Chapter 105

1790 PART 5 ■ Anesthetic, Surgical, and Interventional Procedures: Considerations
face of significant donor shortage and substantial mortality during
waiting for transplantation, especially in infants. 26 In fact, the first
successful heart transplantation in an adult involved a donor who
died from cardiocirculatory death. 48 Although attractive, this stra -
tegy has stayed within laboratory medicine up until very recently
because of substantial hypoxic myocardial injury during the
agonal period and reperfusion injury after a long warm ischemic
period. The Loma Linda group has published a landmark animal
study looking at the possibility of pediatric heart transplantation
from DCD. 49 The study showed that the animals survived as long
as 34 days after as long as 30 minutes of warm ischemia with
reasonable left ventricular ejection fraction (mean 76%). 49 Nume -
rous experimental studies have been performed on this particular
subject focusing on myocardial protection; however, many of
those studies involved multiple premedications before withdrawal
of care, which limits clinical application of those strategies. 50 The
Denver group recently published their experience of three pedi -
atric heart transplantations from DCD. The protocol indicates that
if death occurs within 30 minutes after extubation, the patient is
considered to be a candidate for donation. The mean time of
donors was 3.7 days. All donors suffered birth asphyxia as a cause
of death. Extubation was performed after heparin (100 U/kg)
administration and sedation and analgesia (fentanyl and loraze -
pam). The mean time to death after withdrawal of life support was
18 minutes (11 to 27 minutes). When cardiocirculatory function
ceased, the patients was observed for 3 minutes (the first patient)
or 75 minutes (the rest) and the organ donation process was
initiated with the administration of cold cardioplegia into the
aortic root through the long balloon catheter placed in the
ascending aorta. The 6-month survival time was 100% compared
to 84% in 17 control patients in the same period. There were no
late deaths. These three patients had reasonable left ventricular
systolic function at 6 months and a similar number of rejection
episodes compared to controls (0.3 per patient versus 0.4 per
patients in controls). The first clinical experience is indeed
encouraging but still holds some medical and/or ethical issues to
be overcome. One of the major issues is the duration between the
declaration of cardiocirculatory death and organ retrieval. A 1997
report from the Institute of Medicine suggested that 5 minutes
should elapse between cardiocirculatory death and organ retrie -
val. 51 The second report from the Institute of Medicine in 2000
reassessed the time interval and stated that the empirical data
available indicate that cardiopulmonary arrest becomes irrever -
sible within a shorter time interval—60 seconds or less. 52 On the
basis of this report, the Denver group used 75 seconds as the
duration from death to retrieval; however, no scientific data have
yet been elucidated to support this practice. Pediatric heart
transplantation from DCD seems to be feasible, but graft preser -
vation technique, long-term graft function, and ethical issues
including time interval from declaration of death to retrieval
should be well discussed and established before regular clinical
application.
Management of Highly Sensitized Patients
Undergoing Heart Transplantation
Some patients awaiting heart transplantation have circulating
antibodies against human leukocyte antigens (HLA). The process
by which antibodies are formed is called sensitization. Sensitiza -
tion may result from previous blood transfusion, 53 homograft
materials used for reconstruction in congenital heart surgery, 54 or
use of mechanical circulatory assist devices. 55 Patients who require
retransplantation often have allosentization. 56 There has been an
increase in heart transplant candidates who have been allosensi -
tized to HLA antigens over the years. The recent study showed
that panel-reactive antibody (PRA) higher than 25% is associated
with poor survival after heart transplantation. 57 Recent experience
showed that 13 (8%) out of 167 patients who had undergone trans -
plantation from 1990 to 2006 met the criteria for being allosensi -
tized before heart transplantation, characterized by a PRA greater
than 10%. 58 Nine (69%) were infants who had had previous
palliation for CHD. Antibody-mediated rejection occurred in
9 (69%) patients and acute cellular rejection (>ISHLT Grade 2 R)
occurred in 7 (53%) patients, which seems more frequent than a
regular transplant group. The actuarial survival at 1 year was 71%.
Pretransplant treatment includes weekly intravenous administra -
tion of immune globulin or an oral low dose of MMF (20 mg/
kg/d) in an attempt to reduce circulating alloantibodies. Perio -
perative management includes plasma exchange during transplan -
tation as described above and induction of thymoglobulin. Most
recently, rituximab, an anti-CD20 monoclonal antibody that
rapidly causes destruction of CD20 positive cells, has been used
empirically perioperatively. Postoperative management includes
induction therapy with thymoglobin (1.5 mg/kg/day) for 2 to 7
days and standard triple immunosuppression with tacrolimus,
MMF, and steroid.
In summary, current practice in pediatric heart transplantation
has attained reasonable early and long-term survival and graft
function in all subsets of patients with end-stage heart failure.
Ventricular assist device as a means of bridge to transplantation,
ABO-incompatible transplantation, and possibly transplantation
from DCD are the key practices to improve overall outcomes by
reducing mortality while awaiting transplantation or by improving
the preoperative condition of such patients. High pretransplant
mortality, management of the growing number of transplantations
for failed Fontan procedure patients, and the sensitization issue
have to be overcome.
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