Cause
End diastolic area
End systolic area
Contractility
Other findings
Hypovolaemia
↓↓
↓
Normal
Vasoplegia
Normal
↓↓
Normal
LV dysfunction
Normal or ↑
↑
↓↓
If severe, spontaneous echo contrast in LV cavity
RV dysfunction
Normal or ↑
↑
↓↓
Tricuspid regurgitation
Abnormal septal motion
Tamponade
↓
↓↓
Normal or hyperdynamic
Pericardial collection
Distended vena cavae
Pseudohypertrophy
RV diastolic collapse
Right atrial (RA) or left atrial (LA) systolic collapse
Restrictive transmitral and pulmonary venous patterns on pulsed wave (PW) Doppler
Respiratory variation in transmitral flow velocities (>25 %)
Laboratory Investigations
Routine laboratory investigations performed on arrival in the ICU include ABG, mixed venous oxygen saturation (SvO2), full blood count (FBC), serum electrolytes, creatinine and liver function tests, and coagulation studies including activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, platelet count, activated clotting time (ACT), and thromboelastography (TEG). Troponin levels are initially measured on the first postoperative day. The frequency of ongoing monitoring of these parameters varies, but occurs at least every 6 h for ABG and SvO2, and daily for other parameters in stable patients; with more frequent measurement in patients with organ dysfunction or bleeding. Immunosuppressant drugs, such as cyclosporine and tacrolimus, have levels measured daily, and drug doses adjusted accordingly.
Hemodynamic Management
Optimal hemodynamic parameters include a mean arterial blood pressure (MAP) ≥65 mmHg, a CVP ≤12 mmHg, and PCWP or LAP ≤12–14 mmHg, CI ≥2.5 L/min/m2, with an SvO2 of ≥65 %. However, in the early postoperative period, increased atrial pressures (CVP 12–15 mmHg and PCWP 14–18 mmHg) may be necessary due to graft dysfunction [3].
Vasoactive drugs are usually required to achieve and maintain optimal hemodynamics in the early postoperative period (Table 14.2). Ideally, continuous infusions of agents with chronotropic and inotropic effects are used to maintain CI, (e.g., epinephrine, dobutamine, dopamine, isoproterenol, and milrinone) whilst agents with vasoconstrictor effects (e.g., norepinephrine, epinephrine, phenylephrine, and vasopressin) are used to maintain target MAP. The lowest effective dose is recommended [1]. Agents with pulmonary vasodilator effects (e.g., milrinone, sodium nitroprusside, nitroglycerine, prostacyclin, prostaglandin E1, sildenafil, and inhaled nitric oxide) are useful in the management of right ventricular (RV) dysfunction and pulmonary hypertension [4–6]; however, intravenous agents are often associated with systemic hypotension. Inhaled nitric oxide has been consistently demonstrated to lower pulmonary vascular resistance (PVR), pulmonary artery pressure, and transpulmonary gradient, and increase CO following cardiac transplant, without significant systemic hypotension [4, 7]. Vasopressin and methylene blue are both effective in the treatment of catecholamine resistant vasoplegia following cardiopulmonary bypass (CPB) [8, 9]. Vasopressin in low dose (0.03–0.1 U/min) does not significantly reduce inotropy or CO, but may significantly increase systemic vascular resistance (i.e., MAP). Vasopressin may be particularly useful in patients with pulmonary hypertension and RV dysfunction as, unlike other vasopressors, it causes selective pulmonary vasodilatation at low doses [10].
Table 14.2
Properties of vasoactive drugs used following heart transplantation
Drug | Peripheral vasoconstriction | Peripheral vasodilatation | Chronotropic effect | Inotropic effect | Arrhythmia effect |
|---|---|---|---|---|---|
Epinephrine | +++ | + | ++ | ++++ | +++ |
Dobutamine | − | ++ | ++ | +++ | + |
Dopamine | ++ | + | ++ | +++ | ++ |
Isoproterenol | − | +++ | ++++ | ++++ | ++++ |
Milrinone | − | ++ | + | +++ | ++ |
Norepinephrine | ++++ | − | + | +++ | + |
Vasopressin | ++++ | − | − | − | − |
Importantly, each vasoactive drug has different potential side effects, and no agent has been demonstrated alone to improve mortality after heart transplantation—thus, vasoactive therapy is usually adjusted to hemodynamic parameters and altered if unacceptable side effects, such as arrhythmias or metabolic disturbance, occur. Weaning of vasoactive supports usually occurs over a period of 3–5 days, even in stable patients, and is dictated by hemodynamic parameters, and end-organ function.
