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Pediatric and AdultPediatric and Adult TransplantationTransplantation
• ORGANS Heart
Lung (single or double)
Heart & Lung
Kidney
Pancreas
Kidney & Pancreas
Intestine
• TISSUESBone Marrow
Stem Cell
Cornea
Heart valves
Tendons
Skin
Bone
The Numbers - CompletedThe Numbers - Completed
http://www.unos.org
The NumbersThe Numbers
http://www.unos.org
0
5,000
10,000
15,000
20,000
25,000
30,000
1988 1990 1995 2000 2005
Total
Deceased
Living
The Numbers – By OrganThe Numbers – By Organ
http://www.unos.org
ORGAN
Heart
Lung (single or double)
Heart & Lung
Kidney
Pancreas
Kidney & Pancreas
Liver
Feb 2006
38,878
13,866
903
218,381
4,813
13,309
75,532
The Numbers – Still WaitingThe Numbers – Still Waiting
http://www.unos.org
ORGAN
Heart
Lung (single or double)
Heart & Lung
Kidney
Pancreas
Kidney & Pancreas
Liver
Feb 2006
3,023
3,122
150
69,752
1,772
2,585
17,734
As of
The Numbers – The WaitThe Numbers – The Wait
http://www.optn.org
ORGAN
Heart
Lung (single or double)
Heart & Lung
Kidney
Pancreas
Kidney & Pancreas
Liver
Days
206+22
704+30
889+120
1099+30
179+35
442+35
517+35
The Numbers – Die WaitingThe Numbers – Die Waiting
http://www.optn.org
ORGAN
Heart
Lung (single or double)
Heart & Lung
Kidney
Pancreas
Kidney & Pancreas
Liver
2/16/04
465
386
15
2,980
28
181
1,506
51,17951,179 DEATHS awaiting ’95-’04
DEATHS awaiting ’95-’04
This yr.
50556065707580859095
100
1-Year 3-Year
Heart
Lung
HL
Kidney
Pancreas
SPK
Liver
Survival Rates (%)Survival Rates (%)
http://www.optn.org
Organ ShortageOrgan Shortage
• less than half of the nation's donor pool is being utilized
• rate of organ donation varies: age, racial, and demographic groups - the family of a donor <50 years old is 5x more likely to consent to
organ donation than a family of a donor >60 years old - African Americans donate organs half as frequently as Caucasians
(Asians, Hispanic)
• differences attributed to several factors: - way families are approached and informed about organ donation
clergy members or social workers are involved in these discussions, higher donation rates
- distrust of the organ donation system
Indiana Donor Choice LawIndiana Donor Choice Law
• supports your donation decision – legal directive• Previously, family consent was required for organ
donation• Now, if 18+ and have signed driver's license, donor card,
or other legal document indicating that you want to be a donor, qualified medical personnel have the legal authority to carry out your last wish
• <18yrs old, can still be a donor, but parents or guardian will be asked for consent
*House Enrolled Act 1628, Amended IC 29-2-16-2.5, effective July, 2001.
Cadaver Donor ProcessCadaver Donor Process• UNOS maintains a centralized computer network linking all organ
procurement organizations & transplant centers.
• When a deceased organ donor is identified, a transplant coordinator from an organ procurement organization accesses UNOS system
• Each patient in the "pool" is matched by the computer against the donor characteristics
• A ranked list of patients for each organ that is procured from that donor is generated
• Factors affecting ranking: tissue match, blood type, length of time on the waiting list, immune status and the distance between the potential recipient and the donor
• The organ is offered to the transplant team of the first person on the list: Often, top patient will not get the organ: must be compatible with donor, must be healthy enough to undergo major surgery, and willing to be transplanted immediately.
http://www.unos.org
Live DonationLive Donation
Living donor transplants are a viable alternative for patients in need of new organs:
• 1954, 23-yr-old identical twins - ktx - Donor went on to live an active, normal life, died from causes unrelated to the transplant
• Related: parents, children, siblings, and other relatives donate to family members
• Unrelated donors (ie. spouses or close friends) may also donate their organs if a match
• Living "stranger-to-stranger" donation is new & growing source of donors – ethics?
