It is important to recognize and diagnose brain death especially in patients who are potential organ donors. Early diagnosis, documentation and initiation of the organ donation process and appropriate management of brain-dead organ donorsforms an important part of intensive care unit management.
Ministry of Health and Family Welfare has come out with the Standard Treatment Guidelines for Brain Death And ICU Management. Following are its major recommendations.
Brain death is defined as the irreversible loss of all function of the brain, including the brainstem. The three essential findings to confirm brain death are coma (known irreversible cause), absence of brainstem reflexes, and apnea.
An evaluation for brain death should be considered in patients who have suffered a massive, irreversible brain injury of identifiable irreversible cause as established by history, clinical exam, lab testing or neuro imaging (CT scan or MRI). Once brain death criteria are met a person clinically determined to be brain dead is legally dead in the context of organ donation under the Transplantation of Human Organ Act 1994. Always consider Medico legal, philosophical and religious perspective.
Optimal Diagnostic Criteria, Investigations, Treatment & Referral Criteria
Situation 1: At Secondary Hospital/ Non-Metro situation: Optimal Standards of Treatment in Situations where technology and resources are limited
The diagnosis of brain death is primarily clinical. No other tests are required if the full clinical examination, including each of two assessments of brain stem reflexes and a single apnea test, are conclusively performed. In the absence of either complete clinical findings consistent with brain death, or confirmatory tests demonstrating brain death, brain death cannot be diagnosed.
Neurologic states that can mimic brain death
- Locked-in syndrome (Present in case of GBS); Patient cannot move the limbs, grimace or swallow, but blinking and vertical eye movements remains intact.
- Vegetative state; No awareness of self and environment using a series of stimuli after CPR may take 1 month to become fully apparent and is permanent if no change after 3 months is observed.
Brain death Examination
1. Irreversible loss of clinical brain function. (Definitive cause leading acute brain catastrophe compatible with diagnosis of brain death evidenced on clinical or neuroimaging)
2. Achieve Systolic Blood Pressure>100mmHg and core body temperature >32 C (>90°F).
3. Exclusion of confounding factorin prognostication.
- Drugs (sedatives or neuromuscular blocking agents).
- Hypothermia (induced hypothermia therapy).
Brain death test
- Sufficient time period has been passed to exclude possibility of possible recovery of meaningful neurological function, several hours to days as per clinical factors.
- The relevant family member or appropriate party has been notified of the intention to initiate the determination of brain death.
- Neurological exam then proceeds with aim of determining three principle findings in brain death: coma, absence of brainstem reflexes and apnea (coma and apnea must coexist).
- Two physician as per local institutional protocol do the brain death test
- The second physician should not be involved in the patient’s care.
- Neither physician should be involved with organ transplantation.
- Intensivist, neurologist or any physician competent doing brain death test appointed by the institute as per local law can do the brain death test, both physician do the test individually.
Determination of unresponsiveness(Coma)
- Absence of supraspinal motor response to pain in all extremities and no eye opening to pain (standardized painful stimuli – supraorbital pressure, TMJ pressure, sternal rub and nail bed pressure) Glasgow coma scale 3/15.
Examination of brain stem reflex
- Dilated pupils at mid position (4–6 mm).
- Absence of bilateral pupillary responses to light.
- Absent oculocephalic reflex (doll’s eye )
- Absent cold caloric responses (vestibulo-ocular reflex)
Absent Facial sensory and motor response
Absent Pharyngeal reflex and Tracheal reflex
- Absence of gag reflex.
- Absence of coughing in response to tracheal suctioning.
- Core body temperature >36.5°C(>97°F).
- Euvolemia with appropriate fluid balance in the previous 6 hours.
- Normal PaO2.
- Normal PaCO2.
- Connect SpO2 probe and preoxygenation at 100% Fio2 for 10 minutes, draw baseline ABG, Pao2 >200 mmHg and Paco2 ~40mmHg (may require to reduce ventilator rate to get eucapnia) is needed.
- Disconnect the ventilator.
- Delivering oxygen by tracheal catheter at carina with flow of 6 liters per minute or Tpiece system using 12 l/min O2 flow or use CPAP of 10 cmH2O (less hypoxia with CPAP method).
- Observe the chest and the abdominal wall movement for respiration for 8 to 10 minutes and monitor the patient for changes in vital functions.
- Rate of rise of PaCO2 is 3mmHg per minute so 8 – 10 minutes are sufficient for apnea test to get rise of 20 mmHg of PaCO2.
- Draw post test ABG and then reconnect the ventilator.
