Organ Donor Management:
Survey of Guidelines and
Eligibility Criteria
Prepared for the Forum:
Medical Management to Optimize Donor
Organ Potential
February 23-25, 2004
by
Lead Investigator
Sam D. Shemie, MD, Chair,
on behalf of the MEMODOP Steering Committee
Coordinator
Karen Hornby
Montreal Children’s Hospital
Contents
Acknowledgements ...................................................................................................................v
Executive Summary ..................................................................................................................1
I. Survey of Canadian and Selected International Organ Donor Management
Guidelines and Eligibility Criteria.......................................................................................8
Methodology for Data Gathering and Inclusion ...............................................................8
Survey Responses............................................................................................................8
II.
Analysis of Canadian Management Guidelines Received ..........................................10
Oxygenation and Ventilation .........................................................................................10
Organ Perfusion ............................................................................................................11
Fluid Balance and Electrolytes ......................................................................................13
Hematology...................................................................................................................17
Temperature ..................................................................................................................17
Infection........................................................................................................................18
Additional Treatments ...................................................................................................18
III. Canadian Donor Organ Eligibility Criteria ....................................................................20
OPO Organ Donor Eligibility Criteria ...........................................................................20
IV. International Issues in Organ Donor Management.........................................................21
V. Conclusion ..........................................................................................................................24
Appendix I – Canadian Organ Procurement Organizations ................................................25
Appendix II – Spanish Guidelines..........................................................................................27
Appendix III — UNOS Critical Pathway ..............................................................................32
Appendix IV – New England Organ Bank.............................................................................39
Appendix V – Papworth approach.........................................................................................45
Appendix VI – Leuven University Hospital ...........................................................................48
References ...............................................................................................................................52
iii
Acknowledgements
The Steering Committee for the Forum on Medical Management to Optimize Donor Organ
Potential (February 23-25, 2004) commissioned this paper, a working draft, as a background
information piece for participants attending the Forum. During the Forum, consideration will be
given to editing this working draft for wider circulation.
The views of the paper do not necessarily reflect the official policy of the Forum host, the
Canadian Council for Donation and Transplantation, and are not intended for publication in their
current format.
iv
Executive Summary
This report summarizes the results of a survey of Canadian intensive care units, organ
procurement organizations (OPOs) and transplant associations. The survey requested copies of
organ donor management guidelines and eligibility criteria. Selected international OPOs were
also contacted, and a brief summary of their activities is included. This research was conducted
in preparation for the Canadian Forum on Medical Management to Optimize Donor Organ
Potential, sponsored by the Canadian Council for Donation and Transplantation (CCDT).
Canadian Donor Management Guidelines
Half of the pediatric centers and 43% of the adult centers surveyed stated that they used their
OPO’s guidelines. All OPOs stated that they were involved (to varying degrees) in organ donor
management at intensive care units within their respective provinces and provided these units
with OPO guidelines. The intent of the survey was to identify existing guidelines; the survey was
not intended to assess the utilization of these documents (i.e., if guidelines were actually in use
and how many sites were using them). As a result, this analysis is based on 17 unique
documented guidelines. (Refer to the tables on pages 3 and 4).
Canadian Donor Organ Eligibility Criteria
Donor organ eligibility is not an intensive-care-based responsibility according to the centers
surveyed. All hospital centers (except one) referred decisions to determine eligibility to their
respective OPOs. Ten OPOs provided information on donor organ eligibility criteria. One OPO
currently addresses eligibility by encouraging all centers to refer potential organ donors to it,
stipulating that the only contraindication is HIV/AIDS. Six OPOs stated that “eligibility was
assessed on a case by case basis”; three of these provided absolute contraindications. One OPO
provided a draft protocol (approval is outstanding, and the protocol is therefore not included in
the analysis). Another OPO uses the Canadian Standards (tissue and organ donation), and its
only absolute contraindication is West Nile virus. One OPO cited that it “looks at everything …
and then consults with individual transplant programs”.
International Issues in Organ Donor Management
Worldwide, organ donation and the medical management of organ donors is at various stages of
development. Among the countries with mature systems in this field, recent efforts have been on
optimizing medical management to maximize organ yield. Refer to pages 6 and 7 for
management details. Countries at the forefront of this movement are Spain, the United States, the
United Kingdom, Australia and members of Eurotransplant.
Spain
The Spanish Model consists of a team of specially trained individuals (physicians and nurses)
separate from the medical/transplant teams who are responsible for raising the donor rate in all
hospitals. Among other things, these teams identify all potential donors and handle the
evaluation and management of the donor.
1
United States
The United Network for Organ Sharing has developed a Critical Pathway for the Organ Donor,
endorsed by the Association of Organ Procurement Organizations, the American Society of
Transplantation, the American Society of Transplant Surgeons and the North American
Transplant Coordinators Organization.
United Kingdom
A standardized donor management technique was developed at the Papworth Hospital in
Cambridge, England. Details on the Papworth approach to organ donor management will be
provided in a separate presentation.
Australia
South Australia adopted the Spanish Model and experienced a significant increase in its donor
rate compared to other states. As well, the Alfred Hospital in Melbourne has developed a
successful system of transplant coordination and organ allocation. Its system is considered a
good example of the Australian approach.
Eurotransplant
Eurotransplant is an international framework including all transplant hospitals, tissue-typing
laboratories and hospitals where organ donation takes place in Austria, Belgium, Germany,
Luxembourg, the Netherlands and Slovenia. The Leuven University Hospital in Belgium has
developed a secure-access website containing organ donation information and protocols. This
website is accessible to all members of their donor hospital network. Since its implementation, a
substantial increase in donors has occurred.
2
Summary table 1. Canadian organ donor management guidelines
Respiratory
Targets
O2 sat (%)
FiO2 (%)
PaO2 (mm Hg)
PCO2 (mm Hg)
pH Lower limit
pH Upper limit
PEEP (mm Hg)
TV lower limit (ml/kg)
Peak airway
pressure (mm Hg)
Hemodynamic
MAP
Electrolytes
Serum sodium
Lower (mmol/L)
Upper
Serum potassium
Lower (mEq/L)
Upper
< 50
85
N/Ab
7.35
7.45
5
9
≤ 30
GLa
10
6
3
10
9
8
8
6
9
4
≥ 70
N/A
> 100
N/A
≥ 60
≤ 120
N/A
6
10
8
10
5
3
7
2
5
7
2
15
12
3
3
125–130
≤ 150 – ≤ 155
130
≤ 150
5
6
> 3.0 – > 4.0
< 4.5 – < 5.5
> 3.5
< 5.5
6
5
Range
≥ 90 – ≥ 96
“any value to maintain O2 sat”
< 40 – < 60
65–100
35–45
7.30–7.35
7.45
4–7.5
5–12
≤ 30
Adults (mm Hg)
Peds
Adults (mm Hg)
Peds
Adults (bpm)
≥ 70
age adjusted
SBP
> 90 – > 100
age adjusted
HR
≥ 60–70
≤ 110 – ≤ 160
Peds
age adjusted
CVP
(mm Hg)
≥ 4–7
≤ 8–12
PCWP Lower (mm Hg) 8
Upper
10–12
Median
≥ 95
Urine Output
Adults Lower (ml/h)
Upper
Peds
Lower (ml/kg/h)
Upper
≥ 30 – ≥ 120
≤ 180 – ≤ 300
1–2
2–3
≥ 100
≤ 250
1
2
9
6
5
5
Diabetes
Insipidus (DI)
Adults U/O (ml/h)
Osmol (mOs/L)
Na+ (mmol/L)
SG
Serum osmol
Peds
U/O (ml/kg/h)
Osmolality
Na+ (mmol/L)
SG
Serum osmol
> 180–400
< 300
< 10
≤ 1.000
> 300 mOs/kg & _
>4–>5
“low”
> 145
< 1.000 – < 1.010
“high”
> 240
< 300
< 10
≤ 1.000
> 300 mOs/kg & _
> 4 ml
“low”
> 145
<1.005
“high”
9
2
2
1
2
4
1
2
3
1
Blood Sugar
Lower limits (mmol/L)
Upper limits
4–8
10–20
6
12
5
6
3
Summary table 1. Canadian organ donor management guidelines (cont’d)
Insulin
Adults (U/h)
Peds (U/kg/h)
0.5 –1
0.025–0.1
0.75
0.025
2
3
Hematology
Hematocrit (%)
Hemoglobin (g/dL)
20–35
8–12
30
9
6
3
Temperature
Lower limit (°C)
Upper limit
35–36.5
37–38
35.3
37.5
14
11
Invasive Monitoring
Arterial line
Central venous line
Pulmonary artery catheterization
Cardiovascular Support
Dopamine (max dose) (µg/kg/min)
Norepinephrine Lower (µg/min)
Upper
Epinephrine
Lower (µg/min)
Upper
Vasopressin
Lower (U/h)
Upper
Percentage
93%
100%
53%
Range
10–15
0.6–3
36–60
0.6–3
36–60
1.1–3
2.4–6
Median
< 10
1.2
48
1.8
48
1.2
4.2
GLa
15
15
15
GLa
11
3
2
2
2
3
2
Desmopressin Suggested Dosages to Treat DI
Adults
Pediatrics
1 µg q6h prn
intranasal (no dose indicated)
1 µg push _ 2
0.25–1 µg per dose
1–2 µg push
5–10 µg ETT or 0.25–4 µg IV
2 µg infuse over 30 minutes
(2 guidelines)
1–4 µg IV, IM or SC q12–24h prn
2–4 µg q4–6h or 1 µg/h infusion
2 µg, then 4 µg repeat as needed
4 µg q2h _ 2 call MD if 3rd dose required (2 guidelines)
Vasopressin Suggested Dosages to Treat DI
Adults
1 U/h, titrate to target u/o
2 U bolus, 1 U/h titrate to target u/o
(2 guidelines)
2.5–5 units IV q4h
Antibiotics
One hour prior to OR:
Or if hospital > 72 hrs
AND
Pediatrics
0.5–3 mU/kg/h
5–15 mU/kg/h
(2 guidelines)
6–15 mU/kg/h
cefazolin IV
Adults: 1 gm (n = 1)
cefotaxime IV
Adults: 1 gm (n = 1)
metronidazole IV Adults: 500 mg (n = 1)
Corticosteriods
The following dosages were suggested:
10 mg/kg, max 1g (n = 1)
15 mg/kg, max 1g (n = 2)
1 g IV _ 1 (n = 3)
4
Peds: 30 mg/kg, max 1gm (n = 2)
