Transcript LTX Case Study - Indiana University Bloomington

Pediatric and Adult
Transplantation
• ORGANS
• TISSUES
Heart
Lung (single or double)
Heart & Lung
Kidney
Pancreas
Kidney & Pancreas
Intestine
Bone Marrow
Stem Cell
Cornea
Heart valves
Tendons
Skin
Bone
The Numbers - Completed
http://www.unos.org
The Numbers
30,000
25,000
20,000
Total
Deceased
Living
15,000
10,000
5,000
0
1988 1990 1995 2000 2005
http://www.unos.org
The Numbers – By Organ
ORGAN
Feb 2006
Heart
38,878
Lung (single or double)
13,866
Heart & Lung
Kidney
Pancreas
903
218,381
4,813
Kidney & Pancreas
13,309
Liver
75,532
http://www.unos.org
The Numbers – Still Waiting
ORGAN
Heart
Lung (single or double)
Heart & Lung
Kidney
As of
Feb 2006
3,023
3,122
150
69,752
Pancreas
1,772
Kidney & Pancreas
2,585
Liver
17,734
http://www.unos.org
The Numbers – The Wait
ORGAN
Heart
Days
206+22
Lung (single or double)
704+30
Heart & Lung
889+120
Kidney
1099+30
Pancreas
179+35
Kidney & Pancreas
442+35
Liver
517+35
http://www.optn.org
The Numbers – Die Waiting
ORGAN
This yr.
2/16/04
Heart
465
Lung (single or double)
386
Heart & Lung
Kidney
15
2,980
Pancreas
28
Kidney & Pancreas
181
Liver
1,506
http://www.optn.org
Survival Rates (%)
100
95
90
85
80
75
70
65
60
55
50
Heart
Lung
HL
Kidney
Pancreas
SPK
Liver
1-Year
3-Year
http://www.optn.org
Organ 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 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 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 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 Donation
• Single kidney
most frequent type of living organ donation
• Liver
donate segments of the liver- ability to regenerates &
regains full function
• Lung
donate lobes of the lung- lung lobes do not regenerate
• Pancreas
donate a portion of the pancreas - the pancreas does not
regenerate, 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.
Blood Type Compatibility Chart
Recipient
O
A
B
AB
=
=
=
=
Donor
O
A or O
B or O
A, B, AB, or O
http://www.unos.org
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 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 doublelung or heart-lung tx
-lower lobe of one lung (2
living donors -related or not)
transplanted into the
recipient
-complex & performed rarely
Heart Transplant
Heart Transplant
Orthotopic vs Heterotopic
Heart - Orthotopic
Heterotopic -"backup battery“
• blood flow diverted from • recipient’s heart not removed
heart to heart-lung
-chambers & blood vessels of
bypass machine & heart
both hearts
stopped with chemical
• very rarely used (d-heart
solution
need extra help to fx in
• front part of heart cut
recipient)
away & back walls of left
-recipient’s body > donor's
& right atria stay
-donor's heart functions
• donor heart (minus its
poorly
back walls) grafted into
-pulmonary hypertension
remaining part heart
Pancreas Transplant
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
Islet Transplantation
• local anaesthetic & 60 mins.
-islets injected into liver & secrete insulin directly into
circulatory system to control blood sugars.
Liver 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 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 Specific Med/Surg Concerns
Liver
•
•
•
•
•
Biliary leaks, strictures, obstructions
Vascular problems: HAT, HVT
Ascites
Recurrent Disease (HBV, HCV)
Malignanacies - imaging, labs
Organ Specific Med/Surg Concerns
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)
Rejection
•
•
•
•
Fever or not
Tenderness or not
Elevated labs (CBC & organ specific)
Biopsy
Rejection
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
• Coagulopathy
prothrombin time (PT)
Rejection
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
• Electrolytes
potassium, sodium, chloride, bicarbonate, calcium,
phosphorus
Rejection
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
Post Transplant Medications
For Transplant:
For Side Effects:
•
•
•
•
•
•
•
•
•
•
•
Immunosuppressants
Antifungals
Antivirals
Antibiotics
Anti ulcers
Digestant
Antihypertensives
Antihyperlipidemics
Glucose regulators
Antiosteoporotics
Antidepressants
PLUS other medications for pre-existing conditions
Current 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 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
Transplant Recipient
Peak Oxygen Uptakes in Adult
PRE Transplant Recipients
35
30
25
VO2
(ml/kg/min)
20
15
10
5
0
Heart
D-Lung
Heart &
Lung
Kidney
Liver
Age-Pred.
40-49yo
Improvements with
Transplantation
Reasons for low functioning
following 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
Testing
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
Transplant Games: cardiorespiratory fitness
150
40
p=.0001
30
20
% age-predicted VO2
Peak VO2 (ml/kg/min)
50
active
p=.000
inactive
100
50
10
0
0
Painter, Transplantation. 64 (12): 1795, 1997
Transplant Games: body composition
40
active
40
Skinfold % fat
inactive
30
30
p=.05
20
BMI
p=.02
20
10
10
0
0
Painter, Transplantation. 64 (12): 1795, 1997
Transplant Games Survey: SF-36 Scales Scores
120
active
p=.05
inactive
Scale Scores
100
p=.08
p=.07
80
p=.05
p=.03
60
40
20
0
PF
RP
BP
GH
VT
SF
RE
MH
Painter, Transplantation. 64 (12): 1795, 1997
Transplantation and Exercise
Heart Transplant & Exercise
Exercise
BL 9.2 ml/kg/min
6-mth 13.6 ml/kg/min
Control
BL 10.4 ml/kg/min
6-mth 12.3 ml/kg/min
49% improvement
18% improvement
n= 27 post heart transplant recipients
6 mth aerobic exercise training – rehab.
Kobashigawa, N Engl J Med. 340: 272, 1999.
Heart & Lung Transplant & Exercise
n=10
60
-41 days post tx
50
& followed for 18 mths
40
-supervised increm.
30
ex. to BID 30 min.
20
sessions
10
-cont. walking
(70% max)
0
-inspiratory muscle training
-only 10 completed rehab.
VO2peak
Admit
DC
6-mth
12-mth
18-mth
Ambrosino N. Eur Respir J., 9:108, 1996.
Lung Transplant & Exercise
Exercise
Baseline = 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 ergometer
30 – 60% of HRR; 60 min increased to 120 min
Stielbellehner L. Chest 1998; 113:906-12
Liver Transplant & Exercise
n = 17, 1mth post OLT
step, cycle ergometry
2x/week, 1hr – intensity individualized
Relative change (%)
Liver Transplantation & Exercise
200
180

