Download Critical Care of Organ Transplant

Critical Care
of Organ
Transplant
Transplantation
Treatment of choice for many
patients with end-stage failure of
kidneys, endocrine pancreas,
heart, lungs, liver, and small bowel
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GENERAL PRINCIPLES
The increased number of organ transplants
:
1-The availability antilymphocyte antibody preparations to prevent
and treat rejection episodes
2- Immunosuppressant agent
3-Improvements in organ preservation
4-preoperative patient screening.
5-Increasing sophistication in postoperative intensive care
6-Availability of potent, yet nontoxic antibacterial, antifungal, and
antiviral agents
7-Refinements in surgical techniques
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Current absolute contraindications to
transplantation
- Malignancy (untreated, metastatic, or at high
risk for recurrence)
-Uncontrolled infection
-Medical-surgical contraindications to undergo
-Inability to recover from, major surgery
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The gap between available
organs and patients awaiting
transplantation is widening. As
a result, transplant wait list
mortality is increasing
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THE ORGAN DONOR SHORTAGE
POTENTIAL SOLUTIONS
1- Live donors (kidney ,liver, small bowel,
pancreas, and lung )
2- Deceased organ donors , Brain-dead
donors
3- Unconventional donor organ
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ORGAN-SPECIFIC
CONSIDERATIONS
Kidney transplantation:
1/Treatment of choice for nearly all patients of all ages
with advanced chronic kidney failure and end-stage
renal disease
2/Kidney transplants do not only improve quality of life,
but also prolong life
3/Less expensive from a socioeconomic standpoint
than chronic hemodialysis
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ORGAN-SPECIFIC
CONSIDERATIONS
Liver transplantation:
1/Treatment of choice for patients
with acute and chronic end-stage
liver disease.
2/Dramatic improvement in graft
survival after introduction of
cyclosporine in the late 1970s.
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ORGAN-SPECIFIC CONSIDERATIONS
Pancreas and islet transplantation
1/Indications: Most pancreas transplants are done for selected,
medically suitable patients with type I diabetes who have
developed significant secondary diabetic complications or
have poor quality of life
2/At present, pancreas transplantation is the only effective
option to consistently restore normal glucose homeostasis
and normalize glycosylated hemoglobin (HbA1c) levels.
3/Successful pancreas transplants significantly improve
quality of life and decrease incidence and severity of
secondary diabetic complications.
4/Most pancreas transplants are performed simultaneously
with a kidney transplant in preuremic patients with
significant renal dysfunction, or in uremic patients with endstage diabetic nephropathy.
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ORGAN-SPECIFIC CONSIDERATIONS
Small bowel transplantation:
1/Indications: Congenital or acquired short bowel
syndrome, especially if liver dysfunction occurs because
of long-term parenteral nutrition or if establishing or
maintaining central venous access becomes difficult.
2/In patients who have also advanced liver disease, a
combined liver &small bowel transplant may be
indicated.
3/With refinement of surgical techniques, more specific
immunosuppression, and better postoperative monitoring
for rejection, graft survival has considerably improved
over the past decade and approaches that of other solid
organ grafts (e.g., lung transplants).
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ORGAN-SPECIFIC
CONSIDERATIONS
Heart transplantation:
1/Treatment of choice for patients with end-stage
congenital and acquired parenchymal and vascular
diseases of the heart after exhaustion of all conventional
medical and surgical options.
2/Considerably improved results since introduction of
cyclosporine in the early 1980s and refinements in
diagnosing and treating rejection episodes.
3/Mechanical devices (e.g., total artificial heart, ventricular
assist device) can serve as a temporary bridge between
heart failure and transplant.
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ORGAN-SPECIFIC
CONSIDERATIONS
Heart-lung and lung transplantation:
1/Effective treatment for patients with advanced pulmonary
parenchymal or vascular disease with or without primary
or secondary cardiac involvement.
2/Increase in lung transplants (most frequently done as
single or bilateral single lung transplants) is in large part
due to technical improvements, resulting in fewer
surgical complications, and to advances in perioperative
and postoperative care.
3/Mechanical ventilation or extracorporeal membrane
oxygenation (ECMO) can be a temporary bridge to
transplant.
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FUTURE CHALLENGES IN
ORGAN TRANSPLANTATION




