Intestinal Transplant Manual - Pediatric Residency Program

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Center for Intestinal Care and Transplant

Intestinal Transplant Protocol

Thomas M. Fishbein, M.D.

Stuart S. Kaufman
,

M.D.

Cal Matsumoto, M.D.

Yulyia Rekhtman, M.D.


Georgetown Transplant Institute

The Georgetown University

Hospital

Children’s National Medical Center


-

1

-

Revised:
February 2006


Contents


Introduction








2

Indications









3

Patient Evaluation







3

Operative Procedures







4

Maintenance Immunosuppressive Management



7

Patient Management







8

Refe
rences









13

Appendices


Initial pre
-
op orders






15



I
nitial post
-
op orders






17



Central line care







20

Fever protocol







25



Immunosuppression protocol





27



Prophylactic antimicrobial therapy




31


Protocol for feeding






34

P
ost
-
transplant referring MD instructions



38


-

2

-


Introduction


Intestinal transplantation was first attempted
in animals almost a century ago by Alexis Carrel.
The first successful experimental model was
developed by Lillehei in 1959 and involved
autotrans
plantation of the isolated intestine in
dogs (1,2). Shortly thereafter, Starzl successfully
transplanted the intestine as part of multi
-
visceral
homografts, also in dogs (3). This organ complex
consisted of the liver, stomach, pancreatico
-
duodenal complex
and the small and large
intestine and was transplanted after exenteration
of the abdominal cavity of the recipient.
Although transient technical success could be
achieved with these models, adequate
immunosuppression was not available to allow
long
-
term s
urvival. Further, little clinical
application was envisioned, and it was therefore
another 30 years before the first technically
successful human application of these operations.


In the modern era of transplantation,
intestinal transplants are receiving
renewed
interest as a potential therapy for short gut
syndrome.

Prior to the development of total
parenteral nutrition by Dudrick et al in 1968 (4),
short
-
gut syndrome was

usually lethal and
survival was a function primarily of intestinal
remnant length an
d intestinal adaptation (5). With
the development of parenteral nutrition, survival
in patients with short gut syndrome could be
reliably achieved for the first time. Three
-
year
survival rates now range from 65 to 80 percent
with this therapy (6). Life on

parenteral nutrition
can be extremely restrictive, however, and many
patients develop life
-
threatening complications.
Intestinal transplantation is now a clinical option
that may return such patients to a normal lifestyle
and treat or avoid the life
-
threa
tening
complications of parenteral nutrition.


In 1988, Grant transplanted a liver and
intestine together to treat a woman with
antithrombin III deficiency and short
-
gut
syndrome secondary to mesenteric thrombosis
(7). This patient is still at home, eating

a normal
diet. The same year, Starzl performed a
modification of his original canine multi
-
visceral
procedure on a child, who survived 6 months (8).
These individuals first demonstrated the potential
of transplantation to offer patients with intestinal
f
ailure the hope of a return to a normal lifestyle.
In 1990, long
-
term survival in animals was
consistently achieved with the new
immunosuppressive agent FK506 (tacrolimus)
(9), ushering in an era wherein rejection could be
more reliably controlled.


Since

1990, more than 700 intestinal
transplants have been performed worldwide, with
increasing success. Currently, 60
-
80 intestinal
transplants are performed each year in the United
States. According to Medicare data, 19,700

patients were on home parenteral nu
trition in the
U.S. in 1987 (10), 15% of whom are considered
to be intestinal transplantation candidates. Overall
in the U.S., it is estimated that 2 to 4 new patients
per million per year will require life
-
long
parenteral nutrition. Some have estimated th
at in
Europe, there are far fewer candidates for
intestinal transplantation, because there are far
fewer patients on home parenteral nutrition (11).
The leading indication for home TPN in the
United States is cancer (10).


Sepsis, major vessel thrombosis a
nd liver
failure ultimately contribute to 28% of deaths
occurring during parenteral nutrition treatment.
Among children, the risks of chole
stasis and
subsequent liver failure are much higher,
particularly among premature infants (12,13). At
the Universi
ty of Pittsburgh, 43% of pediatric
patients accepted as candidates for intestinal
transplantation die within one year on the waiting
list (unpublished observations), illustrating the
inability of alternative therapy to adequately treat
these patients. Fur
ther, this finding points to a
need for additional clinical centers in disparate
organ distribution regions to facilitate more
timely transplantation of these desperately ill
patients. Currently, intestinal transplantation is
restricted by the number of ap
propriate donors in
the few organ distribution areas where this
service is available.


Results with intestinal transplantation have
improved similarly to the survival increases seen

-

3

-

in the past with transplantation of other solid
organs. The International
Intestinal Transplant
Registry in London, Ontario reported worldwide
results in 1997. Of 273 intestinal transplants
reported, 113 were isolated intestines, 130 were
liver/intestine and 30 were multivisceral grafts.
Graft survival at 1 and 2 years was 60%.
Patient
survival was 90% at 1 year in intestine alone
transplants. As with other high technology
therapies, centers that performed more than 10
transplants had better results, but only half the
cases were done at such centers. Results have
improved over th
e last 5 years. Graft losses were
primarily due to rejection (60%), thrombosis
(17%) and sepsis (9%). Deaths were usually due
to sepsis, multiple organ failure or thrombosis.
Rejection was seen in 79% of isolated intestinal
allografts, 71% of intestine/l
iver allografts, and
56% of multi
-
visceral allografts. These results are
comparable to those reported for liver and
pancreas grafts a decade ago, as transplantation of
transplantation of these organs matured.


Indications

The indications for intestinal t
ransplantation vary
widely. The basic requirement for candidacy is
end
-
stage intestinal failure requiring either partial
or complete intravenous alimentation. In children,
the leading indication is the short
-
gut syndrome
arising from neonatal or childhood

catastrophe.
Midgut volvulus, malrotation, necrotizing
enterocolitis, combined jejunal
-
ileal atresia,
gastroschisis and ruptured omphalocele are the
most common causes. However, long segment
Hirschsprung’s disease, pseudo
-
obstruction and
other motility d
isorders, and malabsorption from
microvillus inclusion disease
or
Tufting
enteropathy

account for the majority of other
patients. Among adults, the most common
indications are short
-
gut syndrome secondary to
inflammatory bowel disease, trauma, mesenteric
thrombosis often associated with hyper
coagulable
states, multiple polyposis syndromes, and
desmoid tumors involving the root of the
mesentery (14).


The small intestine normally ranges from
365
-
600 cm, depending on measurement
methods. Sho
rt gut syndrome is usually defined
as the presence of less than 200 cm of small
intestine in adults, or less than two
-
thirds of the
normal intestinal length (15). Although survival
with short gut syndrome was low prior to
parenteral nutrition, it could be

correlated to some
extent with intestinal remnant length, presence or
absence of the ileocecal valve, and the patient’s
age. The ability to achieve nutritional autonomy
can also be predicted to some extent based on
these factors (16,17). The absolute leng
th of
intestine needed for nutritional independence in
childhood is more variable (18
-
20).


When severe cholestasis or cirrhosis
accompany intravenous hyperalimentation, the
liver disease may mandate combined liver and
intestinal transplantation. In some
patients,
however, fibrosis and cholestasis in the native
liver have regressed after isolated intestinal
transplantation and return to an enteral diet (21).
The decision to include the liver in the allograft
must be individualized, with the benefit of the

less complex isolated transplant weighed against
the risk of post
-
operative liver failure. I.V. access
problems and recurrent line
-
related sepsis limit
long
-
term parenteral nutrition as well and may
also be indications for isolated intestinal
transplantat
ion. Motility disorders vary in site of
involvement and severity and may mandate full
multi
-
visceral transplantation or a modification of
this procedure. Gastric emptying is sometimes
severely impaired in these patients, and the native
stomach may not be

functional if the stomach is
included in the graft. Disease progression may
also affect the previously normally functioning
stomach late after transplant.


Patient Evaluation

The first aim of the evaluation process is to
confirm the diagnosis of end
-
s
tage intestinal
failure. This may require a multi
-
disciplinary
approach, with review of medical history,
histopathologic confirmation of the diagnosis
when possible, and review of pertinent

-

4

-

radiographic studies. In patients who have had
resection, the int
erval from resection to
evaluation is critical, as postoperative adaptation
of the small intestine can continue for up to 2
years. The length and caliber of remaining
intestine, presence or absence of the ileocecal
valve, and exactly which anatomical porti
on of
small intestine is left are also important.


The absence of obstructive lesions in the
remnant intestine must be proven, as partial
obstruction can cause malabsorption and bacterial
overgrowth of the remnant intestine. If bowel
lengthening or taperi
ng has been done, the
postoperative course should be reviewed. The
absence of recurrent bacterial overgrowth may
need to be documented by hydrogen breath
testing. A history of recurrent or severe TPN
-
induced pancreatitis is significant and may
mandate gluc
ose tolerance testing and stool
studies for fecal fat and may alter the operative
plan. Inclusion of the pancreas in the allograft is
sometimes recommended in such cases.


The nutrition support component of our
service should render an opinion as to the
a
dequacy of candidates’ current parenteral
nutritional support formula and the likely impact
of any anticipated changes on liver function. If
changes in the nutritional regimen are
recommended, patients may be managed
accordingly and followed. Some patien
ts may
initially present with cholestasis and appear to
require combined liver/intestinal transplantation,
only to show improved liver function with
changes in their parenteral nutrition regimen. In
some pediatric cases, bowel lengthening or
tapering proce
dures may be recommended
instead of transplantation. Further measures of
nutritional status will be employed based on the
pre
-
evaluation process for liver transplantation
candidates. The degree of jaundice, portal
hypertension and synthetic dysfunction mus
t be
assessed. Growth failure should be documented
in children, with anthropomorphic as well as
biochemical data. Prealbumin, retinol binding
protein and
blood

urea nitrogen will generally be
measured, as will 24
-
hour urine creatinine.
Accurate assessment

of pediatric patients’ ability
to eat is important. Many have never learned or
have forgotten how to eat.


Because most intestinal transplantation
candidates have had multiple indwelling
catheters, assessment of available access is
important.

Patency o
f major neck and leg veins
should be assessed and documented by MRV
when indicated. Duplex assessment for portal
vein patency is also of paramount importance to
document venous outflow of the remaining
abdominal viscera (e.g., stomach, pancreas,
spleen an
d sometimes the colon)

after
transplantation. Abdominal MRV may be
required for confirmation of patency. Portal and
mesenteric thrombosis do not contraindicate
transplantation but may mandate multi
-
visceral
transplantation rather than a more limited graft.

Additionally, anomalies of the venous system
sometimes accompany short bowel syndrome or
motility disturbances in children (e.g.
preduodenal portal vein).


A thorough search for active sources of
infection should also be undertaken. In addition,
the inte
grity of other organ systems must be
assessed as appropriate. Most patients will
require cardiac and pulmonary consultation. In
patients with pseudo
-
obstruction or
Hirschsprung’s disease, full upper and lower GI
tract motility studies should be done, and
p
sychiatric evaluation of the family and the
patient is usually indicated. In patients with
thrombotic disorders, hematologic evaluation and
sometimes visceral angiography will be required.
Patients with microvillus inclusion disease,
radiation enteritis a
nd polyposis syndromes
should have histology. Desmoid tumors should be
evaluated radiographically, with particular
attention to the relationship to major vascular
structures such as the mesenteric vessels and
portal vein.


Operative Procedures

In intes
tinal transplantation, the operative
approach must be individualized. Because
indications vary widely and the existing anatomy
is different in each patient, flexibility in planning
the donor and recipient operations is critical (22).



There are three bas
ic transplant procedures

5

which correspond with concomitant donor
procedures and can be modified according to
need. These are briefly detailed below.



Isolated Intestinal Transplantation
:

The
donor should be hemodynamically stable, with
no history of re
cent intestinal disease, prolonged
cardiac arrest, or high
-
dose pressors, and of equal
or smaller size than the recipient (23). Selective
intestinal decontamination containing an
aminoglycoside, amphotericin B and polymyxin
E should be given enterally ever
y 4 hours from
the time of donor acceptance until the donor
operation when possible. Broad
-
spectrum
antibiotics are given intravenously. No
mechanical bowel preparation is used.



The donor operation commences with a
xiphisternal incision and transverse ab
dominal
incision. A nasogastric tube should be placed to
instill another dose of selective gut
decontaminant. The liver can be mobilized in the
usual fashion. The operation historically
precluded the use of the pancreas from the same
donor. A Cattell ma
neuver and Kocher maneuver
are performed and the aorta is exposed up to the
superior mesenteric vessels. The gastrocolic
omentum is divided, and the left colon is
mobilized such that the base of the mesentery is
also mobilized with division of the ligamen
t of
Treitz. The small intestinal luminal contents
should then be advanced down into the colon.
The mesentery of the colon is ligated and divided,
and the colon is stapled at the pelvic brim and
removed to eliminate portal venous drainage of
the organ, whi
ch will become ischemic. The tail
of the pancreas is mobilized, with the spleen
exposing the left side of the aorta and the origin
of the mesenteric vessels. The proximal jejunum
is then divided with a stapling device. The donor
is then prepared for the fl
ush through the distal
aorta. No portal flush is used, to avoid obstruction
of intestinal venous outflow and intestinal edema.
After the flush, performed with suprahepatic
caval venting, the pancreas is split along the axis
of the mesenteric vessels. A C
arrel patch is taken
with the entire intestine and root of the
mesentery. The portal vein is divided at the
confluence, leaving the orifice of the splenic vein
with the intestinal side to be used as a patch if
required. The liver is then excised in the st
andard
fashion and flushed on the back table through the
portal vein.