http://www.unos.org
Organ Types for Living DonationOrgan Types for Living Donation • Single kidney
most frequent type of living organ donation
• Liverdonate segments of the liver- ability to regenerates & regains full function
• Lungdonate lobes of the lung- lung lobes do not regenerate
• Pancreasdonate a portion of the pancreas - the pancreas does notregenerate, but usually no problems w/ reduced function
-------------------------------• Domino transplant
http://www.unos.org
Qualifications for Living Donors• physically fit, in good general health, & free from high blood
pressure, diabetes, cancer, kidney disease, and heart disease
• usually 18-60 yrs of age
• gender & race are not factors in determining a successful match
• living donor must first undergo a blood test to determine blood type compatibility with the recipient.
http://www.unos.org
Blood Type Compatibility Chart
Recipient DonorO = OA = A or OB = B or OAB = A, B, AB, or O
Qualifications for Living Donors
• Medical history & physical examination
• Tissue Typing: blood draw for tissue typing of the WBCs
• Crossmatching: blood test to check if react to the donor organ"positive," = incompatible, "negative" tx proceeds routinely performed for kidney and pancreas transplants
• Antibody Screen: Donor’s WBCs and recipient’s serum are mixed to see if there are antibodies in the recipient that react with the antigens of the donor
• Urine Tests: kidney donation, urine samples are collected for 24 hours to assess the donor's kidney function
• X-rays & ECG: screen the donor for heart and lung disease
• Arteriogram: screen for CVD
• Psychiatric and/or psychological evaluation: donor & recip.http://www.unos.org
Kidney Transplant
Kidney• Donor kidney ureter is
attached directly to the bladder & is connected to the recipient's blood vessels
Lung TransplantLung Transplant
Lung - uni/bilateral C under armpit - remove rib/s
Lung• Orthotopic - single, double or
heart-lung • living-donor lobar lung tx
-extends lives for double-lung or heart-lung tx-lower lobe of one lung (2 living donors -related or not) transplanted into the recipient-complex & performed rarely
Heart TransplantHeart Transplant
Heart TransplantHeart Transplant
Orthotopic vs HeterotopicOrthotopic vs Heterotopic
Heart - Orthotopic• blood flow diverted from
heart to heart-lung bypass machine & heart stopped with chemical solution
• front part of heart cut away & back walls of left & right atria stay
• donor heart (minus its back walls) grafted into remaining part heart
Heterotopic -"backup battery“
• recipient’s heart not removed -chambers & blood vessels of both hearts
• very rarely used (d-heart need extra help to fx in recipient)
-recipient’s body > donor's
-donor's heart functions
poorly
-pulmonary hypertension
Pancreas TransplantPancreas Transplant
Islet Transplantation • local anaesthetic & 60 mins.
-islets injected into liver & secrete insulin directly into circulatory system to control blood sugars.
Pancreas (PA/SPK)• diseased pancreas & the
duodenum not removed
• donor pancreas & duodenum inserted in right lower portion of patient's abdomen & attached to their blood vessels and intestine
Liver TransplantLiver Transplant
Liver - orthotopic• Removal of the patient's liver,
leaving portions of major blood vessels in place
• donor liver will then be inserted and attached to these blood vessels and to the patient's bile ducts
Heterotopic – • provides an auxiliary liver – fewer
technical difficulties• won't need lifetime
immunosuppressant therapy• worst-case scenario, liver doesn't
come back & donor liver functions in its place just like a regular transplant
• results discouraging rarely used
Liver – live donation
Medical/Surgical ConcernsMedical/Surgical Concerns
• Primary non-function (early) • Bleeding, thrombosis (early)• Infection - bacterial, viral, fungal • Wound infections• Medication toxicities• Rejection • Anastomotic leaks• Other: electrolyte imbalance• Immunosuppressive side effects
- Diabetes- Hypertension- Hyperlipidemia- Increased bone resorption (osteoporosis)
Organ SpecificOrgan Specific Med/Surg ConcernsMed/Surg Concerns
Liver• Biliary leaks, strictures, obstructions• Vascular problems: HAT, HVT • Ascites• Recurrent Disease (HBV, HCV)• Malignanacies - imaging, labs
Kidney/Pancreas• delayed graft function • kidney imaging: renal scan, renal arteriogram
