Organ Donor Management:Survey of Guidelines and

Eligibility Criteria

Prepared for the Forum:Medical Management to Optimize DonorOrgan PotentialFebruary 23-25, 2004

by

Lead Investigator

Sam D. Shemie, MD, Chair,on behalf of the MEMODOP Steering Committee

CoordinatorKaren HornbyMontreal Children’s Hospital

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Contents

Acknowledgements ...................................................................................................................v

Executive Summary ..................................................................................................................1

I. Survey of Canadian and Selected International Organ Donor ManagementGuidelines and Eligibility Criteria.......................................................................................8

Methodology for Data Gathering and Inclusion ...............................................................8Survey Responses............................................................................................................8

II. Analysis of Canadian Management Guidelines Received..........................................10Oxygenation and Ventilation .........................................................................................10Organ Perfusion ............................................................................................................11Fluid Balance and Electrolytes ......................................................................................13Hematology...................................................................................................................17Temperature ..................................................................................................................17Infection........................................................................................................................18Additional Treatments ...................................................................................................18

III. Canadian Donor Organ Eligibility Criteria ....................................................................20OPO 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

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AcknowledgementsThe Steering Committee for the Forum on Medical Management to Optimize Donor OrganPotential (February 23-25, 2004) commissioned this paper, a working draft, as a backgroundinformation piece for participants attending the Forum. During the Forum, consideration will begiven to editing this working draft for wider circulation.

The views of the paper do not necessarily reflect the official policy of the Forum host, theCanadian Council for Donation and Transplantation, and are not intended for publication in theircurrent format.

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Executive SummaryThis report summarizes the results of a survey of Canadian intensive care units, organprocurement organizations (OPOs) and transplant associations. The survey requested copies oforgan donor management guidelines and eligibility criteria. Selected international OPOs werealso contacted, and a brief summary of their activities is included. This research was conductedin preparation for the Canadian Forum on Medical Management to Optimize Donor OrganPotential, 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 theirOPO’s guidelines. All OPOs stated that they were involved (to varying degrees) in organ donormanagement at intensive care units within their respective provinces and provided these unitswith OPO guidelines. The intent of the survey was to identify existing guidelines; the survey wasnot intended to assess the utilization of these documents (i.e., if guidelines were actually in useand how many sites were using them). As a result, this analysis is based on 17 uniquedocumented 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 centerssurveyed. All hospital centers (except one) referred decisions to determine eligibility to theirrespective OPOs. Ten OPOs provided information on donor organ eligibility criteria. One OPOcurrently 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 wasassessed on a case by case basis”; three of these provided absolute contraindications. One OPOprovided a draft protocol (approval is outstanding, and the protocol is therefore not included inthe analysis). Another OPO uses the Canadian Standards (tissue and organ donation), and itsonly 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 ofdevelopment. Among the countries with mature systems in this field, recent efforts have been onoptimizing medical management to maximize organ yield. Refer to pages 6 and 7 formanagement details. Countries at the forefront of this movement are Spain, the United States, theUnited 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 allhospitals. Among other things, these teams identify all potential donors and handle theevaluation and management of the donor.

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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 ofTransplantation, the American Society of Transplant Surgeons and the North AmericanTransplant Coordinators Organization.

United Kingdom

A standardized donor management technique was developed at the Papworth Hospital inCambridge, England. Details on the Papworth approach to organ donor management will beprovided in a separate presentation.

Australia

South Australia adopted the Spanish Model and experienced a significant increase in its donorrate compared to other states. As well, the Alfred Hospital in Melbourne has developed asuccessful system of transplant coordination and organ allocation. Its system is considered agood example of the Australian approach.

Eurotransplant

Eurotransplant is an international framework including all transplant hospitals, tissue-typinglaboratories and hospitals where organ donation takes place in Austria, Belgium, Germany,Luxembourg, the Netherlands and Slovenia. The Leuven University Hospital in Belgium hasdeveloped a secure-access website containing organ donation information and protocols. Thiswebsite is accessible to all members of their donor hospital network. Since its implementation, asubstantial increase in donors has occurred.

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Summary table 1. Canadian organ donor management guidelines

Targets Range Median GLa

Respiratory O2 sat (%) ≥ 90 – ≥ 96 ≥ 95 10FiO2 (%) “any value to maintain O2 sat” 6

< 40 – < 60 < 50 3PaO2 (mm Hg) 65–100 85 10PCO2 (mm Hg) 35–45 N/Ab 9pH Lower limit 7.30–7.35 7.35 8

pH Upper limit 7.45 7.45 8PEEP (mm Hg) 4–7.5 5 6TV lower limit (ml/kg) 5–12 9 9Peak airway ≤ 30 ≤ 30 4

pressure (mm Hg)

Hemodynamic MAP Adults (mm Hg) ≥ 70 ≥ 70 5Peds age adjusted N/A 3

SBP Adults (mm Hg) > 90 – > 100 > 100 7Peds age adjusted N/A 2

HR Adults (bpm) ≥ 60–70 ≥ 60 5≤ 110 – ≤ 160 ≤ 120 7

Peds age adjusted N/A 2CVP (mm Hg) ≥ 4–7 6 15

≤ 8–12 10 12PCWP Lower (mm Hg) 8 8 3

Upper 10–12 10 3

Electrolytes Serum sodiumLower (mmol/L) 125–130 130 5Upper ≤ 150 – ≤ 155 ≤ 150 6

Serum potassiumLower (mEq/L) > 3.0 – > 4.0 > 3.5 6Upper < 4.5 – < 5.5 < 5.5 5

Urine Output Adults Lower (ml/h) ≥ 30 – ≥ 120 ≥ 100 9Upper ≤ 180 – ≤ 300 ≤ 250 6

Peds Lower (ml/kg/h) 1–2 1 5Upper 2–3 2 5

Diabetes Adults U/O (ml/h) > 180–400 > 240 9Insipidus (DI) Osmol (mOs/L) < 300 < 300 2

Na+ (mmol/L) < 10 < 10 2 SG ≤ 1.000 ≤ 1.000 1

Serum osmol > 300 mOs/kg & _ > 300 mOs/kg & _ 2Peds U/O (ml/kg/h) > 4 – > 5 > 4 ml 4

Osmolality “low” “low” 1Na+ (mmol/L) > 145 > 145 2SG < 1.000 – < 1.010 <1.005 3Serum osmol “high” “high” 1

Blood Sugar Lower limits (mmol/L) 4–8 6 5Upper limits 10–20 12 6

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Summary table 1. Canadian organ donor management guidelines (cont’d)

Insulin Adults (U/h) 0.5 –1 0.75 2Peds (U/kg/h) 0.025–0.1 0.025 3

Hematology Hematocrit (%) 20–35 30 6Hemoglobin (g/dL) 8–12 9 3

Temperature Lower limit (°C) 35–36.5 35.3 14Upper limit 37–38 37.5 11

Invasive Monitoring Percentage GLa

Arterial line 93% 15Central venous line 100% 15Pulmonary artery catheterization 53% 15

Cardiovascular Support Range Median GLa

Dopamine (max dose) (µg/kg/min) 10–15 < 10 11Norepinephrine Lower (µg/min) 0.6–3 1.2 3

