LUNG TRANSPLANTATION
LUNG TRANSPLANTATION
LUNG TRANSPLANTATION
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<strong>LUNG</strong> <strong>TRANSPLANTATION</strong><br />
PROTOCOL<br />
Iskander S. Al-Githmi, MD<br />
Anthony P. Yim, MD<br />
The Chinese University of Hong Kong<br />
and<br />
Prince of Wales Hospital
TABLE OF CONTENTS<br />
1. INTRODUCTION<br />
2. CURRENT STATUS<br />
3. PREOPERATIVE EVALUATION OF TRANSPLANT CANDIDATES<br />
3.1 Criteria for Candidate Selection<br />
3.2 Absolute Contraindications for Transplantation<br />
3.3 Logistics of Patient Referral<br />
3.4 Letter of Transplantation Program<br />
3.5 Introduction to the Referring Physician<br />
3.6 Transplantation Referral Guidelines & questionairs<br />
3.7 Guidelines for the Social Worker<br />
3.8 Worksheet for the Referring Centre<br />
3.9 Candidate Evaluation Orders for Lung Transplantation<br />
3.10 Preoperative Orders for Lung Transplant Recipient<br />
4. DONOR-RECIPIENT MATCHING<br />
5. PREOPERATIVE MANAGEMENT OF MULTIORGAN DONORS<br />
5.1 Criteria for Acceptable Lung Donors<br />
5.2 Preoperative Assessment of Multiorgan Donors<br />
5.3 Management of Multiorgan Donors<br />
5.4 Special Considerations for the Preoperative Management o<br />
5.5 Multiorgan Donor Assessment and Record<br />
5.6 Donor Orders For Multi-Organ Transplantation<br />
6. COORDINATION OF THE <strong>TRANSPLANTATION</strong> PROCEDURE: A CHECKLIST<br />
7. PROCEDURE FOR <strong>LUNG</strong> <strong>TRANSPLANTATION</strong><br />
7.1 Preparation of Perfadex Solution<br />
7.2 Procedure for Donor Double Lung Resection<br />
7.3 Procedure for Double Lung Transplantation<br />
8. POST-TRANSPLANT ORDERS AND MANAGEMENT<br />
8.1 Immediate Postoperative Orders<br />
8.2 Transfer Orders<br />
9. IMMUNOSUPPRESSION<br />
9.1 Introduction<br />
9.2 Immunosuppressive Protocol<br />
9.3 Administration Procedure for Anti-Thymocyte Globulin<br />
10. IMMUNOLOGIC MONITORING<br />
10.1 Immune Activation<br />
10.2 Cyclosporine Levels<br />
10.3 Absolute Lymphocyte Count<br />
10.4 Chest Roentgenography, Bronchoscopy and Lung Biopsies
11. TREATMENT OF REJECTION<br />
11.1 Rejection In the First Three Months Post-transplant<br />
11.2 After the First Three Months Post-transplant<br />
11.3 Management of bronchiolits obliterans<br />
12. PROPHYLAXIS AND TREATMENT OF INFECTION<br />
12.1 Technique for Transtracheal Aspiration<br />
12.2 Administration Procedure for Amphotericin B<br />
12.3 CMV, HSV, EBV Prophylaxis Protocol<br />
13. PATIENT ISOLATION<br />
13.1 Criteria for Reverse Isolation<br />
13.2 Patient Isolation in the ICU<br />
13.3 Patient Isolation in the Ward Private Room<br />
13.4 Visitation by Children, Friends, Family<br />
14. VENTILATORY SUPPORT<br />
15. RENAL FUNCTION<br />
16. CENTRAL NERVOUS SYSTEM<br />
17. POST-<strong>LUNG</strong> TRANSPLANT ASSESMENT<br />
18. DATE DISCHARGE PROTOCOL GUIDELINES<br />
18.1 0-3 months protocol guidelines<br />
18.2 3-6 months protocol guidelines<br />
18.3 6 months-1 year protocol guidelines<br />
18.4 1-2 year protocol guidelines<br />
18.5 > 2 years protocol guidelines
1. INTRODUCTION<br />
The purpose of this syllabus is to review the management guidelines for recipients<br />
of, single lung and bilateral single lung transplants. Concepts contained herein<br />
derive predominantly from the experience at the Toronto lung program, Stanford<br />
University Medical Centre, the international transplantation experience, and the<br />
input of the recent literature.<br />
The enclosed protocols for patient assessment and management represent our own<br />
view on the current state-of-the-art assessment and management principles.<br />
1
2. CURRENT STATUS<br />
Lung transplantation are currently indicated for patients with advanced forms of<br />
lung disease, in whom no realistic hope for extension of life or palliation exists<br />
with ordinary forms of medical or surgical intervention. Since, the introduction of<br />
Cyclosporine in December, 1980, and further refinements in management<br />
strategies have moved biologic lung transplantation from an experimental study to<br />
a truly therapeutic procedure with a one year survival rate of 75% to 80% and an<br />
expected five year survival rate of 45% to 55% in the best centres. As of 2003, the<br />
most recent data from the International Heart Transplant Registry indicates that<br />
more than 15000 lung transplants, were performed worldwide.<br />
2.1 Indications<br />
a. Single Lung Transplantation - emphysema (44%), idiopathic pulmonary<br />
fibrosis (17.9%), alpha 1 anti-trypsin deficiency (12.8%), primary<br />
pulmonary hypertension (7.5%), re-transplant (3.3%), cystic fibrosis<br />
(1.6%), miscellaneous (12.9%).<br />
b. Bilateral/Double Lung Transplantation - cystic fibrosis (37.5%),<br />
emphysema (15.6%), alpha 1 anti-trypsin deficiency (10.2%), primary<br />
pulmonary hypertension (11%), idiopathic pulmonary fibrosis (5.8%), retransplant<br />
(3.6%), miscellaneous (16.3%).<br />
2.2 Outcomes<br />
Lung actuarial survival for single lung at 1year is approximately 75%, 5 years<br />
is approximately 45-55%. Bilateral or double lung transplantation survival is<br />
similar.<br />
Better results may be achieved with emphysema and alpha I anti-trypsin<br />
deficiency with 1year and 2 year survival rates in the order of 77% and 70%<br />
respectively compared to idiopathic pulmonary fibrosis and primary<br />
pulmonary hypertension with 1 and 2 year survival rates of 65% and 57%<br />
respectively.<br />
Comparable results have been achieved with double lung transplantation in<br />
this same era. Of interest, single lung transplantation and has a one year<br />
survival rate for patients with emphysema of 80% at 1year as opposed to<br />
bilateral or double lung transplantation for which the 1 year survival rate<br />
has been 60%. For primary pulmonary hypertension, the 18-month survival<br />
rate for single lung and bilateral double lung transplantation is<br />
approximately 64% and for heart/lung transplantation approximately 55%.<br />
2
2.3 Causes of death following lung transplantation include:<br />
• 0-30 days<br />
Nonspecific graft failure, infection, dehiscence, hemorrhage, acute<br />
rejection, other.<br />
• 31 days to 1 year<br />
Infection, non-specific graft failure, bronchiolitis, malignancy, other.<br />
• >1 year<br />
Bronchiolitis, infection, non-specific graft failure, other.<br />
2.4 Re-transplantation<br />
Lung re-transplants account for 2.2 to 3%,of all lung transplants.Only 450<br />
lung re-transplants have been performed worldwide.Actuarial survival is<br />
approximately 45% at 1 year and 30% at 3 years. Because of lack of<br />
available donors lung and increasing number of waiting for lung<br />
transplantation, most of lung transplants center do not offer lung<br />
retransplantation.The basic indication for redo lung transplantation are<br />
acute and chronic graft failure.<br />
3
3. PREOPERATIVE EVALUATION OF <strong>LUNG</strong> <strong>TRANSPLANTATION</strong> CANDIDATES<br />
The goal of preoperative evaluation is the identification of individuals most likely<br />
to benefit in terms of survival and rehabilitation following transplantation. Such<br />
individuals are those with end-stage pulmonary disease for which no efficacious or<br />
clinically proven form of treatment other than lung transplantation exists.<br />
Personnel capable of the accurate assessment of such patients include an<br />
appropriately trained pulmonologist, thoracic surgeon, with the assistance of a<br />
social worker and transplantation coordinator.<br />
The general criteria for the selection of potential lung transplantation candidates<br />
include:<br />
3.1 Criteria for Candidate Selection<br />
3.1.1 Evidence of advanced physical incapacitation due to lung disease.<br />
The patient should be functionally limited.<br />
3.1.2 Life expectancy estimated to be weeks or months. Stated<br />
differently, the patient must have less than a 20% likelihood of<br />
surviving one year.<br />
3.1.3 An exception to conditions (3.1.1) and (3.1.2) above is the patients<br />
with intractable respiratory failure.<br />
3.1.4 Agreement that previous medical therapy has been optimal and that<br />
no surgical procedure other than transplantation offers realistic<br />
expectation of functional improvement and extension of life.<br />
3.1.5 The absence of sepsis, irreversible renal or liver dysfunction or other<br />
disease processes (eg. HIV positivity) that might otherwise cause an<br />
early death or be seriously aggravated by transplantation.<br />
3.1.6 Strong family support to aid the patient emotionally during the preand<br />
post-operative period, and for the rest of his/her life.<br />
3.1.7 Satisfactory intelligence, motivation and compliance to compulsively<br />
follow all medical recommendations including attendance at followup<br />
appointments and changes in exercise and dietary regimes.<br />
3.1.8 A reasonable understanding by the patient of his/her current illness<br />
with a realistic attitude and understanding of what transplantation<br />
can offer as well as the potential complications.<br />
3.1.9 A strong will and desire to live and to return to his/her family and<br />
community as a functioning member.<br />
4
3.2 ABSOLUTE CONTRAINDICATIONS FOR <strong>TRANSPLANTATION</strong><br />
During the evolution of the clinical transplantation internationally, multiple<br />
patient-related factors have come to be recognized as adversely affecting<br />
the outcome of lung transplantation. These factors constitute, relative or<br />
absolute contraindications to transplantation. However, selection criteria<br />
have already undergone considerable change and are expected to undergo<br />
further modification with the development of less toxic methods for<br />
immunosuppression. Restraints currently observed reflect the present<br />
`state of the art' in lung transplantation. The following factors exert an<br />
adverse influence on the outcome of transplantation:<br />
3.2.1 Severe pulmonary hypertension (> than 6 wood units. 640 dyne-seccm2,<br />
an indication for heart/lung transplantation).<br />
3.2.2 Severe irreversible hepatic or renal dysfunction.<br />
3.2.3 Active systemic infection (i.e. sepsis).<br />
3.2.4 Systemic disease such as systemic lupus, muscular dystrophy, HIV<br />
positivity, metastatic cancer, Hepatitis B positivity with active<br />
hepatitis or cirrhosis.<br />
3.2.5 Severe non-correctable peripheral or cerebrovascular disease.<br />
3.2.6 History of significant behaviour problem, e.g. frankly psychotic, drug<br />
or alcohol abuse.<br />
3.2.7 Clear history of non-compliance.<br />
3.3 LOGISTICS OF PATIENT REFERRAL, EVALUATION AND ACCEPTANCE<br />
For referring physicians of potentialcandidates for lung transplantation, it<br />
has been determined that a patient is a suitable candidate, the `Lung<br />
Transplantation Worksheet' for the referring center must be completed by<br />
the referring physician, nurse and/or secretary, and submitted with a<br />
complete psychosocial history (family background, education, work history,<br />
family constellation,available support systems,etc.) of the patient and<br />
his/her family to the lung transplantation center at Prince of Wales<br />
hospital.<br />
Once it appears likely that sufficient financial resources can be mobilized to<br />
meet the needs of the potential recipient candidate, and once a suitable<br />
psychosocial history for the patient and family have been obtained, this<br />
5
information and all relevant medical information will be reviewed and a<br />
final assessment and decision made at the Prince of Wales hospital.<br />
The `Candidate Evaluation Orders for LungTransplantation' details the final<br />
evaluation required for potential recipients of lung transplantation at the<br />
Prince of Wales Hospital.<br />
The format for listing accepted transplant candidates is by name; age; sex;<br />
medical record number; diagnosis; height; weight; date accepted into the<br />
program; local address; local phone and cell phone number; referring<br />
physician; blood type including the patient's ABO and RH blood type; most<br />
recent cardiac catheterization data (including pulmonary vascular<br />
resistance); cytotoxic lymphocyte antibody screen; information and date of<br />
previous transfusions or; HLA phenotype; complete blood count and<br />
differential; coagulation data; liver and kidney function analyses; serology<br />
for HBsAg, HIV, EBV, CMV and Toxoplasmosis; skin testing for T.B.; and most<br />
recent chest film. All data is dated.<br />
The preoperative orders for, lung transplant patients at the time of<br />
transplantation are detailed on page....... These orders are useful for<br />
candidates accepted via the aforementioned described process as well as<br />
emergency patients for whom a full workup cannot be fully completed with<br />
all data in hand at the time of acceptance and urgent request for a donor.<br />
In addition, for patients who undergo conventional evaluation and<br />
acceptance, these orders ensure that all tests have been performed<br />
preoperatively.<br />
6
3.4 LETTER OF INTRODUCTION TO THE REFERRING PHYSICIAN<br />
Dear Doctor:<br />
The Lung Transplantation Program at the Prince of Wales Hospital began in 2006.<br />
We believe it is time to inform our colleagues in the region we serve of the status<br />
of our program. In the interests of both busy physicians and sick patients, we<br />
would also like to simplify the process of referral to the program.<br />
It appears that some patients who might be accepted for transplant are not being<br />
referred because the indications are not well publicized or understood.<br />
Conversely, physicians may expend a great deal of effort preparing data, to refer a<br />
patient who turns out to be unsuitable for transplant.<br />
The simplest method of referral is to send a referral letter and a medical summary<br />
of the patient to:<br />
Lung Transplantation program<br />
Prince of Wales Hospital<br />
Shatin, N.T.<br />
When deciding whether to refer a patient for lung transplant, you should read the<br />
enclosed `Lung Transplant Referral Guidelines'. It should be emphasized that these<br />
are guidelines only, and are not cast in stone. Most of the contraindications are<br />
relative ones.<br />
If you have questions as to the suitability of a patient, please feel free to call the<br />
centre.<br />
If you would prefer to leave a message and have one of us return your call, then<br />
phone 852-2632-2211 and ask for the Recipient Transplant Coordinator on call .<br />
The Transplant Coordinator will ensure that one of us will return your call as soon<br />
as possible. We would be happy to answer any enquiries general or specific.<br />
Yours sincerely,<br />
-------------------------------MD.<br />
Lung Transplantation program<br />
Prince of Wales Hospital<br />
Shatin, N.T.<br />
Hong Kong<br />
7
LETTER OF INTRODUCTION TO THE REFERRING PHYSICIAN<br />
Dear Dr.:<br />
Thank you for your interest in the Chinese University,Prnice of Wales Hospital Lung<br />
Transplant Program.<br />
Potential transplant candidates must be young (under age 65), or biologically young<br />
(and chronologically older), vigorous and healthy except for end stage lung disease<br />
with a stable psychological and social situation. Patients should be functional Class<br />
III- IV (NYHA) and/or have a life expectancy of less than two years.<br />
The patient and supportive family member must be financially able to meet<br />
transportation expenses and cost of living in the Hong Kong area for a period of<br />
several months.<br />
There are two major components for completion of your referral:<br />
1. Medical - For the Physician<br />
a) Please review the enclosed `Lung Transplantation Guidelines for the<br />
Physician'.<br />
b) Please discuss the transplant procedure, survival rates and outcome,<br />
financial and logistical requirements with your patient and his/her<br />
family.<br />
c) If you and your patient decide to pursue lung transplantation evaluation<br />
at the Prince of Wales Hospital, please complete the enclosed `Lung<br />
Transplantation Worksheet for the Referring Center' to accompany your<br />
referral material.<br />
d) If, upon review of the enclosed material, you or your patient decide not<br />
to pursue transplantation at the Prince of Hospital, or If your patient<br />
expires during the period of referral, we would greatly appreciate a<br />
