a later date, which generally should have no adverse sequelae.

Then the donor heart is then sutured into place using one of the following techniques:

•Bicaval technique – Most centers employ a bicaval technique to perform cardiac transplantation (ie, cannulation of the superior vena cava [SVC] and inferior vena cava [IVC] are accomplished individually for venous cannulation). Snares are placed on the SVC and IVC when the patient is on CPB to isolate blood flow away from the right atrium (RA). Resection of the entire recipient RA is followed by end-to-end anastomoses of the vena cavae that are separately created with the donor superior and inferior vena cava vessels [30-34]. This bicaval approach leaves behind a minimal cuff of the recipient's left atrium (LA) surrounding the pulmonary veins to facilitate reconstruction of the LA. If organ procurement did not include resection of the donor's lungs, enough intact donor LA tissue may remain to allow nearly complete resection of the recipient's LA, and this approach may be referred to as a total technique. The recipient's pulmonary veins are divided to create a single left atrial orifice for anastomosis to the wall of the donor's LA [31]. Compared with the classic biatrial surgical approach, advantages of the bicaval technique include reduced incidence of sinus node dysfunction and thus lower incidence of bradycardia [35,36], improved postoperative atrioventricular (AV) valve function, lower incidence of tricuspid regurgitation [32,33,37-40], and reduced size and improved performance of the LA [32,33,41,42]. These factors may improve overall graft function [32,33,38,39]. However, a disadvantage of the bicaval technique is that it may require a longer cross-clamp time than the biatrial approach. Furthermore, evidence has not demonstrated improvement in survival [31,43]. (See "Heart transplantation in adults: Arrhythmias", section on 'Prevalence and causes'.)

•Biatrial approach – The earlier (classic) biatrial surgical approach is still used by some surgeons. A cuff from each atrium is left behind in the recipient, and anastomoses are subsequently created to connect recipient and donor atria. Note that when the biatrial technique is used, the remnant right atrial cuff of the recipient contains conductive tissue, which typically results in a duplicate P wave on the electrocardiogram (ECG) following cardiac transplantation. One P wave arises from the recipient's native sinoatrial (SA) node, but is not conducted across the atrial suture line, while the second P wave arises from the donor heart SA node.

•Tricuspid valve annuloplasty – Some institutions perform prophylactic tricuspid valve annuloplasty repair prior to suturing the donor heart into place to reduce the risk of postoperative tricuspid regurgitation (TR). Moderate to severe TR eventually occurs in 10 to 30 percent of patients after cardiac transplantation and may be associated with decreased allograft performance [44-48], and graft failure [40,45,46,49], although study results are not consistent. In one randomized trial of 60 patients who had cardiac transplantation with the bicaval technique, prophylactic tricuspid valve annuloplasty was associated with improved right ventricular (RV) performance at the time of surgery and a lower incidence of significant TR or mortality at one postoperative year compared with those who did not undergo tricuspid annuloplasty [50]. Conversely, an observational study that included 330 cardiac transplantation recipients reported no association between donor tricuspid valve repair (in 52 percent) and a composite outcome of death, need for post-transplant tricuspid valve repair, or need for post-transplant dialysis [51].

●Epicardial pacing leads are placed. The pulse generator and remaining attached leads for the CIED are typically removed after sternal closure at the end of the surgical procedure. Occasionally the pulse generator and wire remnants cannot easily be removed and are left in place for removal at a later date.

●The patient is weaned from CPB.

●Thoracostomy tubes are placed, and the sternotomy is closed.

INTRAOPERATIVE ANESTHETIC MANAGEMENT

Management of induction and the prebypass period

Monitoring considerations — Monitoring for cardiac transplantation is like other types of cardiac surgery with cardiopulmonary bypass (CPB) such as cardiac valve repair or replacement procedures. (See "Anesthesia for cardiac surgery: General principles", section on 'Prebypass transesophageal echocardiography' and "Anesthesia for cardiac valve surgery", section on 'Transesophageal echocardiography: General considerations' and "Anesthesia for cardiac surgery: General principles", section on 'Postbypass transesophageal echocardiography'.)

