MANAGEMENT OF BRAIN DEATH

REQUEST FOR ORGAN DONATION

Brain death is relatively a new concept and making request fororgan donation in these circumstances can be an extremely difficulttask 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 desireabout organ donation) the task of asking organ donation becomes easier, otherwise the question of donation should be only carefully taken up.
In 1995 a large survey of 5008 members of the public undertaken to findout their attitude towards organ donation. Seventy two percent of thepeople surveyed were willing to donate eyes. Less than 50% wereagreeable for solid organ donation ( heart, liver, lungs, kidney, Pancreas). On the basis of this survey a simple protocol was devisedcalled Ramachandra Protocol when asking for organs. In this protocol Eyes ' were first requested for and only if the relatives agreed otherorgan donations were requested,. In the tragic circumstance it was feltthat by asking for the eyes first the relatives were less likely toget upset with a request for organ donation (Table-IV).Usually therequest is made in the time interval between the diagnosis of braindeath and discontinuation of the ventilator. If the relatives areagreeable the process of organ donation is a undertaken and vital organlike heart, lunge, liver, pancreas and kidneys are removed fortransplantation. Tissues like corneas, skin, bone and cartilages can beremoved after death. The process of organ donation and transplantationrequires co-ordination (Table-V) between different teams operatingalmost simultaneously and sometimes in different locations. It mayrequire getting surgeons from different specialties together for bothdonor and recipient surgery. Generally there is no bar to organdonation and one or the other organ or tissues can be donated at anyage (Table.V). However, it is important to do some essential virologyscreening prior to accepting the donor. All potential donors willrequire a virology screen to prevent possible transmission from donorto the recipient (Table.VI). The next of kin should be made aware thatthis is necessary, if there are any objections these should berespected. 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 shouldswitch the focus of the management of the cadaver from therapy forelevated intracranial pressure and brain protection, to preservation oforgan function and optimization of tissue oxygen delivery.
During this process consent for organ donation from the family shouldbe sought.. This will keep the organs in optimum condition so that therecipient has the best chance of recovery after transplant. Supportivetreatment should start early as soon as brain death has been recognizedirrespective of the consent otherwise there can be rapid deteriorationof initially suitable donors at which stage the whole exercise of organdonation 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 statusdonors have been transplanted into positive hepatitis status recipient.Given the severe shortage of donor organs, the criteria for donoracceptance have been expanded. This has led to the concept of marginaldonors as against ideal donors. Marginal donors may be elderlypatients, patients with hypertension, poisoned victims(organophosphrous poisoning) patients with significant complications ofbrainstem death, etc. When there is concern about the suitability oforgans, this may have to be resolved during the organ procurementprocedure, by direct inspection and in some cases by open biopsy andfrozen 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 affect post transplant organ function. This is of 
significance in chemo-sensitive organs like the heart and liver. Following the autonomic 
storm there is a profound reduction in sympathetic outflow and catecholamine levels 
decrease to below baseline values. The resting vagal tone is abolished because of 
destruction of the ??? nucleus ambiguus. The subsequent chronicmaintenance phase of brain stem dead donors is frequently characterizedbyhypotension.

There is evidence that brainstem death eventually leads to cardiacarrest, even when cardio-respiratory support is maintained.Complications related to the profound physiological disturbancesconsequent on brainstem death include hypotension arrhythmias, pulmonary edema, hypoxia, diabetes insipidus, metabolic acidosis, DICand infections. The incidence of complications increases progressivelyafter brainstem death and may affect organ function. The common anduncommon problems usually encountered in these patients is enlisted inTable VII.
Although adequate time must be allowed to confirm the diagnosis, unnecessary delays must be avoided. Meanwhile aggressive and meticuloussupportive care is required to maintain organ perfusion to enhancegraft survival and function. While optimizing the function of differentorgans, it is necessary to pay attention to the details. For instancelarge volume fluid resuscitation is important for maintaining kidneyfunction, but may result in pulmonary edema rendering the lungsunsuitable 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. The problems encountered are 1)Hypotension 2) Arrhythmias and cardiac arrest 3) Hypoxemia and 4) Ventilatory support.

Hypotension 

This is most common problem seen in brainstem dead organ donors.This is commonly multifactorial  volume depletion and to a lesserextent impaired myocardial contractility. The volume depletion is both1) absolute, related to therapy for raised intracranial pressure; and2) relative, related to the loss of sympathetic tone. The latter is dueto complete vasomotor collapse with significant peripheral venouspooling.