brief note to that effect.<br />
2. Psychosocial/Financial History for the Social Worker<br />
Please give your social worker the enclosed `Lung Transplantation Guidelines - for<br />
the Social Worker' to assist in completion of a written psychosocial and financial<br />
history.<br />
Copies of all referral data (medical as well as psychosocial and financial) must be<br />
received before the transplant team can make a decision regarding the patient's<br />
suitability for final transplant candidacy evaluation at this centre. You will be<br />
contacted regarding your patient's candidacy status upon review of all materials by<br />
the transplant team.<br />
We hope we can be of assistance to you and your patient. Thank you for your<br />
cooperation.<br />
8
Yours sincerely,<br />
________________________MD.<br />
Lung Transplantation Program<br />
Prince of Wales Hospital<br />
Shatin, N.T<br />
Hong Kong<br />
JRB<br />
Enclosures: as stated<br />
9
3.5 <strong>LUNG</strong> <strong>TRANSPLANTATION</strong> REFERRAL GUIDELINES<br />
Introduction<br />
Age<br />
These should be viewed as guidelines only since criteria are<br />
constantly changing. The only absolute contraindications are,<br />
serology positive for HIV, Hepatitis B, Hepatitis C, uncontrolled<br />
sepsis, metastatic cancer.<br />
Physiologic not chronologic age is more important. Our nominal age<br />
limit is 65 but we would transplant older patients if otherwise<br />
healthy with no other contraindications.<br />
Functional Class<br />
Patients should be functional Class III- IV (NYHA). However, we<br />
would consider patients temporarily in a better functional class due<br />
to therapy, particularly those on maximal therapy.<br />
General Health<br />
Compliance<br />
Except for end-stage lung disease, patients should be healthy.<br />
Patients must be capable of following a complex medical regimen.<br />
Those with a history or likelihood of major problems with<br />
compliance may not be accepted.<br />
Emotional Stability & Motivation<br />
Support<br />
Patients should be emotionally stable and have realistic attitudes<br />
toward illness, outcome, and transplantation. They will do better if<br />
they have a strong desire to live and to return to normal productive<br />
lives.<br />
Candidates need some person(s) able and willing to provide support<br />
before and after transplantation. Either at home, or if necessary,<br />
someone who will relocate to the transplant centre.<br />
10
Expectations<br />
Patients should have an understanding of what is involved in<br />
transplantation and should realize that they are coming for<br />
evaluation. Acceptance for transplantation occurs after our<br />
assessment and review of the clinical data.<br />
Physician Support<br />
The referring or some other local physician should be prepared to<br />
assist in caring for transplant patients following transplantation and<br />
return to their communities. Following our first clinical assessment<br />
of the patient, it would be of considerable assistance to our program<br />
if the referring physician were able to undertake the preliminary<br />
laboratory assessment of the patient. If this is possible, a detailed<br />
list of the requirements would be forwarded by the Recipient<br />
Transplant Coordinator.<br />
Contraindications<br />
1. Systemic disease such as lupus, muscular dystrophy, noncorrectable<br />
vascular disease, HIV, Hepatitis B with active<br />
hepatitis or cirrhosis, cancer, etc..<br />
2. Active infection, sepsis.<br />
3. Pre-renal azotemia and/or hepatic dysfunction.<br />
4. Morbid obesity.<br />
5. History of major alcohol or drug abuse or mental illness.<br />
6. Clear history of non-compliance<br />
3.6 <strong>LUNG</strong> <strong>TRANSPLANTATION</strong> QUESTIONAIR<br />
For consideration for transplantation at the Prince of Wales Hospital, please<br />
direct your attention to the following:<br />
1. Is the patient under 65 years of age?<br />
2. Is the patient functional ClassIII- IV (NYHA)? Does he/she have a life<br />
expectancy of less than two years?<br />
3. Except for end stage lung disease, is the patient a vigorous and<br />
healthy individual who would benefit from the procedure?<br />
11
4. Has the patient demonstrated the ability to take medications<br />
faithfully and comply with medical recommendations? (The<br />
postoperative transplant course demands rigorous attention to a<br />
complex immunosuppressive drug, exercise, and dietary regimen for<br />
the rest of the patient's life and also requires the patient to return<br />
for repeat clinical and laboratory evaluations in the future).<br />
5. Has the patient demonstrated emotional stability and a realistic<br />
attitude in response to past and current illness? (Denial of<br />
symptoms or recurrent situational depression are likely to recur<br />
post-transplantation if they are present now.)<br />
6. Does the patient have a strong desire to live and have a stable,<br />
rewarding family and/or vocational environment to return to posttransplantation?<br />
7. Does that patient have a spouse, family, and/or companion who is<br />
able and willing to make a long-term commitment to providing<br />
emotional support of the patient both pre- and post-transplantation?<br />
8. Does that patient have a strong, supportive family constellation that<br />
is able and willing to tolerate the family upheaval and stresses of<br />
lung transplantation? (Family conflict is likely to recur if present<br />
now.)<br />
9. Are financial resources available to the patient to pay for:<br />
a) Travel to Hong Kong accompanied by a supportive family<br />
member for final evaluation of transplantation candidacy<br />
(and return home)?<br />
b) Living expenses for the patient and family while in the Hong<br />
Kong area before, during and after transplantation?<br />
c) Semi-annual travel to the Prince of Wales Hospital,<br />
indefinitely, for medical follow-up and during acute rejection<br />
episodes.<br />
10. Have you discussed these guidelines with the patient and/or family<br />
and factually informed them of the transplant procedure, survival<br />
statistics, current risks, complications, and financial commitment<br />
required?<br />
11. Are you or another person willing to care for this patient if he<br />
returns to your community post-transplantation? The responsible<br />
pulmonologist or internist must be available, aggressive,<br />
12
knowledgeable (or willing to become so) in the care and<br />
complications of the immunosuppressed patient, and absolutely<br />
dedicated to keeping the patient alive long-term.<br />
3.7 GUIDELINES FOR THE SOCIAL WORKER<br />
These guidelines have been developed to assist you in the completion of a<br />
written psychosocial and financial history to aid in the evaluation of your<br />
patient as a possible candidate for lung transplantation at the Prince of<br />
Wales Hospital.<br />
1. Please provide a factual and complete psychosocial history (family<br />
background, education, work history, current family constellation,<br />
available support system, etc.) of the patient and of his/her family.<br />
Please comment on the patient's ability (coping mechanisms) to<br />
comply with a rigorous therapeutic regimen pre and postoperatively.<br />
Are there any psychosocial impediments that may interfere with the<br />
medical treatment plan? Does the patient have a history of drug or<br />
alcohol abuse and, if so, has the problem been resolved and, if so,<br />
how and to what extent?<br />
2. Your written psychosocial and financial history should be sent to the<br />
Recipient Transplant Coordinator to facilitate referral of your<br />
patient. Please give a copy of your report to your patient's physician.<br />
If necessary, for assistance in completion of your report/assessment, please<br />
contact the Transplant Social Worker, (852) 2632-2211 at the Prince of<br />
Wales Hospital.<br />
13
3.8 <strong>LUNG</strong> <strong>TRANSPLANTATION</strong> WORKSHEET<br />
FOR THE REFERRING CENTRE<br />
(To be completed by referring physician, nurse, and/or secretary)<br />
Patient's Name:<br />
Address:<br />
Home Phone:<br />
Work Phone:<br />
Sex: Male ( ) Female ( )<br />
Birthdate:<br />
Diagnosis:<br />
Social Status:<br />
Single ( ) Married ( )<br />
Divorced ( ) Separated ( )<br />
Widowed ( ) Student ( )<br />
Name of Spouse:<br />
Name of Referring Physician:<br />
Address:<br />
Phone:<br />
Name of Patient's Current and/or Past<br />
Employment:<br />
Name of Social Worker:<br />
Phone:<br />
Status of Social Worker's Assessment:<br />
Completed ( ) In Preparation ( )<br />
Languages Spoken: Cantonese Yes ( ) No ( )<br />
Other:<br />
Patient's Height:_____Weight:<br />
Date of Last Cath Study:<br />
Month Day Year<br />
Check-List for Materials Accompanying<br />
Worksheet:<br />
__Medical Summary of Current Illness<br />
__Pulmonary Function Tests & ABG's<br />
__Copy of Cath Report(s) Including<br />
Pulmonary Artery Pressures and<br />
Vascular Resistance<br />
__Cine Film(s) of Coronary Arteriography<br />
__Chest X-rays (LATEST ONLY, NON-<br />
RETURNABLE)<br />
__Past Medical/Hospital Summary(s)<br />
__Psychosocial/Financial Evaluation<br />
__Date of all Materials Mailed to the<br />
Prince of Wales Hospital<br />
Patient's Insurance:<br />
Is Patient in Hospital now?<br />
Yes ( ) No ( )<br />
Name of Hospital:<br />
Phone:<br />
Please mail to:<br />
Lung transplantation program<br />
Division of cardiothoracic surgery<br />
Prince of Wales Hospital<br />
Chinese University of Hong Kong<br />
Shatin, N.T.<br />
14
3.9 CANDIDATE EVALUATION ORDERS FOR <strong>LUNG</strong> <strong>TRANSPLANTATION</strong><br />
ON ADMISSION (Day 0)<br />
1. Diet<br />
2. Activity<br />
3. Notify the following:<br />
a. Transplant coordinator ( pager: )<br />
b. Transplant social worker (Pager: )<br />
c. Transplant dietitian (Pager: )<br />
Day 1<br />
4. Consultations as follows:<br />
a. Dentistry<br />
b. Dr……………… (for lung transplant assessment)<br />
c. Dr……………….( for cardiac assessment )<br />
d. Dr……………….( Endocrinology assessment )<br />
5. Record weight in kg and height in cm and daily a.m. weights.<br />
6. Book pulmonary function studies and arterial blood gases.<br />
7. Skin test for T.B. (5TU PPD intradermal).<br />
8. Urinalysis including microscopic.<br />
9. ECG (leave copy on chart).<br />
10. PA and lateral chest x-ray.<br />
11. Echocardiogram.<br />
12. Sputum and urine for C & S.<br />
13. Special virology:<br />
a. Mid-stream urine for CMV - 20 mL urine in sterile container.<br />
b. Throat swab for CMV in viral transport medium.<br />
c. Throat washings for EBV virus.<br />
14. Routine viral serology:<br />
a. Anti-CMV (IgG and IgM) serology.<br />
b. Anti VZV serology (Anti-HSV for lung patients).<br />
c. Anti-VCA EBV (IgG)<br />
15
15. Serology: HBsAG; Anti-Hepatitis C and Anti-HIV.<br />
10-mL gelled red-top tube to Microbiology Lab.<br />
16. Anti-toxoplasmosis IgG.<br />
Send 10-mL gelled red-top tube to Microbiology Lab.<br />
17. Hematology:<br />
a. CBC, manual differential, reticulocyte count, platelets and<br />
ESR.<br />
b. PT, PTT.<br />
18. Blood Bank:<br />
Blood type and screen.<br />
19. Biochemical Studies:<br />
_________________________M.D.<br />
Day 2<br />
a. Serum electrolytes, creatinine, glucose, BUN, alkaline<br />
phosphatase, AST, CK, LD, Total bilirubin, CA++, Mg++,<br />
phosphate, uric acid, albumin, T. Prot.<br />
b. Ferritin<br />
c. TSH.<br />
d. Quantitative immunoglobulins<br />
requisition to be signed by transplant service physician.<br />
e. Serum immunoelectrophoresis (3 mL blood in 5-mL red-top<br />
tube to Immunochemistry) - requisition to be signed by<br />
transplant service physician.<br />
f. 24-hour creatinine clearance - ensure serum creatinine drawn<br />
during 24 hour period of urine collection.<br />
20. 14-hour fasting lipid profile - requisition to be signed by transplant<br />
service physician.<br />
21. Lymphocyte cytotoxic screen. Send 2 10 mL red-top clotted tubes<br />
to Transplant Immunology Lab. Mark on requisition "possible lung<br />
transplant - Attn: Tissue Typing Lab."<br />
22. Lung Scan with quantitation of ventilation/perfusion.<br />
16
23. Thoracic dimensions to be recorded by transplant coordinator as<br />
follows:<br />
a. Circumference of chest at axilla.<br />
b. Length of chest at mid axillary and mid clavicular levels.<br />
c. Depth at mid sternum.<br />
_______________________________M.D.<br />
3.10 PREOPERATIVE ORDERS FOR <strong>LUNG</strong> TRANSPLANT RECIPIENTS<br />
When recipient for lung transplantation arrives on floor:<br />
1. Nursing Care<br />
a. Vital signs and weight STAT; old chart to floor ASAP.<br />
b. NPO after ______ except for medications ordered<br />
henceforth.<br />
c. Consent forms to be signed:<br />
i. consent for lung transplantation;<br />
ii. consent for multiple lung biopsies as required;<br />
iii. consent for rabbit antithymocyte globulin;<br />
antilymphocyte globulin and OKT3.<br />
d. Surgical prep neck to knees, bedline to bedline. Scrub entire<br />
body with Povidone - Iodine (Betadine) 10 min. following prep.<br />
e. Peripheral IV for medications 2/3 - 1/3 TKVO.<br />
2. Stat Blood Work<br />
a. CBC and 3-part diff, reticulocyte count, electrolytes, glucose,<br />
urea, creatinine.<br />
b. PT, PTT, platelets, fibrinogen.<br />
c. STAT donor specific lymphocyte X-match. (One 10-mL red top<br />
gelled tube).<br />
3. Regular Blood Work:<br />
a. Chemical profile, Serum iron and TIBC. (MD to sign req.)<br />
b. FANA, rheumatoid factor.<br />
c. Serum protein electrophoresis. (MD to sign req.)<br />
d. HbsAg, anti-Hepatitis C, and anti-HIV serum titres STAT.<br />
17
4. Studies<br />
a. Virology testing:<br />
i. serum for anti-CMV, VCA IgG (EBV), - in one 5 mL red top<br />
gelled tube;<br />
ii. urine for CMV - 20 ml urine in a sterile container;<br />
iii. throat washings for EBV detection;<br />
iv. throat swab for CMV in viral transport media.<br />
Label all requisitions, "Attention: Lung Transplant Recipient."<br />
PLACE IN REFRIGERATOR<br />
b. Two sets of blood cultures (aerobic and anerobic) for C&S<br />
from 2 different sites.<br />
c. Type and X-match for 8 U packed cells, 6 U FFP, 8 U<br />
cryoprecipitate and 12 U platelets for OR ASAP.<br />
d. STAT PA and lateral chest film in Radiology, if possible,<br />
otherwise - portable film. Send with patient to OR.<br />
e. Routine sputum and urine bacterial and fungal cultures.<br />
5. Medications<br />
a. Ranitidine _______mg p.o. Send ______mg for IV injection.<br />
b. Mycophenolate Mofetil ----------mg po.<br />
c. Antibiotics: Send with patient to OR.<br />
i. Cefuroxime _____mg IV.<br />
ii. _____________________ mg IV.<br />
6. Notify Dr. ________________when patient back from Radiology and<br />
old chart on floor.<br />
7. Call results of CBC< electrolytes, creatinine, BUN, PT, PTT, and<br />
platelets to Dr. _____________.<br />
_____________________________MD<br />
18
4. DONOR-RECIPIENT MATCHING<br />
Patients selected for transplantation are chosen from the recipient candidate list<br />
immediately upon availability of a suitable donor, who will be managed in most<br />
instances by the Transplant coordinators and medical staff locally, or by telephone<br />
consultation at the distant centre. In most cases, the transplant coordinator at the<br />
Prince Of Wales Hospital will receive the first call from the donor centre and<br />
obtain the pertinent information on the suitability of the donor for the lung<br />
donation. Due to the difficulty in obtaining satisfactory lung donors, donors are<br />
first screened for their suitability for lung donation. Recipient matching is then<br />
based on:<br />
1. ABO compatibility<br />
2. Less than 20% discrepancy between donor and recipient lung<br />
transplantation. Note: There may be exceptions in which a larger donor<br />
may be considered for a recipient with borderline acceptable pulmonary<br />
vascular resistance. In this setting a short donor ischemic time is<br />
desirable.<br />
3. Absence of a positive lymphocyte cross match. The lymphocyte cross match<br />
may be done post transplant if the preoperative PRA is negative; otherwise<br />
it is desirable to perform the cross match pre-transplant.<br />
If several otherwise suitable recipient candidates exist for transplantation,<br />
recipient selection will be based on the:<br />
1. Acuteness of the clinical state.<br />
2. Prospect for heart-lung transplantation.<br />
3. Elapsed time as an acceptable candidate.<br />