Peds: 40 mg/kg, max 1 gm (n = 2)
Peds: 15 mg/kg, max 500 mg (n = 2)
Summary table 1. Canadian organ donor management guidelines (cont’d)
Hormonal Therapy
One guideline suggested:
methylprednisolone: 15 mg/kg IV (not to exceed 1 gm)
insulin infusion: 0.5–1.0 U/h starting dose
T4: 40 µg bolus IV _ 1
desmopressin infusion: 1µg/h
Investigations
Supportive Testing
Chest x-ray
82%
Electrocardiogram
71%
Echocardiogram
65%
Bronchoscopy
41%
Cardiac angiogram
24%
Cardiology consult
18%
a
Number of guidelines that provided target values for variable of interest.
b
N/A = not applicable
5
Summary table 2. International organ donor management guidelines
The following details have been extracted from guidelines provided by the Organización Nacional de Trasplantes
(Spain), the United Network for Organ Sharing (U.S.), the Papworth Hospital (U.K.) and the Leuven University
Hospital (Belgium).
Targets
O2 sat (%)
FiO2 (%)
PaO2 (mm Hg)
PCO2 (mm Hg)
pH
PEEP (cm H20)
Spain
95–100
up to 100
90–100
35–45
7.35–7.45
5
U.S.
≥ 95
up to 100
≥ 90
30–35
N/A
5
U.K.
> 98%
min for sat
~ 264 @ 50%
35–45
N/A
5
Belgium
N/Aa
min for PaO2
100
35–45
7.35–7.45
5
Respiratory
TV (ml/kg)
Peak airway
pressure (mm Hg)
8–10
< 30
10–15
< 30
15
N/A
15
N/A
Hemodynamic
MAP
SBP (mm Hg)
HR (bpm)
CVP (mm Hg)
PCWP (mm Hg)
SVR (dynes/sec/cm5)
N/A
≥ 100
≤ 100
10–12
8–14
≥ 60
≥ 90
≥ 70 – ≤ 120
4–11
8–12
800–1200
> 60
N/A
N/A
< 12
< 12
800–1200
> 70
N/A
N/A
8–10
N/A
N/A
Electrolytes
Serum Na (mEq/dl)
Serum K+ (mEq/dl)
N/A
N/A
< 150
> 4.0
N/A
N/A
N/A
N/A
Urine Output
Adults (ml/kg/h)
Peds (ml/kg/h)
>1
>2
≥1–≤3
N/A
N/A
N/A
≥ 1– ≤ 3
N/A
DI
U/O (ml/kg/h)
Osmolality
Na+
SG
Serum osmol
N/A
N/A
N/A
N/A
N/A
>3
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
>3
N/A
N/A
N/A
N/A
Blood Sugar (mg/dl)
150
120–180
70–115
(4–6 mmol/L)
N/A
Insulin
no doses given
see HRT
see HRT
see HRT
≥ 30
≥ 30
≥ 35 multi-organ
10–12
≥ 10
N/A
≥ 30
> 10
≥ 11
Temperature (°C)
> 35
36.5–37.5
N/A
> 35
Invasive Monitoring
Arterial line
Central venous line
Pulmonary artery catheterization
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
Respiratory
Hematology
Hematocrit (%)
Hemoglobin (g/dl)
6
Summary table 2. International organ donor management guidelines (cont’d)
Cardiovascular Support
Dopamine (max dose) (µg/kg/min)
Norepinephrine
Epinephrine
Vasopressin
≤ 10
no dose given
no dose given
N/A
< 10
N/A
N/A
see HRT
≤ 10
N/A
N/A
see HRT
≤ 10
N/A
N/A
N/A
Desmopressin Suggested Dosages
(to treat DI)
no dose given
N/A
N/A
2–4 µg (max 6)
Vasopressin Suggested Dosages
(to treat DI)
N/A
see HRT
see HRT
N/A
Antibiotics
prophylactic
use
broadspectrum
vancomycin 1 g on basis of
meropenem 1 g cultures
Corticosteriods
N/A
see HRT
500 mg
see HRT
methylprednisolone
Hormonal Therapy
T3
N/A
4 µg bolus, 3 µg/h
same as US
Vasopressin/Pitressin
N/A
1 U bolus, 0.5–4.0 U/hb
Steroids
N/A
methylprednisolone
15 mg/kg bolus q24h
1 U bolus,
0.5–2.0 U/h
N/A
Insulin
N/A
min 1 U/hc
sliding scale
Investigations/Supportive Testingd
Chest x-ray
N/A
yes
no
Electrocardiogram
N/A
yes
yes
Echocardiogram
N/A
yes
yes
Bronchoscopy
N/A
yes
yes
Cardiac angiogram
N/A
yes
yes
Cardiology consult
N/A
yes
yes
a
N/A = not applicable
b
Titrate to SVR.
c
Titrate to blood glucose.
d
These may be mentioned in sections on donor organ evaluations that were not provided.
7
2–4 µg in 1h,
then 1.8 u/h
N/A
hydrocortisone
3 _ 200 mg/24h
up to 600 mg
1–2 U/h
no
yes
no
no
no
no
I. Survey of Canadian and Selected International
Organ Donor Management Guidelines and Eligibility
Criteria
This report summarizes the results of a survey of Canadian intensive care units, organ
procurement organizations (OPOs) and transplant associations. The survey consisted of a request
for organ donor management guidelines and eligibility criteria. Documents were received from
three categories of institutions: adult centers, pediatric centers and provincial OPOs. Selected
international OPOs were also contacted, and a brief summary of their activities relating to organ
donor management is included. This research was conducted in preparation for the Canadian
Forum on Medical Management to Optimize Donor Organ Potential, sponsored by the Canadian
Council for Donation and Transplantation (CCDT).
Methodology for Data Gathering and Inclusion
A total of 55 centers were contacted across Canada. Twelve OPOs responded, and two provided
pediatric guidelines in addition to adult ones. (See Appendix I for further details on provincial
differences in OPOs.) Adult intensive care units in all major Canadian cities as well as all
Canadian pediatric intensive care units were contacted. Table 1 categorizes their responses.
Table 1. Canadian centers contacted/responded
Centers Contacted (n = 55)
No. Responses
OPOSs
14
Adult centers
21
Pediatric centers
16
Canadian Association of Transplantation
N/Aa
Canadian Society of Transplantation
N/A
Other (Yukon, P.E.I.)
N/A
a
N/Aa = not applicable
Survey Responses
Table 2 breaks down the survey responses by type of center and guidelines used. Half of the
pediatric centers and 43% of the adult centers surveyed stated that they used their OPO’s
guidelines. All OPOs stated that they were involved (to varying degrees) in organ donor
management at intensive care units within their respective provinces and provided these units
with OPO guidelines. Some OPOs provided lists of intensive care units within their provinces.
The intent of the survey was to identify existing guidelines; the survey was not intended to assess
the utilization of these documents (i.e., if guidelines were actually in use and how many sites
were using them). Therefore, only unique guideline documents were entered into the study
database.
8
Table 2. Breakdown of survey responses
Guidelines
Uses
No Guidelines
Provided
OPO’s
Documented
Adult center
24% (5/21)
43% (9/21) 33% (7/21)
Pediatric center
25% (4/16)
50% (8/16) 25% (4/16)
OPO
64% (9/14)a
N/Ab
36% (5/14)
a
One pediatric guideline not included, as it was based on a hospital guideline already analysed.
b
na = not applicable
For a variety of reasons, 16 centers did not provide guidelines: no guidelines available (n = 8);
management is at MD discretion (n = 5); management is on a case-by-case basis (n = 1);
guidelines are in draft format and not yet approved (n = 1); unable to locate (n = 1). As a result,
this analysis is based on 17 unique documented guidelines. All guidelines were for multi-organ
management in the following formats: documents (n = 9), standing orders (n = 5), algorithms
(n = 2) and pamphlet (n = 1). Many guidelines did not address all the variables of interest to this
study; therefore, percentages in the following sections are based on the number of guidelines that
addressed those particular issues of interest.
9
II. Analysis of Canadian Management Guidelines
Received
Oxygenation and Ventilation
Oxygenation and ventilation management includes respiratory targets, the use of the O2
challenge test and lung treatments.
Respiratory targets
There was agreement among the guidelines for a majority of the respiratory management targets
(table 3). Discord occurred in the areas of PaO2 and tidal volume targets, with a variety of values
cited.
O2 challenge
Ten guidelines mentioned the use of the O2 challenge test, with some variations. All cited using
an FiO2 of 100% with a PEEP of 5 mm Hg and a predetermined delay before blood is drawn for
arterial blood gases (ABGs). Recommended tidal volumes and delay prior to ABG measurement
varied. Only two guidelines identified desirable PaO2 targets (≥ 300 mm Hg and ≥ 250 mm Hg)
for the O2 challenge.
Lung treatments
Suctioning frequencies (n = 6) were either q2h (n = 4), q3–4h (n = 1) or prn only (n = 1). Other
lung treatments suggested were repositioning (n = 4), chest physiotherapy (n = 2), postural
drainage (n = 1) and manual lung inflation (n = 1).
Table 3. Respiratory management targets
Targets
O2 sat
FiO2
PaO2
PCO2
pH
Lower limit
Upper limit
PEEP
TV (lower limit)
Peak airway pressure
a
Range
Median
≥ 90% – ≥ 96%
≥ 95%
“any value to maintain O2 sat”
< 40% – < 60%
< 50%
65–100 mm Hg
85 mm Hg
35–45 mm Hg
35–45 mm Hg
7.30–7.35
7.35
7.45
7.45
4–7.5 mm Hg
5 mm Hg
5–12 ml/kg
9 ml/kg
≤ 30 mm Hg
≤ 30 mm Hg
Number of guidelines that provided target values for variable of interest.
10
GLa
10
6
3
10
9
8
8
6
9
4
Organ Perfusion
Organ perfusion management includes target pressures, invasive monitoring and cardiovascular
support.
Target pressures
Table 4 outlines the hemodynamic management targets. Not unexpectedly, most pediatric
guidelines indicated age-adjusted values for these targets.
Table 4. Hemodynamic management targets
Targets
MAP Adults
Peds
SBP Adults
Peds
HR
Adults
Peds
CVP
PCWP Lower limit
Upper limit
a
Range
≥ 70 mm Hg
age adjusted
> 90 – > 100 mm Hg
age adjusted
≥ 60–70 bpm
≤ 110 – ≤ 160 bpm
age adjusted
≥ 4–7 mm Hg
≤ 8–12 mm Hg
8 mm Hg
10–12 mm Hg
Median
≥ 70 mm Hg
N/Ab
> 100 mm Hg
N/A
≥ 60 bpm
≤ 120 bpm
N/A
6 mm Hg
10 mm Hg
8 mm Hg
10 mm Hg
GLa
5
3
7
2
5
7
2
15
12
3
3
Number of guidelines that provided target values for variable of interest.
N/A = not applicable
b
One pediatric guideline provided age-adjusted values for the central venous pressure target. Only
one guideline (adult) mentioned targets for systemic vascular resistance (800–1200 dynes/sec _
cm5), cardiac index (2.4–3.0) and left ventricular stroke volume (1800–2400 dynes/sec _ cm5).
Invasive monitoring
Standard care for invasive monitoring consists of an arterial line and a central venous line. Five
guidelines gave instructions for placement in specific anatomical locations. Table 5 breaks down
the types of invasive monitoring identified.
Table 5. Invasive monitoring
Arterial line
Central venous line
Pulmonary artery catheterization
a
Percentage
93%
100%
53%
Number of guidelines that referred to invasive monitoring.
11
GLa
15
15
15
The indications for pulmonary artery catheterization were heart/lung donors, or management
difficulties or both (n = 5), desirable (n = 2) and absolutely necessary (n = 1). One pediatric
guideline suggested the use of an intra-osseous line if access was difficult.
Cardiovascular support
Eighty-two percent of the guidelines provided suggestions for the use of inotropes or
vasopressors. In a majority of cases (n = 9), adequate fluid resuscitation prior to starting any
inotrope or vasopressor was indicated. Dopamine is the drug of choice in 59% of the guidelines.
Indications for the use of other vasopressors varied greatly: “avoid if possible” (n = 3), “as an
option” (n = 1) and “as required” (n = 1). Table 6 summarizes the dosing information provided.
In most cases, these drugs were used in addition to dopamine.
Table 6. Inotropes and vasopressors
Drug
Dopamine (maximum dose)
Norepinephrine Lower
Upper
Epinephrine
Lower
Upper
Vasopressin
Lower
Upper
a
Range
10–15 µg/kg/min
0.6–3 µg/min
36–60 µg/min
0.6–3 µg/min
36–60 µg/min
1.1–3 U/h
2.4–6 U/h
Median
10 µg/kg/min
1.2 µg/min
48 µg/min
1.8 µg/min
48 µg/min
1.2 U/h
4.2 U/h
GLa
11
3
2
2
2
3
2
Number of guidelines that provided target values for variable of interest.
Only 35% of guidelines mentioned the use of short-acting antihypertensives. The following
drugs were identified: nitroprusside (n = 4), labetalol (n = 3), propranolol (n = 2) and
