Transplant

Question 1

By reading this article, you should be able to:

Answer 1

By reading this article, you should be able to:

1. Describe the evaluation of potential heart transplant recipients.
2. Discuss the management of primary graft dysfunction in the operating theatre and ICU.
3. Identify the indications for initiating venoarterial extracorporeal membrane oxygenation.
4. Explain the challenges faced by an anaesthetist at different stages of heart transplant surgery.

Question 2

Key Points

Answer 2

1. In selected patients, heart transplantation is the definitive treatment for acute or end-stage heart failure.
2. Thorough preoperative evaluation by a multidisciplinary team is essential for optimal selection of patients and timing of heart transplantation.
3. Primary graft dysfunction is the most important cause of
   early death after heart transplantation.
4. Prolonged reperfusion of the donor heart is
   critical for successful weaning from cardiopulmonary bypass
   and avoiding primary graft dysfunction.
5. A low threshold should be used for initiating mechanical circulatory support, ideally extracorporeal membrane oxygenation, for treating graft dysfunction that is not responsive to moderate-dose inotropic drugs.

Question 3

Conclusions

Answer 3

In this paper, we have reviewed the key issues faced by anaesthetists and intensivists caring for heart transplant recipients.

Perhaps the key point to emphasise is that when faced
with deteriorating LV or RV function
and escalating inotropic support,

early initiation of VA ECMO is essential—
and may be life-saving.

Given the number of patients awaiting heart transplantation
exceeds the supply of DBD donor organs,

it is likely there will be an increasing demand
for DCD organs over time,
further increasing the requirement for postoperative ECMO.

Question 4

How many world wide

Most performed for

Waut time

Answer 4

Worldwide, there are approximately 5000 heart transplants annually.

In the year to February 2020, 174 adult heart transplants were performed in the UK, and there were 307 adult patients on the waiting list

Most heart transplants are performed for end-stage cardiomyopathy, either ischaemic or non-ischaemic

Patients classified as ‘non-urgent’,

the median wait time is about 4 yrs,

being shortest for blood group AB and longest for blood group O

Question 5

How many world wide

Most performed for

Waut time

Answer 5

Worldwide, there are approximately 5000 heart transplants annually.

In the year to February 2020, 174 adult heart transplants were performed in the UK, and there were 307 adult patients on the waiting list

Most heart transplants are performed for end-stage cardiomyopathy, either ischaemic or non-ischaemic

Patients classified as ‘non-urgent’,

the median wait time is about 4 yrs,

being shortest for blood group AB and longest for blood group O

Question 6

Median Survival

Death

Answer 6

Median survival after heart transplantation exceeds 12 yrs.3

Survival after heart transplantation is approximately twice that after lung transplantation

Early death is primary graft dysfunction (PGD);
the other main causes are infection and acute rejection

late death is cardiac allograft vasculopathy
(chronic rejection),
with other causes including

malignancy, infection and renal failure

Question 7

Changes

Answer 7

Increased use of hearts from DCD donors 15%

is perhaps the most significant change in practice in heart transplantation medicine over the last 5 yrs

there is an increased requirement for postoperative mechanical circulatory support

Anaesthesia management for patients undergoing heart transplantation is demanding and frequently occurs on an emergency basis because of unpredictable availability of organs.

Question 8

Assessment and management of common problems during heart transplantation.

Pretransplant assessment

Answer 8

1. Increased PVR

Echocardiogram and right-heart catheter

If PVR >3 WU and limited reversibility,
consider inotropes, sildenafil and diuretics;
if not responsive, consider durable LVAD

2. Impaired end-organ function

Renal and hepatic function tests

Consider a prolonged course of inotropes; if not responsive, consider durable LVAD

3.

Question 9

Before surgery

Answer 9

ll patients Fragile cardiac status
Avoid giving sedative–hypnotic drugs in uncontrolled ward environment;

preserve right internal jugular vein for myocardial biopsy access; induce anaesthesia slowly with vasopressors to hand

2. Patients with congenital heart disease or chronic indwelling CVCs

CT chest
May need alternative site of central venous access

3.Timing
Expected arrival of donor heart
Allow at least 1 h for anaesthesia and
1 h for preimplantation surgery; ensure native heart is not excised before the donor heart has been inspected by the surgeon

4. Revision cardiac surgery
   CT chest
   Prepare for emergency CPB and blood transfusion

Question 10

During surgery, before separating from CPB

Answer 10

1. Haemodynamic instability

Haemodynamic monitoring and TOE;

discuss with surgeon,
as may be attributable to surgical manipulations.

