Perioperative management of the organ donor after diagnosis of death using neurological criteria

Learning objectives.

By reading this article you should be able to:

• •Specify the adverse effects on organs after the diagnosis of death using neurological criteria.
• •Describe the management of the donor's physiology to optimise the quality of organs donated.
• •Outline the retrieval process and procedure, and the associated anaesthesia interventions required at each stage.

Key points.

• •Communication between the anaesthetist and the retrieval team is key to a successful retrieval operation.
• •The medical management of the deceased organ donor that began in ICU should continue through the retrieval process.
• •The aim of medical management is to optimise the quality of transplantable organs.
• •The donor is dead and so drugs are given to attenuate physiological responses, not to provide ‘anaesthesia’.

Diagnosis of death using neurological criteria (DNC), previously termed brain death or brainstem death, is a clinical diagnosis. A diagnosis of DNC is made when severe, irreversible, structural brain injury leads to irreversible loss of both the capacity to breathe and the capacity for consciousness.¹ Each year, organs are retrieved for transplantation from approximately 1600 deceased organ donors in the UK and 80 deceased organ donors in the Republic of Ireland (ROI).^2,3 Sixty percent of deceased organ donations in the UK take place after death has been diagnosed by neurological criteria and 40% after death has been diagnosed by circulatory criteria.² In this article, we describe the perioperative management of the organ donor following DNC in the UK and ROI.

Personnel and their roles

Intensive care

The anaesthetist is one member of a large team of professionals that facilitates the donation, retrieval and transplantation of organs. Patients are admitted to the ICU, often for a number of days before the diagnosis of death. Intensivists, intensive care nurses, physicians, surgeons and support staff care for the patient and ensure that the family is informed and supported at all stages. The intensive care team is responsible for the medical management of the patient up until the point at which death is declared. Once death has been declared the intensive care team turns their focus to the medical management of the potential organ donor.

Specialist nurse-organ donation

The specialist nurse-organ donation (SNOD) is the local coordinator of the donation and retrieval process in the UK. The National Institute for Health and Care Excellence describes the criteria for referral of patients who have suffered a catastrophic brain injury to the SNOD.⁴ These include the absence of one or more cranial nerve reflexes, a Glasgow Coma Score of 4 or less, or a clinical decision to perform brainstem testing.

The SNOD can ascertain whether the patient has made his or her wishes regarding organ donation known by referring to the NHS Organ Donor Register. This is a national register where a person can record their decision to donate or not to donate organs after death. The register is managed by NHS Blood and Transplant (NHSBT), which oversees organ donation and transplantation in the UK.²

In ROI the SNOD role is split into a centralised retrieval component (National Organ Procurement Service) and a local ICU-based coordination component (organ donation nurse managers [ODNM]).⁵ Organ Donation and Transplantation Ireland (ODTI) oversees organ donation in ROI.

A collaborative approach involving the consultant ICU physician, bedside nurse and SNOD or ODNM ensures that the family understands the diagnosis of death. The family will interact with many staff, but discussions regarding the diagnosis of death are usually limited to a small number of clinicians familiar with the patient. Only when the family understands and accepts that death has taken place is a discussion regarding organ donation introduced as a routine part of end-of-life care. The SNOD has specific expertise and training in approaching family members for assent to organ donation.

Anaesthetist

The anaesthetist continues the medical management of the deceased organ donor from transfer out of the ICU through the retrieval procedure. The anaesthetist facilitates the retrieval team's assessment and retrieval of donor organs while maintaining physiological homeostasis throughout. The anaesthetist also contributes to ensuring a calm and respectful atmosphere during transfer to the operating theatre and during the retrieval operation. The respectful ambience acknowledges the impact that the process of organ donation and retrieval has on family members, clinical and non-clinical hospital staff.

National Organ Retrieval Service

A team of retrieval surgeons and nurses from the National Organ Retrieval Service (NORS) arrives before the retrieval procedure to meet with local staff and to prepare the operating theatre.⁶ In the UK there are six thoracic organ retrieval teams and 10 abdominal organ retrieval teams, of which three thoracic and seven abdominal teams are on call at any one time. The teams that attend are assigned to each hospital in the UK based on travel time and even distribution of workload and are the only teams authorised to perform retrieval operations in most situations.^6,7 In ROI the retrieval teams are mobilised from the three national transplant centres.

