|Year : 2020 | Volume
| Issue : 2 | Page : 66-70
Pediatric brain stem death: Perspectives for the future in India
Department of Anaesthesiology and Critical Care, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
|Date of Submission||27-Apr-2020|
|Date of Acceptance||02-May-2020|
|Date of Web Publication||18-Aug-2020|
Dr. Lakshmi Kumar
Department of Anaesthesiology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala
Source of Support: None, Conflict of Interest: None
Pediatric brain stem death needs to be recognized both for futility in resuscitative efforts and in scope for organ donation. Pediatric donation can be performed from 37 weeks gestational age to 18 years. The diagnosis of brain stem death is completed by two clinical examinations separated by an interval of 24 h in term newborns and neonates and 12-h interval infants and children. Apnea testing is the main diagnostic test supported by tests of cranial nerve functions. Ancillary tests have not been approved for the diagnosis of brain stem death in India. Donor management is critical and needs invasive lines and attention to the maintenance of hemodynamics, fluid management, temperature, and hormonal resuscitation.Shifting the goals of care to organ maintenance can be challenging for the medical team. Counseling for donation needs to be sympathetic and honest while letting the parents understand that return back to life is impossible. Religious, cultural, and social customs of the family need to be respected and supported and the medical social worker is the key person in the establishment of a rapport with the grieving family. Creation of awareness among public and health-care professionals beside the involvement of governmental organizations both to endorse the process and support costs toward the program at least in its developmental phase is needed for this program in India.
Keywords: Brain stem death, organ donation, pediatric
|How to cite this article:|
Kumar L. Pediatric brain stem death: Perspectives for the future in India. Amrita J Med 2020;16:66-70
| Introduction|| |
The detection and management of brain stem death have gained importance in the past decade in India not only with the growing awareness of the potential for organ donation but also to prevent futility in care. Brain stem death is the cessation of cerebral function by a proximate cause that is recognized and deemed to be irreversible. The American Association of Neurology has defined brain death as a condition associated with three cardinal signs: cessation of the functions of the entire brain including the brain stem, coma or unresponsiveness, and apnea. Media portrayal of brain stem death has perhaps limited scope for organ donation in general and more so among the pediatric population. Care of the potential pediatric donor should be undertaken preferably by trained pediatric intensivists. The extended scope for recovery in an infant versus an adult mandates the need for repeating tests over a longer duration of time in comparison with an adult. Care and support of the parents and relatives while they go through the process of determination of brain stem death of their child is paramount.
| Background in Pediatric Organ Donation|| |
Organ transplantation in children began in the year 1960, but discrepancies between limitations in organ supply versus overwhelming demand continue to exist, more among children where size, weight, and technical challenges contribute. The challenges to organ donation include family and cultural resistance to donation, issues relating to authorization and consent, misunderstanding and confusion on the diagnosis of brain stem death, and inadequate levels of donor management.
Brain stem death differs from a persistent vegetative state in which the brain stem functions are intact, but higher cortical functions are lost. This would mean that respiratory and circulatory functions are maintained, but that the patient is unaware of oneself or environment yet does not classify for a diagnosis of brain stem death.
The absence of brain stem reflexes is consistent with brain death and this implies a futility of sustenance of life subsequently. The United Kingdom has based a diagnosis of brain death based on the absence of brain stem reflexes only with a variable interval between two examinations. The United States mandates a complete physical examination for determination of lack of function of both the cortex as well as the brain stem and recommends the use of ancillary tests when these tests cannot be performed.,,,, The acceptable age for donation varies among different countries. The United States and United Kingdom have guidelines for donation from 37 week gestational age. The major difference from adults is the need for allowance of an observation period between the examinations in children.
In India, awareness on organ donation and family willingness to donate has grown over the past two decades; however, negative publicity and questions on the legitimacy of the process have dampened the move. In India, the pediatric donation is very rare, although bilateral kidneys matched to a small adult recipient and pediatric heart donations have both been performed.
Scope for pediatric donation in an Indian intensive care unit (ICU) occurs in the context of limited potential for survival of the child, orders for de-escalation of care, or a do-not-resuscitate order. In countries with an established organ donation program, this point of de-escalation is considered as a point to involve the organ procurement team.
