Model protocol for organ donation

This protocol describes the procedure for post-mortem organ donation. Here you will find a description of all steps and the actions that must take place.

Diagram 1 shows the process of post-mortem organ donation. The diagram shows at what time which steps apply, who is responsible for which step, and what each step entails. The steps are explained in the chapters.

The diagram distinguishes between the DBD procedure and the DCD procedure. Different steps are taken for each procedure.

• A DBD procedure starts with the determination of death.
• In a DCD procedure, death is only determined in the final phase.

The registration of the donor and the organization of logistics are the same for both procedures. These tasks are described in chapter 7.

The donation process starts with the identification of a potential donor. This chapter provides tools for that. The chapter describes the criteria and contraindications for organ donation. The colored block in Figure 2 shows which step is described in this chapter.

If a doctor decides to stop a patient's life-prolonging treatment and the patient is expected to die, the possibility of organ donation must be considered. Whether donation is possible depends on whether there are contraindications. A distinction is made between general contraindications, relative contraindications, and organ-specific contraindications.

2.2.1 General contraindications

The general contraindications for organ donation are:

• The patient's identity is unknown
• < 24 hours of adequately treated sepsis
• Active tuberculosis
• An active infection with rabies, herpes zoster, or rubella
• Anencephaly

In all these cases, organ donation is excluded.

2.2.2 Relative contraindications

The relative contraindications are:

• HIV
• Chronic/active untreatable infections, for example Q fever
• Hepatitis B (download the national protocol)
• Malignancies
• An unknown cause of death

Note: In the case of malignancies, donation is sometimes possible, namely:

• In some primary, non-metastatic brain tumors.
• If the malignancy has been treated with curative intent.

In case of a relative contra-indication, consult the Organ Center (071 579 57 95) or the on-duty ODC.

2.2.3 Organ-specific contra-indications and age criteria

Organs can be excluded from donation due to underlying diseases or for not meeting the age criteria.

Table 1 shows the contra-indications and age criteria per organ. The age criteria per organ differ for a DBD and a DCD procedure.

Table 1: Organ-specific contra-indications and age criteria

In the Netherlands, children can also be organ donors. Children aged 12 and over can register in the Donor Register, and children under 12 can be donors if their parents give permission.

Therefore, consult the Donor Register for children aged 12 and over, and for any potential organ donor under 18, contact the Organ Centre (071 579 57 95) or the on-duty ODC. Do this before the conversation with the parents/family. See 3.4 for more information about children as donors or go to the Protocol Child as donor.

In case of doubt about a contra-indication or doubt about a patient's suitability for organ donation, contact the Organ Centre via 071 579 57 95, or with the on-duty ODC.

Are there no general contraindications? If so, consult the Donor Register and then contact the Organ Center via 071 579 57 95, or with the on-duty ODC.

If organ donation turns out not to be possible for a patient, check chapter 2 of the Model Protocol for Tissue Donation to see if the patient might be able to donate tissues. The tissue donation procedure can be initiated after the patient's death.

View the national overarching protocol for hepatitis B here.

Download the national protocol

2.8.1 Introduction

Due to the introduction of direct-acting antiviral (DAA) therapy, the treatment of hepatitis C virus (HCV) has greatly improved, with >95% effectiveness. As a result, there are more opportunities to transplant HCV-positive organs (kidneys, hearts, lungs, and livers). Transplantation from HCV-positive donors to HCV-negative recipients has proven to be safe, which can shorten waiting lists and reduce waiting list mortality and morbidity.

This protocol serves as a guideline for the diagnostics and treatment of HCV after solid organ transplantation (SOT), in the case of an HCV-positive donor and an HCV-negative recipient.

2.8.2 HCV-positive donors - categories

There are three categories of HCV-positive donors, with different interpretations and recommendations. The subsequent paragraphs focus on category 3, and category 2 if the HCV PCR result is positive.

Note: If there are indications that the donor has failed DAA therapy, this protocol does not apply and the organ should not be accepted.

2.8.3 Considerations for accepting an HCV+ organ

The probability that the recipient becomes positive after transplantation in a donor positive/recipient negative (D+/R-) HCV setting is nearly 100% for all types of organs. The primary treating physician must make an evaluation in which factors such as organ quality, potential co-infections, availability of HCV DAA therapy post-transplantation, and waitlist morbidity and mortality play a role. If the organ is a liver, these will in principle not be accepted, unless the presence of cirrhosis/fibrosis can be ruled out by the gastroenterologist.

2.8.4 Informed consent

It is strongly preferred to ask patients for consent during preparation or electively for the acceptance of a potential anti-HCV positive donor. It should be discussed that the chance of a recipient becoming positive in a D+/R- HCV setting is nearly 100%, but that treatment for this is successful. It is discouraged to ask for consent at the time of an offer.

2.8.5 Diagnostics

As previously described, in a D+/R- HCV positive setting the chance of a recipient becoming HCV positive is nearly 100%, and prophylactic treatment can be considered without plasma HCV PCR. If one wishes to establish HCV infection in the recipient, a plasma HCV PCR can be drawn from the recipient between days 3 and 5 post-transplantation. If the HCV PCR is negative, determine the HCV PCR again on day 7. 90% of HCV recipients are viremic within 7 days. In these cases, pre-emptive initiation is still possible. If the HCV PCR is still negative on day 7, repeat weekly until week 4. If the PCR is negative after week 4, an HCV infection in the recipient is nearly unlikely. Consult a virologist, infectious disease specialist, and/or gastroenterologist regarding follow-up diagnostics.

2.8.6 Treatment

Treatment takes place after consultation with a virologist, infectious disease specialist, and/or gastroenterologist.

Timely treatment should take place as described below to prevent complications such as acute hepatitis and non-hepatic complications such as acute HCV-related glomerulonephritis, acute pancreatitis, acute cellular rejection, and vasculopathy.

Monitor the treatment effect by means of HCV PCR at the end of treatment (EOT). In addition, HCV PCR should take place at week 12 (SVR12) and week 24 (SVR24) after the end of treatment. Consult with an infectious disease specialist/gastroenterologist and/or virologist if the EOT measurement or SVR measurements turn out to be positive.

2.8.8 Considerations for renal impairment, hepatic impairment and DAA interactions

In HCV patients with chronic renal insufficiency, including patients with eGFR <30 ml/min and patients on hemodialysis, DAAs can be prescribed according to recommendations without dose adjustment.

For interactions, see www.hep-druginteractions.org for the most up-to-date advice, in addition to the tables in the EASL Guideline on interactions of DAAs with common co-medication.

This guideline specifically addresses the following interactions:

This chapter discusses the procedure for consulting the Donor Register:

• Who is allowed to do this, and when and how (3.1)?
• What do the various registrations mean?
• Per type of registration: what is expected of the officer? Distinction between competent patients (3.2), incompetent patients (3.3) and children (3.4).
• What are the guidelines in the event of an unnatural death (3.5).
• When the physician may begin the preparatory procedures for a potential organ donation (3.6)?

3.1.1 When to consult?

The Organ Donation Act requires hospital physicians to always consult the Donor Register if a patient:

• Is suitable as an organ and/or tissue donor and there is a reasonable chance that they will die within the foreseeable future or
• Is suitable as a tissue donor and has just died.

Does a patient die outside the hospital and are you involved as a general practitioner or other extramural physician? Then it is your professional responsibility to consult the Donor Register.

Consult the Donor Register before discussing donation with the family.

Will/Declaration of intent

The Donor Register must also be consulted if another statement of intent has been found with the patient. This is necessary to check whether the statement of intent does not conflict with the registration in the Donor Register. You can read more about this in 3.1.2.

The Donor Register does not need to be consulted in these cases:

• The patient does not meet the criteria for organ and tissue donation or there are general contraindications. See also:
  • Donor recognition organs
  • Donor recognition tissues
  • If in doubt about suitability, call the Organ Centre: 071 579 57 95.
• The patient is younger than 12 years old. Special rules for consent apply in that case (see 3.4).
• The identity is unknown and it is therefore not possible to consult the register. Donation is not permitted in that case.
• The potential donor died more than 24 hours ago. Donation is no longer possible in that case.

The official can consult the Donor Register by calling the Organ Centre: 071 579 57 95.

The Organ Centre acts as an intermediary for consulting the register. The official cannot view the Donor Register directly.

Consulting the Donor Register requires the following information:

Requesting official

• Name (optionally the name of the employee calling on behalf of the official for consultation)
• BIG registration number
• Telephone number at which this contact person can be reached (only in the event of organ donation)

Institution

• Name
• Address (only when consulting from outside a hospital)
• Department (where the patient is currently located)

Patient

• BSN
• Initials - Predicates - Last name
• Date of birth
• Gender
• Address

During the telephone consultation, the Organ Centre employee may first ask a few medical questions to rule out the most common contraindications for donation. This takes about 5 minutes.