Upper 36–60 48 2Epinephrine Lower (µg/min) 0.6–3 1.8 2

Upper 36–60 48 2Vasopressin Lower (U/h) 1.1–3 1.2 3

Upper 2.4–6 4.2 2

Desmopressin Suggested Dosages to Treat DIAdults Pediatrics

1 µg q6h prn intranasal (no dose indicated)1 µg push _ 2 0.25–1 µg per dose1–2 µg push 5–10 µg ETT or 0.25–4 µg IV2 µg infuse over 30 minutes (2 guidelines)1–4 µg IV, IM or SC q12–24h prn2–4 µg q4–6h or 1 µg/h infusion2 µg, then 4 µg repeat as needed4 µg q2h _ 2 call MD if 3rd dose required (2 guidelines)

Vasopressin Suggested Dosages to Treat DIAdults Pediatrics1 U/h, titrate to target u/o 0.5–3 mU/kg/h2 U bolus, 1 U/h titrate to target u/o 5–15 mU/kg/h(2 guidelines) (2 guidelines)2.5–5 units IV q4h 6–15 mU/kg/h

AntibioticsOne hour prior to OR: cefazolin IV Adults: 1 gm (n = 1) Peds: 30 mg/kg, max 1gm (n = 2)Or if hospital > 72 hrs cefotaxime IV Adults: 1 gm (n = 1) Peds: 40 mg/kg, max 1 gm (n = 2)AND metronidazole IV Adults: 500 mg (n = 1) Peds: 15 mg/kg, max 500 mg (n = 2)

CorticosteriodsThe following dosages were suggested: 10 mg/kg, max 1g (n = 1)

15 mg/kg, max 1g (n = 2)1 g IV _ 1 (n = 3)

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Summary table 1. Canadian organ donor management guidelines (cont’d)

Hormonal TherapyOne guideline suggested: methylprednisolone: 15 mg/kg IV (not to exceed 1 gm)

insulin infusion: 0.5–1.0 U/h starting doseT4: 40 µg bolus IV _ 1desmopressin infusion: 1µg/h

InvestigationsSupportive Testing Chest x-ray 82%

Electrocardiogram 71%Echocardiogram 65%Bronchoscopy 41%Cardiac angiogram 24%Cardiology consult 18%

aNumber of guidelines that provided target values for variable of interest.bN/A = not applicable

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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 UniversityHospital (Belgium).

Targets Spain U.S. U.K. BelgiumRespiratory O2 sat (%) 95–100 ≥ 95 > 98% N/Aa

FiO2 (%) up to 100 up to 100 min for sat min for PaO2

PaO2 (mm Hg) 90–100 ≥ 90 ~ 264 @ 50% 100PCO2 (mm Hg) 35–45 30–35 35–45 35–45pH 7.35–7.45 N/A N/A 7.35–7.45

PEEP (cm H20) 5 5 5 5

Respiratory TV (ml/kg) 8–10 10–15 15 15Peak airway < 30 < 30 N/A N/A

pressure (mm Hg)

Hemodynamic MAP N/A ≥ 60 > 60 > 70SBP (mm Hg) ≥ 100 ≥ 90 N/A N/AHR (bpm) ≤ 100 ≥ 70 – ≤ 120 N/A N/ACVP (mm Hg) 10–12 4–11 < 12 8–10PCWP (mm Hg) 8–14 8–12 < 12 N/ASVR (dynes/sec/cm5) 800–1200 800–1200 N/A

Electrolytes Serum Na (mEq/dl) N/A < 150 N/A N/ASerum K+ (mEq/dl) N/A > 4.0 N/A N/A

Urine Output Adults (ml/kg/h) > 1 ≥ 1 – ≤ 3 N/A ≥ 1– ≤ 3Peds (ml/kg/h) > 2 N/A N/A N/A

DI U/O (ml/kg/h) N/A > 3 N/A > 3Osmolality N/A N/A N/A N/A

Na+ N/A N/A N/A N/A SG N/A N/A N/A N/A

Serum osmol N/A N/A N/A N/A

Blood Sugar (mg/dl) 150 120–180 70–115 N/A(4–6 mmol/L)

Insulin no doses given see HRT see HRT see HRT

Hematology Hematocrit (%) ≥ 30 ≥ 30 N/A ≥ 30≥ 35 multi-organ

Hemoglobin (g/dl) 10–12 ≥ 10 > 10 ≥ 11

Temperature (°C) > 35 36.5–37.5 N/A > 35

Invasive MonitoringArterial line yes yes yes yesCentral venous line yes yes yes yesPulmonary artery catheterization yes yes yes yes

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Summary table 2. International organ donor management guidelines (cont’d)

Cardiovascular SupportDopamine (max dose) (µg/kg/min) ≤ 10 < 10 ≤ 10 ≤ 10Norepinephrine no dose given N/A N/A N/AEpinephrine no dose given N/A N/A N/AVasopressin N/A see HRT see HRT N/A

Desmopressin Suggested Dosages no dose given N/A N/A 2–4 µg (max 6) (to treat DI)

Vasopressin Suggested Dosages N/A see HRT see HRT N/A (to treat DI)

Antibiotics prophylactic broad- vancomycin 1 g on basis ofuse spectrum meropenem 1 g cultures

Corticosteriods N/A see HRT 500 mg see HRTmethylprednisolone

Hormonal TherapyT3 N/A 4 µg bolus, 3 µg/h same as US 2–4 µg in 1h,

then 1.8 u/hVasopressin/Pitressin N/A 1 U bolus, 0.5–4.0 U/hb 1 U bolus, N/A

0.5–2.0 U/hSteroids N/A methylprednisolone N/A hydrocortisone

15 mg/kg bolus q24h 3 _ 200 mg/24hup to 600 mg

Insulin N/A min 1 U/hc sliding scale 1–2 U/h

Investigations/Supportive Testingd

Chest x-ray N/A yes no noElectrocardiogram N/A yes yes yesEchocardiogram N/A yes yes noBronchoscopy N/A yes yes noCardiac angiogram N/A yes yes noCardiology consult N/A yes yes noaN/A = not applicablebTitrate to SVR.cTitrate to blood glucose.dThese may be mentioned in sections on donor organ evaluations that were not provided.

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I. Survey of Canadian and Selected InternationalOrgan Donor Management Guidelines and EligibilityCriteria

This report summarizes the results of a survey of Canadian intensive care units, organprocurement organizations (OPOs) and transplant associations. The survey consisted of a requestfor organ donor management guidelines and eligibility criteria. Documents were received fromthree categories of institutions: adult centers, pediatric centers and provincial OPOs. Selectedinternational OPOs were also contacted, and a brief summary of their activities relating to organdonor management is included. This research was conducted in preparation for the CanadianForum on Medical Management to Optimize Donor Organ Potential, sponsored by the CanadianCouncil 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 providedpediatric guidelines in addition to adult ones. (See Appendix I for further details on provincialdifferences in OPOs.) Adult intensive care units in all major Canadian cities as well as allCanadian pediatric intensive care units were contacted. Table 1 categorizes their responses.

Table 1. Canadian centers contacted/responded

Centers Contacted (n = 55) No. ResponsesOPOSs 14Adult centers 21Pediatric centers 16Canadian Association of Transplantation N/Aa

Canadian Society of Transplantation N/AOther (Yukon, P.E.I.) N/AaN/Aa = not applicable

Survey Responses

Table 2 breaks down the survey responses by type of center and guidelines used. Half of thepediatric centers and 43% of the adult centers surveyed stated that they used their OPO’sguidelines. All OPOs stated that they were involved (to varying degrees) in organ donormanagement at intensive care units within their respective provinces and provided these unitswith 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 assessthe utilization of these documents (i.e., if guidelines were actually in use and how many siteswere using them). Therefore, only unique guideline documents were entered into the studydatabase.

