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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 2  |  Page : 61-65

Management of the brain stem dead organ donor


Department of Anaesthesia and Critical Care, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India

Date of Submission06-Feb-2020
Date of Acceptance09-Mar-2020
Date of Web Publication18-Aug-2020

Correspondence Address:
Dr. S Gokul Das
Anandham, House No. 8/227, North Parur, Ernakulam - 683 513, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AMJM.AMJM_16_20

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  Abstract 


The diagnosis of brain stem death is quintessential in modern medical practice. It not only identifies the patients who will not benefit from continuing treatment but also opens the possibility of the patient becoming an organ donor. The increasing demand for organs has resulted in an evidence-based and scientific approach to optimizing these patients to ensure smooth conduct of brain stem death testing and ensuring the viability of organs. These guidelines describe the decision-making process for identifying the potential donors, medico-legal concerns regarding consent, exclusion criteria for eligibility, and suggested age limits of the donor as a consideration for the viability of different organs. The system-wise approach of assessing these patients, optimizing those using pharmacological and nonpharmacological interventions, and the targets for resuscitation are described in detail.

Keywords: Brain stem death, organ care, organ donor, transplantation


How to cite this article:
Das S G. Management of the brain stem dead organ donor. Amrita J Med 2020;16:61-5

How to cite this URL:
Das S G. Management of the brain stem dead organ donor. Amrita J Med [serial online] 2020 [cited 2020 Sep 19];16:61-5. Available from: http://www.ajmonline.org.in/text.asp?2020/16/2/61/292423




  Introduction Top


India legalized deceased organ donation by passing the bill-Transplantation of Human Organs Act in 1994. Compared to Western countries, cadaver organ donation in India is still very low 0.8 million in India (32.0/million in Spain and 25.6/million in USA). There is an ever-increasing organ demand but less numbers are avilable for transplantation. A multidisciplinary coordinated attempt is necessary to tackle this problem.

Who is a Potential Organ Donor?

A potential organ donor is defined by the presence of either brain stem death or a catastrophic injury to the brain, which would progress beyond reversibility and may fulfill brain death criteria.[1] The American Association of Neurology has defined brain death with three cardinal signs - cessation of the functions of the brain including the brain stem, coma or unresponsiveness and apnea.[2]

When the patient is diagnosed as brain stem dead, the intensive care unit (ICU) physician will communicate with the transplant coordinator who in turn will communicate with the family regarding organ donation. Once the family gives their consent, the authorities in the respective states are informed, and the process of organ retrieval and transplantation is set in motion. In India the further expenses of the deceased organ donor should be borne either by hospital administration, recipient's family, government, or Non Governmental Organizations.

Who Can Give Consent? The deceased

Any written documents signed by the deceased pledging organ transplant.

According to Indian laws, even if the deceased has pledged, consent from the immediate relatives is required.

Next of kin

Includes spouse, children >18 years and parents

If there is any medico-legal case involved, a copy of the consent form should be sent to the officer of the nearest police station.

Exclusion criteria for organ transplantation

  1. Infection with human immunodeficiency virus, human T-cell leukemia virus, human lymphoma virus
  2. Systemic viral infections with high risk of transmission
  3. Malignant diseases.
  4. Bactremia and fungemia are not absolute contraindications for organ transplant[3]
  5. Age of the donor: There is no upper age limit for organ donation.