Are there no contraindications present? Then the employee will consult the Donor Register and communicate the result by phone. In doing so, the employee will also indicate for which organs and/or tissues consent has been given and for which not.

During the procedure (at the request of the family), the official may at any time request a printout of the statement of will from the Organ Centre. The hospital's donation coordinator can find the result of the consultation via the DC application. If desired, this information can be added to the patient file. This is not mandatory.

Conversations with the Organ Centre are recorded on tape for training purposes, to be able to listen back to the conversation and for archiving.

What the step is after consulting the Donor Register depends on the outcome of the consultation as well as the capacity and age of the patient.

• Was the patient 12 years of age or older at the time of death? And was he/she competent at the time of registration? Then follow the flowchart in 3.2.1.
• In 3.2.2 through 3.2.7 you will find the steps per registration.
• Was the patient incompetent at the time of registration? Read the procedure in 3.3.
• Was the patient younger than 18 years old at the time of death? Read the (additional) guidelines in 3.4.

Is the patient registered in the Donor Register with 'no objection' to donation? This means that the donation of tissues and organs for the purpose of transplantation is permitted. No additional consent is required. However, the official must inform the relatives about how this registration came about.

The registration is legally valid if the patient was competent at the time of registration. Read in 3.3 what to do if the patient was incompetent at the time of registration.

Starting points for the conversation

The starting points for the conversation with the relatives are described in chapter 4. The conversation must take place prior to the donation. The official can use the information in the following box for this purpose.

Is the patient registered in the Donor Register with 'yes, I give permission for donation' and is this registration legally valid? Then this means that the removal of tissues and organs for transplantation is permitted. No additional permission is needed. However, the officer must inform the loved ones about the way in which this permission came about. The registration is legally valid if the patient was 12 years of age or older and capable of making decisions at the time of the registration.

• Read in 3.3 what to do if the patient was incompetent at the time of registration.

Particulars for specific organs or tissues

• Has the patient excluded certain organs and tissues from the permission for donation? Then no donation of these organs and tissues will take place. Nor does that happen if the surviving relatives up to the 2nd degree indicate that they do wish to give permission for this.
• Were there any tissues or organs at the time of registration that could not yet be transplanted then and can be now? Then ask the surviving relatives for additional permission for the donation of those organs or tissues.

Example: Previously only the cornea was transplanted, now other parts of the eye are also transplanted. The patient only gave permission for transplantation of the cornea during their registration. Therefore, additional permission must be asked of the surviving relatives for the transplantation of eye tissue.

Is the patient registered in the Donor Register with a 'no' and is this registration legally valid? Then this means that they consciously chose not to give consent for donation. In that case, no donation takes place. However, the official must inform the patient's loved ones of this registration. The registration is legally valid if the patient was 12 years of age or older and mentally competent at the time of registration.

Read in 3.3 what to do if the patient was incompetent at the time of registration.

Donation never permitted

With this type of registration, donation is under no circumstances permitted, not even if the patient is 12 to 16 years old and the parents exercising parental authority or the guardian have a different wish.

Has the patient registered in the Donor Register that they leave the decision regarding donation to their surviving relatives and is this registration legally valid? Then the official must inform the patient's loved ones of this registration. They must also ask for consent for donation from the surviving relatives up to the 2nd degree.

Read in 3.3 what to do if the patient was incompetent at the time of registration.

Starting points for the conversation

For the conversation with the surviving relatives, the principles described in apply chapter 4, in 4.6 and 4.7 describes how the official must request consent, which surviving relatives have decision-making authority, and how to act if these surviving relatives disagree with one another.

What if it is not possible to reach the surviving relatives (in time) or if there are no surviving relatives?

Is it not possible to reach any of the surviving relatives? Then the official will try to postpone the donation until someone has been reached. 4.5 states which steps the official takes to reach the surviving relatives.

Until the surviving relatives have been reached, the official is already permitted to perform preparatory actions for the donation, as described in 3.6.

Can the official reach none of the surviving relatives? Or can the donation no longer be postponed? Then there is no consent and no donation takes place. After all, asking the surviving relatives for consent is a mandatory part of the procedure in this case. In addition, through the surviving relatives, the official can also obtain information about the medical and social history of the patient, including their capacity to make decisions.

Are there no longer any surviving relatives up to the 2nd degree alive? Then donation is not permitted. There is then no consent for donation.

Has the patient registered in the Donor Register that they leave the decision regarding donation to a specific person, and is this registration legally valid?

Then the official must inform that person about the registration and ask them for consent for donation. Where applicable, the official must also inform other close relatives about this registration. The registration is legally valid if the patient was 12 years of age or older and capable of making decisions at the time of the registration.

Read in 3.3 what to do if the patient was incompetent at the time of registration.

Starting points for the conversation

The principles described in apply to the conversation with the designated person chapter 4, in 3.6 state the guidelines for requesting consent for donation.

Does consulting the Donor Register reveal that the registration in question is blocked? Or is there no registration present? In that case, the official must inform the patient's family about this and explain how this is possible. The official can use the information provided in the box below for this purpose.

In this case, the official must make a reasonable effort to see if the patient has recorded their decision regarding donation in another way. If there are no other declarations present, no choice of the patient is known. This choice can therefore not serve as a starting point for the conversation with the family. There is also no permission for donation. Therefore, the official must ask the surviving relatives up to the 2nd degree for permission.

Sometimes there may be suspicions that the patient lacked capacity during (part of) their life. This may become apparent, among other things, from the conversation with the family, from the medical file, or from other available information, for example about a stay in a residential facility for people with an intellectual disability. Did the patient lack capacity at the time of registration in the Donor Register? Then, since the amendment of the Wod on July 1, 2020, they can sometimes still be a donor. Therefore, in the case of suspected lack of capacity, the official takes the following steps.

3.3.1. Verifying whether the patient lacked capacity at the time of registration

First of all, the official verifies whether the patient actually lacked capacity during (part of) their life. To this end, they consult various sources. Determining decision-making capacity is seen as a medical skill: it is part of general medical practice.

If the patient was mentally incompetent during (part of) their life, the official checks whether the registration in the Donor Register is valid. To this end, they ask the Donor Register when and by whom the registration was made.

The registration is valid:

1. The patient made it themselves at a time when they were 12 years of age or older and mentally competent, or
2. The patient was registered with 'no objection' at a time when they were mentally competent, or
3. A legal representative of the patient made the registration at a time when the patient was 18 years of age or older and mentally incompetent.

In the first 2 cases, the official can act as if the patient has been mentally competent their entire life. See 3.2.

In the third case, the official follows the procedure described in:

• 3.3.3 and 3.3.4: if the donation conversation takes place before the patient's death (organ donation)
• 3.3.5 and 3.3.6 :if the donation conversation takes place after the patient's death (tissue donation)

The registration is not valid:

1. The patient made the registration themselves during a period when they were incompetent. Or:
2. The patient was registered with 'no objection' during a period when they were incompetent.

If the registration is invalid, it cannot serve as the basis for the discussion with the relatives. The official must then request consent for donation. The same applies if no registration is present.

Whom the official must ask for consent depends on whether the discussion takes place before the patient's death (organ donation) or after the patient's death (tissue donation). See the following paragraphs for this.

Does the patient die in the hospital and are they suitable as an organ donor and possibly also as a tissue donor? Then the official conducts the donation discussion shortly before the patient actually passes away. With whom they conduct this discussion and whether they must ask for consent for donation in it, you can see in the following schedule.

As appears from the schedule in 3.3.3, the subsequent steps for incompetent patients depend on who made the registration and when. The various situations are further explained below.

1. The registration was made by a legal representative of the patient

A legal representative (for example, a curator, mentor, or authorized representative in writing) can record the patient's choice in the Donor Register on their behalf. Did a legal representative do this during the time the patient was incompetent? And is the patient 18 years of age or older upon death? Then this registration is valid. The official must then discuss the registration with the legal representative and/or the surviving relatives. The following applies in this regard:

• Is the patient registered with 'yes'? Then the official must ask the legal representative whether they confirm this registration. If so, the donation can proceed. If not, no donation takes place.
• Is the legal representative unreachable? Then the official can ask the surviving relatives up to the 2nd degree for confirmation. If they confirm the registration, the donation can proceed. Do they not confirm the registration or are there no surviving relatives up to the 2nd degree reachable? Then no donation takes place.
• Is the patient registered with 'decision left to the surviving relatives'? Then the official must ask the surviving relatives up to the 2nd degree for consent for donation. See 3.2.5.
• Is the patient registered with 'decision left to a specific person'? Then the official must ask the designated person for consent for donation. See 3.2.6. Incidentally, a legal representative may also have designated themselves as the specific person authorized to decide on the donation.
• Is the patient registered with 'no'? Then no donation takes place. The official informs the legal representative and the relatives about this.