nitroglycerin (n = 1), with some guidelines identifying more than one drug. Only two guidelines
provided dosing information. Both indicated 1–2 mg propranolol IV push, and one provided an
alternative of 5–10 mg labetalol IV.
12
Fluid Balance and Electrolytes
Fluid and electrolyte management requires attention to IV fluids, electrolytes and fluid balance,
including monitoring for diabetes insipidus.
IV fluids
All guidelines provided indications for the use of intravenous fluids, with a variety of
suggestions for the type of fluid used, the quantity and fluid management targets. Seven
guidelines based the decision of which fluid to use on electrolyte laboratory values, four of
which were specifically based on serum sodium values. Both crystalloids (n = 8) and colloids
(n = 6) were indicated for volume expansion. Two guidelines targeted specific levels of urine
output as their fluid management strategies, and three guidelines targeted pressures (MAP or
CVP). One guideline recommended avoiding the use of Ringer’s lactate. The same guideline
contraindicated the use of plasma, hetastarch and Pentaspan (pentastarch) for organ donors. One
other guideline had a contraindication for the use of Pentaspan, and five guidelines
recommended its use.
Electrolytes
Fifty-three percent of guidelines surveyed indicated the importance of strict monitoring and
correction of electrolyte imbalances. Six centers provided target values for serum sodium and
potassium (table 7).
Table 7. Electrolyte targets
Range
Median
GLa
Serum sodium
Lower limit
Upper limit
125–130 mmol/L
≤ 150 – ≤ 155 mmol/L
130 mmol/L
≤ 150 mmol/L
5
6
Serum potassium
Lower limit
Upper limit
> 3.0 – > 4.0 mEq/L
< 4.5 – < 5.5 mEq/L
> 3.5 mEq/L
< 5.5 mEq/L
6
5
a
Number of guidelines that provided target values for variable of interest.
13
Fluid balance
All centers identified upper and lower urine output targets. Table 8 details these values.
Table 8. Target urine outputa
Adults Lower limit
Upper limit
Peds Lower limit
Upper limit
Range
≥ 30 – ≥ 120 ml/h
≤ 180 – ≤ 300 ml/h
1–2 ml/kg/h
2–3 ml/kg/h
Median
≥ 100 ml/h
≤ 250 ml/L
1 ml/kg/h
2 ml/kg/h
GLb
9
6
5
5
a
When urine output for adults was provided in ml/kg/h, it was converted into ml/h based on an average adult weight
of 60 kg.
b
Number of guidelines that provided target values for variable of interest.
Diabetes insipidus
Diagnosis. Ninety-four percent of guidelines provided instructions for the management of urine
output, with 88% suggesting the use of antidiuretics. A definition of diabetes insipidus (DI) was
provided by 76% of guidelines. Urine output limits for DI are presented in table 9.
Table 9. Indicators of DIa
Adults
Urine Output
Osmolality
Na+
SG
Serum osmolality
Pediatrics
Urine Output
Osmolality
Na+
SG
Serum osmolality
Range
Median
GLb
> 180–400 ml/h
< 300 mOs/L
< 10 mmol/L
≤ 1.000
> 300 mOs/kg
and rising
> 240 ml/h
< 300 mOs/L
< 10 mmol/L
≤ 1.000
> 300 mOs/kg
and rising
9
2
2
1
2
> 4 – > 5 ml/kg/h
“low”
> 145 mmol/L
< 1.000 – < 1.010
“high”
> 4 ml/kg/h
“low”
> 145 mmol/L
<1.005
“high”
4
1
2
3
1
a
When urine output for adults was provided in ml/kg/h, it was converted into ml/h based on an average adult weight
of 60 kg.
b
Number of guidelines that provided target values for variable of interest.
14
Therapy. All of the guidelines that recommended using antidiuretics to treat DI suggested using
desmopressin, with a variety of doses and methods. Two guidelines indicated that desmopressin
was preferred over vasopressin to treat DI. Fifty-nine percent provided information on the use of
vasopressin. One guideline indicated that its use should be avoided, and another suggested
contacting the transplant team prior to use for extra-renal organ donors. One pediatric guideline
recommended the use of vasopressin if the donor was not hemodynamically stable; otherwise,
desmopressin was indicated. When vasopressin was recommended, three guidelines indicated
that it had to be discontinued 1 h prior to OR (n = 1), 1–2 h prior to OR (n = 1) or 2 h prior to
OR (n = 1). Tables 10 and 11 list the recommended dosages.
Table 10. Desmopressin: Suggested dosages
Adults
Pediatrics
1 µg q6h prn
intranasal (no dose indicated)
1 µg push _ 2
0.25–1 µg per dose
1–2 µg push
5–10 µg ETT or 0.25–4 µg IV
2 µg infuse over 30 minutes
(2 guidelines)
1–4 µg IV, IM or SC q12–24h prn
2–4 µg q4–6h or 1 µg/h infusion
2 ug, then 4 µg repeat as needed
4 µg q2h _ 2 call MD if 3rd dose required (2 guidelines)
Table 11. Vasopressin: Suggested dosages
Adults
1 U/h, titrate to target u/o
2 U bolus, 1 U/h titrate to target u/o
(2 guidelines)
2.5–5 units IV q4h
Pediatrics
0.5–3 mU/kg/h
5–15 mU/kg/h
(2 guidelines)
6–15 mU/kg/h
Oliguria diagnosis and therapy
Only 24% of guidelines provided indications on oliguria. Each of these suggested the use of
diuretics to treat oliguria. Three specifically identified using furosemide to treat a urine output of
< 50 ml/h, ensuring a corrected central venous pressure and blood pressure prior to its use. The
remaining guideline defined oliguria as a urine output of < 50 ml/h with a CVP of > 12 mm Hg,
with no indication of treatment.
15
Glucose
Seventy-one percent of guidelines provided information on regulation of blood sugar (BS). The
use of insulin to maintain target BS was identified in 65% of guidelines. Two of these suggested
that insulin be used with caution for increased BS as potassium boluses may be required prior to
insulin use. Two adult guidelines recommended a sliding scale for insulin infusions (no dosages
given), and two others simply indicated “insulin drip”. All titrated dosages to meet target BS
levels; however, many did not provide target parameters. Table 12 outlines the target values
provided for BS and insulin dosages.
Table 12. Regulation of blood sugar
BS Targets
Lower limits
Upper limits
Insulin Dosages
Adults
Pediatrics
a
Range
Median
GLa
4–8 mmol/L
10–20 mmol/L
6 mmol/L
12 mmol/L
5
6
0.5 –1 U/h
0.025–0.1 U/kg/h
0.75 U/h
0.025 U/kg/h
2
3
Number of guidelines that provided target values for variable of interest.
16
Hematology
Sixty-five percent of guidelines referred to the use of blood products. Six of these identified the
use of packed red blood cells; of these, four indicated this was to maintain a target hematocrit,
one that it was to maintain a target hemoglobin and one indicated no target. Three guidelines
provided a general comment concerning the use of blood products, such as “treat
coagulopathies”. Three others identified the use of whole blood to maintain either a target
hematocrit (n = 2) or a circulating blood volume (n = 1). Other blood products mentioned were
fresh frozen plasma (n = 3), platelets (n = 2) and cryoprecipitate (n = 1). Only one guideline
specified the use of CMV negative-only products. Table 13 lists hematocrit and hemoglobin
targets. Two guidelines linked their hematocrit targets to specific organs: ≥ 20% for kidney
donors or ≥ 30% for heart or liver donors.
Table 13. Hematocrit and hemoglobin targets
Hematocrit
Hemoglobin
a
Range
20–35%
8–12 g/dL
GLa
6
3
Median
30%
9 g/dL
Number of guidelines that provided target values for variable of interest.
Temperature
Targets
All but one guideline mentioned the importance of body temperature control. When the method
for temperature measurement was identified (n = 8), 63% indicated that temperatures should be
measured rectally. Table 14 summarizes body temperature targets.
Table 14. Body temperature targets
Lower limit
Upper limit
a
Range
35–36.5° C
37–38° C
GLa
14
11
Median
35.3° C
37.5° C
Number of guidelines that provided target values for variable of interest.
Methods to maintain temperature
Various methods to maintain body temperature within target limits were suggested (n = 16):
warming blankets (75%), warming IV fluids (43%), warming inspired gases (25%), heating
lamps (13%) and cooling blankets (13%). Other guideline-specific suggestions to maintain target
body temperatures were ambient room temperature, hats, socks, Bair huggers and uncovering the
patient.
17
Infection
Only 35% of guidelines mentioned antibiotic use. Of these, 2 had general comments:
“antibiotherapy indicated” and “discuss with transplant coordinator”. One guideline suggested
broad spectrum antibiotics, and three had very specific indications for antibiotic use: “1 hour
prior to OR: cefazolin IV (1 gm adults, 30 mg/kg peds to max 1gm) or if in hospital > 72 hrs,
cefotaxime IV (1 gm adults, 40 mg/kg peds to max 1 gm), and metronidazole IV (500 mg adults,
15 mg/kg max 500 mg peds).”
Additional Treatments
Corticosteroids
Only 35% of guidelines suggested the use of methylprednisolone. Three guidelines indicated its
use for lung donors, and another guideline stated, “it contributes to stability and improved
oxygenation”.
The following dosages were provided:
•
10 mg/kg, max 1g (n = 1)
•
15 mg/kg, max 1g (n = 2)
•
1 g IV _ 1 (n = 3)
Hormone therapy
Only 1 guideline mentioned the use of hormonal replacement therapy. It consisted of the
following:
•
methylprednisolone: 15 mg/kg IV (not to exceed 1 gm)
•
insulin infusion: 0.5–1.0 U/h starting dose
•
T4: 40 µg bolus IV _ 1
•
desmopressin infusion: 1µg/h
This therapy was indicated to “to replace the loss of hypothalamic function and to maintain cell
metabolism”.
18
Investigations/Supportive Testing
Supportive investigations required during the management of organ donors is detailed in
table 15.
Table 15. Supportive testing
Chest x-ray
% of GL
82%
Electrocardiogram
Echocardiogram
71%
65%
Bronchoscopy
41%
Cardiac angiogram
Cardiology consult
24%
18%
a
Indicationsa
Lung donors (n = 5)
Heart donors (n = 1)
Heart donors (n = 1)
Heart donors (n = 5)
Tx coordinator request (n = 1)
Lung donors (n = 4)
Tx coordinator request (n = 1)
N/Ab
N/A
When mentioned.
N/A = not applicable
b
19
III. Canadian Donor Organ Eligibility Criteria
Information on donor organ eligibility criteria was obtained using the same methodology as that
used to obtain donor organ management guidelines (see “Methodology for Data Gathering and
Inclusion”, page 3). According to the centers surveyed, donor organ eligibility is not an
intensive-care-based responsibility. One adult center provided donor organ eligibility criteria. All
other hospital centers refer decisions to determine eligibility to their respective OPOs.
OPO Organ Donor Eligibility Criteria
Ten OPOs provided information on donor organ eligibility criteria. One provided a detailed
document outlining eligibility criteria for individual organs as well as donor-specific
contraindications. This document was dated 1993, and the OPO explained that it currently
assesses eligibility by encouraging all centers to refer potential organ donors to the OPO,
stipulating that the only contraindication is HIV/AIDS. Six OPOs stated that “eligibility was
assessed on a case by case basis”. Three of these also provided a list of absolute
contraindications (table 16). One OPO provided a draft protocol for organ donor eligibility;
however, approval is outstanding, and the protocol is therefore not included in this analysis.
Another OPO indicated it uses the Canadian Standards for tissue and organ donations, and its