Ask surgeon to briefly cease dissection;
augment preload and administer vasopressors;
if not successful, consider initiating CPB

2. Reperfusion

TOE evaluation of donor heart

Allow at least 1 h for reperfusion with heart ejecting, but full CPB support; low-dose inotropic support and DOO pacing at 50–60 beats min

Question 11

During surgery, after separating from CPB

Answer 11

1. Haemodynamic instability

Haemodynamic monitoring and TOE
(including CI) to distinguish

between hypovolaemia,
vasoplegia and PGD

Augment preload based on TOE and CVP (CVP >15 mmHg unlikely to be beneficial);

inotropes and vasopressors to moderate doses;
avoid adrenaline (epinephrine) (or equivalent) >0.2 μg kg−1 min−1;

low threshold for initiating mechanical circulatory support,
ideally VA ECMO;

use iNO routinely to reduce PVR and minimise likelihood of PGD

2. Bleeding
   Platelet count, PT, aPTT, fibrinogen concentration and TEG

Administer blood component therapy based on test results;
for LVAD patients, consider desmopressin;

for warfarin reversal, consider prothrombin complex concentrate and vitamin K

Question 12

Before surgery

Answer 12

Indications for heart transplantation

Heart transplantation may be considered in patients with

(i) Advanced heart failure with New York Heart Association Class III or IV functional status or recurrent hospitalisations despite maximal medical therapy

(ii)Recurrent life-threatening ventricular arrhythmias despite an implantable cardiac defibrillator (ICD)

(iii) Acute cardiogenic shock, requiring infusions of inotropic agents or temporary mechanical circulatory support

(iv) Refractory angina without further therapeutic options

Question 13

Evaluation for heart transplantation

Answer 13

1. multidisciplinary team at a regional transplant centre,

and they undergo a comprehensive

2. physical, psychological and social evaluation.

Successful outcome from heart transplantation requires

strict adherence to complex
medical therapies together with the r
esilience to cope with unexpected setbacks.

3. For ambulatory patients, scoring systems,
   such as the Heart Failure Survival Score and the

Heart Failure Survival Score of medium to high risk
deemed potential transplant candidates

Seattle Heart Failure Model

4. Cardiopulmonary exercise testing is also helpful, with a peak
   V˙ o2 <12–14 mL kg−1 min−1 used as an indication for listing

Question 14

Contraindications to heart transplantation

Absolute

Answer 14

1. Advanced irreversible renal failure (creatinine clearance <30–50 mL min−1) without planned concurrent renal transplant
2. Advanced irreversible liver disease without planned concurrent liver transplant
3. Advanced irreversible lung parenchymal disease (FEV1 <1 L min−1)
4. Advanced irreversible pulmonary hypertension (systolic pressure >60 mmHg; pulmonary vascular resistance >4–5 WU)
5. Solid organ or haematological malignancy in the last 5 yrs

Question 15

Contraindications to heart transplantation

Relative

Answer 15

Severe peripheral vascular disease

Severe cerebrovascular disease

Severe osteoporosis

BMI >35 kg m−2

Active infection (excluding LVAD-related infection)

Diabetes mellitus with end-organ damage

Psychological instability

Active or recent substance abuse (within 6 months)

Lack of social support

Question 16

Pretransplant optimisation

Answer 16

1. patients with cachexia—
   defined as oedema-free body weight loss of more than 5% in 12 months—should be referred to a dietitian for nutritional support.
2. For patients with elevated PVR and limited reversibility, diuretics,

vasodilators, sildenafil and i.v. inotropes should be
given and the right-heart catheter study repeated

Question 17

Assessment for anaesthesia

Answer 17

1. presence of elevated PVR, RV dysfunction and renal impairment.

2.Congenital heart disease may have abnormal central veins, which might limit access sites for central venous access

3. catheters (CVCs) may have thrombosed central veins.
4. Previous cardiac surgery identifies an increased risk of bleeding.
5. anticoagulated or have hepatic dysfunction and may need reversal agents or clotting factors before surgery
6. LVAD, warfarin reversal should be performed in the operating theatre, at the time the device is explanted, to minimise the risk of intra-device thrombosis
7. . Anti-tachycardia and defibrillation features of an ICD should be disabled before surgery.

Consent for anaesthesia should include the usual risks associated with cardiac surgery, such as blood transfusion and placement of a transoesophageal echocardiography (TOE) probe. Also, the anaesthetist should discuss the potential for postoperative ECMO, renal replacement therapy (RRT) and the risk of prolonged ICU stay and multiple organ failure.

Caution with sedatives on ward

Question 18

During surgery

Routine anaesthesia managemen

Answer 18

In addition to standard monitoring,

a pulmonary artery catheter (PAC) and TOE are appropriate for all heart transplant recipients.