If the pancreas is to be used from the same
donor, we will dissect the base of the small bowel
mesentery in situ prior to the flush. The
mesentery is isolated upon a lap pad, the
mesen
teric vessels isolated below the inferior
pancreaticoduodenal artery and vein, which
provide necessary flow to the pancreas allograft,
and the first jejunal arcade may require ligation.
Small vascular clamps are placed on the superior
mesenteric artery and

vein after the flush, and
these vessels transected. The pancreatic side are
oversewn with 6
-
0 prolene individually and the
bowel graft is then flushed on the back table. The
pancreas and liver are then removed en bloc in
the usual fashion. Iliac or common

femoral artery
and vein grafts are required for implantation of
the small bowel graft.


The back
-
table procedure entails cleaning of
any ganglion tissue that will bleed from the
Carrel patch. In some cases, placement of iliac
arterial and venous condui
ts onto the graft vessels
will be required. We prefer aortic inflow and
caval drainage for patients who have
demonstrated significant liver cholestasis,
fibrosis, or ultra
-
short bowel syndrome. This is
the case if the portal vein piggy
-
back method of
veno
us reconstruction will be used (24), or if the
pancreas has been procured for transplantation
and the superior mesenteric artery is divided
distal to the origin of the inferior
pancreaticoduodenal artery. The base of the
mesentery is then examined for hemo
stasis.
Alternatively, the entire liver, pancreas, small
bowel and spleen can be removed en bloc and
separated on the back table, as is done for
combined organ procedures.


The recipient operation requires exposure of
the infrarenal aorta for anastomosis
of the arterial
graft. This must be performed in a tension free
manner, as the weight of the bowel can tear the
graft from the aorta or lead to decreased flow and
thrombosis. The venous anastomosis is to the
side of the portal vein in piggy
-
back fashion
(24),
end to end to the superior mesenteric vein, or to
the vena cava end to side, as is done for a
portocaval shunt. The superior mesenteric vein

sometimes cannot be exposed, as the base of the
mesentery may be contracted after multiple prior

6

resections.
Systemic drainage has not been shown
to yield inferior nutritional results, as some had
initially predicted (25). Enteral continuity is
reestablished proximally and distally in
conjunction with either an end or a loop
ileostomy. These decisions will depen
d on how
much and which portions of native intestine
remain. Gastrostomy, jejunostomy or the
combined “G
-
J” tubes are placed to avoid
prolonged need for nasogastric suction and
facilitate early feeding.


Combined Liver/Intestinal Transplantation
:
Donor man
agement and operation begin as for
isolated intestinal transplantation. However, no
hepatic hilar dissection is undertaken (26). The
gallbladder is incised and the biliary tract is
flushed with saline. After removal of the colon,
the flush is performed w
ith only aortic
cannulation and suprahepatic caval venting into
the pericardium. The tail of the pancreas and
spleen are then mobilized from the retro
-
peritoneum, with care taken to avoid injury of the
superior mesenteric vessels or the inferior
pancreati
coduodenal arcade. The proximal
duodenum is then dissected at the level of the
pylorus and divided with a stapling device. The
Carrel patch containing origins of the celiac and
superior mesenteric arteries is then taken with a
wide margin, so that an aorti
c conduit can be used
if required. If the kidneys are not being used, the
entire infrarenal aorta should be removed with the
graft. The entire pancreas, spleen, small intestine
and liver are removed
en bloc
with intact inferior
vena cava and duodenum. The

back table
procedure requires resection of the distal pancreas
to the right of the mesenteric vessels, ligating the
branches draining the uncinate process and
oversewing the pancreatic remnant. The left
gastric artery and splenic arteries must be ligated
.
The gastroduodenal and inferior pancreatico
-
duodenal arteries are preserved. The vena cava
of the graft is then prepared as for isolated liver
transplantation.


The recipient is explored through a midline
incision with bilateral subcostal extension.
Initial
dissection of the liver hilus will allow ligation of
the hepatic artery and common bile duct. The
portal vein is then skele
tonized and the
infrahepatic vena cava is isolated for construction
of a portacaval shunt. Most of these patients have
maj
or vessel thrombosis due to parenteral
nutrition access for extended periods of time, and
venovenous bypass is not used. Thereafter, the
liver is dissected from the cava as for piggyback
liver transplantation. The infrarenal aorta is then
exposed for ana
stomosis. A thoracic aortic donor
conduit can now be placed on the infrarenal aorta
to facilitate graft inflow to the graft. The hepatic
veins can now be clamped and the liver removed.
An end to side portocaval shunt is now
constructed. With relief of the

portal
hypertension, the adhesions from multiple prior
operations can be lysed with care to avoid
enterotomy, which can be disastrous. The graft is
brought to the table and the suprahepatic caval
anastomosis is done in piggyback fashion. The
Carrel patc
h can now be anastomosed either
directly to the aorta or preferably to the
interposition conduit of donor thoracic aorta or
bifurcating iliac artery. The interposition aortic
conduit can be placed in either the infrarenal or
supraceliac position depending

on the anatomy of
the recipient. The stump of the splenic vein may
be used for venting preservation solution, and if
this is planned, the surgeon should isolate and
prepare the splenic vein orifice during the back
table procedure. Enteral continuity is
reestablished with either side
-
to
-
side duodeno
-
duodenostomy or jejunojejunostomy, whichever
is suitable. Distal anastomosis is as with isolated
intestinal allo
grafting


Multivisceral Transplantation
:
Donor
management is fundamentally the same as in the
liver
-
intestine

procurement except that variable
amounts of the stomach and colon will be
preserved with the graft. Children with intact anal
sphincter function but microcolon or long
segment Hirschsprung’s disease may benefit from
inclusion of the right c
olon for later performance
of a pull
-
through procedure. Pseudo
-
obstruction
cases with significant gastric emptying
dysfunction will benefit from inclusion of the
stomach. Patients with pancreatic insufficiency
or diabetes from TPN
-
induced is as previousl
y
described.

The operation is pancreatitis will
benefit from inclusion of the entire pancreas.
Finally, some patients, such as children with
megacystis
-
microcolon syndrome,

may rarely
require concomitant renal transplantation. In this
case, one or both p
ediatric kidneys can be kept in

7

continuity with the allograft, with either the distal
or the thoracic allograft aorta used for inflow.
The fundamental differences in the donor
operation are preservation of the left gastric
artery, preservation of the gast
roepiploic arcade
when removing the colon, and division of the
distal esophagus instead of the jejunum or
pylorus. The abdominal viscera are then removed

en bloc
with the vena cava and the same Carrel
patch, or intact aorta, as for liver
-
intestine. The
t
ransplant procedure is different in that the entire
splanchnic circulation is removed; no portocaval
shunt or bypass can be employed. The pancreas
and spleen, the root of the intestinal mesentery,
the stomach and the liver are removed together,
preserving

vena caval continuity. This is most
easily done proceeding from the left with a
medial visceral rotation, ligation of the celiac and
superior mesenteric arteries, and then removal of
the pancreas, spleen and liver together, preserving
the inferior vena c
ava for piggyback allograft
implantation. Sometimes, the stomach will be
removed as well. Vascular anastomoses are done
as for liver
-
intestine grafting. Enteral continuity
is reestablished with gastrostomy and
jejunostomy tubes and ileostomy construction.

Transplantation of the stomach often results in
prolonged gastric stasis, and some form of gastric
decompression tube is mandatory.


Each transplant may vary slightly according
to patient needs. Conventional portal drainage of
the isolated intestine ma
y not be feasible, and the
graft may be drained systemically. The liver
-
intestine allograft may contain no duodenum, and
a primary biliary reconstruction to the proximal
jejunum will be required. Multi
visceral
allografting may be accomplished with splenic

and gastric preservation after distal splenorenal
shunting. Thus, each case must be planned and
carried out on an individualized basis.


Maintenance Immunosuppressive Management

The intestinal transplant immunosuppression
regimen consists of a three
-
dr
ug combination.
Solumedrol, 50 mg I.V., should be given to the
recipient on call to the operating room. One gram
of intravenous bolus steroid injection (Solucortef)
is given intra
-
operatively and followed by a
standard Solumedrol taper, as with liver
tra
nsplantation. Children receive 20 mg/kg bolus
and the standard taper
.


Rapamycin (sirolimus) is
used combined with tacrolimus, in doses of 5
mg/D adult and 1mg/M
2

pediatric. Levels are
measured weekly

and
targeted to 10
-
15 for the
first month post
-
transpla
nt.
Ra
pamycin

typically
will
be
started on the fifth day

after transplant.


Tacrolimus (Prograf) is the mainstay of
therapy. If there is no contraindication Prograf
will be given via J
-
tube immediately after
transplant. Because of malabsorption and
decre
ased transit time in the intestinal graft with
severe reperfusion injury, in such cases Prograf
may be given intravenously at first, starting intra
-
operatively at 0.1
-
0.15 mg/kg/d as a continuous
infusion and continuing for the first few days
after transpl
antation. Doses are altered according
to trough levels. The early postoperative target
range for the trough level should be 20
-
25 ng/ml.
Once tube feedings are tolerated, the patient is
switched to an oral dose of 0.2
-
0.3 mg/kg/d, with
an overlapping wean

of the I.V. dose. If early
rejection is not encountered, the trough level may
be adjusted down to the 15
-
20 ng/ml range after
the first 3 weeks. When ischemic injury to the
allograft is minimal, I.V. administration is not
required, and Prograf may be star
ted via the
feeding tube immediately after transplant, as with
liver recipients. The jejunal and gastric ports of
the tube should be clamped for one hour before
and after tacrolimus and sirolimus administration
early after transplant to avoid gastric drain
age of
medication. When only oral Prograf is given,
fluconazole administration helps maintain
adequate trough levels.


Lymphocyte depletion in the recipient has
been associated with increased rates of lympho
-
proliferative disorder (27) and has not been
sh
own to improve patient or graft survival and is
therefore not routinely employed. However, as
increased experience with newer anti
-
lymphocyte
agents such as thymoglobulin increase, this may
warrant reevaluation. Pre
-
treatment of the graft or
donor with lym
phocyte depletion has been shown
to decrease graft
-
versus
-
host reaction in animal
models and in some instances to improve graft
survival in animals (28). Therefore, grafts may

8

be pre
-
treated in such a fashion when this is
acceptable to the other transplan
t teams procuring
organs from the intestinal donor, using a single
dose of thymoglobulin brought to the donor OR.


Prostaglandin E1 (Prostin) may be
administered as continuous infusion in selected
instances for renal protection or to improve
perfusion of t
he graft. It should be given at 0.02
µg/kg/hr
and increased to 0.06
-
0.08 µg/kg/hr as
tolerated. In children, hydrocortisone is used in
place of methylprednisolone, and the taper is
adjusted based on the patient’s weight
.

Neurotoxicity is more common with

I.V. Prograf
and levels must be followed closely, sometimes
requiring measurement every 12 hr

.

Further, part
of the response of the transplanted intestine to
immunological insult is development of secretory
diarrhea. Electrolyte imbalances must be
aggres
sively managed with I.V. replacement and
drugs, or hypokalemia, hypocalcemia and
hypomagnesemia will result, further potentiating
drug toxicity. Management of these problems,
and I.V. replacement of the resulting fluid and
electrolyte losses, in a proactiv
e, anticipatory and
aggressive style is of paramount importance to
early postoperative outcome.


Treatment of rejection must be
individualized. Mild or moderate clinical
rejection, evidenced by increased or de
creased
stomal output, should be treated by
bolus steroid
therapy and the institution of a steroid taper in the
usual fashion. Rejection present only on
surveillance biopsies but not yet clinically
manifest may be treated by restrained bolus
steroid therapy alone. When bloody diarrhea is
present, or

endoscopy reveals exfoliation, or
histological mucosal denudation is present, then
more aggressive treatment is warranted or the
graft may be lost. It is important not to delay the
treatment of severe rejection in these instances.
Steroids should be giv
en empirically if symptoms
are present, even if biopsy results are pending and
other diagnoses are being considered. OKT3 or
thymoglobulin will be warranted if a prompt
response is not seen with steroids in cases of
exfoliation of the graft mucosa. In cas
es of
severe exfoliating rejection, broad spectrum
antibiotics, including fluconazole, should be
given intravenously until evidence of mucosal
recovery is observed endoscopically.



