pediatric and adult transplantation organs heart lung (single or double) heart & lung kidney...

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


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


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


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


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

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


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


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


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


% 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


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


PRECAUTIONSPRECAUTIONS

• No nervous Intervention

• Rejection


• 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


PRECAUTIONSPRECAUTIONS


• Cannot Feel Angina


• Cannot Feel Angina

Transplant AtherosclerosisTransplant Atherosclerosis

Fyfe, A.I., Canadian Journal of Cardiology 8:509-519, 1992

0102030405060708090

100

1 2 5

Incid

ence (%

)



• As early as three months

• Not isolated to heart

• Renal Arteries of Kidney



• Diffuse

• All Epicardial & Intramural arteries

• Intimal inflitrate

• Lacking calcification

• Without marked disruption of the internal elastic lamina



0

10

20

30

40

50

60

70

1 2 5

Surv

ival (

%)



• 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


Kidney/Pancreas• Diabetic - neuropathy blunted HR

response


pediatric and adult transplantation organs heart lung (single or double) heart & lung kidney...

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