Increase number of available donor organs.
Minimize rates of chronic graft failure (e.g.,
secondary to chronic rejection, graft
atherosclerosis).
Develop immunosuppressive drugs and protocols
that have fewer side effects and further improve
long-term graft survival.
Develop tolerance-promoting protocols, which would
obviate need for chronic immunosuppression
beyond the induction phase.
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Rejection, Infection, and
Malignancy in Solid Organ
Transplant Recipients
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GENERAL PRINCIPLES
Immunosuppressive therapy
must be balanced to prevent
transplant rejection and
minimize risk of infection and
malignancy
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REJECTION
The alloimmune response :
1/Highly polymorphic human leukocyte
antigens (HLA) are expressed on cell
surfaces in different individuals.
2/Foreign HLA molecules expressed on
transplants are recognized by recipient helper
and cytotoxic T lymphocytes, B lymphocytes,
and natural killer cells.
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REJECTION
3/T lymphocytes are central to alloimmunity as
well as immunity to viruses and malignant
cells.
4/B lymphocytes produce antiâ donor HLA
antibodies. Sensitization to donor HLA may
occur in recipients with repeated exposures
from previous transplant, multiple blood
transfusions, or multiple pregnancies.
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REJECTION
5/ Immunosuppression targets T lymphocytes. Dual or
triple maintenance therapy permits lower drug doses
while providing synergy:
a- Corticosteroids inhibit lymphocyte activation and
are
cytolytic at high doses
b- Antimetabolites (azathioprine, mycophenolate
mofetil)
inhibit lymphocyte proliferation
c- Calcineurin inhibitors (cyclosporine, tacrolimus)
inhibit production of interleukin-2 (IL-2), a critical
signal for
T lymphocyte activation
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Acute Rejection
General:
Transplant dysfunction is the most common presentation, but often
subclinical rejection is identified on biopsy.
Systemic inflammatory symptoms are less common.
Acute cellular rejection is characterized histologically by
lymphocytic cellular infiltrate with active parenchymal injury.
Humoral rejection is characterized by vascular endothelial cell injury
with intravascular antibody deposition, fibrin formation, and
complement activation.
Biopsy is essential to confirm presence and severity of rejection.
Therapy with high-dose corticosteroids or antilymphocyte antibody
is required.
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Acute Rejection
Kidney:
Acute rise of serum creatinine. Rule out
drug nephrotoxicity, pyelonephritis,
systemic infection, urologic obstruction,
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Acute Rejection
Liver:
Acute rise in serum transaminases. Rule
out recurrent disease, biliary
complications, hepatic artery thrombosis,
and drug toxicity.
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Acute Rejection
Heart:
Acute decrease in left ventricular ejection
fraction, or rejection identified on routine
endomyocardial biopsy. Rule out infection
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Acute Rejection
Pancreas:
Acute serum amylase elevation and decreased
urinary amylase excretion .Hyperglycemia is
a late manifestation. Rule out arterial graft
thrombosis, impaired exocrine drainage, drug
toxicity, or infection.
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Acute Rejection
Lung:
Acute decrease in ventilation and
oxygenation, or rejection identified on
routine bronchoscopic biopsy. Rule out
infection, airway or vascular anastomotic
complications, malignancy, and recurrent
disease.
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Chronic Rejection
Chronic rejection occurs as coronary artery disease
in heart, bronchiolitis obliterans in lung, or ischemia
and fibrosis in kidney, pancreas, and liver grafts.
Immunologic and nonimmunologic risk factors are
important, including frequency and severity of acute
rejection, recurrence of original disease, drug
toxicity, and infection.
Therapy includes increased immunosuppression,
avoidance of drug toxicity, or treatment of recurrent
disease.
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INFECTION
General :
1/Because immunosuppression targets T
lymphocytes, risk of opportunistic infection by
pathogens controlled by T cell immunity is
increased
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INFECTION
General :
2/Risk decreases over time with immunosuppression
intensity:
a-Peritransplant infection due to nosocomial infection
as in other postoperative patients.
b-Opportunistic infection most common 3 to 6 months
after transplant.
c-Later infection generally community-acquired or
persistent opportunistic infection.
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INFECTION
General :
3/Antimicrobial prophylaxis and empiric therapy
are guided by time after transplant and level
of immunosuppression, but a wide differential
diagnosis and rapid identification of
pathogens are always required.
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INFECTION
Bacterial:
1/Peritransplant nosocomial infection: pneumonia,
catheter infection, superficial or deep wound
infection, or urinary tract infection.
2/Community-acquired respiratory and urologic
tract pathogens predominate later.
3/Consider Legionella in pneumonia.
4/Consider Listeria in acute meningitis.
5/Tuberculosis may occur at any time and often
presents as disseminated disease.
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INFECTION
Viral:
Cytomegalovirus (CMV)