  Care of the Organ Donor Top


Proper care of the brain stem dead donor is essential for improving the quality of organs and successful transplant.[4] Various physiological changes occur during brain stem death and to maintain normal physiological balance is important for maintaining the quality of organs. A series of goals which can be easily remembered is the rule of 100. Maintain systolic blood pressure (SBP) >100 mm Hg, urine output >100 ml/h, PaO2 > 100mm Hg, and hemoglobin > 100gms/L. The longer the time interval between the retrieval of the organ and diagnosis of brain stem death, the greater will be the instability of the patient.[5]

Care of the Organ Donor

Includes Monitoring, Investigations, General care, and Problem specific care

Monitoring

All donors should have basic monitoring such as electrocardiogram, SPO2, temperature, and urine output. The deceased donor also requires arterial and central venous pressure monitoring. Echocardiography may be required for assessing cardiac function and fluid deficit (Grade 1A). Unstable donors with signs of hypoperfusion and persistent acidosis (Grade 2B) may require pulmonary catheter/cardiac output monitoring. Continuous monitoring of arterial BP and hourly monitoring of vital signs, urine output, and body temperature are required.

Investigations

Serum electrolytes, blood sugar, arterial blood gas, and lactate should be checked every 2–4 hourly (Grade 1A). Investigations such as complete blood count, urine analysis, blood urea nitrogen, serum creatinine, liver function tests, and coagulation profile have to be done daily. Microbiological screening for hepatitis B and C, hepatitis B core and surface antigen, HIV, IgM and IgG for cytomegalovirus are necessary (Grade 1A). Blood and urine cultures should be taken if there is evidence of infection or if the patient is hospitalized for >72 h (Grade 2B). Multi-organ donors require additional tests like echocardiography for cardiac transplant and bronchoscopy for lung transplant.

General care

General measures to reduce the risk of infection and improve the quality of organs should be applied.

  • Elevate the head end – 30°-40°
  • Warming blanket to keep the body temperature around 36.5°C
  • Hand hygiene – As per standard medical care (Grade 1A)
  • Decubitus ulcer prophylaxis: Frequent turning of patients and meticulous care of the skin
  • Care of urinary and intravascular catheter to minimize the risk of infection (Grade 1A)
  • Eye care: Care to prevent corneal abrasion or ulcer to improve chances of corneal donation
  • Nasogastric tube: For enteric feeding, gastric decompression and the prevention of aspiration (Grade 1B)
  • Frequent suctioning of the airway
  • Arterial and central venous lines should be inserted, preferably into the upper extremities, as the femoral line readings can become inaccurate during the surgical procedure for organ retrieval (Grade 2B)
  • Use of pneumatic compression device and anticoagulants for deep vein thrombosis prophylaxis.


Problem specific care

The medical management of organ donor can be broadly divided into:

  • Management of hemodynamics
  • Management of metabolic derangement
  • Management of temperature
  • Management of respiration
  • Management of infection
  • Management of hematologic derangements
  • Management of nutrition.



  Management of Hemodynamics Top


During brain stem death, the intracranial pressure (ICP) rises above cerebral perfusion pressure, resulting in cessation of blood flow to the brain. Rise in ICP is accompanied by hypertension and bradycardia (Cushing's reflex). Brain stem death is followed by excessive secretion of catecholamines (sympathetic storm), which results in hypertension, tachycardia and arrhythmia. This autonomic storm does not last long. High levels of catecholamines cause the necrosis of myocardium and the conduction system leading to myocardial dysfunction and arrhythmia.[4],[6] Slowly spinal cord ischemia occurs with the deactivation of autonomic storm and loss of cardiac stimulation. This leads to vasodilation and cardiac dysfunction resulting in hemodynamic instability. Many other factors also cause hypotension such as osmotic diuresis induced by mannitol and hyperglycemia, hypovolemia due to diabetes insipidus, inadequate fluid resuscitation and blood loss, relative adrenal insufficiency due to trauma and critical illness and reduced triiodothyronine secretion. Approximately 25% of patients have myocardial dysfunction following brain stem death, and nearly 40% show echocardiographic changes.[7] Hypotension, if not properly managed, will lead to hypoperfusion of organs and rapid donor loss.

Goals of hemodynamic management include:

  1. Maintain normovolemia and blood pressure
  2. Maintain cardiac function and tissue perfusion with minimal inotropic support.