●Invasive cardiovascular monitors – Prior to anesthetic induction, an intra-arterial catheter is inserted. Also, defibrillator/pacing pads are placed before induction so that rapid cardioversion, defibrillation, or pacing can be accomplished prior to sternotomy, if necessary. (See "Perioperative management of patients with a pacemaker or implantable cardioverter-defibrillator", section on 'Placement of transcutaneous pacing/defibrillator pads'.)

Either before or shortly after anesthetic induction, a large-bore central venous catheter (CVC) is inserted. In addition, a pulmonary artery catheter (PAC) is typically positioned so that cardiac output, mixed venous oxygen saturation (SVO₂), and pulmonary artery pressures can be measured.

After induction, a transesophageal echocardiography (TEE) probe is inserted. During the prebypass period, TEE is useful to diagnose causes of hemodynamic instability [52]. Also, TEE examination is critically important during weaning from CPB, and to assess function of the donor heart following bypass. (See "Intraoperative transesophageal echocardiography for noncardiac surgery" and 'Transesophageal echocardiography after cardiopulmonary bypass' below.)

●Cerebral monitors – Many transplant centers also employ cerebral monitoring with a processed electroencephalography (EEG) device and/or near-infrared spectroscopy (NIRS) cerebral oximetry monitoring, although an impact on clinical outcomes has not been established in cardiac transplantation patients [53-56].

●Device monitors – If mechanical circulatory support (MCS), such as a left ventricular assist device (LVAD), intraaortic balloon pump (IABP), or extracorporeal membrane oxygenation (ECMO) system is in situ, the monitor for the device is placed within view of the anesthesiology team so that the device's function, flow and/or pump speed can be continuously assessed in the prebypass period. (See 'Perioperative management of cardiac implantable electronic devices' above.)

Induction and maintenance of anesthesia — Slow titration is prudent for all agents used for premedication in the immediate preinduction period. Excessive sedation and hypoventilation should be avoided prior to anesthetic induction, as this may result in hypoventilation with hypercarbia and hypoxemia leading to increased pulmonary vascular resistance (PVR) and worsening right ventricular (RV) function. Similarly, slow titration is prudent for all anesthetic and adjuvant agents selected for induction to avoid hemodynamic instability. Anesthesiologists should be aware that patients who have been chronically exposed to inotropic agents are likely to be less responsive to vasoactive agents administered to treat acute hemodynamic instability.

●Induction – We typically administer a small dose of a short-acting benzodiazepine (eg, midazolam 1 to 4 mg), followed by a moderate dose of an opioid, such as fentanyl 2 to 4 mcg/kg or sufentanil 0.2 to 0.5 mcg/kg, followed by an induction agent, such as:

•Propofol – If propofol is selected for a hemodynamically stable patient, very slow administration of 0.5 to 1 mg/kg (over two to three minutes) will attenuate the hemodynamic changes seen with induction and allow for treatment of blood pressure with phenylephrine as needed.

•Etomidate 0.2 to 0.4 mg/kg is typically selected for hemodynamically unstable patients in cardiogenic shock due to its minimal effect on hemodynamics.

A nondepolarizing neuromuscular blocking agent is administered when the patient becomes unresponsive with loss of consciousness during induction.

●Maintenance – During the maintenance phase of the prebypass period, anesthetic depth is typically maintained with a volatile anesthetic (eg, sevoflurane, isoflurane) in combination with additional doses of an opioid. Nitrous oxide is avoided since it increases PVR.

Preparations for cardiopulmonary bypass — General considerations for preparations, initiation, and management of CPB in patients undergoing cardiac surgery include anticoagulation, antifibrinolytic administration, ascending aorta cannulation, and venous cannulation. General management of CPB for any cardiac surgical procedure is discussed separately. (See "Initiation of cardiopulmonary bypass" and "Management of cardiopulmonary bypass".)