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Table 2. Breakdown of survey responses

Guidelines Uses No GuidelinesProvided 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)aOne pediatric guideline not included, as it was based on a hospital guideline already analysed.bna = 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-organmanagement 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 thisstudy; therefore, percentages in the following sections are based on the number of guidelines thataddressed those particular issues of interest.

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II. Analysis of Canadian Management GuidelinesReceived

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 valuescited.

O2 challenge

Ten guidelines mentioned the use of the O2 challenge test, with some variations. All cited usingan FiO2 of 100% with a PEEP of 5 mm Hg and a predetermined delay before blood is drawn forarterial blood gases (ABGs). Recommended tidal volumes and delay prior to ABG measurementvaried. 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). Otherlung treatments suggested were repositioning (n = 4), chest physiotherapy (n = 2), posturaldrainage (n = 1) and manual lung inflation (n = 1).

Table 3. Respiratory management targets

Targets Range Median GLa

O2 sat ≥ 90% – ≥ 96% ≥ 95% 10FiO2 “any value to maintain O2 sat” 6 < 40% – < 60% < 50% 3PaO2 65–100 mm Hg 85 mm Hg 10PCO2 35–45 mm Hg 35–45 mm Hg 9pH Lower limit 7.30–7.35 7.35 8 Upper limit 7.45 7.45 8PEEP 4–7.5 mm Hg 5 mm Hg 6TV (lower limit) 5–12 ml/kg 9 ml/kg 9Peak airway pressure ≤ 30 mm Hg ≤ 30 mm Hg 4aNumber of guidelines that provided target values for variable of interest.

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Organ Perfusion

Organ perfusion management includes target pressures, invasive monitoring and cardiovascularsupport.

Target pressures

Table 4 outlines the hemodynamic management targets. Not unexpectedly, most pediatricguidelines indicated age-adjusted values for these targets.

Table 4. Hemodynamic management targets

Targets Range Median GLa

MAP Adults ≥ 70 mm Hg ≥ 70 mm Hg 5Peds age adjusted N/Ab 3

SBP Adults > 90 – > 100 mm Hg > 100 mm Hg 7Peds age adjusted N/A 2

HR Adults ≥ 60–70 bpm ≥ 60 bpm 5≤ 110 – ≤ 160 bpm ≤ 120 bpm 7

Peds age adjusted N/A 2CVP ≥ 4–7 mm Hg 6 mm Hg 15

≤ 8–12 mm Hg 10 mm Hg 12PCWP Lower limit 8 mm Hg 8 mm Hg 3

Upper limit 10–12 mm Hg 10 mm Hg 3aNumber of guidelines that provided target values for variable of interest.bN/A = not applicable

One pediatric guideline provided age-adjusted values for the central venous pressure target. Onlyone 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. Fiveguidelines gave instructions for placement in specific anatomical locations. Table 5 breaks downthe types of invasive monitoring identified.

Table 5. Invasive monitoring

Percentage GLa

Arterial line 93% 15Central venous line 100% 15Pulmonary artery catheterization 53% 15aNumber of guidelines that referred to invasive monitoring.

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The indications for pulmonary artery catheterization were heart/lung donors, or managementdifficulties or both (n = 5), desirable (n = 2) and absolutely necessary (n = 1). One pediatricguideline 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 orvasopressors. In a majority of cases (n = 9), adequate fluid resuscitation prior to starting anyinotrope 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 anoption” (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 Range Median GLa

Dopamine (maximum dose) 10–15 µg/kg/min 10 µg/kg/min 11Norepinephrine Lower 0.6–3 µg/min 1.2 µg/min 3

Upper 36–60 µg/min 48 µg/min 2Epinephrine Lower 0.6–3 µg/min 1.8 µg/min 2

Upper 36–60 µg/min 48 µg/min 2Vasopressin Lower 1.1–3 U/h 1.2 U/h 3

Upper 2.4–6 U/h 4.2 U/h 2aNumber of guidelines that provided target values for variable of interest.

Only 35% of guidelines mentioned the use of short-acting antihypertensives. The followingdrugs were identified: nitroprusside (n = 4), labetalol (n = 3), propranolol (n = 2) andnitroglycerin (n = 1), with some guidelines identifying more than one drug. Only two guidelinesprovided dosing information. Both indicated 1–2 mg propranolol IV push, and one provided analternative of 5–10 mg labetalol IV.

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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 ofsuggestions for the type of fluid used, the quantity and fluid management targets. Sevenguidelines based the decision of which fluid to use on electrolyte laboratory values, four ofwhich 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 urineoutput as their fluid management strategies, and three guidelines targeted pressures (MAP orCVP). One guideline recommended avoiding the use of Ringer’s lactate. The same guidelinecontraindicated the use of plasma, hetastarch and Pentaspan (pentastarch) for organ donors. Oneother guideline had a contraindication for the use of Pentaspan, and five guidelinesrecommended its use.

Electrolytes

Fifty-three percent of guidelines surveyed indicated the importance of strict monitoring andcorrection of electrolyte imbalances. Six centers provided target values for serum sodium andpotassium (table 7).

Table 7. Electrolyte targets

Range Median GLa

Serum sodiumLower limit 125–130 mmol/L 130 mmol/L 5Upper limit ≤ 150 – ≤ 155 mmol/L ≤ 150 mmol/L 6

Serum potassiumLower limit > 3.0 – > 4.0 mEq/L > 3.5 mEq/L 6Upper limit < 4.5 – < 5.5 mEq/L < 5.5 mEq/L 5

aNumber of guidelines that provided target values for variable of interest.

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Fluid balance

All centers identified upper and lower urine output targets. Table 8 details these values.

Table 8. Target urine outputa

Range Median GLb

Adults Lower limit ≥ 30 – ≥ 120 ml/h ≥ 100 ml/h 9Upper limit ≤ 180 – ≤ 300 ml/h ≤ 250 ml/L 6

Peds Lower limit 1–2 ml/kg/h 1 ml/kg/h 5Upper limit 2–3 ml/kg/h 2 ml/kg/h 5

a When urine output for adults was provided in ml/kg/h, it was converted into ml/h based on an average adult weightof 60 kg.bNumber of guidelines that provided target values for variable of interest.

Diabetes insipidus

Diagnosis. Ninety-four percent of guidelines provided instructions for the management of urineoutput, with 88% suggesting the use of antidiuretics. A definition of diabetes insipidus (DI) wasprovided by 76% of guidelines. Urine output limits for DI are presented in table 9.

Table 9. Indicators of DIa

Range Median GLb

AdultsUrine Output > 180–400 ml/h > 240 ml/h 9

Osmolality < 300 mOs/L < 300 mOs/L 2Na+ < 10 mmol/L < 10 mmol/L 2SG ≤ 1.000 ≤ 1.000 1

Serum osmolality > 300 mOs/kg > 300 mOs/kg 2and rising and rising

PediatricsUrine Output > 4 – > 5 ml/kg/h > 4 ml/kg/h 4

Osmolality “low” “low” 1Na+ > 145 mmol/L > 145 mmol/L 2SG < 1.000 – < 1.010 <1.005 3

Serum osmolality “high” “high” 1aWhen urine output for adults was provided in ml/kg/h, it was converted into ml/h based on an average adult weightof 60 kg.bNumber of guidelines that provided target values for variable of interest.

