LUNG TRANSPLANTATION

LUNG TRANSPLANTATION
PROTOCOL
Iskander S. Al-Githmi, MD
Anthony P. Yim, MD
The Chinese University of Hong Kong
and
Prince of Wales Hospital

TABLE OF CONTENTS
1. INTRODUCTION
2. CURRENT STATUS
3. PREOPERATIVE EVALUATION OF TRANSPLANT CANDIDATES
3.1 Criteria for Candidate Selection
3.2 Absolute Contraindications for Transplantation
3.3 Logistics of Patient Referral
3.4 Letter of Transplantation Program
3.5 Introduction to the Referring Physician
3.6 Transplantation Referral Guidelines & questionairs
3.7 Guidelines for the Social Worker
3.8 Worksheet for the Referring Centre
3.9 Candidate Evaluation Orders for Lung Transplantation
3.10 Preoperative Orders for Lung Transplant Recipient
4. DONOR-RECIPIENT MATCHING
5. PREOPERATIVE MANAGEMENT OF MULTIORGAN DONORS
5.1 Criteria for Acceptable Lung Donors
5.2 Preoperative Assessment of Multiorgan Donors
5.3 Management of Multiorgan Donors
5.4 Special Considerations for the Preoperative Management o
5.5 Multiorgan Donor Assessment and Record
5.6 Donor Orders For Multi-Organ Transplantation
6. COORDINATION OF THE TRANSPLANTATION PROCEDURE: A CHECKLIST
7. PROCEDURE FOR LUNG TRANSPLANTATION
7.1 Preparation of Perfadex Solution
7.2 Procedure for Donor Double Lung Resection
7.3 Procedure for Double Lung Transplantation
8. POST-TRANSPLANT ORDERS AND MANAGEMENT
8.1 Immediate Postoperative Orders
8.2 Transfer Orders
9. IMMUNOSUPPRESSION
9.1 Introduction
9.2 Immunosuppressive Protocol
9.3 Administration Procedure for Anti-Thymocyte Globulin
10. IMMUNOLOGIC MONITORING
10.1 Immune Activation
10.2 Cyclosporine Levels
10.3 Absolute Lymphocyte Count
10.4 Chest Roentgenography, Bronchoscopy and Lung Biopsies

11. TREATMENT OF REJECTION
11.1 Rejection In the First Three Months Post-transplant
11.2 After the First Three Months Post-transplant
11.3 Management of bronchiolits obliterans
12. PROPHYLAXIS AND TREATMENT OF INFECTION
12.1 Technique for Transtracheal Aspiration
12.2 Administration Procedure for Amphotericin B
12.3 CMV, HSV, EBV Prophylaxis Protocol
13. PATIENT ISOLATION
13.1 Criteria for Reverse Isolation
13.2 Patient Isolation in the ICU
13.3 Patient Isolation in the Ward Private Room
13.4 Visitation by Children, Friends, Family
14. VENTILATORY SUPPORT
15. RENAL FUNCTION
16. CENTRAL NERVOUS SYSTEM
17. POST-LUNG TRANSPLANT ASSESMENT
18. DATE DISCHARGE PROTOCOL GUIDELINES
18.1 0-3 months protocol guidelines
18.2 3-6 months protocol guidelines
18.3 6 months-1 year protocol guidelines
18.4 1-2 year protocol guidelines
18.5 > 2 years protocol guidelines