Patient Management

The early post
-
operative period:

Patients will
requ
ire ICU care immediately after transplant.
They will generally remain intubated in the early
postoperative period, although isolated intestinal
transplant patients may be extubated early. In the
first 24 hours, the transplanted intestine will
usually prod
uce minimal stool, but third space
losses can be significant, requiring aggressive
hydration. If kidneys are transplanted with the
graft, the urine output should be replaced on an
hourly basis with 0.45% NS, with 1 ampule of
sodium bicarbonate and 10 mEq o
f potassium
chloride per liter of fluid. If the urine output
exceeds 500 cc/hr, then the replacement volume
should be ½ cc/1 cc of the excess over 500 cc
with the same fluid. Finally, pulmonary artery
catheter pressures or transthoracic
echocardiography m
ay be employed to help guide
fluid management at the discretion of the critical
care team. No wedge pressures should be
performed on these patients. The intestinal
vasculature is sensitive to vasoconstrictive agents,
particularly Levophed. Levophed is not

employed
for the care of intestinal transplant patients, and
any vaso
con
stricting pressors should be used only
after thorough consultation with the critical care
attending staff and the surgical team including
Dr. Fishbein. Sepsis that r
equires such
interventions usually indicates the need for
reoperation.


Electrolyte imbalances must be corrected
aggressively with intravenous delivery. The
transplanted bowel will often exhibit calcium and
magnesium malabsorption with high ileostomy
out
puts. Water, sodium and bicarbonate are often
lost in large quantities with high ileostomy
outputs. This may lead to a characteristic
metabolic acidosis requiring sodium bicarbonate
added to the intravenous or enteral formula for
correction. These patie
nts often require oral
doses of 8
-
12 g of bicarbonate daily in divided
doses for months after transplantation, as is
common during management of the short gut
syndrome. Hypomagnesemia will potentiate

9

Prograf
neurotoxicity

(therefore, frequent
monitoring an
d early supllementation with
preferably Magnesium gluconate is important)
.
Hypocalcemia in patients with

the short gut
syndrome or intestinal failure may result in
decreased intraluminal binding of oxalate, partly
due to increased chelation of calcium by
malabsorbed fat delivered to the distal ileum.
Less calcium is thus available to bind oxalate to
the nonabsorbed complex, and increased oxalate
absorption results, sometimes leading to the
formation of calcium oxalate stones and renal
failure. Aggressive
intravenous calcium repletion
will avoid this problem. Trace elements such as
zinc and copper are sometimes difficult to
maintain at adequate levels and should be
checked frequently.


Intravenous broad
-
spectrum antibiotics
should be continued for 3 days

after
transplantation or until the first biopsy confirming
mucosal integrity of the transplanted bowel.
Antibiotic use after this time should be guided by
cultures and sensitivities, or by the results of such
studies in the late pre
-
transplant period in
the case
of patients with recurrent bouts of line
-
related
sepsis. Selective digestive decontamination
should also be continued during this time and
discontinued when enteral feedings are begun via
the jejunal access tube. Selective gut
decontamination shou
ld be restarted in
conjunction with systemic antibiotics during
bouts of severe or exfoliative rejection, due to the
high incidence of translocation during these
episodes. Mechanical ventilation will be
discontinued according to standard measures used
by t
he critical care team, in conjunction with the
transplant surgeon and a view of the upcoming
course of the particular patient. Some patients
will have lost the right of domain of the
abdominal cavity and will return to the intensive
care unit closed with
a prosthetic mesh, with the
plan of sequential abdominal lavage and staged
closure. These patients may still benefit from
extubation between washouts. Deep venous
thrombosis should be prevented with sequential
compression stockings. A dedicated line for

parenteral nutrition should be maintained during
the intensive care unit stay, as the average time to
the achievement of complete enteral nutrition
after intestinal transplantation is 28 days.


Immune surveillance:

The initial assessment
of the intestinal

allograft for functional integrity
begins in the operating room with examination of
the mucosa for hemorrhage or edema, and for the
presence of contractions.
Serial
(visual
inspections as well as Doppler)

exam
inations of
the stoma provide useful informat
ion about the
vascularity of the graft and the early onset of
immune processes. The diagnosis of allograft
rejection is based on multiple parameters, the
three most important of which are the clinical
course, the endoscopic appearance of the
allograft, an
d the histology of biopsy specimens
(29,30).


Clinical changes that may indicate the onset
of a rejection episode are various and non
-
specific, so that clinical acumen and close
observation are critical. The ileostomy output
should be assessed for volum
e, color, consistency
and the presence of reducing substances, which
may be seen in malabsorption, bacterial
overgrowth or rejection. Stomal output in the
first week after transplantation is usually 1
-
2
liters/day for adults and 40
-
60 cc/kg/day for
childr
en, and this is usually clear or blood
-
tinged
in the first few days. If the patient is receiving
any form of enteral nutrition, the color may
change accordingly. Effluent that becomes
increasingly bloody and that is associated with a
cyanotic or congested

stoma is indicative of
possible rejection or allograft ischemia.
Increased stomal output is also a typical sign of
rejection, and this may involve a secretory
component of diarrhea. This will result in very
high outputs and require cc/cc fluid replaceme
nt
to avoid severe dehydration. Rejection may also
be associated with any or all of the following
symptoms: abdominal pain, cramping, decreased
stomal output and an obstructive picture. These
complaints should prompt radiologic evaluation
to rule out me
chanical obstruction and
endoscopic biopsy of the allograft, not immediate
operative intervention. Internal herniation of the
intestine can occur; obstruction should be dealt
with operatively if this situation is confirmed.
Mild fever and leukocytosis and

pronounced
bandemia are also often seen with intestinal
rejection. If the graft includes other organs,
appropriate serum markers for rejection of those
organs can be followed, but one must keep in

10

mind that about half of intestinal rejection
episodes occ
ur in isolation, even when the bowel
is transplanted with the liver. The amylase and
lipase should be followed for multi
-
visceral
allografts.


Liver chemistries are followed with liver
-
containing allografts. There is currently no
reliable serum marker f
or intestinal rejection.
Because of this, routine surveillance endoscopy
has become the standard and most reliable
method of diagnosing early intestinal rejection.
In the early post
-
operative period, the patient
should undergo endoscopy through the ileos
tomy
twice weekly, usually on Monday and Thursday.
The degree of sedation if any is judged on
individual basis
.

If the patient is to undergo re
-
operation, the endoscopy should be performed in
the operating room

prior to operation when
possible. This all
ows the operative plan to be
adjusted accordingly. The stomach is never the
site of severe rejection and should not be used as
the basis for judging allograft integrity. Further,
when the colon is included in the allograft, the
small intestine must be ex
amined as well, as the
colon is notoriously less often the site of rejection
and therefore unreliable if normal in appearance
(30). Finally, as the rejection process is often
patchy, the patient
should undergo endoscopy
from above and below

( rather then
through the
stoma if available)

if the diagnosis is suspected
highly but is not easily

confirmed. Isolated
jejunal rejection can and does occur in
approximately 10% of cases. Although it was
initially theorized that the ileum alone would be
reliable as an

indicator of rejection due to its
large lymphoid load, this has not proven to be the
case. After the patient is discharged, endoscopic
surveillance should be performed weekly on an
outpatient basis for the remainder of the first
three months. Thereafter
it may be employed
monthly for the remainder of the first post
-
transplant year.


Functional Studies:

Examination of the
functional integrity of the transplanted intestine
can also provide useful information and should be
done liberally in the early post
-
op
erative period.
The absorption of D
-
xylose serves as one
indicator of carbohydrate absorption (31). This
test may be performed weekly in the early post
-
transplant period, then as clinically indicated by
malabsorption after discharge from the hospital.
A
dequate absorption heralds the ability of the
transplanted intestine to provide nutrition. This is
usually evident within the first month after
transplantation. Failure of adequate absorption
after that time should prompt a search for
rejection or another
cause.



Fat malabsorption is nearly universal early
after transplantation and should be managed
pharmacologically, as with any other cause of
steatorrhea. However, significant amounts of
dietary fat may be present in the stool in the
absence of clinical
findings. Fecal fat excretion
and D
-
xylose absorption should be measured as
clinically indicated. The ability of the
transplanted intestine to adequately absorb
Prograf and maintain levels with only enteral
dosing also serves as an indicator of the integ
rity
of the graft.


Finally, radiologic exams can indicate
rejection even when they have been ordered for
other reasons. Slight mucosal edema is often
present when mild rejection occurs. Loss of
mucosal folds in intervening segments of
intestine which
appear tubulized is characteristic
of severe rejection. This appearance may exist
throughout the graft in the case of chronic
rejection and may coincide with pruning of the
distal arterial tree with chronic rejection.


Infectious Disease Prophylaxis:

Bloo
d
cultures should be sent automatically on the day
of transplantation, because of the frequency of
recurrent line sepsis and bacterial translocation in
these patients. Systemic antibiotics will be
written pre
-
transplant and should be continued
for at leas
t three days after transplant. These will
be according to protocol. Selective digestive
decontamination will be given, as mentioned
above, because of the recognized potential for
both bacterial and fungal translocation. All
patients should receive Bactrim

for prophylaxis
of
Pneumocystis carinii
, with one single
-
strength
tablet daily for adults and 5 mg/kg every
Monday, Wednesday and Friday for pediatric
patients

. Nystatin swish and swallow and vaginal
suppositories are used as for liver transplant
patient
s. Alternative for allergic patients will be
per protocol.


Prophylaxis of cytomegalovirus (CMV) will

11

consist of 2 weeks of I.V. ganciclovir, 5 mg/kg
twice daily. After the 2
-
week course of I.V.
ganciclovir, and in the absence of evidence of
active CMV d
isease, patients should be switched
to oral ganciclovir for the remainder of the first 3
months. The patient’s renal function must be
considered, and ganciclo
vir should be dosed
according to the creatinine level in those with
renal
insufficiency.
In all r
ecipients, intravenous
immune globulin as Cytogam 150 mg/kg weekly
should also be administered for 3 months (it looks
better her
e
)




The quantitative CMV PCR assay will also
be employed to allow preemptive therapy of
CMV disease. This should be ordered w
ithin 1
week of transplantation and then weekly for the
remainder of the in
-
hospital stay. After discharge,
the assay should be sent monthly for the
remainder of the first
year. Intravenous
ganciclovir at 10 mg/kg in divided doses twice
daily for 2 weeks s
hould again be given

for
positive CMV serology.
If

histologic evidence of
intestinal disease is present, clinical and
endoscopic findings should be considered before
discontinuing therapy. The CMV assay should be
negative before discontinuing therapy
. CM
V
enteritis has much more severe implications in
intestinal recipients than in other transplant
patients. Particularly in the population of
seronegative patients receiving seropositive
grafts, intractable or recurrent disease can limit
enteral intake and
lead to graft loss (32). These
patients will require an individualized approach
to treatment, and some in the past have continued
ganciclovir therapy weekly as an outpatient for an
entire first post
-
transplant year.


Prophylactic strategy against the
deve
lopment of lymphoproliferative disorder,
more common in these patients than in recipients
of other solid organs, will entail pre
-
emptive
therapy guided by serial measurement of Epstein
-
Barr virus DNA levels by quantitative
-
competitive PCR. This strategy w
ill be employed
for all pediatric patients and all EBV antibody
negative adult patients, those at high risk for the
complication. This should be performed first
within 1 week of transplantation, then weekly,
with the level of increase followed closely.
A
lthough the normal range for this value is wide
and not well established, the levels are rarely
above 40 genomes/10
5

peripheral blood
lymphocytes (PBL) for patients seronegative for
EBV antibody pre
-
transplant and 200
genomes/10
5

PBL for seropositive patie
nts.
Therefore, our protocol will utilize these levels as
the indication for pre
-
emptive treatment against
the virus in these two patient populations.
Ganciclovir treatment, with the same dosing as
for CMV, will be employed, and Cytogam will be
given wee
kly in each case. The quantitative
DNA level will then be followed weekly to
monitor the success of treatment. Endoscopy
should be performed at the time of initiation of
treatment to attempt to correlate an early
histological diagnosis with viral levels.

Immunosuppression should be decreased in each
case as allograft acceptance permits, based on the
patient’s clinical course. The duration of therapy
will depend on the clinical course of the patient
and may depend on input from the infecious
disease or
hematology consultants in selected
instances. These consults should also be obtained
by the operating surgical team. If
immunosuppression cannot be lowered due to
recurrent rejection, the monoclonal anti CD
-
20
antibody Rituximab should be considered.


Fin
ally, a note about other pathogens
involved in transplantation of the intestine.
Viruses that usually cause a mild gastroenteritis
may produce severe malabsorption and illness in
the transplanted intestine, and caution should be
used in making a diagnosis

when malabsorption
or signs of sepsis appear. Adult patients have
suffered severe gastroenteritis from adenovirus
and herpesviruses. Pediatric patients have
experienced severe enteritides from both common
agents such as rotavirus and
C. difficile
, as wel
l
as less common agents such as parvovirus,
adenovirus and enterovirus. If fever is present
without a known cause, then workup should
include urinalysis, nasopharyngeal swabs and
buffy coat for viral pathogens. The timing of
fever after transplantation wi
ll help in the
diagnosis; after the first few weeks, CMV
becomes a more common cause of fever. Stool
evaluation for rotavirus and
C. difficile

should be
performed on patients with diarrhea. Parvovirus
should be suspected in patients with anemia,
fever an
d a low reticulocyte count, and serum
titers may be checked. Cryptococcal antigen can

12

also be checked in these patients.