2. The registration was made by the patient themselves at a time when they lacked capacity

Did the officer check the date of registration with the Donor Register/Organ Centre? And was the patient lacking capacity on that date? If so, this registration is invalid. The officer must then ask the legal representative for consent to donation. If they give consent, the donation can proceed. If they do not give consent, no donation will take place.

Is the legal representative unreachable? Then the officer can ask the next of kin up to the 2nd degree for consent. If they give consent, the donation can proceed. If they do not give consent or if no next of kin up to the 2nd degree can be reached? Then no donation will take place.

3. The patient is registered with 'no objection' at a time when they lacked capacity

The same procedure applies here as in point 2.

4. There is a block on the Donor Register or there is no registration present

The same procedure applies here as in point 2.

If a patient is exclusively suitable as a tissue donor, the officer conducts the donation conversation after the patient has died. The legal representative no longer has decision-making authority at that point. Therefore, the officer conducts the donation conversation with the next of kin up to the 2nd degree. What is discussed with them can be seen in the following flowchart:

As appears from the schedule in 3.3.5, the subsequent steps for incompetent patients depend on who made the registration and when. The various situations are further explained below.

1. The registration was made by a legal representative of the patient

A legal representative (for example, a curator, mentor, or authorized representative in writing) can record the patient's choice in the Donor Register on behalf of the patient. Did a legal representative do this at a time when the patient lacked capacity? And is the patient 18 years of age or older at the time of death? Then this registration is valid.

The officer must then discuss the registration with the next of kin up to the 2nd degree. They cannot discuss this with the legal representative, as the latter no longer has decision-making authority after the patient's death.

The following applies to the conversation with the next of kin:

• Is the patient registered with 'yes'? Then the officer must ask the next of kin whether they confirm this registration. If so, the donation can proceed. Do they not confirm the registration or are there no next of kin up to the 2nd degree reachable? Then no donation will take place.
• Is the patient registered with 'decision left to the surviving relatives'? Then the official must ask the surviving relatives up to the 2nd degree for consent for donation. See 3.2.5.
• Is the patient registered with 'decision left to a specific person'? Then the officer must ask that designated person for consent for the donation. See3.2.6.
• Is the patient registered with 'no'? Then no donation will take place. The officer informs the relatives of this.

2. The registration was made by the patient at a time when they lacked capacity

Did the officer check the date of the registration with the Donor Register/Organ Centre? And was the patient lacking capacity on that date? Or did they lack capacity their entire life? If so, this registration is invalid. The officer must then ask the next of kin up to the 2nd degree for consent to donation. If they give consent, the donation can proceed. If they do not give consent or if no next of kin up to the 2nd degree can be reached? Then no donation will take place.

3. The patient is registered with 'no objection' at a time when they lacked capacity

The same procedure applies here as in point 2.

4. There is a block on the Donor Register or there is no registration present

The same procedure applies here as in point 2.

If the patient is younger than 18 at the time of death, special rules apply to donation. A distinction is made between children under 12, children aged 12 to 15, and children aged 16 and older. Look here for the Child as a Donor protocol.

If the attending physician cannot issue a declaration of natural death, organ or tissue donation is still a possibility. However, permission from the public prosecutor is required.

If there is a possibility of organ donation, preparatory procedures for the donation may be performed before the potential donor has died. The purpose of this is to keep the organs suitable for transplantation. Below is an explanation of what preparatory procedures entail and which conditions apply. These rules originate from the Organ Donation Act (Wod).

3.6.1 What are preparatory procedures?

The preparatory procedures for organ donation are:

• Performing examinations that are necessary in preparation for the donation.
• Initiating or maintaining artificial ventilation.
• Artificially maintaining the blood circulation.
• Taking other measures necessary to keep the organs suitable for donation.

In concrete terms, this means, for example, that a patient may be intubated to make organ donation possible. This is only permitted if the conditions below are met.

3.6.2 When may preparatory procedures be started?

The physician may begin the preparatory procedures if all of the following conditions are met:

• The Donor Register has been consulted.
  • If the patient is registered with 'yes' or 'no objection', preparatory procedures may be started immediately.
  • If the patient is registered with 'No', no preparatory procedures may be performed. Donation is then not applicable.
  • If the patient has left the choice to the surviving relatives or a specific person, preparatory procedures may be started pending the conversation with the surviving relatives or the specific person.
  • If there is a block in the Donor Register or if there is no registration of the patient present, preparatory procedures may be started pending the conversation with the surviving relatives.
  • It is medically pointless to treat the patient further.
• The decision to discontinue treatment must have been made before procedures are performed that are solely intended for donation.
• The patient will die within the foreseeable future.
• The preparatory procedures do not conflict with medical treatment.
• The preparatory procedures cannot wait until after death.
• The family has not objected to the preparatory procedures. If the family has not yet been reached, preparatory procedures may be started.

After consulting the Donor Register, a conversation always takes place with the patient's loved ones about the registration in the Donor Register. We call this conversation the initial part of the donation conversation.
You will find here:

• Starting points for this conversation and dealing with the loved ones. These starting points apply to all conversations described in 3.2 through 3.4.
• Information about who conducts the conversation (4.2), with which loved ones and surviving relatives the conversation takes place (4.5 through 4.7)
• How the official can deal with any objections to the registration or the donation (4.10 and 4.11).

Please note:

• This chapter is partly based on the Quality Standard for Donation, which was developed in the context of the amendment to the Organ Donation Act (Wod) – effective 1 July 2020. All physicians are required to adhere to this standard.
• Tissue donation is also discussed in this chapter, because the conversation with next of kin regarding organ donation is similar to that regarding tissue donation. Sometimes the conversation also covers both tissue and organ donation.
• All sections in this chapter are an elaboration of the Organ Donation Act (Wod) and are therefore normative. They may not be deviated from.

Figure 4 shows which step in the organ donation process this chapter describes.

Interaction with next of kin

The starting point for the donation conversation and the interaction with next of kin is to do as much justice to the patient's will as possible. In this regard, the patient's registration in the Donor Register is in principle leading.

The official conducting the conversation with the next of kin makes every effort to ensure that the patient's registered wish is carried out. They always discuss the registration with the next of kin. There is room and time for them to respond to this.

If, according to the surviving relatives, the registration does not correspond to the actual wish of the patient, the official enters into a dialogue with them to determine whether that is plausible. In doing so, the official tries as much as possible to reach an agreement with the surviving relatives.

Please note:

• If a patient is registered with 'No, I do not give consent', the surviving relatives cannot change this conclusion. In that case, no donation takes place.
• Has the patient excluded certain organs or tissues from donation? Then the surviving relatives cannot change this either. In that case, no donation of the relevant organs or tissues takes place.

The hospital designates officials from one or more professional groups who are authorized to conduct the donation conversation. The hospital fills this in on atemplate document.

The official who enters into the conversation about donation with the next of kin is there solely for the patient and their next of kin. The standard is that this official has no involvement whatsoever with patients who are on the waiting list for an organ and/or tissue transplantation. If the next of kin so wish, it is possible to ask other professionals to join the conversation. The official can also actively point out this possibility to the next of kin. Think for example of a social worker, a psychologist, or a spiritual caregiver.

In addition, other physicians or specialists can also provide support during the conversation. To be able to provide good information about donation, it is important to have a physician present at the donation conversation who has completed the 'Communication regarding Donation' training, or who has experience in discussing donation. For organ donation, the latter is mandatory.

The conversation with the next of kin about donation generally takes place after the 'breaking bad news' conversation. During the breaking bad news conversation, the next of kin have been told that the patient is expected to pass away shortly (whether or not after stopping treatment), or that the patient has already passed away (in the case of tissue donation).

Only after the next of kin have been informed about this can the conversation about a possible donation take place. Sometimes the next of kin bring up donation themselves during the 'breaking bad news' conversation.

The conversation only takes place if there are no contraindications and there is a reasonable suspicion that the patient's organs and/or tissues are suitable for donation (see chapter 2). If that is not the case, no donation conversation takes place, but the surviving relatives are informed of this out of considerations of due care.

Before the donation conversation takes place, the official must have consulted the Donor Register.

In case of doubts about suitability or questions about the donation procedure in general, the official can always contact the Organ Centre via 071 579 57 95. In the event of organ donation, the Organ Centre will, if necessary, transfer the official to the on-duty ODC.