Patients are externally paced via temporary epicardial wires, at 90–110 beats/min. Moderate tachycardia is beneficial because graft ischemia and subsequent reperfusion cause significant diastolic dysfunction in the immediate postoperative period, with limited ability of the graft to increase stroke volume in response to increased preload. Thus, chronotropy is essential to maintain adequate cardiac output. It is preferential to use atrial pacing if atrioventricular (AV) conduction is normal, but in the presence of AV conduction abnormalities, sequential pacing is used.
In the event of severe graft dysfunction, which is refractory to high inotrope and vasopressor support, the use of an intra-aortic balloon pump (IABP) or mechanical circulatory support (MCS) may be considered. The ISHLT guidelines recommend escalating support from pharmacotherapy, to IABP, to MCS [1]. The indications for, and use of MCS are discussed in Chap. 18.
Fluid therapy to maintain target CVP 5–12 mmHg ensures adequate cardiac filling and output, but avoids over distension of the left ventricle (LV) or RV. Blood and blood components therapy are commonly required to maintain target hemoglobin (usually >80 g/L) and normalise coagulation parameters. The ISHLT guidelines recommend blood and blood components are leucocyte-depleted, and cytomegalovirus (CMV)-negative if both donor and recipient are CMV negative [1]. Blood products must be appropriately matched, and in the case of non-ABO compatible transplant patients, blood and blood products must be compatible for both donor and recipient. Other fluids used may include albumin solutions (e.g., 4 % albumin) as colloid replacement, or crystalloid solutions (e.g., Plasmalyte®). Evidence indicates the use of synthetic starch colloid solutions is associated with increased renal injury and possibly increased mortality, and thus these solutions are avoided [11, 12]. Perioperative use of sodium chloride 0.9 % has been implicated in renal, gastrointestinal, and metabolic dysfunction [13–15], and thus, a balanced electrolyte solution is the most appropriate crystalloid solution.
Respiratory Management
Mechanical ventilation allows control of arterial oxygen and carbon dioxide levels, with target normal PaO2 (>80 mmHg) and low-normal PaCO2 (35–40 mmHg) levels avoiding increases in PVR. Commonly used ventilation modes are pressure control or volume control. Regardless of which mode is used, lung-protective strategies are recommended. Lung-protective strategies include:
- 1.
Low tidal volume ventilation (4–8 mL/kg predicted body weight)
- 2.
Use of positive end-expiratory pressure (PEEP) (usually 5–10 cmH2O)
- 3.
Plateau airway pressures ≤30 cmH2O
- 4.
Intermittent recruitment manoeuvres
Recruitment manoeuvres reduce ventilation-perfusion mismatch, helping to minimise increases in PVR by optimising gas exchange, but also by optimising lung mechanics. The use of lung-protective ventilation may reduce ventilator-associated lung injury (VALI), and reduce morbidity and mortality in postoperative and critically ill patients [16, 17]. It is important to note that high levels of PEEP may raise intrathoracic pressure significantly, and increase PVR, and RV afterload. PEEP levels should be carefully adjusted to avoid deleterious effects on CO.
Once patients are stable and receiving low levels of inotrope and ventilator support, with no excess bleeding, weaning and progress to extubation can occur. A small number of patients will not be able to routinely progress and wean, due to ongoing hemodynamic, respiratory, metabolic, or neurologic dysfunction. In those receiving ongoing mechanical ventilation, ventilator-associated pneumonia (VAP) is a major morbidity risk. VAP prevention strategies include: [18]
- 1.
Regular surveillance for VAP (CXR, microbiology samples of sputum and airway secretions)
- 2.
Strict adherence to hand hygiene protocols
- 3.
Nursing patient in a semi-recumbent position (30–45°)
- 4.
Regular antiseptic (e.g., chlorhexidine) mouthwashes
- 5.
In-line or subglottic suctioning of endotracheal tube
- 6.
Maintain endotracheal cuff pressure >20 cmH2O
- 7.
Avoidance of proton-pump inhibitor drugs in patients not at high risk of ulceration or gastritis
- 8.
Daily review of sedation ± sedation reduction or breaks
- 9.
Asepsis in respiratory equipment and cares
For patients requiring prolonged mechanical ventilation and weaning, percutaneous tracheostomy is usually performed.