1. INTRODUCTION
The purpose of this syllabus is to review the management guidelines for recipients
of, single lung and bilateral single lung transplants. Concepts contained herein
derive predominantly from the experience at the Toronto lung program, Stanford
University Medical Centre, the international transplantation experience, and the
input of the recent literature.
The enclosed protocols for patient assessment and management represent our own
view on the current state-of-the-art assessment and management principles.
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2. CURRENT STATUS
Lung transplantation are currently indicated for patients with advanced forms of
lung disease, in whom no realistic hope for extension of life or palliation exists
with ordinary forms of medical or surgical intervention. Since, the introduction of
Cyclosporine in December, 1980, and further refinements in management
strategies have moved biologic lung transplantation from an experimental study to
a truly therapeutic procedure with a one year survival rate of 75% to 80% and an
expected five year survival rate of 45% to 55% in the best centres. As of 2003, the
most recent data from the International Heart Transplant Registry indicates that
more than 15000 lung transplants, were performed worldwide.
2.1 Indications
a. Single Lung Transplantation - emphysema (44%), idiopathic pulmonary
fibrosis (17.9%), alpha 1 anti-trypsin deficiency (12.8%), primary
pulmonary hypertension (7.5%), re-transplant (3.3%), cystic fibrosis
(1.6%), miscellaneous (12.9%).
b. Bilateral/Double Lung Transplantation - cystic fibrosis (37.5%),
emphysema (15.6%), alpha 1 anti-trypsin deficiency (10.2%), primary
pulmonary hypertension (11%), idiopathic pulmonary fibrosis (5.8%), retransplant
(3.6%), miscellaneous (16.3%).
2.2 Outcomes
Lung actuarial survival for single lung at 1year is approximately 75%, 5 years
is approximately 45-55%. Bilateral or double lung transplantation survival is
similar.
Better results may be achieved with emphysema and alpha I anti-trypsin
deficiency with 1year and 2 year survival rates in the order of 77% and 70%
respectively compared to idiopathic pulmonary fibrosis and primary
pulmonary hypertension with 1 and 2 year survival rates of 65% and 57%
respectively.
Comparable results have been achieved with double lung transplantation in
this same era. Of interest, single lung transplantation and has a one year
survival rate for patients with emphysema of 80% at 1year as opposed to
bilateral or double lung transplantation for which the 1 year survival rate
has been 60%. For primary pulmonary hypertension, the 18-month survival
rate for single lung and bilateral double lung transplantation is
approximately 64% and for heart/lung transplantation approximately 55%.
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2.3 Causes of death following lung transplantation include:
• 0-30 days
Nonspecific graft failure, infection, dehiscence, hemorrhage, acute
rejection, other.
• 31 days to 1 year
Infection, non-specific graft failure, bronchiolitis, malignancy, other.
• >1 year
Bronchiolitis, infection, non-specific graft failure, other.
2.4 Re-transplantation
Lung re-transplants account for 2.2 to 3%,of all lung transplants.Only 450
lung re-transplants have been performed worldwide.Actuarial survival is
approximately 45% at 1 year and 30% at 3 years. Because of lack of
available donors lung and increasing number of waiting for lung
transplantation, most of lung transplants center do not offer lung
retransplantation.The basic indication for redo lung transplantation are
acute and chronic graft failure.
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3. PREOPERATIVE EVALUATION OF LUNG TRANSPLANTATION CANDIDATES
The goal of preoperative evaluation is the identification of individuals most likely
to benefit in terms of survival and rehabilitation following transplantation. Such
individuals are those with end-stage pulmonary disease for which no efficacious or
clinically proven form of treatment other than lung transplantation exists.
Personnel capable of the accurate assessment of such patients include an
appropriately trained pulmonologist, thoracic surgeon, with the assistance of a
social worker and transplantation coordinator.
The general criteria for the selection of potential lung transplantation candidates
include:
3.1 Criteria for Candidate Selection
3.1.1 Evidence of advanced physical incapacitation due to lung disease.
The patient should be functionally limited.
3.1.2 Life expectancy estimated to be weeks or months. Stated
differently, the patient must have less than a 20% likelihood of
surviving one year.
3.1.3 An exception to conditions (3.1.1) and (3.1.2) above is the patients
with intractable respiratory failure.
3.1.4 Agreement that previous medical therapy has been optimal and that
no surgical procedure other than transplantation offers realistic
expectation of functional improvement and extension of life.
3.1.5 The absence of sepsis, irreversible renal or liver dysfunction or other
disease processes (eg. HIV positivity) that might otherwise cause an
early death or be seriously aggravated by transplantation.
3.1.6 Strong family support to aid the patient emotionally during the preand
post-operative period, and for the rest of his/her life.
3.1.7 Satisfactory intelligence, motivation and compliance to compulsively
follow all medical recommendations including attendance at followup
appointments and changes in exercise and dietary regimes.
3.1.8 A reasonable understanding by the patient of his/her current illness
with a realistic attitude and understanding of what transplantation
can offer as well as the potential complications.
3.1.9 A strong will and desire to live and to return to his/her family and
community as a functioning member.
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3.2 ABSOLUTE CONTRAINDICATIONS FOR TRANSPLANTATION
During the evolution of the clinical transplantation internationally, multiple
patient-related factors have come to be recognized as adversely affecting
the outcome of lung transplantation. These factors constitute, relative or
absolute contraindications to transplantation. However, selection criteria
have already undergone considerable change and are expected to undergo
further modification with the development of less toxic methods for
immunosuppression. Restraints currently observed reflect the present
`state of the art' in lung transplantation. The following factors exert an
adverse influence on the outcome of transplantation:
3.2.1 Severe pulmonary hypertension (> than 6 wood units. 640 dyne-seccm2,
an indication for heart/lung transplantation).
3.2.2 Severe irreversible hepatic or renal dysfunction.
3.2.3 Active systemic infection (i.e. sepsis).
3.2.4 Systemic disease such as systemic lupus, muscular dystrophy, HIV
positivity, metastatic cancer, Hepatitis B positivity with active
hepatitis or cirrhosis.
3.2.5 Severe non-correctable peripheral or cerebrovascular disease.
3.2.6 History of significant behaviour problem, e.g. frankly psychotic, drug
or alcohol abuse.
3.2.7 Clear history of non-compliance.
3.3 LOGISTICS OF PATIENT REFERRAL, EVALUATION AND ACCEPTANCE
For referring physicians of potentialcandidates for lung transplantation, it
has been determined that a patient is a suitable candidate, the `Lung
Transplantation Worksheet' for the referring center must be completed by
the referring physician, nurse and/or secretary, and submitted with a
complete psychosocial history (family background, education, work history,
family constellation,available support systems,etc.) of the patient and
his/her family to the lung transplantation center at Prince of Wales
hospital.
Once it appears likely that sufficient financial resources can be mobilized to
meet the needs of the potential recipient candidate, and once a suitable
psychosocial history for the patient and family have been obtained, this
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information and all relevant medical information will be reviewed and a
final assessment and decision made at the Prince of Wales hospital.
The `Candidate Evaluation Orders for LungTransplantation' details the final
evaluation required for potential recipients of lung transplantation at the
Prince of Wales Hospital.
The format for listing accepted transplant candidates is by name; age; sex;
medical record number; diagnosis; height; weight; date accepted into the
program; local address; local phone and cell phone number; referring
physician; blood type including the patient's ABO and RH blood type; most
recent cardiac catheterization data (including pulmonary vascular
resistance); cytotoxic lymphocyte antibody screen; information and date of
previous transfusions or; HLA phenotype; complete blood count and
differential; coagulation data; liver and kidney function analyses; serology
for HBsAg, HIV, EBV, CMV and Toxoplasmosis; skin testing for T.B.; and most
recent chest film. All data is dated.
The preoperative orders for, lung transplant patients at the time of
transplantation are detailed on page....... These orders are useful for
candidates accepted via the aforementioned described process as well as
emergency patients for whom a full workup cannot be fully completed with
all data in hand at the time of acceptance and urgent request for a donor.
In addition, for patients who undergo conventional evaluation and
acceptance, these orders ensure that all tests have been performed
preoperatively.
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3.4 LETTER OF INTRODUCTION TO THE REFERRING PHYSICIAN
Dear Doctor:
The Lung Transplantation Program at the Prince of Wales Hospital began in 2006.
We believe it is time to inform our colleagues in the region we serve of the status
of our program. In the interests of both busy physicians and sick patients, we
would also like to simplify the process of referral to the program.
It appears that some patients who might be accepted for transplant are not being
referred because the indications are not well publicized or understood.
Conversely, physicians may expend a great deal of effort preparing data, to refer a
patient who turns out to be unsuitable for transplant.
The simplest method of referral is to send a referral letter and a medical summary
of the patient to:
Lung Transplantation program
Prince of Wales Hospital
Shatin, N.T.
When deciding whether to refer a patient for lung transplant, you should read the
enclosed `Lung Transplant Referral Guidelines'. It should be emphasized that these
are guidelines only, and are not cast in stone. Most of the contraindications are
relative ones.
If you have questions as to the suitability of a patient, please feel free to call the
centre.
If you would prefer to leave a message and have one of us return your call, then
phone 852-2632-2211 and ask for the Recipient Transplant Coordinator on call .
The Transplant Coordinator will ensure that one of us will return your call as soon
as possible. We would be happy to answer any enquiries general or specific.
Yours sincerely,
-------------------------------MD.
Lung Transplantation program
Prince of Wales Hospital
Shatin, N.T.
Hong Kong
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LETTER OF INTRODUCTION TO THE REFERRING PHYSICIAN
Dear Dr.:
Thank you for your interest in the Chinese University,Prnice of Wales Hospital Lung
Transplant Program.
Potential transplant candidates must be young (under age 65), or biologically young
(and chronologically older), vigorous and healthy except for end stage lung disease
with a stable psychological and social situation. Patients should be functional Class
III- IV (NYHA) and/or have a life expectancy of less than two years.
The patient and supportive family member must be financially able to meet
transportation expenses and cost of living in the Hong Kong area for a period of
several months.
There are two major components for completion of your referral:
1. Medical - For the Physician
a) Please review the enclosed `Lung Transplantation Guidelines for the
Physician'.
b) Please discuss the transplant procedure, survival rates and outcome,
financial and logistical requirements with your patient and his/her
family.
c) If you and your patient decide to pursue lung transplantation evaluation
at the Prince of Wales Hospital, please complete the enclosed `Lung
Transplantation Worksheet for the Referring Center' to accompany your
referral material.
d) If, upon review of the enclosed material, you or your patient decide not
to pursue transplantation at the Prince of Hospital, or If your patient
expires during the period of referral, we would greatly appreciate a
brief note to that effect.
2. Psychosocial/Financial History for the Social Worker
Please give your social worker the enclosed `Lung Transplantation Guidelines - for
the Social Worker' to assist in completion of a written psychosocial and financial
history.
Copies of all referral data (medical as well as psychosocial and financial) must be
received before the transplant team can make a decision regarding the patient's
suitability for final transplant candidacy evaluation at this centre. You will be
contacted regarding your patient's candidacy status upon review of all materials by
the transplant team.
We hope we can be of assistance to you and your patient. Thank you for your
cooperation.
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Yours sincerely,
________________________MD.
Lung Transplantation Program
Prince of Wales Hospital
Shatin, N.T
Hong Kong
JRB
Enclosures: as stated
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3.5 LUNG TRANSPLANTATION REFERRAL GUIDELINES
Introduction
Age
These should be viewed as guidelines only since criteria are
constantly changing. The only absolute contraindications are,
serology positive for HIV, Hepatitis B, Hepatitis C, uncontrolled
sepsis, metastatic cancer.
Physiologic not chronologic age is more important. Our nominal age
limit is 65 but we would transplant older patients if otherwise
healthy with no other contraindications.
Functional Class
Patients should be functional Class III- IV (NYHA). However, we
would consider patients temporarily in a better functional class due
to therapy, particularly those on maximal therapy.
General Health
Compliance
Except for end-stage lung disease, patients should be healthy.
Patients must be capable of following a complex medical regimen.
Those with a history or likelihood of major problems with
compliance may not be accepted.
Emotional Stability & Motivation
Support
Patients should be emotionally stable and have realistic attitudes
toward illness, outcome, and transplantation. They will do better if
they have a strong desire to live and to return to normal productive
lives.
Candidates need some person(s) able and willing to provide support
before and after transplantation. Either at home, or if necessary,
someone who will relocate to the transplant centre.
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Expectations
Patients should have an understanding of what is involved in
transplantation and should realize that they are coming for
evaluation. Acceptance for transplantation occurs after our
assessment and review of the clinical data.
Physician Support
The referring or some other local physician should be prepared to
assist in caring for transplant patients following transplantation and
return to their communities. Following our first clinical assessment
of the patient, it would be of considerable assistance to our program
if the referring physician were able to undertake the preliminary
laboratory assessment of the patient. If this is possible, a detailed
list of the requirements would be forwarded by the Recipient
Transplant Coordinator.
Contraindications
1. Systemic disease such as lupus, muscular dystrophy, noncorrectable
vascular disease, HIV, Hepatitis B with active
hepatitis or cirrhosis, cancer, etc..
2. Active infection, sepsis.
3. Pre-renal azotemia and/or hepatic dysfunction.
4. Morbid obesity.
5. History of major alcohol or drug abuse or mental illness.
6. Clear history of non-compliance
3.6 LUNG TRANSPLANTATION QUESTIONAIR
For consideration for transplantation at the Prince of Wales Hospital, please
direct your attention to the following:
1. Is the patient under 65 years of age?
2. Is the patient functional ClassIII- IV (NYHA)? Does he/she have a life
expectancy of less than two years?
3. Except for end stage lung disease, is the patient a vigorous and
healthy individual who would benefit from the procedure?
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4. Has the patient demonstrated the ability to take medications
faithfully and comply with medical recommendations? (The
postoperative transplant course demands rigorous attention to a
complex immunosuppressive drug, exercise, and dietary regimen for
the rest of the patient's life and also requires the patient to return
for repeat clinical and laboratory evaluations in the future).
5. Has the patient demonstrated emotional stability and a realistic
attitude in response to past and current illness? (Denial of
symptoms or recurrent situational depression are likely to recur
post-transplantation if they are present now.)
6. Does the patient have a strong desire to live and have a stable,
rewarding family and/or vocational environment to return to posttransplantation?
7. Does that patient have a spouse, family, and/or companion who is
able and willing to make a long-term commitment to providing
emotional support of the patient both pre- and post-transplantation?
8. Does that patient have a strong, supportive family constellation that
is able and willing to tolerate the family upheaval and stresses of
lung transplantation? (Family conflict is likely to recur if present
now.)
9. Are financial resources available to the patient to pay for:
a) Travel to Hong Kong accompanied by a supportive family
member for final evaluation of transplantation candidacy
(and return home)?
b) Living expenses for the patient and family while in the Hong
Kong area before, during and after transplantation?
c) Semi-annual travel to the Prince of Wales Hospital,
indefinitely, for medical follow-up and during acute rejection
episodes.
10. Have you discussed these guidelines with the patient and/or family
and factually informed them of the transplant procedure, survival
statistics, current risks, complications, and financial commitment
required?
11. Are you or another person willing to care for this patient if he
returns to your community post-transplantation? The responsible
pulmonologist or internist must be available, aggressive,
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knowledgeable (or willing to become so) in the care and
complications of the immunosuppressed patient, and absolutely
dedicated to keeping the patient alive long-term.
3.7 GUIDELINES FOR THE SOCIAL WORKER
These guidelines have been developed to assist you in the completion of a
written psychosocial and financial history to aid in the evaluation of your
patient as a possible candidate for lung transplantation at the Prince of
Wales Hospital.
1. Please provide a factual and complete psychosocial history (family
background, education, work history, current family constellation,
available support system, etc.) of the patient and of his/her family.
Please comment on the patient's ability (coping mechanisms) to
comply with a rigorous therapeutic regimen pre and postoperatively.
Are there any psychosocial impediments that may interfere with the
medical treatment plan? Does the patient have a history of drug or
alcohol abuse and, if so, has the problem been resolved and, if so,
how and to what extent?
2. Your written psychosocial and financial history should be sent to the
Recipient Transplant Coordinator to facilitate referral of your
patient. Please give a copy of your report to your patient's physician.
If necessary, for assistance in completion of your report/assessment, please
contact the Transplant Social Worker, (852) 2632-2211 at the Prince of
Wales Hospital.
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3.8 LUNG TRANSPLANTATION WORKSHEET
FOR THE REFERRING CENTRE
(To be completed by referring physician, nurse, and/or secretary)
Patient's Name:
Address:
Home Phone:
Work Phone:
Sex: Male ( ) Female ( )
Birthdate:
Diagnosis:
Social Status:
Single ( ) Married ( )
Divorced ( ) Separated ( )
Widowed ( ) Student ( )
Name of Spouse:
Name of Referring Physician:
Address:
Phone:
Name of Patient's Current and/or Past
Employment:
Name of Social Worker:
Phone:
Status of Social Worker's Assessment:
Completed ( ) In Preparation ( )
Languages Spoken: Cantonese Yes ( ) No ( )
Other:
Patient's Height:_____Weight:
Date of Last Cath Study:
Month Day Year
Check-List for Materials Accompanying
Worksheet:
__Medical Summary of Current Illness
__Pulmonary Function Tests & ABG's
__Copy of Cath Report(s) Including
Pulmonary Artery Pressures and
Vascular Resistance
__Cine Film(s) of Coronary Arteriography
__Chest X-rays (LATEST ONLY, NON-
RETURNABLE)
__Past Medical/Hospital Summary(s)
__Psychosocial/Financial Evaluation
__Date of all Materials Mailed to the
Prince of Wales Hospital
Patient's Insurance:
Is Patient in Hospital now?
Yes ( ) No ( )
Name of Hospital:
Phone:
Please mail to:
Lung transplantation program
Division of cardiothoracic surgery
Prince of Wales Hospital
Chinese University of Hong Kong
Shatin, N.T.
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3.9 CANDIDATE EVALUATION ORDERS FOR LUNG TRANSPLANTATION
ON ADMISSION (Day 0)
1. Diet
2. Activity
3. Notify the following:
a. Transplant coordinator ( pager: )
b. Transplant social worker (Pager: )
c. Transplant dietitian (Pager: )
Day 1
4. Consultations as follows:
a. Dentistry
b. Dr……………… (for lung transplant assessment)
c. Dr……………….( for cardiac assessment )
d. Dr……………….( Endocrinology assessment )
5. Record weight in kg and height in cm and daily a.m. weights.
6. Book pulmonary function studies and arterial blood gases.
7. Skin test for T.B. (5TU PPD intradermal).
8. Urinalysis including microscopic.
9. ECG (leave copy on chart).
10. PA and lateral chest x-ray.
11. Echocardiogram.
12. Sputum and urine for C & S.
13. Special virology:
a. Mid-stream urine for CMV - 20 mL urine in sterile container.
b. Throat swab for CMV in viral transport medium.
c. Throat washings for EBV virus.
14. Routine viral serology:
a. Anti-CMV (IgG and IgM) serology.
b. Anti VZV serology (Anti-HSV for lung patients).
c. Anti-VCA EBV (IgG)
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15. Serology: HBsAG; Anti-Hepatitis C and Anti-HIV.
10-mL gelled red-top tube to Microbiology Lab.
16. Anti-toxoplasmosis IgG.
Send 10-mL gelled red-top tube to Microbiology Lab.
17. Hematology:
a. CBC, manual differential, reticulocyte count, platelets and
ESR.
b. PT, PTT.
18. Blood Bank:
Blood type and screen.
19. Biochemical Studies:
_________________________M.D.
Day 2
a. Serum electrolytes, creatinine, glucose, BUN, alkaline
phosphatase, AST, CK, LD, Total bilirubin, CA++, Mg++,
phosphate, uric acid, albumin, T. Prot.
b. Ferritin
c. TSH.
d. Quantitative immunoglobulins
requisition to be signed by transplant service physician.
e. Serum immunoelectrophoresis (3 mL blood in 5-mL red-top
tube to Immunochemistry) - requisition to be signed by
transplant service physician.
f. 24-hour creatinine clearance - ensure serum creatinine drawn
during 24 hour period of urine collection.
20. 14-hour fasting lipid profile - requisition to be signed by transplant
service physician.
21. Lymphocyte cytotoxic screen. Send 2 10 mL red-top clotted tubes
to Transplant Immunology Lab. Mark on requisition "possible lung
transplant - Attn: Tissue Typing Lab."
22. Lung Scan with quantitation of ventilation/perfusion.
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23. Thoracic dimensions to be recorded by transplant coordinator as
follows:
a. Circumference of chest at axilla.
b. Length of chest at mid axillary and mid clavicular levels.
c. Depth at mid sternum.
_______________________________M.D.
3.10 PREOPERATIVE ORDERS FOR LUNG TRANSPLANT RECIPIENTS
When recipient for lung transplantation arrives on floor:
1. Nursing Care
a. Vital signs and weight STAT; old chart to floor ASAP.
b. NPO after ______ except for medications ordered
henceforth.
c. Consent forms to be signed:
i. consent for lung transplantation;
ii. consent for multiple lung biopsies as required;
iii. consent for rabbit antithymocyte globulin;
antilymphocyte globulin and OKT3.
d. Surgical prep neck to knees, bedline to bedline. Scrub entire
body with Povidone - Iodine (Betadine) 10 min. following prep.
e. Peripheral IV for medications 2/3 - 1/3 TKVO.
2. Stat Blood Work
a. CBC and 3-part diff, reticulocyte count, electrolytes, glucose,
urea, creatinine.
b. PT, PTT, platelets, fibrinogen.
c. STAT donor specific lymphocyte X-match. (One 10-mL red top
gelled tube).
3. Regular Blood Work:
a. Chemical profile, Serum iron and TIBC. (MD to sign req.)
b. FANA, rheumatoid factor.
c. Serum protein electrophoresis. (MD to sign req.)
d. HbsAg, anti-Hepatitis C, and anti-HIV serum titres STAT.
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4. Studies
a. Virology testing:
i. serum for anti-CMV, VCA IgG (EBV), - in one 5 mL red top
gelled tube;
ii. urine for CMV - 20 ml urine in a sterile container;
iii. throat washings for EBV detection;
iv. throat swab for CMV in viral transport media.
Label all requisitions, "Attention: Lung Transplant Recipient."
PLACE IN REFRIGERATOR
b. Two sets of blood cultures (aerobic and anerobic) for C&S
from 2 different sites.
c. Type and X-match for 8 U packed cells, 6 U FFP, 8 U
cryoprecipitate and 12 U platelets for OR ASAP.
d. STAT PA and lateral chest film in Radiology, if possible,
otherwise - portable film. Send with patient to OR.
e. Routine sputum and urine bacterial and fungal cultures.
5. Medications
a. Ranitidine _______mg p.o. Send ______mg for IV injection.
b. Mycophenolate Mofetil ----------mg po.
c. Antibiotics: Send with patient to OR.
i. Cefuroxime _____mg IV.
ii. _____________________ mg IV.
6. Notify Dr. ________________when patient back from Radiology and
old chart on floor.
7. Call results of CBC< electrolytes, creatinine, BUN, PT, PTT, and
platelets to Dr. _____________.
_____________________________MD
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4. DONOR-RECIPIENT MATCHING
Patients selected for transplantation are chosen from the recipient candidate list
immediately upon availability of a suitable donor, who will be managed in most
instances by the Transplant coordinators and medical staff locally, or by telephone
consultation at the distant centre. In most cases, the transplant coordinator at the
Prince Of Wales Hospital will receive the first call from the donor centre and
obtain the pertinent information on the suitability of the donor for the lung
donation. Due to the difficulty in obtaining satisfactory lung donors, donors are
first screened for their suitability for lung donation. Recipient matching is then
based on:
1. ABO compatibility
2. Less than 20% discrepancy between donor and recipient lung
transplantation. Note: There may be exceptions in which a larger donor
may be considered for a recipient with borderline acceptable pulmonary
vascular resistance. In this setting a short donor ischemic time is
desirable.
3. Absence of a positive lymphocyte cross match. The lymphocyte cross match
may be done post transplant if the preoperative PRA is negative; otherwise
it is desirable to perform the cross match pre-transplant.
If several otherwise suitable recipient candidates exist for transplantation,
recipient selection will be based on the:
1. Acuteness of the clinical state.
2. Prospect for heart-lung transplantation.
3. Elapsed time as an acceptable candidate.
*Note: If a recipient candidate has not had previous surgery or blood transfusions,
and if the preoperative cytotoxic lymphocyte screen is negative (i.e. there
is an absence of cytotoxic antibodies in the recipient serum against a
random panel of donor lymphocytes, e.g. 50/50 negative), and if the donor
is at a centre from which the procurement of donor blood is difficult or too
time consuming, then it is acceptable to conduct the cytotoxic lymphocyte
cross match post-transplant. For onsite donors, all compatibility studies
should be conducted pre-transplant when the PRA is even partly positive.
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5. PREOPERATIVE MANAGEMENT OF MULTIORGAN DONORS
5.1 Criteria for Acceptable Lung Donor
(i)
Age
Donors for lung transplantation should be less than 65 years of age.
Older donors are, in general, acceptable for older recipient
candidate.
(ii)
Absence of systemic sepsis or malignancy. Treated infection and
remote cured malignancy, on the other hand, do not preclude organ
donation.
(iii)
Lung Donors
Normal pulmonary physiology, mechanics, an absence of purulent
pulmonary sections and a clear chest film are required: PO 2 > 300
mg Hg on an FIO 2 100%, with normal lung compliance, normal to
scant pulmonary secretions and normal chest roentgenographic
appearances indicate satisfactory lung status for donation.
5.2 Preoperative Assessment of Multi-organ Donors
The transplant coordinator should be contacted at the time of brain death
declaration or, preferably, before brain death is declared if that diagnosis is
likely forthcoming, in order to facilitate management and multiple organ
harvesting. All relevant patient related factors must be communicated to
the transplant personnel to ensure optimal, multi-organ management.
It is the responsibility of the Transplant program Coordinators to ensure
that donors are optimally managed,and they should be able to make
management decisions based on clinical assessment at the time. In
conjunction with medical transplant personnel, along with the physician
managing the patient directly, the coordinators must ensure that the donor
is optimally managed. Determinants of donor acceptability.
(i)
Assessment of the Lung Donor
Determination of suitability for lung donation requires evaluation of
arterial blood gases, lung compliance, nature and extent of
pulmonary secretions (deep bronchial aspirate or bronchoscopic
aspirate for gram smear and C&S) and chest roentgenography.
20