*Note: If a recipient candidate has not had previous surgery or blood transfusions,<br />
and if the preoperative cytotoxic lymphocyte screen is negative (i.e. there<br />
is an absence of cytotoxic antibodies in the recipient serum against a<br />
random panel of donor lymphocytes, e.g. 50/50 negative), and if the donor<br />
is at a centre from which the procurement of donor blood is difficult or too<br />
time consuming, then it is acceptable to conduct the cytotoxic lymphocyte<br />
cross match post-transplant. For onsite donors, all compatibility studies<br />
should be conducted pre-transplant when the PRA is even partly positive.<br />
19
5. PREOPERATIVE MANAGEMENT OF MULTIORGAN DONORS<br />
5.1 Criteria for Acceptable Lung Donor<br />
(i)<br />
Age<br />
Donors for lung transplantation should be less than 65 years of age.<br />
Older donors are, in general, acceptable for older recipient<br />
candidate.<br />
(ii)<br />
Absence of systemic sepsis or malignancy. Treated infection and<br />
remote cured malignancy, on the other hand, do not preclude organ<br />
donation.<br />
(iii)<br />
Lung Donors<br />
Normal pulmonary physiology, mechanics, an absence of purulent<br />
pulmonary sections and a clear chest film are required: PO 2 > 300<br />
mg Hg on an FIO 2 100%, with normal lung compliance, normal to<br />
scant pulmonary secretions and normal chest roentgenographic<br />
appearances indicate satisfactory lung status for donation.<br />
5.2 Preoperative Assessment of Multi-organ Donors<br />
The transplant coordinator should be contacted at the time of brain death<br />
declaration or, preferably, before brain death is declared if that diagnosis is<br />
likely forthcoming, in order to facilitate management and multiple organ<br />
harvesting. All relevant patient related factors must be communicated to<br />
the transplant personnel to ensure optimal, multi-organ management.<br />
It is the responsibility of the Transplant program Coordinators to ensure<br />
that donors are optimally managed,and they should be able to make<br />
management decisions based on clinical assessment at the time. In<br />
conjunction with medical transplant personnel, along with the physician<br />
managing the patient directly, the coordinators must ensure that the donor<br />
is optimally managed. Determinants of donor acceptability.<br />
(i)<br />
Assessment of the Lung Donor<br />
Determination of suitability for lung donation requires evaluation of<br />
arterial blood gases, lung compliance, nature and extent of<br />
pulmonary secretions (deep bronchial aspirate or bronchoscopic<br />
aspirate for gram smear and C&S) and chest roentgenography.<br />
20
5.3 Management of Multiorgan Donors<br />
The urgency with which donors frequently have been rushed to the<br />
operating room for kidney harvest reflects the hemodynamic instability and<br />
metabolic derangements that often occur with brain death. While this<br />
approach has expeditiously disposed of donors in a timely fashion and<br />
allowed renal and other non vital organs to be harvested, this practice<br />
unfortunately frequently prevents the use of other vital organs, ie. the<br />
liver, heart and lungs. In general, more time maybe required to mobilize<br />
`other transplant teams', and assess adequacy of organ function. It has not<br />
infrequently been the case in the past, as well, that the kidneys have not<br />
been used because of such severe donor hemodynamic instability that not<br />
even the kidneys could be harvested in time. Accordingly, if more<br />
transplants of all vital organs are to be performed in the future and if all or<br />
nearly all potential donors are to be used for multiorgan transplantation,<br />
there must be: first, a common understanding by the personnel of each<br />
transplant program of the physiological derangements that accompany<br />
brain death and, second, agreement on the therapeutic strategies<br />
required for optimal donor management to ensure immediate and<br />
normal function of each vital organ post transplantation.<br />
Consternation between various transplant programs may develop as one<br />
group attempts to insure that their `vested interest' organ is `optimally'<br />
managed; not infrequently to the detriment of other vital organs. One<br />
group may attempt to push fluids and accept systemic arterial hypotension,<br />
tachycardia and markedly elevated urinary outputs, the latter of which may<br />
be interpreted as a sign that the kidneys are well perfused and therefore<br />
protected. One might question whether or not hypotension (MAP
Recognizing that brain death may well be associated with hemodynamic<br />
instability, the following addresses the concerns surrounding the unstable<br />
donor, particularly the physiologic derangements that frequently occur in<br />
brain death, following by the treatment strategies that aim to correct these<br />
abnormalities that have been tried and proved over a number of years of<br />
collaborative transplantation efforts between many multiorgan transplant<br />
centers.<br />
Brain death is often accompanied by a loss of vasomotor tone, with<br />
resultant fall in blood pressure. Hypotension may also be due to<br />
hypovolemia (blood loss, therapeutic dehydration to decrease cerebral<br />
edema, third space losses and osmotic diuresis due to hyperglycemia) or<br />
myocardial injury and dysfunction. A high urine output from diabetes<br />
insipidus (DI) may contribute to hypovolemia, hypernatremia and<br />
hypokalemia (hyperosmolar dehydration). Homeostatic temperature<br />
control is often lost and the patient becomes hypothermic. Neurogenic<br />
pulmonary edema may occur.<br />
When first evaluating a potential donor, complete the data record for<br />
multiorgan donors, which facilitates the assessment and management of the<br />
donor. Then, determine the adequacy of cardiac function by inquiring as to<br />
the mean arterial pressure (MAP), the central venous pressure (CVP), and<br />
the state of tissue perfusion as reflected by peripheral skin color and<br />
temperature, pedal pulses, urine output, oxygenation and acid-base status.<br />
Check for cardiac murmurs. Check EKG. Although ST segment and T wave<br />
abnormalities are often present in severely brain injured patients, if the<br />
myocardial CPK is not elevated then the heart has not likely been injured.<br />
With control of blood pressure and tachycardia the ST segments usually<br />
normalize. Cardiac output may be low, normal or in excess of 10 L/min<br />
with a low MAP and an elevated, normal or low CVP, depending upon<br />
circulating blood volume, systemic vascular resistance (SVR) and the state<br />
of myocardial contractility. Check for adequate respiratory function by<br />
reviewing for evidence of chest injury, the arterial blood gases, tracheal<br />
secretions and the CXR. Check for adequate renal function by reviewing<br />
urine output in relation to serum creatinine and BUN. Check for adequacy<br />
of liver function by reviewing liver function tests.<br />
Every effort is made to maintain a stable and adequate blood pressure with<br />
the judicious use of volume replacement, inotropes and/or vasopressors.<br />
To clarify a common misconception on the use of vasopressors, the goal of<br />
`pressor' therapy for specific patients only who are normovolemic (CVP 6-10<br />
mm Hg) but hypotensive (MAP
enal or hepatic function in the volume repleted donor, and may be<br />
demonstrated to improve organ perfusion.<br />
In patients without a Swan-Ganz catheter, a low SVR is suspected if the MAP<br />
is low and the extremities are warm and well perfused with bounding pedal<br />
pulses. If the CVP is 6-10 mm Hg and the MAP 10 mm Hg and a controlled Dl or absence of<br />
Dl, place a Swan-Ganz catheter in order to differentiate myocardial<br />
dysfunction from excessive volume expansion or high output `failure'<br />
secondary to a markedly depressed SVR. Hemodynamic stability can only<br />
be achieved if wide swings in intravascular volume and systemic vascular<br />
resistance can be avoided. Following the administration of vasopressin<br />
there is often a fall in the CVP and an increase in the MAP, allowing<br />
satisfactory weaning of the Dopamine. Inability to wean the Dopamine at<br />
this point indicates either a contractility problem, hypervolemia or high<br />
output cardiac `failure' due to a total loss of vasomotor tone wherein the<br />
circulating blood volume passes rapidly from left to right elevating the CVP.<br />
The markedly increased cardiac work associated with increased cardiac<br />
filling pressures and high cardiac output in the setting of a decreased<br />
transmural myocardial perfusion gradient (hypotension, MAP < 70 mm Hg),<br />
decreased diastolic perfusion time (tachycardia HR > 140) may lead to<br />
23
myocardial ischemia and arrhythmias causing severe hemodynamic<br />
instability and subendocardial infarction. The right ventricle is particularly<br />
prone to injury secondary to excessive wall tension and myofibril stretch<br />
from large volumes of administered fluid, hence the value of CVP<br />
measurement. Subendocardial or transmural infarction in this setting may<br />
be difficult to diagnose, but may clearly lead to loss of the heart for<br />
donation, or even worse, if transplanted, death of the recipient.<br />
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<br />
normal, with or without evidence of a metabolic acidosis, and the<br />
Dopamine is less than or equal to 5 mcg/kg/min, there is good evidence of<br />
severely compromised contractility and the heart should not be used.<br />
On the other hand, if the C.I. > 3.5 L/min/m 2 along with the above<br />
parameters except that SVRI is low (often 800-1200), then the problem is<br />
one of a total loss of vasomotor tone, which is associated with left to right<br />
shunting and regional hypoperfusion, as reflected by a mild metabolic<br />
acidosis (may also be related to decreased tissue O 2 delivery secondary to<br />
anemia, decreased 2,3 DPG or respiratory alkalosis) and an elevated CVP.<br />
Urine ouput may be unacceptably reduced due to intra-renal shunting as<br />
well. This problem is easily solved by the judicious use of vasopressors to<br />
raise the systemic vascular resistance index only to the normal range (1800-<br />
2000 dynes sec cm -5 ).<br />
5.4 Special Considerations for the Preoperative Management of Donors for<br />
Lung Transplantation<br />
Donors for lung transplantation frequently develop early pneumonic or nonpneumonic<br />
pulmonary disease which is associated with unacceptably low<br />
compliance and compromised respiratory function. Neurogenic pulmonary<br />
edema may occur. Every effort is made to maintain a stable and adequate<br />
blood pressure, and to protect alveolar-capillary integrity, thus assuring<br />
immediate and adequate graft function post-transplantation. Satisfactory<br />
pulmonary function is demonstrated by clear lung fields on chest<br />
roentgenography, normal lung compliance, PO 2 greater than 120 mm Hg on<br />
40% Fl0 2 and the absence of purulent pulmonary secretions. The following<br />
measures, in addition, are essential in the management of potential heartlung<br />
donors, and lung donors.<br />
1. Intubate with an endotracheal tube with a high compliance, high<br />
volume, low pressure cuff.<br />
2. Continuous volume cycled respiratory with 40% FlO 2 , tidal volume<br />
12-15 mL/kg, PEEP 5 cm H 2 O, respiratory rate 6-12 breaths/min.<br />
24
3. Record ventilation pressure q1h (should be less than 25 cm H 2 O for<br />
size adjusted normal tidal volume).<br />
4. Vigorous chest physiotherapy with postural drainage q2h and<br />
nasotracheal suctioning q1h.<br />
25
5.5 MULTIORGAN DONOR ASSESSMENT AND RECORD<br />
General Information<br />
Donor Data Record<br />
Date: Time: Race:<br />
Donor Name: Sex: Age/DOB:<br />
Donor Hospital:<br />
Referring MD:<br />
Contact Name/#:<br />
Admission Diagnosis:<br />
Date of Injury:<br />
Cause of Death:<br />
Patient Declared Brain Dead: Physician:<br />
Date/Time: 1st<br />
2nd<br />
Consent for Donation of:<br />
Medical Examiner Notified: Yes No Name:<br />
Who Initiated Donor Referral?:<br />
Relevant Past History:<br />
Malignancy:<br />
Diabetes:<br />
Hepatitis:<br />
Hypertension:<br />
Admission History & Hospital Stay:<br />
Surgery:<br />
Substance Abuse:<br />
High Risk:<br />
Clinical:<br />
Blood Group: Rh: HLA A B C DR<br />
Serology: HIV HTLV-I HbsAg HCV Syphilis<br />
CMV (pre/post)__________<br />
Donor Weight (kg):<br />
Abdominal Girth (cm):<br />
Height (cm):<br />
Chest Circumference (cm):<br />
Any SHOCK: Yes No Duration/Treatment:<br />
Cardiac Arrest: Yes No Intubation date/time:<br />
Urine output: /hour /24 hours<br />
26
Laboratory Data:<br />
Date:<br />
Time:<br />
FIO2 Rate:<br />
BE (-2,+2)<br />
PEEP<br />
P.P.<br />
PO2 (90-100)<br />
PCO2 (35-45)<br />
O2 Sat.<br />
H+ (35-45)<br />
pH (7.35-7.45)<br />
HCO3 (22-26)<br />
Hgb<br />
(M:13 - 17:F:11.5-16)<br />
Hct<br />
(M:0.38-0.50; F:0.34-0.46)<br />
WBC (4-9)<br />
Plts (140-340)<br />
Na (135-150)<br />
K+ (3.3-5.0)<br />
Cl (96-107)<br />
CO2 (23-31)<br />
Urea (2.5-8.0)<br />
Creatinine (50-115)<br />
Osmol (280-295)<br />
Glucose (3.5-9.0)<br />
Amylase (25-115)<br />
Ca++ (2,10-2.65)<br />
Uric Acid (150-475)<br />
T Bili (3-20)<br />
Alk Phos (100-275)<br />
AST (SGOT) (10-55)<br />
ALT (SGPT) (5-40)<br />
PT (10.3-12.7)<br />
PTT (26-37)<br />
LDH (90-210)<br />
CPK<br />
(M:10-130; F:10-120)<br />
MB (1 0-60)<br />
Other<br />
CXR<br />
Echo<br />
ECG<br />
Sputum Culture<br />
Urine Culture<br />
Blood Culture<br />
Urinalysis<br />
27
Parameters:<br />
VITAL SIGNS<br />
MEDICATIONS<br />
IV FLUIDS<br />
29
Organ/Tissue Retrieval Procedures:<br />
Date:_______________________________<br />
Insitu flush:_____ Yes ______ No Solution used: ________ Perfadex _______UW<br />
________RL<br />
Flush Start Time: Aortic _______________________<br />
Portal________________________________<br />
Stop Time: Aortic<br />
________________________Portal________________________________<br />
Amt Sol'n Infused: Aortic<br />
________________________Portal________________________________<br />
Amt & Sol'n Infused on Back Table:<br />
Liver________________Kidneys_________________________<br />
Kidneys: Removed en bloc: ___ Yes ____No<br />
R L R L<br />
# of arteries Clamp of renal artery<br />
cuff of aorta<br />
initial flush<br />
# of renal veins Warm Ischemic<br />
Cuff of Cava<br />
Liver: Hepatic artery: no: patch: long/short<br />
Portal vein:<br />
long/short<br />
Infrahepatic inf. vena cava:<br />
long/short<br />
Suprahepatic inf. vena cava:<br />
long/short<br />
Phrenic veins: no: tied off: yes/no<br />
Bile duct: long/short flushed: yes/no<br />
Cholecystectomy:<br />
yes/no<br />
Iliac arteries: enclosed: yes/no cms<br />
Iliac veins: enclosed yes/no cms<br />
Remarks Re: Liver<br />
30
Organ Clamp on Clamp Off Ischemic Time Procuring Surgeon<br />
Rt kidney<br />
Lt kidney<br />
Lungs<br />
Heart/Lung<br />
Liver<br />
Pancreas<br />
Cornea<br />
Skin<br />
Bone<br />
31
Communication Log:<br />
Organ<br />
Centre Coordinator<br />
1.<br />
Response<br />
2.<br />
Response<br />
3.<br />
Response<br />
4.<br />
Response<br />
5.<br />
Reponse<br />
6.<br />
Response<br />
Time<br />
Placed-Reached<br />
Organ<br />
Centre-Coordinator<br />
1.<br />
Response<br />
2.<br />
Response<br />
3.<br />
Response<br />
4.<br />
Response<br />
5.<br />
Response<br />
6.<br />
Response<br />
Time<br />
Placed-Reached<br />
Visiting Teams: Centre: Personnel.<br />
1.<br />
2.<br />
3.<br />
32
5.6 DONOR ORDERS FOR MULTI-ORGAN <strong>TRANSPLANTATION</strong><br />
PHYSICIAN: Please draw a line through any orders which do not pertain to<br />
your patient.<br />
I. NURSING CARE<br />
1. Admit to ICU. Semi-Fowlers position. ECG monitor.<br />
2. V/S including CVP and MAP q 20 minutes if unstable, otherwise<br />
q1h.<br />
3. Foley catheter to gravity drainage, hourly outputs.<br />
4. N.G. tube or O.G. tube to wall suction, 100 cm H2O. Irrigate<br />
with 30 mL N/S q3h and prn.<br />
5. I & O q1h.<br />
6. Warming blanket to maintain temperature of 35 to 37oC.<br />
7. Surgical prep neck to knees, bedline to bedline. Scrub entire<br />
body with Povidon-iodine (Betadine) for 10 min following prep.<br />
8. Weigh once in kg and measure height in cm.<br />
9. Chest physiotherapy with postural drainage q2h.<br />
10. Nasotracheal suctioning q2h, or q1h if secretions are thick or<br />
copious.<br />
II.<br />
VENTILATORY MANAGEMENT<br />