Hypertension

The effect is usually transient and may not require treatment. If medication is required, use of short-acting drugs such as esmolol, sodium nitroprusside, labetalol or nitroglycerine may be enough.

Hypotension

Hypotension will decrease tissue perfusion and damage the quality of organs unless aggressively managed. Steps have to be taken to control active bleeding along with transfusion of blood and blood products (Grade 1A). All antihypertensive medications have to be discontinued (Grade 1A). Hypotension is treated by correcting hypovolemia and using inotropes. If there is no response with the above management, hormone replacement may be needed.


  Assessing Volume Status Top


As already mentioned, various factors can lead to hypovolemia in a brain stem dead patient. Central venous pressure though commonly used, is a poor guide to volume resuscitation. Urine output (1-3 ml/kg/h) is a good indicator (Grade 1A), but unreliable in a patient with diabetes insipidus. Pulse pressure variation, systolic blood pressure variation and echocardiography can be used to assess fluid deficits. Cardiac index >2.5 L/min/m2 is unreliable in vasodilatory shock (Grade 2B). As the brain stem dead donor has low brain metabolism, the central venous oxygen saturation >70% is not a reliable indicator of volume status (Grade 2B).


  Correction of Hypovolemia Top


Volume correction depends on the blood/fluid status. Anemia has to be corrected by transfusion of packed red cells to achieve a hematocrit of 30% (Grade 2B). The choice of fluid depends on serum electrolytes, blood sugar, fluid deficiency, and hemodynamics of the patient. Most commonly used fluids are Ringers' lactate, Ringers' acetate, plasmalyte –A, and 0.45% saline (Grade 1A). Albumin (20% and 4%) is only moderately effective in volume resuscitation but can reduce the amount of volume replacement[8] (Grade 2B). Hydroxyethyl starch is better to be avoided as it can cause renal epithelial cell damage and graft rejection[9] (Grade 1A). Care should be taken to prevent fluid overload as it can adversely affect pulmonary function.[10]


  Vasopressors Top


The goal of treatment is to keep a target systolic BP >100 mm Hg and mean arterial pressure (MAP) >70 mm Hg so that the tissue perfusion and quality of organs are maintained (Grade 1A). Vasopressors are added if hypotension persists even after volume correction. Vasopressin is the first choice of vasopressors for donor resuscitation. Vasopressin is useful to treatDiabetes Insipidus (DI), to increase vascular tone, and to reduce the use of catecholamines. Recommendation for vasopressin is up to 4 IU/h intravenous infusion (Grade 1B).

Inotropes (epinephrine and norepinephrine] are added to treat myocardial depression. High dose of norepinephrine >0.05 μg/kg/min should be avoided (Grade 2A) as it is associated with increased cardiac graft dysfunction, particularly right ventricular performance and higher mortality among recipients.[11] Combination of vasopressin and norepinephrine increases both MAP and cardiac index. Dopamine can also used to treat hypotension, but it increases the incidence of arrhythmia.

Arrhythmia

The goal should be to prevent the development of arrhythmia. Serum electrolytes, temperature and BP are maintained within the normal limits (Grade 1A). Tachyarrhythmia is managed with standard therapy such as amiodarone or cardioversion (Grade 2B), whereas bradyarrhythmia is treated with adrenaline, isoprenaline, or pacing. Atropine may not be useful in the management of bradycardia in the deceased donor.[12]


  Management of Endocrine and Metabolic Derangement Top


There are conflicting reports about hormone deficiency in brain stem dead patients. Some studies show the deficiency of triiodothyronine. Thyroxine (300–400 μg) is given through nasogastric tube to patients who are hemodynamically unstable in spite of volume resuscitation and ionotropic support[13] (Grade 2B). Critically ill donors also may require steroid supplementation to maintain adequate BP.

Diabetes insipidus

More than 80% of brain stem dead persons may develop DI with hypernatremia and hypovolemia. Hypernatremia may adversely affect the outcome of renal and liver transplants. Desmopressin or vasopressin is used to treat DI. Volume replacement is by low sodium fluid to keep sodium in the physiological range of 135–145 meq/L (Grade 1A).