External defibrillator pads should be applied in all cases.

Large-bore i.v. access and an arterial catheter should be sited before inducing anaesthesia

Arterial catheterisation can be challenging in patients with LVADs because of non-pulsatile blood flow; ultrasound guidance is helpful. A CVC is usually sited after induction of anaesthesia, but may be done beforehand in very-high-risk recipients

septic technique, as the patient will be immunosuppressed postoperatively.

Question 19

During surgery

Routine anaesthesia managemen

Answer 19

In addition to standard monitoring,

a pulmonary artery catheter (PAC) and TOE are appropriate for all heart transplant recipients.

External defibrillator pads should be applied in all cases.

Large-bore i.v. access and an arterial catheter should be sited before inducing anaesthesia

Arterial catheterisation can be challenging in patients with LVADs because of non-pulsatile blood flow; ultrasound guidance is helpful. A CVC is usually sited after induction of anaesthesia, but may be done beforehand in very-high-risk recipients

septic technique, as the patient will be immunosuppressed postoperatively.

Question 20

Particulars

Answer 20

he CVC and PAC should be sited in the left internal jugular vein, as the right vein is reserved for subsequent myocardial biopsy. To avoid interference in the surgical field, the PAC should not be advanced into the pulmonary artery until after implantation of the graft.

considered extremely fragile and prone to excessive hypotension in response to standard doses of sedative and opioid drugs

iven slowly, allowing adequate time to determine their peak haemodynamic and hypnotic effects, which may be prolonged because of low cardiac output.

Vasopressor drugs for treating hypotension should be drawn up beforehand. Hypoxia and hypercarbia should be avoided to prevent abrupt increases in PVR, which can precipitate acute RV failure

Question 21

Abx + Immunosuprresions

Answer 21

Antimicrobial and immunosuppressive drugs are given after induction of anaesthesia according to institutional protocol.

I.V. methylprednisolone is usually given at induction and again after reperfusion of the graft.

y. An antifibrinolytic drug such as tranexamic acid should be given to reduce bleeding and transfusion requirements.

Question 22

Surgical considerations

Answer 22

CPB, i.v. heparin is given at a standard dose (350–450 U kg−1), targeting an activated clotting time above 400–500 s.

Repeat heparin dosing or antithrombin III concentrate (500 U) may be required in patients who have heparin resistance

Nowadays, heart transplantation is typically performed using a bicaval technique, whereby the entire native right atrium (RA) is excised and the donor SVC, IVC, aorta and pulmonary artery are individually anastomosed to the respective recipient vessels.

cuff of native LA containing the four pulmonary veins is anastomosed to the donor LA. The bicaval approach is associated with reduced mortality and a lower incidence of postoperative complications—notably, a reduced likelihood of permanent atrioventricular block—compared with the classical biatrial technique

Question 23

Management before allograft implantation

Answer 23

Detailed TOE evaluation of the native heart is not required. However, the anaesthetist should alert the surgeon to the presence of intra-cardiac thrombus, aortic atheroma and pleural effusions, which may require the surgeon to alter the cannulation technique. Pleural effusions should be drained

Question 24

Preparation for separating from CPB

Answer 24

During graft implantation, the anaesthetist should prepare for separating from CPB. Important considerations include the potential need for pacing, haemodynamic support and blood component therapy. The temporary pacemaker should be checked and infusions of inotropic, pulmonary vasodilator and anti-arrhythmic agents prepared.

Initially, a combination of DOO pacing (90–110 beats min−1) and low-dose dopamine (3–5 μg kg−1 min−1) or dobutamine (3–5 μg kg−1 min−1) is a reasonable strategy.

milrinone (0.25–0.5 μg kg−1 min−1) or enoximone as an inotrope and pulmonary vasodilato

Inhaled nitric oxide (iNO) at 10–20 ppm can be used as a pulmonary vasodilator and to attenuate PGD

Question 25

Blood component therapy

Answer 25

Blood component therapy

The development of antibodies to human leucocyte antigens as a
consequence of exposure to blood products and other ‘foreign’ substances (allosensitisation) is associated with adverse outcome after heart transplantation.

To minimise this problem, all blood products should be leucodepleted. If the recipient is cytomegalovirus antibody negative, donor blood should also be cytomegalovirus antibody negative

Question 26

Management after allograft implantation

Answer 26

After the left-sided anastomoses (aorta and LA) are complete, the aortic cross-clamp is released and the graft reperfused. The right-sided anastomoses (pulmonary artery, SVC and IVC) can then be completed while the graft continues reperfusing.