Diagnosis of DNC

Death can be diagnosed by somatic, circulatory and neurological criteria.⁸ Regardless of how death is diagnosed, death has occurred when there is irreversible loss of both the capacity for consciousness and the ability to breathe. A recent international consensus statement recommends a definition of DNC as ‘the complete and permanent loss of brain function as defined by an unresponsive coma with loss of capacity for consciousness, brainstem reflexes and the ability to breathe independently’.⁹

Although different countries have varying definitions of DNC, the clinical diagnostic tests are similar.^10,11 First is an assessment of brainstem reflex function through examination of the cranial nerves. Second is an apnoea test. Some countries may require ancillary tests, such as a four-vessel cerebral angiogram in addition to clinical tests.

In the UK and ROI, the diagnosis of DNC requires a number of preconditions to be met before clinical brainstem tests can be relied upon to confirm death. These preconditions include diagnostic certainty of irreversible structural brain injury with known aetiology and the absence of confounders that may mimic irreversible apnoea and coma.¹ Confounders include depressant drugs, hypothermia, or certain reversible circulatory, metabolic, or endocrine disturbances.¹ Sometimes, ancillary tests are necessary to inform the clinical diagnosis of death.⁸ Examples include where the preconditions cannot be fully met or where all cranial nerves cannot be reliably tested, such as in cases of high cervical injury or facial trauma.

Brainstem tests are performed on two separate occasions by two doctors who are familiar with the testing procedure. Both doctors must be fully registered with the General Medical Council (in the UK) or the Medical Council (in ROI) for 5 yrs. At least one of the two doctors must be a consultant.^1,8 No time interval is specified between the two sets of tests, only that the patient must have completely recovered after the first apnoea test. The time of death is the time of completion of the first set of tests in the UK. In the ROI the time of death is the time of completion of the second set of tests.

Process from the diagnosis of death to transfer to the operating theatre

The process of organ donation and transplantation is complex. Multiple factors affect the time from the diagnosis of death to organ retrieval. It is important that the anaesthetist is aware of those factors in order to plan the timing of the retrieval operation within the confines of limited operating theatre resources, and to prioritise other elective, urgent and emergency surgeries.

Organ retrieval is timed to afford the best possible organ quality at the time of retrieval and to minimise the time between retrieval and transplantation (see below). At the same time, every effort is made to minimise the risk of transmitting infection or cancer from the donor to the recipient by assessing the clinical history, examination and investigations.

Donor and recipient matching

Tests for immunological matching are carried out to reduce the risk of organ rejection in the recipient.¹² This process begins when potentially transplantable organs are offered to recipient centres. The proportion of this process that must take place before the retrieval operation depends on the organs to be transplanted and the timeframe in which transplantation needs to occur after organ retrieval. Cold ischaemia time refers to the interval between starting cold perfusion of the organs in the donor's body after the circulation has ceased until normal blood perfusion in the recipient is restored. Organs are kept cool to reduce metabolic demand. Organs that only tolerate short cold ischaemia times require more of the immunological testing and matching process to take place before organ retrieval, because the transplant operation must take place soon after retrieval. This is especially the case for heart and lung transplantation. A suitably matched heart recipient undergoes surgery in the recipient's hospital simultaneously to the retrieval operation in the donor hospital, because the cold ischaemia time for a transplanted heart is approximately 4–6 h. The kidney, liver, pancreas and bowel tolerate longer cold ischaemia times and so the time between retrieval and transplantation can be longer. Less of the immunological testing and matching process needs to be completed before the retrieval operation starts. Therefore the specific organ(s) to be retrieved affect the timing of the retrieval surgery.

Time from death to organ retrieval

The mean time taken from initial donor referral to the beginning of the retrieval operation increased from 20 h in 2011–2 to 39 h in 2017–8 according to NHSBT audit data.¹³ Delays in the donation process have resulted in a small number of families deciding not to proceed with organ donation.