Following brain stem death, posterior pituitary function is usually lost, leading to DI with fluid and electrolytes imbalance. Anterior pituitary function is either preserved or partially lost. Most donors show normal values of thyroid-stimulating hormones, adrenocorticotrophic hormones, and human growth hormone.[14] Hemodynamically, unstable patients may require thyroxine. Since intravenous T3 is not available in India, thyroxine T4 300–400 μg is given through NG tube.

Attempt should be made to maintain the serum electrolytes, acid-base balance and intravascular volume within the normal range. Both hypoglycemia and hyperglycemia adversely affect the organs. Insulin infusion may be required for maintaining blood sugar in the range of 80–150 mg/dl. The insulin requirement of the donor will be higher than in other patients because of reduced insulin secretion and increased insulin resistance.

There is no strong evidence for hormone resuscitation though some studies recommend it in donors with hemodynamic instabilities. High dose of methylprednisolone improves lung function and oxygenation in potential lung donors. It also reduces inflammation in the liver, heart, and kidney. The administration of steroids reduces cytokine release both before retrieval and during surgery.[15]

Methylprednisolone is given at a high dose of 15 mg/kg immediately after the diagnosis of brain stem death and 24th hourly thereafter (Grade 1B). Another option is to administer 250mg bolus followed by 100 mg/h infusion till the organ retrieval. Haemodynamically unstable patients may also require thyroxine.


  Management of Temperature Top


Various factors such as loss of thermoregulation, reduced metabolic rate, excessive heat loss, loss of protective mechanisms like vasoconstriction and shivering may result in hypothermia. Hypothermia has to be avoided as it may lead to myocardial dysfunction, arrhythmia, coagulopathy, metabolic acidosis and impairment of oxygen delivery to tissues. The prevention of hypothermia is easier than treating it. Attempts should be made to maintain temperature > 35°C (Grade 1 A).

Techniques such as surface warming, use of warm humidified air and administration of warm fluids are employed (Grade 2B) to reduce the incidence of hypothermia. Donors with core temperature <34°C should be given core warming.


  Management of Respiration Top


Brain stem death results in cessation of the function of the respiratory center with a need for mechanical ventilation to survive. The catecholamine surge following brain stem death raises pulmonary artery pressure and causes pulmonary capillary damage both leading to pulmonary edema.

The goals of mechanical ventilation include maintaining: (1) Peak airway pressure: <40 cmH2O, (2) Plateau airway pressure: < 30 cm H2O, (3) Fraction of inspired oxygen (FiO2): Lowest possible to maintain arterial oxygen saturation (SpO2) >92% and PaO2>70 mmHg, (4) Positive End Expiratory Pressure (PEEP): Minimum 5 cm of H2O, adjust to maintain PaO2 >70 mmHg, (5) Auto PEEP < 5 cm H2O and (6) ABG values: PH 7.35–7.45; arterial PaCO2-30–35 mmHg; PaO2>70 mm Hg.[16]

Frequent suctioning, changing position and chest physiotherapy are needed to keep the airway patent. Re-recruitment should be done after the tracheal suction and apnea test. Bronchoscopy is required for lung donor.


  Hematological Management Top


Aggressive management to control traumatic bleeding which is the major cause of anemia and correction of coagulopathy should be initiated. Disseminated intravascular coagulation occurs with the release of tissue thromboplastin from necrotic tissues.[17] Anemia has to be treated with packed red cells transfusion to keep a hematocrit of 30%. Transfusion of blood and blood products is done only if it is necessary (Grade 2B). In case of worsening of coagulopathy, organ retrieval should be hastened.


  Management of Infection Top


All patients with signs of infection or 72 hours post admission should have their blood and urine cultures done. Antibiotic treatment should be based on the gram staining and positive cultures. Prophylactic antibiotic use is not recommended (Grade 2B).