- Positive apnea test – Absence of respiratory drive at a Paco2 of 60 mm Hg or 20 mm Hg above normal base-line values, apnea is confirmed.
- If respiratory movement occurs or any sign of hemodynamic instability, abandon the test, draw sample for ABG and then reconnect the ventilator.
Routine use is not recommended.
Observation period between two examination
Depends on the age of the patient;
- 7 days to 2 month old minimum 48 hr interval.
- 2 month to 1 year old minimum 24 hr interval.
- >1 year to <18 years old minimum 12 hr interval.
- >18 years old, interval is optional, minimum 6 hr.
Number of Confirmatory tests
- Neonate < 7 days Brain death testing is not valid.
- 7 days to 2 months old, 2 confirmatory tests.
- >2 months to 1 year old, 1 confirmatory test.
- >1 year to <18 years old, optional.
- >18 years old, optional.
Brain death declaration
- If clinical criteria’s are met.
- No need of confirmatory test.
Documentation of brain death
- Etiology and irreversibility of condition.
- Absence of brainstem reflexes.
- Absence of motor response to pain.
- Absence of respiration with Paco2 ≥ 60 mm Hg.
- Timing of first and repeat neurologic examination.
- Justification for confirmatory test and result of confirmatory test.
- Brain death time – time of rise of Pao2 >60mmHg after second set of test.
- Two physician signatures should be obtained.
Primary or secondary health care centre
- Brain death test are clinical.
- Brain death can be declared at these centers if all three criteria’s are fulfilled.
Communication with family and further decision making
After the clinical criteria of brain death have been met, the physician should inform the next of kin, who can be approached about organ donation. The physician is required to abide by state law with respect to organ donation.
- Basic intensive care, cardivascular, respiratory, hemodynamic and metabolic support Routine ICU care and monitoring
- Nursing care.
- Skin care.
- Turning and positioning.
- Care of lines.
- Ryle’s tube to prevent risk of aspiration.
- Pulse oximetry.
- Arterial and central venous pressure monitoring.
- Pulmonary artery catheter placement If necessary.
- Foleys catheter for urine out put monitoring.
- Core temperature monitoring.
- Antibiotic therapy.
- Anticipation of complications.
- Prevention and treatment of complications.
- Frequent assessment and titration of therapies.
- Maintenance of vital organ function;
- Oxygen delivery to the tissues.
- Hydration and perfusion.
- Routine laboratory testing ABG, CBC, SE, BUN, Cr and LFT.
- Testing for HIV, HBV & HCV on all donors after first apnea test.
- Additional tests may be necessary as per local protocol.
- Support of the family.
- The family should be counseled that the patient cannot recover
- Family should be counseled for organ donation
- If the patient cannot become an organ donor, withholding or withdrawing of life support may be discussed with the family.
- If the patient is a potential organ donor, he should be transferred to a tertiary level centre that is certified by the competent authority and is capable of supporting the brain dead organ donor
- If in some cases further diagnostic studies are required to confirm brain death
o Difficulty to determine coma.
o Incomplete brain stem reflex testing.
o Incomplete apnea testing.
o Toxic drug levels.
o Facial trauma.
o Preexisting pupillary abnormality.
o Sleep apnea or severe pulmonary disease resulting in chronic retention of CO2 .
o Children younger than 1 year old (<1 year age not recommended).
o As required by institutional policy
*Situation 2: At Super Specialty Facility in Metro location where higher-end technology is available
a)Clinical Diagnosis: As per situation 1
b)Investigations: as per situation 1 plus
- Bispectral index (BIS)
- Cerebral angiography (CTA, MRA) when ICP exceeds MAP angiography demonstrates absence of blood flow beyond carotid bifurcation.
- Cerebral scintigraphy (technetium tc-99m brain scan)
- Noninvasive study also knownas a cerebral blood flow study.
- Absent uptake of isotope in brain parenchyma is supportive of a diagnosis of brain death- Hollow skull phenomenon.
- Single photon emission computed tomography(SPECT) at 48 hrs is 100 % diagnostic.
- In case of barbiturate coma neuroimaging can be used without the necessary wait (5 half life provided normal renal and hepatic function) for the medication to leave the system.
- Transcranial Doppler Ultrasonography
However, the clinical criteria of brain stem death are considered adequate under the Transplantation of Human Organ Act and special investigation are not mandatory to declare brain stem death in India.
Treatment as in Situation 1 above plus
ICU management of Brain dead organ donor
ICU management of the potential organ donor plays a key role in maintaining and increasing current number of donor organs aim is to improve organ survival.