Heart• echo for left ventricular function (global graft
atherosclerosis)
Lung• bronchoscopy• PFTs (FVC, FEV1, F25/75)
Organ SpecificOrgan Specific Med/Surg ConcernsMed/Surg Concerns
RejectionRejection
• Fever or not
• Tenderness or not
• Elevated labs (CBC & organ specific)
• Biopsy
Liver – fever, ↑ labs, bx
Transaminase aspartate aminotransferase (AST)
alanine aminotransferease (ALT)-elevation reflects hepatocyte injury
• Cholestatic enzymes alkaline phosphatase (ALK), bilirubin (tot. bili)
-reflect secretion of bile
• Coagulopathyprothrombin time (PT)
RejectionRejection
Kidney - tenderness, acidic urine and/or ↓urine output, labs, bx
• Blood urea nitrogen (BUN)waste product excreted by kidney – elevated with rejection but can be skewed by high protein intake
• Creatinine (Cr)waste product excreted by kidney – elevated with rejection, dehydration, and with elevated levels of drugs that are toxic to kidney
• Electrolytespotassium, sodium, chloride, bicarbonate, calcium, phosphorus
RejectionRejection
Heart • reduced exercise tolerance and/or SOB• transjugular biopsy• echo for left ventricular function (global graft
atherosclerosis)• Labs: CBC (WBC)
Lung• dyspnea• bronchoscopy with biopsy• PFTs (FVC, FEV1, F25/75)• Labs: CBC (WBC
RejectionRejection
Post Transplant MedicationsPost Transplant Medications
For Transplant:• Immunosuppressants• Antifungals• Antivirals• Antibiotics• Anti ulcers• Digestant
For Side Effects:• Antihypertensives• Antihyperlipidemics• Glucose regulators• Antiosteoporotics• Antidepressants
PLUS other medications for pre-existing conditions
Current ImmunosuppressantsCurrent Immunosuppressants
• cyclosporin (ie.) Sandimmune, Neoral, Gengraf
- inhibit cytokine synthesis & release – early t-cell activation
tacrolimus (ie.) Prograf
- 10-200x more potent than cyclosporin – same mechanism
• azathioprine (ie.) Imuran
- inhibits lymphocyte proliferation
• mycophenolate mofetil (ie.) Cellcept
- inhibits lymphocyte (T & B cells) proliferation – more specific,<toxicity
• sirolimus (ie.) Rapamune
-inhibits cytokine signaling transduction – late t-cell act. & maturation
• corticosteroid (ie.)prednisone
Newest ImmunosuppressantsNewest Immunosuppressants
• daclizumab (ie.) Zenapax
- monoclonal antibodies that inhibit antigen recognition
• basiliximab (ie.) Simulect
- monoclonal for injection only
• anti-thymocyte globulin (rabbit) (ie.) Thymoglobulin
-polyclonal antibodies that inhibit antigen recognition
• muromonab –CD3 (ie.) OKT3 - monoclonal, depletes blood of CD3+ t-cells - leads to restoration of allograft function
Exercise for the Organ Exercise for the Organ Transplant RecipientTransplant Recipient
Peak Oxygen Uptakes in Adult Peak Oxygen Uptakes in Adult PRE Transplant RecipientsPRE Transplant Recipients
0
5
10
15
20
25
30
35
Heart D-Lung Heart &Lung
Kidney Liver Age-Pred.40-49yo
VO2
(ml/kg/min)
Improvements with Improvements with Transplantation Transplantation
Reasons for low functioning Reasons for low functioning following transplantationfollowing transplantation
• Residual effects of pre-transplant disease
• Physical deconditioning / bedrest
• Maintenance of sedentary behavior following transplant
Transplant Rehab Intervention Project
1996 U.S. Transplant Games Fitness 1996 U.S. Transplant Games Fitness TestingTesting
N = 128 • 76 kidney• 16 liver• 19 heart• 6 lung ( 4 single; 2 double)• 8 kidney/pancreas ( 1 pancreas only)• 4 bone marrow
Painter, Transplantation. 64 (12): 1795, 1997
0
50
100
150
% a
ge-
pre
dic
ted
VO
2
0
10
20
30
40
50
Pea
k V
O2
(ml/
kg/m
in)
active
inactive
Transplant Games:Transplant Games: cardiorespiratorycardiorespiratory fitnessfitness
p=.0001p=.000
Painter, Transplantation. 64 (12): 1795, 1997
0
10
20
30
40
0
10
20
30
40
p=.05p=.02
Ski
nfo
ld %
fat
active
inactive
Transplant Games: body compositionTransplant Games: body composition
BMI
Painter, Transplantation. 64 (12): 1795, 1997
0
20
40
60
80
100
120
PF RP BP GH VT SF RE MH
p=.05
p=.08p=.05p=.07
p=.03
Sca
le S
core
s
active
inactive
Transplant Games Survey: SF-36 Scales Scores Transplant Games Survey: SF-36 Scales Scores
Painter, Transplantation. 64 (12): 1795, 1997
Transplantation and ExerciseTransplantation and Exercise
Heart Transplant & ExerciseHeart Transplant & Exercise
ExerciseBL 9.2 ml/kg/min
6-mth 13.6 ml/kg/min
49% improvement
Kobashigawa, N Engl J Med. 340: 272, 1999.
