11/21/17 1 Transplant Basics for Acute Care NPs Alison Mitchell MSN, ACNP, FAANP Adjunct Clinical professor Disclosure: Conflicts of Interest Alison Mitchell has no commercial financial relationships to disclose This presentation uses a number of slides prepared by Julie Stanik-Hutt, PhD, ACNP/GNP, FAANP, FAAN ” Managing Transplant Recipients in a Primary Care Setting” presented at 2017 AANP Conference Learning Objectives Describe the management of common side effects of immunosuppressant medications Analyze clinical situations common in solid organ transplant recipients in order to develop an appropriate list of differential diagnoses Describe the role of the patient and their transplant center providers role in minimizing complications after transplantation Why transplant? To prolong recipients life Decrease morbidity related to their underlying organ failure Improve quality of recipients life Transplant Options Solid organs Avascular tissue Vascular composite allotransplant Transplant Options Solid organs Kidney Heart Intestine Liver Lungs Pancreas Avascular tissue Cornea Heart valves Bone Teeth Skin Vascularized composite allotransplant -hands/arms/face/penis
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Presentation4[1] · 11/21/17 2 Transplant History u 1954-1st successful transplant in North America u Living related renal transplant between identical twins u No immunosuppression
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11/21/17
1
Transplant Basics for Acute Care NPsAlison Mitchell MSN, ACNP, FAANPAdjunct Clinical professor
Disclosure: Conflicts of Interest
Alison Mitchell has no commercial financial relationships to disclose
This presentation uses a number of slides prepared by
Julie Stanik-Hutt, PhD, ACNP/GNP, FAANP, FAAN
” Managing Transplant Recipients in a Primary Care Setting” presented at 2017 AANP Conference
Learning Objectives
Describe the management of common side effects of immunosuppressant medications
Analyze clinical situations common in solid organ transplant recipients in order to develop an appropriate list of differential diagnoses
Describe the role of the patient and their transplant center providers role in minimizing complications after transplantation
Why transplant?
To prolong recipients life
Decrease morbidity related to their underlying organ failure
Improve quality of recipients life
Transplant OptionsSolid organs
Avascular tissue
Vascular composite allotransplant
Transplant Options
Solid organs
Kidney
Heart
Intestine
Liver
Lungs
Pancreas
Avascular tissue
Cornea
Heart valves
Bone
Teeth
Skin
Vascularized composite allotransplant
-hands/arms/face/penis
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Transplant History
u 1954- 1st successful transplant in North America
u Living related renal transplant between identical twins
u No immunosuppression and graft survived for 8 years
u > 650,000 people in the USA have received a transplant since 1988
u Today, >200,00 Americans live with a functioning organ transplant
So what has improved?
Operative technique and immunosuppressants
Control of complications
Addition organs available for transplant
Liver, Heart, Lung, Pancreas, Intestines(solid organs) and face and hands
Donors expanded to:
-Living Donors that are HLA mismatch
Extended criteria donors- non beating heart
So how long do the grafts survive?(2017 data)
Living related kidney
Cadaver renal transplant
Pancreas
Liver
Heart
Lung
1 yr 98% 3 yr 93% 5 yr 88%
1 yr 93% 3yr 85% 5 yr 74%
1 yr 81% 3 yr 71% 5 yr 60%
1yr 90% 3yr 81% 5 yr 73%
1yr 91% 3yr 85% 5 yr 78%
1yr 88% 3yr 67% 5 yr 53%
ChallengesOrgan shortage
Increased number of minority recipients>50 yrs
>6,700 die waiting( 22 daily)
>33,595 transplants annually
5,975 living donations
Despite living donations there are 144 new listings every day
Long term complications
Rejection
Infection
Cancer
Fractures from long term steroids
Medication effects
Americans waiting…
> 118,786 Americans wait for
Kidneys 82%
Liver 12%
Pancreas 9%
Heart 3%
Lung 1 %
Who qualifies?Eligibility
End stage organ disease despite optimal medical management
Otherwise healthy
No contraindication for immunosuppression
Adequate social supports to comply with post transplant care
ExclusionsActive smoking and drug abuse( livers now being transplanted in ETOH abusers)