Nutritional Management:
Patients should
be continued on total parenteral nutrition in the
early postoperative period. The formula

will be
managed by the nutrition support team and
should follow the tube feeding protocol for
pediatric patients. Adults will begin tube feedings
of ½ strength Vivonex per our nutritional support
service. Tube feeding orders should be decided
on daily rou
nds by the transplant team or
transplant nutrition coordinator. The function of
the intestinal allograft is assessed daily,
beginning in the operating room at the time of
transplantation. Preservation injury or a positive
cytotoxic crossmatch may result i
n edema and
congestion of the allograft mucosa in the first few
days after transplantation. Further, the migrating
motor complex and ordered motility are disrupted
due to denerva
tion of the graft; these functions
return at variable times after transplant
ation.
Even when the allograft appears grossly normal,
the histology taken at the time of transplantation
may reveal severe mucosal disruption that would
cause malabsorption. These factors conspire to
produce a state of malabsorption in the early post
-
op
erative period. Once both the histologic and
gross appearance of the allograft confirm mucosal
integrity, the patient may be transitioned to an
enteral diet. This should also be started in the
setting of fairly stable levels of stomal output. A
rapid in
crease in the daily level of stomal output
often heralds rejection and should prompt another
endoscopic and histologic attempt to confirm and
treat this event prior to beginning enteral
formulas. This decision should be made by the
transplant surgeon afte
r confirmation of the
integrity of the enteral anastomoses by barium
study.


Tube feedings are initially begun as a
dipeptide
-
based isotonic or hypotonic formula in
small volumes. The pediatric patients should
receive Vivonex plus diluted to ½ strength
at 1
-
2
cc/hr and then increased, still in this
concentration, slowly over a few days. This will
provide increasing amounts of the fluid
requirements in the tube feedings and aid in
discontinuing the parenteral nutrition. Once the
patient is tolerating tub
e feedings, the
concentration can be increased to full strength.
Never increase both the rate and concentration
concomitantly. Patients less than 1 year of age
should receive feeding according to protocol, at
the discretion of the pediatric gastroenterol
o
-
gists. If feedings are being given through a
jejunostomy tube, gastric residual volumes should
not be checked. Adults should receive Alitraq or
another elemental or semi
-
elemental formula,
again given in diluted form with the rate first
increased, and t
hen the concentration increased.
The nutrition support service will mix enteral
glutamine into the adult tube feedings to provide
approximately 30 g/day, the dose that has been
shown to be efficacious for bowel rehabilitation.
Parenteral nutrition can be
tapered and
discontinued when absorption is good, as
demonstrated with D
-
xylose measurements, and
evidence suggests that the patient is meeting the
estimated caloric and protein needs. Intravenous
fluids may still be required until free water can be
given

via the tube to compensate for losses.
These elemental feedings can later be modified as
tolerated to provide increased caloric or protein
needs as guided by nutritional support
recommendations. Usually, patients will need
lactose diets initially.


Ora
l diets can be started early after the
initiation of tube feedings and the tube feedings
used to supplement the oral intake. Pediatric
patients often will not feed by mouth adequately
to maintain their nutrition, whereas adults will
adjust much more quick
ly. Fluid and electrolyte
losses can be replaced orally late in the hospital
and post
-
hospital course with supplements such
as Pedialyte and Gatorade.


Other Issues:

The early post
-
operative
period may be marked by the development of
sepsis, and positive

cultures are often obtained
from the abdominal drain fluid. These cultures
usually grow gram
-
negative organisms and
require antibiotic treatment. This is usually from
lymphatic leakage from the graft and
translocation of bacteria. If there is no adequat
e
response to antibiotic treatment, the patient will
require exploration and washout. Large
-
volume
lymphatic leakage or chylous ascites may
necessitate intravenous replacement to avoid
volume depletion, and some of this replacement
fluid should be in the
form of colloid. After this
initial period, the most common problems relate
to high stomal output due to disordered motility

13

and malabsorption.



Management of high stomal output in the
absence of rejection will depend on studies of
absorption, fecal fat

content, motility and transit
time. Watery diarrhea will often respond initially
to loperamide. Paragoric and pectin can be added
to the enteral intake, but pectin should not be
placed through a jejunostomy tube. Tincture of
opium is effective if there
is rapid transit.
Further, the addition of an alpha
-
adrenergic agent
may improve intestinal motility due to an effect
of the efferent reflex arc. Fat malabsorption and
steatorrhea may be improved by pancrease in
patients who have had TPN
-
related pancreat
itis
and did not receive a pancreas with the allograft.
Finally, cholestyramine may decrease choleretic
diarrhea in patients with no ileocecal valve and
bile salt malabsorption. These problems are at
times difficult to delineate, and the evaluation for
suc
h etiologies of diarrhea, in the absence of
evidence of rejection, should be thorough.
Bacterial overgrowth should also be considered,
and hydrogen breath testing may be indicated in
conjunction with quantitative stool cultures,
which should be sent on al
l such patients. If an
isolate in excess of 10
6

is found, then systemic
antibiotic treatment may eliminate the problem
and is not uncommonly required. Serum folate
levels may be helpful. Such problems should
always be pursued in joint effort by both the
surgeon and gastroenterologist after obligatory
endoscopy and biopsy have ruled out rejection.

Late problems with absorption that are less
common should also be assumed to be rejection
until proven otherwise. However, eosinophilic
gastroenteritis is not u
ncommon in these patients.
Food allergies can be sought and the process
treated with augmented steroids, as with non
-
transplant patients. However, RAST and skin
testing will often reveal allergies to such a wide
variety of foods that dietary restrictions a
re
impractical. Vitamin B12 deficiency may arise
when reduced intestinal allografts are taken from
adult donors for children, or when the abdomen
will not close without distal intestinal resection.
Various other vitamin and trace element
deficiencies may

arise depending on the
functional state of the graft and the enteral
nutrition taken by the patient. The long
-
term
management of these patients will evolve, with an
individualized approach to each recipient
.

References


1.


Lillehei RC, Goott B, Miller F
A. The physiological response ofthe small bowel of the dog to ischemia
including prolonged in vitro preservation of the bowel with successful replacement and survival. Ann Surg
1959;150:543
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560.

2.


Lillehei RC, Goott B, Miller FA. Homografts of the sma
ll bowel. Surg Forum 1959; 10:197
-
199.

3.


Starzl TE, Kaupp HA Jr., Brock DR, et al. Homotransplantation of multiple visceral organs. Am J Surg
1962;103:219
-
229.

4.


Dudrick SJ, Wilmore DW, Vars HM, Rhoads JE. Long
-
term parenteral nutrition with growth,

development
and positive nitrogen balance. Surgery 1968; 64:134
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142.

5.


Haymond HE. Massive resection of the small intestine. Surg Gynecol Obstet 1935;61:693
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705.

6.


Howard L, Ament M, Fleming R, et al. Current use and clinical outcome of home paren
teral nutrition
therapies in the United States. Gastro 1995;109:355
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365.

7.


Grant D, Wall W, MimeaultR, et al. Successful small
-
bowel/liver transplantation. Lancet 1990;335:181.

8.

Starzl TE, Rowe MI, Todo S, et al. Transplantation of multiple abdomi
nal viscera. JAMA 1989; 261:1449.

9.

Murase N, Demetris AJ, Matsuzaki T, et al. Long survival in rats after multivisceral versus isolated small
-
bowel allotransplantation under FK
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506. Surgery 1990;110:87
-
97.

10.

OASIS, Home Nutritional Support Patient

Registry. Annual Report, 1989 Data. The Oley Foundation,
Albany, New York, and A.S.P.E.N., Silver Spring, Md.

11.

Van Gossum A. Preliminary results of the European survey of home parenteral nutrition. Presented to the
Europeal Society for Parenteral

and Enteral Nutrition XVI Congress. Birmingham, England, September 1,
1994.


14

12.

Whitington PF. Cholestasis associated with total parenteral nutrition in infants. Hepatology 1985; 5:693
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696.

13.

Cooper A, Floyd TF, Ross AJ, et al. Morbidity and mio
rtality of short
-
bowel syndrome aquired in infancy:
an update. J Ped Surg 1984;19:711
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718.

14.

Todo S, Tzakis AG, Abu
-
Elmagd K, et al. Intestinal transplantation in composite visceral grafts or alone.
Ann Surg 1992; 216:223
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234.

15.

Haubrick WS. Gr
oss anatomy of the small intestine. In Berk JE, editor. Gastroenterology. Philadelphia:
WB Saunders, 1985:1475
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1478.

16.

Gouttebel MC, Aubert BS, Colette C, et al. Intestinal adaptation in patients with the short bowel syndrome.
Dig Dis Sci 1989;34:
709
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715.

17.

Carbonnel F et al. The role of anatomical factors in the nutritional autonomy after extensive bowel
resection. JPEN 1996;20:275
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280.

18.

Wilmore DW. Factors correlating with a successful outcome following extensive intestinal resection

in
newborn infants. J Pediatr 1972; 80:88
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95.

19.

Goulet OJ, Revillon Y, Jan D, et al. Neonatal short bowel syndrome. J Pediatr 1991;119:18
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23.

20.

Grosfield JL, Rescorla FJ, West KW. Short bowel syndrome in infancy and childhood: Analysis of surv
ival
in 60 patients. Am J Surg 1986; 151:41
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21.

Sudan DL, Kaufman SS, Fox IJ, et al. Intestinal transplantation at the University of Nebraska Medical
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August 1997

22.

Starzl TE, Todo S, Tzakis A, et al. The many faces of multivisceral transplantation.
Surg Gynecol Obstet
1991; 172:335
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344.

23.

Casavilla A, Selby R, Abu
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Elmagd, et al.
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24.

Tzakis AG, Todo S, Reyes J, et al. Piggyback orthotopic intestinal transplantation. Surg Gynecol Obstet
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25.

Shaffer D, Diflo T, Love W, et al. Immunologic and metabolic effects of caval v
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Sindhi R, Fox IJ, Hefron T, et al. Procurement and preparation of human isolated small intestinal grafts for
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T
odo S, Reyes J, Furukawa H, et al. Outcome analysis if 71 intestinal transplantations. Ann Surg 1995;
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28.


Diflo T, Schaffer D, DeMichele SJ, et al. Prevention of graft versus host disease with preservation of
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Garau P, Orenstein SR, Neigut DA, et al. Role of endoscopy following small intestinal transplantation in
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1014.





15



INITIA
L P
RE
-

OPERATIVE
TRANSPLANT
ORDERS


Date/Time:

1.

Admit
to

Dr. Thomas
M.
Fishbein

or Dr. Cal

Matsumoto

2.

Diagnosis: Liver Failure / Intestinal Failure (Circle applicable)

3.

Condition:

4.

Vitals: q 2 hours

5.

PEDIATRIC:
Obtain and chart recipient height

______cm
, weight (without diaper
or stoma bag if applicable; ______ kg), and head circumference

______

(
for infants)

6.

Ascertain donor weight from Dr. Fishbein
/Dr. Matsumoto
: ______ kg

7.

Activity: ad lib

8.

Document a
llergies:

9.

Diet: NPO

10.

Strict
intake and output

11.

Normal saline enemas
,
10 mL/kg

(MAXIMUM 250 mL)
, repeat
ed

until clear

12.

I
ntravenous fluid
:
DC TPN and sta
rt

D5 ½ NS at
standard maintenance for size/age
=
_____________

(
MAXIMUM

100 mL/hour
)


13.

Medications to be ordered in ICU based on
RECIPIENT WEIGHT

and sent with
patient to OR:



Unasyn 75 mg/kg (max 3 gm) = _______ IV STAT



Fluconazole 10mg/kg (max 400mg) =

_______IV STAT



Ganciclovir 5 mg/kg (max 300 mg) = _______IV STAT



(Unasyn, Fluconazole, and Ganciclovir may be administered in ICU if time
permits.)



S
elective digestive decontamination

(SDD)
suspension (gentamicin 80mg,
polymyxin B 100mg, nystatin 10
mL)

1 mL/kg (
MAXIMUM

30 mL
) either

PO,
NG, or G
-
tube STAT



Basiliximab 10 mg
if

< 35 kg
and

20 mg

if


35 kg IV

=
______ mg X two (2)

unit
doses

14.

Medications to be ordered in PICU to be picked
-
up by donor surgeon or designee
and
ADMINISTERED IN THE
DONOR OPE
RATING ROOM



Thymoglobulin 1.5 mg/kg (based on DONOR WEIGHT) IV: _______ with
extra vial (25mg)



???? SDD



??? methylprednisone

15.