1. Respirator at setting of _____% F1O2, (
starting Metaraminol (Aramine) ________mg in 500 mL D5W<br />
via CVP line (Min - max rate 0-10 mcg/kg/min) or<br />
Norepinephrine 4 mg in 250 ml D5W (min-max rate 0-10<br />
mg/min) to keep MAP 70-80 mm Hg). For MAP < 70 mm Hg,<br />
CVP > 10 mm Hg and SVR < 900 dynes/sec cm -5, start<br />
metaraminol at _____mcg/kg/min or Norepinephrine and<br />
check CO, MAP and SVRI. Increase metaraminol or<br />
norepinephrine as required to raise MAP to > 70 mm Hg and<br />
ensure that SVRI does not exceed 2000 dynes sec cm-5.<br />
d) Peripheral IV keep open with Normal Saline at 30 ml/h when<br />
blood, blood products or antibiotics not running.<br />
2. KCl scale (use only if urine output > 60 mL/h). Give _____mmol<br />
(mEq) KCl per volutrol for each 0.1 mmol serum K+ < 5.0 to be<br />
given at a rate of ______mmol (mEq)/2 min. (To each 2 mL IV<br />
fluid in the volutrol, add _____mmol (mEq) KCl). (CENTRAL LINE<br />
ONLY).<br />
3. Antibiotics to be given after cultures and blood work obtained.<br />
a) Cefuroxine ______g IV q4h.<br />
b) Chloramphenicol ______g IV q6h.<br />
c) _______________________ ________g IV q ______h.<br />
IV.<br />
STUDIES<br />
1. STAT<br />
a) ECG<br />
b) CXR, repeat q6h for potential heart/lung or lung donor.<br />
c) ABG's, then q 2-4h, along with SVO2 if Swan Ganz Catheter<br />
present.<br />
d) CBC and diff, glucose, serum electrolytes, serum ionized<br />
calcium, magnesium, osmolality, BUN, creatinine then q4h.<br />
e) Chem panel, GGT.<br />
f) Bilirubin and SGOT, then q8h.<br />
g) CK and CKMB Q and LD isoenzymes (if ECG suggests injury).<br />
h) PT, PTT, platelets.<br />
i) HBsAg and HIV serum titres - 10 mL blood in one plain 10<br />
mL corvac red top tube.<br />
j) Blood barbiturate level and toxicology screen if patient has<br />
not been pronounced neurologically dead (potential donors<br />
only).<br />
k) Type and crossmatch for 4 units packed red blood cells.<br />
l) Tracheal aspirate and urine for routine culture, urinalysis.<br />
m) Two sets (aerobic and anaerobic) of blood cultures for C &<br />
S from 2 different sites.<br />
34
n) HLA typing and Lymphocytotoxic antibody screen against<br />
recipient's serum. Send fourteen heparinized 10 mL green<br />
top tubes and one 10 mL red top tube to Transplant<br />
Immunology Lab Transplant Coordinator. Label Lung<br />
Transplant Donor.<br />
2. Blood for the following tests must be drawn stat, but the<br />
analysis may be done during regular lab hours.<br />
a) Chemical panel.<br />
b) CMV and EBV serum titres - 10 mL blood in one plain 10 mL<br />
gelled red top tube. Notify Transplant Coordinator when<br />
done, and REFRIGERATE SPECIMEN WHEN OBTAINED.<br />
c) Toxoplasmosis serum titre - 10 mL blood in one 10 mL<br />
gelled red top tube. Forward to Microbiology lab.<br />
V. PARAMETERS<br />
- Notify Dr. _________ and Transplant Coordinator:<br />
1. MAP > 100 or < 70 mm Hg.<br />
2. CVP > 10 or < 6 mm Hg.<br />
3. PAD > 12 or < 8 mm Hg. (or mean PCWP > 14 or < 8).<br />
4. Temp < 34 or > 37oC.<br />
5. HR > 110 or < 60 beats/min.<br />
6. PO2 > 120 or < 70 torr, PCO2 > 42 or < 30 torr, pH > 7.50 or <<br />
7.35.<br />
7. SVO2 < 60% or PVO2 < 30 mm Hg.<br />
8. Serum K+ > 5.5 or < 3.0. Ionized Ca++ < 1.2 or > 1.34 mmol/L.<br />
9. HCT < 30.<br />
10. Urine output < 1.5 mL/kg/h for 1 hour.<br />
11. For MAP < 70 mm Hg, CVP > 10 mm Hg, normal serum Ca++,<br />
SVO2 < 60% PVO2 < 30 mm Hg, consider Swan Ganz catheter.<br />
12. SVR < 1200 dynes sec cm-5.<br />
35
6. COORDINATION OF THE <strong>TRANSPLANTATION</strong> PROCEDURE: A CHECKLIST<br />
To avoid sudden surprises, the transplant coordinator (in conjunction with the<br />
transplant surgeons and residents) must thoroughly check that all relevant<br />
personnel are notified, that all times are agreed upon, that the donor is optimally<br />
managed, that all relevant consents are obtained, that the recipient is admitted<br />
and free of disease processes which would interdict transplantation at that time<br />
and that the appropriate preoperative orders are carried out.<br />
Lung transplantation constitutes an emergency procedure due to the unstable<br />
nature of most donors and the short ischemic time that the heart or lung will<br />
tolerate.<br />
It is anticipated that most, if not all, donors would be harvested at the referring<br />
centre. For thoracic organ procurement:<br />
Obtain an Operating Room (O.R.) start time at the referring centre.<br />
Obtain an estimate of the transport time from the donor center to the recipient<br />
center. Calculate in the actual harvest time (from cross-clamping the donor<br />
aorta to leaving the donor O.R. - usually approximately 10-15 minutes),<br />
transport to the donor airport, actual flying time including approximately 5<br />
minutes each for take-off and landing, and the ground transport from the<br />
airport to the recipient center.<br />
Inform the recipient anesthetist as to the time you wish to make the thoracic<br />
(lung) incision and the expected time of arrival of the donor lungs.<br />
For lung recipients not previously operated on, plan to make the incision 90<br />
minutes prior to donor organ arrival.<br />
For recipients previously operated on, plan to start operating on the recipient<br />
after the donor heart has been visualized. Allow at least 1-1/2 to 2 hours to<br />
obtain adequate exposure. Depending on the donor location it may be<br />
necessary to delay the donor harvest until the recipient dissection is far enough<br />
along, so that when the donor organ(s) arrives at the recipient Operating Room<br />
it is not sitting in storage for an unduly long period. Keep the donor ischemic<br />
time to a minimum and definitely less than 4 - 5 hours.<br />
Inform the O.R. at the recipient center that a transplant will be performed, the<br />
approximate time, and whether a nurse will or will not be required to go on the<br />
donor run. The O.R. should also inform the perfusionist.<br />
36
Inform the recipient candidate or candidates by phone, if the patient(s) is/are<br />
not already in the hospital. It may be necessary to locate the potential<br />
recipient(s) by cell phone.<br />
Inform Admitting: that the patient to be admitted is being admitted for<br />
`transplantation', otherwise errors in billing or nursing protocols may ensue.<br />
Admit the patient to a ward prepared for the preparation of such patients for<br />
transplantation, where preoperative order forms and consents are immediately<br />
available. (The recipient candidate may already be in hospital in a pulmonary<br />
bed. Fill out the preoperative orders before the patient arrives so that the old<br />
chart will be on the ward and the chest roentgenogram and laboratory data<br />
obtained when you arrive to admit the patient.<br />
Inform the ICU at least 6 hours in advance so that staffing can be arranged.<br />
Inform the transfusion service that they may need to perform a preop cytotoxic<br />
lymphocyte x-match (if potential recipient highly sensitized), and that 6 units<br />
blood, 8 units platelets, 8 units of cryoprecipitate and 4 units of fresh frozen<br />
plasma will be needed for the recipient.<br />
Inform the personnel to be involved with the donor harvest: surgeon, assistant,<br />
scrub nurse, anesthetist and any interested visiting physicians or other<br />
personnel. Review the donor status with the individual harvesting the donor to<br />
avoid surprises.It is the responsibility of the surgeon harvesting the lung to<br />
check that the name on the donor's wrist band is the same as the one in the<br />
donor chart, that the blood type is confirmed, that the brain death notes are<br />
written, that the consents for lung donation are written, and that the donor is<br />
hemodynamically stable,chest roentgenogram or electrocardiogram. A copy of<br />
the face sheet, blood type, admission history and physical examination, brain<br />
death notes and consent forms must be returned to the recipient center. It is<br />
helpful to have the data copied and assembled for the donor team prior to<br />
arrival at the referring center.<br />
Inform other researchers interested in blood or various tissues for experimental<br />
purposes.<br />
37
7. COORDINATION OF A <strong>LUNG</strong> TRANSPLANT<br />
DONOR CALL PWH <br />
TRANSPLANT SURGEON RECIPIENT SELECTION<br />
(Preliminary Call or (Discussion with Pulmonary physician)<br />
All Relevant Donor<br />
Info Available)<br />
<br />
DONOR COORDINATOR RECIPIENT COORDINATOR<br />
Confirms Acceptable Donor Status 1. Informs ICU.<br />
(May require further discussions with transplant Surgeon/Resident<br />
and donor management physician) 2. Calls in Recipient<br />
<br />
Confers With transplant Surgeon/Senior Resident/OR 1. Prepares Recipient Resident<br />
Assessment,<br />
and Recipient Coordinator . . . for OR Hx,<br />
P/E<br />
1. that transplant will proceed 2. Confirms OR Time with donor coordinator<br />
2. the time of departure to retrieve organ(s) (ensures sufficient lead time for<br />
anesthetist<br />
3. who will go & surgeon)<br />
4. likely timing of retrieval & arrival of donor<br />
organ(s) at recipient center (NB: Need 90 min from<br />
skin incision to organ arrival for first time thoracotomy<br />
patients and 180 min for reops lung recipients).<br />
Transplant coordinator (Donor end)<br />
• Arranges ground and air transportation to Donor Centre.<br />
• Organizes Donor Equipment & Preservation Solutions to Donor Centre.<br />
• Informs Donor OR & Cold Saline/Slush Managements.<br />
38
• On arrival at donor centre, informs transplant Surgeon/Senior Resident of donor status &<br />
likely time of retrieval to signal when recipient should go to the O.R.<br />
• Following donor sternotomy, inform transplant Surgeon lung is O.K<br />
• Inform transplant Surgeon/Senior Resident that organ has (has) been retrieved, and that all<br />
has gone well and when it is likely to arrive.<br />
• Inform transplant Surgeon/Senior Resident that organ will arrive in approximately 30 - 45<br />
minutes.<br />
• Delivers organ(s) to recipient O.R.<br />
• Confirms donor-recipient blood type.<br />
7.1 Preparation of Perfadex Solution<br />
Perfusion<br />
• 4x1 L bags of Perfadex each loaded with the following:<br />
‣ 4 cc THAM, 0.6 cc CaCl<br />
‣ 2.5 cc PEGI –Water mixture (1 ml PGEI with 9 ml NS)<br />
• THAM and CaCl can be added before leaving for retrieval<br />
• PEGI should be added in the OR after lungs have been accepted<br />
Storage<br />
• 2x1 L bags of Perfadex each loaded with the following<br />
‣ 4cc THAM, 0.6 cc CaCl<br />
Back Flush<br />
• 1x1 L bag of Perfadex loaded with the following<br />
‣ 4 cc THAM, 0.6 cc CaCl<br />
Points to Remember<br />
• Perfusion bags should be hung only 1 foot above the height of the donor<br />
chest<br />
• A foley catheter (12 Fr) should be on the back table for the back flush<br />
• Perfusion solutions should be hung as late as possible to ensure that they<br />
are cold<br />
• The perfusion volume is 50 cc per kg body weight<br />
39
7.2 Procedure for donor lung resection<br />
As per routine, the organ donor’s chest and abdomen had been previously<br />
entered through a midline incision to expose the intra-abdomenal and intrathoracic<br />
organs. A sternal retractor was inserted and opened to expose the<br />
anterior pericardium and medial surface of the pleural spaces bilaterally. A<br />
vertical pericardiotomy incision was made to expose the underlying heart. The<br />
heart was assessed by the cardiac transplant surgeon for suitability for<br />
transplantation.<br />
Dissection of the inferior vena cava at the level of the diaphragmatic surface<br />
of the pericardium was undertaken to free up an adequate length for<br />
transaction and venting for the liver during perfusion.<br />
The superior vena cava was mobilized in the pericardial space to superior<br />
pericardial reflection and encircled with a heavy silk ligature. Extrapericardial<br />
dissection to the level of the azygos vein was performed and a separate silk<br />
ligature was placed around the IVC.<br />
The pleural spaces were entered bilaterally to facilitate gross inspection and<br />
palpation of the lungs.<br />
The ascending aorta was reflected laterally and the posterior surface of the<br />
pericardium was incised between the superior vena cava and aorta to expose<br />
the trachea. Sharp and blunt dissection was utilized to encircle the trachea 3<br />
cm proximal to the level of the main carina.<br />
Attachment between the main pulmonary and ascending aorta were divided to<br />
expose and properly separate these great vessels.<br />
In simultaneous heat and lung extractions a cardioplegic catheter is inserted in<br />
the ascending aorta. A 5-0 purse string suture is placed in the main pulmonary<br />
artery just proximal to the bifurcation to the left and right main pulmonary<br />
vessels. Systemic heparinization is provided by IV injection of a suitable dose<br />
of heparin. The hepatic transplant surgeons then insert the hepatic and renal<br />
perfusion catheters through the abdominal aorta after transaction the aorta<br />
distal to the superior mesenteric artery.<br />
The pulmonary arterial catheter is then inserted in the main pulmonary artery<br />
and secured with the purse string.<br />
With all transplant surgeons appropriately ready to perfuse their respective<br />
organs, a direct injection of 500 micrograms of prostaglandin PEG1 into the<br />
main pulmonary artery was made.<br />
When systemic pressure reaches 80 mmHg, the SVC ligated. The left atrial<br />
appendage was transacted in order to vent the lungs.<br />
40
Cardioplegia and pulmonary flush was then instituted. Through the entire<br />
pulmonary flush process, mechanical ventilation was maintained by the<br />
anesthetist. Cold solution and crushed ice were placed in the pericardial and<br />
pleural spaces bilaterally to facilitate hypothermia of the heart and lung bloc.<br />
Once the flush solutions had passed through the heart and lung completely, we<br />
proceeded to remove the heart-lung bloc.<br />
This was done by elevating the heart out of the pericardial sac and transecting<br />
the left atrium just proximal to the confluence with the right and left<br />
pulmonary veins. Once the left atrium was completely detached posteriorly,<br />
the heart was dropped back into the pericardial sac and the main pulmonary<br />
artery was transacted just proximal to the bifurcation. The aortic route and<br />
posterior pericardium transacted working backwards into the pericardial sac.<br />
The superior vena cava was then transected within the pericardium and the<br />
heart removed from the donor pericardial sac.<br />
The pericardium was transacted at the diaphragm; to enter retropericardial<br />
space. Blunt dissection was carried forward along the line of the esophagus<br />
and aorta posteriorly up to the level of the trachea just above the carina. The<br />
inferior pulmonary ligaments were then transected bilaterally to free up the<br />
entire lung bloc inferiorly.<br />
The trachea was then transected with a bronchial stapler proximal to the main<br />
carina with the lungs having been previously manually inflated to an inflation<br />
pressure of 30 mm Hg. Tissue in the right and left paratracheal spaces superior<br />
were transacted in order to free up the lung bloc completely and it was<br />
removed from the donor chest cavity.<br />
The donor lung bloc was then placed in cold perfadex solution within sterile<br />
containers for transport.<br />
7.3 Procedure for bilateral lung transplantation<br />
A. Anesthesia: General, Thoracic epidural, Double lumen ETT<br />
B. Cardiopulmonary bypass machine on standby<br />
C. Position: The patient is placed supine on the operating table with the<br />
arm abducted, shoulder roll to be placed under the shoulder blades.<br />
D. Incision: (Clampshell ) bilateral inframammary thoracotomy incision and<br />
transverse sternotomy.<br />
Description of the procedure<br />
1) Hilar pleura is incised anteriorly and the dissection carried superiorly.<br />
2) The pulmonary artery is encircled as far proximally as possible.<br />
3) The pericardium is opened just anterior to the pulmonary vein posteriorly.<br />
41
4) The pulmonary artery is divided with vascular stapler usually just distal to<br />
the first upper lobar branch.<br />
5) The veins are divided by ligating individual branches as they enter the<br />
pulmonary parenchyma.<br />
