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Beating heart organ donation 

Beating heart organ donation
Beating heart organ donation

Martin Smith

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date: 01 December 2020

Key points

  • Donation after brain death provides an opportunity to maximize the number and condition of organs for transplantation, and currently the only reliable source of donor hearts.

  • Brain death is associated with haemodynamic instability and other physiological changes that can jeopardize donor organ function.

  • Aggressive donor management increases the number of potential donors who become actual donors, increases the total number of organs transplanted per donor, and improves transplantation outcomes.

  • Optimization of haemodynamic variables is the cornerstone of donor management.

  • Hormone replacement remains controversial and should only be used in unstable donors requiring large doses of vasopressors, or in those with poor ventricular function.


Transplantation is the optimal treatment of end-stage dysfunction of many organs and can be life-saving. The principal factor restricting access to transplantation is the availability of suitable donor organs; there is an ever widening gap between the rising demands for transplantation and a diminishing supply of organs. Although living donation and donation after circulatory death are important and increasing sources of organs for transplantation, it is donation after brain death (DBD) that remains the most important. In DBD there is the opportunity to maximize the number and condition of potentially transplantable organs and also to provide a reliable source of hearts for transplantation.

The process of donation

Organ donor management begins with timely identification of potential donors, including those with a severe neurological injury that is likely to progress to brain death. Although adequate time must be allowed for the proper confirmation of brain death, unnecessary delays should be avoided because the incidence of systemic complications that jeopardise transplantable organ function increases progressively with time. Once brain death has been confirmed there should be a uniform request for consent for donation undertaken in conjunction with a representative from the local organ donation/procurement organization.

Following the confirmation of brain death there is a change in emphasis of care. Brain protective strategies that have previously been aimed at preserving residual brain function are replaced by physiological support designed to optimize organ function for subsequent transplantation. If a patient wishes to become an organ donor, it is the duty of the intensive care team to fulfil this wish by providing organs in the optimum condition. The management of the potential organ donor is thus the beginning of the management of up to seven potential recipients (Table 389.1).

Table 389.1 Physiological goals during donor management



Target range


Heart rate


Systolic blood pressure

>100 mmHg

Mean blood pressure

>70 mmHg

Cardiac index

2.4 L/min/m2


Tidal volume

8–10 mL/kg

Positive end expiratory pressure

5 cmH20 (15 cmH20 during recruitment manoeuvres)

Peak airway pressure

<30 cmH2O

Arterial blood gases




>10.5 kPa


4.7–6.0 kPa





130–150 mmol/L

Potassium, calcium, magnesium, phosphate

Normal range


4–8 mmol/L

Urine output

0.5–3 mL/kg/hour


>10.0 g/dL

Physiological changes after brain death

Brain death is associated with profound physiological changes that can jeopardize transplantable organ function (Table 389.2).

Table 389.2 Complications of brainstem death


Reported range of complication


100% (unless active rewarmed)

Hypotension requiring vasopressors


Diabetes insipidus




Myocardial dysfunction


Cardiac arrhythmias


Pulmonary oedema






Cardiovascular changes

Intractable increases in intracranial pressure (ICP), usually following catastrophic neurological injury, may lead to brain ischaemia, cerebral herniation, and brain death. As ICP increases, brainstem ischaemia progresses in a rostral-caudal direction with typical clinical correlates. Cerebral ischaemia precipitates vagal activation resulting in bradycardia and hypotension. Pontine ischaemia produces a mixed vagal and sympathetic activation, and the classic Cushing response characterized by bradycardia and hypertension. Finally, ischaemia of the medulla results in a massive autonomic sympathetic surge in a last ditch attempt to maintain cerebral perfusion [1]‌. This sympathetic storm, which lasts between one and six hours, increases heart rate, blood pressure, cardiac output, and systemic vascular resistance, and leads to central redistribution of blood volume, increased cardiac afterload, and splanchnic ischaemia [2]. It is also associated with widespread myocardial damage characterized by mitochondrial swelling, myocytolysis, and necrosis in up to 25% of donor hearts. Myocardial dysfunction, demonstrated by echocardiography, occurs in approximately 40% of brain dead donors [3].

Following the onset of brain death, the period of intense autonomic activity is followed by loss of sympathetic tone, profound vasodilatation and capillary leakage. The resulting hypotension and hypovolaemia is compounded by central diabetes insipidus and causes donor organ hypoperfusion if untreated.

ECG abnormalities are common after brain death and include ST segment and T wave changes, atrial and ventricular arrhythmias, and conduction abnormalities. They are multifactorial in origin reflecting loss of vagal tone, sympathetic over activity, myocardial ischaemia, blood gas and electrolyte abnormalities, as well as the effects of drug therapy.