If a PAC was previously positioned, the catheter can either be retracted from the right heart just prior to SVC snare placement, then refloated into position in the pulmonary artery after weaning from CPB. An alternative method is manipulation of the catheter directly within the surgical field before final anastomosis of the pulmonary artery to the donor heart.

Management of hyperglycemia — General management of CPB for any cardiac surgical procedure is discussed separately. (See "Initiation of cardiopulmonary bypass" and "Management of cardiopulmonary bypass".)

Hyperglycemia is common during any type of cardiac surgical procedure requiring CPB, but particularly in patients with diabetes undergoing cardiac transplantation because of administration of high-dose glucocorticoids for immunosuppression (see 'Planning for antibiotic prophylaxis and pretransplant immunosuppression' above). Early initiation of an insulin infusion during CPB if blood glucose >200 mg/dL is prudent since use of beta-agonists for separation from CPB is common and may worsen hyperglycemia. (See 'Planning for antibiotic prophylaxis and pretransplant immunosuppression' above.)

WEANING FROM CPB AND EARLY POSTOPERATIVE CONSIDERATIONS — General considerations regarding preparations for weaning from cardiopulmonary bypass (CPB) and the weaning process itself are described separately. (See "Weaning from cardiopulmonary bypass".)

Key challenges — Hemodynamic expectations during weaning from CPB and during the early postoperative period differ after cardiac transplantation compared with other types of cardiac surgery because the transplanted heart is denervated and early graft dysfunction is common. Therefore, chronotropic support as well as inotropic support are often needed to achieve weaning from CPB support. Although there are many pharmacologic options to achieve these goals, combinations of agents, such as dobutamine, dopamine, epinephrine, milrinone, or isoproterenol (table 4), as well as placement of atrial and ventricular pacing wires are typically necessary. (See 'Early graft dysfunction' below and 'Denervation of the transplanted heart' below and "Intraoperative problems after cardiopulmonary bypass", section on 'Vasoactive drug therapy'.)

Additional challenges that may occur after cardiac transplantation include pulmonary hypertension with right ventricular (RV) dysfunction and systemic vasoplegia. (See 'Pulmonary hypertension' below and 'Vasoplegia' below.)

Denervation of the transplanted heart — The denervated transplanted heart typically has a high intrinsic heart rate (90 to 110 beats/minute), preserved atrioventricular (AV) conduction and increased sensitivity to changes in left ventricular (LV) end-diastolic volume [57]. Inotropes are often required to support the newly transplanted heart, often resulting in a heart rate of 100 to 130 beats/minute. In spite of this, epicardial atrial and ventricular wires are routinely placed so that bradycardia can be treated by pacing.

Bradycardia or arrythmias after aortic cross-clamp removal indicate ischemia-reperfusion injury that may resolved with increasing reperfusion time. If emergency treatment of bradycardia is required and functional pacemaker wires are not in place, treatment with intravenous (IV) isoproterenol should be administered to increase heart rate. The denervated transplanted heart will not respond to treatment with atropine or glycopyrrolate. (See "Heart transplantation in adults: Arrhythmias" and "Weaning from cardiopulmonary bypass", section on 'Maintenance of optimal pacemaker function'.)

Approximately 10 percent of heart transplant recipients will require permanent pacemaker placement due to sinus node dysfunction or AV block [58,59]. Pacemaker placement is performed as a separate procedure after a trial of temporary pacing with epicardial wires and usually a period of outpatient sinus nodal support with albuterol or theophylline. The biatrial surgical technique is more likely to be associated with need for a permanent pacemaker than the bicaval approach due to a higher risk of surgical injury to the sinoatrial (SA) node or disruption of the SA nodal artery [35,37,43,59-64]. (See 'Surgical techniques' above.)