  Management of Nutrition Top


Nutrition should be continued in the potential organ donor as per the standard ICU protocol (Grade 1B). Enteral feed reduces the translocation of bacteria and endotoxin release from the intestine. Continuing enteral feed may have beneficial effects in the function of the transplanted organ.


  Conclusion Top


With less number of relatives of deceased patients willing to donate organs, utmost importance should be given to the care of the brain stem dead donor. Ultimately, the care and preservation of the organ will lead to successful organ transplantation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
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2.
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.  Back to cited text no. 2
    
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Angelis M, Cooper JT, Freeman RB. Impact of donor infections on outcome of orthotopic liver transplantation. Liver Transpl 2003;9:451-62.  Back to cited text no. 3
    
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McKeown DW, Bonser RS, Kellum JA. Management of the heartbeating brain-dead organ donor. Br J Anaesth 2012;108 Suppl 1:i96-107.  Back to cited text no. 4
    
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Nygaard CE, Townsend RN, Diamond DL. Organ donor management and organ outcome: A 6-year review from a level I trauma center. J Trauma 1990;30:728-32.  Back to cited text no. 5
    
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Smith M. Physiologic changes during brain stem death–lessons for management of the organ donor. J Heart Lung Transplant 2004;23:S217-22.  Back to cited text no. 6
    
7.
Dujardin KS, McCully RB, Wijdicks EF, Tazelaar HD, Seward JB, McGregor CG, et al. Myocardial dysfunction associated with brain death: Clinical, echocardiographic, and pathologic features. J Heart Lung Transplant 2001;20:350-7.  Back to cited text no. 7
    
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Pandit RA, Zirpe KG, Gurav SK, Kulkarni AP, Karnath S, Govil D, et al. Management of potential organ donor: Indian society of critical care medicine: Position statement. Indian J Crit Care Med 2017;21:303-16.  Back to cited text no. 8
[PUBMED]  [Full text]  
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Slakey LM, Slakey CM, Slakey DP. Deceased donor management and demographic factors related to kidney allograft rejection and graft survival. Transplant Proc 2010;42:1513-8.  Back to cited text no. 9
    
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Pennefather SH, Bullock RE, Dark JH. The effect of fluid therapy on alveolar arterial oxygen gradient in brain-dead organ donors. Transplantation 1993;56:1418-22.  Back to cited text no. 10
    
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Stoica SC, Satchithananda DK, White PA, Parameshwar J, Redington AN, Large SR. Noradrenaline use in the human donor and relationship with load-independent right ventricular contractility. Transplantation 2004;78:1193-7.  Back to cited text no. 11
    
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Vaghadia H. Atropine resistance in brain-dead organ donors. Anesthesiology 1986;65:711-2.  Back to cited text no. 12
    
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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.  Back to cited text no. 13
    
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Novitzky D, Cooper DK, Rosendale JD, Kauffman HM. Hormonal therapy of the brain-dead organ donor: Experimental and clinical studies. Transplantation 2006;82:1396-401.  Back to cited text no. 14
    
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Kotsch K, Ulrich F, Reutzel-Selke A, Pascher A, Faber W, Warnick P, et al. Methylprednisolone therapy in deceased donors reduces inflammation in the donor liver and improves outcome after liver transplantation: A prospective randomized controlled trial. Ann Surg 2008;248:1042-50.  Back to cited text no. 15
    
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Powner DJ, Darby JM, Kellum JA. Proposed treatment guidelines for donor care. Prog Transplant 2004;14:16-26.  Back to cited text no. 16
    
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  In this article
Abstract
Introduction
Care of the Orga...
Management of He...
Assessing Volume...
Correction of Hy...
Vasopressors
Management of En...
Management of Te...
Management of Re...
Hematological Ma...
Management of In...
Management of Nu...
Conclusion
References

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