Renal and Metabolic Management
In cardiac surgery, acute kidney injury (AKI) occurs in approximately 20–30 % of patients [19, 20], with 1–2 % of patients requiring renal replacement therapy (RRT) [21]. AKI following heart transplantation is less well studied and reported, with reported rates between 5 and 30 % [22–24], and RRT in 5–15 % of patients [22, 24, 25]. Risk factors for post-heart transplant AKI include previous cardiac surgery, length of ischemic time, blood transfusion, and degree of troponin release [22]. AKI is independently associated with increased mortality [22, 25, 26].
Strategies to prevent AKI include:
- 1.
Intraoperative avoidance of anaemia and blood transfusion (e.g., cell salvage, meticulous surgical technique, consideration of small CPB circuits)
- 2.
Careful postoperative monitoring of urine output and creatinine
- 3.
Optimisation of hemodynamic and respiratory parameters—with particular attention to volume status and perfusion pressures
- 4.
Avoidance of nephrotoxins
- 5.
Immunosuppression adjustment in the presence of preoperative renal dysfunction, early oliguria, or creatinine increase (e.g., delayed initiation of calcineurin inhibitors).
Several drugs have been studied as preventative agents for AKI, including dopamine, frusemide, nesiritide (B-type natriuretic peptide), fenoldopam, diltiazem, N-acetylcysteine, atrial natriuretic peptide, and corticosteroids. Fenoldopam, atrial natriuretic peptide, and nesiritide may have some efficacy; however, studies are small and no large randomised controlled trials exist to support their use currently [27].
It is common for heart transplant patients to have intravascular fluid overload following transplantation, due to fluid administration, effects of corticosteroids and the stress response to surgery, and renal dysfunction. Increased intravascular fluid can cause worsened RV dysfunction and tricuspid regurgitation (TR). Loop diuretics are used to initiate diuresis and improve fluid balance, as bolus or infusion, and may be combined with thiazide diuretics or aldosterone antagonists. For patients with early oliguria, anuria, or other indications (e.g., hyperkalaemia, acidemia), RRT may be necessary, and should be initiated early to avoid worsening RV dysfunction.
Abnormalities of serum electrolytes, especially sodium, potassium, and magnesium, are common, with hypokalaemia, hyponatraemia, and hypomagnesaemia due to diuretic therapy, fluid therapy, or nutritional deficit, and hyperkalaemia due to renal dysfunction. Hypocalcaemia can occur with large volume blood product transfusion. It is important to monitor serum electrolytes regularly and supplement as necessary. The optimal serum potassium level in the immediate postoperative period is usually high-normal (e.g., 4.5–5.0 mmol/L).
Infection Control
Heart transplant patients are at increased risk of nosocomial and opportunistic infections, due to the combination of major surgery, invasive lines and monitors, immunosuppression, and, often, preoperative debilitation. Patients are ideally nursed in a single room, with strict hand hygiene maintained by healthcare workers and visitors. Maintaining asepsis during procedures and access of invasive lines is mandatory. Early removal of tubes, lines, drains, and catheters minimises the risk of infection. Blood glucose levels should be controlled to within normal limits. Prophylactic antibiotics are commenced prior to transplant, with selection based on prevalent skin flora (especially Staphylococcus species) and sensitivities [1]. Cephalosporins are most frequently used as prophylaxis. In patients with chronically infected pacemakers or ventricular assist devices in situ, or if bacterial infection was present in the donor, antibiotic therapy is based on microbiologic culture and sensitivities. Anti-viral prophylaxis (against CMV) is recommended, with therapy (CMV immunoglobulin, ganciclovir) based on both donor and recipient CMV status [28, 29]. Oral anti-fungal prophylaxis (nystatin drops or clotrimazole lozenges) is commenced following extubation. Anti-protozoal (Pneumocystis jirovecii and Toxoplasma gondii) prophylaxis is also commenced in the early postoperative period. Most commonly, trimethoprim/sulfamethoxazole is used. Infection control is further discussed in Chap. 4.
Immunosuppression
Immunosuppression usually consists of triple therapy with:
- 1.
A calcineurin inhibitor (CNI) (e.g., tacrolimus, cyclosporin)
- 2.
A corticosteroid (e.g., methylprednisolone, prednisone)
- 3.
And an antiproliferative agent (e.g., azathioprine, mycophenolate mofetil, sirolimus, everolimus)
CNI-based therapy remains the cornerstone in adult heart transplant immunosuppression protocols. Tacrolimus is now the preferred CNI used worldwide—used in 81 % of heart transplants in 2012 [30]. Whilst corticosteroids are used in the majority of recipients, corticosteroid weaning or avoidance may be accomplished in patients with significant side effects and without recent rejection episodes [31]. Antiproliferative agents reduce the onset and progression of cardiac allograft vasculopathy (CAV), and are therefore recommended [1, 32].
