Brain death / support brain death organ donor

• Evolution of  the concept of brain death
• Diagnosis of brain stem death
• Request for organ donation
• Support of the Brain Dead Organ Donor
• Contraindications to organ donation
• Cardio-respiratory support
• Ventilatory support
• Renal support
• Endocrine changes
• Hyperglycemia
• Other harmones
• Miscellaneous problems
• Conclusion

REQUEST FOR ORGAN DONATION

Brain death is relatively a new concept and making request for organ donation in these circumstances can be an extremely difficult task for a doctor or a nurse to undertake. If the decreased carries a 'Donor Card' (a card the size of a credit card expressing their desire about organ donation) the task of asking for organ donation becomes easier.

Usually the organ donation request is made in the time interval between the diagnosis of brain death and discontinuation of the ventilator. If the relatives are agreeable the process of organ donation is undertaken and vital organ like heart, lunge, liver, pancreas and kidneys are removed for transplantation. Corneas should be kept moist and eyelids should be closed and retrieval surgery can be done for up to 12 hours after cardiac standstill. Other tissues like heart valves, skin, bone and cartilages can be removed for up to 48 hrs after death. The process of organ donation and transplantation requires co-ordination (Table-IV) between different teams operating almost simultaneously and sometimes in different locations. It may require getting surgeons from different specialties together for both donor and recipient surgery.

Generally there is no bar to organ donation and one or the other organ or tissues can be donated at any age (Table.V). However, it is important to do some essential virology screening prior to accepting the donor. All potential donors will require a virology screen to prevent possible transmission of disease from donor to the recipient (Table.VI). The next of kin should be made aware that this is necessary, if there are any objections these should be respected. However, it does mean that donation cannot then take place.

Support of the Brain Dead Organ Donor

Once there is confirmation of brainstem death the clinicians should switch the focus of the management of the cadaver from therapy for elevated intracranial pressure and brain protection, to preservation of organ function and optimization of tissue oxygen delivery.

This will keep the organs in optimum condition so that the recipient has the best chance of recovery after transplant. Supportive treatment should start early as soon as brain death has been recognized irrespective of the consent; otherwise there can be rapid deterioration of initially suitable donors. In a poorly managed cadaver, the exercise of organ donation would yield organs that will result in poor graft outcomes.

Contraindications to organ donation :

The absolute contraindications to organ donation are:

1. Malignancy (except primary brain tumors, low grade skin malignancies and carcinoma in situ of the cervix),
2. Uncontrolled sepsis,
3. Active viral infections-hepatitis A and B, cytomegalovirus, herpes simplex virus and AIDS.

Specific criteria and contraindications exist for individual organs. There have been instances where kidneys from positive hepatitis status donors have been transplanted into positive hepatitis status recipient. Given the severe shortage of donor organs, the criteria for donor acceptance have been expanded. This has led to the concept of marginal donors as against ideal donors. Marginal donors may be elderly patients, patients with hypertension or poisoned victims (organophosphrous poisoning) with significant complications of brain stem death. When there is concern about the suitability of organs, this may have to be resolved during the organ procurement procedure, by direct inspection and in some cases by open biopsy and frozen section histopathology examination.

Hemodynamic instability occurring during 'coning' or brain herniation is the result of an "autonomic storm". This is the result of massive increase in systemic catecholamine levels and increase in sympathetic activity. This phase occurs unheralded and is of variable duration. During brain herniation major metabolic stress and impairment of organ perfusion occur which affects post transplant organ function. This is of critical significance in chemo-sensitive organs like the heart and liver where immediate graft function is essential. Following the autonomic storm there is a profound reduction in sympathetic outflow and catecholamine levels decreases to below baseline values. The resting vagal tone is abolished because of destruction of the nucleus ambiguus. The subsequent chronic maintenance phase of brain stem dead donors is frequently characterized by hypotension.

There is evidence that brainstem death eventually leads to cardiac arrest, even when cardio-respiratory support is maintained. Complications related to the profound physiological disturbances consequent on brain stem death include hypotension arrhythmias, pulmonary edema, hypoxia, diabetes insipidus, metabolic acidosis, Disseminated intravascular coagulation and infections. The incidence of complications increases progressively after brainstem death and may affect organ function. The common and uncommon problems usually encountered in these patients are enlisted in Table VII. While optimizing the function of different organs, it is necessary to pay attention to the details. For instance large volume fluid resuscitation is important for maintaining kidney function, but may result in pulmonary edema rendering the lungs unsuitable for transplantation.