Lab tests:



Type and Cross; CIRCLE:

[ ] Isolated intestinal transplant: 5 units of washed PRBC or fresh PRBC


< 5 days old
for children
<

5 years of age and 5 units of FFP
STAT

[ ] Liver/intestinal transplant: 5 units of washed PRBC or fresh PRBC <


5 days old for children
<

5 years of age, 5 units of FFP and 5 units of
platelets



All blood products

must be

CMV ne
gative, leuko
-
depleted, and irradiated


16



Chem 18, GGT, amylase, lipase, triglycerides, cholesterol
STAT



CBC with manual differential
STAT



PT/PTT
STAT



Blood culture from TPN line



3
mL

blood in red top tube to HLA lab for lymphocytoxic crossmatch



If not obtain
ed in previous 30 days
:

o

Varicella antibody, IgG

o

CMV antibody, IgG and IgM

o

HIV antibody

o

EBV capsid antibody, IgG, and IgM

o

HAV antibody, total

o

HBsA
g,

HBc
Ab
-
total, HBs antibody

o

HCV

antibody

o

Toxoplasma
antibody,
IgG
only

o

Beta HCG (
post
-
pubertal
females)

16.

Urinal
ysis STAT, urine culture, urine CMV culture

17.

Chest x
-
ray

18.

Notify Dr. Fishbein
/Dr. Matsumoto

if:



Temperature > 38
o

C, axillary



Serum potassium
>

5.0 or
<

2.9 mEq/L



Hemoglobin
<

8.0 g/dL

(
All blood products CMV neg
ative
, leuko
-
depleted,
and irradiated
)



Serum c
alcium
<

8.0 mEq/L



Abnormal
c
hest
x
-
ray





















17




INITIA
L P
OST
-

OPERATIVE
TRANSPLANT
ORDERS


Date/Time:

1.

Admit

to

Dr.
Thomas M. Fishbein
/ Dr. Cal Matsumoto

2.

Condition critical

3.

Diet: NPO

4.

Vital Signs: per ICU routine,

document

CVP q 1hr

5.

Document
a
llergies:

6.

Activity: Bedrest; HOB 30 degrees, turn Q2H when stable

7.

Daily weight (
SAME DAY AS CHARTED
)

8.

Neurochecks Q 1 hr

9.

Glucose monitoring q 4 hr

(and document)

for 24 hr then q 12 for 24 hr

10.

Strict
intake and output
;
s
pecif
y

NG
/OG
, gastrostomy, jejunost
omy, ileostomy, urine, J
-
P drain
(s)



J
-
P drain
(
s
)

to self suction; empty & record Q 4 hrs



Foley to bedside
gravity
bag



NG/OG tube

(sump)

to low continuous suction



Gastrostomy tube (GT) to gravity Foley bag



J
ejunostomy
tube

(JT)

to gravity
F
oley bag



C
lamp al
l upper GI tubes, including jejunostomy tube after doses of
tacrol
imus and sirolimus for one hour

12.

Gastric pH q 6 hr (if pH < 5.0, notify MD to adjust med)

13.

Sterile dressing changes to tube, drain, and catheter sites daily

14.

Abdominal wound dressing change dai
ly

15.

Daily

central line site care; tubing changes Q 48 hrs

16.

Ventilator settings:


Mode: IMV: /min It: secs TV: cc


PIP/PEEP/PS ___/___/___

17.

I.V. fluids:



D5___NS (<10 kg =
¼
NS; >10 kg =

½
NS) at _____
mL/hr (maintenance)

(NOTE: A
djust based on ongoing
BP,CVP,
renal, GI, and other losses
)



Arterial line:
½
NS with 1 unit/cc heparin at 2cc/hr (
<

10kg), no heparin for
pts > 10 kg

18.

Chest X
-
Ray (AP) on arrival to ICU and daily AM STAT w
hile intub
ated

19.

Duplex ultrasound on POD #1 (for pts who also receive liver transplant)
; early AM


notify
radiology reside
nt night before

20.

Doppler of ileal stoma q 1 h
our

x 24 hr, q 2 h
ours

x 24h
r
, q 4 h
ours

x 24 h
r
, then q shift

21.

Laboratory:



On admission
: CBC with m
anual diff, PT/PTT, fibrinogen, chem
-
18,
direct
bilirubin,
GGT, amylase, lipase, ammonia (if also liver transplant), LDH,
ABG
, blood culture
from

TPN line (or other central line if not available)


18



Post
-
op day # 0 and post
-
op day #1
,

q 4 hours
: CBC with man
ual diff,
PT/PTT, fibrinogen, ABG, chem
-
18,
direct bilirubin,
GGT, amylase, lipase,
ammonia (if also liver transplant)



Post
-
op days #2


#4,

q 12 hours
: CBC with manual diff, PT/PTT,
fibrinogen,
chem.
-
18
,
direct bilirubin,
GGT, amylase, lipase, ammonia (if

also liver transplant)



Prograf trough level

(½ hour before AM dose) q AM beginning POD #1



Every Monday: Transplant EBV PCR (Order under “T”), transplant CMV
PCR (Order under “T”), and adenovirus PCR, triglyceride, cholesterol, and
iron, and IBC level

22.

Tran
sfusion criteria, routine



Packed RBC’s: maintain hematocrit between 25
-
35% (ideal = 30%)



Platelets: at direction of Dr. Fishbein
/ Dr. Matsumoto



Fresh frozen plasma: at direction of Dr. Fishbein
/ Dr. Matsumoto


All
b
lood
p
roducts should be CMV
neg
ative
, leuko
-
depleted, and



irradiated

23.

Anti
-
microbial m
edication



Unasyn
®

___ mg (75mg/kg/dose, max 3 g) IV q 6hours. If pre
-
transplant
infection history indicates high
-
risk of colonization with resistant flora, then
discuss
alternate

choice with Transplant Team.



Fluconazole (Diflucan
®
) ___mg (5mg/kg/day, max 200mg) IV q 24hours.
Discontinue if 1
st

intestinal allograft biopsy is normal. If pre
-
transplant
infection history indicates high
-
risk of colonization with resistant flora, the
n
discuss
alternate
choice with Transplant Team.



SDD (gentamicin 80 mg, polymyxin B 100 mg, nystatin 10 ml), 1 ml/kg
(MAXIMUM 30 mL) = ______ mL per GT q 6hours while NPO



Nystatin ____ml rinse PO or GT q 6 hours (5ml < 10 yrs, 10 ml>10 yrs);
start once SDD

is discontinued



Pentamidine (NebuPent
®
) ___mg (4mg/kg) IV q month, 1
st

dose on POD #1



Ganciclovir ____ mg (5mg/kg/dose, max 300 mg) IV q 12 hours x 14 days



Cytomegalovirus Immune Globulin (Cytogam
®
) ___mg (150mg/kg) IV

on
POD #1,

then q weekly until POD
#30, and then biweekly from POD #31 to
POD #90
. Available as 2.5 gm/
50 ml vial, no need to dilute.


24.

Immunosuppression Medication



Methylprednisolone (Solu
-
Medrol
®
)

o

___mg (10 mg/kg/dose, max 200mg) IV q AM POD #1

o

___mg (8 mg/kg/dose, max 160mg) IV q AM POD
#2

o


___mg (6 mg/kg/dose, max 120mg) IV q AM POD #3

o


___mg (4 mg/kg/dose, max 80mg) IV q AM POD #4

o


___mg (2 mg/kg/dose, max 40mg) IV q AM POD #5

o


___mg (1 mg/kg/dose, max 20 mg) IV or PO q AM POD #6
-
30



Basiliximab (Simulect
®
) ___mg (<35 kg, 10mg; >35kg, 2
0mg) POD #4
ONLY


19



Tacrolimus (Prograf
®
) liquid, 1 mg/ml, ___mg (0.15mg/kg/dose,
MAXIMUM initial 5 mg) per jejunostomy tube q
8

hours at 5:00 AM
, 1:00
PM,
and
9
:00 PM. Clamp NG, G
-
T,
and

J
-
tube for 1 hour after each dose.

25.

Pain medication



Fentanyl ____ microg
rams q ___hours IV PRN. Start at 1

microgram
/kg/dose (MAXIMUM 25 micrograms) q 1
-
2 hours PRN. If requiring
repeated hourly dosing, consider continuous IV infusion @ ___

micrograms/hour; initial = 1

microgram/kg/hour, MAXIMUM 25
micrograms)



Midazolam (
Ve
rsed
®
)

___

milligrams q __hour
s

IV PRN. Start at 0.1
milligram/kg/dose (MAXIMUM 2 milligrams) q 1

2 hours. If requiring
repeated hourly dosing, consider continuous infusion Versed
®

___

milligrams/hr; initial = 0.1 milligrams /kg/hour,

MAXIMUM 2 milligram
s.

26.

Miscellaneous medications



Prevacid
®

____mg

(1 mg/kg/dose, max 30 mg) IV q 12 hour; adjust

dose to
keep gastric pH ≥
5
. Switch to PO or per gastrostomy tube when patient
tolerating diet



Aspirin __mg (<30 kg = 40

mg
,


30 kg = 81 mg) PO q day (not routinely
given if patient
receiving

heparin or dextran)



Heparin drip __units/hr (10 units/kg/hr)

when requested by Transplant
T
eam
(start when INR <2). No boluses should be given. Check PTT every 6 hrs
and increase drip by 5 units/kg/h
ou
r to goal
=

PTT 55
-
60 seconds. If PTT >
80, stop heparin and recheck PTT every 4 hours until in goal range and
r
estart at ½ prior rate. Duration is 3


5 days.



Stomatitis/Mouth Ulcers: “Magic Mouthwash”


1:1:1 solution of
Benadryl/Lidocaine/Maalox
:
apply to affected areas prn pain.

27.

Notify Resident if:



Temp > 38° C



Urine Output < 0.5
mL
/kg/hr over 2 hrs or < 30
mL
/hr for pts
>

60 kg



MAP > ___or < ___, SBP >___or <___, DBP >___ or <___



Pulse > 160 or < 80



CVP > ___or <___

28.

Notify Dr. Fishbein
/Dr. Matsumoto

if:



Change in color of J
-
P drain output



Change in color of stoma

or Doppler signal



Vasopressor therapy contempla
ted



Greater than 3% change in hematocrit



Platelet count less than 30,000

(
to determine transfusion guidelines
)



PT
≥ 20 seconds

(
to determine transfusion guidelines
)








20



CENTRAL VENOUS LINE CARE FOR ALL INTESTINAL

TRANSPLANT PATIENTS



PREFACE:

There is a high rate of bacterial and fungal infection and limited venous access sites in
intestinal transplant candidates

and recipients. Strict adherence to sterile technique reduces
the risk of infection and is therefore essential. The updated hospital protocol is herein
reprinted in order to emphasize this point.


PROCEDURES:

I.

Administration of Medications t
hrough a M
edication (Luer Lock®)
Port

Gather Supplies:

3
-
9 alcohol swabs

Medication to administer/necessary NS Flushes

Frequency: PRN medication administration

Procedure

1.

Wash hands with approved antimicrobial soap, running water, and friction for 10
-
15
seconds. Dry

thoroughly. Don clean gloves.

2.

Visually inspect the cap for signs of cracks, leaking, or poor integrity.

3.

Using the first of three consecutive alcohol swabs, vigorously scrub all areas of the catheter
Luer Lock® cap for a full 15 seconds. Repeat with each
successive alcohol swab, until you
have used all three.

4.

Allow to dry completely (takes approximately 15
-
30 seconds).

5.

Flush line with 10 cc normal saline flush if appropriate.

6.

Repeat steps 2
-
4.

Attach appropriate medication syringe to Luer Lock® port. Adm
inister
medication according to manufacturer recommendations.

7.

Repeat steps 2
-
4 prior to

attaching final saline flush syringe, if needed.

Note: Do not run blood products through medica
tion ports or Luer Lock®

caps. Blood products should
infuse directly int
o central line ports (hub
-
to
-
hub). See Below.

II. Administration of Blood Products Directly Through a Central Line

Gather Supplies:

3 alcohol swabs

Blood product ready to infuse with appropriate tubing attached

Sterile gloves

1 package 4x4 gauze

Mask

if y
ou have URI Symptoms

Procedure

1.

Wash hands with approved antimicrobial soap, running water, and friction for 10
-
15
seconds. Dry thoroughly.

2.

Open sterile gloves. Make a sterile field out of the sterile glove package and open the 4x4s
onto this field. Open 3
alcohol swabs onto the 4x4s. Don sterile gloves. Hold the Catheter
with your non
-
dominant hand.

3.

With your other hand, unfold the first alcohol swab and vigorously scrub the area where the

21

cap and the catheter hub meet for a full 15 seconds. Repeat.

4.

With t
his second alcohol swab, remove the Luer Lock® cap and discard.

5.

With the third alcohol swab, clean the grooves of central line hub vigorously, being careful
no to touch the grooves themselves with anything but the alcohol swab. Maintain the
sterility of yo
ur dominant hand at all times.

6.

Attach ordered blood product via appropriate tubing and tape to secure. Infuse as ordered.
See GUH Policy No. 107, “Blood Product Administration”

7.

When blood product has completely infused, remove the tubing by using this sam
e
procedure (i.e., use alcohol swab scrub x 2 > groove clean > saline flush > second alcohol
swab scrub> groove clean. Maintain sterility at all times.
Use sterile gloves at all times
when entering a line.

8.

Place new Luer Lock® cap.

9.

Flush line with 10 cc o
f normal saline, using a turbulent flush technique
.

10.

Flush with heparin flush (see below) or reattach IV tubing to resume infusion.