Preoperative assessment

Before the retrieval operation, the anaesthetist attends the ICU to receive a detailed handover before transferring the organ donor to the operating theatre. Handover should include details of the event leading to the catastrophic brain injury, the method of diagnosing death and confirmation of family assent to organ donation. The results of all investigations should be reviewed and an organ-specific assessment should be performed. The anaesthetist should be familiar with the organs to be transplanted, medical management to date and the plan for ongoing medical management.

The circumstances of death of neurologically injured patients often require the coroner or procurator fiscal to be informed and to consent to organ donation.¹⁴ The coroner may place certain restrictions on which organs may be donated.

Timing of the retrieval operation

The operating theatre starting time is agreed between the SNOD, the ICU team, the donor operating theatre supervisor and the anaesthesia team. The wishes and requests of family members and the needs of the ICU staff, operating room staff and the NORS team are all taken into consideration when deciding upon an agreed starting time.

Medical management of the organ donor

The aim of medical management of the organ donor is to optimise the quality of donated organ(s), thereby increasing the likelihood of a successful outcome for the transplant recipients.

The pathophysiology of neurological death has been well described.¹⁵ Autonomic, metabolic and endocrine disturbances associated with brainstem infarction and the process of dying have effects on multiple systems.¹⁶ Attentive management of the potential organ donor can attenuate or even reverse these effects, though any particular management strategy that improves the function of one organ may worsen the function of another.¹⁷ It is important that the anaesthetist is aware of which organs are planned for organ transplantation. The medical management of those organs planned for transplantation should be prioritised over those not planned for transplantation. The medical management of those organs planned for transplantation should balance the physiological requirement of each organ.

Medical management of the organ donor begins in the ICU once death has been diagnosed and continues right through the retrieval surgery to the point of organ removal. Active management of the organ donor has been shown to increase the number of organs suitable for transplantation.¹⁸ The anaesthetist is responsible for continuing the medical management strategy started in the ICU through the transportation and operative phases (Table 1).19, 20, 21

Table 1.

Summary of the management of the potential organ donor.²¹

Specific aspects of management

Several aspects of management are specific to patients in whom death has been diagnosed using neurological criteria.

Catecholamine ‘surge’

Brainstem herniation is associated with a surge in circulating catecholamines that can cause myocardial damage and cardiac dysfunction.^15,20,22 Cardiac retrieval may need to be delayed and the heart monitored for improvement when function is initially impaired but the heart is structurally normal.^21,23 Vasopressin should be considered the first-line drug treatment for hypotension caused by vasodilatory shock (see below).

Fluids

Where intravascular resuscitation is necessary, isotonic crystalloids such as Hartmann's solution or 0.9% saline are preferred.²¹ Colloid solutions can also be used but starches are generally avoided as these have been associated with worse graft outcomes.¹⁶ There is no contraindication to transfusing blood or blood products where necessary.

Lung-protective ventilation

Lung-protective ventilation is standard of care in the ICU and should be continued throughout the transport and retrieval phases.²⁰ Maintaining tidal volumes of 6–8 ml kg⁻¹ ideal body weight, plateau inspiratory pressures <30 cmH₂O and PEEP titrated to Fio₂ may lead to an increase in the number of donor lungs being transplanted.²⁴

Diabetes insipidus

Central diabetes insipidus is a common complication of severe neurological injury.²¹ Decreased circulating antidiuretic hormone concentrations cause the kidneys to excrete large volumes of dilute urine.²⁰ Untreated, this can cause hyperosmolar hypernatraemia and hypovolaemia with reduced organ perfusion. A urine output >4 ml h⁻¹ should alert the anaesthetist to this possibility. Treatment comprises hypotonic fluids i.v. to replace water losses and an infusion of vasopressin (especially where concurrent vasopressor therapy is required) or s.c. desmopressin if necessary (Table 1).