- Early identification of potential donors;
Critically ill patient in an intensive care unit – severity of acute brain injury is such that there is a high probability of brain death occurring.
- Early notification of Organ Procurement Organization(OPO), State Authorization Committee, Zonal Transplant Coordinating Centre (ZTCC) or Local Authorization Committee(LAC)as per institutional protocol.
- Designated requestor – OPO or LAC coordinator, as per institutional protocol.
- Requesting consent to organ donation from the family are ethical and professional responsibilities of the intensive care specialist. Preparation of the family.
- Consider family’s psychological, religious and cultural needs.
- Enquiring about the stated wishes of the patient.
- Ensuring the wishes, dignity and privacy of the donor are respected.
- Provide sufficient information and time.
- Support family to make an informed decision concerning organ donation without undue pressure.
- Clarification of ongoing physiologic support despite brain death.
- The family should have adequate emotional and social support after giving consent to organ donation and during the follow up period.
- Details of all discussions with the families should be documented.
Supportive treatment should start early as soon as brain death has been recognized irrespective of the consent.Switch the focus of the management for elevated intracranial pressure and brain protection, to preservation of organ function and optimization of tissue oxygen delivery.
- Hypertension and bradycardia preceding brain death characterize the Cushing’s response.
- Ischemia of the vagal nucleus in the medulla oblongata results in uncontrolled sympathetic stimulation- catecholamine “storm” results in systemic hypertension, tachycardia and possibly tissue ischemia including;
o Pituitary ischemia.
o Myocardial injury – right and/or left ventricular dysfunction.
- Duration and severity of this “storm “ varies but within hours results in depletion of catecholamine with subsequent generalized vasodilatation and homodynamic collapse.
- Initial period of severe HTN – short acting ß-blocker esmolol.
- Most common problem seen in brainstem dead organ donors.
- Chronic maintenance phase of brain stem dead donors is frequently characterized by hypotension.
- Invasive monitoring of arterial and central venous pressure should be instituted.
- Proper fluid management is the cornerstone of therapy;
o Fluid resuscitation may require several liters of fluid.
o Combination of crystalloids and colloids is used.
o Relying on urine output alone to determine adequacy of fluid resuscitation is misleading because of polyuria due to diabetes insipidus.
o If possible use of vasopressors should be minimized because of their splanchnic vasoconstrictive effects.
o The first choice is usually Dopamine, preferably at a dose below 10mcg/kg/min.
o Dobutamine should be used for impaired myocardial contractility; and
o Norepinephrine or Epinephrine for severe systemic vasodilatation.
- In donors who remain unstable despite routine management, pulmonary artery catheterization may help in determining the problem.
- Rule of 100’s for management of brain death organ donor;
o SBP 100 mmHg
o U/O 100 ml/hr
o PaO2 100 mmHg
o Hb 100 g/L
- Brady arrhythmias and tachyarrhythmia are common after brain death.
- Brady arrhythmias occurring as part of the Cushing reflex, during coning, do not require treatment.
- Correct acidosis, electrolyte abnormalities and try to optimize Inotropes.
- Atropine is ineffective for Brady arrhythmias after brain death has occurred.
- Increase ET cuff pressure immediately after BD declaration.
- HOB up 30°.
- Turning q2h.
- Pulmonary toilet.
- Paco2 should be maintained in the normal range.
- Routine use of PEEP at 5 cm H2O in brainstem dead organ donors is recommended to prevent microatelectasis.
- Plateau pressures should <35cmH2O to reduce the risk barotrauma.
- FiO2 <0.6 to reduce the risk of oxygen toxicity.
- PaO2 of >100 and a saturation >95%.
- Monitor ABG’s q2h or as required.
- Chest X-Ray.
- Bronchoscopy in some cases.
- CT chest in some cases
- Maintain urine output 1-3 ml/kg/hr.
- Avoid nephrotoxic drug.
- Maintain Euvolemia.
o 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;
- Diabetes insipidus.
- Osmotic diuresis due to mannitol or hyperglycemia.
- Physiologic diuresis due to massive fluid resuscitation.
As neurologic death occurs, alteration in the hypothalamic-pituitary-adrenal axis (HPA axis) is inevitable.
- DI results in problems with homodynamic stability and fluid and electrolyte balance;
o Urine volumes exceed 300ml/hr (or 7ml/kg/hr).
o Hypernatremia (serum sodium greater than 150mEq/l).
o Serum osmolality (>310mOsm/L).
o Low urinary sodium concentration.
- Desmopressin (dDAVP) preferred;
o (DDAVP) 1 mcg IV, may repeat x 1 after 1 hour.
o 1-4 mcg every 8 to 12hrly SC.
o Nasal spray.