III.

Heparin Flush

Gather supplies:

Clean gloves of appropriate size

Appropriate Heparin amount for line type

3 alcohol swab
s

Procedure

The port must
at all times

be accessed according to the guidelines described under Section
I. Administration of Medications Through a Medication (Luer Lock®) Port

1.

The catheter must be flushed using the SASH (saline, administration, saline, hepa
rin)
method, as described below, when administering medications, or blood products during
withdrawal of blood for laboratory testing, and every 12 hours when not in use.

2.

Wash hands with approved antimicrobial soap, running water, and friction for 10
-
15
sec
onds. Dry thoroughly.

3.

Don clean gloves.

4.

Flush catheter with 10cc normal saline (NS), using a turbulent flush technique (push
-
stop
-
push
-
stop, and so forth).

5.

Never use less than a 5cc syringe for accessing a central venous catheter.

6.

Administer medication.

7.

Fl
ush with 10cc normal saline, again using a turbulent flush technique.

8.

Follow with 3cc of Heparin flush solution of 10 units/cc, unless otherwise specified by the
catheter manufacturer.

9.

Maintain positive pressure when flushing and clamping to prevent back
flow of blood
and
clotting of the catheter.


IV. Obtain

Blood for Laboratory Testing

Gather supplies:

Clean Gloves of appropriate size

1 or 2 sterile red cap(s)

depending on the number of IV lines you wish to maintain sterile

4x4 gauze pad to use as a sma
ll sterile field (if needed)

6
-
9 alcohol pads

Appropriately labeled lab tubes

Assembled double stopcock (sterile)
-
NO Vacutainers


Yellow Vacutainer Transfer device

Procedure

1.

Wash hands with approved antimicrobial soap,

running water, and friction
for 10
-
15
seconds. Dry thoroughly.


22

2.

Don clean gloves.


3.

Stop all IV infusions in all ports and turn off infusion

pumps.

4.

Unhook IV tubing from the Central Venous Line port Luer Lock® cap
most
proximal

to
patient
,
but do not remove the cap
.

Check the date on the IV

tubing: does the tubing need
to be changed? If so, gather supplies to han
g

new IV tubing at the end of this procedure.
(See Appendix II for CDC recommendations for line changes):

To Unhook IV Tubing
: Use one alcohol swab at IV connection site; scrub vigoro
usly for
15 seconds. Repeat with second alcohol swab. Untwist IV tubing from Luer Lock® cap and
attach red “dead
-
ender cap,” maintaining sterility at all times.
Pause or turn off all IV
infusions during procedure.

5.

Visually inspect the Luer Lock® cap for si
gns of cracks, leaking, or poor integrity. Evaluate
whether or not it is time to

change the cap. If so, prepare

to change the cap
prior

to
obtaining your lab specimen (see procedure below).

6.

Using the first of three consecutive alcohol

swabs, vigorously scr
ub all areas
of the catheter
Luer Lock® cap for a full 15 seconds. Repeat with each successive alcohol swab, until you
have used all three.

7.

Allow to dry completely (takes approximately 15
-
30 seconds).

8.

Attach the double stopcock to the Luer Lock®

cap, mai
ntaining the sterility
of your double
stopcock end and the asepsi
s of your alcohol
-
prepared Luer Lo
ck cap. Twist until secure.

When secured, open stopcock to the syringe #1 (the one most proximal to the patient) and
aspirate 5cc.

NOTE:
This blood is alway
s given back to the patient except when a patient is
newly
febrile

(
Rationale
: in the newly febrile patient, there is the possibility that the line is
colonized, and that giving back the initial “waste” volume is not recommended
-
this sample
should be colle
cted and sent to the lab as a culture).



9.

Close stopcock to filled syringe#1 and open stopcock to syringe #2.

10.

Withdraw desired quantity of blood based on the labs you need to draw.
Remember there
should be
NO VACUTAINER

IN THIS SLOT.


Please N
ote:
For collection of Blood Cultures, please use the following guidelines:


For infants
-
2years: 3 ml/per bottle

For children 2
-
12 years: 4 ml/per bottle

For children 12 years & over: 5 ml/per bottle

The discard (blood from syringe #1
-
most proximal to the
patient) is NOT to be utilized for
specimen collection for blood cultures (except as noted in #7 above).

11.

The appropriate order of placement of culture samples in culture tubes is: (anaerobic) >
(aerobic) > (fungal).

12.

Culture tube tops should be prepped vig
orously with alcohol swabs for 15 seconds prior to
transfer of samples.

13.

Close the stopcock to this syri
nge when you have withdrawn the

necessary amount of blood
for your specimen sample(s).

14.

Open the stopcock to syringe #1 and return the blood from syringe
#1
(see #7 to be sure
this is an appropriate action)
to the patient,
unless more than 60 seconds has elapsed
during the time it took to obtain the specimen

15.

Flush line with 10cc normal saline from
syringe #3 using a continuous
“turbulent flush”
technique (p
ush
-
stop
-
p
ush
-
stop
-
and so forth) to clear
the line of all blood.

16.

Remove stopcock.
Scrub the cath
eter port vigorously with three

alcohol swabs, repeating
steps 4 and 6 above. Then:



Flush catheter with 3 ml of heparinized saline (10 U/ml) if the line will no

longer be
infusing fluids after your specimen collection.
Document the date, time, and
indicate the port that you heparinized the catheter

on the patient Medication
Administration Record. OR


23



If the line will continue to infuse, reattach the IV tubing, mai
ntaining the sterility of
the tubing end. Tape the connections at each leur lock site.

17.

Label any new tubing that you have initiated

with date, time, and

initials, and document on
the Patient Daily Flow

Sheet that you have
changed IV Tubing. If caps were c
han
ged,
document this on the Flow
sheet as well. Be sure to include the date and time.

V. Changing the Cap

Gather supplies:

Sterile gloves of the appropriate size

New CLC2000 (PICC Line) or blue Clave cap

1 4x4 gauze pad

3 alcohol swabs

1 red cap (“dead
ender”) if the port you will change is infusing fluids

Frequency: Every 72 hours and whenever cracked, leaking, or unable to clear cap of blood or precipitate


Procedure

1.

Wash hands with approved antimicrobial soap, running water, and friction for 10
-
15
sec
onds. Dry thoroughly.

2.

Open the sterile gloves and create a sterile field. Open the gauze and the new CLC2000 or
Clave cap onto this sterile field. Open the 3 alcohol swabs and place them onto the 4x4
gauze on this sterile field.

3.

Unhook IV tubing from the

Central Venous Line port Luer Lock® cap
most proximal

to
patient
. Check the date on the IV tubing: does the tubing need to be changed? If so, gather
supplies to hang new IV tubing at the end of this procedure.

To Unhook IV Tubing
: Use one alcohol swab at

IV connection site; scrub vigorously for
15 seconds. Repeat with second alcohol swab. Untwist IV tubing from Luer Lock® cap and
attach red “dead
-
ender cap,” maintaining sterility at all times.
Pause or turn off all IV
infusions during procedure.

4.

Don steri
le gloves.

5.

With your non
-
dominant hand, hold the catheter. With your other hand,

unfold the first
alcohol swab and vigorously scrub the area where the cap and the catheter hub meet for a
full 15 seconds. Repeat.

this with

second alcohol swab, remove the

Luer Lock® cap and discard.

6.

With the third alcohol swab, clean the grooves of central line hub vigorously, being careful
not to touch the grooves themselves with anything but the alcohol swab. Maintain the
sterility of your dominant hand at all times.

7.

Pl
ace a new Luer Lock® cap on central line. Maintain sterility of line.

8.

Reattach IV tubing, maintaining sterility of IV tubing end or flush with heparin, using 3
-
alcohol swab technique to access port (see procedure under section I).

9.

Repeat process for each
port cap change.


VI. Dressing Change

Gather Supplies:

Chlorhexidine gluconate (CHG) swab stick (one)

One package povidone
-
iodine swab sticks for infants two months or less

One package alcohol swabsticks

4x4 Gauze

Tegaderm® or gauze sterile occlusive

Ste
rile gloves of an appropriate size

Mask (if patient line is less than one week old or if you have URI)

Seri
-
strips (if catheter is unsutured)

Frequency: Tegaderm® dressings will be changed once a week on Thursday, or when soiled, loose, damp, or with

24

drain
age as needed. Gauze sterile occlusive dressings will be changed 3x a week and will be documented on the
patient Kardex on an individualized basis.



Procedure

1.

Wash hands with approved antimicrobial soap, running water, and friction for 10
-
15

seconds. Dry
thoroughly.

2.

Don
clean gloves.

3.

Mask self
if line is less than one week old

and have patient turn head away from insertion
site. Have a helper assist a younger child to sit, lay, or be held, so that the head is turned
away from the line site.

Prior to remov
ing the dressing, assess the site for tenderness by
gently pressing on the site. Carefully remove old dressing in the direction the catheter was
inserted and discard in hazardous waste bag. If catheter is not sutured, secure the catheter
while removing th
e dressing. Determine if there is any drainage and what type of dressing is
appropriate for today (clear
-
no drainage or gauze sterile occlusive if there is any drainage).
Remove gloves and discard with dressing.

4.

Using sterile technique, open sterile glove
s and other supplies onto sterile field, maintaining
the sterility of products.

5.

Don sterile gloves.

6.

Assess the site for old crusted drainage or exudates. If there is any present, determine the
need for a site culture with the physician, and then use the a
lcohol swabsticks to remove this
from the site completely.

7.

Crack the swab and shake down the fluid. Clean the insertion site with chlorhexidine
gluconate (CHG) swab stick by scrubbing with gentle motion. Be sure to cover the area that
will be covered by t
he occlusive dressing. There is no need for concentric circles. Clean the
catheter length itself, beginning at the insertion site and working down the catheter about
three inches.

NOTE: If the patient is 2 months old or less, use povidone
-
iodine in the fo
llowing
fashion:



Using the first of three alcohol swabs, begin at the insertion site. Clean the site by
applying the povidone
-
iodine in concentric circles moving from the insertion site
outward until you have cleaned an area approximately 2
-
inches in diame
ter.



Repeat this process with the second swab, beginning at the insertion site and
working your way outward over the same area.



Use the third swab to clean the catheter itself, beginning at the insertion site, and
moving up and down the catheter approximat
ely 3 inches. Return to the insertion
site and use a different surface of the swab to clean up the other side of the catheter.
Repeat this process until you have cleaned all sides of the catheter.



Repeat this exact process with 3 povidone
-
iodine swab stic
ks.

8.

Allow to dry (approximately 60 seconds)

9.

Pat off excess with sterile 4x4 gauze.

10.

Use sterile steri
-
strips to anchor an unsutured catheter.

11.

Create a loop before applying the transparent dressing, directing the distal exposed end of
the catheter cephalad

(if the exit site on upper chest wall) to avoid the diaper area in
infants). If there is drainage, use the gauze to dress the site occlusively.

12.

Label with the date, time of dressing change and initial. Document dressing change on the
Patient Daily Flow Sh
eet and on the patient dressing.

13.

Indicate frequency on the Patient Kardex on patient admission or when line is placed.
Update when any changes in care occur.



25



PROTOCOL FOR FEVER


A. Points to Consider in Clinical Assessment


1.

Is the patient immunosuppres
sed by drugs (i.e., corticosteroids, tacrolimus), end
-
stage
liver disease, or severe renal dysfunction (increased propensity for
bacteremia/fungemia)?

2.

Does patient have a central venous catheter or Foley catheter?

3.

Is the central venous catheter tunneled or

non
-
tunneled (changeable over wire)?

4.

Does the patient have drainage from a stoma or from the colon and are either in close
proximity to a central venous catheter exit site (potential fecal contamination)?

5.

Is there a recent history of sepsis and/or antibio
tic administration (relapse and/or
resistant flora)?

6.

Is the patient’s clinical appearance consistent with sepsis?



Tachycardia (especially if greater than 160/min in infants)



Respiratory distress (oxygen desaturation, tachypnea, nasal flaring, grunting)



Pal
lor or new decrease in blood pressure



Altered level of consciousness



Headaches, back and limb pain



Note: in immunosuppressed patients, these symptoms may be present with only
transient or no fever

B. Routine Actions


1.

Blood culture via peripheral stick and

central catheter (if present) at time of fever and
repeat, either peripheral and via central line, with next scheduled blood draw

2.

CBC with differential and platelet count


compare with previous values

3.

Chest X
-
ray

4.

Urinalysis and culture

5.

Possible but unli
kely actions: spinal tap, stool culture, throat culture/streptococcus
screen, nasal viral culture and direct fluorescent antibody test

C. Empiric antibiotic therapy


1.

Favoring empiric therapy

a.

Septic appearance (looks ill, heart rate > 160/min, reduced bloo
d pressure, new
pallor)

b.

Central line replacement or repair within previous 72 hours

c.

Frequent sepsis in past

d.

Receiving immunosuppressive drug therapy

e.

Liver failure (pre
-
transplant) or delayed liver and/or intestinal allograft function
after transplant

f.

Very
increased
or

decreased WBC/ANC

g.

Recent deterioration in renal function


26


2.