5.3 Management of Multiorgan Donors
The urgency with which donors frequently have been rushed to the
operating room for kidney harvest reflects the hemodynamic instability and
metabolic derangements that often occur with brain death. While this
approach has expeditiously disposed of donors in a timely fashion and
allowed renal and other non vital organs to be harvested, this practice
unfortunately frequently prevents the use of other vital organs, ie. the
liver, heart and lungs. In general, more time maybe required to mobilize
`other transplant teams', and assess adequacy of organ function. It has not
infrequently been the case in the past, as well, that the kidneys have not
been used because of such severe donor hemodynamic instability that not
even the kidneys could be harvested in time. Accordingly, if more
transplants of all vital organs are to be performed in the future and if all or
nearly all potential donors are to be used for multiorgan transplantation,
there must be: first, a common understanding by the personnel of each
transplant program of the physiological derangements that accompany
brain death and, second, agreement on the therapeutic strategies
required for optimal donor management to ensure immediate and
normal function of each vital organ post transplantation.
Consternation between various transplant programs may develop as one
group attempts to insure that their `vested interest' organ is `optimally'
managed; not infrequently to the detriment of other vital organs. One
group may attempt to push fluids and accept systemic arterial hypotension,
tachycardia and markedly elevated urinary outputs, the latter of which may
be interpreted as a sign that the kidneys are well perfused and therefore
protected. One might question whether or not hypotension (MAP

Recognizing that brain death may well be associated with hemodynamic
instability, the following addresses the concerns surrounding the unstable
donor, particularly the physiologic derangements that frequently occur in
brain death, following by the treatment strategies that aim to correct these
abnormalities that have been tried and proved over a number of years of
collaborative transplantation efforts between many multiorgan transplant
centers.
Brain death is often accompanied by a loss of vasomotor tone, with
resultant fall in blood pressure. Hypotension may also be due to
hypovolemia (blood loss, therapeutic dehydration to decrease cerebral
edema, third space losses and osmotic diuresis due to hyperglycemia) or
myocardial injury and dysfunction. A high urine output from diabetes
insipidus (DI) may contribute to hypovolemia, hypernatremia and
hypokalemia (hyperosmolar dehydration). Homeostatic temperature
control is often lost and the patient becomes hypothermic. Neurogenic
pulmonary edema may occur.
When first evaluating a potential donor, complete the data record for
multiorgan donors, which facilitates the assessment and management of the
donor. Then, determine the adequacy of cardiac function by inquiring as to
the mean arterial pressure (MAP), the central venous pressure (CVP), and
the state of tissue perfusion as reflected by peripheral skin color and
temperature, pedal pulses, urine output, oxygenation and acid-base status.
Check for cardiac murmurs. Check EKG. Although ST segment and T wave
abnormalities are often present in severely brain injured patients, if the
myocardial CPK is not elevated then the heart has not likely been injured.
With control of blood pressure and tachycardia the ST segments usually
normalize. Cardiac output may be low, normal or in excess of 10 L/min
with a low MAP and an elevated, normal or low CVP, depending upon
circulating blood volume, systemic vascular resistance (SVR) and the state
of myocardial contractility. Check for adequate respiratory function by
reviewing for evidence of chest injury, the arterial blood gases, tracheal
secretions and the CXR. Check for adequate renal function by reviewing
urine output in relation to serum creatinine and BUN. Check for adequacy
of liver function by reviewing liver function tests.
Every effort is made to maintain a stable and adequate blood pressure with
the judicious use of volume replacement, inotropes and/or vasopressors.
To clarify a common misconception on the use of vasopressors, the goal of
`pressor' therapy for specific patients only who are normovolemic (CVP 6-10
mm Hg) but hypotensive (MAP

enal or hepatic function in the volume repleted donor, and may be
demonstrated to improve organ perfusion.
In patients without a Swan-Ganz catheter, a low SVR is suspected if the MAP
is low and the extremities are warm and well perfused with bounding pedal
pulses. If the CVP is 6-10 mm Hg and the MAP 10 mm Hg and a controlled Dl or absence of
Dl, place a Swan-Ganz catheter in order to differentiate myocardial
dysfunction from excessive volume expansion or high output `failure'
secondary to a markedly depressed SVR. Hemodynamic stability can only
be achieved if wide swings in intravascular volume and systemic vascular
resistance can be avoided. Following the administration of vasopressin
there is often a fall in the CVP and an increase in the MAP, allowing
satisfactory weaning of the Dopamine. Inability to wean the Dopamine at
this point indicates either a contractility problem, hypervolemia or high
output cardiac `failure' due to a total loss of vasomotor tone wherein the
circulating blood volume passes rapidly from left to right elevating the CVP.
The markedly increased cardiac work associated with increased cardiac
filling pressures and high cardiac output in the setting of a decreased
transmural myocardial perfusion gradient (hypotension, MAP < 70 mm Hg),
decreased diastolic perfusion time (tachycardia HR > 140) may lead to
23

myocardial ischemia and arrhythmias causing severe hemodynamic
instability and subendocardial infarction. The right ventricle is particularly
prone to injury secondary to excessive wall tension and myofibril stretch
from large volumes of administered fluid, hence the value of CVP
measurement. Subendocardial or transmural infarction in this setting may
be difficult to diagnose, but may clearly lead to loss of the heart for
donation, or even worse, if transplanted, death of the recipient.
If, in the presence of a normal serum ionized calcium, the MAP 10 mm Hg, PCWP > 14 mm Hg, C.I. < 2.4 L/min/m 2 and SVR is
normal, with or without evidence of a metabolic acidosis, and the
Dopamine is less than or equal to 5 mcg/kg/min, there is good evidence of
severely compromised contractility and the heart should not be used.
On the other hand, if the C.I. > 3.5 L/min/m 2 along with the above
parameters except that SVRI is low (often 800-1200), then the problem is
one of a total loss of vasomotor tone, which is associated with left to right
shunting and regional hypoperfusion, as reflected by a mild metabolic
acidosis (may also be related to decreased tissue O 2 delivery secondary to
anemia, decreased 2,3 DPG or respiratory alkalosis) and an elevated CVP.
Urine ouput may be unacceptably reduced due to intra-renal shunting as
well. This problem is easily solved by the judicious use of vasopressors to
raise the systemic vascular resistance index only to the normal range (1800-
2000 dynes sec cm -5 ).
5.4 Special Considerations for the Preoperative Management of Donors for
Lung Transplantation
Donors for lung transplantation frequently develop early pneumonic or nonpneumonic
pulmonary disease which is associated with unacceptably low
compliance and compromised respiratory function. Neurogenic pulmonary
edema may occur. Every effort is made to maintain a stable and adequate
blood pressure, and to protect alveolar-capillary integrity, thus assuring
immediate and adequate graft function post-transplantation. Satisfactory
pulmonary function is demonstrated by clear lung fields on chest
roentgenography, normal lung compliance, PO 2 greater than 120 mm Hg on
40% Fl0 2 and the absence of purulent pulmonary secretions. The following
measures, in addition, are essential in the management of potential heartlung
donors, and lung donors.
1. Intubate with an endotracheal tube with a high compliance, high
volume, low pressure cuff.
2. Continuous volume cycled respiratory with 40% FlO 2 , tidal volume
12-15 mL/kg, PEEP 5 cm H 2 O, respiratory rate 6-12 breaths/min.
24

3. Record ventilation pressure q1h (should be less than 25 cm H 2 O for
size adjusted normal tidal volume).
4. Vigorous chest physiotherapy with postural drainage q2h and
nasotracheal suctioning q1h.
25

5.5 MULTIORGAN DONOR ASSESSMENT AND RECORD
General Information
Donor Data Record
Date: Time: Race:
Donor Name: Sex: Age/DOB:
Donor Hospital:
Referring MD:
Contact Name/#:
Admission Diagnosis:
Date of Injury:
Cause of Death:
Patient Declared Brain Dead: Physician:
Date/Time: 1st
2nd
Consent for Donation of:
Medical Examiner Notified: Yes No Name:
Who Initiated Donor Referral?:
Relevant Past History:
Malignancy:
Diabetes:
Hepatitis:
Hypertension:
Admission History & Hospital Stay:
Surgery:
Substance Abuse:
High Risk:
Clinical:
Blood Group: Rh: HLA A B C DR
Serology: HIV HTLV-I HbsAg HCV Syphilis
CMV (pre/post)__________
Donor Weight (kg):
Abdominal Girth (cm):
Height (cm):
Chest Circumference (cm):
Any SHOCK: Yes No Duration/Treatment:
Cardiac Arrest: Yes No Intubation date/time:
Urine output: /hour /24 hours
26

Laboratory Data:
Date:
Time:
FIO2 Rate:
BE (-2,+2)
PEEP
P.P.
PO2 (90-100)
PCO2 (35-45)
O2 Sat.
H+ (35-45)
pH (7.35-7.45)
HCO3 (22-26)
Hgb
(M:13 - 17:F:11.5-16)
Hct
(M:0.38-0.50; F:0.34-0.46)
WBC (4-9)
Plts (140-340)
Na (135-150)
K+ (3.3-5.0)
Cl (96-107)
CO2 (23-31)
Urea (2.5-8.0)
Creatinine (50-115)
Osmol (280-295)
Glucose (3.5-9.0)
Amylase (25-115)
Ca++ (2,10-2.65)
Uric Acid (150-475)
T Bili (3-20)
Alk Phos (100-275)
AST (SGOT) (10-55)
ALT (SGPT) (5-40)
PT (10.3-12.7)
PTT (26-37)
LDH (90-210)
CPK
(M:10-130; F:10-120)
MB (1 0-60)
Other
CXR
Echo
ECG
Sputum Culture
Urine Culture
Blood Culture
Urinalysis
27

Parameters:
VITAL SIGNS
MEDICATIONS
IV FLUIDS
29

Organ/Tissue Retrieval Procedures:
Date:_______________________________
Insitu flush:_____ Yes ______ No Solution used: ________ Perfadex _______UW
________RL
Flush Start Time: Aortic _______________________
Portal________________________________
Stop Time: Aortic
________________________Portal________________________________
Amt Sol'n Infused: Aortic
________________________Portal________________________________
Amt & Sol'n Infused on Back Table:
Liver________________Kidneys_________________________
Kidneys: Removed en bloc: ___ Yes ____No
R L R L
# of arteries Clamp of renal artery
cuff of aorta
initial flush
# of renal veins Warm Ischemic
Cuff of Cava
Liver: Hepatic artery: no: patch: long/short
Portal vein:
long/short
Infrahepatic inf. vena cava:
long/short
Suprahepatic inf. vena cava:
long/short
Phrenic veins: no: tied off: yes/no
Bile duct: long/short flushed: yes/no
Cholecystectomy:
yes/no
Iliac arteries: enclosed: yes/no cms
Iliac veins: enclosed yes/no cms
Remarks Re: Liver
30

Organ Clamp on Clamp Off Ischemic Time Procuring Surgeon
Rt kidney
Lt kidney
Lungs
Heart/Lung
Liver
Pancreas
Cornea
Skin
Bone
31

Communication Log:
Organ
Centre Coordinator
1.
Response
2.
Response
3.
Response
4.
Response
5.
Reponse
6.
Response
Time
Placed-Reached
Organ
Centre-Coordinator
1.
Response
2.
Response
3.
Response
4.
Response
5.
Response
6.
Response
Time
Placed-Reached
Visiting Teams: Centre: Personnel.
1.
2.
3.
32

5.6 DONOR ORDERS FOR MULTI-ORGAN TRANSPLANTATION
PHYSICIAN: Please draw a line through any orders which do not pertain to
your patient.
I. NURSING CARE
1. Admit to ICU. Semi-Fowlers position. ECG monitor.
2. V/S including CVP and MAP q 20 minutes if unstable, otherwise
q1h.
3. Foley catheter to gravity drainage, hourly outputs.
4. N.G. tube or O.G. tube to wall suction, 100 cm H2O. Irrigate
with 30 mL N/S q3h and prn.
5. I & O q1h.
6. Warming blanket to maintain temperature of 35 to 37oC.
7. Surgical prep neck to knees, bedline to bedline. Scrub entire
body with Povidon-iodine (Betadine) for 10 min following prep.
8. Weigh once in kg and measure height in cm.
9. Chest physiotherapy with postural drainage q2h.
10. Nasotracheal suctioning q2h, or q1h if secretions are thick or
copious.
II.
VENTILATORY MANAGEMENT
1. Respirator at setting of _____% F1O2, (

starting Metaraminol (Aramine) ________mg in 500 mL D5W
via CVP line (Min - max rate 0-10 mcg/kg/min) or
Norepinephrine 4 mg in 250 ml D5W (min-max rate 0-10
mg/min) to keep MAP 70-80 mm Hg). For MAP < 70 mm Hg,
CVP > 10 mm Hg and SVR < 900 dynes/sec cm -5, start
metaraminol at _____mcg/kg/min or Norepinephrine and
check CO, MAP and SVRI. Increase metaraminol or
norepinephrine as required to raise MAP to > 70 mm Hg and
ensure that SVRI does not exceed 2000 dynes sec cm-5.
d) Peripheral IV keep open with Normal Saline at 30 ml/h when
blood, blood products or antibiotics not running.
2. KCl scale (use only if urine output > 60 mL/h). Give _____mmol
(mEq) KCl per volutrol for each 0.1 mmol serum K+ < 5.0 to be
given at a rate of ______mmol (mEq)/2 min. (To each 2 mL IV
fluid in the volutrol, add _____mmol (mEq) KCl). (CENTRAL LINE
ONLY).
3. Antibiotics to be given after cultures and blood work obtained.
a) Cefuroxine ______g IV q4h.
b) Chloramphenicol ______g IV q6h.
c) _______________________ ________g IV q ______h.
IV.
STUDIES
1. STAT
a) ECG
b) CXR, repeat q6h for potential heart/lung or lung donor.
c) ABG's, then q 2-4h, along with SVO2 if Swan Ganz Catheter
present.
d) CBC and diff, glucose, serum electrolytes, serum ionized
calcium, magnesium, osmolality, BUN, creatinine then q4h.
e) Chem panel, GGT.
f) Bilirubin and SGOT, then q8h.
g) CK and CKMB Q and LD isoenzymes (if ECG suggests injury).
h) PT, PTT, platelets.
i) HBsAg and HIV serum titres - 10 mL blood in one plain 10
mL corvac red top tube.
j) Blood barbiturate level and toxicology screen if patient has
not been pronounced neurologically dead (potential donors
only).
k) Type and crossmatch for 4 units packed red blood cells.
l) Tracheal aspirate and urine for routine culture, urinalysis.
m) Two sets (aerobic and anaerobic) of blood cultures for C &
S from 2 different sites.
34