- Vasopressin – splanchnic and renal vasoconstrictive effects.
o 1-4 units/hr.
- Hypernatremia (>155mEq/L)
o Free water, i.e. D5% or half strength 0.45% Saline.
- Insulin 0.05-0.1U/kg/hour titrated to maintain glucose at 80-120.
- Hourly glucose checks so as to avoid hypoglycemia.
Thyroid hormone replacement
- Thyroid hormone administration typically with T3 (triiodothyronine) which is the active form of thyroid hormone.
- T3 is converted from T4 and T3 is 4 X more active than T4
- Use T3 preferably if not available use T4 (T3 dose 0.05-0.15 mcg/kg/hour) titrate to keep SBP >100
- Monitor Potassium levels closely.
- Protocols may use hydrocortisone 1.5 mg/kg IV Q 6 hours (max dose of 100 mg) or single dose of methylprednisolone 15 mg/kg in adults and 1 mg/kg in children (max dose of 2 gm).
- The use of hormonal replacement therapy, Thyroxin, triiodothyronine (T3), corticosteroid and insulin, has been advocated to improve cardiovascular stability. At present, such therapies are regarded as experimental. Studies regarding ACTH and cortisol levels inconclusive. Unclear whether steroids make any significant improvement in organ preservation.
- Core temperature should be monitored using rectal thermometers.
- Maintain above 35°C.
- If core temperature <35°C
- Warm inspired gas.
- Warmed IV fluids.
- Warming lights.
- Warming blankets.
- Hot packs in the axilla.
- Systemic infection is a relative contraindication to organ donation.
- All unnecessary indwelling devices should be removed.
- All lines and catheters must be inserted aseptically.
- Care of dressings and wounds is vital.
- Tracheal suction should be done with sterile precautions.
- Appropriate samples from suspected sources of infection should be sent for culture and sensitivity.
- Prophylactic antibiotics are indicated only immediately prior to organ retrieval.
- If clinically significant mucocutaneous bleeding, treatment with appropriate blood components is required.
- Keep hematocrit > 30%.
Ischemic reperfusion injury
- Keep FiO2 <0.6.
- Avoid hyperthermia (>37°C).
- Avoid hyperglycemia (>180 mg/dl).
- Steroid and N-acetylcysteine may have sort term and long organ survival.
Absolute Contraindications to organ donation
- Malignancy (except primary brain tumors, low grade skin malignancies and carcinoma in situ of the cervix).
- Uncontrolled sepsis.
- Active viral infections-hepatitis A and B, CMV, HSV, AIDS.
Age and Organ Harvesting
- Corneas 0 – 100 years (poor eyesight is not a contraindication).
- Heart Valves 0 – 60 years (Heart Attack not a contraindication).
- Trachea 15 – 60 years.
- Skin 16 – 85 years.
- Kidneys 0 – 75 years (Pediatric donors consider weight and size).
- Liver 0 – 70 years (size matching is usually recommended).
Organ Preservation Time
- Heart – 4 to 6 hours.
- Lungs – 4 to 6 hours.
- Small Intestines – 4 to 6 hours.
- Liver – 12 hours.
- Pancreas – 12 to 18 hours.
- Cause of irreversible brain injury.
- Absence of other potentially reversible causes of coma.
- Clinical and other findings that confirmed brain death.
- Time of brain death.
- Information to the patient’s family on brain death and organ donation.
- Consent for organ or tissue donation.
- Signatures required
- Medical officer treating the patient.
- Neurologist/Neuro Surgeon (Where Neurologist/Neurosurgeon are not available, then anaesthetist/intensivist).
- Authorized Specialist (from panel of experts approved by the Appropriate Authority).
- Medical Administrator In charge of the hospital.
A severe shortage of organs the world over has led to increased pressure on the intensive care staff for early identification of the brain dead donor and optimum management of this condition. The diagnosis of brain death as per the Transplantation Human Organ Act 1994 is based on simple clinical bedside tests,no need of routine confirmatory test. This Act has made it possible in India to use this pool of patients for organ retrieval and transplantation. The process of organ donation and transplantation requires co-ordination between multidisciplinary teams operating almost simultaneously and sometimes in different locations like getting surgeons from different specialties together for both donor and recipient surgery.
Guidelines by The Ministry of Health and Family Welfare :
FN Kapadia, Consultant Physician & Intensivist, PD Hinduja National Hospital, Mumbai
Rishi Kumar Badgurjar, Associate Intensive Care Unit Consultant, PD Hinduja National Hospital, Mumbai