Susan L. Smith, MN, PhD


March 28, 2003

Donor Management: Physiologic Alterations of Brain Death

After the diagnosis of brain death, the focus of patient care shifts from interventions aimed at saving the patient's (donor's) life to interventions aimed at maintaining viability of potentially transplantable organs. The main goal of organ donor management is the maintenance of optimal conditions that will ensure functional, intact, and infection-free organs. The quality of organs to be recovered is preserved by optimal management of hydration and perfusion, oxygenation, diuresis, temperature control, and prevention of infection.

A number of physiologic changes occur with brain death, including hemodynamic instability, endocrine abnormalities, hypothermia, coagulopathy, pulmonary dysfunction, and electrolyte imbalances. Therefore, medical management ideally begins as soon as brain death appears imminent, as the window of time for optimal recovery is narrow. Irreversible cardiac arrest usually occurs within 48 to 72 hours of brain death in adults. The reader is referred to a critical pathway developed for management of the organ donor.[25] This pathway provides a multidisciplinary approach to promote communication in the care of organ donors and incorporates key events, multidisciplinary processes, and corresponding timelines or phases that caregivers should anticipate in the care of an organ donor. The components of the pathway include collaborative practice guidelines, referral of potential donors, declaration of brain death, and acquisition of consent for donation, donor evaluation, donor management, and the surgical recovery of donor organs.

Hemodynamic Instability

Hemodynamic changes begin to occur prior to the diagnosis of brain death. A decrease in blood pressure and heart rate is noted during the onset of brain death. As cerebral ischemia progresses and reaches the brainstem, a severe increase in systemic vascular resistance (SVR) and blood pressure occurs due to the release of endogenous catecholamines, commonly referred to as a "catecholamine storm." These changes reflect the body's attempt to maintain cerebral circulation and reverse brain ischemia.

However, at the peak of increased SVR, cardiac output decreases and perfusion to abdominal organs is decreased due to intense vasoconstriction. As ischemia continues, the catecholamine storm subsides with a decline in SVR. Blood pressure then drops to a hypotensive level, resulting in further hypoperfusion of vital organ systems unless treated. Hypotension is the most frequently encountered problem in the patient being managed as a potential organ donor.

In addition to the loss of central vasomotor control, other factors contribute to hemodynamic instability in the organ donor. Hypovolemia is the most common cause of hemodynamic instability in the organ donor and may result from therapeutic dehydration to decrease cerebral edema, incomplete fluid resuscitation after hemorrhage, diabetes insipidus, or osmotic diuresis from hyperglycemia or mannitol administration. Ventricular dysfunction from a myocardial contusion, electrolyte imbalances, and acute pulmonary hypertension also contribute to hemodynamic instability in the potential organ donor.

Endocrine Abnormalities

Brain death leads to rapid disturbances that affect the hypothalamus-pituitary axis. In most cases, vasopressin release is decreased, resulting in diabetes insipidus, which leads to polyuria, dehydration, hypernatremia, a hyperosmolar state, hypocalcemia, hypophosphatemia, hypokalemia, and hypomagnesemia. Brain death also affects the hypothalamus-pituitary-thyroid axis; however, it remains unclear how it is affected. It has been suggested that this endocrine abnormality is characteristic of the "euthyroid sick syndrome" (low T3, low T4, low TSH, or all 3), more commonly associated with acute major stress than actual hypothyroidism. The roles of other pituitary hormones, including adrenocorticotrophic hormone, prolactin, growth hormone, and gonadotropin, are less clear.


Many brain-dead patients become poikilothermic (core temperature drifts toward ambient temperature as a result of interruption of the temperature-regulating center in the hypothalamus) due to the lack of hypothalamic regulation of temperature and as a result become hypothermic. Hypothermia contributes to hemodynamic instability. As body temperature falls, myocardial depression occurs, leading to decreased cardiac output. At very low temperatures, the ventricles become irritable and refractory dysrhythmias often develop. Other harmful effects of hypothermia include reduced tissue oxygen delivery, impaired ability of the kidneys to maintain tubular concentration gradients, and coagulopathy.


Coagulopathy is common in the brain-dead patient, but is usually not the primary problem; it generally occurs secondary to other disorders. Coagulopathy results from the continuous release into the systemic circulation of large amounts of tissue thromboplastin and plasminogen from ischemic or necrotic brain tissue. Hypothermia and catecholamines also affect clotting factors and contribute to coagulopathy, and fluid resuscitation may also cause a dilutional coagulopathy.

Pulmonary Injury

Brain death is also associated with numerous pulmonary problems. The lungs are highly susceptible to injury resulting from the rapid changes that occur during the catecholamine storm. At the moment of peak vasoconstriction, left-sided heart pressures exceed pulmonary pressure, temporarily halting pulmonary blood flow. Exposed lung tissue is severely injured, resulting in interstitial edema and alveolar hemorrhage, a state commonly referred to as neurogenic pulmonary edema.

Hypoxia in the absence of pulmonary edema is often seen in the brain-dead patient, and a variety of factors are involved, including ventilation-perfusion mismatch, microatelectasis, and increased oxygen consumption. Pneumonia, aspiration, pneumothorax, pulmonary contusion, or other residual effects of the morbid event that caused brain death can also lead to hypoxia.

Electrolyte and Glucose Imbalances

Abnormal serum concentrations of electrolytes and glucose are common in the brain-dead patient and may result from the events that led to hospital admission, from treatment given prior to brain death, or from the effects of brain death. The effects of individual abnormalities may alter cellular processes, potentially interfering with cardiovascular stability and organ viability in the recipient, but may not always be appreciated clinically.

Hypoglycemia is rarely encountered in the brain-dead patient; however, mild-to-severe hyperglycemia is often seen. Hyperglycemia results from a variety of factors such as the stress response to injury, reduced insulin levels due to catecholamine release or inotropic infusion, and resuscitation with glucose-containing fluids. The major consequences of hyperglycemia are a hyperosmolar state leading to dehydration and a shift in electrolytes from intracellular to extracellular fluids, osmotic diuresis with a subsequent loss of water and electrolytes, metabolic acidosis, and ketosis.

Sodium is primarily an extracellular electrolyte and is responsible for osmolality in the extracellular space. Hyponatremia is uncommon in the brain-dead patient and when it occurs is often secondary to hyperglycemia. Hypernatremia, on the other hand, is common in the brain-dead patient as a result of dehydration, sodium administration, and free water loss secondary to administration of diuretics or diabetes insipidus. The impact of hypernatremia on posttransplant organ function is not fully understood.

Potassium is primarily an intracellular electrolyte, and its regulation becomes impaired in the brain-dead patient. Hyperkalemia, although somewhat rare, is most often the result of situations that impair renal elimination of potassium (ie, kidney failure) or that cause potassium to move into the extracelluar fluid (ie, metabolic acidosis).[6] Ninety percent of brain-dead patients develop hypokalemia. The most common causes are the use of diuretics, polyuria from any cause, and alkalosis.

Hypocalcemia, hypophosphatemia, and hypomagnesemia are common in the brain-dead patient and are most often related to the polyuria associated with osmotic diuresis, the use of diuretics, and diabetes insipidus. Hypocalcemia is often present when the brain-dead patient has been aggressively transfused with blood. Below-normal levels of magnesium may cause dysrhythmias and other electrocardiographic changes, and low levels of calcium and phosphorus may affect cardiac contractility and blood pressure, leading to an increased need for vasopressor support. Hypercalcemia, hyperphosphatemia, and hypermagnesemia as a consequence of brain death are rare.


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