n) HLA typing and Lymphocytotoxic antibody screen against
recipient's serum. Send fourteen heparinized 10 mL green
top tubes and one 10 mL red top tube to Transplant
Immunology Lab Transplant Coordinator. Label Lung
Transplant Donor.
2. Blood for the following tests must be drawn stat, but the
analysis may be done during regular lab hours.
a) Chemical panel.
b) CMV and EBV serum titres - 10 mL blood in one plain 10 mL
gelled red top tube. Notify Transplant Coordinator when
done, and REFRIGERATE SPECIMEN WHEN OBTAINED.
c) Toxoplasmosis serum titre - 10 mL blood in one 10 mL
gelled red top tube. Forward to Microbiology lab.
V. PARAMETERS
- Notify Dr. _________ and Transplant Coordinator:
1. MAP > 100 or < 70 mm Hg.
2. CVP > 10 or < 6 mm Hg.
3. PAD > 12 or < 8 mm Hg. (or mean PCWP > 14 or < 8).
4. Temp < 34 or > 37oC.
5. HR > 110 or < 60 beats/min.
6. PO2 > 120 or < 70 torr, PCO2 > 42 or < 30 torr, pH > 7.50 or <
7.35.
7. SVO2 < 60% or PVO2 < 30 mm Hg.
8. Serum K+ > 5.5 or < 3.0. Ionized Ca++ < 1.2 or > 1.34 mmol/L.
9. HCT < 30.
10. Urine output < 1.5 mL/kg/h for 1 hour.
11. For MAP < 70 mm Hg, CVP > 10 mm Hg, normal serum Ca++,
SVO2 < 60% PVO2 < 30 mm Hg, consider Swan Ganz catheter.
12. SVR < 1200 dynes sec cm-5.
35

6. COORDINATION OF THE TRANSPLANTATION PROCEDURE: A CHECKLIST
To avoid sudden surprises, the transplant coordinator (in conjunction with the
transplant surgeons and residents) must thoroughly check that all relevant
personnel are notified, that all times are agreed upon, that the donor is optimally
managed, that all relevant consents are obtained, that the recipient is admitted
and free of disease processes which would interdict transplantation at that time
and that the appropriate preoperative orders are carried out.
Lung transplantation constitutes an emergency procedure due to the unstable
nature of most donors and the short ischemic time that the heart or lung will
tolerate.
It is anticipated that most, if not all, donors would be harvested at the referring
centre. For thoracic organ procurement:
Obtain an Operating Room (O.R.) start time at the referring centre.
Obtain an estimate of the transport time from the donor center to the recipient
center. Calculate in the actual harvest time (from cross-clamping the donor
aorta to leaving the donor O.R. - usually approximately 10-15 minutes),
transport to the donor airport, actual flying time including approximately 5
minutes each for take-off and landing, and the ground transport from the
airport to the recipient center.
Inform the recipient anesthetist as to the time you wish to make the thoracic
(lung) incision and the expected time of arrival of the donor lungs.
For lung recipients not previously operated on, plan to make the incision 90
minutes prior to donor organ arrival.
For recipients previously operated on, plan to start operating on the recipient
after the donor heart has been visualized. Allow at least 1-1/2 to 2 hours to
obtain adequate exposure. Depending on the donor location it may be
necessary to delay the donor harvest until the recipient dissection is far enough
along, so that when the donor organ(s) arrives at the recipient Operating Room
it is not sitting in storage for an unduly long period. Keep the donor ischemic
time to a minimum and definitely less than 4 - 5 hours.
Inform the O.R. at the recipient center that a transplant will be performed, the
approximate time, and whether a nurse will or will not be required to go on the
donor run. The O.R. should also inform the perfusionist.
36

Inform the recipient candidate or candidates by phone, if the patient(s) is/are
not already in the hospital. It may be necessary to locate the potential
recipient(s) by cell phone.
Inform Admitting: that the patient to be admitted is being admitted for
`transplantation', otherwise errors in billing or nursing protocols may ensue.
Admit the patient to a ward prepared for the preparation of such patients for
transplantation, where preoperative order forms and consents are immediately
available. (The recipient candidate may already be in hospital in a pulmonary
bed. Fill out the preoperative orders before the patient arrives so that the old
chart will be on the ward and the chest roentgenogram and laboratory data
obtained when you arrive to admit the patient.
Inform the ICU at least 6 hours in advance so that staffing can be arranged.
Inform the transfusion service that they may need to perform a preop cytotoxic
lymphocyte x-match (if potential recipient highly sensitized), and that 6 units
blood, 8 units platelets, 8 units of cryoprecipitate and 4 units of fresh frozen
plasma will be needed for the recipient.
Inform the personnel to be involved with the donor harvest: surgeon, assistant,
scrub nurse, anesthetist and any interested visiting physicians or other
personnel. Review the donor status with the individual harvesting the donor to
avoid surprises.It is the responsibility of the surgeon harvesting the lung to
check that the name on the donor's wrist band is the same as the one in the
donor chart, that the blood type is confirmed, that the brain death notes are
written, that the consents for lung donation are written, and that the donor is
hemodynamically stable,chest roentgenogram or electrocardiogram. A copy of
the face sheet, blood type, admission history and physical examination, brain
death notes and consent forms must be returned to the recipient center. It is
helpful to have the data copied and assembled for the donor team prior to
arrival at the referring center.
Inform other researchers interested in blood or various tissues for experimental
purposes.
37

7. COORDINATION OF A LUNG TRANSPLANT
DONOR CALL PWH
TRANSPLANT SURGEON RECIPIENT SELECTION
(Preliminary Call or (Discussion with Pulmonary physician)
All Relevant Donor
Info Available)
DONOR COORDINATOR RECIPIENT COORDINATOR
Confirms Acceptable Donor Status 1. Informs ICU.
(May require further discussions with transplant Surgeon/Resident
and donor management physician) 2. Calls in Recipient
Confers With transplant Surgeon/Senior Resident/OR 1. Prepares Recipient Resident
Assessment,
and Recipient Coordinator . . . for OR Hx,
P/E
1. that transplant will proceed 2. Confirms OR Time with donor coordinator
2. the time of departure to retrieve organ(s) (ensures sufficient lead time for
anesthetist
3. who will go & surgeon)
4. likely timing of retrieval & arrival of donor
organ(s) at recipient center (NB: Need 90 min from
skin incision to organ arrival for first time thoracotomy
patients and 180 min for reops lung recipients).
Transplant coordinator (Donor end)
• Arranges ground and air transportation to Donor Centre.
• Organizes Donor Equipment & Preservation Solutions to Donor Centre.
• Informs Donor OR & Cold Saline/Slush Managements.
38

• On arrival at donor centre, informs transplant Surgeon/Senior Resident of donor status &
likely time of retrieval to signal when recipient should go to the O.R.
• Following donor sternotomy, inform transplant Surgeon lung is O.K
• Inform transplant Surgeon/Senior Resident that organ has (has) been retrieved, and that all
has gone well and when it is likely to arrive.
• Inform transplant Surgeon/Senior Resident that organ will arrive in approximately 30 - 45
minutes.
• Delivers organ(s) to recipient O.R.
• Confirms donor-recipient blood type.
7.1 Preparation of Perfadex Solution
Perfusion
• 4x1 L bags of Perfadex each loaded with the following:
‣ 4 cc THAM, 0.6 cc CaCl
‣ 2.5 cc PEGI –Water mixture (1 ml PGEI with 9 ml NS)
• THAM and CaCl can be added before leaving for retrieval
• PEGI should be added in the OR after lungs have been accepted
Storage
• 2x1 L bags of Perfadex each loaded with the following
‣ 4cc THAM, 0.6 cc CaCl
Back Flush
• 1x1 L bag of Perfadex loaded with the following
‣ 4 cc THAM, 0.6 cc CaCl
Points to Remember
• Perfusion bags should be hung only 1 foot above the height of the donor
chest
• A foley catheter (12 Fr) should be on the back table for the back flush
• Perfusion solutions should be hung as late as possible to ensure that they
are cold
• The perfusion volume is 50 cc per kg body weight
39

7.2 Procedure for donor lung resection
As per routine, the organ donor’s chest and abdomen had been previously
entered through a midline incision to expose the intra-abdomenal and intrathoracic
organs. A sternal retractor was inserted and opened to expose the
anterior pericardium and medial surface of the pleural spaces bilaterally. A
vertical pericardiotomy incision was made to expose the underlying heart. The
heart was assessed by the cardiac transplant surgeon for suitability for
transplantation.
Dissection of the inferior vena cava at the level of the diaphragmatic surface
of the pericardium was undertaken to free up an adequate length for
transaction and venting for the liver during perfusion.
The superior vena cava was mobilized in the pericardial space to superior
pericardial reflection and encircled with a heavy silk ligature. Extrapericardial
dissection to the level of the azygos vein was performed and a separate silk
ligature was placed around the IVC.
The pleural spaces were entered bilaterally to facilitate gross inspection and
palpation of the lungs.
The ascending aorta was reflected laterally and the posterior surface of the
pericardium was incised between the superior vena cava and aorta to expose
the trachea. Sharp and blunt dissection was utilized to encircle the trachea 3
cm proximal to the level of the main carina.
Attachment between the main pulmonary and ascending aorta were divided to
expose and properly separate these great vessels.
In simultaneous heat and lung extractions a cardioplegic catheter is inserted in
the ascending aorta. A 5-0 purse string suture is placed in the main pulmonary
artery just proximal to the bifurcation to the left and right main pulmonary
vessels. Systemic heparinization is provided by IV injection of a suitable dose
of heparin. The hepatic transplant surgeons then insert the hepatic and renal
perfusion catheters through the abdominal aorta after transaction the aorta
distal to the superior mesenteric artery.
The pulmonary arterial catheter is then inserted in the main pulmonary artery
and secured with the purse string.
With all transplant surgeons appropriately ready to perfuse their respective
organs, a direct injection of 500 micrograms of prostaglandin PEG1 into the
main pulmonary artery was made.
When systemic pressure reaches 80 mmHg, the SVC ligated. The left atrial
appendage was transacted in order to vent the lungs.
40

Cardioplegia and pulmonary flush was then instituted. Through the entire
pulmonary flush process, mechanical ventilation was maintained by the
anesthetist. Cold solution and crushed ice were placed in the pericardial and
pleural spaces bilaterally to facilitate hypothermia of the heart and lung bloc.
Once the flush solutions had passed through the heart and lung completely, we
proceeded to remove the heart-lung bloc.
This was done by elevating the heart out of the pericardial sac and transecting
the left atrium just proximal to the confluence with the right and left
pulmonary veins. Once the left atrium was completely detached posteriorly,
the heart was dropped back into the pericardial sac and the main pulmonary
artery was transacted just proximal to the bifurcation. The aortic route and
posterior pericardium transacted working backwards into the pericardial sac.
The superior vena cava was then transected within the pericardium and the
heart removed from the donor pericardial sac.
The pericardium was transacted at the diaphragm; to enter retropericardial
space. Blunt dissection was carried forward along the line of the esophagus
and aorta posteriorly up to the level of the trachea just above the carina. The
inferior pulmonary ligaments were then transected bilaterally to free up the
entire lung bloc inferiorly.
The trachea was then transected with a bronchial stapler proximal to the main
carina with the lungs having been previously manually inflated to an inflation
pressure of 30 mm Hg. Tissue in the right and left paratracheal spaces superior
were transacted in order to free up the lung bloc completely and it was
removed from the donor chest cavity.
The donor lung bloc was then placed in cold perfadex solution within sterile
containers for transport.
7.3 Procedure for bilateral lung transplantation
A. Anesthesia: General, Thoracic epidural, Double lumen ETT
B. Cardiopulmonary bypass machine on standby
C. Position: The patient is placed supine on the operating table with the
arm abducted, shoulder roll to be placed under the shoulder blades.
D. Incision: (Clampshell ) bilateral inframammary thoracotomy incision and
transverse sternotomy.
Description of the procedure
1) Hilar pleura is incised anteriorly and the dissection carried superiorly.
2) The pulmonary artery is encircled as far proximally as possible.
3) The pericardium is opened just anterior to the pulmonary vein posteriorly.
41

4) The pulmonary artery is divided with vascular stapler usually just distal to
the first upper lobar branch.
5) The veins are divided by ligating individual branches as they enter the
pulmonary parenchyma.
6) The bronchus is divided as far distally as possible after application of a TA-
55 stapler and the lung is removed.
7) The pericardium should be opened widely around the entire hilum.
8) The donor lung which had already been prepared on the back table brought
into the field and properly oriented.
9) The bronchial anastomosis is constructed first. It is extremely important to
trim the donor bronchus as short as possible usually one or two rings above
the origin of the upper lobe bronchus.
10) Monofilament suture (PDS-4-0) is used to approximate the membranous
bronchus, and a monofilament non-absorbable suture(Prolene 4-0) is used
for the cartilaginous portion. The anastomosis is constructed so as to
telescope one bronchus into the other.
11) The arterial anastomossis usually is completed next. It is constructed using
continuous suture 5-0 Prolene.
12) The left atrial cuff anastomosis is usually completed last.
13) The allograft de-airing is usually carried out through the atrial anastomosis
after de-clamping the pulmonary artery.
14) The lung fully inflated.The ischemic time end at this point.
15) The vascular suture lines are checked to assure that there are no significant
defects.
16) The second lung is implanted In the same way as the first lung.
17) Chest tubes are placed and the incision is closed.
42