only absolute contraindication is West Nile virus. One final OPO indicated that it “looks at
everything and does a medical assessment, and then consults with individual transplant
programs”.
Table 16. Absolute contraindications to donor eligibility
Positive tests for
anti-HIV-1 or anti-HIV-2
hepatitis B or C
human T-cell lymphotropic viruses types I and II
History or evidence of HIV high-risk behaviours, even if HIV-antibody negative
Death with neurological disease of an unestablished etiology (i.e., ALS, Alzheimer’s, multiple
sclerosis, Parkinson’s)
Prion-related disease (i.e., CJD, family hx CJD, recipient of human-derived pituitary growth
hormone or dura mater)
Active systemic bacterial, viral or fungal infections
Rabies
Leukemias, lymphomas and active malignancies
Progressive multi-focal leukoencephalopathy
Subacute sclerosing panencephalopathy
20
IV. International Issues in Organ Donor Management
Worldwide, organ donation and the medical management of organs donors are at various stages
of development. Among the countries with mature systems in this field, recent efforts have
focused on optimizing the medical management of organ donors to maximize organ yield per
potential donor. Countries such as Spain, the United States, the United Kingdom, Australia and
members of Eurotransplant (comprising Austria, Belgium, Germany, Luxembourg, the
Netherlands and Slovenia) are at the forefront of this movement.
Nonetheless, standardized international donor management strategies remain elusive. According
to Leo Roels, Scientific Program Director of the International Transplant Coordinators Society,
“Organ exchange organizations and organ procurement organizations may have some guidelines,
but at the bottom end it’s the ICU physician who will decide upon how to treat a potential
donor.”1 He also highlighted recent efforts by the North American Transplant Coordinators
Organization and Donor Action Foundation to encourage standardization; the former edited
Donor Management Issues, published by D.J. Powner, and the latter is developing an
international e-learning course on donor management.
Spain
The Organización Nacional de Trasplantes (ONT) was formed in 1989 to address declining
organ donation rates in Spain. ONT focuses on identifying potential donors and obtaining
consent. They have implemented a standardized donation process in every hospital in Spain. The
Spanish Model2 consists of a team of specially trained individuals (physicians and nurses),
separate from the medical/transplant teams, who are responsible for raising the donor rate in all
hospitals. Among other things, these teams identify all potential donors and handle the
evaluation and management of the donor. Donor management guidelines included in the Spanish
model are outlined in Appendix II.3
The United States
The United Network for Organ Sharing (UNOS), incorporated in 1984, is “a private, non-profit
corporation that, with government oversight, develops, implements, and monitors policies in a
national health system relative to transplantation. In 1986, UNOS was awarded the federal
government contract to operate the national Organ Procurement and Transplantation Network
(OPTN). Subsequent regulations required all transplant centers to join the OPTN and be
governed by UNOS policies. The OPTN is mandated to assure the effectiveness, equity and
quality of the nation’s organ procurement, allocation and distribution system.”4
UNOS has developed a Critical Pathway for the Organ Donor (see Appendix III). This document
has been endorsed by the Association of Organ Procurement Organizations, the American
Society of Transplantation, the American Society of Transplant Surgeons and the North
American Transplant Coordinators Organization. Its use has resulted in an 11.3% increase in the
number of organs transplanted per 100 donors.5
21
There are 59 organ procurement organizations governed by UNOS policies. All were contacted
and requested to provide donor organ management guidelines and eligibility criteria (as it is not
mandatory that they use the Critical Pathway). Details on organ donor management in the United
States will be provided in a separate presentation at the Canadian Forum on Medical
Management to Optimize Donor Organ Potential.
Another example of U.S. organ donor management guidelines is provided in Appendix IV. It is
the New England Organ Bank guideline (revised Jan 2001).
The United Kingdom
UK Transplant is a special health authority within the National Health Service. Its key role is to
match and allocate donated organs. It also supports transplantation services across the United
Kingdom and is responsible for “contributing to the development of performance indicators,
standards and protocols which guide the work of organ donation and transplantation”.6 UK
Transplant is directly accountable to health ministers in Scotland, Wales and Northern Ireland
and to Parliament through the Department of Health in England.
The United Kingdom Transplant Coordinators Association is the association that promotes organ
donation, best practices in transplantation and supports transplant coordinators working in the
United Kingom. (See also United Kingdom Hospital Policy for Organ and Tissue Donation.7)
A standardized donor management technique was developed at the Papworth Hospital in
Cambridge, England. Murali et al. (2003)8 have published the most recent description of this
approach. Guidelines from the Papworth Hospital for the management of the multi-organ donor
are provided in Appendix V. Further details on the Papworth approach to organ donor
management will be provided in a separate presentation at the Canadian Forum on Medical
Management to Optimize Donor Organ Potential.
Australia
The Federation of Australia is composed of six states and one territory. Five states have
transplant programs. “The delivery and organization of health services is a state responsibility
although only the central (Federal) government has taxing powers; it therefore controls the funds
available for health care.”9 In 1977, South Australia adopted the Spanish Model, described
above. “Since the introduction of the modified Spanish model, the organ procurement rate in
South Australia is double the rate of the rest of Australia”10 (23 vs. 10.5 donors per million
population).
The Alfred Hospital in Melbourne has developed a successful system of transplant coordination
and organ allocation.11 Its system is considered a good example of the Australian approach to
organ donation and transplantation. A detailed description of the medical management of the
potential organ donor at the Alfred Hospital has been published.12
22
Eurotransplant
The Eurotransplant International Foundation is responsible for the organization and allocation of
organ donation in Austria, Belgium, Germany, Luxembourg, the Netherlands and Slovenia. This
international framework includes all transplant hospitals, tissue-typing laboratories and hospitals
where organ donation takes place.13
The Leuven University Hospital in Belgium has developed a secure-access website containing
organ donation information and protocols, including multi-organ donor management guidelines
(see Appendix VI). The information contained on this website is accessible to all members of the
hospital’s donor hospital network and is licensed and protected for the hospital and the network.
According to Frank Van Gelder, Senior Transplant Coordinator, Department of Transplant
Surgery, since the implementation of this simplified protocol the hospital has seen a 40%
increase in donors.14
23
V. Conclusion
This analysis of Canadian management guidelines was based on 17 unique documents. These
guidelines are for multi-organ donation and are generally consistent in content, although many
do not address all variables of interest. For oxygenation and ventilation, discord occurs in PaO2
and tidal volume targets, with a variety of values cited. Target pressures for organ perfusion
often differ between adult and pediatric guidelines (the latter providing age-adjusted values).
Few guidelines provide targets for pulmonary capillary wedge pressure, systemic vascular
resistance, cardiac index and left ventricular stroke volume.
Standard care for invasive monitoring consists of an arterial and a central venous line. Only eight
guidelines provide information on pulmonary artery catheterization. A majority of guidelines cite
dopamine as the drug of choice for cardiovascular support. The management of fluid balance,
electrolytes, hematology and body temperature do not differ greatly from standard ICU care.
Definitions of diabetes insipidus are mainly based on exceeding a specific urine output, with a
few guidelines including targets for urine osmolality (and serum), sodium and specific gravity.
Therapy consists of desmopressin (in all cases), at a wide variety of dosages, and (in some cases)
vasopressin.
Supportive testing and investigations identified, to varying degrees, are chest x-ray,
electrocardiogram, echocardiogram, bronchoscopy, cardiac angiogram and cardiology
consultations. Areas covered by a minority of guidelines include the use of antibiotics,
corticosteroids and hormone replacement therapy.
Decisions to determine donor organ eligibility are referred to the provincial organ procurement
organizations. Generally, eligibility is assessed on an individual basis, taking into consideration
recipient need at that point in time. Slight variations exist between OPOs for absolute
contraindications; however most included HIV/AIDS, West Nile virus, active infections and
malignancies.
International issues in organ donor management are directly related to the level of maturity of a
country’s particular program. Recent efforts to optimize the medical management of organ
donors (and thus maximize organ yield per potential donor) are under way. Countries at the
forefront of this movement are Spain, the United States, the United Kingdom, Australia and
members of Eurotransplant.
24
Appendix I – Canadian Organ Procurement
Organizations
Note: The following descriptions are based on the authors’ understanding of surveys received.
British Columbia
OPO is a separate entity from hospitals. Stated that their guidelines covered the entire province
but did not provide a list of hospitals. Received a reply from one PICU to confirm this. Received
separate GL from one adult center.
Alberta
2 OPOs (Northern and Southern Alberta). Stated they each cover specific territory of province
and provided list of hospitals covered. Hospitals (in both regions) that responded confirmed they
are covered by OPOs. Northern provided pediatric and adult guidelines, Southern has no
documented guidelines at this time. PICU in Northern provided additional GL.
Saskatchewan
OPO located and functions within hospital. Only reply received from this province was that of
OPO. Stated their guidelines covered all hospitals within the province, provided list of hospitals.
Manitoba
OPO located and functions within hospital. Stated their guidelines covered hospitals in province
and provided list. Responses from hospitals confirmed this. No additional GL received.
Ontario
3 OPOs functioning within the province (transitional period). Trillium has in-hospital