Financial
> 75 yrs old
Cancer in the last 5 years
Active infections or colonizations with pan resistant organisms
Foreign nationals
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Vascularized composite allotransplantation VCA
Hand
Arm
Face
Penis
Composite Tissue Allotransplantation CTA
Skin
Soft tissue(muscle, nerve, vessels)
Bone
teeth
Vascular(VCA) & Composite(CTA)
Vascular Composite Allo-transplantation
Upper extremities
First in 1964, first successfully in 1998
12 US hospitals
> 100 patients worldwide, 20 patients in the USA
Bilateral deficit below the shoulder-6 months post amputation and failed myoelectric prosthesis
Face
First in 2005
8 US hospitals
30 pts. worldwide ,10 patients in USA
Loss of >25% facial structure
5 deaths- 2 infections, 1 graft lost to non adherence, 1 cancer reoccurrence, 1 GSW
Hand & Arm RecipientsPost Operative Care
Frequent vascular checks
Position hand at level of heart
Strict use of pressure relieve
Topical & systemic immunosuppression
Post Operative care
Extensive PT/OT
Passive ROM at 24-48 hrs
PT/OT 6 hrs a day 5 days a week
for 3-6 months
Psychosocial support
Face recipientsPost Operative care
Sedation and analgesia
Airway management
Hemostasis
Flap healing- maintain patency of drains and minimize movement
Post Operative Care
Prevent edema by having a neg I/O, Elevate HOB
PT/OT/speech
Enteric feeding
Nerve impulse detection with exercises
Psychosocial and family support
Long term complications
Ischemia-reperfusion
Bleeding vs. thrombosis
Vascular stenosis-renal, pulmonary
Wound Infection
Interrupted lyphatics-lymphocele, chest
Luminal disruption-ureter, smal bowel, bile duct, bronchus
Drug interactions and drug toxicities frequently checked
Infection
Procedural Complication
Malignancies
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Types of Rejection
Acute-
Abrupt, commonly in the first months of the first year, usually treatable but predisposes to chronic rejection
Major cause of mortality/morbity in 1st year after transplant
Chronic-
Months and years post transplant, diffuse & progressive thickening and fibrosis, poorly understood- antibody related
Microvasculature obstruction and sclerosis of graft
Mechanisms of Rejection
Humoral-
Antibody mediated (Vascular rejection), B –lymphocytes
Presence of donor specific HLA antibodies, vascular endothelium
Cellular-
Cell mediated, T-lymphocytes
Recipient tissue recognized as foreign, activated then proliferative that destroys graft
Immunology 101Human leukocyte antigens ( HLA)
Class I ( A&B) and II (DR)
Panel Reactive Antibody(PRA) serology
DNA testing to match donor to recipient
Cell surface glycoproteins, >histocompatibility antigens, >help body recognize self versus non self
Major histocompatibility complex ( MHC), inherit 1 allele with 6 loci from ca. parent,
MHC I ( on all cells)
MHC H (on Antigen Producing Cells), brain, eyes, articular cartilage, testes, fetus, and placenta
Immunology 101
T- cells activate then bind to MHC if not trained to recognize
Class 1- Natural killer cells- innate
Class I-CD8 recognition ( killer)
Class II-CD4 recognition ( Helper)
Induction-Anti Lymphocytic antibodies or II-2 Receptor
antagonistsProfound immunosuppression
Near total inactivation T cells
Maximize infection control
Increased long term risk for malignancy
Goal-delay onset first acute rejection
At time of initial exposure to foreign antigen-before and during transplant surgery, short term, high dose immunosuppression
70% receive a specific induction agent
Immunomodulation
Induction antibodies
Donor bone marrow transplant
Minimal maintenance immunosuppression
From a therapeutic point of view, immunomodulation refers to any process in which an immune response is altered to a desired level. Microorganisms are also capable of modulating the response of the immune system to their presence, in order to establish or consolidate an infection
Immunomodulation by microorganisms is directed at several aspects of the immune system. One target are the small molecules known as cytokines , which function as messengers of the immune system. In other words, cytokines stimulate various immune responses such as inflammation of the manufacture of antibodies. Other cytokines are involved in down-regulating the immune responses.