Early graft dysfunction — Inability to wean from bypass with standard doses of inotropic drugs may result from primary or secondary graft dysfunction with low cardiac output. (See "Heart transplantation in adults: Graft dysfunction", section on 'Early graft dysfunction'.)

●Primary graft dysfunction – Primary graft dysfunction (PGD) is diagnosed when a secondary cause is not identified and may involve isolated dysfunction of the left ventricle (termed PGD-LV), the RV (termed PGD-RV), or may be biventricular. PGD most commonly refers to early (<24 hours after transplant) graft dysfunction with low cardiac index <2.0 L/min/m² or low left ventricular (LV) ejection fraction ≤40 percent. PGD-LV severity can be classified as mild (requiring low-dose inotropes), moderate (requiring high-dose inotropes or insertion of an intraaortic balloon pump [IABP]), or severe (requiring a left ventricular assist device [LVAD], biventricular assist device, or extracorporeal membrane oxygenation [ECMO]) [65]. PGD-RV is diagnosed by the presence of right atrial pressure >15 mmHg with pulmonary artery wedge pressure <15 mmHg and/or pulmonary artery systolic pressure <50 mmHg, transpulmonary gradient <15 mmHg, or the need for an RV assist device [65]. (See "Heart transplantation in adults: Graft dysfunction", section on 'Early graft dysfunction' and "Short-term mechanical circulatory assist devices" and "Treatment of advanced heart failure with a durable mechanical circulatory support device".)

Although the etiology of PGD is not well understood, multiple factors likely contribute, including ischemia-reperfusion injury as well as preexisting donor heart disease [65]. (See "Heart transplantation in adults: Graft dysfunction", section on 'Primary graft dysfunction'.)

Management of PGD includes ruling out secondary causes or exacerbating conditions, initiating or escalating inotropic support, increasing reperfusion time on CPB (>30 minutes), insertion of a mechanical circulatory support (MCS) device, initiating a pulmonary vasodilator for PGD-RV, and/or initiation of ECMO for failure to wean from CPB after multiple attempts. Successful weaning and survival after heart transplantation is higher when temporary ECMO is initiated for support rather than temporary LVAD placement [66].

●Secondary graft dysfunction – Secondary graft dysfunction is diagnosed when a discernible cause of graft dysfunction can be identified, such as hyperacute rejection, a surgical complication such as a restrictive anastomosis or kinked major vessel, or excessive pressure or volume load on the RV. The latter may result from exacerbated pulmonary hypertension or extensive intraoperative bleeding treated with massive blood product transfusion resulting in RV volume overload [65].

With hyperacute rejection, the transplanted heart typically becomes mottled, cyanotic, and asystolic after reperfusion, with profound biventricular dysfunction [67,68].

Factors that contribute to development of hyperacute rejection include preformed antibodies from the recipient that react with donor lymphocytes resulting in antibody-mediated rejection. Fortunately, this occurs rarely in ABO-compatible transplants [68,69]. Plasmapheresis can be employed to rapidly reduce such circulating antibodies with administration of additional immunosuppression agents. Subsequently, IV immunoglobulin may be used to prevent further rejection.

Although myocardial recovery has been documented with institution of MCS [68], overall prognosis is poor and survival after retransplantation is lower than after primary surgery [70].

Pulmonary hypertension — In some patients, difficulties in weaning from CPB may be caused by RV dysfunction due to elevated pulmonary vascular resistance (PVR). For patients with preoperative pulmonary hypertension, particularly those receiving preoperative pulmonary vasodilator therapy, such therapy will likely need to be continued to avoid RV dysfunction during separation from bypass. Options for reducing PVR include IV agents, such as milrinone (0.375 to 0.75 mcg/kg/min), or inhaled agents, such as nitric oxide administered via a specialized apparatus (typically at 10 to 20 parts per million, with up to 40 parts per million used in some institutions), or epoprostenol administered via a nebulizer in the ventilation circuit (typically at 30 to 50 ng/kg/min). Since inhaled epoprostenol inhibits platelet aggregation, systemic bleeding may be increased after CPB [71]. (See "Intraoperative problems after cardiopulmonary bypass", section on 'Right ventricular dysfunction' and "Inhaled nitric oxide in adults: Biology and indications for use".)