Cardio-respiratory support

As indicated earlier the overall management goal is to ensure adequate tissue oxygen delivery. Parameters that suggest this, in the absence of lactic acidosis are indicated in the Table.VIII.. The usual problems encountered in a brain death patient are related to

1. Hypotension
2. Arrhythmias and cardiac arrest
3. Hypoxemia
4. Ventilatory support.

Hypotension

This is most common problem seen in brainstem dead organ donors. This is commonly multifactorial, mainly due to volume depletion and to a lesser extent impaired myocardial contractility. The volume depletion is both 1) absolute, related to therapy for raised intracranial pressure; and 2) relative, related to the loss of sympathetic tone. The latter is due to complete vasomotor collapse with significant peripheral venous pooling.The differential diagnosis includes, hypovolemia, cardiac dysfunction, electrolyte abnormalities, and hypothermia and drug effect.

Invasive monitoring of arterial and central venous pressure should be instituted. In the management of hypotension, it is important to remember that proper fluid management is the cornerstone of therapy. If possible the use of vaso-pressors should be minimized because of their splanchic vaso constrictive effects. All inotropes and vasopressors have been used. The first choice is usually Dopamine, preferably at a dose below 10mcg/kg/min. Dobutamine should be used for impaired myocardial contractility; and Norepinephrine or Epinephrine for severe systemic vasodilation. If the patient has tachycardia, dopamine will cause further tachycardia and in these situations dobutamine is useful as this will not increase the heart rate. Norepinephrine can be used in short bursts to maintain the blood pressure. Sometimes all the three drugs are used simulataneously to maintain an adequate pressure. If heart retrieval is contemplated for transplant these ionotropes should be controlled carefully and monitored.

Fluid resuscitation may require several litres of fluid. A combination of crystalloids and colloids is used. Relying on urine output alone to determine adequacy of fluid resuscitation is misleading because of polyuria due to diabetes insipidus. In donors who remain unstable despite routine management, pulmonary artery catheterization may help in determining the problem.

Arrhythmias

Hemodynamic instability can be pronounced after brainstem death with a spectrum of bradyarrhythmias and tachyarrhythmias Bradyarrhythmias occurring as part of the Cushing reflex, during coning, do not require treatment . Correctable factors like acidosis, electrolyte abnormalities and inotrope- related arrhythmias should be treated. Thereafter, medications that possess rapid reversibility and a short half-life should be used. Atropine is ineffective for bradyarrhythmias after brain death has occurred.

Hypoxia

This may be related to infections, collapse or pulmonary edema. The etiology of pulmonary edema may be cardiogenic, fluid overload, neurogenic or Adult Respiratory Distress Reproduction. This is treated by titrating the fractional inspired oxygen concentrations (FiO2) and positive and expiratory pressure (PEEP). While high FiO2, greater than 0.6, increases the risk of oxygen toxicity; highPEEP>15cmH2O reduces cardiac output.

Ventilatory support

This is an essential part of the support of brainstem dead organ donors as they are apneic. Discontinue hyperventilation which is likely to have been employed for control of raised intracranial pressure. The partial pressure of CO2 should be maintained in the normal range. This may require a considerable reduction in minute volume. Routine use of PEEP at 5 cm H2O in brainstem dead organ donors is recommended to prevent microatelectosis. Airway pressures, i.e. the plateau pressures should be below 35cmH2O to reduce the risk barotrauma.

Renal support

If the urine output is less than 1ml/kg/hr, despite adequate filling pressures and blood pressure, loop diuretics or osmotic diuretics should be used to initiate diuresis. Polyuria, a frequent finding in brainstem dead organ donors, is due to diabetes insipidus. Other causes include osmotic diuersis due to mannitol or hyperglycemia and physiologic diuersis due to massive fluid resuscitation. Electrolyte abnormalities observed during diabetes insipidus include hypernatremia, hypokalemia, hypocalcemia and hypomagnesemia.