Hormone replacement

A number of hormone replacement therapies including vasopressin, glucocorticoids, thyroid hormone and insulin may also be given.²⁰ Although the level of evidence is low that hormone replacement increases the number of transplantable donor organs, these therapies appear to be safe.²¹

Hypothermia

Hypothermia is common, because thermoregulatory control from the hypothalamus is lost. Active heating measures are often needed to maintain normothermia.^21,25 Although some data support using moderate hypothermia to decrease delayed graft function after renal transplant, there are few data to support the general use of intraoperative hypothermia.²⁶

Transfer to the operating theatre

Transfer to the operating theatre is the same as for any other patient receiving artificial ventilation and leaving the ICU for a procedure. The donor can usually be transferred on a transport ventilator or with a C-circuit. In donors with hypoxic respiratory failure, the mode of ventilation must not lead to worsening hypoxia with resultant damage to potentially transplantable organs. Spinal reflexes are common after DNC (see below). The anaesthetist may consider giving a neuromuscular blocking agent before transfer.

Family members may wish to say a final goodbye to their deceased loved one just before leaving the ICU for the operating room and this should be facilitated wherever possible.

The retrieval operation

Communication

The operating theatre may look and feel different to usual. It is likely that the anaesthetist will be working with unfamiliar staff over the next number of hours. It is a good idea to meet with the SNOD and the NORS team and to make introductions before transporting the donor from the ICU as this facilitates good communication between teams. The retrieval surgeons may need to make decisions about the suitability of an organ for transplantation because this has consequences for potential recipients. In addition, there are often technical anatomical challenges to removing organs. Good communication enhances the likelihood of a successful outcome. Haemodynamic disturbances are common during retrieval surgery, so the anaesthetist and retrieval team need to be able to anticipate, discuss and manage these events before and as they occur.

Spinal reflexes

Both motor and autonomic spinal reflexes and reflex arcs remain intact after DNC. These reflexes include movement of the trunk, limbs and neck. They may be more pronounced because of loss of descending inhibitory input from the brain. Noxious and non-noxious stimuli may provoke both motor and autonomic responses in up to 50% of DNC cases.⁶ These responses may need to be moderated by the anaesthetist during the retrieval procedure.^16,19 Spinal reflexes can also be upsetting to those who may not understand their basis or significance. For this reason, neuromuscular blocking drugs may be given during transfer to the operating theatre to avoid unwanted reflexes and unnecessary concern among staff. Neuromuscular blockade is also used to prevent reflex motor activity throughout the retrieval operation.^16,20

Volatile anaesthetics can reduce the autonomic spinal reflex arc that causes hypertension and tachycardia in response to a surgical stimulus. Volatile anaesthetics may also contribute to ischaemic preconditioning and improve graft function in the recipient.^19,20 Volatile anaesthetics are not given to provide ‘anaesthesia’ as the donor is dead.

Monitoring

All donors should have intra-arterial, central venous and urinary catheters placed whilst in the ICU.¹⁶ Invasive arterial BP, arterial oxygen saturation, ECG and temperature should be monitored from the ICU to the operating theatre. At least one large bore peripheral i.v cannula should be inserted to facilitate large volumes of fluids if necessary.

For cardiac retrieval, a second transducer system should be prepared to monitor CVP and, when required, intracardiac pressures during cardiac assessment. The cardiothoracic surgeon will commonly attach sterile monitoring tubing to a needle and pass the end to the anaesthetist who, in turn, attaches it to the transducer, flushes the tubing, zeroes it to atmospheric pressure and displays the pressure waveform on the anaesthesia monitor. A pulmonary artery catheter may have been placed in the ICU and can be used to assess right-sided cardiac pressures and cardiac output.

Inspired oxygen (Fio₂) and end-tidal carbon dioxide (Pe′co₂) should be monitored. End-tidal inhalation agent concentrations should also be measured when volatile agents are used. Airway pressures and tidal volumes should be measured to ensure lung-protective ventilation where lung retrieval is planned.

Arterial blood gas analysis can be helpful to monitor tissue perfusion (lactate concentration), oxygenation, ventilation (Paco₂), electrolytes and blood glucose concentrations during the procedure.