Type of empiric therapy

a.

Vancomycin



If recent history of MRSA or coagulase
-
negative Staphylococcal sepsis with
central line



10 mg/kg (maximum = 500 mg) q 6 hours



Adjustment based on curr
ent renal function and/or recent pharmacokinetics

b.

Zosyn
®

85 mg/kg (maximum & adult = 3.375 grams) q 6 hours



Adjustment based on current renal function

c.

Linezolid

(Zyvox
®
)



If recent history of VRE or patient already receiving vancomycin



Pediatric < age 12

years: 10 mg/kg/dose, repeated q 8 hours



Adult: 600 mg/dose, repeated q 12 hours


3.

Duration of empiric therapy

a.

48 to 72 hr if all cultures negative

b.

Variation depending on clinical appearance and overall severity of illness


4.

Potential issues for discussion

with Transplant Service prior to initiation of therapy

a.

Appropriateness of empiric therapy

b.

Need for concurrent anti
-
fungal coverage

c.

Presence of penicillin or other drug allergy

d.

Need for additional diagnostic testing prior to initiating therapy

e.

Need for rep
lacement of catheter(s) and culture of catheter tips

f.

Increased ileostomy output concurrent with fever


query schedule for endoscopy
to assess for rejection









27

PROTOCOL FOR IMMUNOS
UPPRESSION


I. Primary Immunosuppression


A.


Methylprednisolone




Give en
tire quantity as a single daily dose



20 mg/kg (maximum = 1 gm) IV on day of transplant



10 mg/kg (maximum = 200 mg) IV q AM on POD 1



8 mg/kg (maximum = 160 mg) IV q AM on POD 2



6 mg/kg (maximum = 120 mg) IV q AM on POD 3



4 mg/kg (maximum = 80 mg) IV q AM on

POD 4



2 mg/kg (maximum = 40 mg) IV q AM on POD 5



B.

Prednisone




1.0 mg/kg (maximum 20 mg) JT q AM from POD # 6 until
POD

30



0.75 mg/kg (maximum 15 mg) JT q AM from
POD

30 until
POD

60



0.50 mg/kg (maximum 10 mg) JT q AM from
POD

61 until
POD

90



0.25 mg/kg
(maximum 7.5mg) JT q AM from until
POD

91


POD 120



0.25 mg/kg (maximum 5 mg) JT q AM POD 121 until 1 year post transplant



0.
1
5 mg/kg (maximum
3

mg) JT q
AM

beginning
1
year post
-
transplant


C.


Basiliximab (Simulect
®
)


Up to 3 Doses




For patients < 35 kg

1.

10

mg IV pre
-
reperfusion in the OR

2.

10
mg

IV
in OR (within 6 hours after reperfusion)
IF

high intra
-
op blood loss

3.

10
mg on POD 4




For patients > 35kg

1.

20 mg IV pre
-
reperfusion in the OR

2.

20 mg IV in OR (within 6 hours after reperfusion)
IF
high intra
-
op blood l
oss

3.

20 mg IV on
POD

4



D.


Tacrolimus (Prograf
®
)




0.15 mg/kg (MAXIMUM initial dose 5 mg) via JT q 8 hours (
5
:00 AM and
5
:00
PM if q 12h, and
5
:00 AM,
1

PM, and
9

PM if q 8h)



Begin day of transplant



Clamp all upper GI drainage tubes for 1 hour post
-
dose



Draw

trough blood level immediately before
morning
dose

Note: Initial Q 8 hour dosing is designed to achieve a therapeutic tacrolimus
concentration rapidly immediately after transplant. Dosing frequently is
usually reduced to Q 12 hours subsequently


28



E.

Siroli
mus (Rapamune
®
)




2.5 mg/M
2
(MAXIMUM initial dose 4 mg) via JT q
5
:00 AM (with Prograf
®
)



Begin POD 7



Clamp all upper GI drainage tubes for 1 hour post
-
dose



Diluted with equal amount of sterile water before administration and flush JT
with a minimum of 5mL
NS or sterile water post
-
dose to prevent JT clogging



Draw blood trough level simultaneous with Prograf
®

level, first time 4 to 5 days
after initiation


II. Monitoring Schedules and Target Levels


A.


Tacrolimus (Prograf
®
)




For hospitalized patients



Daily, unl
ess directed otherwise by the transplant team




For ambulatory patients



Daily until about POD 30
-

45 or until initial discharge, which ever comes first



Twice weekly until post
-
op month 3



Weekly for post
-
op months 4 and 5



Biweekly for post
-
op months 6 to 7



Once monthly for post
-
op months 8 to 12



Bimonthly after 1 year post
-
transplant indefinitely




Desired trough levels



25 ng/mL during post
-
op month 1



16
-
18 ng/mL during post
-
op months 2 & 3



12
-
14 ng/mL during post
-
op months 4 & 5



9
-
11 ng/mL post
-
op months 6
-
9



7
-
9 ng/mL post
-
op months 10
-
15



Then, 5
-
7 ng/mL indefinitely


B.

Sirolimus (Rapamune
®
)




Schedule



Every Monday during post
-
op months 1 through 5



Biweekly for post
-
op months 6 to 7



Once monthly for post
-
op months 8 to 12



Bimonthly after 1 year post
-
transplant i
ndefinitely




Desired blood level



10
-
12

ng/mL for post
-
op month 1



8
-
10ng/mLfor post
-
op months 2 & 3


29



6
-
8 ng/mL for post
-
op months 4


6



5 ng/mL for post
-
op months 7
-

indefinitely



III
.
Methods to Maintain Adequate Blood Concentrations of Tacrolimus
(Progra
f
®
) and Sirolimus (Rapamune
®
)


A.

Generally employ when 1 mg/kg doses (up to 20 mg) via
GI Tract

inadequate




Increase dosing frequency of tacrolimus to q 8 hours and sirolimus to q 12 hours



Inhibit drug metabolism with fluconazole



Give tacrolimus IV as contin
uous infusion over 24 hours, 0.01
-

0.02 mg/kg/day



Implies severe rejection;
see below


B.

Route of delivery administration




In general, initiate via JT post
-
transplant if present



In general, continue via same route as for tube feeding (which is also initiate
d via
JT)



When change feeding infusion from JT to GT, change also for drugs


IV. Immunosuppression for Rejection

A.

Mild rejection




Methylprednisolone, 20 mg/kg IV for children or 1 gm for adults once daily for 2
days



Then, resume pre
-
rejection prednisone dos
e


B.

Moderate rejection




Methylprednisolone, 20 mg/kg IV for children or 1 gm for adults once daily for 2
days



Then, standard methylprednisolone taper (refer to section guidelines for
immunosuppresion management)



Then, restart prednisone at 1 mg/kg/day for

children or 20 mg for adults for 2
weeks



Then, give prednisone as standard wean (refer to guidelines for immunosuppresion
management)
but with dose reduction every 2 weeks



Increase tacrolimus and sirolimus trough levels to 33
-
50% above prior levels



If no
histological response in 48


72 hours, then start to OKT
®
3 or
Thymoglobulin
®

(see below)

C.

Severe

rejection

(mucosal sloughing)






Start Muromonab
-
CD3 (OKT
®
3) or Thymoglobulin
®

immediately


30



OKT
®
3



2.5 mg IV daily for weight < 30 kg



5.0 mg IV for daily f
or weight


30 kg



Thymoglobulin
®



1.5 mg/kg/dose



Duration usually 5
-
14 days



Monitoring



Daily CBC with WBC differential and platelet count



Endoscopy once


twice weekly



CD3 counts (T cell subsets) treatment day 0 and 4



Anti


murine antibodies (OKT
®
3 only) t
reatment day 0



Prophylaxis



Trim
-
sulfa for PCP, Toxoplasma at prophylactic dose (see Prophylactic
Antimicrobial Therapy guidelines)



Ganciclovir for CMV at therapeutic dose IV (see Prophylactic
Antimicrobial Therapy guidelines )




Steroids



Methylprednisol
one, 20 mg/kg IV for children, 1 gm for adults, once on day 1,
then 10 mg/kg IV on days 2 and 3



Prednisone, 1 mg

/

kg for children or 20 mg for adults daily starting on
treatment day 4, then standard wean (refer to section B under primary
immunosuppresion
, page 21)




Tacrolimus



Maintain level 15


20 ng/mL



Use IV route if enteral therapy does not achieve target blood level



Dose: 0.01
-
0.02 mg/kg/day by continuous (24 hour) IV infusion alone or in
supplementation with enteral tacrolimus

















31

POST
-
OPERATIVE PROPHYLACTIC ANTIMICROBIAL THERAPY


I. Anti
-
Bacterial Prophylaxis


A.

Unasyn
®



Standard therapy



75 mg/kg/dose (maximum & adult = 3 g) repeated q 6 hours IV



Reduce dose by 50% for > two
-
third reduction in renal function



Discontinue if first surveill
ance endoscopy demonstrates normal mucosa (see below)


B.

Aztreonam (Azactam
®
)




Use in place of Unasyn
®
if penicillin allergy



30 mg/kg/dose (maximum & adult = 2 g) repeated q 6 hours IV



Reduce dose by 50% for > two
-
third reduction in renal function



Duration a
s per Unasyn
®


C.

Vancomycin



Use in place of Unasyn
®
if penicillin allergy



10


12.5 mg/kg/dose (maximum & adult = 500 mg) repeated q 6 hours IV



Follow levels; trough 5


10 ng/mL



Duration as per Unasyn
®


D.

Other broad spectrum agents



Examples



Zosyn
®



Meropenem
®



Linezolid
®



Use in place of Unasyn
®

when pre


transplant infection history indicates high
-
risk of
post


transplant infection with resistant flora in discussion with Transplant Team.



II.

Anti


Viral Prophylaxis

A.

Ganciclovir (Cytovene
®
) IV



5 mg/kg/dose repea
ted q 12 hours



Duration = 14 days



Adjust dose for renal function

Creatinine Clearance (mL/min)

Dose (mg/kg)


Interval (hours)

50

69





2.5



12

25

49





2.5



24

10

24





1.25



24


B.

Ganciclovir PO
-

Pediatrics



From POD 14 to POD 90



600
-
800mg/M
2
/do
se given PO q 8 hours



Adjust dose for renal function



32

C.

Valganciclovir (ValCyte
®
)
-

Adults



From POD 14 to POD 90



900 mg po q day



Adjust for renal function.

Creatinine Clearance (mL/min)

Dose (mg/kg)


Interval (hours)

40
-
60





450 mg


12

25
-
40





450 mg


24

10
-
25





450



48





D.

CMV immune globulin (CytoGam
®
)



150 mg/kg/dose IV



Schedule



Weekly until POD 30



Biweekly from POD 31 to POD 90


E.

Therapeutic a
cute EBV management

1.

A positive EBV
-

PCR test result is > 200 copies/10
5

lymphocytes for documented
ser
opositive patients and > 40 copies in previously seronegative patients

2.

In event of positive result, EBV
-
PCR should be repeated within 48 hours

3.

Treatment



Indications



Symptomatic with 1 positive EBV
-
PCR result



Asymptomatic with 2 positive EBV
-
PCR results



Pro
tocol



Preemptive IV ganciclovir for 2
-
3 weeks, with weekly EBV
-
PCR level



Discontinue ganciclovir IV 1 week after decrease in EBV DNA load



CytoGam
®
, 150 mg/kg IV q weekly, discontinued simultaneously with ganciclovir


F.

Therapeutic a
cute CMV management

1.

A posi
tive PCR test result is > 400 copies/10
5

2.

In event of positive result, CMV
-
PCR should be repeated within 48 hours

3.

Treatment



Indications



Symptomatic with 1 positive CMV
-
PCR result



Asymptomatic with 2 positive CMV
-
PCR results



Protocol



Preemptive IV ganciclovi
r for 2
-
3 weeks, with weekly CMV
-
PCR level



Discontinue ganciclovir IV 1 week after decrease in CMV DNA load



CytoGam
®
, 150 mg/kg IV q weekly, discontinued simultaneously with
ganciclovir



33

III.
Anti


Protozoan Prophylaxis


A.

Pentamidine (NebuPent
®
)



4 mg/kg IV



Once monthly for post
-
op months 1


3 (POD 1, 30, and 60)



After the first 3 months, may be given via inhalation


B.

Trim
-
sulfa (Bactrim
®
)



0.5 ml/kg/day (maximum = 1 SS tab) PO q Monday, Wednesday and Friday



Post operative months 4 to 12



Monitor renal functio
n and CBC


C.

Additional considerations



Continue monthly IV pentamidine in place of trim
-
sulfa if



Sulfa allergy



Persistently low ANC despite G
-
CSF therapy (or decision to avoid G
-
CSF)


IV.
Anti


Fungal Prophylaxis


A.

Fluconazole (Diflucan
®
)



5 mg/kg/day (maximu
m and adult = 200 mg) IV q 24 hours



Continue after transplant



Double dose if ANC < 500/µL



Discontinue if 1
st

intestinal allograft biopsy is normal


B.

Nystatin



Dose



5 mL for < age 10 years



10 mL > age 10 years




Route and time



PO (preferably) or GT q 6 hours



Begin after transplant



Continued until the central line removed


C.