Immunomodulation
Some microorganisms are able to produce and excrete proteins that mimic the structure and function of cytokines. Often the result is a suppression of the host's inflammatory response. Examples of microbes that produce cytokine-like molecules are the Epstein-Barr virus , poxvirus, vaccinia virus.
World of Microbiology and Immunology. . Encyclopedia.com. 5 Sep. 2017
T- Cell Co-stimulation Blockade
Epstein Barr Virus sero positive renal transplants only
Induction in OR and on day 5
Maintenance doses at 2,4, 8 &16 weeks
Adverse reactions-pancytopenia, infections and increased risk of post transplant liver disease
Belatacept (Nulojix)
IgG immunoglobin fragment- selective T cell co-stimulation blocker, used with steroids,
basiliximab & MMF
Avoid Calcincurin inhibitors
MaintenanceLife long maintenance
What is the goal?
Promote graft survival and prevent rejection
Triple Therapy to prevent rejection
Dosage titration-levels, side effects, clinical status
Balance risks; Rejection vs. Infection
1/Calcinurin Inhibitors-Cyclosporine or Tacrolimus
2/Purine Synthesis inhibitors-Azathioprine or Mycophenolate Mofetil (MMF). Consider Sirolimus or Everolimus
3/Steroids-Prednisone
Belatacept
CyclosporineSandimmune
Neoral
Gengraf
Cyclosporine
Inhibit T Cell activation
Dosage-titrate to target which varies by patient history and organ
Infection Control Procedures- hand washing, immunizations, prophylactic anti microbials, transfusions(irradiated, almost all lungs need CMV negblood), self surveillance
Clinical ManagementTransplant coordinator and clinican-consult them
Drug interactions-problems emerge anytime after starting or stopping
Maintain prophylactic protocols
Listen to your patient
Update meds
Trend lab results
Focused exam considering rejection/infection, drug interactions
Consider is it a side effect? Is the patient taking d
Meds as prescribed? Brand change?
Malignancy
Skin cancers-
Maximal SPF, hats, cover ups
Annual skin exams
Post Transplant Lympho-Proliferative Disease (PTLD) B –lymphocyte & EBV related
Rx with radiation/Rituxan/Chemo and reduction of immunosuppression
3-4 fold increased risk
Oncogenic viruses
DNA damage from immunosuppressants
Induction and Rescue with T-Cell antibodies
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Major pointsOrgan shortage demands optimal use
Team approach to management
NEVER hesitate to call Transplant center to advise
Meds constitute major source of comorbities
Manage symptomatic side effects
Nephrotoxic-HTN-DM-Dyslipidemia
Pancotopenia-CNS-GI problems
Multiple interactions-manage therapeytic as well as toxic effects
REJECTION vs. INFECTION plus MALIGNACY
Transplant, coming to a hospital near [email protected] 713 515 5508
ReferencesWorld of Microbiology and Immunology. . Encyclopedia.com. 5 Sep. 2017
Gulliford J, Gama D S,(2000) Postgrad Med
Wong CJ,Pagalilauan G,(2015)Primary Care of the Solid organ Transplant Recipient.Medical Clinics of North America99(5), 1075-103
Allison TL, (2016)Immunosuppressive Therapy in Transplantation,Nursing Clinics of North America 51 (1) 107-20
ChelalaL,Kovacs CS, Taege AJ, Hanouneh IA (2015) Common infectious complications of liver transplant Cleveland Clinic journal of Medicine 82 (110, 773-84