No donation can take place without the registration in the Donor Register having been discussed with the patient's next of kin. The function of this conversation is to inform the next of kin about the registration regarding donation. The purpose is to help ensure that the next of kin can come to terms with the final decision, whatever it may be.

During the conversation with the next of kin, the official discusses the outcome of the consultation of the Donor Register and – if applicable – the rest of the procedure. They may also provide information about the procedure (partly) in writing, but never as a replacement for verbal information. The written/digital information then serves for review or to share with next of kin who could not attend the conversation.

Sometimes the official must also explicitly ask for consent for donation during the conversation. This is only necessary in certain cases, for example if the patient has explicitly indicated this in the Donor Register. You can read when this is exactly necessary in 3.2 through 3.4, in 4.6 you will find the procedure to follow if consent is required.

In all cases – regardless of whether consent is needed or not – the conversation with the next of kin is a dialogue. The official reports what has been registered and how the registration came about. The next of kin are given the opportunity to respond to this and to ask questions. In 4.10 and 4.11 it is explained how the official can deal with any objections from the surviving relatives against the registration or against the donation.

Do the next of kin have many questions? And is the official unable to answer them? Then it is possible to involve another professional with expertise in the field of donation in the conversation. The official can reach them via the Organ Centre (071 579 57 95).

If the next of kin so desire, they may make an audio recording of the conversation about the registration (and the donation) for their own use. If they wish to do so, they must inform the official in advance. Under no circumstances are the next of kin or others allowed to film the conversation.

Which next of kin the official must conduct the registration conversation with depends on the content of the conversation. The Organ Donation Act (Wod) makes a distinction in this regard.

Does the official only need to discuss the registration in the Donor Register and not ask for consent for donation, due to a 'yes' or 'no objection' registration? Then the official can conduct the conversation about the registration with a 'next of kin' of the patient. This can be anyone who played a (major) role in the patient's life and thus knew the patient well and was actively involved in their life. Whether the person present at the hospital falls under this definition is up to the professional judgment of the official.

Does the official have to ask the surviving relatives for consent for donation, due to the registration 'decision left to surviving relatives', incapacity to make decisions, no registration, a blockage of the register, or a registration of a minor? Then they must conduct the conversation with surviving relatives up to the 2nd degree. According to the Wod, only they have decision-making authority. See 4.6 for more information.

Is it necessary to request consent for donation from relatives up to the 2nd degree or from a specific person, such as in cases of 'decision left to relatives', 'decision left to a specific person', mental incapacity, no registration, a register block, or registration by a minor? If so, the officer explains at the beginning of the conversation how the registration came about and what that means. They then ask for consent.

Multiple people may be present during this conversation. The officer engages in a dialogue with them and provides the information they need to make an informed decision. This information can also be provided in writing so that the relatives or the designated person can read through it calmly. Afterwards, the officer gives those with decision-making authority time to think and let the information sink in. This may mean resuming the conversation at a later time to hear the decision. It is of great importance that the relatives are given time to process all information regarding the (imminent) death and potential organ and/or tissue donation.

At the end of the conversation, the officer summarizes what has been discussed and states whether consent for donation has been given or not. They also inform those with decision-making authority that they can withdraw consent up until the moment the patient is in the operating room/morgue and the donation of organs or tissues has started. This information can also be reviewed in writing.

The Organ Donation Act (Wod) states that only relatives up to the 2nd degree are authorized to grant consent for donation (for persons lacking capacity and children: see 3.3 and 3.4). Furthermore, only relatives have the right to object to a 'no objection' or 'yes' registration or to the donation itself (see 4.10 and 4.11). Relatives include the following categories:

1. Spouse, registered partner, or other life companion of the patient.
2. Adult blood relatives up to the 2nd degree: (adoptive) children, (adoptive) parents, brothers, sisters, grandparents, and grandchildren.
3. Adult relatives by marriage up to the 2nd degree: children of the spouse (or registered partner), parents-in-law, grandparents-in-law, brothers-in-law, sisters-in-law, sons-in-law, daughters-in-law, and step-grandchildren.

The order above determines the decision-making hierarchy. This means the officer first contacts a person from category 1 (if one exists). If this person is successfully reached, the choice made by this person applies. The officer then does not need to seek consent from a person in a 'subsequent' category.

If the patient has no relative in category 1 or if they cannot be reached, the officer moves on to category 2, and so on. The officer must make reasonable efforts to reach the persons in the relevant categories. However, they do not need to reach all relatives within every category.

Under the Wod, blood relatives and relatives by marriage in the 3rd degree are not permitted to grant consent for donation.

What if the surviving relatives do not agree with each other?

Does the decision-making authority lie with multiple people within the same category (see the text above for the ranking) and do they still not agree after extensive consultation? Then the official can propose involving an outsider, for example a social worker or a spiritual caregiver, in this conversation. If there is still no consensus on consent for donation, the official must stop the procedure.

If there is consent for organ donation, or if the relatives want more information about organ donation, it is recommended to discuss at least the following:

• Indicate that further research must determine which organs (and tissues) are suitable.
• Tell them that the examination into the suitability of the organs is focused on the interests of the recipients and not on the recovery of the donor.
• Provide a realistic estimate of the time the donation procedure takes. If the procedure is urgent, be clear about that, but also indicate that procedures may take longer (between 10 and 24 hours) due to the required care.
• Indicate that the patient will be treated with respect and that as much comfort as possible will be offered.
• Tell them that the deceased can be laid out and buried or cremated in the usual manner.
• In the event of an unnatural death: indicate that permission from the public prosecutor is required for the removal of organs and the release of the body.
• Tell about the preparatory actions that must be performed (in particular the actions that cannot wait, such as intubation/ventilation and stabilization).
• With DBD: provide an explanation of the legally required brain death tests.
• With DCD: provide an explanation of the policy and the way in which treatment is terminated.

Call an ODC via the Organ Centre (071 579 57 95) if the family needs more information. Announce to the family that the ODC is coming.

If there is consent for tissue donation, or if the family wants more information about this, the advice is to discuss the topics that you read in the tissue donation procedure (chapter 5).

It may become apparent from the donation conversation that the surviving relatives object to the nature of the patient's registration in the Donor Register. In that case, the following procedure applies.

If there is a registration with ‘yes’ or ‘no objection’, the surviving relatives can indicate during the conversation that the registration does not correspond to the patient’s wishes as the relatives understood them to be. For example, the patient may have recently expressed a different wish to their relatives. In addition, it is possible that the patient did not receive the letters regarding the registration or was unable to understand their content. As a result, they may not have been aware that they were registered with ‘no objection’.

Are the surviving relatives convinced that the 'yes' or 'no objection' registration is incorrect? If so, they can make this known and explain it to the official. How they do this is form-free. The law speaks of "rendering plausible" without this being further defined. It is not about 'proving', but about 'setting out' and 'explaining'. The official asks the surviving relatives to explain why they believe the registration does not correspond to the patient's wishes. If they can explain this sufficiently convincingly, the registration can become invalid and the information from the surviving relatives will apply. It is up to the professional judgment of the official to decide whether he can trust that the registration corresponds to the patient's wishes.

Please note:

• If a patient is registered with "No, I do not give consent," surviving relatives cannot change this. In that case, no donation will take place.
• Has the patient excluded certain organs or tissues from donation? Then the surviving relatives cannot change this either. In that case, no donation of the relevant organs or tissues takes place.

When the officer conducts the conversation with the surviving relatives about donation, their approach is always to realize the patient's wishes. In the case of a registration with 'yes' or 'no objection', this means that the officer's starting point is to let the donation take place. It is possible that the surviving relatives object to the donation itself. This is a different kind of objection than the objection to the nature of the registration (see4.10). In this case, the following procedure applies.

During the donation conversation, the surviving relatives can indicate that they personally struggle with the donation. If this happens, the official tries to ascertain what can help the surviving relatives to accommodate their values and needs. In doing so, the official looks at whether religious or philosophical views might play a role and enters into a conversation about this. During this conversation, the official can point out that the surviving relatives are not being asked to give consent (in the event of a 'yes' or 'no objection' registration); after all, the patient has already done that themselves. However, the official must explain how this registration came about (see3.2.2 and 3.2.3).

In a conversation where the personal objections of the surviving relatives are raised, it is extra important to engage in a dialogue with them and map out the backgrounds of these objections. Sometimes, for example, they do not have a general objection to donation, but make a reservation for certain organs or tissues.

Below are some factors that may play a role in the objection of the next of kin. In the dialogue, the official will address these.

Is there consent for donation? Then this consent must be recorded in the donor's medical file and on the donation form. Below is who is responsible for what. If possible, also describe the consent process.