Respiratory changes

The cardiovascular changes associated with the sympathetic storm lead to increases in pulmonary hydrostatic pressure, capillary endothelial damage, and the risk of pulmonary oedema. Pulmonary damage is aggravated by the profound inflammatory response associated with brain death [4]‌.

Endocrine and metabolic changes

Brain death is associated with hypothalamic and pituitary dysfunction or failure characterized by a classic endocrinopathy and thermoregulatory impairment. In particular, there are decreases in circulating tri-iodothyronine (T3), cortisol, and anti-diuretic hormone (ADH) which may contribute to cardiovascular deterioration [2]‌. The changes in anterior pituitary function are variable because pituitary blood flow may be preserved to some extent after brain death. Reduction in circulating T3 concentration occurs in 60–80% of brain dead donors, but only a few (around 15%) have very low levels [5]. This has been implicated in the deterioration of myocardial function because of a shift to anaerobic metabolism. Posterior pituitary failure is almost ubiquitous and leads to reduced levels of ADH and diabetes insipidus in 90% of brain dead donors. This results in hypovolaemia, hypernatraemia and hyperosmolality if untreated. Blood cortisol levels are also low and associated with impairment of donor stress responses. Hyperglycaemia is common because of decreased insulin concentrations and the development of insulin resistance. Hypothalamic failure causes loss of temperature control; early hyperpyrexia is followed by hypothermia because of reduction in metabolic rate and muscle activity, and peripheral vasodilatation.

Inflammatory response

Brain injury and brain death result in a profound neuro-inflammatory response. This leads to a systemic inflammatory response that can cause or aggravate established non-neurological organ dysfunction [4]‌.


Release of tissue thromboplastin from ischaemic brain may lead to disseminated intravascular coagulation. Other factors that contribute to the high incidence of coagulopathy in brain dead organ donors include massive transfusion, hypothermia, acidosis, and dilution of coagulation factors during fluid resuscitation.

Monitoring the organ donor

Optimum donor management requires invasive monitoring and management of cardiorespiratory variables. Continuous ECG, SpO2, direct arterial blood pressure, core-peripheral temperature gradient, and hourly urine output and arterial blood gases are monitored routinely. Central venous pressure measurement is a poor guide to fluid resuscitation after brain death, and cardiac output monitoring using pulse contour analysis or transpulmonary thermodilution is increasingly employed. Echocardiography is required to assess ventricular function in potential heart donors, and sequential assessment is a useful guide to fluid resuscitation. A pulmonary artery catheter should be inserted in those with cardiovascular instability and is invariably required for the assessment of cardiac function in potential heart donors [6]‌.

Resuscitation and maintenance of the organ donor

Aggressive donor management is crucial for several reasons. First, it facilitates donor somatic survival between confirmation of brain death and organ retrieval. This period can be prolonged because of the time required for the consent process, donor screening, identification and preparation of recipients, and mobilization of the retrieval team. Secondly, it maintains donor organs in the best possible condition and thereby improves the functionality of transplanted organs and the quality of life of the recipient. Minimizing on-going ischaemia reperfusion injury in donor organs by maintenance of haemodynamic stability is crucial in this regard. Standardized donor management results in an increase in the number of potential donors who become actual donors, an increase in total organs transplanted per donor, and improved post-transplantation outcomes [7]‌. Historically, it has been estimated that up to 25% of organ donors are lost because of poor donor management [8].

Cardiovascular support

Optimization of haemodynamic variables is the cornerstone of donor management, but is not straightforward because of the multiple contributors to cardiovascular instability after brain death. These include hypovolaemia secondary to osmotic diuretics used to treat intracranial hypertension, diabetes insipidus, hyperglycaemia-induced osmotic diuresis, and brain-death related cardiac dysfunction and peripheral vasodilation [1]‌.

Treatment of the autonomic storm with a short acting β‎-adrenergic receptor blocker is associated with a reduced risk of myocardial damage and increased probability of subsequent heart transplantation [9]‌. However, this treatment must be provided before brain death has been declared and therefore raises considerable ethical issues. The subsequent combination of myocardial depression, loss of peripheral vascular tone, arrhythmias and hypovolaemia leads to hypotension requiring support in 90% of donors. It is vital for organ preservation that adequate perfusion pressures are maintained and a mean arterial pressure >70 mmHg should be the goal. Fluid resuscitation is the initial treatment, but there is no evidence to support the preferential use of crystalloid or colloid. Although renal graft function benefits from a more aggressive fluid regime, euvolaemia is the goal if thoracic organs are to be donated because excessive fluid loading is associated with a decreased likelihood of lung transplantation [5]. However, lung protective strategies using relatively modest fluid replacement do not adversely affect post-transplant renal function if donor haemodynamic variables are monitored and managed appropriately [10]. Blood and other blood products should be administered as indicated.