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Therapy. All of the guidelines that recommended using antidiuretics to treat DI suggested usingdesmopressin, with a variety of doses and methods. Two guidelines indicated that desmopressinwas preferred over vasopressin to treat DI. Fifty-nine percent provided information on the use ofvasopressin. One guideline indicated that its use should be avoided, and another suggestedcontacting the transplant team prior to use for extra-renal organ donors. One pediatric guidelinerecommended the use of vasopressin if the donor was not hemodynamically stable; otherwise,desmopressin was indicated. When vasopressin was recommended, three guidelines indicatedthat it had to be discontinued 1 h prior to OR (n = 1), 1–2 h prior to OR (n = 1) or 2 h prior toOR (n = 1). Tables 10 and 11 list the recommended dosages.

Table 10. Desmopressin: Suggested dosages

Adults Pediatrics1 µg q6h prn intranasal (no dose indicated)1 µg push _ 2 0.25–1 µg per dose1–2 µg push 5–10 µg ETT or 0.25–4 µg IV2 µg infuse over 30 minutes (2 guidelines)1–4 µg IV, IM or SC q12–24h prn2–4 µg q4–6h or 1 µg/h infusion2 ug, then 4 µg repeat as needed4 µg q2h _ 2 call MD if 3rd dose required (2 guidelines)

Table 11. Vasopressin: Suggested dosages

Adults Pediatrics1 U/h, titrate to target u/o 0.5–3 mU/kg/h2 U bolus, 1 U/h titrate to target u/o 5–15 mU/kg/h

(2 guidelines) (2 guidelines)2.5–5 units IV q4h 6–15 mU/kg/h

Oliguria diagnosis and therapy

Only 24% of guidelines provided indications on oliguria. Each of these suggested the use ofdiuretics 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. Theremaining guideline defined oliguria as a urine output of < 50 ml/h with a CVP of > 12 mm Hg,with no indication of treatment.

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Glucose

Seventy-one percent of guidelines provided information on regulation of blood sugar (BS). Theuse of insulin to maintain target BS was identified in 65% of guidelines. Two of these suggestedthat insulin be used with caution for increased BS as potassium boluses may be required prior toinsulin use. Two adult guidelines recommended a sliding scale for insulin infusions (no dosagesgiven), and two others simply indicated “insulin drip”. All titrated dosages to meet target BSlevels; however, many did not provide target parameters. Table 12 outlines the target valuesprovided for BS and insulin dosages.

Table 12. Regulation of blood sugar

Range Median GLa

BS TargetsLower limits 4–8 mmol/L 6 mmol/L 5Upper limits 10–20 mmol/L 12 mmol/L 6Insulin DosagesAdults 0.5 –1 U/h 0.75 U/h 2Pediatrics 0.025–0.1 U/kg/h 0.025 U/kg/h 3aNumber of guidelines that provided target values for variable of interest.

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Hematology

Sixty-five percent of guidelines referred to the use of blood products. Six of these identified theuse 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 guidelinesprovided a general comment concerning the use of blood products, such as “treatcoagulopathies”. Three others identified the use of whole blood to maintain either a targethematocrit (n = 2) or a circulating blood volume (n = 1). Other blood products mentioned werefresh frozen plasma (n = 3), platelets (n = 2) and cryoprecipitate (n = 1). Only one guidelinespecified the use of CMV negative-only products. Table 13 lists hematocrit and hemoglobintargets. Two guidelines linked their hematocrit targets to specific organs: ≥ 20% for kidneydonors or ≥ 30% for heart or liver donors.

Table 13. Hematocrit and hemoglobin targets

Range Median GLa

Hematocrit 20–35% 30% 6Hemoglobin 8–12 g/dL 9 g/dL 3aNumber 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 methodfor temperature measurement was identified (n = 8), 63% indicated that temperatures should bemeasured rectally. Table 14 summarizes body temperature targets.

Table 14. Body temperature targets

Range Median GLa

Lower limit 35–36.5° C 35.3° C 14Upper limit 37–38° C 37.5° C 11aNumber 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%), heatinglamps (13%) and cooling blankets (13%). Other guideline-specific suggestions to maintain targetbody temperatures were ambient room temperature, hats, socks, Bair huggers and uncovering thepatient.

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Infection

Only 35% of guidelines mentioned antibiotic use. Of these, 2 had general comments:“antibiotherapy indicated” and “discuss with transplant coordinator”. One guideline suggestedbroad spectrum antibiotics, and three had very specific indications for antibiotic use: “1 hourprior 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 itsuse for lung donors, and another guideline stated, “it contributes to stability and improvedoxygenation”.

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 thefollowing:

• 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 cellmetabolism”.

19

Investigations/Supportive Testing

Supportive investigations required during the management of organ donors is detailed intable 15.

Table 15. Supportive testing

% of GL Indicationsa

Chest x-ray 82% Lung donors (n = 5)Heart donors (n = 1)

Electrocardiogram 71% Heart donors (n = 1)Echocardiogram 65% Heart donors (n = 5)

Tx coordinator request (n = 1)Bronchoscopy 41% Lung donors (n = 4)

Tx coordinator request (n = 1)Cardiac angiogram 24% N/Ab

Cardiology consult 18% N/AaWhen mentioned.bN/A = not applicable

20

III. Canadian Donor Organ Eligibility CriteriaInformation on donor organ eligibility criteria was obtained using the same methodology as thatused to obtain donor organ management guidelines (see “Methodology for Data Gathering andInclusion”, page 3). According to the centers surveyed, donor organ eligibility is not anintensive-care-based responsibility. One adult center provided donor organ eligibility criteria. Allother 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 detaileddocument outlining eligibility criteria for individual organs as well as donor-specificcontraindications. This document was dated 1993, and the OPO explained that it currentlyassesses 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 wasassessed on a case by case basis”. Three of these also provided a list of absolutecontraindications (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 itsonly absolute contraindication is West Nile virus. One final OPO indicated that it “looks ateverything and does a medical assessment, and then consults with individual transplantprograms”.

Table 16. Absolute contraindications to donor eligibility

Positive tests foranti-HIV-1 or anti-HIV-2hepatitis B or Chuman T-cell lymphotropic viruses types I and II

History or evidence of HIV high-risk behaviours, even if HIV-antibody negativeDeath with neurological disease of an unestablished etiology (i.e., ALS, Alzheimer’s, multiplesclerosis, Parkinson’s)Prion-related disease (i.e., CJD, family hx CJD, recipient of human-derived pituitary growthhormone or dura mater)Active systemic bacterial, viral or fungal infectionsRabiesLeukemias, lymphomas and active malignanciesProgressive multi-focal leukoencephalopathySubacute sclerosing panencephalopathy

21

IV. International Issues in Organ Donor ManagementWorldwide, organ donation and the medical management of organs donors are at various stagesof development. Among the countries with mature systems in this field, recent efforts havefocused on optimizing the medical management of organ donors to maximize organ yield perpotential donor. Countries such as Spain, the United States, the United Kingdom, Australia andmembers of Eurotransplant (comprising Austria, Belgium, Germany, Luxembourg, theNetherlands and Slovenia) are at the forefront of this movement.

Nonetheless, standardized international donor management strategies remain elusive. Accordingto 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 potentialdonor.”1 He also highlighted recent efforts by the North American Transplant CoordinatorsOrganization and Donor Action Foundation to encourage standardization; the former editedDonor Management Issues, published by D.J. Powner, and the latter is developing aninternational e-learning course on donor management.