160
140
80


120
100




VO2max (l/min)

KE conc (Nm)
0
Pre OLT
3
Months post OLT
6
12
Beyer, Liver Transplantation 5(4): 301, 1999.
Kidney Transplant & Exercise
Cardiorespiratory Fitness (VO2max)
PEAK VO2 (ml/Kg/min)
45
40
exercise
35
usual care
30
*
25
20
15
BASELINE
6 MONTHS
12 MONTHS
Kidney-Transplant Rehab Intervention Project
Painter, Transplantation, 74(1): 42, 2002.
Kidney Transplant & Exercise
% Age - Predicted VO2 max
% AGE-PREDICTED PEAK VO2
120
exercise
100
usual care
**
80
60
40
BASELINE
6 MONTHS
12 MONTHS
Kidney-Transplant Rehab Intervention Project
Painter, Transplantation, 74(1): 42, 2002.
Kidney Transplant & Exercise
Quadriceps Muscle Strength
60
Extension Peak Torque/
Body Weight
exercise
usual care
50
**
40
30
20
BASELINE
6 MONTHS
12 MONTHS
Kidney-Transplant Rehab Intervention Project
Painter, Transplantation, 74(1): 42, 2002.
Goals 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 Risk
Reduces risk of:
• dying from heart disease
• developing diabetes
• developing hypertension
Helps reduce and control:
• hypertension
• hypercholesterolemia
• obesity
• hyperglycemia
Exercise 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 Testing
Strength
maximal voluntary contraction (1 RM),
isokinetic work and peak torque
Muscular endurance
maximal number of repetitions
Flexibility
sit and reach distances, goniometry (ROM)
Cardiorespiratory endurance
maximal oxygen consumption (VO2max),
submaximal bike test, step test
Fitness 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 Activity
Mode:
utilizes large muscle groups in a
continuous, repetitive motion (ing’s)
Frequency: 3-5x/week - 2x/day
Duration: 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 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 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 Transplant
PRECAUTIONS
• No nervous
Intervention
• Rejection
Heart Transplant PRECAUTIONS
Higher Resting
Slower Response
Heart Rate
Lower Max
Longer Recovery
Exercise Time
Heart Transplant
PRECAUTIONS
• No nervous
Intervention
• Cannot Feel
Angina
Incidence (%)
Transplant Atherosclerosis
100
90
80
70
60
50
40
30
20
10
0
1
2
5
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
Transplant Atherosclerosis
• As early as three months
• Not isolated to heart
• Renal Arteries of Kidney
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
Transplant Atherosclerosis
• Diffuse
• All Epicardial & Intramural arteries
• Intimal inflitrate
• Lacking calcification
• Without marked disruption of the
internal elastic lamina
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
Transplant Atherosclerosis
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
Transplant Atherosclerosis
70
Survival (%)
60
50
40
30
20
10
0
1
2
5
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
Transplant Atherosclerosis
• Treatment is re-transplantation
• 25% of organs
Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992
Organ Specific Special
Considerations
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
Considerations
Liver
•
•
•
•
Incisional hernia
Low back pain
Bile leaks, strictures, obstruction
Recurrent disease
- HCV: IFN treatment, fatigue, anemia
Organ Specific Special
Considerations
Kidney/Pancreas
• Diabetic - neuropathy blunted HR
response