8. POST-LUNG TRANSPLANT ORDERS AND MANAGEMENT
In order to avoid errors of omission and commission in post operative care,
standardized orders have been developed. This format originated at Stanford
University Medical Center and has been modified on several occasions as a
consequence of new knowledge.
8.1 Lung Transplantation Immediate Post-Operative Orders
Date/Time Weight kg; Height cm.
1. Nursing Care:
a. Admit to ICU.
b. ECG monitor, pulse oximetry.
c. Neurovital signs q1h until awake, then q4h.
d. Vital Signs including HR, CVP, PAP, LAP and MAP prn q 20 minutes x 2 - 4h, then q1h if stable.
e. Temp q1h until 36.5°C, then q4h.
f. Cardiac index and PCWP q4h x 24 hours, then q8h x 24 hours and prn.
g. NPO except ice chips. NG tube to intermittent wall suction. Irrigate with 30 mL Normal Saline q4h prn.
h. Chest tubes to collection chamber, -20 cm H 2 O suction pressure.
i. Strip chest tubes q 20 minutes x 2 - 4 hours, then q1h if stable.
j. Aim for following parameters (range should not exceed 5 mmHg):
i. Keep CVP ___________________ to ___________________________ mmHg.
ii. PAD ________________________ to ___________________________ mmHg.
iii. PCWP ______________________ to ___________________________ mmHg.
iv. LAP ________________________ to ___________________________ mmHg.
Contact physician about amount and type of volume replacement.
If HCT > ____________________ , replace with ___________________________________ .
Transfuse ___________________ unit of packed cells for HCT < ______________________ .
k. In and Out q1h.
l. Weigh daily.
m. Implement physio protocol.
n. Implement incision care protocol.
o. Inform MD of incisional drainage.
2. Ventilatory Management:
a. Ventilator settings as per respiratory therapy protocol.
Physician’s Signature ____________________________________________________________________ ,
43

Date/Time
Ventilatory Management continued:
b. Endotracheal suctioning prn and instillation 3 - 5 mL Normal Saline prn.
c. For hemodynamically stable, ventilated patients, ABG 20 minutes after arrival, then as per early
extubation / weaning protocol. If patient unstable, ABG q1 - 2h.
d. Weaning and extubation per protocol. Notify MD prior to extubation.
e. Remove NG tube at time of extubation if bowel sounds present and abdomen not distended.
3. IV and Drug Therapy:
a. IV’s:
i. Pulmonary artery catheter for central monitoring. Keep CVP and PA ports patent with Normal Saline.
ii. Keep arterial line patent with Normal Saline 500 mL.
iii. Drive solution for drips through introducer sheath: 2/3 - 1/3 with _______ mmol / L KCL at _______
iv. Peripheral IV: 2/3 - 1/3 at _______ mL / h or saline lock prn when blood not running.
b. Cardiac Drugs: Maintain MAP _______ mmHg to _______ mmHg (range should not exceed 12 mmHg).
i. Dopamine 400 mg in 250 mL D 5 W to keep MAP > _______ mmHg. Start at ______ mcg / kg / min.
Min - max rate _______ mcg / kg / min. DO NOT INCREASE DOSE IF HR EXCEEDS 120 / MINUTE.
ii. Dobutamine 500 mg in 250 mL D 5 W to keep MAP > _______ mmHg. Start at ______ mcg / kg / min.
Min - max rate _______ mcg / kg / min.
iii. Epinephrine _______ mg in 250 mL D 5 W to keep MAP > _______ mmHg. Start at ______ mcg / kg /
Min - max rate _______ mcg / kg / min. DO NOT INCREASE DOSE IF HR EXCEEDS 120 / MINUTE.
iv. Milrinone 20 mg in 100 mL Normal Saline or D 5 W to keep MAP > _______ mmHg.
Start at ______ mcg / kg / min. Min - max rate _______ mcg / kg / min.
v. Norepinephrine 4 mg in 250 mL D 5 W via central venous / LAP line to keep MAP > _______ mmHg.
Start at ______ mcg / kg / min. Min - max rate _______ mcg / kg / min.
DO NOT INCREASE DOSE IF HR EXCEEDS 120 / MINUTE.
vi. Sodium Nitroprusside 50 mg in 250 mL D 5 W to keep MAP < _______ mmHg.
Start at ______ mcg / kg / min. Min - max rate _______ mcg / kg / min.
vii. Nitroglycerine 100 mg in 250 mL D 5 W to keep MAP < _______ mmHg and PADP < _______ mmHg.
Start at ______ mcg / kg / min. Min - max rate _______ mcg / kg / min.
viii. Lidocaine 2 g in 250 mL D 5 W at _______ mg / min.
ix. Isoproterenol _______ mg in _______ mL D 5 W at _______ mcg / kg / min.
Start at ______ mcg / kg / min. Min - max rate _______ mcg / kg / min.
Physician’s Signature ____________________________________________________________________ ,
44

Date/Time
c. Routine Medication:
i. For serum ionized Ca ++ 38.0°C.
d. Antibiotics, Anti-fungals and Anti-virals:
i. Cefazolin 1 g IV per buretrol q8h x 3 doses. D / C on ______________________________________ .
ORii. ___________________________ Vancomycin _______ mg IV q _______ h per buretrol. D / C on .
iii. _______________________ _____________ mg IV per buretrol q _______ h.
iv. Cotrimoxazole 1 single strength tab po / NG daily when bowel sounds present. (PCP prophylaxis).
v. Chlorhexidine 0.12% 10 mL to gargle and rinse mouth qid prior to Nystatin.
vi. Nystatin 100,000 units (1 mL) to swish and swallow qid.
vii. Fluconazole 100 mg po / IV daily. (Lung transplant patients only for Fungal prophylaxis)
viii. Acyclovir 400 mg bid po / NG when bowel sounds present. (HSV prophylaxis).
Physician’s Signature ____________________________________________________________________ ,
45

D O N O T W R I T E I N T H I S S P A C E
Date/Time
Antibiotics, Anti-fungals and Anti-virals continued:
ix. FOR HEART TRANSPLANT PATIENTS who are CMV negative and receive a CMV positive organ start on:
Ganciclovir _______ mg (2.5 mg / kg) IV q24h immediately post op. Adjust for renal function.
Ganciclovir _______ mg _______ times per day po for 14 weeks when bowel sounds present.
Adjust for renal function.
x. FOR TRANSPLANT PATIENTS who are CMV positive or negative and
receive a CMV positive organ start on:
Ganciclovir _______ mg (5 mg / kg) IV q12h for 2 weeks. Adjust for renal function.
Ganciclovir _______ mg (5 mg / kg) IV q24h for: 8 weeks / 12 weeks. Adjust for renal
e. Immunosuppressive therapy:
i. Methylprednisolone _______ mg (2 mg / kg) IV q12h x 3 doses.
ii. ATGAM _______ mg (10 mg / kg) IV daily by continuous infusion over 24 hours. ( _______ mg / h).
iii. Mycophenolate Mofetil 1000 mg IV q12h. Change to po when bowel sounds present. Hold for WBC 38.0°C or 120 or _______ or < _______ mmHg.
d. CVP > _______ or < _______ mmHg.
e. ABG results per early extubation / weaning protocol.
f. Resident to assess 12 lead ECG and chest x-ray.
g. Chest drainage >2 mL / kg / h.
h. Serum K + >5.5 or _______ mmol / L.
k. Blood glucose >14 mmol / L.
Physician’s Signature ____________________________________________________________________ ,
46

Date/Time
Parameters continued - Notify MD for:
l. Serum ionized Ca ++

D O N O T W R I T E I N T H I S S P A C E
Date/Time
6. Virology testing:
a. For CMV IgG positive patients or donor positive patients, serum buffy coat every Sunday
(2 mauve top tubes) to be performed 2 weeks post-transplant and repeated every _______ weeks.
Start date __________________ .
b. For EBV seronegative patients: EBVCA IgG and IgM and Monospot q2weeks.
- Tests to be done on Tuesday and must be delivered to Virology lab before 1130.
- Label requisition: “Attention Post Heart and / or Lung Transplant Recipient.”
7. Additional Orders:
Physician’s Signature ____________________________________________________________________ ,
48

8.2 Lung Transplantation Transfer Orders
Date/Tim Weight kg; Height cm.
8. Nursing Care:
a. Transfer to 2 North.
b. Vital Signs q4h x 48 hours, then q8h.
c. Weigh daily.
d. Chest tubes to collection chamber, -20 cm H 2 O suction pressure.
e. Diet:
i. 2 gm Sodium cardiac diet or _____________________ kcal CDA; or ___________________________ .
ii. Tube feed _________________ at _______________ mL / h per NG / PEG. Dietitian to assess goal
iii. Total IV and po intake not to exceed _____________________________ mL per 24 hours.
f. Consultation with dietitian for home diet instruction.
g. I & O q12h. Reassess in 48 hours.
h. Walk in hall qid as tolerated. Increase as tolerated. Implement physio protocol.
i. Remove chest tube sutures 21 days after chest tubes are removed.
j. Remind patient to flex and extend feet 100 times every hour while awake.
k. Contact Transplant Coordinator to begin discharge teaching.
9. Pulmonary Care:
a. Nasal cannula O 2 at 1 - 6 L / min.
b. Monitor SaO 2 q8h, and 20 minutes after FiO 2 change.
c. Titrate FiO 2 to maintain SaO 2 ≥ 92% or ______________________________________________________ .
d. Discontinue O 2 therapy if SaO 2 > 92% on room air or ___________________________________________ .
e. Incentive spirometer q1h while awake.
f. Chest physiotherapy q4h x 24 hours then qid.
Physician’s Signature ____________________________________________________________________ ,
49

Date/Tim
Pulmonary Care continued:
g. Aerosol therapy nebulization mask. Treat q _______ h with:
Ventolin 2.5 mg in 2.5 mL Normal Saline prn.
10. IV and Drug therapy:
a. IV’s:
i. Central line: Heparin lock (100 units / mL) with 3 mL q12h and prn.
ii. Peripheral line: Saline lock for medications q8h and prn.
iii . Notify physician if HR > ____________ or SBP < ____________ .
b. Antibiotics, Anti-fungals and Anti-virals:
i. Cefazolin 1000 mg per IV q8h. D / C on __________________________________________________ .
ORii. ___________________________ Vancomycin _______ mg IV q12h. D / C on __________________ .
iii. _______________________ _____________ mg IV q _______ h. D / C on .
iv. Cotrimoxazole 1 single strength tab po / NG daily when bowel sounds present. (PCP prophylaxis).
v. Chlorhexidine 0.12% mouthwash 10 mL po qid to gargle and rinse mouth prior to Nystatin.
vi. Nystatin 100,000 units (1 mL) qid to swish and swallow.
vii. Fluconazole 100 mg po / IV daily. (Lung transplant patients only for Fungal prophylaxis)
viii. Acyclovir 400 mg bid po / NG when bowel sounds present. (HSV prophylaxis).
ix. FOR HEART TRANSPLANT PATIENTS who are CMV negative and receive a CMV positive organ start on:
Ganciclovir _______ mg (2.5 mg / kg) IV q24h immediately post op. Adjust for renal function.
Ganciclovir _______ mg _______ times per day po for 14 weeks, when bowel sounds present.
Adjust for renal function.
x. FOR LUNG TRANSPLANT PATIENTS who are CMV positive or negative and
receive a CMV positive organ start on:
Ganciclovir _______ mg (5 mg / kg) IV q12h for 2 weeks. Adjust for renal function.
Ganciclovir _______ mg (5 mg / kg) IV q24h for: 8 weeks / 12 weeks.. Adjust for renal
Physician’s Signature ____________________________________________________________________ ,
50

D O N O T W R I T E I N T H I S S P A C E
Date/Tim
c. Immunosuppressive therapy:
i. Neoral Cyclosporine / Tacrolimus q12h. Give _______ mg po / NG (clamp x q2h) tonight and tomorrow
Dose to be adjusted on daily levels. (Give at 0800 and 2000 daily).
ii. Mycophenolate Mofetil 1000 mg po q12h. Hold for WBC 4.5 mmol / L.
iii. Colace 100 mg po bid.
iv. Senokot 2 tablets po hs.
v. ECASA 81 mg po daily.
vi. Analgesia:
Morphine _______ mg IM / SC q _______ h prn while CT in situ.
Meperidine _______ mg IM / SC q _______ h prn while CT in situ.
Percocet 1 - 2 tab po q4 - 6 h prn for pain
Acetaminophen with codeine 30 mg (Tylenol #3 ® ) 1 - 2 tabs po q3 - 4h prn for pain.
vii. Acetaminophen 325 - 650 mg po q4h prn for Temperature >38.0°C.
viii. Ranitidine _______ mg po q _______ h. Adjust for renal function.
ix. _________________ _________________ mg po qhs prn for sleep.
x. IV fluid ___________ with __________ mmol (mEq) KCL / L at __________ mL / h.
xi. Insulin:
______________________________________________________Add __________ units
and run per perioperative insulin protocol.
______________________________________________________Chemstrips q2h while on insulin
______________________________________________________Consult Endocrinology /
Physician’s Signature ____________________________________________________________________ ,
51

D O N O T W R I T E I N T H I S S P A C E
Date/Tim
Routine Medications continued:
xii. Diltiazem / Diltiazem CD / Tiazac __________ mg po / NG q _______ h.
Reassess for HR < _______ beats / min or cuff SBP < _______ mmHg.
xiii. Ferrous Gluconate 300 mg po tid.
xiv. Dimenhydrinate 25 -50 mg po / IM / IV q4h prn for nausea.
xv. Metoclopramide 10 mg po / IM / IV __________ ac meals and HS.
xvi. Heparin 5,000 IU SC q12h until mobile.
11. Parameters - Notify MD for:
a. Temperature >38.0°C.
b. HR >120 or 160 or 30 / minute or O 2 saturation 5.5 or 14,000 or 300 mL / h or 2000 mL in 8 hours.
k. Serum creatinine > _______ mmol / L.
l. Blood glucose >14 or

Date/Tim
Studies continued (review afer 48 hours):
e. Whole blood Cyclosporine / Tacrolimus levels every a.m. just before morning dose. (3 mL mauve top
f. PA and lateral chest film daily x 5 days then reassess.
g. 12h Creatinine clearance every Tuesday and Friday.
h. Urine and sputum for routine bacterial and fungal cultures every Tuesday and Friday.
i. C & S of any incisional drainage. Inform Physician.
13. Virology testing:
a. For CMV IgG positive patients or donor positive patients, serum buffy coat every Tuesday
(2 mauve top tubes) to be performed 2 weeks post-transplant and repeated every _______ weeks.
Start date __________________ .
b. For EBV seronegative patients: EBVCA IgG and IgM and Monospot q2weeks.
- Tests to be done on Tuesday and must be delivered to Virology lab before 1130.
- Label requisition: “Attention: Lung Transplant Recipient.”
14. Additional Orders:
MD.
Physician’s Signature ____________________________________________________________________ ,
53