Additional considerations



Clotrimazole lozenges



May substitute for nystatin in older patients who can suck



10 mg q 6 hours



Substitute lipid


soluble amphotericin

(Ambisome
®
)

for fluconazole



Pre
-
transplant fluconazole
-

resistant Candida sepsis



High risk for molds (Examples: Aspergillus, Mucor)



Prolonged neutropenia, poor renal function, steroids pre
-

transplant




34

PROTOCOL FOR FEEDING

POST
-
TRANSPLANTATION


I. Requirements For and Timing of Fi
rst Feeding


A.

Begin POD 5 to POD 7

B.

Requirements



First ileal endoscopy/biopsy normal



Low aspiration hazard



Tracheal intubation



Stable respiratory function



Clinically adequate gastric drainage



Adequate allograft motility



Bowel sounds present and/or



Ileostomy
output


5 mL/kg/day

II.

Formulas and Diets


A. Pediatrics



First:

clear liquid



Composition based on serum electrolytes, CO
2

content



Pedialyte
®
(D2½W & 1/3 NS with potassium & bicarbonate equivalent)
usually



D5W



D5 & ¼NS



D5 & ½NS



Infusion rate = 5 to 20 mL/ho
ur based on body size



5 mL/hour for < 10 kg



Up to 20 mL/hour > 35 kg



Hold infusion 1 hour post immunosuppression dose



Second:

Vivonex RTF
®
1
0
-
1
5 cal/oz (low lipid, amino acid
-
based)



Start after 12 to 24 hours tolerating clear liquid



Absence of emesis



Ile
ostomy output


15 mL/kg/day



Infusion rate initially same as for clear liquid. Then, increase based on:



Body size and tolerance


35



< 10 kg = by 5 mL/hour every 12 to 24 hours



> 35 kg = by up to 20 mL/hour every 12 to 24 hours



Hold infusion 1 hour post immuno
suppression dose



Tacrolimus level



Adequate to high level = increase infusion rate more aggressively



Low level = increase infusion rate less aggressively



Ileostomy ouput



< 20 mL/kg/day = increase more aggressively



> 20 mL/kg/day = increase less aggressively



Reduce parenteral nutrition isocalorically as increase Vivonex RTF
®



Emphasize early reduction in glucose/amino acid solution to compensate for
low lipid content and dilution of Vivonex RTF
®



Maximum Vivonex RTF
®

infusion rate determined in consultation wit
h
transplant nutritionist



Addition of MCT oil (2.5 mL per 4 oz) to Vivonex RTF
®

optional for more
enteral calories before POD 30 (pre
-
lymphatic continuity)



Increases density from 15 to 20 cal/oz



Trouble
-
shooting high ileostomy output (> 40
-
50 mL/kg/day)



Ve
rify repeatedly the absence of rejection or allograft infection with biweekly
endoscopy (see below)



Add Benefiber
®
, 10
-
20 grams/day, to formula



Start loperamide (Imodium
®
), 12
-
24 mg/day and/or Lomotil
®
, ½ to 1 tab 2 to 3
times daily (
watch for lethargy, ab
dominal distention, emesis
)



If hypertensive, use clonidine patch in place of amlodipine or propranolol



Add intravenous ileostomy replacement fluid in presence of clinical indications
of dehydration (usually sterile water with ½ Normal saline with 30
-
75 mEq

NaHCO
3
/L based on serum electrolytes)



Generally, do not advance enteral feeds when ileostomy output > 50 to 55
mL/kg/day



Consider occult peritonitis or infected abdominal fluid collection




Third:

EleC
are
®

15 to 20 cal/oz.



Start after POD 30 to POD 45 day




Initial volume and density same as existing Vivonex RTF
®



Generally PN ending at this time



Increase
EleC
are
®

over succeeding 7
-
10 days to optimal caloric intake in

36

consultation with transplant nutritionist



Hold infusion 1 hour post immunosuppression dose



Tolerance of EleC
are
®

permits introduction of low


osmolality, cow milk
-
free
solids



Introduce items individually for optimal assessment of tolerance



Oral intake may replace or supplement continuous infusion per GT/JT



Fourth:

cow milk
-
based



Types



Formula <

age 1 year



Yogurt, ice cream, Pediasure
®

with fiber > age 1 to 2 years



Requirements



No pre


transplant history of cow milk intolerance



Close monitoring for adverse reaction (which is not unusual)



Introduce as graded challenge post
-
op months 3 to 4


B.

Adul
t



First:

Peptinex
®

30 cal/oz



Initial infusion rate = 20 mL/hour



Hold infusion 1 hour post immunosuppression dose



Criteria for advancement of feeds, generally 10
-
20 mL/hour every 8 to 12 hours



No emesis



Ileostomy output < 500 to 1000 mL/day



Final volume det
ermined in consultation with transplant nutritionist



Solid foods

initiated based on desire and tolerance of formula



Liquids should be sugar
-
free, no regular fruit juice; order “low fat, low
concentrated sweets” diet


III. Formula Delivery

A.

First:

via JT if

present



Initially with GT at drainage



Trial GT clamping when tolerating feeds

B.

Second:

trial via GT or NGT POD 21 to POD 30



Continuous GT clamping tolerated with minimal emesis



Stable respiratory status


IV. Additional Dietary Considerations

A.

Emesis



Consid
er post
-
transplant gastroparesis; trial metaclopramide (Reglan
®
)


37



Consider ileus secondary to rejection; upper GI endoscopy



Consider abscess/peritonitis/perforation; abdominal CT



Consider mechanical obstruction (unusual); upper GI and small bowel x
-
ray seri
es


B.

Severe rejection in pediatrics;

revert to Vivonex RTF
®


C.

Chylous ascites



First
:

give
10
-
15 cal/oz Vivonex RTF
®

or
15 cal/oz Portagen
®
(high MCT oil, whole
cow milk protein


based)



Second:
resume parenteral nutrition for 2 to 6 weeks


D.

Medications





Imm
unosuppression



Initially deliver only by JT if present.



Deliver by GT if levels stable 2 to 4 weeks and GT tolerated for feeds and other
meds



Clamp both GT and JT for 1 hour after all meds, including immunosuppression.



Meds other than immunosuppression
alw
ay
s by GT, NGT, or PO (will clog JT)




















38

GENERAL MANAGEMENT OF THE INTESTINAL TRANSPLANT
RECIPIENT


I.



Endoscopy


A.

Ileoscopy

1.

Purpose: Surveillance for rejection or other pathology.

2.

We request the following schedule:

a.

Routine



Twice weekly for 1½

months after transplant



Weekly from 1½ to 3 months after transplant



Biweekly from 3 to 5 months after transplant



Monthly from 5 to 12 months after transplant or until ileostomy closure,
(whichever comes first)



Yearly thereafter

b.

As needed based on symptoms
:



Increased ileostomy output or other feeding intolerance



Gastrointestinal bleeding



Change in color or appearance of the stoma


B.

Indications for upper GI endoscopy and colonoscopy

1.

Surveillance once yearly after ileostomy closure

2.

Indications of allograft dys
function with negative or equivocal ileoscopy findings


II.
Liver Biopsy (with combined intestinal and liver, or multi
-
visceral transplant)


A.

Purpose: Assessment rejection or other pathology when some or all liver injury tests are
significantly and progre
ssively elevated for more than 1


2 weeks in absence of definable
intestinal allograft pathology


B.

Note that liver rejection in the absence of intestinal rejection is unusual while transient
increases in liver injury tests are commonly seen with small bowe
l rejection or sepsis.


III.
Ileostomy Closure


A.

Closure is done 4 to 9 months following transplant, provided there has been no significant
rejection or other graft dysfunction within the preceding 3 months


B.

If rejection occurs during the first 6 months a
fter transplant, we delay closure until 1 year or

39

more after transplant. Patients with Hirschsprung disease are considered for ileoanal pull
-
through on a case by case basis.


IV.
Laboratory Tests


A.

Routine blood tests




We ask that all results be reported
/faxed to the transplant team, as well as office visit
summaries with current weights and vital signs.
We will manage immunosuppressive therapy
for all patients.


1.

Requested schedule



After hospital discharge to home, blood testing is often required more fr
equently than
ileoscopy for the first few months due to erratic immunosuppression levels.



Twice weekly for 1½ months after transplant



Weekly from 1½ to 3 months after transplant



Biweekly from 3 to 5 months after transplant



Monthly from 5 to 12 months after

transplant




Bimonthly from 12 months after transplant indefinitely




Specific tests



CBC with platelet count and WBC differential



Comprehensive metabolic panel, also including phosphorus and magnesium
levels, cholesterol, and triglycerides



Trough level of t
acrolimus (and sirolimus or mycophenolic acid level, if
applicable)



Liver tests including GGT, ALT, AST, alkaline phosphatase


B.

Quantitative EBV and CMV


PCR testing

1.

Once monthly until 1 year after transplant

2.

Bimonthly after 1 year from transplant indefini
tely


V.

Diet and Growth


A.

Disordered feeding behavior

1.

Adverse behaviors existing before transplant usually continue afterward.

2.

We recommend that you continue supplemental tube feeding as necessary to maintain
adequate total caloric intake and weight gain base
d on your regular assessment.

3.

Most intestinal transplant recipients have no physical limitation to swallowing either
solids or liquids. We recommend that you manage feeding problems in the same fashion
as in other chronically ill children. Indefinite jej
unal tube feeding is required in only a

40

minority of instances

4.

Persistently poor gastric emptying raises the possibility of rejection in the jejunal side of
the graft or obstruction and warrants evaluation.


B.

Nutritional needs

1.

Children with good graft functi
on typically require no vitamin supplementation.

2.

Iron supplementation is commonly needed. Inability to correct iron deficiency suggests
excessive GI loss, raising a question of occult rejection or other inflammatory process.

3.

Cow milk intolerance is relati
vely common after intestinal transplantation. However, loss
of previous tolerance of cow milk, weight loss with no change in intake, or obvious
steatorrhea with should be considered an indication of rejection that warrants endoscopy
and biopsy.


VI.

Vaccinati
ons


A.

Before transplantation

1.

It is desirable but not always possible to keep vaccinations up
-
to
-
date before
transplantation.

2.

All age
-
appropriate vaccines, including MMR
®
, Varivax
®
, Havrix
®
, Energix
®
, Prevnar
®
,
and Hib can be given while waiting for an inte
stinal transplant.


B.

After transplantation

1.

We customarily resume the age
-
appropriate,
inactivated
vaccinations 6 months after
transplantation if rejection has been absent with the previous 3
-
4 months.

2.

If not given before transplantation, we would recommend
delaying MMR
®

until
prednisone has been reduced to alternate
-
day therapy.

3.

Varivax
®
should be employed on an individualized basis after transplant in consultation
with the transplant team. Customary recommendations, e.g. the Red Book
®
, apply
concerning mana
agement of varicella exposure in varicella


naïve, immunosuppressed
patients.



Zoster immune globulin within 96 hours, and, preferably, within 48 hours of close
exposure.



Acyclovir. We request that the route of acyclovir administration be discussed with
us
in advance of treatment.

4.

When vaccines are given for the
first time

after transplantation, we recommend that
antibody titers, when available, be checked to ascertain response.

5.

Splenectomy is not commonly required in intestinal transplantation. If perfo
rmed, usual
antibiotic prophylaxis is appropriate in addition to vaccination.


VII.

Surveillance for Neoplasia and Infection


A.

EBV
-
related infection and disease

1.

Evolution of post
-
transplant EBV infection into post
-
transplantation

41

lymphoproliferative disease (PTL
PD) is greater in recipients of an intestinal compared
to a kidney or liver graft. EBV
-
PCR surveillance is carried out in the manner
requested above for this reason.

2.

Any combination of fever of undetermined origin, Streptococcus
-
negative pharyngitis,
lymp
hadenopathy, new nighttime snoring or stridor, or dysphagia/anorexia, abdominal
pain, diarrhea, or vomiting for more than a few days raises the possibility of PTLPD.

3.

If symptoms present and an EBV
-
PCR test has not been performed within the past 1
-
2
weeks,
recheck is essential in consultation with us.


B.

CMV
-
related infection and disease

1.

Symptoms of CMV disease can be similar to EBV and also include acute non
-
bacterial
pneumonitis.

2.

A quantitative blood CMV
-
PCR test should generally be done at the same time as
an
EBV PCR test.



VIII.

Viral Gastroenteritis

A.

Intestinal transplant recipients become more severely and rapidly dehydrated than other
infants and children with acute viral infection. The denervated intestinal graft does not have
auto
-
regulation of blood flow

and is vulnerable to ischemia with even mild dehydration,
particularly within the setting of previous rejection.

B.

Increased ileostomy or stool output of more than 12 hours duration should prompt office
evaluation for consideration of usual interventions such as clear liquid diet, intravenous fluids,
and/or stool cultures.

C.

Life
-

threatening electrolyte abnormalities s
uch as hyperkalemia and metabolic acidosis can
develop quickly in dehydrated intestinal transplant patients, particularly if electrolyte
supplements are given. When there is any question, a check of the serum electrolytes is
essential.