General considerations

As with any major operation, large fluid shifts and haemodynamic changes may occur and the anaesthetist should be prepared. Cardiac arrhythmias are not infrequent in the DNC donor and should be anticipated and managed in the usual way (electrolyte replacement, antiarrhythmic drugs, internal DC cardioversion and organ-preserving cardiopulmonary resuscitation if necessary).²⁷ I.V. infusion pumps and rapid fluid infusers should be available and the anaesthetist should be familiar with their use. The availability of blood products should be confirmed before the start of surgery.

It is important to note that there are times when parts of the procedure may be delayed or prolonged. Reasons include the unexpected finding of suspicious lesions after inspection of the organs that may need to be biopsied and reviewed before proceeding with procurement.⁶ In the case of heart transplantation, the preimplantation phase of the recipient operation may be complex. For example, the recipient may have had previous surgeries making dissection difficult. Donor aortic cross-clamping may need to be delayed (see below) to reduce the risk of a prolonged cold ischaemia time of the donor heart if the recipient is not ready for immediate transplantation. Such unanticipated delays are all part of the donation process.

Procedure common to any organ retrieval

The donor is positioned supine usually with the arms by the sides. Because the length of the incision makes placement of a forced air warmer difficult, a warming device may be placed underneath the patient. Antibiotics and steroids (if not already receiving as part of hormone replacement therapy) are given as per advice from the NORS team or SNOD. A neuromuscular blocking agent is given to optimise operating conditions. Many centres will observe a moment of silence or a senior member of staff will say a few words of thanks to acknowledge the donor's gift before the start of the operation.⁶

A laparotomy and sternotomy are performed (Fig. 1).¹⁵ Any associated spinally-mediated hypertension, tachycardia, or both can be managed using volatile agents or opioids.²⁰ After a period of preoxygenation, the ventilator tubing is disconnected from the tracheal tube during sternotomy to avoid damage to the underlying lungs from the sternotomy saw.⁶ The surgeons begin with a thorough visual inspection of the organs for previously undiagnosed disease, particularly malignancy.²⁸ The initial dissection of each organ focuses on preparing for the rapid ligation of blood vessels should severe haemodynamic instability or cardiac arrest necessitate immediate organ retrieval.²⁵ Once adequate dissection has taken place, heparin is given (300 IU kg⁻¹ i.v.) and the thoracic aorta, abdominal aorta or both are cannulated (Fig. 1). Significant blood loss may occur at this stage.

Fig 1.

Schematic representation of the aortic cross-clamp and perfusion catheters in situ in the organ donor after laparotomy and sternotomy. Figure adapted with permission from Wunderlich et al. Commission of Organ Donation and Removal German Transplantation Society. DTG procurement guidelines in heart beating donors. Transpl Int. 2011 Jul;24(7):733-57.

The organs are removed in the following order: heart, lungs, liver, small bowel, pancreas, kidneys.¹⁹ The order of removal is related to the cold ischaemia tolerance of each organ. Lymph nodes and sections of the spleen are taken and accompany each organ for immunological testing.²⁵

Procedure specific to the retrieval of abdominal organs

The aorta is cross-clamped and the aortic cannulae are flushed with cold perfusate (Fig. 1). At the same time, the venous outflow vessels are divided and the perfusate continues to flow until the venous outflow runs clear. The heart ceases to beat. Suction catheters ensure that blood and perfusate are immediately removed from the venous side of the circulation and are not allowed to pool within the thoracic or abdominal cavities. The organs are bathed in ice slush as an external aid to organ cooling.⁶

The liver has multiple ligamentous attachments that must be divided to facilitate mobilisation and inspection.²⁸ If the liver is being divided for transplantation into two recipients, dissection may be prolonged. The small and large bowel must also be mobilised in order to identify the great vessels in the retroperitoneum.¹⁹ The liver has a dual blood supply, so the inferior mesenteric vein may also be cannulated allowing the portal circulation to be flushed with cold perfusate.²⁸ If the pancreas is to be retrieved, a nasogastric tube and clamp are placed for antimicrobial decontamination of the small bowel with povidone-iodine (Betadine) solution, as the pancreas is removed with a cuff of duodenum.¹⁹ Cold preservation solution is given through a cannula in the abdominal aorta, and the perfusate is vented through the divided inferior vena cava.