coordinators, “draft” guidelines provided which were not recorded as not yet in use.
Quebec
OPO separate entity from hospitals, provided pediatric and adult guidelines. Resource Nurses
(IRs) have dedicated organ donor roles within the hospitals (OPO “Red Binders” on units with
IRs). OPO coordinators also help manage patients.
New Brunswick
OPO located and functions within hospital. Only received reply from OPO for this province,
stated their guidelines covered all hospitals within the province, provided list of hospitals.
Prince Edward Island
No OPO covered by Nova Scotia and New Brunswick OPOs.
25
Nova Scotia
OPO located and functions within one of hospitals contacted. Stated their guidelines covered
hospitals in province and provided list. Responses from hospitals confirmed this. No additional
GL received.
Newfoundland
OPO located and functions within hospital contacted. Only received reply from OPO, stated their
guidelines covered all hospitals within the province and provided list.
Yukon
Not an OPO. Their donors are covered by BC Tx.
Canadian Association of Transplantation and Canadian Society of
Transplantation
No guidelines or eligibility criteria.
26
Appendix II – Spanish Guidelines
MANUAL OF DONATION OF ORGANS FOR HEALTH PROFESSIONALS
MAINTENANCE OF THE DONOR OF ORGANS
(These guidelines have been translated from the original Spanish.)
Once established, encephalic death, independently of the cause that originates it, results in
ischemic-necrosis of the neurological structures. A series of secondary pathophysiological
alterations lead to the absence of function of this great "regulating organ" that is the brain. This
fundamentally produces:
1. Absence of spontaneous breathing.
2. Hemodynamic instability.
3. Loss of control of corporal temperature.
4. Loss of control of fluid and electrolyte balance.
5. Alterations in hormonal secretion.
The most frequently occurring complications are: hypotension, hypotherma and neurogenic
diabetes insipidus (NDI), NDI contributes to the aggravation of hemodynamic instability by
causing polyurias and secondary electrolytic alterations.
All these aspects endanger the viability of the transplantable organs, turning the multi-organ
donor into a critical patient requiring strict control and monitoring (tables I and II), as well as an
energetic treatment and in many occasions the complexity of a patient with multi-system failure.
Table I. Monitoring the organ donor
ECG.
Arterial tension.
Central venous pressure.
Hourly Diuresis.
Arterial Gasometry.
Saturation of O2 by means of pulsoxymetry.
Temperature.
The main targets in the maintenance of the donor of organs are:
1.
2.
3.
Cardiocirculatory Stability
Suitable Oxygenation
Correction and treatment of other problems like neurogenic diabetes insipidus, electrolytic
arrhythmias, alterations, prevention of infections, etc...
In table II a summary of maintenance objectives can be seen.
27
Table II. Maintenance objectives
Cardiac Frequency ≤ 100 bpm.
SBP ≥ 100 mm Hg.
CVP: 10–12 cm H2O.
PCP: 8–14 mm Hg.
Diuresis: > 1 cc/kg/h in adults, > 2 cc/kg/h in children
Temperature > 35ºC.
Arterial Gasometry:
pH: 7,35–7,45.
PaO2 values next to 90–100 mm Hg.
PaCO2: 35–45 mm Hg.
Hematocrit ≥ 30% (if multi-organ donor must be ≥ 35%)
1 HEMODYNAMIC Control :
To maintain hemodynamic stability:
•
•
•
•
•
•
Arterial hypotension is the most frequent alteration.
It is recommended to maintain systolic ABP ≥ 90–100 mm Hg.
The initial treatment consists of volume administration:
o Dependant upon the volume of the losses, electrolyte values and levels of
hemoglobin.
o The contribution must be controlled hourly, because large volumes are
useful to maintain good renal flow but can jeopardize cardiac, pulmonary
and hepatic donation.
Monitoring CVP or PCP using Swan-Ganz catheter.
If normovolemia is obtained (CVP 10–12 cm H2O, PCP 8–14 mm Hg) and
hypotension persists, add vasoactive drugs at minimum doses. Drugs of choice are
DOPAMINE, DOBUTAMINE and NORADRENALINE.
Hourly control of diuresis. Values of concern: < 50 or > 200 cc/h.
If in spite of adequate fluid resuscitation (CVP of 10–12 cm of H20/PCP of 8–14 mm Hg),
arterial hypotension continues, initiate treatment with inotropic drugs. The suggested order is the
following one:
1. Dopamine.
It is the drug of choice for its beneficial effect on renal flow and some authors have found a
relation between the decreased appearance of tubular necrosis acute postransplant and the use of
dopamine in doses < 5 µg/kg/min.
Avoid exceeding doses of 10 µg/kg/min (which worsen cardiac and hepatic perfusion through its
alpha-agonist effect).
28
2. Dobutamine.
Its fundamental indication would be in polytrauma donors with myocardial contusion where it is
suspected that ventricular dysfunction is the fundamental cause of the hypotension. Use with
caution since it can increase vasodilation and worsen the hemodynamic situation, by diminishing
systemic vascular resistance.
3. Other vasopressor drugs: Noradrenaline and adrenalin.
Their use is restricted to donors with persistent hemodynamic instability in spite of adequate
volume resuscitation and support with dopamine of 10 µg/kg/min. It is necessary to consider that
both can produce hyperglycemia. Therefore a strict control of glycemia must be maintained with
precise dosing of insulin. The vasoconstriction invalidates the CVP measurements, thus it is
necessary to place a Swan-Ganz catheter to optimize the handling of fluids and vasoactive drugs.
Noradrenaline produces arterial vasoconstriction, diminishing blood flow to the liver, pancreas
and kidneys. Thus the simultaneous use of low doses of dopamine are advised to improve renal
flow.
If the donor needs large doses of noradrenaline for long periods of time, it is recommended to
change to an infusion of adrenalin. This drug has the advantage of improving hepatic blood flow.
The use of high doses of these alpha-stimulants can cause vasoconstriction producing tissue
hypoperfusion. This results in frequent assessment of the function of the different organs and
must be communicated to the surgical transplant teams (who will evaluate organ viability).
2. ARRHYTHMIAS.
Cardiac arrhythmias of atrial and ventricular origin can occur, as well as diverse degrees of
blockade. Causes are multi-factorial, the most frequent being:
1. Hypovolemia.
2. Hypotension.
3. Hypothermia.
4. Catecholamine use.
5. Myocardial contusion.
6. Gasometric alterations (hypoxia and changes in pH).
7. Secondary electrolytic alterations due to neurogenic diabetes insipidus.
Therefore, in the prevention of arrythmias it is necessary to correct hypotherma and all factors
leading to metabolic or hemodynamic disturbances.
3. SUITABLE OXYGENATION And RESPIRATORY CARE.
• To maintain the permeability of the aerial route.
• To prevent atelectasis by means of respiratory physiotherapy, postural drainage,
bronchial suctioning of secretions, etc.
• To maintain arterial oxygen saturation between 95 and 100% by means of FiO2 up to
100% and hemoglobin up to 10–12 g/L.
• For lung donation, the target FiO2 is < 50% to avoid pulmonary toxicity and PEEP of
5 cm H2O to prevent pulmonary collapse.
29
The lung donor requires maintenance with respirators of volumetric type and the routine use of
PEEP of 5 cm H2O to prevent atelectasis which would contraindicate the extraction of this organ.
In these donors the FiO2 must be strictly controlled to avoid pulmonary toxicity by oxygen.
Maintain CVP between 5–10 cm of H2O avoiding volume overloads that could produce
pulmonary edema. Use a tidal volume of 8–10 ml/kg and obtain a maximum tip of pressure in
aerial routes inferior to 30 cm of H2O to avoid pulmonary damage by hyperpressure.
In some cases donors can present/display neurogenic pulmonary edema. This can produce a
severe hypoxia that can jeopardize the viability of the organs to be transplanted. In donors with
pulmonary edema who require elevated levels of PEEP, it could be necessary to insert a SwanGanz catheter to adapt treatment based on cardio-respiratory variables.
In all cases, frequent control of arterial gasometry and arterial oxygen saturation is necessary to
detect episodes of desaturation early.
Finally and as in any other type of critical patient, the endobronchial suctioning will be carried
out with maximum conditions of asepsis to avoid local respiratory infections or infections
leading to sepsis.
4. METABOLIC ALTERATIONS.
1. Electrolytic Disturbances.
The most frequent are hypernatremia, hypokalemia, hypomagnesemia, hypocalcemia and
hypophosphatemia. Early correction of electrolytic alterations is important in order to avoid
arrhythmias that could lead to cardiovascular instability. With the goal of obtaining a correct
electrolyte administration, measurements should be made q3–4hrs. Besides checking for
imbalances this allows for adequate replacements of Na and K.
2. Hyperglycemia.
The etiology of hyperglycemia is multi-factorial and could also be due also to a peripheral
resistance to insulin.
Amoung its causes it it is necessary to emphasize: infusion of inotropes, resuscitation with
liquids that contain glucose, previous treatment with corticosteroids, endogenous catecholamine
secretion during the process of cerebral coning, hypotherma, etc...
Hyperglycemia can result in a hyperosmolar situation with intracellular dehydration, metabolic
acidosis and polyuria (which in turn contributes to hypovolemia). In all cases it is necessary to
correct hyperglycemia with a rapid intravenous infusion of insulin. Use a continuous infusion of
insulin titrated to maintain serum glucose at approximately 150 mg/dl.
5. HYPOTHERMIA.
Hypothermia results from the destruction of the central hypothalamic thermoregulator.
Bradycardia and other severe arrythmias are the principle consequences.
Maintain a core body temperature ≥ 35ºC.
Maintain donor temperature with warming blankets, heating lamps, an ambient room
temperature of 20–22ºC and warm infusion fluids.
30
6. NEUROGENIC DIABETES INSIPIDUS
Brain death can cause diabetes insipidus which presents as a polyuria. Treat with precise volume
replacement and/or administration of desmopressin.
7. HORMONAL ALTERATIONS
Following brain death there is a rapid depletion of thyroid hormones. Levels of T3 or T4 may be
practically undetectable 14 hours after brain death. Normal levels of thyroid stimulating hormone
(TSH) are maintained in these cases. Also seen is an important reduction in levels of antidiuretic
hormone (ADH), cortisol and insulin.
8. PREVENTION OF INFECTIONS.
• Manipulation of catheters, suctioning, etc., should be performed with strict aseptic
technique.
• Prophylactic use of antibiotics is recommended.
• Ocular hygene is important: keep moist with physiological saline.
The diagnosis of local infections (adequately treated) is not an absolute contraindication to organ
donation. Assessment is based on the results of bacteriological cultures and consultations
between the intensivist and surgical transplant teams.
31
Appendix III — UNOS Critical Pathway
Collaborative
Phase I
Practice
Referral
The following professionals
may be involved to enhance
the donation process.