• Medical file: by the physician
• Donation form/death certificates: by the physician
• Nursing file: by the nurse
• DPA, ODC file (in case of organ donation): by the ODC

In case of unnatural death:

• Death documents: by the forensic physician. (PLEASE NOTE: the donation form must be completed by the involved hospital physician.)

Is there consent from the patient and have the next of kin been informed? Or have you – if necessary – asked for consent from the surviving relatives or a designated person?

And is there – in the event of an unnatural death – also consent from the public prosecutor? Then the donation procedure can be initiated.

In the case of organ donation, the next step depends on the type of procedure. See chapter 5 for the DBD procedure and chapter 6 for the DCD procedure. Always call the on-duty ODC. This can be done via the Organ Centre (071 579 57 95).

In the case of tissue donation, you register the potential tissue donor with the Organ Centre (071 579 57 95). Also view: Part 2: Tissue Donation.

This chapter describes the DBD procedure. The DBD procedure starts after the conversation with the family about donation has taken place. Subsequently, death is determined, donor management is initiated, the required examinations are performed, and the donor is registered.

The examinations and registration are described in Chapter 7. Diagram 5 describes in which step of the donation process this takes place.

After contraindications for donation have been ruled out and donation has been discussed with the family, it is determined which procedure will be started: DBD or DCD. If brain death is suspected, the DBD procedure is initiated. The first step is to determine brain death. Contact the on-duty ODC to determine brain death.

The brain death protocol is used to determine brain death. This protocol has been established by Order in Council. The Brain death protocolmust therefore be followed to determine brain death. The most recent protocol has been in effect since June 1, 2017.

In the Brain Death Protocol, the 'whole brain death' concept is the starting point. According to this concept, brain death occurs when all functions of the brain, including the brainstem and the medulla oblongata, are completely and irreversibly lost. To be able to determine brain death, the following conditions must be met (summarized):

1. It has been established that the so-called pre-conditions have been met:

• The cause of the brain injury is known.
• The brain injury is fatal and untreatable.
• No potentially reversible causes for the functional impairment can be identified, such as hypothermia, intoxication, hypotension, neuromuscular junction blockade, or a severe biochemical or metabolic disorder. Resuscitation in the past 12 hours can also result in functional impairment.

2. Medication-induced neurodepression has been ruled out.

3. A clinical neurological examination was performed.

4. Additional research was conducted, such as electroencephalography (EEG), transcranial Doppler (TCD), or CT angiography of the cerebral blood vessels (CTA).

5. An apnea test was performed.

Apnea test during ECMO treatment

In the advice of theHealth Council ‘Determination of death in post-mortem organ donation’no discussion is included regarding the execution of the apnea test in patients treated with ECMO. This is because at the time of writing that guideline, there was still insufficient clarity on this matter. Consequently, this is also not included in the brain death protocol. By temporarily adjusting the ECMO settings, it is often still possible to perform an apnea test in patients on ECMO.

Through the adjustments below to the technical criteria for performing the apnea test, as described in paragraph G3.5 of the Health Council report, this test is often feasible in patients on ECMO (David M. Greer, JAMA 2020 - Supplement 7).

During the preparation:

• In addition to 10 minutes of ventilation with 100% oxygen, also administer 100% oxygen via the ECMO circuit.
• Maintain the blood flow of the ECMO circuit and reduce the gas flow across the oxygenator until a PaCO2 of at least 40 mmHg (5.3 kPa) is reached, or a PaCO2 of at least 45 mmHg (6 kPa) in individuals with chronic lung disease.

During the test:

• Maintain blood flow in the ECMO circuit and reduce the gas flow across the oxygenator to 0.5-1 L/minute with still 100% oxygen.
• In the case of peripherally cannulated VA-ECMO, simultaneously determine PaCO2 from the right arm and from the ECMO circuit post-oxygenator, in order to be certain about the PaCO2 of the blood flowing towards the head.

Interpretation

The apnea test can be terminated upon reaching a PaCO2 of 50 mmHg (6.65 kPa) or higher (or 60 mmHg, i.e., 8 kPa, in individuals with chronic lung disease) in both blood gas analyses without the occurrence of respiratory movements.

Based on these steps, has brain death been determined and is there consent for donation? If so, fill out the brain death form.

Diagnostics in children younger than 1 year

To determine brain death in children younger than 1 year, it is necessary to repeat the above-mentioned tests after an observation period. See the Brain Death Protocol Decree. The age of the child determines the length of the observation period.

The required observation period is:

• In children in the neonatal period (first week of life): 48 hours.
• In children thereafter up to the age of 2 months: 24 hours.
• In children aged 2 to 12 months: 12 hours.

Brain death cannot be determined: what now?

It is possible that during the execution of the Brain Death Protocol, a test shows that brain death cannot (yet) be determined. There are then 2 possibilities:

1. Repeat the test after a certain period of time.
2. Switch to the DCD procedure.

The decision regarding this is made in consultation with the neurologist, the intensivist, and the patient's family. A DBD procedure is always preferred, because more organs can then be donated and this generally leads to better transplantation outcomes.

After brain death is established, the ODC starts organizing and coordinating the organ donation procedure. These activities include registering the donor with Eurotransplant and organizing the logistics. See chapter 7.

Until the moment of organ retrieval, it is important to preserve or improve organ function as much as possible. This is referred to as 'donor management'. This section provides recommendations for this. These recommendations apply from the moment it is decided to withdraw life-sustaining treatment until the moment of organ retrieval.

The recommendations in this section are guidelines: they should not be followed rigidly if the patient's situation requires something else. It is advised to choose the treatments from the guideline with which you are most familiar. Donor management is largely similar to the management of ICU patients.

There are several specific points of attention, which are described in this section. The treating physician remains responsible for the patient's treatment.

5.3.1. Hemodynamic (in)stability: monitoring

In patients who become brain dead, hemodynamic changes occur. Hemodynamic monitoring is therefore necessary. The goal is to monitor proper organ perfusion.

First, rising intracranial pressure causes compensatory systemic hypertension, possibly associated with bradycardia. Subsequently, a catecholamine storm may occur, during which strong sympathetic activation takes place due to catecholamine release, resulting in strong vasoconstriction combined with increased vascular resistance, and tachycardia.

Following the catecholamine storm, there is a loss of sympathetic activation, leading to peripheral vasodilation. This results in hypotension and, if untreated, can lead to hypoperfusion. In addition, pulmonary edema may occur during the catecholamine storm.

Furthermore, various endocrine changes often occur due to the loss of pituitary function. In particular, the posterior pituitary is often affected to such an extent that diabetes insipidus occurs, accompanied by associated changes in intravascular volume status and electrolyte changes. A high urine output is not always the result of diabetes insipidus. It can also be the result of generous fluid administration and in that case requires no treatment. In addition, insulin concentration may drop and insulin resistance may develop, and it is not uncommon for hyperglycemia to occur. Furthermore, hypothalamic function may be impaired or altered, which can result in the loss of body temperature control.

In addition, an inflammatory reaction often occurs due to the release of inflammatory mediators by the damaged brain. Finally, coagulation problems regularly occur in patients with brain injuries.

Hemodynamic monitoring does not differ from that of standard ICU patients.

In doing so, the clinician must be alert to the potential occurrence of hemodynamic changes and hemodynamic instability, which must be treated quickly and adequately. The minimum monitoring advised consists of: electrocardiography (ECG), invasive blood pressure measurement, and monitoring of urine output. In addition, placing a central venous catheter, possibly with central venous pressure monitoring, can be readily considered given the likelihood or presence of hemodynamic instability. In case of difficult hemodynamic control or deterioration, monitoring can be intensified with other locally available monitoring methods with which the team has experience and expertise. Examples include echocardiography, PiCCO, or a Swan-Ganz catheter.

According current consensus, adequate volume administration—at a low required dosage of vasoactive agents—is present in the event of:

• Mean arterial pressure (MAP) 60 – 90 mmHg
• Urine output > 0.5 – 3 mL/kg/hour
• Heart rate 60 – 120/min

5.3.2. Fluid therapy

In hemodynamically unstable donors, fluid resuscitation is the treatment of first choice and is often necessary. Due to the loss of intravascular volume, volume administration is required to maintain organ perfusion without inducing hypervolemia.

Both crystalloids and colloids, with the exception of synthetic colloids, can be used for this purpose.

A perceived challenge in fluid therapy involves the conflicting goals for kidney and lung donation. However, it has recently been demonstrated that a lower central venous pressure does not lead to delayed function or decreased survival of the kidney graft. A lower central venous pressure does have a protective effect on the heart and lungs. Strict values for central venous pressure are not included in this protocol. However, fluid overload must be avoided and an euvolemic fluid balance should be targeted.