Induction therapy with interleukin-2 receptor (IL-2R) antagonists, antithymocyte globulin, polyclonal or monoclonal antibody preparations may be used in patients at high risk of rejection or renal dysfunction, and can be used to delay or avoid the use of a CNI or corticosteroid [33]. The ISHLT Thirtieth Official Adult Heart Transplant Report notes that induction therapy use is decreasing, with a 47 % overall use in the first 6 months of 2012 [30].
Long-term immunosuppression is associated with side effects including infection, renal dysfunction, and malignancy. These are further discussed later in this chapter.
Nutrition
Optimisation of nutrition is important, as patients are often debilitated prior to transplant, and in a catabolic state post-transplant. Usual targets for caloric intake are 25–30 kcal/kg/day, with enteral nutrition via nasogastric tube commenced early in the postoperative period. If enteral nutrition is not possible, parenteral nutrition is commenced. Essential vitamins and minerals are also administered. Hyperglycaemia is common following heart transplant, due to the surgical stress response and administration of corticosteroids. Insulin is administered by infusion to normalise blood glucose levels.
Early Complications
In the early postoperative period, the most important complications are bleeding and coagulopathy, primary graft failure and hyperacute rejection, tricuspid regurgitation, infection, and arrhythmias.
Bleeding and Coagulopathy
Bleeding is common immediately following heart transplantation. Contributing factors include preoperative anticoagulation with warfarin, CPB effects on the coagulation system, hypothermia during surgery, pre-existing hepatic dysfunction due to RV failure, and previous cardiac surgery or presence of a ventricular assist device. Patients with continuous flow ventricular assist devices have a high incidence (nearing 100 % after 1 month) of acquired von Willebrand disease [36], and increased bleeding associated with this. Preoperatively, warfarin anticoagulation is reversed with low dose vitamin K, and a combination of fresh frozen plasma (FFP) and factor concentrates, targeting a PT <1.5 [1]. Coagulation studies are performed on arrival in intensive care, and include aPTT, PT, fibrinogen, platelet count, ACT, and thromboelastography (TEG). Coagulopathy is corrected with targeted blood product transfusion (e.g., FFP, platelets, cryoprecipitate) as indicated by coagulation results—aiming for near-normal coagulation parameters. Recombinant factor VIIa may be considered in persistent excessive bleeding, but has not been well studied in heart transplantation. Residual heparin effect is corrected with protamine. Tranexamic acid may be used if excess fibrinolysis is present. Hypothermia can be contributory to coagulopathy, and care should be taken to restore normothermia. Coagulation testing is repeated following transfusion of blood products, or in the presence of ongoing bleeding.
Cardiac tamponade may present after excess bleeding, typically with progressive hypotension, rising CVP, and low CO. Tachycardia may not be present, partially due to denervation of the donor graft. The incidences of excess bleeding and cardiac tamponade are not well reported, but in one study of 88 heart transplant patients, 31 (35 %) developed pericardial collections in the immediate postoperative period, and 3 (3.4 %) developed tamponade requiring intervention [37].
Primary Graft Failure
Primary graft failure (PGF) is the leading cause of early mortality after heart transplant, accounting for 36 % of deaths during the first 30 days post-transplant in the years 2002–2012 in the ISHLT Registry [30]. PGF presents as severe ventricular dysfunction (usually predominantly RV dysfunction, however predominant LV dysfunction or biventricular failure also occur) in the immediate post-bypass period. Aetiology of PGF is multifactorial. The graft has often suffered insult due to prolonged ischemic time, limited myocardial protection, and manipulation during transport and surgery. Further insult occurs due to reperfusion injury. The graft is removed from a donor with normal PVR, and often transplanted to a recipient with chronically elevated PVR. Additionally, acute elevations in PVR are common during surgery and anaesthesia due to raised intrathoracic pressure with mechanical ventilation, atelectasis, ventilation-perfusion mismatch, acidemia, or hypoxemia. The systemic inflammatory response of the recipient is likely to contribute further insult to the graft. The process of brain death is also likely to contribute—it is well recognised that brain death causes impaired myocardial contractility [38]. Last, size mismatch between donor and recipient may result in acute increases in workload for the donor graft. Ventricular dysfunction is therefore promoted by many factors, and RV dysfunction is particularly common due to the relative inability for the RV to compensate for increases in afterload, and due to the preload dependence of the RV. Risk factors for PGF are summarised in Table 14.3.
Table 14.3
Risk factors for primary graft failure