Notify physician
regarding OPO referral
Check all that apply.

Physician

Critical care RN

Contact OPO ref:
Potential donor with severe
brain insult

OPC on site and
begins evaluation: Time
___Date ___

Organ Procurement
Organization (OPO)

Ht____ Wt ____ as
documented

OPO Coordinator
(OPC)

ABO as documented
_____

Medical Examiner
(ME)/Coroner

Notify house
supervisor/charge nurse of
presence on unit

Respiratory

Laboratory

Radiology

Anesthesiology

OR/Surgery staff

Clergy

Social worker
Phase II
Phase III
Phase IV
Phase V
Declaration of Brain Death and Consent
Donor Evaluation
Donor Management
Recovery Phase

Brain death documented

Obtain pre/post transfusion
blood for serology testing (HIV,
Hepatitis, VDRL, CMV)
Time _____ Date _____

Pt accepted as potential donor

Obtain lymph nodes and/or
blood for tissue typing
 MD notifies family of death

Plan family approach with OPC

Notify OR & anesthesiology of
pending case

Offer support services to family
(clergy, etc)

OPC/Hospital staff talks to family
about donation

Family accepts donation


Chest & abdominal
circumference

Cardiology consult as
requested by OPC
Time _____ Date _____
ME/Coroner notified

Organ recovery process
discontinued – donor organs
unsuitable for transplantation

ME/Coroner releases body for
donation

Family/ME/Coroner denies
donation – stop pathway – initiate
postmortem protocol – support family.
32

Organ placement

OPC sets tentative
OR time

Checklist for OR

OR
Supplies given to

Prepare patient for
transport to OR

Insert arterial line/
CVP/2 large-bore IVs

Notify house supervisor of
pending donation

Lung measurements per CXR
by OPC

OPC obtains signed consent &
medical/social history

OPC writes new
orders
 IVs
 Pumps
 O2
 Ambu
 Peep valve

Transport to OR
Date ________
Time ________

OR nurse reviews
consent & brain death
documentation & checks
patient’s ID band
Collaborative
Phase I
Practice
Referral
Labs/ Diagnostics
Phase II
Phase III
Phase IV
Phase V
Declaration of Brain Death and Consent
Donor Evaluation
Donor Management
Recovery Phase

Review previous lab results

Blood chemistry

Review previous hemodynamics

CBC + diff

UA

PT, PTT

ABO

Liver function tests
 C&S
 A Subtype

Blood culture _ 2 / 15 minutes
to 1 hour apart

Sputum Gram Stain & C & S

Type & Cross Match ____#
units PRBCs

CXR
 ABGs

EKG
 Echo

Consider cardiac cath

Consider bronchoscopy

Determine need for
additional lab testing

CXR after line
placement (if done)

Serum electrolytes

Rx
H & H after PRBC

PT, PTT

BUN, serum
creatinine after correcting
fluid deficit

Notify OPC for
___ PT >14___ PTT <
28
___ Urine output is
< 1 mL/kg/hr
___ > 3 mL/kg/hr
___ Hct < 30 / Hgb < 10
___ Na > 150 mEq/L
33

Labs drawn in OR as
per surgeon or OPC
request

Communicate with
pathology: Bx liver and/or
kidneys as indicated
Respiratory

Pt on ventilator

Suction q 2 hr

Reposition q 2 hr
Prep for apnea testing: set FiO2
@ 100% and anticipate need to
decrease rate if PCO2.< 45 mm Hg

Maximize ventilator settings to
achieve SaO2 98–99%

Notify OPC for
____ BP < 90 systolic

PEEP = 5cm O2 challenge for
lung placement FiO2 @ 100%, PEEP
@ 5 _ 10 min

Portable O2 @ 100%
FiO2 for transport to OR
____ HR < 70 or > 120

Ambu bag and PEEP
valve
____ CVP < 4 or > 11


ABGs as ordered
____ PaO2 < 90 or

VS q 1°
____ SaO2 < 95%

Check NG placement & output
Move to OR

Use warming/cooling blanket
to maintain temperature at 36.5–37.5
°C
Treatments/ Ongoing
Care

NG to low intermittent suction

Obtain actual Ht _____ & Wt
_____ if not previously obtained
Set OR temp as
directed by OPC
Post mortem care at
conclusion of case