CPB flow while occluding venous return to the CPB machine to control cardiac filling

Ventricular arrhythmias are common during reperfusion and when separating from CPB. Treatment includes a further period of reperfusion, internal defibrillation (10–30 J), maintaining K+ >5 mmol L−1, magnesium (10–20 mmol), amiodarone (150–300 mg i.v., repeated if necessary) and lignocaine (1 mg kg−1).

Question 27

Optimising haemodynamic function

Answer 27

The most common cause of failure to separate from CPB is RV failure caused by impaired systolic function and increased PVR. Right ventricular failure is identified with TOE as RV dilatation and reduced free-wall contractility, tricuspid regurgitation and leftward bowing of the atrial septum. Treatment of RV failure involves optimising preload, augmenting RV contractility and reducing PVR.

Loss of vagal and sympathetic innervation means cardiac output is highly preload dependent. Preload is evaluated by simultaneously assessing RV dimensions with TOE and the central venous pressure (CVP) in response to i.v. fluid.

Simple strategies to reduce PVR include maintaining normoxia, normocarbia and a normal pH, while simultaneously avoiding high ventilatory pressures, which increase RV afterload

Question 28

Mechanical circulatory support

Answer 28

Patients who fail to wean from CPB or who do so with marginal haemodynamics (MAP <65 mmHg, CI <2 L min−1 m−2 and CVP >15 mmHg) despite modest-to high-dose inotropic support (adrenaline or noradrenaline >0.1–0.2 μg kg−1 min−1) should be placed on mechanical circulatory support. Options include venoarterial (VA) ECMO and a temporary RV assist device. Evidence suggests that early institution of VA ECMO is the best option.

Question 29

Critical care management

Answer 29

Routine care
The principles of ICU care after heart transplantation involve optimising haemodynamics and fluid balance, early tracheal extubation, provision of adequate analgesia and giving routine antimicrobial and immunosuppressive therapies. In the absence of haemodynamic instability or excessive bleeding, patients should be extubated within 24 h

Patient-controlled analgesia with i.v. fentanyl provides satisfactory analgesia for most patients.
Morphine is generally avoided because of the high incidence of acute kidney injury (AKI) after heart transplantation.

Even when graft function is satisfactory, fluid retention and RV volume overload are frequently problematic in the first few days after surgery.

Giving regular furosemide (20–40 mg i.v. 8–12 hourly) and maintaining low-dose inotropic support for at least 48 h postoperatively help mitigate this problem.

Prophylactic antimicrobial drugs are typically given for 24 h. However, in the case of donor or recipient infection, targeted antimicrobial therapy of longer duration is appropriate.

Routine immunosuppressant drugs are prescribed by the transplant cardiologist and typically involve a

combination of a corticosteroid (e.g. prednisone),

a calcineurin inhibitor (e.g. tacrolimus) and an

antiproliferative agent (e.g. mycophenolate).24

Tacrolimus dosing is adjusted according to blood concentrations and renal function. Many centres routinely use basiliximab, a monoclonal antibody that inhibits T lymphocytes, in the immediate post-transplant period.

Question 30

Management of complications

Answer 30

The most important complication after heart transplantation is PGD

PGD based on the use of mechanical circulatory support
or an LV ejection fraction <45% despite high-dose inotropic drugs within 24 h after surgery

erioperative strategies to minimise PGD include prolonged reperfusion, iNO, surgical control of bleeding to reduce transfusion requirements and gradual weaning of inotropes postoperatively

Acute kidney injury occurs in about 40% of patients after heart transplantation with about 10% requiring RRT.

Question 31

Risk factors for PGD after heart transplantation.

Answer 31

Donor
Ischaemic time >4 h
LV hypertrophy
Predonation LV dysfunction
Age >60 yrs
DCD donation
Donor–recipient size mismatch
Donor–recipient sex mismatch (female donor–male recipient)

Recipient
Age >60 yrs
LVAD explant
Cardiac reoperation
Congenital heart disease

Question 32

Treatment of either primary or secondary graft dysfunction

Answer 32

Treatment of either primary or secondary graft dysfunction in the ICU mirrors that of the operating theatre:

inotropes to support ventricular function,

optimisation of preload and strategies to reduce PVR.

When faced with escalating vasopressor requirements and deteriorating haemodynamics, prompt bedside TOE is indicated.

Cardiac tamponade should be treated with urgent surgical re-exploration.

For severe LV or RV dysfunction, early initiation of VA ECMO is appropriate.

Question 33

Harlequin syndrome

Answer 33

can occur with peripheral VA ECMO when pulmonary function is impaired, but cardiac function has partially recovered. Deoxygenated blood is ejected from the LV and preferentially perfuses the upper body, potentially causing coronary and cerebral ischaemia.

Central VA ECMO avoids the potential problem of Harlequin syndrome