Conditions associated with brain stem death among children
The major causes of brain stem death among children are traumatic brain injury, and this is common among adolescents with road traffic accidents. Intracranial hemorrhage, ischemic or hypoxemic insult, metabolic encephalopathy, primary brain stem infarct, low-grade central nervous system (CNS) tumors, and treated sepsis and meningitis are the next common conditions among children. Contraindications to donation are active sepsis, active viral infections, extra CNS malignancy, HIV, and Zika virus infections.
| Establishment of Brain Stem Death: Differences from Adults|| |
A clinical examination should precede tests for the establishment of brain stem death. Lack of response to call, and painful stimuli should be checked for. Deep painful stimuli include pressure on the nail bed and supraorbital and sternal points, and absence of response or withdrawal should be noted.
Systemic evaluation of the cranial nerves:
- Pupillary responses direct and consensual (Cranial nerves II and III)
- Gag reflex: Cranial nerves IX and X
- Facial Grimace: Cranial nerves V and VII
- Corneal reflex: Cranial nerves V and VII
- Brain stem:
- Oculocephalic reflex (dolls eye – absent in brain stem death) III and VI
- Oculovestibular: III, VI, and VIII.
Recommendations for the establishment of brain stem death
Guidelines for the determination of brain stem death in infants and children are given below
- Determination of brain stem death in neonates, infants, and children: the diagnosis of brain stem death is made in the absence of neurologic function with a known and irreversible cause of coma
- Prerequisites for the establishment of brain stem death.
- Correction of hypotension, hypothermia, and metabolic disturbances
- Effects of sedatives, analgesics, and muscle relaxants must be corrected. In drug, overdosage, one must allow for 5 ½ life cycles of the drug. A knowledge of the total dose of the drug that has been used and measurements of the levels of anticonvulsant medication are necessary to exclude drug effects
- If a suspicion of brain stem death exists after cardiopulmonary resuscitation, a diagnosis of brain stem death must be made 24 h–48 h after the event keeping in mind inconsistencies during a clinical examination
- Number of examinations: two examinations including apnea testing performed by two different physicians one of whom could be the physician in charge of ventilation separated by a variable observation period
- Recommended interval: 24-h interval between examinations for term newborns and neonates up to 30 days of age
- Recommended interval: 12 h for term infants >30 days until 18 years.
The observational period between two examinations differs in the UK and ANZ guidelines. The UK recommends a long observational interval for children <2 months and a short interval for children more than 2 months of age. ANZ recommends a standard interval of 24 h irrespective of the age.
- Apnea testing remains the main test for confirmation as in adults.
- Documentation of PaCO2 >60 mmHg or 20 mmHg above baseline if baseline is higher due to respiratory disease
- Hypotension during apnea can be handled by fluids or vasopressors
- Desaturation can be preempted by a trial of continuous positive airway pressure (CPAP).
- Indications for ancillary testing
- Inability to perform or complete the apnea testing owing to the medical condition of the patient
- Inconclusive results from the neurological examination
- An attempt to shorten the observation period
- To exclude interference from effects of prior or concurrent medications.
- Declaration of death.
- Death is declared only after the completion of the second clinical examination and apnea test
- All components of the clinical examination and apnea must be appropriately documented
- Tests should be performed only by physicians, pediatricians, and intensivists trained in neurocritical care.
Accepted ancillary tests in children
- Electroencephalogram (EEG): 30-min monitoring is needed
- Radionuclide cerebral blood flow (CBF) (perfusion) study.
Transcranial Doppler, computed tomography (CT) angiography, and magnetic resonance imaging angiography have not been validated in all countries. Four-vessel cerebral angiography is considered a gold standard as an ancillary test but appears very invasive in the documentation of brain stem death. The American guidelines allow a reduction of the observation interval if the EEG and CBF imaging are suggestive of brain death.