9. IMMUNOSUPPRESSION
9.1 Introduction
The illusive immunosuppressive goal following organ transplantation is to
achieve tolerance for the organ without a need for ongoing immunosuppression
and without creating any adverse side effects. Unfortunately,no perfect
immunosuppressive strategy exists to induce immunological tolerance. At best,
for lung transplantation, immunosuppressive protocols must be used which
prevent rejection and, by virtue of minimal toxicity, do not predispose to
infection, malignancy or other potentially life or quality of life threatening
problems. Excellent short and long term survival may be achieved with
cyclosporine in combination with azathioprine or mycophenolate mofetil
immunosuppression with or without monoclonal or polyclonal antilymphocyte
antibodies or prednisone.
9.2 Immunosuppressive Protocol
a) Pre-Operative
1. Azathioprine
3 mg/kg IV or, if PO, 4 to 6 hours pre-transplant.
b) Intra-Operative
1. Methylprednisolone sodium succinate (Solumedrol)
10 mg/kg just prior to release of arterial cross-clamp.
c) Post-Transplant Immunosuppression
1. First Three Months Post-Transplant:
1.1. Azathioprine 1 to 2 mg per kg PO or per NG tube daily to adjust
white blood count to 4,000 - 6000 per mm 3 .
1.2. Methylprednisolone sodium succinate 2 mg per kg IV q12h X 3
doses, then 1 mg/kg/day tapering by 1 mg/day, until prednisone
can be substituted.
1.3. ATGAM (or equivalent RATG) 10-20 mg/kg/d over 24 hours by
continuous infusion until Cyclosporine levels are in the target
range (usually 5-10 days). Following the discontinuation of
ATGAM, Solumedrol 2 mg/kg/d IV for 3 doses, in addition to the
prednisone dosing (see #4) may be especially useful under
certain circumstances (see Table 2 on P. 82 - Monitoring), but
should be routinely administered.
1.4. Prednisone 1 mg/kg/d starting 1st day postop and tapered by 2
mg/d (if under 20 kg, taper by 1 mg/d) until at 0.25 mg/kg/d.
54

1.5. Cyclosporine 4 to 5 mg per kg PO or per NG tube in 2 divided
doses at 12 hour intervals daily beginning on the second to fourth
post-transplant day depending on renal function (at or near
baseline) and fluid status. The cyclosporine is adjusted to
maintain whole blood trough levels ideally at 350 - 500 ng/ml in
the first 3 months and then 200 - 500 ng/ml subsequently
depending on renal function. Dose may have to be adjusted
downward for renal dysfunction or upward for acute
rejection.
2. After Three Months Post-Transplant
The azathioprine, prednisone and cyclosporine are continued as above,
with the following exception:
2.1 In the event of no rejection episodes, the cyclosporine dose may
be reduced to achieve a trough level of 200-500 ng/ml. Monthly
biopsies for 6 months will be required to ensure that rejection is
not triggered by the lower cyclosporine or prednisone doses (see
prednisone below).
2.2 Consideration should be given to weaning the prednisone,
particularly if cyclosporine levels can be easily maintained in the
target range, which also assumes excellent renal function. On
the other hand, if renal function is poor, it is unlikely that
satisfactory cyclosporine levels can be maintained in which case
it is unlikely that prednisone can be weaned off. Should
prednisone weaning be attempted, rigorous monitoring for
rejection should be initiated. Monthly clinical assessment,
including, CXR and lung biopsies (where possible) should be
carried out during the weaning.
55

d) Summary of Immunosuppression
1. Dosing
PREOP INTRAOP 0-3 MONTHS > 3 MONTHS
POSTOP
Azathioprine 3 mg/kg IV PO 0 1-2 mg/kg/d 1-2 mg/kg/d
SOLUMEDROL
0 10 mg/kg prior
to release of
clamps
Prednisone 0 0
1 mg/kg q12h X 3
doses, then 1
mg/kg/d of
equivalent
prednisone dose
until patient can
tolerate oral
prednisone.
Consider and give
an additional 2
mg/kg/d IV X 3
when ATGAM
D/C'd.
1 mg/kg/d taper
by 1 mg/d.
0.25 mg/kg/d
ATGAM (or
equivalent RATG
or OKT 3
0 0 10-20 mg/kg/d
over 24 hours X 5 d
until Cyclo levels
in target range.
Start 4-6 hours
postop when
patient stable.
Cyclosporine 0 0
Start 1-4 days
postop when
satisfactory renal
function evident at
4-5 mg/kg/d PO in
div doses or at 3
mg/kg/d IV by
contin. infusion.
May have to accept
lower cyclo levels
with renal
dysfunction.
(350-500 ng/ml) 200-500 ng/ml
56

2. Monitoring
MONITOR
COMMENTS
AZA WBC maintain at 4-6K
Solumedrol
Consider 2 mg/kg/d IV
bolus daily X 3 when ATGAM
is discontinued, especially
if cyclo levels are low or
rejection is likely.( diffuse
interstitial pulmonary
infiltrate in the absence of
pulmonary secretions; poor
lymphocyte suppression
while on ATG).
*PRED.
ATGAM Abs. lymph ct < 200
CD3 < 100 (if abs lymph
ct > 200)
9.3 Administration Procedure for Anti-Thymocyte Globulin
1. General
Antithymocyte globulin of equine origin (HATG-Horse Antithymocyte
Globulin - ATGAM) or of rabbit (RATG) origin is given IV in the prophylaxis
and treatment of rejection in lung transplantation. Presently, we are
starting with ATGAM. Circulating rosette (T-cell) levels, serum 1/2 life of
ATG as well as lung biopsy may be used to monitor the dose, duration and
effectiveness of therapy. Currently, however, we are simply following the
absolute lymphocyte count, aiming for

Antithymocyte globulin is highly effective in eliminating T-cells, of which
certain subsets mediate graft rejection. Generally, for patients with life
threatening acute rejection or, in patients who have failed to resolve a
rejection episode with 2 courses of methyl prednisolone sodium succinate
therapy (10 mg/kg/d X 3 days), RATG (more potent than ATGAM) or ATGAM
is administered once daily for 3 days by continuous IV infusion.
2. Preferred Administration Procedure for RATG or HATG (By IV infusion)
(i) Pre-medication as ordered by M.D. one hour before first dose of
administration; i.e. Acetaminophen 300 mg po/pr, Diphenhydramine 25
mg IV/po.
(ii) IV HATG
Equine ATG is stored at 2-8 degrees C. It is a transparent to slightly
opalescent aqueous solution, colorless to light brown, and may develop
a slightly granular or flaky deposit during storage.
The total daily dose should be added to N.S. or 0.45 N.S. as a maximum
of 1 mg/mL.The ATG should be added to an inverted solution to avoid
contact with air inside the container. The solution is stable for 12
hours. The total dose should be infused over a maximum of 12 hours
using a 20 micron filter. The usual initial dose is 10-20 mg/kg/d for 5-7
days for immune induction, or for 3 days in combination with
solumedrol 10 mg/kg/d for the treatment of refractory rejection.
(iii) IV RATG
RATG is stored at 4 degrees C. Reconstitute with the diluted provided
(5mL water for injection per 25 mg vial). Each 25 mg/5 ml vial should
be further diluted for subsequent IV infusion in 0.45 or 0.9 N/S (25
mg/50 mL diluent) over 24 hours by continuous infusion for immune
induction, and 6-12 hours for the treatment of rejection. Administer
only freshly prepared solutions. Arthralgia and nausea may occur and
may be reduced or eliminated by a slower infusion rate. The usual
initial dose is 2.5 mg/kg/d for 5-7 days for immune induction, or for 3
days in combination with 10 mg/kg/d of solumedrol for the treatment
of refractory rejection.
59

(iv) Watch for anaphylactic reactions:
1. Flushing, increased temperature
2. Tachycardia
3. Shivering
4. Increased BP, then decreased BP
5. Wheezing, SOB, cyanosis
6. Peripheral constriction
7. Generalized rash.
(v) Treatment of Adverse Reactions from ATG
1. Stop ATG infusion immediately.
2. Give additional diphenhydramine 25 mg IV, acetaminophen 650 mg
po/pr depending on severity of reaction; i.e. flushing, increased
temperature, shivering, etc.
3. Restart IV slowly when anaphylactic signs have disappeared.
4. If reaction continues to increase - Epinephrine may be required.
5. O2 administration as indicated.
60

10. IMMUNOLOGICAL MONITORING
Lung Biopsy
There is currently no simple non-invasive reliable technique to diagnose rejection.
Transbronchial biopsy, unfortunately, remains the current gold standard. This is a safe
technique.
Biopsies are performed shortly after the initial hospitalization at the time of
transplantation (14-21 days post transplant) and then every 2 weeks following
discharge for the first four to six weeks following transplantation. Subsequently, the
frequency of biopsies is decreased as a clear pattern of non-rejection is established.
Conversely, the frequency of biopsies may be increased if rejection is strongly
suspected and the initial biopsy was equivocal. If an attempt is made to wean down
cyclosporine levels or prednisone, monthly biopsies should be performed during the
weaning, for at least six months after the new baseline level is attained and then
quarterly thereafter, to ensure that rejection is not triggered by the lower
immunosuppressive levels.
Grade NEW NOMENCLATURE OLD NOMENCLATURE
0 No rejection No rejection
A1
A2
A3
Scattered,infrequent
perivascular mononuclear
infiltrates in alveolated
lung parenchyma are not
obvious on low
magnification.
Frequent perivascular
mononuclear infiltrates
surrounding small vessels
at low magnification
Dense perivascular
mononuclear infiltrates
extend into alveolar
septae
Minimal rejection
`Mild rejection
Moderate rejection
A4
Diffuse mononuclear
infiltration with
parenchymal necrosis
`Severe Acute' rejection
61

10.1 Immune Activation
While transbronchial biopsies have been our standard for the monitoring of lung
rejection, we recognize that other methodologies are available to assess the
presence or absence of `immune activation'. Cytoimmunological monitoring has
been advocated as just such a technology. Similarly, the measurement of
interleukin-2 and interleukin-2 receptors in the blood has been advocated as a
sensitive index of immune activation. If one were able to accurately correlate
this assay with immune activation, then it would remain only to distinguish
rejection from infectious causes of immune activation. Under the
circumstances of an elevated interleukin-2 or interleukin-2 receptor assay a
diligent search for infection would be carried out and a lung biopsy performed.
While it may be possible to decrease the frequency with which transbronchial
biopsies are performed, what remains undesirable about this assay is that it
relies on `exclusion' of infection to `rule-in' rejection, and therefore has not
generated much enthusiasm for monitoring for rejection.
10.2 Cyclosporine Levels
As all patients are on cyclosporine, whole blood trough levels are measured
daily by radioimmunoassay, 12 hours after the previous dose. The acceptable
target levels in the first three months are 350-500 ng/ml, and subsequently,
200 - 500 ng/ml, depending on renal function. Following discharge from
hospital the assays are performed twice weekly on the day of the clinic visit.
Note: Sudden increases in cyclosporine levels may be artifactual, but may also
represent deterioration of renal function with fluid retention and
hyperkalemia. Immediate reassessment of renal function, electrolyes and
cardiac function, are required.
10.3 Absolute Lymphocyte Count
Since all patients receive perioperative antithymocyte globulin for 5 - 10 days,
the absolute lymphocyte count is measured daily during ATG dosing aiming for
levels below 200 mm 3 . If the absolute lymphocyte count does not promply
fall, the dose of MALG is increased from 10 to 15 or 20 mg/kg/d by continuous
infusion. CD3 levels should be determined if the absolute lymphocyte count
remains elevated, as the batch of ALG could be defective. The only other
explanation for elevated absolute lymphocyte counts in the presence of
sufficient ATG dosing would be the presence of increased numbers of B-cells,
which would imply adequate T-cell suppression if

mg/kg/d, consideration should be given to switching to RATG or OKT 3 , and
administering Solumedrol 2 mg/kg/d X 3 days following the discontinuation of
the polyclonal or monoclonal therapy.
10.4 Chest Roentgenography, Bronchoscopy and Lung Biopsies
We have relied mainly upon ruling out infection on clinical findings, including
chest roentgenography and bronchoscopy. Changes in vitalometry may be
associated with either infection or rejection. In the presence of a pulmonary
infiltrate a transbronchial brushing and washing would be performed, to rule
out infection or rejection. It should be noted, as well, that the infilrates that
occur with rejection tend to be more diffuse and homogenous rather than
localized as might be the case with an infectious process. Rather than subject
patients to a lung biopsy in the setting of bilateral diffuse homogenous
infiltrates and a negative bronchoscopic assessment and negative serology for
CMV or HSV, we have preferred a single diagnostic therapeutic trial dose of
solumedrol 10 mg/kg/IV, which usually results in substantial clearing of the
infiltrate, thus strongly pointing to a diagnosis of rejection. A full course of
antirejection therapy is then given, and baseline immunosuppression adjusted.
While both infection and rejection can be associated with a reduction in FEV 1 ,
and FVC, it is important to remember that infection may lead to rejection by
up-regulating the immune system, which may lead to both acute and chronic
rejection (bronchiolitis obliterans, which is fatal in most instances). A 10% fall
in FEV 1 and FVC must be immediately investigated and, in the absence of
infection, bronchiolitis obliterans assumed and treated at least with Solumedrol
10 mg/kg/d X 3 days and cyclosporine, azathioprine and prednisone adjusted.
(See management of bronchiolitis obliterans )
63