Medication as requested by OPC

Fluid resuscitation – consider
crystolloids, colloids, blood
Medications

DC meds except pressors &
antibiotics

Broad-spectrum antibiotic if
not previously ordered

DC antidiuretics

Diuretics as needed

350 U heparin/kg or
as directed by surgeon

Vasopressor support to
maintain BP > 90 mm Hg systolic

Electrolyte imbalance:
consider K, Ca, PO4, Mg
replacement

Hyperglycemia: consider
Insulin drip

Oliguria: consider diuretics

Diabetes insipidus: consider
antidiuretics

Paralytic as indicated for
spinal reflexes
Optimal Outcomes
The potential donor is
identified & a referral is
made to the OPO.
The family is offered the option of
donation & their decision is
supported.
The donor is evaluated & found to be
a suitable candidate for donation.
Shaded areas indicate Organ Procurement Coordinator (OPC) Activities
34
Optimal organ function is
maintained.
All potentially suitable,
consented organs are
recovered for transplant.
Cardio-Thoracic Donor Management
1.
•
Early echocardiogram for all donors: Insert pulmonary artery
catheter (PAC) to monitor patient management (placement of the
PAC is particularly relevant in patients with an EF < 45% or on high
dose inotropes.)
use aggressive donor resuscitation as outlined below.
2.
•
•
•
Electrolytes
Maintain Na < 150 meq/dl
Maintain K+ > 4.0
Correct acidosis with Na Bicarbonate and mild to moderate
hyperventilation (pCO2 30–35 mm Hg).
3.
•
•
Ventilation Maintain tidal volume 10–15 ml/kg
keep peak airway pressures < 30 mm Hg
maintain a mild respiratory alkalosis (pCO2 30–35 mm Hg).
4.
Recommend use of hormonal resuscitation as part of a
comprehensive donor management protocol  Key elements
Tri-iodothyronine (T3): 4 mcg bolus; 3 mcg/hr continuous infusion
Arginine Vasopressin: 1 unit bolus: 0.5–4.0 unit/hour drip (titrate
SVR 800–1200 using a PA catheter)
Methylprednisolone: 15 mg/kg bolus (Repeat q 24º PRN)
Insulin: drip at a minimum rate of 1 unit/hour (titrate blood glucose
to 120–180 mg/dl)
Ventilator: (See above)
Volume Resuscitation: Use of colloid and avoidance of anemia are
important in preventing pulmonary edema
albumin if PT and PTT are normal
fresh frozen plasma if PT and PTT abnormal (value ≥ 1.5 _ control)
packed red blood cells to maintain a PCWP of 8–12 mm Hg and Hct
> 10.0 mg/dl
•
•
•
•
•
•
•
•
•
5.
•
•
•
•
•
•
•
When patient is stabilized/optimized repeat echocardiogram.
(An unstable donor has not met 2 or more of the following criteria.)
Mean Arterial Pressure ≥ 60
CVP ≤ 12 mm Hg
PCWP ≤ 12 mm Hg
SVR 800–1200 dyne/sec/cm5
Cardiac Index ≥ 2.5 l/min/M2
Left Ventricular Stroke Work Index > 15
dopamine dosage < 10 mcg/kg/min.
The Critical Pathway was developed under contract with the U.S. Department of Health and Human Services,
Health Resources and Services Administration, Division of Transplantation.
36
Hormonal Resuscitation of the Organ Donor
Brain-dead donors who fail conventional resuscitation measures as manifested by a poor cardiac
output, inadequate organ perfusion pressures, and increasing lactic acidosis often respond to
three-drug hormonal resuscitation (1). Administration of a methylprednisilone bolus and
infusions of arginine vasopressin and triiodothyronine to 701 brain-dead donors resulted in a
22.5% increase in the number of organs transplanted per donor(1). Hormonal resuscitation was
beneficial for donors both under, and over, age 40. Hearts recovered from hormonal resuscitation
donors have a significantly reduced 30 day mortality and a significant reduction in prolonged
graft dysfunction (2).
Bibliography
1. Transplantation 75:482–7, 2003. Aggressive Pharmacologic Donor Management Results in
More Transplanted Organs.
2. Abstract, International Congress of the Transplantation Society. Transplantation 74:205,
2002. Hormonal Resuscitation Yields More Transplanted Hearts with Improved Early
Function.
3. Hormonal Resuscitation Yields More Transplanted Hearts with Improved Early Function.
Transplantation 75: April 27, 2003.
Donor-Related Malignancies
Transmission of donor malignancies is rare with 18 cases from 34,933 cadaver donors and 3
cases from 32,052 living donors being reported to UNOS from 1994–2001 (1,2). Donors with
past histories of certain types of cancers may be considered as donors (3) including certain types
of primary CNS tumors (4). Tumors that pose a high transmission risk include choriocarcinoma,
melanoma, lymphoma, and carcinoma of the lung, colon, breast, kidney and thyroid. High risk
donors include glioblastoma multi-forme, high grade astrocytomas, medulloblastomas, and any
brain tumor donor who has undergone ventriculo-peritoneal shunting.
Bibliography
1 Transplantation 74:358–62, 2002. Transplant Tumor Registry: Donor Related Malignancies.
2.
Transplantation Reviews 16:177–91, 2002. Donor-Related Malignancies.
3.
Transplantation 70:1747–51, 2000. First Report of the United Network for Organ Sharing
Transplant Tumor Registry: Donors with a History of Cancer.
4.
Transplantation 73:579–82, 2002. Transplant Tumor Registry: Donors with Central
Nervous System Tumors.
37
UNOS Critical Pathway
Bibliography
1. Holmquist M., Chabalewski F., Blount T., Edwards, C. McBride V., Pietroski R. Critical
Care Nurse, 19(2):84–98, 1999. A Critical Pathway: Guiding Care for Organ Donors.
2. American Journal of Transplantation, 2:761–8, 2002. Increased Transplanted Organs from
the Use of a Standardized Donor Management Protocol. UNOS Critical Pathway for the
Organ Donor resulted in a 10.3% increase in organs recovered and an 11.3% increase in
organs transplanted. There was no reduction in the quality of the organs transplanted.
3. Circulation 106:836–41, 2002. Consensus Conference Report: Maximizing Use of Organs
Recovered from the Cadaveric Donor: Cardiac Recommendations. Heart donor criteria and
a donor management algorithm for heart recovery.
4. Abstract, International Congress of the Transplantation Society. Hormonal Resuscitation
Yields More Transplanted Hearts with Improved Early Function. Hearts from hormonal
resuscitation donors had significantly reduced early graft dysfunction and one-month patient
mortality.
38
Appendix IV – New England Organ Bank
The purpose of this document is to describe the principles of organ donor evaluation and
management to be followed for New England Organ Bank (NEOB) organ donors.
For each organ donor, the goals of donor evaluation and management include:
•
•
•
Determination of organ suitability for transplantation
Optimization of the function of these organs
Maximization of the number of organs recovered
General Principles
1. Absolute Contraindications to Organ Donation:
• Donor age > 80 years
• AIDS or HIV seropositivity
• Malignancy other than primary intracranial tumor or non-melanoma skin cancer
2. Donor Evaluation
Initial assessment shall include a review of the admission history and physical, hospital course,
temperature, electrolytes, CBC, fluid balance, hemodynamics, medications, infections,
pulmonary function, cardiac function, renal function, and liver function.
In extremely unstable cases (i.e., severe hypotension refractory to volume replacement and
pressors), plans should be made in consultation with the AMD to proceed to the operating room
(OR) as soon as possible for rapid hepatonephrectomy or nephrectomy. Aggressive management
should continue through the recovery surgery.
3. Determination of Organs Suitable for Transplantation
Organs may be deemed unsuitable based on donor age, organ injury, disease or gross
abnormality. Questions regarding organ suitability in marginal cases should be directed to the
medical director on call.
4. Initial Management Goals
• Restore and maintain normothermia
• Correct acid/base imbalances
• Optimize lung function
• Restore intravascular volume
• Normalize blood pressure
• Maintain hematocrit _ 30 %
• Treat severe hyperglycemia, central DI, DIC
39
5. Organ-specific Considerations
Lung / Heart-lung
Prevent pulmonary interstitial fluid overload
Prefer PRBC's for volume expansion if needed
Maintain FIO2 _ 40% and PO2 > 100 mm Hg
Prefer PEEP at 5 cm H20
Large ET tube for bronchoscopy
Liver / Pancreas
Prefer dopamine for tx of hypotension
Prefer minimal or no pitressin therapy (to
minimize splanchnic
vasoconstriction)
Avoid excessive crystalloid infusion (to
minimize liver congestion)
Maintain PO2 > 100 mm Hg
Heart
If hypotensive with low SVR, prefer pure vasoconstrictor
Cardiac cath indicated for pts. at risk for CAD
Maintain PO2 > 100 mm Hg
May request PA catheter to assess cardiac function
and determine appropriate therapy
Kidney
Prefer dopamine for tx of hypotension
Prefer brisk diuresis (urine output > 200
cc/h)
Maintain PO2 > 100 mm Hg
6. Specific Donor Management Problems
Poikilothermia
Loss of thermoregulatory function follows hypothalamic dysfunction in brain dead patients.
Passive heat loss may lead to progressive hypothermia which in turn may result in clinically
significant changes in organ function (EKG changes, depressed cardiac function, altered cellular
metabolism, etc.) It is far easier to prevent hypothermia than to reverse it. Therefore, patient
temperature should be carefully monitored and hypothermia should be treated early.
Treatment:
•
•
•
•
Maintain room temperature _ 75° F
Keep body and head well covered; use warming blanket as needed
Heat IV fluids with blood warmer, if temp < 35° C
Heated (45° C) humidified oxygen via ventilator (may cause thermal injury to airway)
Hypertension
Severe hypertension (systolic BP > 200 torr) is infrequently encountered in brain dead patients.
Most often, it is temporally related to brainstem herniation and is therefore self-limiting. Often,
this hypertension is associated with transient rhythm disturbances.
On occasion, severe hypertension persists following herniation.
Treatment:
•
•
•
•
Sodium nitroprusside (Nipride) infusion is the treatment of choice. The goal of
treatment should be to maintain the diastolic BP below 100 mm Hg. Nipride should
only be used in cases of severe, persistent hypertension, and should be discontinued
as soon as possible.
100 mg Nipride in 250 ml D5W yields a concentration of 400 mcg/ml.
Initial dosage should be 0.5 mcg/kg/min.
Titrate upward in increments of 0.25 or 0.5 mcg/kg/min to achieve desired BP
control.
40
Hypotension
Hypotension (SBP < 90 mm Hg) will develop in most brain dead patients at some point in the
donor management process. Many potential donors are hypotensive at the time of the initial
referral. Even brief intervals of severe hypotension can have significant deleterious effects on
end organs. Therefore, hypotension should be treated aggressively with therapy based on a sound
understanding of the cause of the hypotension.
A central venous pressure line and an arterial line are essential in order to manage hypotension
appropriately. When requested by the cardiac team, especially in hemodynamically unstable
donors, a pulmonary artery catheter may be introduced, and serial cardiac outputs and SVR
measurements can be collected.
Hypovolemia
Excessive intravascular volume loss (hemorrhage, third spacing, DI, fluid restrictions, etc.) is
common in potential organ donors, especially trauma victims. Neurogenic vasodilatation (loss of
both venous and arterial vasomotor tone) is present in the majority of donors as well. One or both
of these factors may contribute to a relative or absolute hypovolemia. Therefore, whenever
possible, intravascular volume deficits should be corrected prior to the use of vasoactive drugs.
(In practice, low to moderate dose dopamine infusion may be required to maintain adequate BP
during the initial interval of volume repletion. Once volume is restored, however, vasoactive
drugs should be used only as needed.) Care should be taken to avoid the development of
pulmonary interstitial fluid overload, especially in potential lung donors. Therefore, in most
cases, colloid (albumin, Plasmanate) and blood products (PRBCs) should be used in combination
with crystalloid solutions for volume expansion.
Treatment:
•
•
•
•
•
In general, IV fluid should be D5_NS at rate of 1 liter per 1/2 hour to raise CVP (in
adult pts. only; consultation with a pediatric intensivist is advised for fluid
management recommendations in pediatric donors)
Use albumin or Plasmanate to supplement crystalloid volume expansion
Monitor CVP closely; target is 8–10 cm H20; avoid excessive increase in CVP
PRBC's are indicated for Hct. < 30 % in hypovolemic donor
Monitor electrolytes carefully and supplement K+ as indicated
41
Decreased Vascular Resistance
Neurogenic vasodilatation (loss of both venous and arterial vasomotor tone) is present in the
majority of donors. Despite adequate volume restoration, some donors will require vasoactive
drug therapy directed at the underlying cause of the hypotension. Effective management of these
donors requires insertion of PA catheter for determination of cardiac filling pressures, CO, and
SVR. Due to the possibility of decreased perfusion to certain organs, vasoconstrictors should be
used with extreme caution. High dose vasoconstrictor therapy should be avoided in this setting.
The systemic vascular resistance (SVR) should be calculated based on thermodilution cardiac
output measurements.
If the SVR [(MAP or CVP) _ 80/CO] is < 400, vasoconstrictor therapy is indicated.
Treatment:
•
•
•
•
Norepinephrine Bitartrate (Levophed) 4 mg/250 ml D5W yields 16 mcg/ml
Initial dose is 0.02 mcg/kg/min; increase gradually to max. of 0.10 mcg/kg/min
Monitor CO, SVR, and cardiac filling pressures closely
Monitor urine output and serum creatinine closely
Depressed Cardiac Function
Following resuscitation from cardiopulmonary arrest, due to pre-existing cardiac disease, or
secondary to brainstem herniation, some donors may exhibit depressed cardiac function. These
patients will be hypotensive despite adequate volume restoration. The use of vasoconstrictors in
these patients will exacerbate cardiac dysfunction. Donors with depressed cardiac function
require inotropic and chronotropic support to maintain an adequate cardiac output. Effective
management of these donors requires insertion of PA catheter for determination of cardiac filling
pressures, CO, and SVR. If the cardiac index (CO/BSA in m2) is less than 2.0 L/min/m2,
inotropic therapy is indicated.
Treatment
•
•
•
•
•
Dopamine hydrochloride (Intropin) 400mg / 250 ml D5W yields 1600 mcg/ml
Initial dose is 2–4 mcg/kg/min. Titrate to increase SBP > 90 mm Hg.
Low dose dopamine (< 5 mcg/kg/min) has a salutary effect on renal blood flow
Monitor CO, SVR, and cardiac filling pressures closely
Monitor urine output
Respiratory Insufficiency
Brain dead patients require frequent pulmonary hygiene to prevent atelectasis and to maintain
adequate oxygenation. Positive end-expiratory pressure of 5 cm H2O ("physiologic PEEP") is
helpful, but higher levels of PEEP should be avoided to minimize potentially deleterious effects
on venous return and cardiac output. High FIO2 levels must also be avoided in potential lung
donors to prevent pulmonary oxygen toxicity. Ventilator settings should include a tidal volume