6) The bronchus is divided as far distally as possible after application of a TA-<br />
55 stapler and the lung is removed.<br />
7) The pericardium should be opened widely around the entire hilum.<br />
8) The donor lung which had already been prepared on the back table brought<br />
into the field and properly oriented.<br />
9) The bronchial anastomosis is constructed first. It is extremely important to<br />
trim the donor bronchus as short as possible usually one or two rings above<br />
the origin of the upper lobe bronchus.<br />
10) Monofilament suture (PDS-4-0) is used to approximate the membranous<br />
bronchus, and a monofilament non-absorbable suture(Prolene 4-0) is used<br />
for the cartilaginous portion. The anastomosis is constructed so as to<br />
telescope one bronchus into the other.<br />
11) The arterial anastomossis usually is completed next. It is constructed using<br />
continuous suture 5-0 Prolene.<br />
12) The left atrial cuff anastomosis is usually completed last.<br />
13) The allograft de-airing is usually carried out through the atrial anastomosis<br />
after de-clamping the pulmonary artery.<br />
14) The lung fully inflated.The ischemic time end at this point.<br />
15) The vascular suture lines are checked to assure that there are no significant<br />
defects.<br />
16) The second lung is implanted In the same way as the first lung.<br />
17) Chest tubes are placed and the incision is closed.<br />
42
8. POST-<strong>LUNG</strong> TRANSPLANT ORDERS AND MANAGEMENT<br />
In order to avoid errors of omission and commission in post operative care,<br />
standardized orders have been developed. This format originated at Stanford<br />
University Medical Center and has been modified on several occasions as a<br />
consequence of new knowledge.<br />
8.1 Lung Transplantation Immediate Post-Operative Orders<br />
Date/Time Weight kg; Height cm.<br />
1. Nursing Care:<br />
a. Admit to ICU.<br />
b. ECG monitor, pulse oximetry.<br />
c. Neurovital signs q1h until awake, then q4h.<br />
d. Vital Signs including HR, CVP, PAP, LAP and MAP prn q 20 minutes x 2 - 4h, then q1h if stable.<br />
e. Temp q1h until 36.5°C, then q4h.<br />
f. Cardiac index and PCWP q4h x 24 hours, then q8h x 24 hours and prn.<br />
g. NPO except ice chips. NG tube to intermittent wall suction. Irrigate with 30 mL Normal Saline q4h prn.<br />
h. Chest tubes to collection chamber, -20 cm H 2 O suction pressure.<br />
i. Strip chest tubes q 20 minutes x 2 - 4 hours, then q1h if stable.<br />
j. Aim for following parameters (range should not exceed 5 mmHg):<br />
i. Keep CVP ___________________ to ___________________________ mmHg.<br />
ii. PAD ________________________ to ___________________________ mmHg.<br />
iii. PCWP ______________________ to ___________________________ mmHg.<br />
iv. LAP ________________________ to ___________________________ mmHg.<br />
Contact physician about amount and type of volume replacement.<br />
If HCT > ____________________ , replace with ___________________________________ .<br />
Transfuse ___________________ unit of packed cells for HCT < ______________________ .<br />
k. In and Out q1h.<br />
l. Weigh daily.<br />
m. Implement physio protocol.<br />
n. Implement incision care protocol.<br />
o. Inform MD of incisional drainage.<br />
2. Ventilatory Management:<br />
a. Ventilator settings as per respiratory therapy protocol.<br />
Physician’s Signature ____________________________________________________________________ ,<br />
43
Date/Time<br />
Ventilatory Management continued:<br />
b. Endotracheal suctioning prn and instillation 3 - 5 mL Normal Saline prn.<br />
c. For hemodynamically stable, ventilated patients, ABG 20 minutes after arrival, then as per early<br />
extubation / weaning protocol. If patient unstable, ABG q1 - 2h.<br />
d. Weaning and extubation per protocol. Notify MD prior to extubation.<br />
e. Remove NG tube at time of extubation if bowel sounds present and abdomen not distended.<br />
3. IV and Drug Therapy:<br />
a. IV’s:<br />
i. Pulmonary artery catheter for central monitoring. Keep CVP and PA ports patent with Normal Saline.<br />
ii. Keep arterial line patent with Normal Saline 500 mL.<br />
iii. Drive solution for drips through introducer sheath: 2/3 - 1/3 with _______ mmol / L KCL at _______<br />
iv. Peripheral IV: 2/3 - 1/3 at _______ mL / h or saline lock prn when blood not running.<br />
b. Cardiac Drugs: Maintain MAP _______ mmHg to _______ mmHg (range should not exceed 12 mmHg).<br />
i. Dopamine 400 mg in 250 mL D 5 W to keep MAP > _______ mmHg. Start at ______ mcg / kg / min.<br />
Min - max rate _______ mcg / kg / min. DO NOT INCREASE DOSE IF HR EXCEEDS 120 / MINUTE.<br />
ii. Dobutamine 500 mg in 250 mL D 5 W to keep MAP > _______ mmHg. Start at ______ mcg / kg / min.<br />
Min - max rate _______ mcg / kg / min.<br />
iii. Epinephrine _______ mg in 250 mL D 5 W to keep MAP > _______ mmHg. Start at ______ mcg / kg /<br />
Min - max rate _______ mcg / kg / min. DO NOT INCREASE DOSE IF HR EXCEEDS 120 / MINUTE.<br />
iv. Milrinone 20 mg in 100 mL Normal Saline or D 5 W to keep MAP > _______ mmHg.<br />
Start at ______ mcg / kg / min. Min - max rate _______ mcg / kg / min.<br />
v. Norepinephrine 4 mg in 250 mL D 5 W via central venous / LAP line to keep MAP > _______ mmHg.<br />
Start at ______ mcg / kg / min. Min - max rate _______ mcg / kg / min.<br />
DO NOT INCREASE DOSE IF HR EXCEEDS 120 / MINUTE.<br />
vi. Sodium Nitroprusside 50 mg in 250 mL D 5 W to keep MAP < _______ mmHg.<br />
Start at ______ mcg / kg / min. Min - max rate _______ mcg / kg / min.<br />
vii. Nitroglycerine 100 mg in 250 mL D 5 W to keep MAP < _______ mmHg and PADP < _______ mmHg.<br />
Start at ______ mcg / kg / min. Min - max rate _______ mcg / kg / min.<br />
viii. Lidocaine 2 g in 250 mL D 5 W at _______ mg / min.<br />
ix. Isoproterenol _______ mg in _______ mL D 5 W at _______ mcg / kg / min.<br />
Start at ______ mcg / kg / min. Min - max rate _______ mcg / kg / min.<br />
Physician’s Signature ____________________________________________________________________ ,<br />
44
Date/Time<br />
c. Routine Medication:<br />
i. For serum ionized Ca ++ 38.0°C.<br />
d. Antibiotics, Anti-fungals and Anti-virals:<br />
i. Cefazolin 1 g IV per buretrol q8h x 3 doses. D / C on ______________________________________ .<br />
ORii. ___________________________ Vancomycin _______ mg IV q _______ h per buretrol. D / C on .<br />
iii. _______________________ _____________ mg IV per buretrol q _______ h.<br />
iv. Cotrimoxazole 1 single strength tab po / NG daily when bowel sounds present. (PCP prophylaxis).<br />
v. Chlorhexidine 0.12% 10 mL to gargle and rinse mouth qid prior to Nystatin.<br />
vi. Nystatin 100,000 units (1 mL) to swish and swallow qid.<br />
vii. Fluconazole 100 mg po / IV daily. (Lung transplant patients only for Fungal prophylaxis)<br />
viii. Acyclovir 400 mg bid po / NG when bowel sounds present. (HSV prophylaxis).<br />
Physician’s Signature ____________________________________________________________________ ,<br />
45
D O N O T W R I T E I N T H I S S P A C E<br />
Date/Time<br />
Antibiotics, Anti-fungals and Anti-virals continued:<br />
ix. FOR HEART TRANSPLANT PATIENTS who are CMV negative and receive a CMV positive organ start on:<br />
Ganciclovir _______ mg (2.5 mg / kg) IV q24h immediately post op. Adjust for renal function.<br />
Ganciclovir _______ mg _______ times per day po for 14 weeks when bowel sounds present.<br />
Adjust for renal function.<br />
x. FOR TRANSPLANT PATIENTS who are CMV positive or negative and<br />
receive a CMV positive organ start on:<br />
Ganciclovir _______ mg (5 mg / kg) IV q12h for 2 weeks. Adjust for renal function.<br />
Ganciclovir _______ mg (5 mg / kg) IV q24h for: 8 weeks / 12 weeks. Adjust for renal<br />
e. Immunosuppressive therapy:<br />
i. Methylprednisolone _______ mg (2 mg / kg) IV q12h x 3 doses.<br />
ii. ATGAM _______ mg (10 mg / kg) IV daily by continuous infusion over 24 hours. ( _______ mg / h).<br />
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.<br />
d. CVP > _______ or < _______ mmHg.<br />
e. ABG results per early extubation / weaning protocol.<br />
f. Resident to assess 12 lead ECG and chest x-ray.<br />
g. Chest drainage >2 mL / kg / h.<br />
h. Serum K + >5.5 or _______ mmol / L.<br />
k. Blood glucose >14 mmol / L.<br />
Physician’s Signature ____________________________________________________________________ ,<br />
46
Date/Time<br />
Parameters continued - Notify MD for:<br />
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<br />
Date/Time<br />
6. Virology testing:<br />
a. For CMV IgG positive patients or donor positive patients, serum buffy coat every Sunday<br />
(2 mauve top tubes) to be performed 2 weeks post-transplant and repeated every _______ weeks.<br />
Start date __________________ .<br />
b. For EBV seronegative patients: EBVCA IgG and IgM and Monospot q2weeks.<br />
- Tests to be done on Tuesday and must be delivered to Virology lab before 1130.<br />
- Label requisition: “Attention Post Heart and / or Lung Transplant Recipient.”<br />
7. Additional Orders:<br />
Physician’s Signature ____________________________________________________________________ ,<br />
48
8.2 Lung Transplantation Transfer Orders<br />
Date/Tim Weight kg; Height cm.<br />
8. Nursing Care:<br />
a. Transfer to 2 North.<br />
b. Vital Signs q4h x 48 hours, then q8h.<br />
c. Weigh daily.<br />
d. Chest tubes to collection chamber, -20 cm H 2 O suction pressure.<br />
e. Diet:<br />
i. 2 gm Sodium cardiac diet or _____________________ kcal CDA; or ___________________________ .<br />
ii. Tube feed _________________ at _______________ mL / h per NG / PEG. Dietitian to assess goal<br />
iii. Total IV and po intake not to exceed _____________________________ mL per 24 hours.<br />
f. Consultation with dietitian for home diet instruction.<br />
g. I & O q12h. Reassess in 48 hours.<br />
h. Walk in hall qid as tolerated. Increase as tolerated. Implement physio protocol.<br />
i. Remove chest tube sutures 21 days after chest tubes are removed.<br />
j. Remind patient to flex and extend feet 100 times every hour while awake.<br />
k. Contact Transplant Coordinator to begin discharge teaching.<br />
9. Pulmonary Care:<br />
a. Nasal cannula O 2 at 1 - 6 L / min.<br />
b. Monitor SaO 2 q8h, and 20 minutes after FiO 2 change.<br />
c. Titrate FiO 2 to maintain SaO 2 ≥ 92% or ______________________________________________________ .<br />
d. Discontinue O 2 therapy if SaO 2 > 92% on room air or ___________________________________________ .<br />
e. Incentive spirometer q1h while awake.<br />
f. Chest physiotherapy q4h x 24 hours then qid.<br />
Physician’s Signature ____________________________________________________________________ ,<br />
49
Date/Tim<br />
Pulmonary Care continued:<br />
g. Aerosol therapy nebulization mask. Treat q _______ h with:<br />
Ventolin 2.5 mg in 2.5 mL Normal Saline prn.<br />
10. IV and Drug therapy:<br />
a. IV’s:<br />
i. Central line: Heparin lock (100 units / mL) with 3 mL q12h and prn.<br />
ii. Peripheral line: Saline lock for medications q8h and prn.<br />
iii . Notify physician if HR > ____________ or SBP < ____________ .<br />
b. Antibiotics, Anti-fungals and Anti-virals:<br />
i. Cefazolin 1000 mg per IV q8h. D / C on __________________________________________________ .<br />
ORii. ___________________________ Vancomycin _______ mg IV q12h. D / C on __________________ .<br />
iii. _______________________ _____________ mg IV q _______ h. D / C on .<br />
iv. Cotrimoxazole 1 single strength tab po / NG daily when bowel sounds present. (PCP prophylaxis).<br />
v. Chlorhexidine 0.12% mouthwash 10 mL po qid to gargle and rinse mouth prior to Nystatin.<br />
vi. Nystatin 100,000 units (1 mL) qid to swish and swallow.<br />
vii. Fluconazole 100 mg po / IV daily. (Lung transplant patients only for Fungal prophylaxis)<br />
viii. Acyclovir 400 mg bid po / NG when bowel sounds present. (HSV prophylaxis).<br />
ix. FOR HEART TRANSPLANT PATIENTS who are CMV negative and receive a CMV positive organ start on:<br />
Ganciclovir _______ mg (2.5 mg / kg) IV q24h immediately post op. Adjust for renal function.<br />
Ganciclovir _______ mg _______ times per day po for 14 weeks, when bowel sounds present.<br />
Adjust for renal function.<br />
x. FOR <strong>LUNG</strong> TRANSPLANT PATIENTS who are CMV positive or negative and<br />
receive a CMV positive organ start on:<br />
Ganciclovir _______ mg (5 mg / kg) IV q12h for 2 weeks. Adjust for renal function.<br />
Ganciclovir _______ mg (5 mg / kg) IV q24h for: 8 weeks / 12 weeks.. Adjust for renal<br />
Physician’s Signature ____________________________________________________________________ ,<br />
50
D O N O T W R I T E I N T H I S S P A C E<br />
Date/Tim<br />
c. Immunosuppressive therapy:<br />
i. Neoral Cyclosporine / Tacrolimus q12h. Give _______ mg po / NG (clamp x q2h) tonight and tomorrow<br />
Dose to be adjusted on daily levels. (Give at 0800 and 2000 daily).<br />
ii. Mycophenolate Mofetil 1000 mg po q12h. Hold for WBC 4.5 mmol / L.<br />
iii. Colace 100 mg po bid.<br />
iv. Senokot 2 tablets po hs.<br />
v. ECASA 81 mg po daily.<br />
vi. Analgesia:<br />
Morphine _______ mg IM / SC q _______ h prn while CT in situ.<br />
Meperidine _______ mg IM / SC q _______ h prn while CT in situ.<br />
Percocet 1 - 2 tab po q4 - 6 h prn for pain<br />
Acetaminophen with codeine 30 mg (Tylenol #3 ® ) 1 - 2 tabs po q3 - 4h prn for pain.<br />
vii. Acetaminophen 325 - 650 mg po q4h prn for Temperature >38.0°C.<br />
viii. Ranitidine _______ mg po q _______ h. Adjust for renal function.<br />
ix. _________________ _________________ mg po qhs prn for sleep.<br />
x. IV fluid ___________ with __________ mmol (mEq) KCL / L at __________ mL / h.<br />
xi. Insulin:<br />
______________________________________________________Add __________ units<br />
and run per perioperative insulin protocol.<br />
______________________________________________________Chemstrips q2h while on insulin<br />
______________________________________________________Consult Endocrinology /<br />
Physician’s Signature ____________________________________________________________________ ,<br />
51
D O N O T W R I T E I N T H I S S P A C E<br />
Date/Tim<br />
Routine Medications continued:<br />
xii. Diltiazem / Diltiazem CD / Tiazac __________ mg po / NG q _______ h.<br />
Reassess for HR < _______ beats / min or cuff SBP < _______ mmHg.<br />
xiii. Ferrous Gluconate 300 mg po tid.<br />
xiv. Dimenhydrinate 25 -50 mg po / IM / IV q4h prn for nausea.<br />
xv. Metoclopramide 10 mg po / IM / IV __________ ac meals and HS.<br />
xvi. Heparin 5,000 IU SC q12h until mobile.<br />
11. Parameters - Notify MD for:<br />
a. Temperature >38.0°C.<br />
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.<br />
k. Serum creatinine > _______ mmol / L.<br />
l. Blood glucose >14 or
Date/Tim<br />
Studies continued (review afer 48 hours):<br />
e. Whole blood Cyclosporine / Tacrolimus levels every a.m. just before morning dose. (3 mL mauve top<br />
f. PA and lateral chest film daily x 5 days then reassess.<br />
g. 12h Creatinine clearance every Tuesday and Friday.<br />
h. Urine and sputum for routine bacterial and fungal cultures every Tuesday and Friday.<br />
i. C & S of any incisional drainage. Inform Physician.<br />
13. Virology testing:<br />
a. For CMV IgG positive patients or donor positive patients, serum buffy coat every Tuesday<br />
(2 mauve top tubes) to be performed 2 weeks post-transplant and repeated every _______ weeks.<br />
Start date __________________ .<br />
b. For EBV seronegative patients: EBVCA IgG and IgM and Monospot q2weeks.<br />
- Tests to be done on Tuesday and must be delivered to Virology lab before 1130.<br />
- Label requisition: “Attention: Lung Transplant Recipient.”<br />
14. Additional Orders:<br />
MD.<br />
Physician’s Signature ____________________________________________________________________ ,<br />
53
9. IMMUNOSUPPRESSION<br />
9.1 Introduction<br />
The illusive immunosuppressive goal following organ transplantation is to<br />
achieve tolerance for the organ without a need for ongoing immunosuppression<br />
and without creating any adverse side effects. Unfortunately,no perfect<br />
immunosuppressive strategy exists to induce immunological tolerance. At best,<br />
for lung transplantation, immunosuppressive protocols must be used which<br />
prevent rejection and, by virtue of minimal toxicity, do not predispose to<br />
infection, malignancy or other potentially life or quality of life threatening<br />
problems. Excellent short and long term survival may be achieved with<br />