ControlBL 10.4 ml/kg/min
6-mth 12.3 ml/kg/min
18% improvement
n= 27 post heart transplant recipients6 mth aerobic exercise training – rehab.
Heart & Lung Transplant & ExerciseHeart & Lung Transplant & Exercise
n=10 -41 days post tx& followed for 18 mths-supervised increm.ex. to BID 30 min.sessions -cont. walking
(70% max) -inspiratory muscle training-only 10 completed rehab.
Ambrosino N. Eur Respir J., 9:108, 1996.
0
10
20
30
40
50
60
Admit DC 6-mth 12-mth 18-mth
VO2peak
Lung Transplant & ExerciseLung Transplant & Exercise
ExerciseBaseline = 18.4
ml/kg/min
6-wks 20.3 ml/kg/min
18% improvement
n = 9 - 1yr post lung tx 6 wks aerobic endurance training, cycle ergometer30 – 60% of HRR; 60 min increased to 120 min
Stielbellehner L. Chest 1998; 113:906-12
Liver Transplant & ExerciseLiver Transplant & Exercise
n = 17, 1mth post OLT
step, cycle ergometry
2x/week, 1hr – intensity individualized
Liver Transplantation & ExerciseLiver Transplantation & Exercise
Pre OLT 3 6 12
160
140
120
100
80
180
200
0
KE conc (Nm)
VO2max (l/min)
Rel
ativ
e ch
ang
e (%
)
Months post OLT
Beyer, Liver Transplantation 5(4): 301, 1999.
BASELINE 6 MONTHS 12 MONTHS
15
20
25
30
35
40
45
PEA
K V
O2
(m
l/K
g/m
in)
*
exercise
usual care
Kidney Transplant & ExerciseKidney Transplant & ExerciseCardiorespiratory Fitness (VO2max)Cardiorespiratory Fitness (VO2max)
Kidney-Transplant Rehab Intervention Project
Painter, Transplantation, 74(1): 42, 2002.
40
60
80
100
120
BASELINE 6 MONTHS 12 MONTHS
% A
GE-P
RED
ICTED
PEA
K V
O2
**
exercise
usual care
Kidney Transplant & ExerciseKidney Transplant & Exercise% Age - Predicted VO2 max% Age - Predicted VO2 max
Kidney-Transplant Rehab Intervention Project
Painter, Transplantation, 74(1): 42, 2002.