of 10 to 15 cc's per kg and a respiratory rate sufficient to maintain arterial PCO2 in the 40–45
mm Hg range.
42
Hypoxemia
Arterial oxygen saturations should be maintained at > 95%.
PAO2 levels should be = 100 mm Hg.
Hypoxemia should be treated aggressively to minimize injury to transplantable organs.
Treatment:
•
•
•
•
•
Maintain hematocrit > 30 %; transfuse PRBC's as necessary
Turn and suction patient frequently
Increase FIO2 by increments of 10%, recheck ABGs
Increase PEEP to > 5 cm H2O only as last resort
Lasix therapy may be indicated if CXR is c/w pulmonary edema
Note: If PAO2 persists at < 250 torr on 100% FIO2 , NEOB lung transplant programs will
exclude donor lungs for transplantation.
Hypercarbia
Apnea testing to confirm the diagnosis of brain death can result in significant hypercarbia
leading to respiratory acidosis. Careful attention should be paid to the patient's ventilatory status
and ABGs, especially following clinical exams for determination of brain death.
The ventilator rate should be increased as needed to normalize PACO2 levels in the 40 to 45 mm
Hg range.
Polyuria
Polyuria (urine output > 500 ml per hour) is frequently seen in brain dead patients. It may be due
to physiological diuresis, osmotic diuresis (mannitol, glucose), diuresis caused by hypothermia,
partial or complete diabetes insipidus, other diuretics, or a combination of the above. Excessive
polyuria due to osmotic diuresis or DI may lead to hypernatremia, hypokalemia, and
hyperosmolality. Serum potassium should be monitored and treated as indicated. Urine and
serum electrolyte levels and osmolality aid in the determination of the cause of polyuria.
Physiological diuresis
Aggressive volume restoration may result in a physiological diuresis. No treatment is warranted,
but intake and output should be monitored carefully.
Osmotic diuresis
Prior mannitol administration or excessive glucose infusion may result in an osmotic diuresis.
Treatment:
•
Mannitol administration should be avoided in this setting. Glycosuria and
hyperglycemia should be treated with sliding scale IV insulin therapy to normalize
blood glucose levels.
43
Diabetes insipidus
Once the abovementioned causes for polyuria have been excluded, the diagnosis of DI can be
made by evaluating the volume of urine output, urine specific gravity, urine and serum
electrolyte levels, and urine and serum osmolality. At least three of the following findings should
be present simultaneously to establish the diagnosis of DI:
•
•
Urine output > 500 ml per hour
Urine specific gravity < 1.005
Serum sodium > 155 mEq/L
Serum osmolality > 305 mOsm/L
Treatment:
•
•
•
•
Aqueous pitressin IV infusion (10 U / 250 ml D5W)
Initial dosage 1.2 U per hour (rate: 30 ml per hour)
Titrate Q. 15 min. to maintain u/o of 150–300 ml/hr
Discontinue for hourly u/o < 150 ml
In addition to Pitressin therapy, the free water deficit should be calculated and 50% of the
calculated deficit should be infused as rapidly as possible, preferably with a hypotonic solution
such as D5W or 0.5 NS.
The use of pitressin should be avoided when possible in liver and pancreas donors to minimize
the possibility of decreased perfusion to these organs.
44
Appendix V – Papworth approach
Philosophy
The Papworth philosophy is to assess the donor organs at the referral hospital whenever possible.
It is also to employ aggressive therapeutic intervention and invasive measurement in order to
optimise the physiological environment for the heart and lungs. Once all the possible
manoeuvres have been employed, the mechanical function of the heart and the gas exchanging
function of the lungs are reassessed. Then, and only then, is it appropriate to reject organs where
function falls below acceptable minimum targets.
The practical implications of this philosophy include increased financial expense and an
increased number of procurement journeys with no transplantable organs being obtained, but the
possibility of wasting transplantable organs will be minimized.
Management of the multi-organ donor
1. Infection Control
Organ retrieval should be carried out in an operating theatre to the standard of any other surgical
procedure. In particular, staff should follow the normal practice of limiting the number of
individuals present to those involved in that part of the procedure and a maximum of two visitors
(at the discretion of the Papworth surgeon). Movement of staff in and out of the theatre should be
kept to a minimum.
2. Ventilation
2.1 Ventilate to normocarbia (4.5–5.5 kPa) using large tidal volumes (15 ml/kg) with either a
low respiratory rate or deadspace and 5 cm H2O) PEEP.
2.2 Use minimal FiO2 consistent with adequate oxygen delivery (SaO2 > 98%).
2.3 Ensure clear airway using tracheal suction and check position of ET tube. Collect sputum
sample for culture.
2.4 Manually inflate lungs under direct vision after sternotomy and opening pleura, and note
any consolidation and trauma.
3. Vascular Access
A separate fresh, venepuncture must be made from which to obtain blood culture samples.
3.1 Prepare the following access lines:
a. Left arterial line (radial or brachial)
b. Right triple lumen (internal jugular)
c. Right Swan-Ganz (internal jugular)
45
3.2 Use these lines in the following manner:
a. Swan introducer – blood & colloids. Venesection and samples.
Use a warming coil for infusion.
b. Triple smallest lumen – ADH/Adrenaline infusion.
c. Triple lumen – T3 and insulin.
d. Triple large lumen – inotropes/dilators.
4. Haemodynamics
4.1 Use Swan-Ganz and arterial pressure to enable calculation of cardiac index, pulmonary and
systemic resistances and LV static power.
4.2 Target the following status: (Use Normogram)
a. SVR 800–1200 dynes/sec/cm5
b. LVPo 0.6–1.0 Watts
c. Minimal preload (< 8 mm Hg)
4.3 Use ADH infusion to increase the afterload (max 4 ml/hr)
4.4 Use Sodium Nitroprusside to decrease the afterload (max 4 µg/kg/min)
4.5 Use Dopamine if all else fails to produce an adequate output in the face of a normal SVR
(max 10 µg/kg/min).
5. Fluid Management
5.1 Use colloids only to replace peri-operative loss and to adjust filling pressures. Infuse via a
warming coil.
5.2 Give whole blood or packed cells to keep Hb > 10 g/dL.
5.3 Replace urinary losses with 4.3% Dextrose/0.25% saline and K+ 20 mmols/L.
6. Antibiotics
6.1 Give the following regime at induction after taking blood samples for culture:
a. Vancomycin 1 g
b. Meropenem 1 g
7. Steroids
7.1 Methyl Prednisolone 500 mg stat dose.
46
THE PAPWORTH DONOR MANAGEMENT HORMONE REPLACEMENT
PROTOCOL
The following infusions should be prescribed and commenced as soon as possible:
1.
•
•
•
T3 (Triiodothyronine)
20 microgram vials, made up with water for injection = 1 µg/ml.
Given an initial bolus of 4 µg followed by an infusion of 3 µg/hr.
•
•
•
Pitressin (Argipressin)
Ampoules 1 ml (20 units/ml). Make up to 40 mls with 5% glucose = 0.5 units/ml.
Give initial bolus of 1 unit followed by an infusion at 0.5–2.0 units/hr (i.e. 1–4 ml/hr).
2.
NB If mean arterial pressure > 90 mm Hg following administration of pitressin, discontinue
infusion.
3.
•
•
Insulin (Human actrapid)
Commence sliding scale insulin to maintain blood sugar between 4–6 mmol/l
Blood sugar
> 15 mmols
8–15 mmols
4–8 mmols
< 4 mmols
Insulin Perfusiona
5.5 IU/hr
3.5 IU/hr
1.5 IU/hr
GIK 1.5 ml/kg/hr
a
These dosages are suitable for patients weighing between 40–100 kg. If the patient is <
40 kg use half the above dose. Discuss with the on call transplant fellow at Papworth if in
any doubt.
47
Appendix VI – Leuven University Hospital
Procedure multi-organ donor
General remarks
In every multi-organ donor (MOD), attempts must be made to achieve optimum protection for all
organs which can potentially be procured. This protocol therefore applies to all cases in which
organs can be procured from donors with a "beating heart". This protocol becomes effective as
soon as the "pronouncement of death" (brain death) has been completed and signed by three
independent doctors, in accordance with Belgian legislation and the procedure applicable in that
specific hospital.
It goes without saying that before brain death occurs, optimum protection for all organs must be
ensured.
If cardiocirculatory stability cannot be achieved by the usual methods, the additional measures of
donor management must be performed.
Every potential donor must be reported to a transplant coordinator.
Sterility
Complete sterility of the donor must be guaranteed when using and positioning catheters, caring
for ventilation appliances, bronchial toilet and all other invasive procedures.
•
•
•
•
•
•
•
ECG : modified V5 lead
Capnography, pulsoxymetry, endotracheal tube and ventilation equipment
Arterial pressure measurement (desirable) with transducer and continuous screen
display
CVD with transducer and continuous screen display, Swan-Ganz (if possible) only
with haemodynamic instability
2 “thick” (14 or 16 gauge) intravenous catheters. Catheters inserted before admission
to hospital or catheters suspected of being infected must be removed immediately –
catheter tip culture!) + blood heater on a peripheral “volume” line
Bladder and stomach catheters
Heating mattress
Infusion therapy
The filling situation is extremely important
Aim for a central venous pressure of 8 mm Hg to 10 mm Hg mean at positive pressure
respiration PEEP +5 and the transducer at the level of the right atrium when the donor is
horizontal. Overfilling can very quickly compromise the lungs and under filling causes
haemodynamic instability.
48
CVD is LOWER than +8 mm Hg
• Check Hct., Na., glycaemia, diuresis. If diabetes insipidus is present, start with
glucose 2.5% and add further solutions as needed. Possibly give K+
• Give PC + SOPP if Hct < 30
• Give SOPP if Hct > 32 and TE < 11 mg/l or < 5g%
• Use Ringer lactate if Hct > 32 and TE > 11 mg/l or > 5g%
CVD is HIGHER than +8 mm Hg
• Give minimum fluids and give diuretics if urine output is low
• Once CVD has been achieved, continue with compensation of abnormal losses. In
addition, give maintenance therapy with physiological 50 ml/hour for an adult donor.
If hypernatremia is present, give glucose 2.5% in quantities per hour equal to the
previous urine output per hour + 50 ml. Avoid hypernatremia at all costs
• BUT: unrestrained administration of a solution containing sodium in order to prevent
diabetes VERY QUICKLY causes dangerous hypernatremia
Urine output
The ideal urine output to aim for is 1,5 ml/kg/hour
Urine output is LOWER than 1 ml/kg/hour
• Optimise filling (see above)
• If no cardiovascular instability is present, give diuretics
• If cardiovascular instability is present, correct haemodynamic situation and then give
diuretics if necessary
Urine output is HIGHER than 3 ml/kg/hour
• This is usually due to excessive use of diuretics or diabetes insipidus. Excessive use
of diuretics usually leads to hyponatremia, diabetes insipidus leads to hypernatremia.
Both cause volume problems and temperature losses
• Stop diuretics
• Correct volume deficiencies and ion anomalies
• If diabetes insipidus is present: give Desmopressin (intravenously) 2–4 up to max, 6
µg (1 amp. = 1 ml = 4 µg). Repeat as soon as necessary, i.e. when diuresis again rises
sharply (usually every 6 hours)
Ventilation
Place a filter on the Y section of the ventilator tubes. Use of an artificial nose is a valid
alternative. However, if the patient is supercooled, use a humidifier and place a filter on the
inspiratory leg of the ventilator tubes in front of the humidifier
Ventilate with a flow volume of 15 ml/kg and PEEP +5. Ventilate up to normal PH, which
implies normal PaCO2 in the absence of a metabolic component. If the tidal minute volume has
to be adjusted, this is done based on frequency, not based on flow volume
Aim for a PaO2 of 100 mm Hg by adjusting the FiO2. Every 2 hours, carry out a strictly aseptic
bronchial toilet, followed by careful bag squeezing.
49
Acid–base equilibriums, electrolytes and glucose
Anomalies are corrected
•
Blood gas values are not corrected for temperature. Ventilate up to normal PH
including where pronounced metabolic acidosis is present. In the mean time, the
metabolic acidosis is corrected based on the base deficit. If the bicarbonate content is
normalised, ventilation can of course take place up to a normal PaCO2
Ion anomalies are corrected. It is often necessary to administer large quantities of K+ (check and
regulations per hour). If hyperglycaemia is present, insulin therapy is started.
Cardiovascular (hormone substitution)
The most important aspect is optimum filling
Aim for an average arterial pressure of > 70 mm Hg. Nonetheless, extreme tachycardia and
hypertension must occasionally be treated with (careful!) use of beta-blockers or labetalol
If average arterial pressure is lower than 70 mm Hg, first optimise filling and correct ions and
acid–base disorders
If average arterial pressure remains lower than 70 mm Hg, start dopamine up to max. 5
µg/kg/min
If dopamine in doses of 5 µg/kg/min. does not solve the problem, start hormone substitution.
Hormone substitution chart
T3 (1 vial=20 µg)
Loading dose of 2 or 4 µg IV over 1 hour, (Adults). Dose dependant upon patient’s reaction.
0.6 µg/kg/24 h. (= 1.8 µg/h dependant upon the patient’s condition and for wt of 70 kg)
Attention: large doses may provoke tachycardia, arrhythmias, hypertension, CO2 production and
increased body temperature.
Hydrocortisone (Solu-Cortef® Upjohn)
3 _ 200 mg/24 h
Up to: 600 mg continuous IV infusion.
Human Insulin: Actrapid®
1 to 2 U/h. (Solution: 50 U/50 ml. NaCl 0.9%)
Independent of the blood sugar value, this signifies that insulin should not be titrated to the blood
sugar values!
Verify ionized Ca ++ and P levels and correct any deficiencies with infusions of Ca2+ / P2+
Always maintain optimal volume replacement. Only in situations when it is certain that the lungs
will NOT be transplanted can a fluid challenge be performed or the CVP be allowed to rise to
10–12 mm Hg.
50
If the previous measures are inadequate, insert a Swan-Ganz catheter. Only after the necessary
interventions have been performed can the dopamine be increased up to a maximum of 10
µg/kg/min or eventually administration of vasoconstrictor infusions
Cardiac arrests are treated « lege artis », and a re-evaluation of the donor is undertaken.
Coagulation
Disseminated intravascular coagulation (DIC) occurs relatively often in multi-organ donors. If
coagulation tests indicate, a thromboelastogram may be required. Severe coagulopathies are
treated « lege artis » when a volume replacement problems exist. (CMV negative preparations).
Aminocaproic acid and tranexamic acid are completely contraindicated. Coagulopathies are only
treated if donor stability is threatened.
Temperature Control
Efforts are made to maintain a temperature > 35°C with the help of a heated mattress, a warmer
for blood infused for volume replacement, an artificial nose filter and eventually a respiratory
humidifier, limitation of volume loss due to excessive diuresis, administration of T3.
Antibiotics
In principal, antibitics are only given on the basis of culture results.
51
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