It is often chosen to fill the donor with isotonic crystalloid solutions. If frequent administration of crystalloid solutions is necessary, switching to non-synthetic colloid solutions can be considered. In practice, however, colloid solutions are rarely or no longer used in the intensive care unit. Administering colloids may reduce the total required volume. This potentially reduces the risk of pulmonary edema.

Recommendations for fluid therapy

• Aim for euvolemia in the donor.
• Preferably choose fluid therapy with bolus administration instead of continuous administration to prevent the risk of hypervolemia.

5.3.3. Hemodynamic support

If fluid therapy is insufficient to achieve hemodynamic goals, the administration of a vasopressor and/or inotrope is advised. Various agents can be used for this purpose.

In many ICUs, norepinephrine is used most frequently. Norepinephrine has an alpha-agonist effect that increases peripheral vascular resistance and consequently raises blood pressure. Furthermore, it also has a beta-1-agonist effect, which leads to an increase in heart rate and cardiac output. Norepinephrine can be combined with other vasoactive medications, such as dobutamine, milrinone, or enoximone. The lowest possible dosage of norepinephrine should be aimed for. At higher dosages, there is a greater chance of cardiac dysfunction after transplantation and higher mortality of the recipients.

Another agent that can be used is dopamine. In practice, however, this is rarely administered.

If higher dosages of catecholamines are needed, vasopressin can also be administered. This has a protective effect on heart function and may result in more organs remaining available for transplantation. Start vasopressin administration at a low dose and titrate up to a maximum dose of 40 mU/kg/hour. As an alternative to vasopressin, terlipressin (1 mg iv bolus) can be given.

An adverse consequence of vasoactive agents that have an agonist effect on alpha-receptors is an increase in pulmonary capillary permeability. This can lead to pulmonary edema. In addition, stimulation of alpha-receptors may lead to vasoconstriction of the coronary and mesenteric arteries. Avoid high doses of beta-agonists in potential heart donors, among other things to prevent down-regulation of beta-receptors. In addition, timely consideration should be given to using additional positive inotropic agents, such as a phosphodiesterase inhibitor.

Recommendations for hemodynamic support

• Start vasopressors and/or inotropes according to the local protocol if hemodynamic goals cannot be met with fluid administration.
• Avoid high doses of beta-agonists in potential heart donors.

5.3.4. Arrhythmias

Arrhythmias frequently occur in brain-dead patients. Sinus tachycardia is the most common arrhythmia, followed by sinus bradycardia and atrial fibrillation. Arrhythmias can be treated according to standard guidelines, but only if medications with shorter half-lives are used.

Tachycardia

Tachycardia frequently occurs as a result of elevated catecholamine concentrations at the onset of brain death or as a result of hypovolemia. If tachycardia leads to hypotension and is thus poorly tolerated by the heart, congestive heart failure may develop.

Recommendations for the treatment of tachycardia

• Rule out reversible contributing causes of the tachycardia before starting pharmacological treatment. A contributing cause may be hypovolemia, for example.
• Poorly tolerated tachycardia must be treated with a beta-blocker. Esmolol is preferred because of its short half-life.
• Preferably choose intravenous administration via a syringe pump.

Bradycardia

In case of increased intracranial pressure, a Cushing's response may occur. This can lead to bradycardias (sinus bradycardia or nodal escape rhythm), in addition to hypertension and a potentially abnormal breathing pattern. Increased intracranial pressure can also cause compression of the brainstem nuclei from which the vagus nerve originates. As a result, atropine is no longer effective.

Recommendations for the treatment of bradycardia

• Preferably administer isoprenaline, due to its direct chronotropic effect on the heart muscle.
• Administer isoprenaline at a dose of 1 mcg intravenously. Repeat this every minute until the heart rate increases, or continue treatment with a continuous infusion titrated to the heart rate.
• Administer adrenaline in case of acute emergency.
• If chronotropic medication proves insufficiently effective, consider intravascular pacing.

Atrial fibrillation

Atrial fibrillation can be pre-existing, but can also occur due to cardiac stress factors after or during the onset of brain death. In addition, it can be triggered by hypovolemia or electrolyte disturbances (such as hypokalemia and hypomagnesemia).

Recommendations for atrial fibrillation

• Correct possible underlying causes of atrial fibrillation, if possible.
• Consider magnesium supplementation.
• Attempt cardioversion – chemical or electrical – to convert the heart rhythm to a sinus rhythm. Heart donation is then theoretically still possible.

5.3.5. Hypertension

In the treatment of hypertension, a distinction must be made between pre-existing hypertension and new hypertension resulting from catecholamine release or increased intracerebral pressure.

Newly developed, acute hypertension must be treated as soon as possible to prevent myocardial damage and pulmonary edema. With systolic blood pressures above 200 mmHg or a mean arterial pressure (MAP) above 130 mmHg, there is an increased risk of cardiac damage, resulting in cardiac arrest. In the event of a catecholamine storm, there is a systolic blood pressure of 200 mmHg for at least 10 minutes and a tachycardia of more than 140 beats per minute, without another attributable cause. If treated immediately, there is still a good chance of a successful heart donation.

Hypertension must be treated according to the local protocol, using antihypertensive medication with which the intensivist has experience. In heart donation, labetalol should be avoided because of its long half-life.

Recommendations for the treatment of hypertension

• Initiate antihypertensive treatment at a systolic blood pressure > 200 mmHg or a MAP > 130 mmHg.
• Preferably use a beta-blocker (metoprolol, esmolol, or labetalol) or nitroprusside, nitroglycerin, or nicardipine. For DCD heart donation, beta-blockers are a second choice after calcium channel blockers.
• In potential heart donors, preferably do not use beta-blockers, but rather one of the alternatives.

5.3.6. Ventilation

Lung injury occurs in 30% of patients with neurological damage. In potential lung donors, follow the same treatment strategy as in patients with lung injury in the intensive care unit. Ventilation is aimed at lung-protective ventilation conditions.

Current protective ventilation guidelines recommend ventilating with a tidal volume of 6-8 ml/ideal body weight (in kg). In addition, PEEP should be optimized if possible with a target PEEP of 8 – 10 cmH2O. Furthermore, it is recommended to perform a recruitment maneuver after the apnea test.

If lung donation is not possible, maintain the settings that achieve good saturation and do not change the ventilation conditions too much. If room permits, PEEP can be lowered to reduce the load of ventilation on hemodynamics.

Recommendations for ventilation in potential lung donation

• Ventilate the lungs protectively according to current lung-protective guidelines.
• Perform a recruitment maneuver after the apnea test.
• Consider recruitment maneuvers to improve the PaO2-FiO2 ratio.
• Improve lung quality through bronchial toilet or suction bronchoscopy.
• Use a restrictive fluid management policy.
• Prevent sputum stasis and suction the endotracheal tube regularly.
• Insert a nasogastric tube with drainage to prevent aspiration.
• Elevate the head of the bed to 30 degrees for proper positioning of the donor.
• Follow local guidelines for the prevention of ventilator-associated pneumonia.

5.3.7. Medication use

Corticosteroids

Little is known about the prevalence of corticosteroid deficiency in brain-dead patients. There are indications that there is an increased chance of relative corticosteroid deficiency, but the clinical consequences of this are not clear. Research shows that intravenous administration of methylprednisolone has a protective effect against ischemia/reperfusion injury. As a result, acute rejection occurs less frequently. It also improves oxygenation.

Recommendations for the use of corticosteroids

• Administer 15 mg/kg of methylprednisolone intravenously after the diagnosis of brain death. This has positive effects on organ function after transplantation. Repeat this every 24 hours.

Vasopressin analogues

Damage to the pituitary gland frequently occurs in brain-dead patients. If damage occurs to the posterior pituitary (neurohypophysis), diabetes insipidus can develop because no or less antidiuretic hormone is released. Diabetes insipidus occurs in 80% of DBD donors. Signs of this include polyuria (diuresis > 4 ml/kg/hour) and hypernatremia (> 145 mmol/l), an increase in serum osmolality (≥ 300 mosm/l), and a decrease in urine osmolality (≤ 200 mosmol/kg).

Other potential causes of diabetes insipidus must be excluded. These include osmotic diuresis as a result of hyperglycemia or high diuresis due to the administration of mannitol or other diuretics. High diuresis can also be the result of large fluid administration and in that case does not require treatment with desmopressin. Sometimes, in the case of high diuresis, it is necessary to supplement the volume and strive for euvolemia.

Recommendations for the use of vasopressin analogues

• Use desmopressin (DDAVP) 1 – 4 mcg IV in case of (suspected) diabetes insipidus. In case of persistent polyuria (> 3 ml/kg/hour), another 1 – 2 mcg of desmopressin IV can be administered. This can be repeated every 6 hours.
• Vasopressin and terlipressin are less effective in the treatment of diabetes insipidus. However, these agents can play a role in the treatment of hemodynamic instability.