11. MANAGEMENT OF REJECTION
11.1 In The First Three Months
Lung Rejection (Treatment Based On Pathological A2, A3, and A4) Or
Compelling Clinical Findings In The Absence of Histological Confirmation).
1. It is important to recognize that the best management of rejection is
the avoidance of rejection, which implies that maintenance
immunosuppression is optimal at all times. It is unacceptable to have
subtherapeutic cyclosporine levels, inadequate ATG dosage in terms of
target absolute lymphocyte counts perioperatively, or not to aim for
maximal azathioprine dosing within the tolerance of the white blood
count, up to 2 mg/kg/d.
2. For patients with normal renal function, the acute rejection episode
should be treated with Solumedrol 10 mg/kg/day for three days, the
Prednisone increased by 20%, the Azathioprine increased to a maximum
of 2 mg/kg/d if the bone marrow can tolerate this dose (maintain WBC >
4000/mm 3 ), and the Cyclosporine levels increased within the target
range.
3. For patients with renal function that is sufficiently compromised to
interdict further increases in cyclosporine, the rejection episode should
be treated with Solumedrol 10 mg/kg/day for 3 days, the Prenisone
increased by 20%, and the Azathioprine increased to a maximum of 2-3
mg/kg/day if the bone marrow can tolerate this dose (maintain
WBC>4000/mm 3 ).
4. For refractory lung rejection, a second course of Solumedrol 10 mg/kg
IV may be given, the prednisone further increased by 20% and the
cyclosporine and azathioprine optimized. Failure to resolve the lung
rejection with 2 courses of Solumedrol requires therapy with a
polyclonal MALG or RATG or monoclonal OKT3 antibody for 3 days, along
with pulsed steroids (10 mg/kg/d X 3 doses) and optimization of
cyclosporine, azathioprine and prednisone dosages. Absolute
lymphocyte counts should be suppressed to less than 200 mm 3 (or CD 3
levels to

with methyprednisolone sodium succinate may be given on a q8 hourly
basis for the first twenty four hours, and then twice daily for a total of
three to five days of therapy until the rejection episode is clearly
brought under control.
7. For mild acute rejection in the absence of any clinical abnormalities
no anti-rejection therapy is initiated, but maintenance
immunosuppression is reviewed to ensure that it is optimal. Under
the circumstances of a clear increase in the numbers of lymphocytes
present within the graft on biopsy, cyclosporine and azathioprine
levels would be optimized and, if mild rejection persisted with an
increase in the infiltrate, the patient would be treated with
Prednisone 50 mg bid for three days with subsequent taper by 5 mg
qd to 0.1 mg/kg/d above the previous dose.
8. Following the treatment of a rejection episode, a follow up biopsy is
performed 7 days later, or approximately 10 days after antirejection
therapy was initiated. Biopsies before this time, in
general, may not show adequate clearing of the lymphocytes from
the graft owing to insufficient time for resolution.
9. In summary, during the first three months, moderate and severe
acute rejection on lung biopsy, are treated with three 10 mg/kg daily
doses of solumedrol, with use of ATG or OKT3 reserved for failure of
two courses of solumedrol alone, A3 or greater rejection persisting
one week after a 3 day course of Solumedrol 10 mg/kg/d, or
rejection associated with hemodynamic instability.
11.2 After The First Three Months Post-Transplant
Severe acute rejection is treated as described above with pulsed doses of
solumedrol, with use of ATG, or OKT3 only for an, A3 or greater rejection
persisting one week after an initial 3-day course of solumedrol 10 mg/kg/d, or
failure of two courses of solumedrol therapy.
Grade A2 rejection would be treated with oral Prednisone 1 mg/kg qd for three
days tapering by 5 mg/d (2 mg/d if less than 20 kg) until 20% above the
previous daily dose of Prednisone. In the event that the patient demonstrated
hemodynamic compromise, we would assume that the biopsy sampling missed
the worst areas of acute rejection, that in fact the pathology is likely severe
acute rejection, for which the patient would be treated more aggressively with
pulsed doses of solumedrol, 10 mg/kg/d for three days, the prednisone dose
increased by 20%, and the cyclosporine and azathioprine would be optimized
within the limits of renal and marrow toxicity.
65

For mild acute rejection (Grade A1 ) unassociated with worrisome clinical
findings suggestive of rejection, the immunosuppressive therapy would simply
be reviewed to ensure that cyclosporine and azathioprine dosing was optimal.
66

11.3 Management of Bronchiolitis Obliterans (B.O.)
The occurrence of B.O. post lung transplantation usually portends a fatal
outcome that may occur within weeks of its onset and is always due to
inadequate immunosuppression. The pathology is likely antibody mediated as a
consequence of up-regulation of the immune system in the setting of either
inadequate immunosuppression or new infection, eg. CMV.
B.O. is initially manifest by a 10% drop in FEV 1 and FVC and may or may not be
associated with biopsy confirmation.
Therapy must take the form of aggressive immunosuppression with:
1. Solumedrol 10 mg/kg/d X 5 days
2. Optimization of cyclosporine levels to the 400-600 mg/ml range with
consideration of renal status.
3. Switch from Azathioprine to Cyclophosphamide 2-5 mg/kg/d to bone
marrow tolerance.
4. Failure to re-establish FEV 1 or VC mandates, a repeat of 1, 2 and 3 above
with a 5 day course of OKT 3 5 mg/d. Consideration may be given to using
OKT 3 in the first course of therapy.
5. Failure of the aforementioned regime may lead to a trial of TLI 80 gy/week
X 10 courses, depending on the clinical status of the patient.
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12. PROPHYLAXIS AND TREATMENT OF INFECTION
Immunization Policy and Protocol For Solid Organ Transplant Patients
a) Preamble
Immunization is important for all children and adults, and particularly for those
who are or are expected to become immunocompromised. A comprehensive
immunization policy for patients being transplanted is vital for two major reasons:
(1) The time before transplantation and immunosuppression, while the patient is
on the waiting list for transplantation, is a window of opportunity for optimal
response to immunization which will be lost after long term immunosuppression
begins.
(2) There are specific indications and contraindications for particular vaccines in
this immunosuppressed population.
The following principles apply to patients receiving immunosuppressive therapy.
(1) Currently available live virus vaccines (measles, mumps, rubella and polio) and
BCG are contraindicated.
(2) The immune response to inactive vaccines (eg. DTP) is lower than in normal
hosts, but is usually adequate.
(3) Certain vaccines may be particularly beneficial to the immunosuppressed
patient (eg. pneumoccoccal, influenza).
(4) Normal siblings and household contacts of immunosuppressed patients should
not receive oral polio vaccine, but should receive MMR and yearly influenza
vaccine.
b) Procedure
Patients who are awaiting transplantation should have their immunization status
reviewed at the initial pre-transplant assessment.They should be entered in one of
the three schedules provided depending on their age and prior immunization
history. An individual schedule for each patient should be constructed with
consideration given to past medical history, current medial status, medications and
time before transplant.
All immunizations should be administered by the public health system to ensure
proper preparation, administration and recording of immunizations given. They will
follow the immunization schedule provided by the infectious disease clinic. A
record should also be kept by the transplant service.
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Immunizations can be given up until 1 month before expected transplant
(especially important for MMR) and may be resumed post-transplant once the
patient is on a stable immunosuppressive regimen (usually not before 3 months
post-transplant).
At the time of transplant work-up, baseline serological response should be
measured for varicella, measles, mumps and rubella to establish the patients
immune status for future reference in the case of exposure.
Recommended Schedule For Active Immunization of Transplant Patients
Recommended Age Immunization Comments
2 mo DTP, IPV Can be started at age 2 wks if
imminent transplant (e.g. neonatal
cardiac)
4 mo DTP, IPV
6 mo DTP
*(6) - 12 mo MMR To be given only if 1 month or greater
before transplant. Measles vaccine
alone may be given as late as 2 weeks
before transplant. *May be given as
early as 6 mo but should be delayed
until 9 mos if transplant schedule
allows.
12 - 18 mo DTP, IPV,
Haemophilus
influenzae vaccine
2 yr Pneumovax
4 - 6 yr DTP, IPV
14 - 16 yr Td Every 10 yrs
Yearly
Influenza
Acyclovir Prophylaxis and Treatment For Herpes Simplex and Varicella Zoster
Infection
Herpes Simplex
Although reactivation of oral and genital herpes simplex infection in the early
postoperative period is common in transplant recipients, particularly those
receiving induction immunotherapy with antilymphocyte globulin, this disease is
usually relatively mild and easily treated with oral acylovir therapy. Therefore
monitoring for oral and genital lesions in the postoperative period should be
69

undertaken. Herpes simplex ulceration is often accompanied by candida
superinfection and swabs for both virus isolation and fungal cultures should be
taken from patients with suspected lesions. The usual dose of therapy is 200 mg 5
times a day for a period of 5 to 7 days. In most cases, oral or genital herpes
simplex infections, are not severe enough to warrant a routine prophylaxis of all
patients. The possible exception to this is the heart-lung transplant recipient.
Because asymptomatic reactivation of herpes simplex is extremely common posttransplant
and these patients are at high risk of aspiration and possible primary
HSV infection of the lung. It may be appropriate for this subgroup of patients to
receive acylovir prophylaxis at an initial dose of 200 mg 3 times a day. If the
patient breaks through this prophylactic dose, higher doses of 200 mg 5 times a day
may be required. In the single and double lung transplant recipients, the risk of
aspiration should be significantly lower and it is not clear that routine acylovir
prophylaxis is required for these patients.
Patients who have a very frequent recurrence of either oral or genital herpes
simplex should be considered for longterm low-dose acylovir prophylaxis at a dose
of 200 mg 3 times a day.
Varicella Zoster Infection
Because of the risk of dissemination of varicella zoster infection in the
immunocompromised host, transplant recipients with varicella zoster infections
should be treated with antiviral therapy. Treatment should begin with the initial 5
days of outbreak and patients should be advised to seek therapy early should they
develop symptoms. As a rule, the patient who is afebrile and has no evidence of
extensive extradermatomal or visceral dissemination can be treated as an
outpatient. The usual dose of acyclovir therapy is 800 mg 5 times a day for a
period of 7 days. This dose may require adjustment for renal failure. Please see
the protocol outlined for dosage adjustment for acylovir prophylaxis for CMV
infection prevention.
All patients are screened for varicella zoster antibody in the pretransplant period.
This is far more accurate than a clinical history of chicken pox. If the patient has
been exposed to chicken pox, please refer to their pretransplant varicella zoster
antibody status. If they have antibody they are immune and no further prophylaxis
is required. However, if they are seronegative and have a history of clear exposure
to chicken pox they should receive varicella zoster hyperimmune globulin.
Cotrimoxazole Prophylaxis For Pneumocystic Carinii Pneumonia (PCP)
Historical Perspective
Cotrimoxazole prophylaxis was initiated in March of 1988. The dose of prophylaxis
which was used was 1 double-strength tablet bid, Monday, Wednesday and Fridays.
Since that time there has not been a single case of PCP pneumonia in patients
receiving prophylactic therapy. The high incidence of PCP pneumonia was
70

undoubtedly due to the very aggressive use of immunosuppression and large doses
of antilymphocyte globulins used in the early transplant patient experience. It is
very likely that our present regimen, which is less aggressive, could result in a
significant lower incidence of infection. However, the continued use of antilymphocyte
globulins as immunoprophylaxis suggest that the risk will remain.
Recent studies in AIDS patients and other patients suggests that significantly lower
doses of cotrimoxazole are effective in the prevention of PCP. A recent study in
renal transplant recipients suggests a dose as low as 1 single strength tablet daily is
sufficient to prevent PCP pneumonia.
Therefore the dose of cotrimoxazole (Bactrim or Septra) used for prophylaxis of
pneumocystic carinii pneumonia will be: 1 single-strength tablet daily. This should
be continued over the first six post-transplant months and for longer periods in
patients who are maintained on higher levels of immunosuppression or have late
rejection events. Please note that patients experiencing CMV infection,
particularly primary CMV infection, are at increased risk of PCP pneumonia. It is
hoped that these very low doses of cotrimoxazole have no significant effects on on
either renal function and no significant bone marrow suppressive activity.
Protocol for CMV Monitoring of Allograft Recipients
Patients will be divided into one of four categories based on recipient donor
serology as follows:
neg-neg 1
neg-pos 2
pos-neg 3
pos-pos 4
Patients in categories 2, 3 and 4 will be monitored at the following intervals pretransplant,
every two weeks for 12 weeks, at six months and one year after
transplant. Patients in category 1 who are very unlikely to develop CMV infection
will be monitored at six months and one year only.
The following specimens should be submitted:
1. buffy coat (lavender top tube - mark requisition for CMV isolation)
2. CMV serology (red top tube - mark requisition CMV, IgG and IgM)
If the patient develops symptoms suggestive of CMV infection, submit an additional
set of specimens as above and appropriate biopsy material. Since specimens will
not be processed if submitted more frequently than every two weeks, specimens
submitted when the patient is symptomatic must be marked "lung transplant,
symptomatic (description of symptoms)".
Patients in categories 1 and 2 will have CMV IgG and IgM assays performed on sera.
Patients in categories 3 and 4 who are seropositive prior to transplant will be
monitored using CMV, IgM only. Routine monitoring should be discontinued when
71

CMV has been isolated from > .2 specimens and/or CMV igM (OD value) > .2 has
been demonstrated in two consecutive sera.
72

HSV Disease
If HSV oral, skin or genital lesions are suspected, submit swab of lesion (vigorously
swab base of ulcers and/or unroof and obtain vesicle fluid) in viral transport media.
Mark requisition "lung transplant for HSV isolation". Note throat swabs submitted
for CMV studies are not cultured for HSV unless this test is specifically requested.
Do not order HSV serology - this test is not useful in this setting.
VZV Disease
If VZV infection is suspected the preferred specimen is vesicle fluid drawn into a
capillary tube and hand delivered to Virology. Swabs of moist ulcers are also
acceptable. Mark requisitions "lung transplant for VZV isolation".
EBV Infection
Throat washes should be submitted as outlined on the attached protocol. EBV
serostatus pretransplant is determined using anti-EBNA IgG and is confirmed by
testing for anti-VCA IgG. A patient is considered seronegative if both assays are
negative. In patients who are seropositive )titre > 1:20), no further EBV serology
should be ordered. In patients who are seronegative, repeat serology for EBV-VCA
IgG and IgM should be performed at two weekly intervals for 12 weeks after
transplant or if antirejection therapy with ATG or OKT-3 are considered.
Acylovir Prophylaxis For CMV Mismatched Organs i.e. donor positive - recipient
negative only.
Dose: Start before transplant: 800 mg po (single dose) or 10 mg/kg IV.
Given another 800 mg po or 10 mg/kg IV 48 hours after transplant then adjust dose
to renal function as follows:
< 10 ml/min 800 mg od po or 5 mg/kg q24h IV
10-25 ml/min 800 mg tid po or 10 mg/kg q24h IV
> 25 ml/min 800 mg qid po or 10 mg/kg 18 h IV
dialysis 800 mg bid po or 10 mg/kg q24h IV and after dialysis
Continue until 12 weeks after transplant, adjust dose as required.
If the patient develops CMV infection, i.e. sheds virus or develops CMV-specific IgM,
stop the acyclovir.
If the patient is symptomatic or has evidence of tissue invasive disease w/u with
appropriate specimens/biopsy, consider ganciclovir Rx & CMV hyperimmune
globulin.
73