cyclosporine in combination with azathioprine or mycophenolate mofetil<br />
immunosuppression with or without monoclonal or polyclonal antilymphocyte<br />
antibodies or prednisone.<br />
9.2 Immunosuppressive Protocol<br />
a) Pre-Operative<br />
1. Azathioprine<br />
3 mg/kg IV or, if PO, 4 to 6 hours pre-transplant.<br />
b) Intra-Operative<br />
1. Methylprednisolone sodium succinate (Solumedrol)<br />
10 mg/kg just prior to release of arterial cross-clamp.<br />
c) Post-Transplant Immunosuppression<br />
1. First Three Months Post-Transplant:<br />
1.1. Azathioprine 1 to 2 mg per kg PO or per NG tube daily to adjust<br />
white blood count to 4,000 - 6000 per mm 3 .<br />
1.2. Methylprednisolone sodium succinate 2 mg per kg IV q12h X 3<br />
doses, then 1 mg/kg/day tapering by 1 mg/day, until prednisone<br />
can be substituted.<br />
1.3. ATGAM (or equivalent RATG) 10-20 mg/kg/d over 24 hours by<br />
continuous infusion until Cyclosporine levels are in the target<br />
range (usually 5-10 days). Following the discontinuation of<br />
ATGAM, Solumedrol 2 mg/kg/d IV for 3 doses, in addition to the<br />
prednisone dosing (see #4) may be especially useful under<br />
certain circumstances (see Table 2 on P. 82 - Monitoring), but<br />
should be routinely administered.<br />
1.4. Prednisone 1 mg/kg/d starting 1st day postop and tapered by 2<br />
mg/d (if under 20 kg, taper by 1 mg/d) until at 0.25 mg/kg/d.<br />
54
1.5. Cyclosporine 4 to 5 mg per kg PO or per NG tube in 2 divided<br />
doses at 12 hour intervals daily beginning on the second to fourth<br />
post-transplant day depending on renal function (at or near<br />
baseline) and fluid status. The cyclosporine is adjusted to<br />
maintain whole blood trough levels ideally at 350 - 500 ng/ml in<br />
the first 3 months and then 200 - 500 ng/ml subsequently<br />
depending on renal function. Dose may have to be adjusted<br />
downward for renal dysfunction or upward for acute<br />
rejection.<br />
2. After Three Months Post-Transplant<br />
The azathioprine, prednisone and cyclosporine are continued as above,<br />
with the following exception:<br />
2.1 In the event of no rejection episodes, the cyclosporine dose may<br />
be reduced to achieve a trough level of 200-500 ng/ml. Monthly<br />
biopsies for 6 months will be required to ensure that rejection is<br />
not triggered by the lower cyclosporine or prednisone doses (see<br />
prednisone below).<br />
2.2 Consideration should be given to weaning the prednisone,<br />
particularly if cyclosporine levels can be easily maintained in the<br />
target range, which also assumes excellent renal function. On<br />
the other hand, if renal function is poor, it is unlikely that<br />
satisfactory cyclosporine levels can be maintained in which case<br />
it is unlikely that prednisone can be weaned off. Should<br />
prednisone weaning be attempted, rigorous monitoring for<br />
rejection should be initiated. Monthly clinical assessment,<br />
including, CXR and lung biopsies (where possible) should be<br />
carried out during the weaning.<br />
55
d) Summary of Immunosuppression<br />
1. Dosing<br />
PREOP INTRAOP 0-3 MONTHS > 3 MONTHS<br />
POSTOP<br />
Azathioprine 3 mg/kg IV PO 0 1-2 mg/kg/d 1-2 mg/kg/d<br />
SOLUMEDROL<br />
0 10 mg/kg prior<br />
to release of<br />
clamps<br />
Prednisone 0 0<br />
1 mg/kg q12h X 3<br />
doses, then 1<br />
mg/kg/d of<br />
equivalent<br />
prednisone dose<br />
until patient can<br />
tolerate oral<br />
prednisone.<br />
Consider and give<br />
an additional 2<br />
mg/kg/d IV X 3<br />
when ATGAM<br />
D/C'd.<br />
1 mg/kg/d taper<br />
by 1 mg/d.<br />
0.25 mg/kg/d<br />
ATGAM (or<br />
equivalent RATG<br />
or OKT 3<br />
0 0 10-20 mg/kg/d<br />
over 24 hours X 5 d<br />
until Cyclo levels<br />
in target range.<br />
Start 4-6 hours<br />
postop when<br />
patient stable.<br />
Cyclosporine 0 0<br />
Start 1-4 days<br />
postop when<br />
satisfactory renal<br />
function evident at<br />
4-5 mg/kg/d PO in<br />
div doses or at 3<br />
mg/kg/d IV by<br />
contin. infusion.<br />
May have to accept<br />
lower cyclo levels<br />
with renal<br />
dysfunction.<br />
(350-500 ng/ml) 200-500 ng/ml<br />
56
2. Monitoring<br />
MONITOR<br />
COMMENTS<br />
AZA WBC maintain at 4-6K<br />
Solumedrol<br />
Consider 2 mg/kg/d IV<br />
bolus daily X 3 when ATGAM<br />
is discontinued, especially<br />
if cyclo levels are low or<br />
rejection is likely.( diffuse<br />
interstitial pulmonary<br />
infiltrate in the absence of<br />
pulmonary secretions; poor<br />
lymphocyte suppression<br />
while on ATG).<br />
*PRED.<br />
ATGAM Abs. lymph ct < 200<br />
CD3 < 100 (if abs lymph<br />
ct > 200)<br />
9.3 Administration Procedure for Anti-Thymocyte Globulin<br />
1. General<br />
Antithymocyte globulin of equine origin (HATG-Horse Antithymocyte<br />
Globulin - ATGAM) or of rabbit (RATG) origin is given IV in the prophylaxis<br />
and treatment of rejection in lung transplantation. Presently, we are<br />
starting with ATGAM. Circulating rosette (T-cell) levels, serum 1/2 life of<br />
ATG as well as lung biopsy may be used to monitor the dose, duration and<br />
effectiveness of therapy. Currently, however, we are simply following the<br />
absolute lymphocyte count, aiming for
Antithymocyte globulin is highly effective in eliminating T-cells, of which<br />
certain subsets mediate graft rejection. Generally, for patients with life<br />
threatening acute rejection or, in patients who have failed to resolve a<br />
rejection episode with 2 courses of methyl prednisolone sodium succinate<br />
therapy (10 mg/kg/d X 3 days), RATG (more potent than ATGAM) or ATGAM<br />
is administered once daily for 3 days by continuous IV infusion.<br />
2. Preferred Administration Procedure for RATG or HATG (By IV infusion)<br />
(i) Pre-medication as ordered by M.D. one hour before first dose of<br />
administration; i.e. Acetaminophen 300 mg po/pr, Diphenhydramine 25<br />
mg IV/po.<br />
(ii) IV HATG<br />
Equine ATG is stored at 2-8 degrees C. It is a transparent to slightly<br />
opalescent aqueous solution, colorless to light brown, and may develop<br />
a slightly granular or flaky deposit during storage.<br />
The total daily dose should be added to N.S. or 0.45 N.S. as a maximum<br />
of 1 mg/mL.The ATG should be added to an inverted solution to avoid<br />
contact with air inside the container. The solution is stable for 12<br />
hours. The total dose should be infused over a maximum of 12 hours<br />
using a 20 micron filter. The usual initial dose is 10-20 mg/kg/d for 5-7<br />
days for immune induction, or for 3 days in combination with<br />
solumedrol 10 mg/kg/d for the treatment of refractory rejection.<br />
(iii) IV RATG<br />
RATG is stored at 4 degrees C. Reconstitute with the diluted provided<br />
(5mL water for injection per 25 mg vial). Each 25 mg/5 ml vial should<br />
be further diluted for subsequent IV infusion in 0.45 or 0.9 N/S (25<br />
mg/50 mL diluent) over 24 hours by continuous infusion for immune<br />
induction, and 6-12 hours for the treatment of rejection. Administer<br />
only freshly prepared solutions. Arthralgia and nausea may occur and<br />
may be reduced or eliminated by a slower infusion rate. The usual<br />
initial dose is 2.5 mg/kg/d for 5-7 days for immune induction, or for 3<br />
days in combination with 10 mg/kg/d of solumedrol for the treatment<br />
of refractory rejection.<br />
59
(iv) Watch for anaphylactic reactions:<br />
1. Flushing, increased temperature<br />
2. Tachycardia<br />
3. Shivering<br />
4. Increased BP, then decreased BP<br />
5. Wheezing, SOB, cyanosis<br />
6. Peripheral constriction<br />
7. Generalized rash.<br />
(v) Treatment of Adverse Reactions from ATG<br />
1. Stop ATG infusion immediately.<br />
2. Give additional diphenhydramine 25 mg IV, acetaminophen 650 mg<br />
po/pr depending on severity of reaction; i.e. flushing, increased<br />
temperature, shivering, etc.<br />
3. Restart IV slowly when anaphylactic signs have disappeared.<br />
4. If reaction continues to increase - Epinephrine may be required.<br />
5. O2 administration as indicated.<br />
60
10. IMMUNOLOGICAL MONITORING<br />
Lung Biopsy<br />
There is currently no simple non-invasive reliable technique to diagnose rejection.<br />
Transbronchial biopsy, unfortunately, remains the current gold standard. This is a safe<br />
technique.<br />
Biopsies are performed shortly after the initial hospitalization at the time of<br />
transplantation (14-21 days post transplant) and then every 2 weeks following<br />
discharge for the first four to six weeks following transplantation. Subsequently, the<br />
frequency of biopsies is decreased as a clear pattern of non-rejection is established.<br />
Conversely, the frequency of biopsies may be increased if rejection is strongly<br />
suspected and the initial biopsy was equivocal. If an attempt is made to wean down<br />
cyclosporine levels or prednisone, monthly biopsies should be performed during the<br />
weaning, for at least six months after the new baseline level is attained and then<br />
quarterly thereafter, to ensure that rejection is not triggered by the lower<br />
immunosuppressive levels.<br />
Grade NEW NOMENCLATURE OLD NOMENCLATURE<br />
0 No rejection No rejection<br />
A1<br />
A2<br />
A3<br />
Scattered,infrequent<br />
perivascular mononuclear<br />
infiltrates in alveolated<br />
lung parenchyma are not<br />
obvious on low<br />
magnification.<br />
Frequent perivascular<br />
mononuclear infiltrates<br />
surrounding small vessels<br />
at low magnification<br />
Dense perivascular<br />
mononuclear infiltrates<br />
extend into alveolar<br />
septae<br />
Minimal rejection<br />
`Mild rejection<br />
Moderate rejection<br />
A4<br />
Diffuse mononuclear<br />
infiltration with<br />
parenchymal necrosis<br />
`Severe Acute' rejection<br />
61
10.1 Immune Activation<br />
While transbronchial biopsies have been our standard for the monitoring of lung<br />
rejection, we recognize that other methodologies are available to assess the<br />
presence or absence of `immune activation'. Cytoimmunological monitoring has<br />
been advocated as just such a technology. Similarly, the measurement of<br />
interleukin-2 and interleukin-2 receptors in the blood has been advocated as a<br />
sensitive index of immune activation. If one were able to accurately correlate<br />
this assay with immune activation, then it would remain only to distinguish<br />
rejection from infectious causes of immune activation. Under the<br />
circumstances of an elevated interleukin-2 or interleukin-2 receptor assay a<br />
diligent search for infection would be carried out and a lung biopsy performed.<br />
While it may be possible to decrease the frequency with which transbronchial<br />
biopsies are performed, what remains undesirable about this assay is that it<br />
relies on `exclusion' of infection to `rule-in' rejection, and therefore has not<br />
generated much enthusiasm for monitoring for rejection.<br />
10.2 Cyclosporine Levels<br />
As all patients are on cyclosporine, whole blood trough levels are measured<br />
daily by radioimmunoassay, 12 hours after the previous dose. The acceptable<br />
target levels in the first three months are 350-500 ng/ml, and subsequently,<br />
200 - 500 ng/ml, depending on renal function. Following discharge from<br />
hospital the assays are performed twice weekly on the day of the clinic visit.<br />
Note: Sudden increases in cyclosporine levels may be artifactual, but may also<br />
represent deterioration of renal function with fluid retention and<br />
hyperkalemia. Immediate reassessment of renal function, electrolyes and<br />
cardiac function, are required.<br />
10.3 Absolute Lymphocyte Count<br />
Since all patients receive perioperative antithymocyte globulin for 5 - 10 days,<br />
the absolute lymphocyte count is measured daily during ATG dosing aiming for<br />
levels below 200 mm 3 . If the absolute lymphocyte count does not promply<br />
fall, the dose of MALG is increased from 10 to 15 or 20 mg/kg/d by continuous<br />
infusion. CD3 levels should be determined if the absolute lymphocyte count<br />
remains elevated, as the batch of ALG could be defective. The only other<br />
explanation for elevated absolute lymphocyte counts in the presence of<br />
sufficient ATG dosing would be the presence of increased numbers of B-cells,<br />
which would imply adequate T-cell suppression if
mg/kg/d, consideration should be given to switching to RATG or OKT 3 , and<br />
administering Solumedrol 2 mg/kg/d X 3 days following the discontinuation of<br />
the polyclonal or monoclonal therapy.<br />
10.4 Chest Roentgenography, Bronchoscopy and Lung Biopsies<br />
We have relied mainly upon ruling out infection on clinical findings, including<br />
chest roentgenography and bronchoscopy. Changes in vitalometry may be<br />
associated with either infection or rejection. In the presence of a pulmonary<br />
infiltrate a transbronchial brushing and washing would be performed, to rule<br />
out infection or rejection. It should be noted, as well, that the infilrates that<br />
occur with rejection tend to be more diffuse and homogenous rather than<br />
localized as might be the case with an infectious process. Rather than subject<br />
patients to a lung biopsy in the setting of bilateral diffuse homogenous<br />
infiltrates and a negative bronchoscopic assessment and negative serology for<br />
CMV or HSV, we have preferred a single diagnostic therapeutic trial dose of<br />
solumedrol 10 mg/kg/IV, which usually results in substantial clearing of the<br />
infiltrate, thus strongly pointing to a diagnosis of rejection. A full course of<br />
antirejection therapy is then given, and baseline immunosuppression adjusted.<br />
While both infection and rejection can be associated with a reduction in FEV 1 ,<br />
and FVC, it is important to remember that infection may lead to rejection by<br />
up-regulating the immune system, which may lead to both acute and chronic<br />
rejection (bronchiolitis obliterans, which is fatal in most instances). A 10% fall<br />
in FEV 1 and FVC must be immediately investigated and, in the absence of<br />
infection, bronchiolitis obliterans assumed and treated at least with Solumedrol<br />
10 mg/kg/d X 3 days and cyclosporine, azathioprine and prednisone adjusted.<br />
(See management of bronchiolitis obliterans )<br />
63
11. MANAGEMENT OF REJECTION<br />
11.1 In The First Three Months<br />
Lung Rejection (Treatment Based On Pathological A2, A3, and A4) Or<br />
Compelling Clinical Findings In The Absence of Histological Confirmation).<br />
1. It is important to recognize that the best management of rejection is<br />
the avoidance of rejection, which implies that maintenance<br />
immunosuppression is optimal at all times. It is unacceptable to have<br />
subtherapeutic cyclosporine levels, inadequate ATG dosage in terms of<br />
target absolute lymphocyte counts perioperatively, or not to aim for<br />
maximal azathioprine dosing within the tolerance of the white blood<br />
count, up to 2 mg/kg/d.<br />
2. For patients with normal renal function, the acute rejection episode<br />
should be treated with Solumedrol 10 mg/kg/day for three days, the<br />
Prednisone increased by 20%, the Azathioprine increased to a maximum<br />
of 2 mg/kg/d if the bone marrow can tolerate this dose (maintain WBC ><br />
4000/mm 3 ), and the Cyclosporine levels increased within the target<br />
range.<br />
3. For patients with renal function that is sufficiently compromised to<br />
interdict further increases in cyclosporine, the rejection episode should<br />
be treated with Solumedrol 10 mg/kg/day for 3 days, the Prenisone<br />
increased by 20%, and the Azathioprine increased to a maximum of 2-3<br />
mg/kg/day if the bone marrow can tolerate this dose (maintain<br />
WBC>4000/mm 3 ).<br />
4. For refractory lung rejection, a second course of Solumedrol 10 mg/kg<br />
IV may be given, the prednisone further increased by 20% and the<br />
cyclosporine and azathioprine optimized. Failure to resolve the lung<br />
rejection with 2 courses of Solumedrol requires therapy with a<br />
polyclonal MALG or RATG or monoclonal OKT3 antibody for 3 days, along<br />
with pulsed steroids (10 mg/kg/d X 3 doses) and optimization of<br />
cyclosporine, azathioprine and prednisone dosages. Absolute<br />
lymphocyte counts should be suppressed to less than 200 mm 3 (or CD 3<br />
levels to
with methyprednisolone sodium succinate may be given on a q8 hourly<br />
basis for the first twenty four hours, and then twice daily for a total of<br />