Thyroid hormone

In the majority of brain-dead patients, concentrations of TSH (thyroid-stimulating hormone), T3, and T4 are below the normal value. In those cases, there is often 'sick euthyroid syndrome' rather than an actual TSH deficiency. These patients often do not require thyroid hormone supplementation. The most recent literature advises against routinely administering thyroid hormones (Dhar NEJM, 2023).

Recommendations for the administration of thyroid hormones

• Do not routinely administer thyroid hormones.
• Consider the use of thyroid hormones if hemodynamic instability persists, despite euvolemia and optimal dosages of vasoactive drug support. Thyroid hormones increase cardiac contractility. This is due to their chronotropic effect and a reduction in systemic vascular resistance.

5.3.8. Combined hormonal therapy

It is advised against routinely supplementing vasopressin, corticosteroids, and thyroid hormone. As described previously, it is recommended to start methylprednisolone in every organ donor as early as possible after brain death. In addition, the advice is to reserve vasopressin and thyroid hormone for patients who remain hemodynamically unstable despite optimal therapy.

Recommendations for applying combined hormone therapy

• Do not routinely opt for combined hormone therapy.

5.3.9. Glucose regulation

Hyperglycemia is common in brain-dead patients and is likely a result of high concentrations of catecholamines and the administration of corticosteroids. Little research is known about the effect of glucose control in organ donors.

Recommendations for glucose management

• Follow current practice: aim for a serum glucose level of 6 – 8 mmol/l.

5.3.10. Electrolytes

Electrolyte disturbances may occur in DBD donors. Therefore, special attention is required for hypernatremia resulting from diabetes insipidus (see 5.3.7).

It is recommended to treat electrolyte disturbances according to the guideline on electrolyte disturbances, advising to aim for normal values. Electrolyte disturbances are not a contraindication for transplantation.

Recommendations for the treatment of electrolyte disturbances

• Aim for normal electrolyte values.
• Follow the guideline on electrolyte disturbances for the treatment of electrolyte disturbances.

5.3.11. Transfusion thresholds

There is no known literature on the influence of red blood cell transfusions on the short-term preservation of donor organs. Therefore, follow current practice, accepting a hemoglobin level down to 4.3 mmol/l. If the value is lower than 4.3, transfusion of red blood cells is advised. This advice is based on large randomized controlled trials in critically ill patients, which showed no difference in survival between a high threshold (Hb 6 mmol/L) and a low threshold. There is no literature on platelet concentrations or coagulation times in organ donors.

Recommendations for transfusion thresholds

• Follow current practice: Hb > 4.3 mmol/L.
• Administer platelets and/or plasma factors in case of clinical bleeding.
• Consult with the accepting physician before applying perioperative correction of clotting factors.

5.3.12. Temperature regulation

Loss of temperature regulation can occur in brain-dead patients. This can potentially lead to hypothermia. Hypothermia is known to cause various problems, such as coagulation disorders and arrhythmias, among others. Cooling to 34 °C is discouraged (Patel JAMA, 2024). Consider passive cooling in case of fever.

Recommendations for temperature regulation

• Maintain the donor's temperature > 35 °C.
• Consider passive cooling in case of fever.

5.3.13. Nutrition

Brain-dead patients should receive enteral nutrition according to the local protocol (CherciClin transplant, 2023 (37)).

Recommendations for nutrition

• Start or continue enteral nutrition according to the local protocol.

5.3.14. Prevention and treatment of bacterial infections

During ICU admission, the prophylactic administration of antibiotics in potential organ donors is not recommended. An exception applies to the administration of SDD, which is part of standard ICU treatment.

Antibiotic treatment of existing infections must be continued or initiated according to the local or national protocol. This also applies to new infections confirmed by microbiological diagnostics. These (existing and new) infections are not always a contraindication for organ donation. In the event of an infection, a decision regarding the suitability of the organs for transplantation must be made in consultation with the transplant physicians.

Recommendations for the prevention and treatment of infections

• Collect blood, sputum, urine, and wound cultures (if applicable) from all donors. Repeat this in case of fever, after 24 hours if necessary.
• Continue antibiotic treatments that have already been started.
• Treat proven infections according to the local or national protocol.
• Administer SDD/SOD according to the protocol.

The deceased is transferred to the operating room at the time previously agreed upon with all involved parties, including the family. This is a few hours after the determination of brain death.

Forms

The following forms must be sent from the ICU to the OR:

• The brain death form.
• The donation form completed by the physician.

This chapter describes the DCD procedure. It discusses the withdrawal of treatment, the agonal phase, and the determination of death based on circulatory criteria. Diagram 6 shows which step of the donation process this chapter covers.

The DCD procedure starts when the decision has been made to terminate a patient's life-sustaining treatment and brain death cannot be established. DCD specifically concerns a situation where—based on a careful prognosis—the patient's death is expected and the moment of death can be foreseen within certain time limits. If the family has given consent for donation, the ODC is called. This can be done directly or via the Organ Centre (071 579 57 95).

It takes a few hours before the patient's treatment is actually stopped. During this period, actions are taken in accordance with the NVIC guidelines for providing end-of-life care. Providing comfort is an essential part of this.

In addition, in the case of a potential donor, it is important to (continue to) ensure good organ function. This means that it may be necessary to perform medical procedures.

These procedures are not in the patient's interest, but are performed for the benefit of organ donation. The intensivist remains the treating physician and is responsible for this. The ODC can support and advise the intensivist.

6.1.1 Points of attention for DCD heart donation

• Be restrained in administering inotropy, vasopressine, and other cardiodepressant agents. If necessary, preferably use short-acting agents and try to dose them as low as possible.
• For the heart perfusion machine to function, the donor's hematocrit should ideally be > 0.3 l/l.

6.1.2 Points of attention for heparin administration in DCD donation

• This concerns the administration of heparin for the quality of the liver, lungs, kidneys, and pancreas.
• Heparin is administered at the time of switch off.
• It is discouraged to administer heparin in trauma patients with clear external injuries.
• In the case of a retrieval procedure with normothermic regional perfusion (NRP), heparin does not need to be administered in the ICU. This is done during the perfusion procedure in the OR.
• In the case of organ donation after euthanasia, heparin is also administered. Seeguideline for organ donation after euthanasia.

6.1.3 Points of attention for abdominal normothermic regional perfusion (aNRP)

aNRP is an in-situ perfusion technique that can be used in DCD donors; this takes place in the OR. After 1-2 hours of aNRP, organ retrieval takes place according to the standard protocol. If indicated, liver function can be tested during aNRP.

• The ODCs order the required packed red blood cells (packed cells) in a timely manner.
• For the aNRP to function, the donor's hematocrit must be > 0.3 l/l.

Between the decision to withdraw treatment and the actual withdrawal of treatment, the ODC coordinates the donation procedure. For example, the ODC ensures that tests are performed to assess the quality of the organs, registers the donor with Eurotransplant, and coordinates the logistics. These activities are described in Chapter 7.

It is possible that during the period leading up to the withdrawal of treatment, signs pointing toward brain death occur. There are then 2 possibilities:

1. Continue the DCD procedure.
2. Stop the DCD procedure and start following the Brain Death Protocol, in order to subsequently switch to the DBD procedure.

The decision regarding this is made in consultation with the neurologist, the intensivist, and the family. If they decide to execute the Brain Death Protocol and the donor was already registered with Eurotransplant, the donor must be re-registered after brain death has been established. This is because allocation must then be restarted.

Preference is always given to a DBD procedure, because more organs can be donated and this generally leads to better transplantation results.

The time at which life-sustaining treatment is stopped (the switch-off) is coordinated with the family, the intensive care unit, the ODC, and the independent retrieval team.

The withdrawal of treatment almost always takes place in the ICU. After death, there is no circulation. This causes ischemic damage to the organs. The time between death and the start of perfusion in the operating room (warm ischemia time) must therefore be as short as possible. After death, the donor is rapidly transported to the OR, where the retrieval team is standing by.

The switch-off can also take place in the OR. The advantage of this is that the warm ischemia time is shorter. The decision regarding this must always be made in close consultation with the family. They must give permission for this.

The intensivist remains responsible for the treatment and pronounces death.

The period between the switch-off and the patient's death is called the agonal phase. At the moment of switch-off or immediately thereafter, IV heparin 300IU/kg of body weight is administered. This must be done while the patient still has circulation. During the agonal phase, the perfusion and oxygenation of the organs are observed. The ODC documents the heart rate, blood pressure, respiration, and oxygen saturation.