Spain

The Organización Nacional de Trasplantes (ONT) was formed in 1989 to address decliningorgan donation rates in Spain. ONT focuses on identifying potential donors and obtainingconsent. They have implemented a standardized donation process in every hospital in Spain. TheSpanish 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 allhospitals. Among other things, these teams identify all potential donors and handle theevaluation and management of the donor. Donor management guidelines included in the Spanishmodel are outlined in Appendix II.3

The United States

The United Network for Organ Sharing (UNOS), incorporated in 1984, is “a private, non-profitcorporation that, with government oversight, develops, implements, and monitors policies in anational health system relative to transplantation. In 1986, UNOS was awarded the federalgovernment contract to operate the national Organ Procurement and Transplantation Network(OPTN). Subsequent regulations required all transplant centers to join the OPTN and begoverned by UNOS policies. The OPTN is mandated to assure the effectiveness, equity andquality 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 documenthas been endorsed by the Association of Organ Procurement Organizations, the AmericanSociety of Transplantation, the American Society of Transplant Surgeons and the NorthAmerican Transplant Coordinators Organization. Its use has resulted in an 11.3% increase in thenumber of organs transplanted per 100 donors.5

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There are 59 organ procurement organizations governed by UNOS policies. All were contactedand requested to provide donor organ management guidelines and eligibility criteria (as it is notmandatory that they use the Critical Pathway). Details on organ donor management in the UnitedStates will be provided in a separate presentation at the Canadian Forum on MedicalManagement to Optimize Donor Organ Potential.

Another example of U.S. organ donor management guidelines is provided in Appendix IV. It isthe 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 tomatch and allocate donated organs. It also supports transplantation services across the UnitedKingdom and is responsible for “contributing to the development of performance indicators,standards and protocols which guide the work of organ donation and transplantation”.6 UKTransplant is directly accountable to health ministers in Scotland, Wales and Northern Irelandand to Parliament through the Department of Health in England.

The United Kingdom Transplant Coordinators Association is the association that promotes organdonation, best practices in transplantation and supports transplant coordinators working in theUnited Kingom. (See also United Kingdom Hospital Policy for Organ and Tissue Donation.7)

A standardized donor management technique was developed at the Papworth Hospital inCambridge, England. Murali et al. (2003)8 have published the most recent description of thisapproach. Guidelines from the Papworth Hospital for the management of the multi-organ donorare provided in Appendix V. Further details on the Papworth approach to organ donormanagement will be provided in a separate presentation at the Canadian Forum on MedicalManagement to Optimize Donor Organ Potential.

Australia

The Federation of Australia is composed of six states and one territory. Five states havetransplant programs. “The delivery and organization of health services is a state responsibilityalthough only the central (Federal) government has taxing powers; it therefore controls the fundsavailable for health care.”9 In 1977, South Australia adopted the Spanish Model, describedabove. “Since the introduction of the modified Spanish model, the organ procurement rate inSouth Australia is double the rate of the rest of Australia”10 (23 vs. 10.5 donors per millionpopulation).

The Alfred Hospital in Melbourne has developed a successful system of transplant coordinationand organ allocation.11 Its system is considered a good example of the Australian approach toorgan donation and transplantation. A detailed description of the medical management of thepotential organ donor at the Alfred Hospital has been published.12

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Eurotransplant

The Eurotransplant International Foundation is responsible for the organization and allocation oforgan donation in Austria, Belgium, Germany, Luxembourg, the Netherlands and Slovenia. Thisinternational framework includes all transplant hospitals, tissue-typing laboratories and hospitalswhere organ donation takes place.13

The Leuven University Hospital in Belgium has developed a secure-access website containingorgan 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 thehospital’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 TransplantSurgery, since the implementation of this simplified protocol the hospital has seen a 40%increase in donors.14

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V. ConclusionThis analysis of Canadian management guidelines was based on 17 unique documents. Theseguidelines are for multi-organ donation and are generally consistent in content, although manydo 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 perfusionoften differ between adult and pediatric guidelines (the latter providing age-adjusted values).Few guidelines provide targets for pulmonary capillary wedge pressure, systemic vascularresistance, cardiac index and left ventricular stroke volume.

Standard care for invasive monitoring consists of an arterial and a central venous line. Only eightguidelines provide information on pulmonary artery catheterization. A majority of guidelines citedopamine 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 afew 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 cardiologyconsultations. 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 procurementorganizations. Generally, eligibility is assessed on an individual basis, taking into considerationrecipient need at that point in time. Slight variations exist between OPOs for absolutecontraindications; however most included HIV/AIDS, West Nile virus, active infections andmalignancies.

International issues in organ donor management are directly related to the level of maturity of acountry’s particular program. Recent efforts to optimize the medical management of organdonors (and thus maximize organ yield per potential donor) are under way. Countries at theforefront of this movement are Spain, the United States, the United Kingdom, Australia andmembers of Eurotransplant.

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Appendix I – Canadian Organ ProcurementOrganizationsNote: 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 provincebut did not provide a list of hospitals. Received a reply from one PICU to confirm this. Receivedseparate GL from one adult center.

Alberta

2 OPOs (Northern and Southern Alberta). Stated they each cover specific territory of provinceand provided list of hospitals covered. Hospitals (in both regions) that responded confirmed theyare covered by OPOs. Northern provided pediatric and adult guidelines, Southern has nodocumented 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 ofOPO. 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 provinceand provided list. Responses from hospitals confirmed this. No additional GL received.

Ontario

3 OPOs functioning within the province (transitional period). Trillium has in-hospitalcoordinators, “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 withIRs). 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.

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Nova Scotia

OPO located and functions within one of hospitals contacted. Stated their guidelines coveredhospitals in province and provided list. Responses from hospitals confirmed this. No additionalGL received.

Newfoundland

OPO located and functions within hospital contacted. Only received reply from OPO, stated theirguidelines 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 ofTransplantation

No guidelines or eligibility criteria.

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Appendix II – Spanish Guidelines

MANUAL OF DONATION OF ORGANS FOR HEALTH PROFESSIONALSMAINTENANCE 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 inischemic-necrosis of the neurological structures. A series of secondary pathophysiologicalalterations lead to the absence of function of this great "regulating organ" that is the brain. Thisfundamentally 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 neurogenicdiabetes insipidus (NDI), NDI contributes to the aggravation of hemodynamic instability bycausing polyurias and secondary electrolytic alterations.

All these aspects endanger the viability of the transplantable organs, turning the multi-organdonor into a critical patient requiring strict control and monitoring (tables I and II), as well as anenergetic 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. Cardiocirculatory Stability2. Suitable Oxygenation

3. Correction and treatment of other problems like neurogenic diabetes insipidus, electrolyticarrhythmias, alterations, prevention of infections, etc...

In table II a summary of maintenance objectives can be seen.

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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 childrenTemperature > 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 ofhemoglobin.

o The contribution must be controlled hourly, because large volumes areuseful to maintain good renal flow but can jeopardize cardiac, pulmonaryand 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 areDOPAMINE, 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 thefollowing one:

1. Dopamine.It is the drug of choice for its beneficial effect on renal flow and some authors have found arelation between the decreased appearance of tubular necrosis acute postransplant and the use ofdopamine in doses < 5 µg/kg/min.

Avoid exceeding doses of 10 µg/kg/min (which worsen cardiac and hepatic perfusion through itsalpha-agonist effect).

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2. Dobutamine.Its fundamental indication would be in polytrauma donors with myocardial contusion where it issuspected that ventricular dysfunction is the fundamental cause of the hypotension. Use withcaution since it can increase vasodilation and worsen the hemodynamic situation, by diminishingsystemic vascular resistance.

3. Other vasopressor drugs: Noradrenaline and adrenalin.Their use is restricted to donors with persistent hemodynamic instability in spite of adequatevolume resuscitation and support with dopamine of 10 µg/kg/min. It is necessary to consider thatboth can produce hyperglycemia. Therefore a strict control of glycemia must be maintained withprecise dosing of insulin. The vasoconstriction invalidates the CVP measurements, thus it isnecessary 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, pancreasand kidneys. Thus the simultaneous use of low doses of dopamine are advised to improve renalflow.