20
30
40
50
60
BASELINE 6 MONTHS 12 MONTHS
Exte
nsio
n P
eak T
orq
ue/
Bod
y W
eig
ht
*
exercise
usual care
*
Kidney Transplant & ExerciseKidney Transplant & ExerciseQuadriceps Muscle StrengthQuadriceps Muscle Strength
Painter, Transplantation, 74(1): 42, 2002.Kidney-Transplant Rehab Intervention Project
Goals of ExerciseGoals of Exercise
• Prevent physical deconditioning• Optimize/maintain physical functioning• Reduce symptoms of disease • Optimize medical therapies• Optimize surgical interventions• Optimize quality of life• Reduce risk of secondary cardiovascular
events
CV RiskCV Risk
Reduces risk of:• dying from heart disease• developing diabetes• developing hypertensionHelps reduce and control:• hypertension• hypercholesterolemia• obesity• hyperglycemia
Exercise TestingExercise Testing
• lots of recent clinical data on patient
• may not – know the purpose- performance based testing
• standard exercise testing protocols
• ECG and BP monitoring
• same test termination criteria as ACSM
Fitness TestingFitness Testing
Strength maximal voluntary contraction (1 RM),
isokinetic work and peak torque
Muscular endurance maximal number of repetitions
Flexibilitysit and reach distances, goniometry (ROM)
Cardiorespiratory endurancemaximal oxygen consumption (VO2max), submaximal bike test, step test
Fitness TestingFitness Testing
Body Composition
hydrostatic weighting, skinfolds, dual energy x-ray absorptiometry
---------------------------------------------------------------
Motor Skill Performance (neuromuscular)
gait analysis, balance times, reaction time
Functional Performance
sit to stand, 6-minute walk
Cardiovascular ActivityCardiovascular Activity
Mode: utilizes large muscle groups in a continuous, repetitive motion
(ing’s)Frequency: 3-5x/week - 2x/dayDuration: 2x10 mins -45 mins. consecutive Intensity: tolerate, moderate exertion,
“somewhat hard” Progression: duration, frequency and intensity
are adjusted according to patient’s status and goals
Muscular StrengtheningMuscular Strengthening
• Select a weight that can be lifted 10x
without excessive muscular fatigue
• 1 set of 10 repetitions for each muscle group
• When reps. = 15 then wt by 1-2 lbs.
• 3 days per week
* May need to start with Theraband™
Special ConsiderationsSpecial Considerations
• Deconditioning- muscle atrophy
• Side effects of immunosuppressants- diabetes
- hypertension
- hyperlipidemia
- muscle wasting
- reduced bone mineral density
• Rejection • Infection• Wound Management• Procedures
- biopsy, JP drains• Electrolyte imbalance
– ECG & muscle cramping
Heart TransplantHeart Transplant
PRECAUTIONSPRECAUTIONS
• No nervous Intervention
• Rejection
• No nervous Intervention
• Rejection
Heart TransplantHeart Transplant PRECAUTIONSPRECAUTIONSH
eart
Rat
eH
eart
Rat
e
Exercise TimeExercise Time
Higher RestingHigher Resting
Slower ResponseSlower Response
Lower MaxLower Max
Longer RecoveryLonger Recovery
Simila
r BP
Respo
nse
Simila
r BP
Respo
nse
Heart TransplantHeart Transplant
PRECAUTIONSPRECAUTIONS
• No nervous Intervention
• Cannot Feel Angina
• No nervous Intervention
• Cannot Feel Angina
Transplant AtherosclerosisTransplant Atherosclerosis
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
0102030405060708090
100
1 2 5
Incid
ence (%
)
Transplant AtherosclerosisTransplant Atherosclerosis
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
• As early as three months
• Not isolated to heart
• Renal Arteries of Kidney
Transplant AtherosclerosisTransplant Atherosclerosis
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
• Diffuse
• All Epicardial & Intramural arteries
• Intimal inflitrate
• Lacking calcification
• Without marked disruption of the internal elastic lamina
Transplant AtherosclerosisTransplant Atherosclerosis
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
Transplant AtherosclerosisTransplant Atherosclerosis
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
0
10
20
30
40
50
60
70
1 2 5
Surv
ival (
%)
Transplant AtherosclerosisTransplant Atherosclerosis
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
• Treatment is re-transplantation
• 25% of organs
Lung• Lose cough reflex
-pulmonary hygiene (self-induce, postural drainage)
• Bronchial reactivity
• Pneumothorax
• Infectious exacerbations
• Most present with ↓↓ bmd or fxs
• O2 tank= security
• Dyspnea scale
Organ Specific Special Organ Specific Special ConsiderationsConsiderations
Liver• Incisional hernia
• Low back pain
• Bile leaks, strictures, obstruction
• Recurrent disease
- HCV: IFN treatment, fatigue, anemia
Organ Specific Special Organ Specific Special ConsiderationsConsiderations
Kidney/Pancreas• Diabetic - neuropathy blunted HR
response
Organ Specific Special Organ Specific Special ConsiderationsConsiderations