Procedure specific to thoracic organs retrieval

For cardiac retrieval, the heart is inspected and palpated for coronary artery calcification. This may cause brief but significant haemodynamic instability.¹⁹ A transoesophageal echocardiogram may be performed to assist with cardiac assessment if this was not done before surgery. Intracardiac pressures may be measured as described in the monitoring section above. The superior vena cava may be ligated or clamped high in the chest, which may require the withdrawal of any indwelling central venous pulmonary artery catheter.¹⁶ The aortic root is cannulated before cross-clamping and cardioplegia is given.¹⁹ Both sides of the heart are vented to avoid overdistension of the ventricles with cold perfusate or cardioplegia (usually the right side via the inferior vena cava and the left side via the left atrium or the left atrial appendage). The left atrium is excised with an adequate cuff for reimplantation.

If the lungs are to be retrieved, a catheter mount with a bronchoscope port is attached to the tracheal tube so that the surgeon can assess the lungs for anatomical variations, intraluminal disease or infection using bronchoscopy.^27,29

After the pleura have been opened a gentle recruitment manoeuvre may be required to visually assess compliance of the lungs and the ventilator disconnected at full inspiration to assess their elastic recoil.^27,29 Regional gas exchange may be assessed from serial arterial blood gas samples drawn directly from each of the four pulmonary veins with the fraction of inspired oxygen (Fio₂) set at 1.0.²⁷ The diaphragm may be opened during the dissection. This changes lung compliance: pressure control modes of ventilation should be used with care because the lungs can be easily overinflated. The pulmonary artery is cannulated. A pulmonary vasodilator such as a prostaglandin may be given directly into the pulmonary artery before cross-clamping.^19,29 This can cause profound hypotension. The pulmonary artery is perfused with cold preservation solution. Mechanical ventilation continues during lung perfusion.²⁹

Immediately before lung removal the anaesthetist may be required to inflate the lungs gently with Fio₂ 0.5 to an airway pressure of 15–20 cmH₂0. This is to confirm visually that all atelectatic areas have been re-expanded before withdrawal of the tracheal tube and stapling of the trachea.¹⁶

Debriefing

The debrief is an important part of the organ donation and retrieval process.²¹ The process is often unfamiliar to operating theatre staff including non-clinical staff such as porters and cleaners. It is important, at some stage after the donation process, to sit down with those involved and talk through the process, answer questions, facilitate discussion and to offer support to those who need it. NHSBT and ODTI will send a letter to staff in donating hospitals thanking them for their efforts and providing some details on patients who benefited from the donated organs.

Conclusion

The anaesthetist has an important role in ensuring successful retrieval and transplantation of donated organs from patients where death is declared using neurological criteria. By understanding the organ donation and retrieval process and the roles played by so many people, the anaesthetist can safely manage the transfer of the organ donor to the operating theatre. He or she can continue the medical management of the organ donor that began in the ICU, and can ensure the physiologic optimisation, assessment and retrieval of transplantable organs. Ultimately, the anaesthetist can help carry out the wishes of organ donors and their families to give life to others through the gift of organ donation.

The recognition that ICU management can influence the number of transplantable organs has led to the intensive care training bodies in both the UK and ROI including organ donation training as part of core ICU training.³⁰ Less is understood about how intraoperative management may affect either the number or quality of donated organs. This is an area of focus for future research.^19,20

Acknowledgements

The authors wish to acknowledge the contribution of Davin Gaffney for drawing Figure 1.

Biographies

Sarah Corbett FCAI EDIC is a specialist trainee in anaesthesiology at Beaumont Hospital in Dublin.

Dominic Trainor BSc MRCP FCARCSI DICM is a consultant anaesthetist and intensivist, and clinical lead for organ donation at the Royal Victoria Hospital, Belfast.

Alan Gaffney MRCPI FCAI DICM PhD is a consultant anaesthetist and intensivist, and clinical lead for organ donation at Beaumont Hospital, Dublin.

Matrix codes: 1A01; 2A03; 3C00

Declaration of interests

The authors declare that they have no conflicts of interest.

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