If the donor needs large doses of noradrenaline for long periods of time, it is recommended tochange 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 tissuehypoperfusion. This results in frequent assessment of the function of the different organs andmust 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 ofblockade. 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 factorsleading 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.

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The lung donor requires maintenance with respirators of volumetric type and the routine use ofPEEP 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 producepulmonary edema. Use a tidal volume of 8–10 ml/kg and obtain a maximum tip of pressure inaerial 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 asevere hypoxia that can jeopardize the viability of the organs to be transplanted. In donors withpulmonary edema who require elevated levels of PEEP, it could be necessary to insert a Swan-Ganz catheter to adapt treatment based on cardio-respiratory variables.

In all cases, frequent control of arterial gasometry and arterial oxygen saturation is necessary todetect episodes of desaturation early.

Finally and as in any other type of critical patient, the endobronchial suctioning will be carriedout with maximum conditions of asepsis to avoid local respiratory infections or infectionsleading to sepsis.

4. METABOLIC ALTERATIONS.

1. Electrolytic Disturbances.The most frequent are hypernatremia, hypokalemia, hypomagnesemia, hypocalcemia andhypophosphatemia. Early correction of electrolytic alterations is important in order to avoidarrhythmias that could lead to cardiovascular instability. With the goal of obtaining a correctelectrolyte administration, measurements should be made q3–4hrs. Besides checking forimbalances 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 peripheralresistance to insulin.

Amoung its causes it it is necessary to emphasize: infusion of inotropes, resuscitation withliquids that contain glucose, previous treatment with corticosteroids, endogenous catecholaminesecretion during the process of cerebral coning, hypotherma, etc...

Hyperglycemia can result in a hyperosmolar situation with intracellular dehydration, metabolicacidosis and polyuria (which in turn contributes to hypovolemia). In all cases it is necessary tocorrect hyperglycemia with a rapid intravenous infusion of insulin. Use a continuous infusion ofinsulin 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 roomtemperature of 20–22ºC and warm infusion fluids.

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6. NEUROGENIC DIABETES INSIPIDUSBrain death can cause diabetes insipidus which presents as a polyuria. Treat with precise volumereplacement and/or administration of desmopressin.

7. HORMONAL ALTERATIONSFollowing brain death there is a rapid depletion of thyroid hormones. Levels of T3 or T4 may bepractically 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 antidiuretichormone (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 organdonation. Assessment is based on the results of bacteriological cultures and consultationsbetween the intensivist and surgical transplant teams.

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Appendix III — UNOS Critical Pathway

Collaborative

Practice

Phase I

Referral

Phase II

Declaration of Brain Death and Consent

Phase III

Donor Evaluation

Phase IV

Donor Management

Phase V

Recovery Phase

The following professionalsmay be involved to enhancethe donation process.

Check all that apply.

Physician

Critical care RN

Organ ProcurementOrganization (OPO)

OPO Coordinator(OPC)

Medical Examiner(ME)/Coroner

Respiratory

Laboratory

Radiology

Anesthesiology

OR/Surgery staff

Clergy

Social worker

Notify physicianregarding OPO referral

Contact OPO ref:Potential donor with severebrain insult

OPC on site andbegins evaluation: Time___Date ___

Ht____ Wt ____ asdocumented

ABO as documented_____

Notify housesupervisor/charge nurse ofpresence on unit

Brain death documented

Time _____ Date _____

Pt accepted as potential donor

MD notifies family of death Plan family approach with OPC

Offer support services to family(clergy, etc)

OPC/Hospital staff talks to familyabout donation

Family accepts donation

OPC obtains signed consent &medical/social history

Time _____ Date _____

ME/Coroner notified

ME/Coroner releases body fordonation

Family/ME/Coroner deniesdonation – stop pathway – initiatepostmortem protocol – support family.

Obtain pre/post transfusionblood for serology testing (HIV,Hepatitis, VDRL, CMV)

Obtain lymph nodes and/orblood for tissue typing

Notify OR & anesthesiology ofpending case

Notify house supervisor ofpending donation

Chest & abdominalcircumference

Lung measurements per CXRby OPC

Cardiology consult asrequested by OPC

Organ recovery processdiscontinued – donor organsunsuitable for transplantation

OPC writes neworders

Organ placement

OPC sets tentativeOR time

Insert arterial line/CVP/2 large-bore IVs

Checklist for OR

Supplies given toOR

Prepare patient fortransport to OR

IVs Pumps

O2 Ambu

Peep valve

Transport to OR

Date ________

Time ________

OR nurse reviewsconsent & brain deathdocumentation & checkspatient’s ID band

33

Collaborative

Practice

Phase I

Referral

Phase II

Declaration of Brain Death and Consent

Phase III

Donor Evaluation

Phase IV

Donor Management

Phase V

Recovery Phase

Labs/ Diagnostics Review previous lab results

Review previous hemodynamics

Blood chemistry

CBC + diff

UA C & S

PT, PTT

ABO A Subtype

Liver function tests

Blood culture _ 2 / 15 minutesto 1 hour apart

Sputum Gram Stain & C & S

Type & Cross Match ____#units PRBCs

CXR ABGs

EKG Echo

Consider cardiac cath

Consider bronchoscopy

Determine need foradditional lab testing

CXR after lineplacement (if done)

Serum electrolytes

H & H after PRBCRx

PT, PTT

BUN, serumcreatinine after correctingfluid 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

Labs drawn in OR asper surgeon or OPCrequest

Communicate withpathology: Bx liver and/orkidneys as indicated

34

Respiratory

Pt on ventilator

Suction q 2 hr

Reposition q 2 hr

� Prep for apnea testing: set FiO2

@ 100% and anticipate need todecrease rate if PCO2.< 45 mm Hg

Maximize ventilator settings toachieve SaO2 98–99%

PEEP = 5cm O2 challenge forlung placement FiO2 @ 100%, PEEP@ 5 _ 10 min

ABGs as ordered

VS q 1°

Notify OPC for

____ BP < 90 systolic

____ HR < 70 or > 120

____ CVP < 4 or > 11

____ PaO2 < 90 or

____ SaO2 < 95%

Portable O2 @ 100%FiO2 for transport to OR

Ambu bag and PEEPvalve

Move to OR

Treatments/ OngoingCare

Use warming/cooling blanketto maintain temperature at 36.5–37.5°C

NG to low intermittent suction

Check NG placement & output

Obtain actual Ht _____ & Wt_____ if not previously obtained

� Set OR temp asdirected by OPC

� Post mortem care atconclusion of case

Medications

Medication as requested by OPC

Fluid resuscitation – considercrystolloids, colloids, blood

DC meds except pressors &antibiotics

Broad-spectrum antibiotic ifnot previously ordered

Vasopressor support tomaintain BP > 90 mm Hg systolic

Electrolyte imbalance:consider K, Ca, PO4, Mgreplacement

Hyperglycemia: considerInsulin drip

Oliguria: consider diuretics

Diabetes insipidus: considerantidiuretics

Paralytic as indicated forspinal reflexes

DC antidiuretics

Diuretics as needed

350 U heparin/kg oras directed by surgeon

Optimal Outcomes The potential donor isidentified & a referral ismade to the OPO.

The family is offered the option ofdonation & their decision issupported.

The donor is evaluated & found to bea suitable candidate for donation.

Optimal organ function ismaintained.

All potentially suitable,consented organs arerecovered for transplant.