Active infection occurs by reactivation of latent virus

Highest incidence in the first 6 months: pneumonitis,
esophagitis, gastritis, colitis, hepatitis, nephritis, bone
marrow infection, or febrile syndrome. Diagnosis is
confirmed by presence of viremia or biopsy.
Prophylaxis with oral ganciclovir or valganciclovir is
maintained for at least 3 months, especially in high-risk
recipients.

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INFECTION
Viral:
Epstein-Barr virus (EBV) is associated with
posttransplant lymphoproliferative disease
(PTLD). It may cause acute hepatitis or
infectious mononucleosis.
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INFECTION
Viral:
Pneumonitis due to adenovirus, respiratory
syncytial virus, and influenza virus requires
rapid bronchoscopic diagnosis and specific
antiviral therapy.
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INFECTION
Viral:
Hepatitis B and C viruses are most commonly
acquired before transplant.
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INFECTION
Fungal:
Pneumocystis pneumonia presents as acute
pneumonitis in the first 6 months after
transplant. Prophylaxis with trimethoprimsulfamethoxazole is highly effective.
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INFECTION
Fungal:
Aspergillosis is often disseminated and
associated with high mortality.
Cryptococcosis must be considered in
meningitis
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INFECTION
Fungal:
Coccidiomycosis, histoplasmosis, &
blastomycosis should be considered after
careful demographic evaluation to
determine exposure risk. Meningitis,
pneumonitis, and dermatitis are common
presentations.
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INFECTION
Fungal:
Candidiasis may present as disseminated
infection, urinary tract infection, or
intraabdominal abscess.
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INFECTION
Parasitic:
Parasitic infection should be
suspected in the setting of
eosinophilia
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INFECTION
Parasitic:
Toxoplasmosis may present in the first 2
months with systemic inflammation,
meningoencephalitis, pneumonitis,
pericarditis, myocarditis, or retinitis.
Prophylaxis with trimethoprimsulfamethoxazole is effective.
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MALIGNANCY
Skin cancer is the most common malignancy in
all transplant recipients. Risk increases with
levels of sun exposure and immunosuppression.
Squamous cell carcinoma is most common.
Melanoma may present as metastatic disease
with an unidentified primary lesion. Kaposi's
sarcoma is common in patients of
Mediterranean origin.
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MALIGNANCY
Solid organ cancers:
1-Recurrent disease is possible, especially colon,
breast, and melanoma.
2-May present as metastatic disease, but a primary
lesion is commonly identified.
3-Risk is increased approximately threefold over that
for the general population.
4-Risk factors are similar to those for
nonimmunosuppressed patients
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MALIGNANCY
Post transplant lymphoproliferative disease:
Presents typically as polymorphic non-Hodgkin B
cell lymphoma, commonly associated with EBV
infection. The primary lesion may arise in the
small bowel, central nervous system, or allograft.
Lymphadenopathy is easily identified on
physical examination or radiologic imaging.
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MALIGNANCY
Post transplant lymphoproliferative disease:
PTLD usually presents within 1 year after
transplant but may also occur later. Risk is
2% for renal transplant recipients to 10% for
heart and lung recipients.
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MALIGNANCY
Post transplant lymphoproliferative disease:
Therapy
1-Reduce or discontinue immunosuppression.
2-Cytotoxic chemotherapy or therapy with anti-CD20 antibody
(rituximab) targeting B lymphocytes.
3-Antiviral (anti-EBV) therapy with acyclovir or ganciclovir
(limited evidence-based support).
4-Consider surgical resection in cases with isolated, limited
involvement (e.g., allograft, gastrointestinal lymphoma).
5-Radiation most effective for central nervous system PTLD.
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