The differential diagnosis includes, hypovolemia, cardiacdysfunction, electrolyte abnormalities, and hypothermia and drug effect.
Invasive monitoring of arterial and central venous pressure should beinstituted. In the management of hypotension, it is important toremember that proper fluid management is the cornerstone of therapy. Ifpossible the use of vaso pressors should be minimized if at allpossible because of their splanchic vaso constrictive effects. Allinotropes and vasopressors have been used. The first choice is usuallyDopamine, preferably at a dose below 10mcg/kg/min. Dobutamine should beused for impaired myocardial contractility; and Norepinephrine orEpinephrine for severe systemicvasodilation.

Fluid resuscitation may require several litres of fluid. Acombination of crystalloids and colloids is used. Relying on urineoutput alone to determine adequacy of fluid resuscitation is misleadingbecause of polyuria due to diabetes insipidus. In donors who remainunstable despite routine management, pulmonary artery catheterizationmay help in determining the problem.

If the patient has tachycardia, dopamine will cause further tachycardiaand in these situations dobutamine is useful as this will not increasethe heart rate. Norepinephrine can be used in short bursts to maintainthe blood pressure. If heart retrieval is contemplated for transplantthese ionotropes again controlled carefully and monitored.

Arrhythmias

Hemodynamic instability can be pronounced after brainstem deathwith a spectrum of bradyarrhythmias and tachyarrhythmiasBradyarrhythmias occurring as part of the Cushing reflex, duringconing, do not require treatment . Correctable factors like acidosis, electrolyte abnormalities and inotrope- related arrhythmias should betreated. Thereafter, medications that possess rapid reversibility and ashort half-life should be used. Atropine is ineffective forbradyarrhythmias after brain death has occurred.

Hypoxia 

This may be related to infections, collapse or pulmonary edema. Theetiology of pulmonary edema may be cardiogenic, fluid overload, neurogenic or Adult Respiratory Distress Reproduction. This is treatedby titrating the fractional inspired oxygen concentrations(FiO2) andpositive and expiratory pressure (PEEP). While high FiO2, greater than0.6, increases the risk of oxygen toxicity; high PEEP>15cmH2Oreduces cardiac output.

Ventilatory support 

This is an essential part of the support of brainstem dead organdonors as they are apneic. Discontinue hyperventilation which is likelyto have been employed for control of raised intracranial pressure. Thepartial pressure of carbon di-oxide should be maintained in the normalrange. This may require a considerable reduction in minute volume. Routine use of PEEP 5 cm H2O in brainstem dead organ donors isrecommended to prevent microatelectosis. Airway pressures, i.e. theplateau pressures should be below 35cmH2O to reduce the riskbarotrauma.

Renal support

If the urine output is less than 1ml/kg/hr, despite adequatefilling pressures and blood pressure, loop diuretics or osmoticdiuretics should be used to initiatediuresis.

Polyuria, a frequent finding in brainstem dead organ donors, is dueto diabetes insipidus. Other causes include osmotic diuersis due tomannitol or hyperglycemia and physiologic diuersis due to massive fluidresuscitation. Electrolyte abnormalities observed during diabetesinsipidus include hypernatremia, hypokalemia, hypocalcemia andhypomagnesemia.

Endocrine changes

Diabetes insipidus

This should be suspected when urine volumes exceed 300ml/hr (or7ml/kg/hr) in association with hypernatremia (Serum Sodium greater than150mEq/l), elevated serum osmolality (>310mOsm/L) and a low urinarysodium concentration. Desmopressin (dDAVP) should be used in preferenceto Vasopressin. The latter has undesirable splanchnic and renalvasoconstrictive effects. The dose is titrated to maintain urineoutputs of 1-2ml/kg/hr. usual dosages are Desmopressin 1-4 mcg every 8to 12 hours, Vasopressin 1-4 units/h. Replacement intravenous fluidsshould contain free water, i.e. Dextrose and / or half strength (0.45)Normal saline.

Hyperglycemia

This is due to the administration of glucose containing fluids, reduced insulin secretion and increased levels of catecholamines. Hyperglycemia results in an osmotic diuresis and electrolytedisturbances. Blood glucose levels should be controlled withintravenous insulin infusion.

Other hormones

The use of hormonal therapy, tri-iodothyronine corticosteriods andinsulin, has been advocated to improve cardiovascular stability. Atpresent, such therapy is regarded as experimental.


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