Shaded areas indicate Organ Procurement Coordinator (OPC) Activities

Cardio-Thoracic Donor Management

1. Early echocardiogram for all donors: Insert pulmonary arterycatheter (PAC) to monitor patient management (placement of thePAC is particularly relevant in patients with an EF < 45% or on highdose 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 moderatehyperventilation (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 acomprehensive 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 (titrateSVR 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 glucoseto 120–180 mg/dl)

• Ventilator: (See above)

• Volume Resuscitation: Use of colloid and avoidance of anemia areimportant 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

36

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.

37

Hormonal Resuscitation of the Organ DonorBrain-dead donors who fail conventional resuscitation measures as manifested by a poor cardiacoutput, inadequate organ perfusion pressures, and increasing lactic acidosis often respond tothree-drug hormonal resuscitation (1). Administration of a methylprednisilone bolus andinfusions of arginine vasopressin and triiodothyronine to 701 brain-dead donors resulted in a22.5% increase in the number of organs transplanted per donor(1). Hormonal resuscitation wasbeneficial for donors both under, and over, age 40. Hearts recovered from hormonal resuscitationdonors have a significantly reduced 30 day mortality and a significant reduction in prolongedgraft dysfunction (2).

Bibliography1. 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 EarlyFunction.

3. Hormonal Resuscitation Yields More Transplanted Hearts with Improved Early Function.Transplantation 75: April 27, 2003.

Donor-Related MalignanciesTransmission of donor malignancies is rare with 18 cases from 34,933 cadaver donors and 3cases from 32,052 living donors being reported to UNOS from 1994–2001 (1,2). Donors withpast histories of certain types of cancers may be considered as donors (3) including certain typesof 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 riskdonors include glioblastoma multi-forme, high grade astrocytomas, medulloblastomas, and anybrain tumor donor who has undergone ventriculo-peritoneal shunting.

Bibliography1 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 SharingTransplant Tumor Registry: Donors with a History of Cancer.

4. Transplantation 73:579–82, 2002. Transplant Tumor Registry: Donors with CentralNervous System Tumors.

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UNOS Critical Pathway

Bibliography1. 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 fromthe Use of a Standardized Donor Management Protocol. UNOS Critical Pathway for theOrgan Donor resulted in a 10.3% increase in organs recovered and an 11.3% increase inorgans transplanted. There was no reduction in the quality of the organs transplanted.

3. Circulation 106:836–41, 2002. Consensus Conference Report: Maximizing Use of OrgansRecovered from the Cadaveric Donor: Cardiac Recommendations. Heart donor criteria anda donor management algorithm for heart recovery.

4. Abstract, International Congress of the Transplantation Society. Hormonal ResuscitationYields More Transplanted Hearts with Improved Early Function. Hearts from hormonalresuscitation donors had significantly reduced early graft dysfunction and one-month patientmortality.

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Appendix IV – New England Organ BankThe purpose of this document is to describe the principles of organ donor evaluation andmanagement 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 EvaluationInitial 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 andpressors), 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 managementshould continue through the recovery surgery.

3. Determination of Organs Suitable for TransplantationOrgans may be deemed unsuitable based on donor age, organ injury, disease or grossabnormality. Questions regarding organ suitability in marginal cases should be directed to themedical 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

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5. Organ-specific ConsiderationsLung / Heart-lung Liver / PancreasPrevent pulmonary interstitial fluid overload Prefer dopamine for tx of hypotensionPrefer PRBC's for volume expansion if needed Prefer minimal or no pitressin therapy (toMaintain FIO2 _ 40% and PO2 > 100 mm Hg minimize splanchnic vasoconstriction)Prefer PEEP at 5 cm H20 Avoid excessive crystalloid infusion (toLarge ET tube for bronchoscopy minimize liver congestion)

Maintain PO2 > 100 mm HgHeartIf hypotensive with low SVR, prefer pure vasoconstrictor KidneyCardiac cath indicated for pts. at risk for CAD Prefer dopamine for tx of hypotensionMaintain PO2 > 100 mm Hg Prefer brisk diuresis (urine output > 200

cc/h)May request PA catheter to assess cardiac function Maintain PO2 > 100 mm Hgand determine appropriate therapy

6. Specific Donor Management Problems

PoikilothermiaLoss of thermoregulatory function follows hypothalamic dysfunction in brain dead patients.Passive heat loss may lead to progressive hypothermia which in turn may result in clinicallysignificant changes in organ function (EKG changes, depressed cardiac function, altered cellularmetabolism, etc.) It is far easier to prevent hypothermia than to reverse it. Therefore, patienttemperature 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)

HypertensionSevere 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 oftreatment should be to maintain the diastolic BP below 100 mm Hg. Nipride shouldonly be used in cases of severe, persistent hypertension, and should be discontinuedas 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.

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HypotensionHypotension (SBP < 90 mm Hg) will develop in most brain dead patients at some point in thedonor management process. Many potential donors are hypotensive at the time of the initialreferral. Even brief intervals of severe hypotension can have significant deleterious effects onend organs. Therefore, hypotension should be treated aggressively with therapy based on a soundunderstanding of the cause of the hypotension.

A central venous pressure line and an arterial line are essential in order to manage hypotensionappropriately. When requested by the cardiac team, especially in hemodynamically unstabledonors, a pulmonary artery catheter may be introduced, and serial cardiac outputs and SVRmeasurements can be collected.

HypovolemiaExcessive intravascular volume loss (hemorrhage, third spacing, DI, fluid restrictions, etc.) iscommon in potential organ donors, especially trauma victims. Neurogenic vasodilatation (loss ofboth venous and arterial vasomotor tone) is present in the majority of donors as well. One or bothof these factors may contribute to a relative or absolute hypovolemia. Therefore, wheneverpossible, 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 BPduring the initial interval of volume repletion. Once volume is restored, however, vasoactivedrugs should be used only as needed.) Care should be taken to avoid the development ofpulmonary interstitial fluid overload, especially in potential lung donors. Therefore, in mostcases, colloid (albumin, Plasmanate) and blood products (PRBCs) should be used in combinationwith 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 (inadult pts. only; consultation with a pediatric intensivist is advised for fluidmanagement 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

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Decreased Vascular ResistanceNeurogenic vasodilatation (loss of both venous and arterial vasomotor tone) is present in themajority of donors. Despite adequate volume restoration, some donors will require vasoactivedrug therapy directed at the underlying cause of the hypotension. Effective management of thesedonors requires insertion of PA catheter for determination of cardiac filling pressures, CO, andSVR. Due to the possibility of decreased perfusion to certain organs, vasoconstrictors should beused with extreme caution. High dose vasoconstrictor therapy should be avoided in this setting.The systemic vascular resistance (SVR) should be calculated based on thermodilution cardiacoutput 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 FunctionFollowing resuscitation from cardiopulmonary arrest, due to pre-existing cardiac disease, orsecondary to brainstem herniation, some donors may exhibit depressed cardiac function. Thesepatients will be hypotensive despite adequate volume restoration. The use of vasoconstrictors inthese patients will exacerbate cardiac dysfunction. Donors with depressed cardiac functionrequire inotropic and chronotropic support to maintain an adequate cardiac output. Effectivemanagement of these donors requires insertion of PA catheter for determination of cardiac fillingpressures, 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 InsufficiencyBrain dead patients require frequent pulmonary hygiene to prevent atelectasis and to maintainadequate oxygenation. Positive end-expiratory pressure of 5 cm H2O ("physiologic PEEP") ishelpful, but higher levels of PEEP should be avoided to minimize potentially deleterious effectson venous return and cardiac output. High FIO2 levels must also be avoided in potential lungdonors to prevent pulmonary oxygen toxicity. Ventilator settings should include a tidal volumeof 10 to 15 cc's per kg and a respiratory rate sufficient to maintain arterial PCO2 in the 40–45mm Hg range.