India and the UK have not legalized the use of ancillary tests in the establishment of brain stem death. In the US, the documentation of CBF is accepted as an ancillary test from 37 weeks to 30 days of life, but from 30 days to 18 years, both EEG and tests of CBF (equal sensitivity) are acceptable. ANZ recommends the use of four-vessel angiography, CT angiography, and radionuclide imaging of brain perfusion as ancillary tests.
| Pathophysiology and Management Following Brain Stem Death|| |
The pathophysiology of brain stem death in children is quite similar to that in adults, the inciting event being medullary ischemia with catecholamine responses., Brain stem death following traumatic brain injury in children has a higher incidence of myocardial dysfunction and should be kept in mind while considering cardiac donations.
Appropriate donor management includes ongoing evaluation of organ suitability, serial organ function assessments, and infection and immunological screening. The logistics of size matching, allocation, and retrieval are beyond the scope of this article. As with adult donor management, the goal is to restore normal physiology with the aim to retrieve good-quality organs that will provide the maximum benefit for the recipient. Organs that brain stem dead donors may contribute include the lungs, heart, kidneys, liver, pancreas, and intestines. Organs that may be donated following the circulatory determination of death include the lung, liver, kidneys, pancreas, intestines, and heart. Tissues that may be donated include the skin, bones, tendons, ligaments, heart valves, and corneas.
| Stepwise Management of the Donor|| |
- Wide bore IV access: Central line and arterial line are mandatory
- Temperature: External warmers (Bair hugger) forced air body warmers need to be applied to prevent hypothermia. Plastic wraps may be useful in limited-resource settings. If large volumes of fluids are needed to manage diabetes insipidus, fluid warmers can be used. Hypothermia can affect coagulation and worsen perfusion and graft outcomes
- Fluid resuscitation: Crystalloids such as Ringer's lactate/plasmalyte if serum sodium is between 135 and 145 mEq/L, ½ NS if Na >145 mEq/L. The aim is to maintain euvolemia, with normal levels of serum lactates and central venous pressure <8 mm Hg. Restrictive fluid strategies improve the quality of the heart and lung and do not affect the graft function of the kidney
- Colloid: Albumin is the only colloid that is safe and can be used to reduce fluid administration in heart and lung retrieval (10–20 ml/kg of 5% albumin or lesser volumes of 25% albumin)
- Ventilation: Lung protective ventilation with 4–6 ml/kg tidal volume, optimal Positive end expiratory pressure (PEEP), and minimum FiO2 needed to maintain saturation above 94%. Acute lung injury/pulmonary edema may occur as a part of brain stem death., It is usually multifactorial and should be managed with protective ventilation and lung recruitment maneuvres including positioning and suctioning
- Cardiovascular system: Hypotension sets in after the initial hypertensive response. Vasopressors are the first line, with norepinephrine and vasopressin administered early. Dopamine or dobutamine is rarely used today in view of tachycardia and propensity for arrhythmias. Dopamine or beta-agonist therapy in doses greater than 10 μg/kg min may reduce the myocardial energy stores and downregulate beta-agonist receptors in the donor heart. Adrenaline can be considered as an additional support. Milrinone is useful as an afterload reducing agent in patients with myocardial dysfunction, and documentation of improvement by transthoracic echocardiography allows eligibility for donation
- Hormone replacement: Methylprednisolone, vasopressin, and/or desmopressin are replacements for pituitary dysfunction. Thyroxine can be administered when considered useful in the doses mentioned [Table 1]. Thyroid hormones administered improved myocardial performance in adult donors in some studies, although a meta-analysis failed to provide convincing evidence.,,
- Insulin replacement guidelines are unclear, but hyperglycemia is undesirable. Insulin in a dose starting at 0.1 U/Kg can be administered and increased to maintain blood sugars between 80 and 150 mg/dL
- Coagulation needs to be corrected, and fresh frozen plasma and fibrinogen can be administered when needed. Underlying prothrombotic states may need anticoagulation
- Cardiac arrest is to be treated as per the pediatric life support guidelines. Using extracorporeal support for the brain stem dead donor has also been considered in extreme cases and has included dialysis for fluid removal and electrolyte correction.
| Counseling|| |
Counseling the parents and the near relatives is at the core of management and begins from the first interview. Parents should be given honest and unambiguous updates in a language that they can understand. If the disease process progresses and a poor outcome is inevitable, then a sympathetic and truthful explanation of the finality of the child's death must precede counseling for organ donation. Key communication features would include the word “death” and not brain death after the conclusion of second apnea test and mechanical ventilation instead of life support. Allowing time for them to grieve must precede a conversation explaining the scope for donating organs. Institutional or state-level policies need to be adhered while processing the donation.