Vasoplegia — In some patients, difficulties in weaning from CPB may be due to very low systemic vascular resistance (SVR). Such vasoplegia is characterized by systemic hypotension (mean arterial pressure <50 mmHg) with low SVR <800 dyne-s-cm^-5, and normal or high cardiac index >2.5 L/minute/m². Patients with severe vasoplegia are refractory to vasoconstrictor agents such as catecholamines. Vasoplegia occurs in 11 to 34 percent of patients undergoing cardiac transplantation and is more likely in those with previous cardiac surgery, large body surface area, thyroid disease, elevated creatinine, preoperative aspirin use, prolonged duration of CPB (>140 minutes), or preoperative MCS [72-74]. (See 'Considerations for patients requiring mechanical circulatory support' above.).

Management of vasoplegia is discussed separately (table 5). (See "Intraoperative problems after cardiopulmonary bypass", section on 'Vasoplegia' and "Postoperative complications among patients undergoing cardiac surgery", section on 'Vasodilatory shock'.)

Transesophageal echocardiography after cardiopulmonary bypass — The use of intraoperative transesophageal echocardiography (TEE) during and after weaning from CPB is similar to other cardiac surgical procedures. (See "Anesthesia for cardiac valve surgery", section on 'Transesophageal echocardiography: General considerations'.)

After cardiac transplantation, areas of particular focus during the TEE examination include [52]:

●Global LV and RV function are evaluated. As noted above, RV dysfunction is particularly common in the early period after cardiac transplantation. In the midesophageal 4-chamber view, TEE evidence of RV failure includes RV dilation, flattening and displacement of the interventricular septum towards the LV, reduced tricuspid annular plane systolic excursion, and severe tricuspid valve regurgitation (TR). Additional signs of RV dysfunction include reduced RV free wall motion and thickening seen in the midesophageal RV inflow-outflow view. In the transgastric midpapillary LV short axis view, a D-shaped LV cavity (ie, a flattened interventricular septum) in systole, particularly end-systole, suggests RV pressure overload, while a D-shaped LV cavity in diastole suggests RV volume overload. (See "Echocardiographic assessment of the right heart", section on 'Right ventricular function' and "Echocardiographic assessment of the right heart", section on 'Interventricular septal shape'.)

●Anastomotic sites are examined for evidence of obstruction. Inferior vena cava (IVC) and superior vena cava (SVC) anastomoses are examined with color flow Doppler, which is particularly important if a bicaval surgical technique was employed (see 'Surgical techniques' above); turbulent caval flow may indicate a stenotic anastomosis [75].

●The tricuspid valve is assessed for TR. If tricuspid valve annuloplasty has been performed, the valve is assessed for evidence of tricuspid stenosis such as turbulent inflow seen with Doppler color flow mapping, elevated transvalvular gradient, or right atrial enlargement. (See "Echocardiographic evaluation of the tricuspid valve".)

●Right atrium (RA) appearance depends on the surgical approach (ie, biatrial or bicaval technique). After the biatrial surgical approach, a ridge of tissue is visible transecting the RA at the anastomotic site. The left atrium (LA) orientation and appearance will also be altered and a ridge of tissue at the LA anastomosis may be visible. (See 'Surgical techniques' above.)

Considerations during the COVID-19 pandemic — The International Society of Heart and Lung Transplantation (ISHLT) does not recommend cessation of all transplantation activity due to the novel coronavirus disease 2019 (COVID-19) pandemic, although it is recognized that the number of transplants may be reduced in institutions that are temporarily overwhelmed with regional COVID-19 cases [76,77]. Management of potential candidates for cardiac transplantation with suspected or confirmed COVID-19 infection is discussed separately. (See "COVID-19: Issues related to solid organ transplantation".)