If blood pressure cannot be maintained despite adequate fluid resuscitation, dopamine and other catecholamines, such as adrenaline, should be considered [11]. As well as the cardiovascular benefits, the anti-inflammatory actions of catecholamines offer some degree of organ preservation [12]. In patients with low systemic vascular resistance, noradrenaline may be used as a short term measure to maintain arterial pressure during fluid resuscitation. Prolonged and high-dose administration of noradrenaline or adrenaline may worsen neurogenic myocardial injury and transplanted heart dysfunction [13]. Vasopressin (0.5–1.0 milliunits/kg/h) may reduce catecholamine requirements without impairing graft function and the American College of Cardiology and Canadian guidelines recommended vasopressin as the first-line vasopressor for donor resuscitation [6,14]. Regional wall motion abnormalities and poor left ventricular ejection fraction are the most common reasons that donor hearts are deemed unsuitable. However, neurogenic cardiac injury can be reversible [15] and optimization of cardiac function may convert marginal to actual donors.

Cardiac function can be adversely affected by the hormonal changes associated with brain death and hormone replacement has been recommended.

Respiratory support

The lungs are one of the most difficult organs to preserve after brain death and are transplanted from only 15–25% of donors [14]. There are high rates of pulmonary damage before and after brain death including aspiration or ventilator acquired pneumonia, neurogenic pulmonary oedema, systemic inflammation, ventilator-induced pulmonary injury (barotrauma), and over-zealous fluid resuscitation. Lung-protective strategies, including low tidal volumes, minimizing airway pressure, avoiding high inspired oxygen fractions and fluid overload, and recruitment manoeuvres (particularly after the apnoea test) increase the number of eligible and transplanted lungs [16].

Hormone support

Early studies of three-hormone replacement, including thyroid hormone, steroid and vasopressin, reported catecholamine sparing effects, conversion of marginal to actual donors, improved short-term graft function, and increased numbers of transplanted hearts [17,18], but subsequent randomized trials have not confirmed these benefits [19]. Thus, three-hormone replacement remains controversial and, pending larger studies, should only be considered in unstable donors requiring large doses of vasopressors or in those with an ejection fraction less than 40% [20,6].

Some guidelines recommend thyroid hormone replacement only if cardiac function is impaired, whereas others advocate universal application [11]. The improvement in cardiac function and haemodynamic stability associated with thyroid hormone replacement in some studies might reflect the positive inotropic properties of thyroid hormone in the setting of the sick euthyroid syndrome rather than the effects of replacement therapy per se. There is little evidence to support the role of endogenous steroid supplementation as a routine part of donor management, although there has been recent interest in the administration of methylprednisolone to moderate the inflammatory response to brain death [5,11]. The initial treatment of diabetes insipidus is aimed at correcting hypovolaemia and hypernatraemia by the administration of hypotonic intravenous fluids or water via a nasogastric tube. If urine output continues greater than 3–4 mL/kg/hour, continuous vasopressin infusion or intermittent desmopressin, which is specific for the V2-vasopressin receptor and has predominantly antidiuretic effects, should be administered [6]‌.

Other support

Poor glucose control affects recipient renal and pancreatic function. Hyperglycaemia usually responds to standard insulin regimens, but in the presence of severe insulin resistance, substantial doses of insulin may be required to maintain plasma glucose in the required range (4–8 mmol/L) [6]‌.

Blood-product replacement should be aimed at providing adequate oxygen delivery and correction of coagulopathy. There is no evidence to guide the red cell transfusion threshold in brain dead donors, but maintaining a haemoglobin level > 10.0 g/dL (or haematocrit > 30%) has been recommended [20].

The loss of hypothalamic thermoregulation, combined with profound vasodilatation and an inability to shiver, results in a poikilothermic donor. Adverse effects of hypothermia include cardiac dysfunction, arrhythmias, coagulopathy, and cold-induced diuresis. The core temperature should be maintained greater than 35°C by warmed fluids, humidified inspired gases, and convective warming blankets.

General ICU management

General ICU measures should be continued during the period of donor management, although unnecessary drugs should be discontinued. Feeding or a glucose source should be maintained and electrolytes abnormalities corrected. Mechanical methods of thromboprophylaxis should be continued up to, and during, organ retrieval.


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