Experience has shown us that the process of brain stem death certification and organ donation works best in collaboration with a multidisciplinary team. This is usually coordinated by the social workers who liaise with not only the relatives and the parent medical team but also with state and national coordinators and allocation agencies, multiple retrieval teams, and also the forensic and legal department. It takes around 24–48 h from the time of initiation of the first brain stem death test to the final stage of hand over of the body to the relatives. Palliative care teams, chaplains, and psychologists can assist the critical care team, parents, and families while assisting with the organ donation process occurs. It is a period of multiple and intense communication between the coordinator and the family where the accurate information and individualized support based on the family's preference facilitate a seamless process. The social worker not only caters to the emotional requirements of the relatives but also engages their religious, cultural, and social needs. Even though these are highly emotional conversations, our experience is that the social worker usually develops a very strong professional bond with the family that extends beyond hospital discharge.
Providing the option of organ donation can help in the bereavement process and provide a degree of comfort to families in that they have an opportunity to help others during their time of distress. A request to reveal the identity of the recipients is not uncommon from the parents. While acknowledging the emotional solace that this information can provide to the parents, it needs to be informed that the law does not provide that liberty. An update on the number of lives transformed by the donation process and the health status of the recipients after the transplant can be provided. There is, however, the provision to reveal the identity and meet the recipients, at a later stage, based on mutual agreement.
| Ethics in Pediatric Donation|| |
A shifting of treatment goal from saving life to organ preservation can be an emotional challenge for the treatment staff. The perception that all interventions subsequent to brain stem death certification are for the purpose of organ preservation and an insult to the dignity of the dead child can pose a significant ethical dilemma. There need to be a regular update and training session for the staff members that emphasize the importance of maintaining patient dignity and care for the family, during and after the brain stem death certification process.
The role of Extracorporeal membrane oxygenator (ECMO) to maintain organ perfusion, especially in a brain stem dead donor who develops a cardiac arrest before retrieval, sparks another area of controversy. A supradiaphragmatic aortic occlusion is applied and regional perfusion of the abdominal organs to improve the donor pool has been suggested. This involves heparinization and premortem cannulation with incumbent risks and that this process itself could hasten circulatory arrest. Contrarily, the improved circulation to the brain following the institution of ECMO could improve levels of consciousness and possibly result in autoresuscitation. Suggestions for extracorporeal circulation excluding the brain are equally controversial and is not available at this point in time.
Why has pediatric donation not made progress in India?
There is a need for the creation of awareness among public and health-care professionals beside involvement of governmental organizations both to endorse the process and support costs toward the program at least in its developmental phase. As in other parts of the world, adult brain stem death certification needs to be streamlined before pediatric certification process becomes more common place. Although anencephalic children have been organ donors in other countries, Indian guidelines do not mention this option. The current state of acceptance of brain stem death among the Indian population, perhaps, precludes further discussion on this topic.
| Conclusion|| |
Identification of potential brain stem dead donors at the appropriate time, obtaining informed consent, and conducting tests in an appropriate fashion with documentation amid the grief in the families are formidable tasks. Donation after circulatory death may bridge some shortfalls in the brain stem death group. Understandably, there are not many donations in India as of today. Yet, the fulfillment of giving life through their loved ones remains an emotional motivation. Care of the donor is no less a task than care for a hemodynamically unstable patient in the ICU and needs vigilance and periodic interventions to streamline the donor organs optimally. The need for strong governmental and institutional support and transparency in allocation will go a long way to lead the program. Physicians and intensivists who have already gained experience need to educate and establish systems to protocolize the management optimally.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wijdicks EF, Varelas PN, Gronseth GS, Greer DM; American Academy of Neurology. Evidence-based guideline update: Determining brain death in adults: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010;74:1911-8.