Considerations for anesthetic and airway management of patients who might be shedding viral particles are discussed in a separate topic. (See "Overview of infection control during anesthetic care", section on 'Infectious agents transmitted by aerosol (eg, COVID-19)' and "Overview of infection control during anesthetic care", section on 'Considerations with COVID-19 or other agents spread by aerosol'.)

SUMMARY AND RECOMMENDATIONS

●Preanesthetic assessment – General considerations for a candidate for cardiac transplantation include the underlying etiology of heart failure, documented priority status, and updated assessment of comorbidities, some of which may impact the ability to proceed with transplantation. (See 'General considerations' above and "Heart transplantation in adults: Indications and contraindications".)

●Surgical considerations – Heart transplant is performed using a step wise approach (see 'Surgical techniques' above):

•Median sternotomy is performed, and the heart and great vessels are exposed.

•Cardiopulmonary bypass (CPB) is established.

•The recipient heart (or artificial heart) is removed with attention to providing appropriate tissue for reconstruction (bicaval or biatrial approach). Most centers employ a bicaval rather than biatrial technique for cardiac transplantation. (See 'Surgical techniques' above.)

•The donor heart is sutured into place.

•Epicardial pacing leads are placed. Preexisting cardiac implantable electronic device (CIED) wires are transected during removal of the native heart.

•Some institutions perform prophylactic tricuspid valve annuloplasty repair.

•The patient is weaned from cardiopulmonary bypass.

•Thoracostomy tubes are placed, and the sternotomy is closed.

●Anesthetic management – Slow titration is prudent for all anesthetic and adjuvant agents used for premedication in the immediate preinduction period and for induction and maintenance of general anesthesia. Patients who have been exposed chronically to inotropic agents are likely to be less responsive to vasoactive agents administered to treat acute hemodynamic instability. (See 'Induction and maintenance of anesthesia' above.)

●Weaning from CPB – Hemodynamic expectations during weaning from cardiopulmonary bypass (CPB) and the early postoperative period differ after cardiac transplantation compared with other types of cardiac surgery. Common challenges include (see 'Key challenges' above):

•Need for chronotropic and inotropic support with combinations of vasoactive agents to achieve weaning from CPB since the transplanted heart is denervated and early graft dysfunction is common. Although intravenous isoproterenol may be effective to increase heart rate, atropine is not effective. Epicardial atrial and ventricular wires are routinely placed so that bradycardia can be treated by pacing, with a goal heart rate of 100 to 130. (See 'Denervation of the transplanted heart' above.)

•Inability to wean from CPB with standard doses of inotropic drugs may be caused by either primary graft dysfunction (PGD) due to ischemia-reperfusion injury as well as preexisting donor heart disease, or secondary graft dysfunction due to causes such as hyperacute rejection, surgical complications (eg, restrictive anastomosis, vessel kinking), or excessive pressure or volume load on the right ventricle. Management includes ruling out secondary causes or exacerbating conditions, initiating or escalating inotropic support (table 4), increasing reperfusion time on CPB (>30 min), insertion of an intraaortic balloon pump (IABP), initiating a pulmonary vasodilator for RV dysfunction, and/or establishing extracorporeal membrane oxygenation (ECMO) for failure to wean from CPB after multiple attempts. (See 'Early graft dysfunction' above.)

•Pulmonary hypertension. (See 'Pulmonary hypertension' above.)

•Vasoplegia (table 5). (See 'Vasoplegia' above.)

●Use of transesophageal echocardiography (TEE) – Use of TEE during and after weaning from CPB focuses on assessment of both right and left ventricular (RV, LV) function, assessment for tricuspid regurgitation, and evidence of obstruction at anastomotic sites (particularly inferior or superior vena cavae anastomoses if a bicaval surgical approach was employed). (See 'Transesophageal echocardiography after cardiopulmonary bypass' above.)