Please note: The efficacy of this regimen in patients who are CMV seronegative and
receive CMV seronegative donor organs or who are seropositive prior to transplant
has not been proven. Because of the low risk of CMV associated morbidity in these
groups, particularly on the most recent immunosuppressive regimens employing
lower doses of antilymphocyte globulin acylovir prophylaxis for prevention of CMV
infection in these groups is not recommended.
Perioperative Bacterial Prophylaxis
Knowledge of the nature of donor and recipient bronchial secretions plus
knowledge of the infectious patterns in transplant recipients at the PWH provides
the best guide to appropriate bacterial prophylaxis.
Excellent Gram positive and negative prophylaxis is achieved with Cefuroxime 1.5
mg IV preop and then 1.5 gm q12h postop in adults and until 1 dose after the chest
tubes are removed.
Patients undergoing transplantation for cystic fibrosis, bronchiectasis or pulmonary
fibrous frequently will harbor resistant pathogens, such as several pseudomonas
strains and methicillin-resistant staphylococci. These patients will require more
aggressive perioperative coverage with aminoglycosides, third generation
cephalosporins, and Vancomycin.
The special problem of fungal infections poses philosophical considerations, i.e.
when does colonization become infection? Inadequate therapy may lead to
bronchial disruption and upregulation of the immune system, causing rejection
which, if treated, further allows for entrenchment of the fungal infection.
Therefore, fungal infections in lung transplant recipients should be routinely
treated with `liposomal' Amphotericin B.
Management of Postoperative Infection
Postoperative temperatures (greater than 37.5 degrees C) and increased white
blood counts require vigorous investigation which includes 2 sets of blood cultures
(aerobic and anaerobic) with sputum and urine cultures each shift for 48 hours, and
then daily until the pathogen is identified. All intravascular lines are removed and
the tips cultured and new lines placed. Bronchoscopic or transtracheal aspirates
(TTA) are performed in patients with pulmonary infiltrates or positive sputum and
analyzed by gram smear, KOH, AFB, aerobic and anaerobic bacterial cultures, viral
cultures, Legionella and fungal cultures, and GMS (silver stain) for pneumocystis
carina. Antibiotics for pulmonary infection are never begun until a TTA,
bronchoscopy or transthoracic needle aspirate are done. Serology for CMV, EBV,
herpes virus, toxoplasmosis, coccidiomycosis, and cryptococcosis, plus urine,
sputum and throat swabs for shed CMV are carried out at 2 weekly intervals for the
first 3 months and may be helpful in identifying the pathogen. In patients with a
non-diagnosed elevated temperature or leukocyctosis, a white blood cell scan, lung
tomograms or a lumbar puncture may be indicated.
74

Amphotericin B, liposomal amphotericin B, fluocytosine, ketoconazole, miconazole
and rifampin are used alone or in combination (depending on sensitivities and
synergy studies) for the treatment of most fungal infections.
Acyclovir ointment is applied to superficial herpes simplex infections six times per
day. Herpes zoster infections or disseminated herpes infections are treated with IV
Acylovir (5 mg/kg tid or 15 mg/kg tid, respectively) for 14 days. Serum titres for
herpes virus are followed weekly, and in patients who receive ATG, Acylovir is
administered for 14 days for a rising titre.
Acyclovir may also be used for a rising EBV titre, with careful and frequent
examination for enlarging lymph nodes.
Parasitic and Protozoal infections are uncommon in patients treated with
cyclosporine.
12.1 Technique For Transtracheal Aspiration
1. Position patient in bed, sitting at 30 degrees with neck hyperextended, and
roll behind shoulders.
2. Clean neck thoroughly with alcohol, followed by a Poviodine-Iodine prep,
and drape with 4 sterile towels. Use sterile gloves and a mask.
3. Anesthetize the skin and underlying structures with 2% Lidocaine
(approximately 2-3 mL) with #22 gauge needle over the cricothyroid
membrane or between the first and second tracheal rings. It is usually
helpful to steady the trachea between the fingers of one hand during
infiltration or penetration of the trachea.
4. Insert a #18 or 20 gauge Bard intracath through the introducer needle, pull
the needle out of the trachea and advance the catheter as far it will go,
clamp the protective plastic guard over the needle. Instruct the patient to
try to suppress his cough.
5. With a 40 mL syringe, inject 10 mL of N/S and 40 mL of air rapidly during a
slow inspiration. If possible, have the patient take 2 or 3 deep breaths
without coughing, then have the patient cough and aspirate 2-4 times with
the 50 mL syringe. This usually results in 2-5 mL of intratracheal fluid for
analysis.
6. Send fluid for:
i) Gram Smear, KOH, AFB.
ii) Legionella cultures.
iii) Aerobic bacterial and fungal cultures.
iv) Anaerobic cultures.
v) GMS (Silver Stain) for Pneumocystis Carinii if indicated.
75

vi) Viral cultures if indicated.
12.2 Administration Procedure For Amphotericin B
Approximately one-fourth of transplant recipients at some point acquire a fungal
infection that may be responsive to Amphotericin B. Although it is important
always to conduct in vitro sensitivity and synergy studies with other antifungal
agents, results of these studies should not delay onset of therapy. The
antifungal agent should be started as soon as the fungus is speciated.
When Amphotericin is used, the following protocol will minimize adverse
reactions.
1. Assess renal function daily: Cr, BUN, creatinine clearance.
2. The daily dose of Amphotericin should not exceed 0.6 mg/kg per day in
order to minimize renal toxicity, unless liposomal amphotericin B is
used, in which case the tolerable dose will be 1 - 2 mg/kg/d.
3. The total treatment dose of Amphotericin should be 1000 - 2000 mg, the
final dose determined by clinical resolution of the infection.
4. Administration
i) Administer diphenhydramine 50 mg IV, hydrocortisone sodium
succinate (Solucortef) 25 mg IV and meperidine 25 mg IV plus
Acetaminophen 650 mg po or pr 20 minutes prior to a test dose
of Amphotericin 1 mg IV in 50 cc D5W run in over 1 hour.
ii) If there is no adverse reaction, administer 0.2 mg/kg Amphotericin IV
in 200 cc D5W over 4 hours. The pre-meds may be repeated 1-2
hours in the infusion if adverse reactions develop (chills, rigors,
spiking temperature, erythema, wheeze, hypotension,
tachycardia).
iii) If there are no serious adverse reactions to the administration of 0.2
mg/kg IV of Amphotericin, begin the same day with 0.4 mg/kg,
and then the day after with 0.6 mg/kg in 600 cc D5W over 4-6
hours. The diphenhydramine, hydrocortisone sodium succinate,
meperidine, and acetaminophen should be given 20 minutes prior
to the onset of the amphotericin infusion and then again, if
necessary, 1-2 hours after the infusion has begun.
5. Adverse reactions may require temporarily interrupting the infusion,
slowing the rate of infusion or decreasing the dose.
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13. PATIENT ISOLATION
Since the advent of cyclosporine and the concomitant reduction in prednisone
requirements, which has led to a slight decrease in frequency and a marked decrease
in severity of infectious episodes, it has been possible to markedly reduce the ICU and
total hospital stay for transplant recipients. Although the value of reverse isolation
has been questioned, we have discontinued reverse isolation, with no obvious adverse
sequelae. It is still our and others belief that the special circumstances of the
immunocompromised patient demand impeccable technique in managing them, with
handwashing prior to all visits and contact.
13.1 Criteria For Reverse Isolation
i) At any time if the patient is leukopenic (

3. Children with a communicable illness should not be allowed to visit a
transplant recipient in the ICU or on the ward.
4. For patients in a private ward room who are rejecting,visitation be
children should be interdicted.
5. For patients in a private ward room who are not rejecting, children of
any age without evidence of a communicable disease should be allowed
to visit the transplant recipient.
ii) Adult family members and friends who do not have a communicable disease
may visit patients in the ICU, or on the ward. A common sense approach is
used to minimize visitor traffic.
78

14. VENTILATORY SUPPORT
All patients are ventilated with positive pressure ventilation using the following
baseline parameters: Tidal volume 12-15 mL/kg (peak inspiratory pressure less than
40 cm H 2 O), peep 5 cm H 2 O, respiratory rate 8-12,the lowest FIO 2 possible to maintain
a PO 2 >90 mm Hg (generally 40-50% FIO 2 ). Initial respiratory settings are ordered by
the anesthetist,. Subsequent adjustments and weaning of the patients from
ventilatory support using IMV are controlled by the respiratory technician on
instruction from the transplant surgeon and fellow. It is important to maintain
pulmonary vascular resistance as low as possible, which is helped by maintaining PCO 2
at 28-32 until hemodynamics are stabilized.
Aggressive and frequent physiotherapy (q2-4h while awake) including percussion,
postural drainage and IPPB (only indicated with inadequate respiratory effort) is
mandatory to keep lungs well expanded and free from infection, which is the most
important cause of morbidity, mortality and prolongation of hospital stay.The
physiotherapist is responsible for scheduling and performing chest physiotherapy,
assisted by the nursing staff as required.
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15. RENAL FUNCTION
Many transplant recipients have preoperative renal dysfunction that may be
aggravated by cardiopulmonary bypass and cyclosporine. The following measures
greatly reduce the incidence of renal failure post-transplant:
1. Avoidance of preoperative cyclosporine.
2. Monitoring of daily whole blood cyclosporine trough levels post-op; aiming for 400-
600 ng/mL for the first three months and then 200-500 ng/mL thereafter.
3. Use of mannitol (12.5 gm) during cardiopulmonary bypass and then postoperative
with each dose of cyclosporine until baseline dosing is established.
4. Maintenance of an optimal CVP, with `high inflow (IV fluid) and outflow (urine
output: 1.5 - 2.0 mL/kg/hr)'.
5. Use of `renal effective' doses of dopamine (2-4 mcg/kg/min).
6. Use of diuretics as required to maintain a urine output of at least 1 mL/kg/hr.
The long term effects of cyclosporine on renal function are still being evaluated.
Evidence to date suggests that cyclosporine induces interstitial fibrosis and a variable
degree of tubular atrophy and glomerulosclerosis. Follow up renal function studies at
1 and 2 years indicate little further deterioration of renal function, which suggests
that the predominant renal injury occurs early postoperatively and is therefore
possibly due to relatively higher doses of cyclosporine used at that time.
80

16. CENTRAL NERVOUS SYSTEM
Seizures postoperatively may result from air emboli, atheroemboli, clots from
the recipient heart, intracerebral hemorrhage, intracerebral edema,
hypotensive induced ischemic, intracerebral infection or use of OKT3. Once a
quick assessment of the adequacy of respiratory and cardiac function has been
made, rapid initial seizure control is achieved with oxygen, phenytoin plus or
minus diazepam, followed by careful neurological examination, a computerized
tomographic head scan, electroencephalogram and assessment of cerebrospinal
fluid pressure and fluid if indicated. Patients require strict control of their
blood pressure postoperatively especially while being weaned from sodium
nitroprusside or nitroglycerin. Razosin, hydralazine, captopril, enalapril or a
calcium channel blocker, like cardizem are instituted to maintain systolic blood
pressure less than 140. Seizures may occur when this regimen is not followed.
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17. POST-LUNG TRANSPLANT ASSESSMENT
Patients are assessed with the attached tests as per our protocol at:
3 months
6 months
9 months
12 months
18 months
24 months
and yearly thereafter
• Bronchoscopies are done routinely at each assessment listed above up until 2
years post-op. Then the are done on a prn basis only.
• Bone density tests are booked at 3 months, 1 year and then yearly thereafter or
as needed.
• 2D Echo
Eisenmenger’s and Primary Hypertension.
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18. DATE DISCHARGE PROTOCOL GUIDELINES
18.1 0-3 MONTHS
BLOODWORK
THREE TIMES PER WEEK
• MD will assess blood frequency at three months
CBC, CSA/FK, LFT’s, lytes, creatinine profile, bone and
mineral profile (INR if necessary)
CSA and creatinine only
• All lab work must be done at PWH for the first three
months
• Lipid profile will be done at time of assessment.
PFT’S
ONCE WEEKLY
• Must be done before the clinic.
CXR
ONCE WEEKLY
• Should be done before the clinic.
REHABILITATION
THREE TIMES PER WEEK
• To be arranged in the Treadmill Room. Patient is to
arrange this prior to leaving hospital.
GANCYCLOVIR
AS PER PROTOCOL
CLINIC
WEEKLY AND PRN
• At three months post transplant patient should be referred back to the family physician or
respirologist to be followed in conjunction with the Lung Transplant Program.
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18.2 3-6 MONTH PROTOCOL GUIDELINES
BLOODWORK
Q2 weeks and prn
• CSA/FK, CBC, lytes, LFT’s, creatinine profile,
bone and mineral profile.
PFT’S
Q2 weeks or with clinic appt.
CXR
With clinic appt.
CLINIC
Monthly and prn
84

18.3 6 MONTHS – 1 YEAR PROTOCOL GUIDELINES
BLOODWORK
Monthly and prn
• CSA/FK, CBC, lytes, LFT’s, creatinine profile, bone
and mineral profile.
• Sputum on a prn basis.
Note: CF patients will require more frequent
bloodwork depending on absorption history of CSA/FK.
PFT’S
MONTHLY
CXR
WITH CLINIC APPT.
CLINIC
Q3 MONTHS and PRN
85

18.4 1-2 YEAR PROTOCOL GUIDELINES
BLOODWORK
Monthly and prn
• CSA/FK, CBC, lytes, LFT’s, creatinine profile, bone
and mineral profile.
• Sputum on a prn basis.
Note: CF patients will require more frequent
bloodwork depending on absorption history of CSA/FK.
PFT’S
MONTHLY and PRN.
CXR
WITH CLINIC APPT.
CLINIC
Q6 MONTHS (assessment surveillance) and PRN.
NOTE: All assessment appointments to be followed as per previous protocol with full
bloodwork including cholesterol profile and CMV urine and buffy coat at the time of
assessment.
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18.5 More than 2 YEAR PROTOCOL GUIDELINES
BLOODWORK
Monthly and prn
• CSA/FK, CBC, lytes, LFT’s, creatinine profile, bone
and mineral profile.
• Sputum on a prn basis.
Note: CF patients will require more frequent
bloodwork depending on absorption history of CSA/FK.
PFT’S
MONTHLY and PRN.
CXR
WITH CLINIC APPT.
CLINIC
Q6 MONTHS (assessment surveillance) and PRN.
NOTE: All assessment appointments to be followed as per previous protocol with full
bloodwork including cholesterol profile and CMV urine and buffy coat at the time of
assessment.
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