Hoffmann M. Addressing the Challenges in Determining Pediatric Brain Death. 2019. p. 1-3. Available from: https://www.neurologylive.com
. [Last accessed on 2020 Mar 15].
Vyas H, Nagakawa TA. Assessment of a Pediatric Patient for Potential Organ Donation. Section editor George B Mallory. Deputy Section editor. Alison G. Hoppin. Available from: http://www.uptodate.com
. [Last accessed on 2020 Mar 15].
Webb A, Samuels O. Brain death dilemmas and the use of ancillary testing. Continuum (Minneap Minn) 2012;18:659-68.
Young GB, Shemie SD, Doig CJ, Teitelbaum J. Brief review: The role of ancillary tests in the neurological determination of death. Can J Anaesth 2006;53:620-7.
Welschehold S, Boor S, Reuland K, Thömke F, Kerz T, Reuland A, et al
. Technical aids in the diagnosis of brain death: A comparison of SEP, AEP, EEG, TCD and CT angiography. Dtsch Arztebl Int 2012;109:624-30.
Sinha P, Conrad GR. Scintigraphy in the confirmation of brain death: Indian context. Indian J Nucl Med 2012;27:1-4.
] [Full text]
Sharma D, Souter MJ, Moore AE, Lam AM. Clinical experience with transcranial Doppler ultrasonography as a confirmatory test for brain death: A retrospective analysis. Neurocrit Care 2011;14:370-6.
Nakagawa TA, Ashwal S, Mathur M, Mysore MR, Bruce D, Conway EE Jr., et al
. Guidelines for the determination of brain death in infants and children: An update of the 1987 Task Force recommendations. Crit Care Med 2011;39:2139-55.
Mori K, Shingu K, Nakao S. Brain death. In: Miller RD, editor. Miller's Anaesthesia. 7th
ed., Ch. 98. Philadelphia, PA: Churchill- Livingstone, Elsevier; 2010. p. 3007.
Kumar L. Brain death and care of the organ donor. J Anaesthesiol Clin Pharmacol 2016;32:146-52.
] [Full text]
Beckman EJ. Management of the pediatric organ donor. J Pediatr Pharmacol Ther 2019;24:276-89.
Agrawal A, Timothy J, Cincu R, Agarwal T, Waghmare LB. Bradycardia in neurosurgery. Clin Neurol Neurosurg 2008;110:321-7.
McKeown DW, Bonser RS, Kellum JA. Management of the heart beating brain-dead organ donor. Br J Anaesth 2012;108 Suppl 1:i96-107.
Krishnamoorthy V, Prathep S, Sharma D, Fujita Y, Armstead W, Vavilala MS. Cardiac dysfunction following brain death after severe pediatric traumatic brain injury: A preliminary study of 32 children. Int J Crit Illn Inj Sci. 2015;5:103-7.
Novitzky D, Wicomb WN, Rose AG, Cooper DK, Reichart B. Pathophysiology of pulmonary edema following experimental brain death in the chacma baboon. Ann Thorac Surg 1987;43:288-94.
Mascia L, Pasero D, Slutsky AS, Arguis MJ, Berardino M, Grasso S, et al
. Effect of a lung protective strategy for organ donors on eligibility and availability of lungs for transplantation: A randomized controlled trial. JAMA 2010;304:2620-7.
Salim A, Vassiliu P, Velmahos GC, Sava J, Murray JA, Belzberg H, et al
. The role of thyroid hormone administration in potential organ donors. Arch Surg 2001;136:1377-80.
Mi Z, Novitzky D, Collins JF, Cooper DK. The optimal hormonal replacement modality selection for multiple organ procurement from brain-dead organ donors. Clin Epidemiol 2015;7:17-27.
Macdonald PS, Aneman A, Bhonagiri D, Jones D, O'callaghan G, Silvester W, et al
. A systematic review and meta-analysis of clinical trial of thyroid hormone administered to brain dead potential organ donors. Crit Care Med 2012;40:1635-44.
Nakagawa TA, Shemie SD, Dryden-Palmer K, Parshuram CS, Brierley J. Organ donation following neurologic and circulatory determination of death. Pediatr Crit Care Med 2018;19:S26-32.