Duration of the agonal phase

There is considerable variation in the duration of the agonal phase: sometimes circulatory arrest occurs after a few minutes, sometimes after several hours or days. For the quality of the organs, the agonal phase should not last longer than 1 to 2 hours.

After this period, an organ will be less suitable or even unsuitable for transplantation. Exactly how long that period may be depends on the course of the agonal phase and the organs being donated.

Table 2 indicates the maximum time until circulatory arrest.

Table 2: Agonal phase: Maximum time until circulatory arrest

In consultation with the accepting physician, these limits may be deviated from.

In a DCD procedure, death is determined based on circulatory criteria. The procedure for this is described in the advisory report of the Health Council. The procedure involves 2 crucial moments:

1. It has been established that circulatory arrest has occurred.
   1. There must be no doubt whatsoever that the blood circulation has stopped. To prevent any such doubt, it is recommended to use an indwelling arterial line that can measure all changes in arterial pulsations and pressure with sufficient sensitivity and specificity. In addition, non-invasive examinations can be performed if necessary, such as non-invasive blood pressure measurement, auscultation of the heart, electrocardiography, or echocardiography.
   2. Therefore, to determine death, the absence of blood flow is the decisive criterion.
2. Following the determination of circulatory arrest, an observation period is instituted without medical intervention: the 5-minute no-touch period.
   1. The no-touch period is an observation period during which no procedures may be performed on the patient. This observation period begins at the moment it is determined that the blood circulation has stopped. The period ends at the moment there is sufficient certainty that the circulatory arrest is permanent. In the Netherlands, this no-touch period is set at 5 minutes. A prerequisite is that no further interventions take place that might unintentionally lead to the restoration of cerebral circulation.
   2. Only after the 5-minute no-touch period can death be definitively pronounced. During the 5-minute no-touch period, the donor may not be transported.

Immediately after the determination of death, the deceased is taken to the operating room. The time between circulatory arrest and the start of perfusion must be as short as possible in order to preserve the quality of the organs.

Form

The donation form stating the time of death (completed by the physician) must be sent from the ICU to the OR.

This chapter describes the organization surrounding the donation procedure. The ODC coordinates this procedure. The chapter discusses the examinations that are performed, the heteroanamnesis, the registration of the donor with Eurotransplant, and the logistics. These steps are part of both the DBD and the DCD procedures. This is illustrated in Diagram 7.

A number of examinations are performed on a potential donor to assess which organs are suitable for donation. Blood is always drawn for tissue typing and virology. The ODC handles the logistics for this typing and the various examinations. These examinations are listed in Table 3. Receiving centers may request additional examinations.

Please note: For every potential donor, the examinations listed under 'General/Kidneys' must be performed. When other organs are donated, the remaining examinations are added.

Table 3: Medical examinations to be performed on a potential donor

In addition to the investigations mentioned in 7.1, it is important to obtain a complete picture of the medical and social history of the (potential) donor and their current situation. Consider the following:

• Age, gender and occupation.
• (Measured) height and weight.
• Indication for admission.
• Chronic conditions, such as hypertension and diabetes mellitus.
• Medical history.
• Cause of death.
• Intoxications (number of pack-years of nicotine, use of alcohol and drugs).
• Home medication use.
• Risk behavior regarding sexually transmitted infections, such as HIV.
• Undergone surgeries.
• Allergies.
• Travel history in the past year: where and when has a donor been abroad in the year prior to death (both within and outside Europe).
• The clinical course during admission.

The ODC obtains this information by reviewing the medical record and by speaking with the family, the intensivist and/or the general practitioner of the potential donor.

After all necessary information has been collected and the patient has been found suitable as a donor, the ODC registers the patient with Eurotransplant. Eurotransplant allocates organs to recipients in accordance with Dutch allocation rules.

As the coordinator of the donation procedure, the ODC organizes the logistics surrounding the procedure. There must be 4 to 6 hours between the time of donor registration and the start of organ procurement; if heart donation takes place, this is 8 hours.

This time is necessary to call in the recipients and make preparations for the transplantation. The exact number of hours needed depends on the organs being donated.

The ODC arranges the logistics:

• An operating room is available.
• The procurement team is called in.
• The crossmatch material is sent to the laboratory.
• The transport of the organs has been arranged.

This chapter provides tools for the ODC to inform family members about the donation procedure and to guide them during the procedure. In Diagram 8, you can see that the provision of information and care for the family is a process that runs throughout the entire procedure.

Before the ODC speaks with the donor's family, they coordinate the topics to be discussed with the physician. The physician may have already discussed some topics during the donation conversation. The physician can indicate whether or not it is useful to repeat and further explain this information.

It is important to respond to the family's need for information. This is up to the professional judgment of the ODC. It is recommended to involve the attending physician or nurse in the conversations with the family.

Topics for the conversation are:

• The duration of the entire procedure (never give an exact duration, as this is difficult to estimate).
• The required examinations to determine the suitability of the organs, including any inquiries with the general practitioner or other healthcare providers of the patient.
• Opportunities for the family to be present in the ICU.
• Opportunities for the family to say goodbye to the patient and possibly perform specific rituals.
• The time of death in DBD and DCD.
• The donation procedure and the manner in which it is carried out: with care, respect, and within legal standards.
• The medical and social history of the patient (inquire about this with the family).
• Which organs and tissues can be donated.
• The required removal of associated structures to make transplantation possible (such as spleen, blood vessels, and bowel).
• The possibility that the organs are tested before they are transplanted into the recipient.
• The appearance of the deceased after donation: incisions and (pale) appearance.
• The (objective) allocation system used by Eurotransplant to allocate organs to the recipient(s) (indicate that there is an exchange system with other countries).
• Consent for research on organs that are rejected (see 8.2).
• The possibility that donated organs may ultimately prove unsuitable for transplantation.
• The fact that organ donation is always anonymous.

In addition, the ODC assesses the family's needs regarding aftercare (see 8.4 and 8.5), and answers any questions. Arrangements are also made regarding how the family wishes to be further informed about the operation.

Finally, always provide the NTS brochure 'Organ donation, information for family', so that family members can reread the information about the procedure at their leisure.

In a combined organ and tissue donation procedure, the ODC also coordinates the procedure surrounding tissue donation. This is done in accordance with the description in Part 2: Tissue Donation. If necessary, the ODC transfers the tasks regarding tissue donation to the physician.

During the conversation with the family, the ODC discusses whether consent is given for the removal of organs that are not used for transplantation. This can involve 2 situations:

An organ that has already been removed is subsequently rejected for transplantation at a later time. Consider a contraindication or issues related to the recipient.

One or more organs are removed solely for research. In addition, the donor also donates other organs.

If the patient has given consent for donation in the Donor Register without excluding transplantation-related research, the ODC does not need to ask the family for consent for the first situation. The family must be informed that the patient has no objection to the use of the organ for transplantation-related research.

In all other cases and if only certain organs are removed for examination, the family must give specific, written consent. Consent forms are available for this purpose.

All information provided to the family must be recorded in the following files:

• Medical file:by the physician
• Donation form/death certificates: by the physician
• Nursing file: by the nurse
• DPA, ODC file: by the ODC

In case of unnatural death:

• Death paperwork: by the forensic doctor.
• Please note: the donation form must be completed by the involved hospital physician.

During the discussions in the procedure, the ODC asks about the family's need for aftercare. If the family wishes, the ODC will contact the family 6 weeks after the death. They can then provide feedback with the results of the transplantation:

• Has the organ been transplanted?
• What is the gender and age category of the recipient?
• Is the organ still functioning?
• In the case of a combined organ and tissue procedure: have the removed tissues been found suitable for transplantation? And if known: has the transplantation taken place?

Experience shows that the vast majority of surviving relatives greatly appreciate this feedback and that it can support them in their grieving process.

Various forms of aftercare are available for surviving relatives. The ODC brings these up during the conversation with the family (before or after the procedure):

• Did the patient stay in the intensive care unit for a shorter or longer period? If so, the family can have a follow-up conversation with the staff of that department.
• Twice a year, an information bulletin is published by and for surviving relatives of organ and tissue donors. This bulletin is called: 'Nabestaanden Contact' (Surviving Relatives Contact). It can be ordered viainfo@transplantatiestichting.nl.
• If surviving relatives want to know more about the impact of a transplantation on the recipient's life, the book 'Hoe kan ik je ooit bedanken?' (How can I ever thank you?) is recommended. This book contains various thank-you letters from recipients. It can be ordered viainfo@transplantatiestichting.nl.
• It frequently happens that the recipient of an organ or tissue wants to thank the donor's surviving relatives by letter. This is sent to the surviving relatives via the ODC. The ODC checks this letter for traceability. Subsequently, the ODC contacts the donor's family to ask if they wish to receive this letter.