three to five days of therapy until the rejection episode is clearly<br />
brought under control.<br />
7. For mild acute rejection in the absence of any clinical abnormalities<br />
no anti-rejection therapy is initiated, but maintenance<br />
immunosuppression is reviewed to ensure that it is optimal. Under<br />
the circumstances of a clear increase in the numbers of lymphocytes<br />
present within the graft on biopsy, cyclosporine and azathioprine<br />
levels would be optimized and, if mild rejection persisted with an<br />
increase in the infiltrate, the patient would be treated with<br />
Prednisone 50 mg bid for three days with subsequent taper by 5 mg<br />
qd to 0.1 mg/kg/d above the previous dose.<br />
8. Following the treatment of a rejection episode, a follow up biopsy is<br />
performed 7 days later, or approximately 10 days after antirejection<br />
therapy was initiated. Biopsies before this time, in<br />
general, may not show adequate clearing of the lymphocytes from<br />
the graft owing to insufficient time for resolution.<br />
9. In summary, during the first three months, moderate and severe<br />
acute rejection on lung biopsy, are treated with three 10 mg/kg daily<br />
doses of solumedrol, with use of ATG or OKT3 reserved for failure of<br />
two courses of solumedrol alone, A3 or greater rejection persisting<br />
one week after a 3 day course of Solumedrol 10 mg/kg/d, or<br />
rejection associated with hemodynamic instability.<br />
11.2 After The First Three Months Post-Transplant<br />
Severe acute rejection is treated as described above with pulsed doses of<br />
solumedrol, with use of ATG, or OKT3 only for an, A3 or greater rejection<br />
persisting one week after an initial 3-day course of solumedrol 10 mg/kg/d, or<br />
failure of two courses of solumedrol therapy.<br />
Grade A2 rejection would be treated with oral Prednisone 1 mg/kg qd for three<br />
days tapering by 5 mg/d (2 mg/d if less than 20 kg) until 20% above the<br />
previous daily dose of Prednisone. In the event that the patient demonstrated<br />
hemodynamic compromise, we would assume that the biopsy sampling missed<br />
the worst areas of acute rejection, that in fact the pathology is likely severe<br />
acute rejection, for which the patient would be treated more aggressively with<br />
pulsed doses of solumedrol, 10 mg/kg/d for three days, the prednisone dose<br />
increased by 20%, and the cyclosporine and azathioprine would be optimized<br />
within the limits of renal and marrow toxicity.<br />
65
For mild acute rejection (Grade A1 ) unassociated with worrisome clinical<br />
findings suggestive of rejection, the immunosuppressive therapy would simply<br />
be reviewed to ensure that cyclosporine and azathioprine dosing was optimal.<br />
66
11.3 Management of Bronchiolitis Obliterans (B.O.)<br />
The occurrence of B.O. post lung transplantation usually portends a fatal<br />
outcome that may occur within weeks of its onset and is always due to<br />
inadequate immunosuppression. The pathology is likely antibody mediated as a<br />
consequence of up-regulation of the immune system in the setting of either<br />
inadequate immunosuppression or new infection, eg. CMV.<br />
B.O. is initially manifest by a 10% drop in FEV 1 and FVC and may or may not be<br />
associated with biopsy confirmation.<br />
Therapy must take the form of aggressive immunosuppression with:<br />
1. Solumedrol 10 mg/kg/d X 5 days<br />
2. Optimization of cyclosporine levels to the 400-600 mg/ml range with<br />
consideration of renal status.<br />
3. Switch from Azathioprine to Cyclophosphamide 2-5 mg/kg/d to bone<br />
marrow tolerance.<br />
4. Failure to re-establish FEV 1 or VC mandates, a repeat of 1, 2 and 3 above<br />
with a 5 day course of OKT 3 5 mg/d. Consideration may be given to using<br />
OKT 3 in the first course of therapy.<br />
5. Failure of the aforementioned regime may lead to a trial of TLI 80 gy/week<br />
X 10 courses, depending on the clinical status of the patient.<br />
67
12. PROPHYLAXIS AND TREATMENT OF INFECTION<br />
Immunization Policy and Protocol For Solid Organ Transplant Patients<br />
a) Preamble<br />
Immunization is important for all children and adults, and particularly for those<br />
who are or are expected to become immunocompromised. A comprehensive<br />
immunization policy for patients being transplanted is vital for two major reasons:<br />
(1) The time before transplantation and immunosuppression, while the patient is<br />
on the waiting list for transplantation, is a window of opportunity for optimal<br />
response to immunization which will be lost after long term immunosuppression<br />
begins.<br />
(2) There are specific indications and contraindications for particular vaccines in<br />
this immunosuppressed population.<br />
The following principles apply to patients receiving immunosuppressive therapy.<br />
(1) Currently available live virus vaccines (measles, mumps, rubella and polio) and<br />
BCG are contraindicated.<br />
(2) The immune response to inactive vaccines (eg. DTP) is lower than in normal<br />
hosts, but is usually adequate.<br />
(3) Certain vaccines may be particularly beneficial to the immunosuppressed<br />
patient (eg. pneumoccoccal, influenza).<br />
(4) Normal siblings and household contacts of immunosuppressed patients should<br />
not receive oral polio vaccine, but should receive MMR and yearly influenza<br />
vaccine.<br />
b) Procedure<br />
Patients who are awaiting transplantation should have their immunization status<br />
reviewed at the initial pre-transplant assessment.They should be entered in one of<br />
the three schedules provided depending on their age and prior immunization<br />
history. An individual schedule for each patient should be constructed with<br />
consideration given to past medical history, current medial status, medications and<br />
time before transplant.<br />
All immunizations should be administered by the public health system to ensure<br />
proper preparation, administration and recording of immunizations given. They will<br />
follow the immunization schedule provided by the infectious disease clinic. A<br />
record should also be kept by the transplant service.<br />
68
Immunizations can be given up until 1 month before expected transplant<br />
(especially important for MMR) and may be resumed post-transplant once the<br />
patient is on a stable immunosuppressive regimen (usually not before 3 months<br />
post-transplant).<br />
At the time of transplant work-up, baseline serological response should be<br />
measured for varicella, measles, mumps and rubella to establish the patients<br />
immune status for future reference in the case of exposure.<br />
Recommended Schedule For Active Immunization of Transplant Patients<br />
Recommended Age Immunization Comments<br />
2 mo DTP, IPV Can be started at age 2 wks if<br />
imminent transplant (e.g. neonatal<br />
cardiac)<br />
4 mo DTP, IPV<br />
6 mo DTP<br />
*(6) - 12 mo MMR To be given only if 1 month or greater<br />
before transplant. Measles vaccine<br />
alone may be given as late as 2 weeks<br />
before transplant. *May be given as<br />
early as 6 mo but should be delayed<br />
until 9 mos if transplant schedule<br />
allows.<br />
12 - 18 mo DTP, IPV,<br />
Haemophilus<br />
influenzae vaccine<br />
2 yr Pneumovax<br />
4 - 6 yr DTP, IPV<br />
14 - 16 yr Td Every 10 yrs<br />
Yearly<br />
Influenza<br />
Acyclovir Prophylaxis and Treatment For Herpes Simplex and Varicella Zoster<br />
Infection<br />
Herpes Simplex<br />
Although reactivation of oral and genital herpes simplex infection in the early<br />
postoperative period is common in transplant recipients, particularly those<br />
receiving induction immunotherapy with antilymphocyte globulin, this disease is<br />
usually relatively mild and easily treated with oral acylovir therapy. Therefore<br />
monitoring for oral and genital lesions in the postoperative period should be<br />
69
undertaken. Herpes simplex ulceration is often accompanied by candida<br />
superinfection and swabs for both virus isolation and fungal cultures should be<br />
taken from patients with suspected lesions. The usual dose of therapy is 200 mg 5<br />
times a day for a period of 5 to 7 days. In most cases, oral or genital herpes<br />
simplex infections, are not severe enough to warrant a routine prophylaxis of all<br />
patients. The possible exception to this is the heart-lung transplant recipient.<br />
Because asymptomatic reactivation of herpes simplex is extremely common posttransplant<br />
and these patients are at high risk of aspiration and possible primary<br />
HSV infection of the lung. It may be appropriate for this subgroup of patients to<br />
receive acylovir prophylaxis at an initial dose of 200 mg 3 times a day. If the<br />
patient breaks through this prophylactic dose, higher doses of 200 mg 5 times a day<br />
may be required. In the single and double lung transplant recipients, the risk of<br />
aspiration should be significantly lower and it is not clear that routine acylovir<br />
prophylaxis is required for these patients.<br />
Patients who have a very frequent recurrence of either oral or genital herpes<br />
simplex should be considered for longterm low-dose acylovir prophylaxis at a dose<br />
of 200 mg 3 times a day.<br />
Varicella Zoster Infection<br />
Because of the risk of dissemination of varicella zoster infection in the<br />
immunocompromised host, transplant recipients with varicella zoster infections<br />
should be treated with antiviral therapy. Treatment should begin with the initial 5<br />
days of outbreak and patients should be advised to seek therapy early should they<br />
develop symptoms. As a rule, the patient who is afebrile and has no evidence of<br />
extensive extradermatomal or visceral dissemination can be treated as an<br />
outpatient. The usual dose of acyclovir therapy is 800 mg 5 times a day for a<br />
period of 7 days. This dose may require adjustment for renal failure. Please see<br />
the protocol outlined for dosage adjustment for acylovir prophylaxis for CMV<br />
infection prevention.<br />
All patients are screened for varicella zoster antibody in the pretransplant period.<br />
This is far more accurate than a clinical history of chicken pox. If the patient has<br />
been exposed to chicken pox, please refer to their pretransplant varicella zoster<br />
antibody status. If they have antibody they are immune and no further prophylaxis<br />
is required. However, if they are seronegative and have a history of clear exposure<br />
to chicken pox they should receive varicella zoster hyperimmune globulin.<br />
Cotrimoxazole Prophylaxis For Pneumocystic Carinii Pneumonia (PCP)<br />
Historical Perspective<br />
Cotrimoxazole prophylaxis was initiated in March of 1988. The dose of prophylaxis<br />
which was used was 1 double-strength tablet bid, Monday, Wednesday and Fridays.<br />
Since that time there has not been a single case of PCP pneumonia in patients<br />
receiving prophylactic therapy. The high incidence of PCP pneumonia was<br />
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undoubtedly due to the very aggressive use of immunosuppression and large doses<br />
of antilymphocyte globulins used in the early transplant patient experience. It is<br />
very likely that our present regimen, which is less aggressive, could result in a<br />
significant lower incidence of infection. However, the continued use of antilymphocyte<br />
globulins as immunoprophylaxis suggest that the risk will remain.<br />
Recent studies in AIDS patients and other patients suggests that significantly lower<br />
doses of cotrimoxazole are effective in the prevention of PCP. A recent study in<br />
renal transplant recipients suggests a dose as low as 1 single strength tablet daily is<br />
sufficient to prevent PCP pneumonia.<br />
Therefore the dose of cotrimoxazole (Bactrim or Septra) used for prophylaxis of<br />
pneumocystic carinii pneumonia will be: 1 single-strength tablet daily. This should<br />
be continued over the first six post-transplant months and for longer periods in<br />
patients who are maintained on higher levels of immunosuppression or have late<br />
rejection events. Please note that patients experiencing CMV infection,<br />
particularly primary CMV infection, are at increased risk of PCP pneumonia. It is<br />
hoped that these very low doses of cotrimoxazole have no significant effects on on<br />
either renal function and no significant bone marrow suppressive activity.<br />
Protocol for CMV Monitoring of Allograft Recipients<br />
Patients will be divided into one of four categories based on recipient donor<br />
serology as follows:<br />
neg-neg 1<br />
neg-pos 2<br />
pos-neg 3<br />
pos-pos 4<br />
Patients in categories 2, 3 and 4 will be monitored at the following intervals pretransplant,<br />
every two weeks for 12 weeks, at six months and one year after<br />
transplant. Patients in category 1 who are very unlikely to develop CMV infection<br />
will be monitored at six months and one year only.<br />
The following specimens should be submitted:<br />
1. buffy coat (lavender top tube - mark requisition for CMV isolation)<br />
2. CMV serology (red top tube - mark requisition CMV, IgG and IgM)<br />
If the patient develops symptoms suggestive of CMV infection, submit an additional<br />
set of specimens as above and appropriate biopsy material. Since specimens will<br />
not be processed if submitted more frequently than every two weeks, specimens<br />
submitted when the patient is symptomatic must be marked "lung transplant,<br />
symptomatic (description of symptoms)".<br />
Patients in categories 1 and 2 will have CMV IgG and IgM assays performed on sera.<br />
Patients in categories 3 and 4 who are seropositive prior to transplant will be<br />
monitored using CMV, IgM only. Routine monitoring should be discontinued when<br />
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CMV has been isolated from > .2 specimens and/or CMV igM (OD value) > .2 has<br />
been demonstrated in two consecutive sera.<br />
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HSV Disease<br />
If HSV oral, skin or genital lesions are suspected, submit swab of lesion (vigorously<br />
swab base of ulcers and/or unroof and obtain vesicle fluid) in viral transport media.<br />
Mark requisition "lung transplant for HSV isolation". Note throat swabs submitted<br />
for CMV studies are not cultured for HSV unless this test is specifically requested.<br />
Do not order HSV serology - this test is not useful in this setting.<br />
VZV Disease<br />
If VZV infection is suspected the preferred specimen is vesicle fluid drawn into a<br />
capillary tube and hand delivered to Virology. Swabs of moist ulcers are also<br />
acceptable. Mark requisitions "lung transplant for VZV isolation".<br />
EBV Infection<br />
Throat washes should be submitted as outlined on the attached protocol. EBV<br />
serostatus pretransplant is determined using anti-EBNA IgG and is confirmed by<br />
testing for anti-VCA IgG. A patient is considered seronegative if both assays are<br />
negative. In patients who are seropositive )titre > 1:20), no further EBV serology<br />
should be ordered. In patients who are seronegative, repeat serology for EBV-VCA<br />
IgG and IgM should be performed at two weekly intervals for 12 weeks after<br />
transplant or if antirejection therapy with ATG or OKT-3 are considered.<br />
Acylovir Prophylaxis For CMV Mismatched Organs i.e. donor positive - recipient<br />
negative only.<br />
Dose: Start before transplant: 800 mg po (single dose) or 10 mg/kg IV.<br />
Given another 800 mg po or 10 mg/kg IV 48 hours after transplant then adjust dose<br />
to renal function as follows:<br />
< 10 ml/min 800 mg od po or 5 mg/kg q24h IV<br />
10-25 ml/min 800 mg tid po or 10 mg/kg q24h IV<br />
> 25 ml/min 800 mg qid po or 10 mg/kg 18 h IV<br />
dialysis 800 mg bid po or 10 mg/kg q24h IV and after dialysis<br />
Continue until 12 weeks after transplant, adjust dose as required.<br />
If the patient develops CMV infection, i.e. sheds virus or develops CMV-specific IgM,<br />
stop the acyclovir.<br />
If the patient is symptomatic or has evidence of tissue invasive disease w/u with<br />
appropriate specimens/biopsy, consider ganciclovir Rx & CMV hyperimmune<br />
globulin.<br />
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Please note: The efficacy of this regimen in patients who are CMV seronegative and<br />
receive CMV seronegative donor organs or who are seropositive prior to transplant<br />
