Peritransplant Issues - Professor Richard Kirk 2023

Professor Richard Kirk
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At the time of transplant donor cells and recipient plasma are sent to the HLA laboratory for compatibility testing using the CDC and Flow techniques.  An excellent review on this subject hsa been published by Mulley and Kanellis  in Nephrology 2011;16:125-133.
Ventricular Function
Primary Graft Dysfunction
This may be a consequence of prolonged ischemic time due either to long distances or a result of explant issues resulting in prolonged "bucket" (i.e. waiting in OR for implant) or prolonged warm ischemic time if technical implant issues occur. It may also be caused by a "double hit" i.e. retrieval early after death - the first "hit" is the catecholamine storm or cardiopulmonary resuscitation, followed by the second "hit" of ischemic-reperfusion injury". Rarely it may be a result of undiagnosed coarctation or anastomotic issues. Primary graft dysfunction may also be caused by immunological incompatibility due to pre-existing donor specific HLA antibodies. Early utilization of ECMO support, if severe, is important.

LV Function
LV function is often compromised immediately after transplant due to ischemic-reperfusion injury during the procurement and implant procedure. Supportive measures including careful fluid management and inotropic support are often necessary. The ventricular walls often appear thickened in the case of size mismatches as the recipient circulating volume and afterload resistance is less than the donor. The circulation in this case is not compromised and no action is necessary.

RV Function
The donor RV is often the worst affected by the ischemic-reperfusion injury and the need to push against a higher recipient pulmonary vascular resistance compared to the donor. LV impaired function also impacts RV function due to the increased LA pressure. Fluid overload is often a contributing factor. Treatment is with optimizing fluid status and inotropic support including the use of low dose epinephrine (adrenaline), isoproterenol (isoprenaline) and milrinone. Specific pulmonary vasodilator therapy with nitric oxide are also usually employed.
Fluid and Inotropes Management
The CVP should be maintained within normal limits. Colloid replacement is generally preferred in the first 24 hours after HT, but blood, if indicated, is the first choice. Fluid restriction and loop diuretics are used to decrease volume overload. Early recourse should be made to hemofiltration or dialysis if medical measures are ineffective or renal function compromised.

Continuous infusion of inotropic agent (s) are initially used but should be weaned when the hemodynamic conditions are favourable.
Renal Failure
Renal function is often compromised before transplant as the cardiac output in heart failure is lower, the systemic venous pressure raised and hence the trans renal pressure gradient reduced. In addition, drugs to improve cardiac failure symptoms e.g. diuretics are often cardiotoxic. Post transplant therefore renal impairment or renal failure is common. Added to these pre transplant factors are the effects of cardiopulmonary bypass, the continued use of diuretics and often hemodynamic instability. As highlighted above, fluid management in the immediate period after transplant is very important and so if conservative measures are ineffective early recourse to renal support with continuous veno-venous hemofiltration (CVVH) is appropriate.
Systemic Hypertension
This is common post transplant. Transplant candidates in cardiac failure or on continuous flow pumps generally have a low mean blood pressure and abnormal autoregulation. After transplant, with a well-functioning ventricle, the blood pressure is often high. Managing it is important as hypertension is one of the factors triggering posterior reversible encephalopathy syndrome (PRES).

Pulmonary Hypertension
Patients in heart failure often have long standing increased left atrial pressure resulting in post capillary pulmonary hypertension and often a degree of pre capillary hypertension. The donor right ventricle is not prepared to handle high pressures and so most patients require pulmonary vasodilators - especially immediately after transplant, but sometime for longer.
Vasoparesis is associated with pre transplant continuous flow pump support and the Fontan circulation. It is thought to be due to the consequences of cardiopulmonary bypass and dysregulation of the cGMP-NO pathway. The ISHLT guidelines suggest that norepinephrine should be considered the first-line agent for treatment of vasoplegia, followed by vasopressin. Other routine vasoactive medications include epinephrine, norepinephrine, dopamine, and angiotensin II. The additional use of a single dose of methylene blue may also be considered.
Pericardial Effusion
Pericardial effusions are relatively frequent - particularly when there is a significant size mismatch, and the donor heart is smaller than the recipient pericardial space. This usually resolves with time. Effusions may occur with rejection - especially antibody mediated rejection and will require investigation but resolve with treatment.
A slow heart rate may be a sinus bradycardia or due to AV block. It should be managed with AV sequential pacing post transplant or with isoproterenol (isoprenaline) if there is also poor RV function. AV block usually resolves spontaneously. The new development of AV block may be due to rejection.

Persistent tachyarrhythmias, regardless of the mechanism, may be due to rejection and should respond to appropriate steroid pulse. Tachyarrhythmias may be resolved with overdrive pacing but more usually requires amiodarone or sotalol.

Ectopic Activity
Atrial or ventricular ectopics are frequent after transplant and seldom needs specific treatment unless they become sustained or compromise cardiac output.
Posterior Reversible Encephalopathy Syndrome (PRES)
PRES typically presents with visual disturbance, headache, seizures, and impaired consciousness one to two weeks post transplant. Precipitating factors include electrolyte disturbance (especially low magnesium), hypertension and prior Glenn or Fontan physiology. Calcineurin inhibitors have also been implicated but given their universal use and that PRES occurs irrespective of levels their role in PRES is unclear. The mechanism underlying PRES is uncertain, but it is presumed that endothelial dysfunction is important. Magnetic resonance imaging typically demonstrates vasogenic oedema in subcortical white matter of the occipital and parietal regions, but other areas can be involved. Management includes addressing the electrolytes imbalance and especially hypertension while managing the neurological symptoms. The effectiveness of reducing calcineurin levels or switching to an alternative calcineurin remains unclear.
Further Reading
  • The International Society for Heart and Lung Transplantation has recently updated its guidelines on the care of heart transplant recipients with recommendations for both adult and pediatric recipients.
  • False positive CDC X-match after rituximab. Reindl-Schwaighofer & Oberbauer. Transpl Int 2014 Dec;27(12):e124-5

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