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HypoxemiaArterial 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 willexclude donor lungs for transplantation.

HypercarbiaApnea testing to confirm the diagnosis of brain death can result in significant hypercarbialeading to respiratory acidosis. Careful attention should be paid to the patient's ventilatory statusand 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 mmHg range.

PolyuriaPolyuria (urine output > 500 ml per hour) is frequently seen in brain dead patients. It may be dueto physiological diuresis, osmotic diuresis (mannitol, glucose), diuresis caused by hypothermia,partial or complete diabetes insipidus, other diuretics, or a combination of the above. Excessivepolyuria due to osmotic diuresis or DI may lead to hypernatremia, hypokalemia, andhyperosmolality. Serum potassium should be monitored and treated as indicated. Urine andserum electrolyte levels and osmolality aid in the determination of the cause of polyuria.

Physiological diuresisAggressive volume restoration may result in a physiological diuresis. No treatment is warranted,but intake and output should be monitored carefully.

Osmotic diuresisPrior mannitol administration or excessive glucose infusion may result in an osmotic diuresis.

Treatment:

• Mannitol administration should be avoided in this setting. Glycosuria andhyperglycemia should be treated with sliding scale IV insulin therapy to normalizeblood glucose levels.

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Diabetes insipidusOnce the abovementioned causes for polyuria have been excluded, the diagnosis of DI can bemade by evaluating the volume of urine output, urine specific gravity, urine and serumelectrolyte levels, and urine and serum osmolality. At least three of the following findings shouldbe present simultaneously to establish the diagnosis of DI:

• Urine output > 500 ml per hour Serum sodium > 155 mEq/L• Urine specific gravity < 1.005 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 thecalculated deficit should be infused as rapidly as possible, preferably with a hypotonic solutionsuch as D5W or 0.5 NS.

The use of pitressin should be avoided when possible in liver and pancreas donors to minimizethe possibility of decreased perfusion to these organs.

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Appendix V – Papworth approach

PhilosophyThe 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 tooptimise the physiological environment for the heart and lungs. Once all the possiblemanoeuvres have been employed, the mechanical function of the heart and the gas exchangingfunction of the lungs are reassessed. Then, and only then, is it appropriate to reject organs wherefunction falls below acceptable minimum targets.

The practical implications of this philosophy include increased financial expense and anincreased number of procurement journeys with no transplantable organs being obtained, but thepossibility of wasting transplantable organs will be minimized.

Management of the multi-organ donor

1. Infection ControlOrgan retrieval should be carried out in an operating theatre to the standard of any other surgicalprocedure. In particular, staff should follow the normal practice of limiting the number ofindividuals 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 bekept to a minimum.

2. Ventilation2.1 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 sputumsample for culture.

2.4 Manually inflate lungs under direct vision after sternotomy and opening pleura, and noteany consolidation and trauma.

3. Vascular AccessA 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)

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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. Haemodynamics4.1 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 Management5.1 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. Antibiotics6.1 Give the following regime at induction after taking blood samples for culture:

a. Vancomycin 1 g

b. Meropenem 1 g

7. Steroids7.1 Methyl Prednisolone 500 mg stat dose.

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THE PAPWORTH DONOR MANAGEMENT HORMONE REPLACEMENTPROTOCOLThe 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.

2.• 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).

NB If mean arterial pressure > 90 mm Hg following administration of pitressin, discontinueinfusion.

3.• Insulin (Human actrapid)• Commence sliding scale insulin to maintain blood sugar between 4–6 mmol/l

Blood sugar Insulin Perfusiona

> 15 mmols 5.5 IU/hr8–15 mmols 3.5 IU/hr4–8 mmols 1.5 IU/hr< 4 mmols GIK 1.5 ml/kg/hra 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 inany doubt.

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Appendix VI – Leuven University Hospital

Procedure multi-organ donor

General remarksIn every multi-organ donor (MOD), attempts must be made to achieve optimum protection for allorgans which can potentially be procured. This protocol therefore applies to all cases in whichorgans can be procured from donors with a "beating heart". This protocol becomes effective assoon as the "pronouncement of death" (brain death) has been completed and signed by threeindependent doctors, in accordance with Belgian legislation and the procedure applicable in thatspecific hospital.

It goes without saying that before brain death occurs, optimum protection for all organs must beensured.

If cardiocirculatory stability cannot be achieved by the usual methods, the additional measures ofdonor management must be performed.

Every potential donor must be reported to a transplant coordinator.

SterilityComplete sterility of the donor must be guaranteed when using and positioning catheters, caringfor 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 therapyThe filling situation is extremely important

Aim for a central venous pressure of 8 mm Hg to 10 mm Hg mean at positive pressurerespiration PEEP +5 and the transducer at the level of the right atrium when the donor ishorizontal. Overfilling can very quickly compromise the lungs and under filling causeshaemodynamic instability.

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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 theprevious urine output per hour + 50 ml. Avoid hypernatremia at all costs

• BUT: unrestrained administration of a solution containing sodium in order to preventdiabetes VERY QUICKLY causes dangerous hypernatremia

Urine outputThe 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, 6µg (1 amp. = 1 ml = 4 µg). Repeat as soon as necessary, i.e. when diuresis again risessharply (usually every 6 hours)

VentilationPlace a filter on the Y section of the ventilator tubes. Use of an artificial nose is a validalternative. However, if the patient is supercooled, use a humidifier and place a filter on theinspiratory 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, whichimplies normal PaCO2 in the absence of a metabolic component. If the tidal minute volume hasto 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 asepticbronchial toilet, followed by careful bag squeezing.

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Acid–base equilibriums, electrolytes and glucoseAnomalies are corrected

• Blood gas values are not corrected for temperature. Ventilate up to normal PHincluding where pronounced metabolic acidosis is present. In the mean time, themetabolic acidosis is corrected based on the base deficit. If the bicarbonate content isnormalised, 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 andregulations 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 andhypertension 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 andacid–base disorders

If average arterial pressure remains lower than 70 mm Hg, start dopamine up to max. 5µg/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 andincreased body temperature.

Hydrocortisone (Solu-Cortef® Upjohn)3 _ 200 mg/24 hUp 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 bloodsugar 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 lungswill NOT be transplanted can a fluid challenge be performed or the CVP be allowed to rise to10–12 mm Hg.

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If the previous measures are inadequate, insert a Swan-Ganz catheter. Only after the necessaryinterventions have been performed can the dopamine be increased up to a maximum of 10µg/kg/min or eventually administration of vasoconstrictor infusions

Cardiac arrests are treated « lege artis », and a re-evaluation of the donor is undertaken.

CoagulationDisseminated intravascular coagulation (DIC) occurs relatively often in multi-organ donors. Ifcoagulation tests indicate, a thromboelastogram may be required. Severe coagulopathies aretreated « lege artis » when a volume replacement problems exist. (CMV negative preparations).Aminocaproic acid and tranexamic acid are completely contraindicated. Coagulopathies are onlytreated if donor stability is threatened.

Temperature ControlEfforts are made to maintain a temperature > 35°C with the help of a heated mattress, a warmerfor blood infused for volume replacement, an artificial nose filter and eventually a respiratoryhumidifier, limitation of volume loss due to excessive diuresis, administration of T3.

AntibioticsIn principal, antibitics are only given on the basis of culture results.

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