has not been proven. Because of the low risk of CMV associated morbidity in these<br />
groups, particularly on the most recent immunosuppressive regimens employing<br />
lower doses of antilymphocyte globulin acylovir prophylaxis for prevention of CMV<br />
infection in these groups is not recommended.<br />
Perioperative Bacterial Prophylaxis<br />
Knowledge of the nature of donor and recipient bronchial secretions plus<br />
knowledge of the infectious patterns in transplant recipients at the PWH provides<br />
the best guide to appropriate bacterial prophylaxis.<br />
Excellent Gram positive and negative prophylaxis is achieved with Cefuroxime 1.5<br />
mg IV preop and then 1.5 gm q12h postop in adults and until 1 dose after the chest<br />
tubes are removed.<br />
Patients undergoing transplantation for cystic fibrosis, bronchiectasis or pulmonary<br />
fibrous frequently will harbor resistant pathogens, such as several pseudomonas<br />
strains and methicillin-resistant staphylococci. These patients will require more<br />
aggressive perioperative coverage with aminoglycosides, third generation<br />
cephalosporins, and Vancomycin.<br />
The special problem of fungal infections poses philosophical considerations, i.e.<br />
when does colonization become infection? Inadequate therapy may lead to<br />
bronchial disruption and upregulation of the immune system, causing rejection<br />
which, if treated, further allows for entrenchment of the fungal infection.<br />
Therefore, fungal infections in lung transplant recipients should be routinely<br />
treated with `liposomal' Amphotericin B.<br />
Management of Postoperative Infection<br />
Postoperative temperatures (greater than 37.5 degrees C) and increased white<br />
blood counts require vigorous investigation which includes 2 sets of blood cultures<br />
(aerobic and anaerobic) with sputum and urine cultures each shift for 48 hours, and<br />
then daily until the pathogen is identified. All intravascular lines are removed and<br />
the tips cultured and new lines placed. Bronchoscopic or transtracheal aspirates<br />
(TTA) are performed in patients with pulmonary infiltrates or positive sputum and<br />
analyzed by gram smear, KOH, AFB, aerobic and anaerobic bacterial cultures, viral<br />
cultures, Legionella and fungal cultures, and GMS (silver stain) for pneumocystis<br />
carina. Antibiotics for pulmonary infection are never begun until a TTA,<br />
bronchoscopy or transthoracic needle aspirate are done. Serology for CMV, EBV,<br />
herpes virus, toxoplasmosis, coccidiomycosis, and cryptococcosis, plus urine,<br />
sputum and throat swabs for shed CMV are carried out at 2 weekly intervals for the<br />
first 3 months and may be helpful in identifying the pathogen. In patients with a<br />
non-diagnosed elevated temperature or leukocyctosis, a white blood cell scan, lung<br />
tomograms or a lumbar puncture may be indicated.<br />
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Amphotericin B, liposomal amphotericin B, fluocytosine, ketoconazole, miconazole<br />
and rifampin are used alone or in combination (depending on sensitivities and<br />
synergy studies) for the treatment of most fungal infections.<br />
Acyclovir ointment is applied to superficial herpes simplex infections six times per<br />
day. Herpes zoster infections or disseminated herpes infections are treated with IV<br />
Acylovir (5 mg/kg tid or 15 mg/kg tid, respectively) for 14 days. Serum titres for<br />
herpes virus are followed weekly, and in patients who receive ATG, Acylovir is<br />
administered for 14 days for a rising titre.<br />
Acyclovir may also be used for a rising EBV titre, with careful and frequent<br />
examination for enlarging lymph nodes.<br />
Parasitic and Protozoal infections are uncommon in patients treated with<br />
cyclosporine.<br />
12.1 Technique For Transtracheal Aspiration<br />
1. Position patient in bed, sitting at 30 degrees with neck hyperextended, and<br />
roll behind shoulders.<br />
2. Clean neck thoroughly with alcohol, followed by a Poviodine-Iodine prep,<br />
and drape with 4 sterile towels. Use sterile gloves and a mask.<br />
3. Anesthetize the skin and underlying structures with 2% Lidocaine<br />
(approximately 2-3 mL) with #22 gauge needle over the cricothyroid<br />
membrane or between the first and second tracheal rings. It is usually<br />
helpful to steady the trachea between the fingers of one hand during<br />
infiltration or penetration of the trachea.<br />
4. Insert a #18 or 20 gauge Bard intracath through the introducer needle, pull<br />
the needle out of the trachea and advance the catheter as far it will go,<br />
clamp the protective plastic guard over the needle. Instruct the patient to<br />
try to suppress his cough.<br />
5. With a 40 mL syringe, inject 10 mL of N/S and 40 mL of air rapidly during a<br />
slow inspiration. If possible, have the patient take 2 or 3 deep breaths<br />
without coughing, then have the patient cough and aspirate 2-4 times with<br />
the 50 mL syringe. This usually results in 2-5 mL of intratracheal fluid for<br />
analysis.<br />
6. Send fluid for:<br />
i) Gram Smear, KOH, AFB.<br />
ii) Legionella cultures.<br />
iii) Aerobic bacterial and fungal cultures.<br />
iv) Anaerobic cultures.<br />
v) GMS (Silver Stain) for Pneumocystis Carinii if indicated.<br />
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vi) Viral cultures if indicated.<br />
12.2 Administration Procedure For Amphotericin B<br />
Approximately one-fourth of transplant recipients at some point acquire a fungal<br />
infection that may be responsive to Amphotericin B. Although it is important<br />
always to conduct in vitro sensitivity and synergy studies with other antifungal<br />
agents, results of these studies should not delay onset of therapy. The<br />
antifungal agent should be started as soon as the fungus is speciated.<br />
When Amphotericin is used, the following protocol will minimize adverse<br />
reactions.<br />
1. Assess renal function daily: Cr, BUN, creatinine clearance.<br />
2. The daily dose of Amphotericin should not exceed 0.6 mg/kg per day in<br />
order to minimize renal toxicity, unless liposomal amphotericin B is<br />
used, in which case the tolerable dose will be 1 - 2 mg/kg/d.<br />
3. The total treatment dose of Amphotericin should be 1000 - 2000 mg, the<br />
final dose determined by clinical resolution of the infection.<br />
4. Administration<br />
i) Administer diphenhydramine 50 mg IV, hydrocortisone sodium<br />
succinate (Solucortef) 25 mg IV and meperidine 25 mg IV plus<br />
Acetaminophen 650 mg po or pr 20 minutes prior to a test dose<br />
of Amphotericin 1 mg IV in 50 cc D5W run in over 1 hour.<br />
ii) If there is no adverse reaction, administer 0.2 mg/kg Amphotericin IV<br />
in 200 cc D5W over 4 hours. The pre-meds may be repeated 1-2<br />
hours in the infusion if adverse reactions develop (chills, rigors,<br />
spiking temperature, erythema, wheeze, hypotension,<br />
tachycardia).<br />
iii) If there are no serious adverse reactions to the administration of 0.2<br />
mg/kg IV of Amphotericin, begin the same day with 0.4 mg/kg,<br />
and then the day after with 0.6 mg/kg in 600 cc D5W over 4-6<br />
hours. The diphenhydramine, hydrocortisone sodium succinate,<br />
meperidine, and acetaminophen should be given 20 minutes prior<br />
to the onset of the amphotericin infusion and then again, if<br />
necessary, 1-2 hours after the infusion has begun.<br />
5. Adverse reactions may require temporarily interrupting the infusion,<br />
slowing the rate of infusion or decreasing the dose.<br />
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13. PATIENT ISOLATION<br />
Since the advent of cyclosporine and the concomitant reduction in prednisone<br />
requirements, which has led to a slight decrease in frequency and a marked decrease<br />
in severity of infectious episodes, it has been possible to markedly reduce the ICU and<br />
total hospital stay for transplant recipients. Although the value of reverse isolation<br />
has been questioned, we have discontinued reverse isolation, with no obvious adverse<br />
sequelae. It is still our and others belief that the special circumstances of the<br />
immunocompromised patient demand impeccable technique in managing them, with<br />
handwashing prior to all visits and contact.<br />
13.1 Criteria For Reverse Isolation<br />
i) At any time if the patient is leukopenic (
3. Children with a communicable illness should not be allowed to visit a<br />
transplant recipient in the ICU or on the ward.<br />
4. For patients in a private ward room who are rejecting,visitation be<br />
children should be interdicted.<br />
5. For patients in a private ward room who are not rejecting, children of<br />
any age without evidence of a communicable disease should be allowed<br />
to visit the transplant recipient.<br />
ii) Adult family members and friends who do not have a communicable disease<br />
may visit patients in the ICU, or on the ward. A common sense approach is<br />
used to minimize visitor traffic.<br />
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14. VENTILATORY SUPPORT<br />
All patients are ventilated with positive pressure ventilation using the following<br />
baseline parameters: Tidal volume 12-15 mL/kg (peak inspiratory pressure less than<br />
40 cm H 2 O), peep 5 cm H 2 O, respiratory rate 8-12,the lowest FIO 2 possible to maintain<br />
a PO 2 >90 mm Hg (generally 40-50% FIO 2 ). Initial respiratory settings are ordered by<br />
the anesthetist,. Subsequent adjustments and weaning of the patients from<br />
ventilatory support using IMV are controlled by the respiratory technician on<br />
instruction from the transplant surgeon and fellow. It is important to maintain<br />
pulmonary vascular resistance as low as possible, which is helped by maintaining PCO 2<br />
at 28-32 until hemodynamics are stabilized.<br />
Aggressive and frequent physiotherapy (q2-4h while awake) including percussion,<br />
postural drainage and IPPB (only indicated with inadequate respiratory effort) is<br />
mandatory to keep lungs well expanded and free from infection, which is the most<br />
important cause of morbidity, mortality and prolongation of hospital stay.The<br />
physiotherapist is responsible for scheduling and performing chest physiotherapy,<br />
assisted by the nursing staff as required.<br />
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15. RENAL FUNCTION<br />
Many transplant recipients have preoperative renal dysfunction that may be<br />
aggravated by cardiopulmonary bypass and cyclosporine. The following measures<br />
greatly reduce the incidence of renal failure post-transplant:<br />
1. Avoidance of preoperative cyclosporine.<br />
2. Monitoring of daily whole blood cyclosporine trough levels post-op; aiming for 400-<br />
600 ng/mL for the first three months and then 200-500 ng/mL thereafter.<br />
3. Use of mannitol (12.5 gm) during cardiopulmonary bypass and then postoperative<br />
with each dose of cyclosporine until baseline dosing is established.<br />
4. Maintenance of an optimal CVP, with `high inflow (IV fluid) and outflow (urine<br />
output: 1.5 - 2.0 mL/kg/hr)'.<br />
5. Use of `renal effective' doses of dopamine (2-4 mcg/kg/min).<br />
6. Use of diuretics as required to maintain a urine output of at least 1 mL/kg/hr.<br />
The long term effects of cyclosporine on renal function are still being evaluated.<br />
Evidence to date suggests that cyclosporine induces interstitial fibrosis and a variable<br />
degree of tubular atrophy and glomerulosclerosis. Follow up renal function studies at<br />
1 and 2 years indicate little further deterioration of renal function, which suggests<br />
that the predominant renal injury occurs early postoperatively and is therefore<br />
possibly due to relatively higher doses of cyclosporine used at that time.<br />
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16. CENTRAL NERVOUS SYSTEM<br />
Seizures postoperatively may result from air emboli, atheroemboli, clots from<br />
the recipient heart, intracerebral hemorrhage, intracerebral edema,<br />
hypotensive induced ischemic, intracerebral infection or use of OKT3. Once a<br />
quick assessment of the adequacy of respiratory and cardiac function has been<br />
made, rapid initial seizure control is achieved with oxygen, phenytoin plus or<br />
minus diazepam, followed by careful neurological examination, a computerized<br />
tomographic head scan, electroencephalogram and assessment of cerebrospinal<br />
fluid pressure and fluid if indicated. Patients require strict control of their<br />
blood pressure postoperatively especially while being weaned from sodium<br />
nitroprusside or nitroglycerin. Razosin, hydralazine, captopril, enalapril or a<br />
calcium channel blocker, like cardizem are instituted to maintain systolic blood<br />
pressure less than 140. Seizures may occur when this regimen is not followed.<br />
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17. POST-<strong>LUNG</strong> TRANSPLANT ASSESSMENT<br />
Patients are assessed with the attached tests as per our protocol at:<br />
3 months<br />
6 months<br />
9 months<br />
12 months<br />
18 months<br />
24 months<br />
and yearly thereafter<br />
• Bronchoscopies are done routinely at each assessment listed above up until 2<br />
years post-op. Then the are done on a prn basis only.<br />
• Bone density tests are booked at 3 months, 1 year and then yearly thereafter or<br />
as needed.<br />
• 2D Echo<br />
Eisenmenger’s and Primary Hypertension.<br />
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18. DATE DISCHARGE PROTOCOL GUIDELINES<br />
18.1 0-3 MONTHS<br />
BLOODWORK<br />
THREE TIMES PER WEEK<br />
• MD will assess blood frequency at three months<br />
CBC, CSA/FK, LFT’s, lytes, creatinine profile, bone and<br />
mineral profile (INR if necessary)<br />
CSA and creatinine only<br />
• All lab work must be done at PWH for the first three<br />
months<br />
• Lipid profile will be done at time of assessment.<br />
PFT’S<br />
ONCE WEEKLY<br />
• Must be done before the clinic.<br />
CXR<br />
ONCE WEEKLY<br />
• Should be done before the clinic.<br />
REHABILITATION<br />
THREE TIMES PER WEEK<br />
• To be arranged in the Treadmill Room. Patient is to<br />
arrange this prior to leaving hospital.<br />
GANCYCLOVIR<br />
AS PER PROTOCOL<br />
CLINIC<br />
WEEKLY AND PRN<br />
• At three months post transplant patient should be referred back to the family physician or<br />
respirologist to be followed in conjunction with the Lung Transplant Program.<br />
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18.2 3-6 MONTH PROTOCOL GUIDELINES<br />
BLOODWORK<br />
Q2 weeks and prn<br />
• CSA/FK, CBC, lytes, LFT’s, creatinine profile,<br />
bone and mineral profile.<br />
PFT’S<br />
Q2 weeks or with clinic appt.<br />
CXR<br />
With clinic appt.<br />
CLINIC<br />
Monthly and prn<br />
84
18.3 6 MONTHS – 1 YEAR PROTOCOL GUIDELINES<br />
BLOODWORK<br />
Monthly and prn<br />
• CSA/FK, CBC, lytes, LFT’s, creatinine profile, bone<br />
and mineral profile.<br />
• Sputum on a prn basis.<br />
Note: CF patients will require more frequent<br />
bloodwork depending on absorption history of CSA/FK.<br />
PFT’S<br />
MONTHLY<br />
CXR<br />
WITH CLINIC APPT.<br />
CLINIC<br />
Q3 MONTHS and PRN<br />
85
18.4 1-2 YEAR PROTOCOL GUIDELINES<br />
BLOODWORK<br />
Monthly and prn<br />
• CSA/FK, CBC, lytes, LFT’s, creatinine profile, bone<br />
and mineral profile.<br />
• Sputum on a prn basis.<br />
Note: CF patients will require more frequent<br />
bloodwork depending on absorption history of CSA/FK.<br />
PFT’S<br />
MONTHLY and PRN.<br />
CXR<br />
WITH CLINIC APPT.<br />
CLINIC<br />
Q6 MONTHS (assessment surveillance) and PRN.<br />
NOTE: All assessment appointments to be followed as per previous protocol with full<br />
bloodwork including cholesterol profile and CMV urine and buffy coat at the time of<br />
assessment.<br />
86
18.5 More than 2 YEAR PROTOCOL GUIDELINES<br />
BLOODWORK<br />
Monthly and prn<br />
• CSA/FK, CBC, lytes, LFT’s, creatinine profile, bone<br />
and mineral profile.<br />
• Sputum on a prn basis.<br />
Note: CF patients will require more frequent<br />
bloodwork depending on absorption history of CSA/FK.<br />
PFT’S<br />
MONTHLY and PRN.<br />
CXR<br />
WITH CLINIC APPT.<br />
CLINIC<br />
Q6 MONTHS (assessment surveillance) and PRN.<br />
NOTE: All assessment appointments to be followed as per previous protocol with full<br />
bloodwork including cholesterol profile and CMV urine and buffy coat at the time of<br />
assessment.<br />
87