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 2 Dr.yekehfallah-phd of nursing2015 9/18/2015

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 3 Dr.yekehfallah-phd of nursing2015 9/18/2015

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 4 Dr.yekehfallah-phd of nursing2015 9/18/2015

The gap between available organs and patients awaiting transplantation is widening. As a result, transplant wait list mortality is increasing 5 Dr.yekehfallah-phd of nursing2015 9/18/2015

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 6 Dr.yekehfallah-phd of nursing2015 9/18/2015

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 7 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 8 Dr.yekehfallah-phd of nursing2015 9/18/2015

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 end- stage diabetic nephropathy. 9 Dr.yekehfallah-phd of nursing2015 9/18/2015

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). 10 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 11 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 12 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 13 Dr.yekehfallah-phd of nursing2015 9/18/2015

Rejection, Infection, and Malignancy in Solid Organ Transplant Recipients 14 Dr.yekehfallah-phd of nursing2015 9/18/2015

GENERAL PRINCIPLES Immunosuppressive therapy must be balanced to prevent transplant rejection and minimize risk of infection and malignancy 15 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 16 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 17 Dr.yekehfallah-phd of nursing2015 9/18/2015

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 18 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 19 Dr.yekehfallah-phd of nursing2015 9/18/2015

Acute Rejection Kidney: Acute rise of serum creatinine. Rule out drug nephrotoxicity, pyelonephritis, systemic infection, urologic obstruction, 20 Dr.yekehfallah-phd of nursing2015 9/18/2015

Acute Rejection Liver: Acute rise in serum transaminases. Rule out recurrent disease, biliary complications, hepatic artery thrombosis, and drug toxicity. 21 Dr.yekehfallah-phd of nursing2015 9/18/2015

Acute Rejection Heart: Acute decrease in left ventricular ejection fraction, or rejection identified on routine endomyocardial biopsy. Rule out infection 22 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 23 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 24 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 25 Dr.yekehfallah-phd of nursing2015 9/18/2015

INFECTION General : 1/Because immunosuppression targets T lymphocytes, risk of opportunistic infection by pathogens controlled by T cell immunity is increased 26 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 27 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 28 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 29 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 30 Dr.yekehfallah-phd of nursing2015 9/18/2015

INFECTION Viral: Epstein-Barr virus (EBV) is associated with posttransplant lymphoproliferative disease (PTLD). It may cause acute hepatitis or infectious mononucleosis. 31 Dr.yekehfallah-phd of nursing2015 9/18/2015

INFECTION Viral: Pneumonitis due to adenovirus, respiratory syncytial virus, and influenza virus requires rapid bronchoscopic diagnosis and specific antiviral therapy. 32 Dr.yekehfallah-phd of nursing2015 9/18/2015

INFECTION Viral: Hepatitis B and C viruses are most commonly acquired before transplant. 33 Dr.yekehfallah-phd of nursing2015 9/18/2015

INFECTION Fungal: Pneumocystis pneumonia presents as acute pneumonitis in the first 6 months after transplant. Prophylaxis with trimethoprim- sulfamethoxazole is highly effective. 34 Dr.yekehfallah-phd of nursing2015 9/18/2015

INFECTION Fungal: Aspergillosis is often disseminated and associated with high mortality. Cryptococcosis must be considered in meningitis 35 Dr.yekehfallah-phd of nursing2015 9/18/2015

INFECTION Fungal: Coccidiomycosis, histoplasmosis, & blastomycosis should be considered after careful demographic evaluation to determine exposure risk. Meningitis, pneumonitis, and dermatitis are common presentations. 36 Dr.yekehfallah-phd of nursing2015 9/18/2015

INFECTION Fungal: Candidiasis may present as disseminated infection, urinary tract infection, or intraabdominal abscess. 37 Dr.yekehfallah-phd of nursing2015 9/18/2015

INFECTION Parasitic: Parasitic infection should be suspected in the setting of eosinophilia 38 Dr.yekehfallah-phd of nursing2015 9/18/2015

INFECTION Parasitic : Toxoplasmosis may present in the first 2 months with systemic inflammation, meningoencephalitis, pneumonitis, pericarditis, myocarditis, or retinitis. Prophylaxis with trimethoprim- sulfamethoxazole is effective. 39 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 40 Dr.yekehfallah-phd of nursing2015 9/18/2015

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 41 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 42 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 43 Dr.yekehfallah-phd of nursing2015 9/18/2015

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. 44 Dr.yekehfallah-phd of nursing2015 9/18/2015

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