| Home | E-Submission | Sitemap | Contact us |  
Acute and Critical Care > Volume 34(1); 2019 > Article
Anwar and Lee: Medical Management of Brain-Dead Organ Donors


With improving healthcare services, the demand for organ transplants has been increasing daily worldwide. Deceased organ donors serve as a good alternative option to meet this demand. The first step in this process is identifying potential organ donors. Specifically, brain-dead patients require aggressive and intensive care from the declaration of brain death until organ retrieval. Currently, there are no specific protocols in place for this, and there are notable variations in the management strategies implemented across different transplant centers. Some transplant centers follow their own treatment protocols, whereas other countries, such as Bangladesh, do not have any protocols for potential organ donor care. In this review, we discuss how to identify brain-dead donors and describe the physiological changes that occur following brain death. We then summarize the management of brain-dead organ donors and, on the basis of a review of the literature, we propose recommendations for a treatment protocol to be developed in the future.


Every day, the demand for organs [1] is increasing at a faster rate than that at which organs are becoming available for transplants. With this increasing demand, the responsibility with regard to caring for potential organ donors is also rising. Appropriate medical management of a potential organ donor is a very important issue, requiring a multidisciplinary team approach for successful organ transplantation [2]. For graft survival after donation, all available organs in the donor need to be maintained at their normal physiological condition until the time of organ retrieval [1]. Intensivists play a vital role in the management of potential organ donors through the identification of potential donors, declaration of brain death, and proper medical care—all of which can improve the rates of graft survival [2-4]. There are many countries worldwide that lack proper guidelines on the identification and management of potential donors, including Bangladesh. Early identification of a potential donor is critical in starting early medical management for successful organ transplantation.
A potential organ donor is defined by the presence of either brain death or a catastrophic and irreversible brain injury that leads to fulfilling the brain death criteria [5]. Brain death is defined as the irreversible loss of all brain functions, including the brain stem [6]. Brain death occurs in response to increased intracranial volume, which may be caused by brain swelling and the collection or obstruction of cerebrospinal fluid flow (hydrocephalus) [7,8]. As the intracranial pressure (ICP) rises, blood flow to the brain falls and finally stops: the brain dies=irreversible=patient death [7,8].
To diagnose and declare brain death, certain criteria need to be fulfilled, including [7,8]; (1) irreversible coma, (2) absence of brain stem reflexes, and (3) no self-respiration. Evaluation of brain death should be considered in patients who have suffered a massive, irreversible brain injury with identifiable causes. A patient determined to be brain-dead is legally and clinically dead [6]. Sometimes, it may be difficult to differentiate brain death from other medical states, such as barbiturate overdose, alcohol intoxication, sedative overdose, hypothermia, hypoglycemia, coma, and chronic vegetative states [9].
A brain-dead individual shows no clinical evidence of brain function upon physical examination, which includes no response to pain and no cranial nerve reflexes. Additionally, there is no pupillary response (fixed dilated pupils), oculocephalic reflex, corneal reflex, no response to the caloric reflex test, and no spontaneous respiration [9]. Brain electrical activity stops completely or drops to such low levels that they are undetectable with most equipment; an electroencephalogram (EEG) will therefore be flat, although this can also be observed during deep anesthesia or with cardiac arrest [10]. An EEG is considered a confirmatory test, whereas other tests, such as transcranial Doppler ultrasonography and cerebral scintigraphy (technetium Tc 99m exametazime), are regarded as ancillary tests. However, cerebral angiography is considered the most sensitive confirmatory test in the determination of brain death [11].
If the vital organs can be maintained and kept functional in the body of brain-dead patients by continuing mechanical ventilation and other life-support measures, it will provide an optimal opportunity for performing transplantations [9]. Once neurologic death is declared, the intensivist can play an important role in implementing appropriate management strategies to preserve organ function to maximize successful organ procurement. This can even begin prior to family discussions about organ donation [12]. Organ donor management should be started immediately after brain death occurs and should continue once consent from the family for donation is obtained [5].
Data shows that progression from brain death to somatic death results in the loss of 10% to 20% of potential donor tissues, therefore timely treatment of the donor is very crucial [5]. Strict organ-protective intensive care of the potential organ donor is therefore the first step towards a successful transplant and in the treatment of the future organ recipient [13]. Continuing care for the brain-dead donor is often critical, difficult, and complex, and may extend over several hours or even days.
It is assumed that the preferred goal for successful organ donation is to maintain the hemodynamic variables and laboratory parameters within the normal ranges [14]. Thus, the guidelines we propose mainly focus on maintaining normal hemodynamic values and laboratory parameters as the therapeutic goals. It is agreed that portions of these guidelines may differ from established treatment protocols from individual organ procurement organizations (OPOs) across different countries. However, our guidelines have been prepared based on our own clinical experience in brain-dead donor management and standard critical care practice. We offer these considerations to those centers or countries, like Bangladesh, where there are currently no proper guidelines available for donor care. Final treatment objectives and management should be determined by local OPOs or authorities.


Different clinical studies have shown that central sympathoadrenergic regulation of circulation and the pituitary temperature are disrupted during development and irreversible loss of brain function; thus, there is an interruption in hypothalamic-pituitary-adrenocortical regulation [15]. The rising ICP results in a massive release of proinflammatory and anti-inflammatory cytokines and catecholamines [16]. Ultimately, brain death results in the loss of central regulatory mechanisms, which leads to several pathophysiological alterations in hemodynamics, hormone balance, body temperature, and lung function (Table 1) [13,17-19].

Cardiovascular Changes

In a brain-dead patient, ICP rises, which compromises cerebral blood flow and causes hemodynamic changes, described as the “Cushing reflex,” which is a mixed picture of vagal and sympathetic stimulation. As pontine ischemia develops, it clinically manifests as bradycardia and hypertension [20]. When blood supply is further compromised, ischemia progresses to the medulla oblongata, involving the vagal motor nucleus [20]. This results in compensatory arterial hypertension, perhaps associated with bradycardia, followed by marked sympathetic stimulation with intense vasoconstriction, raised systemic vascular resistance, and tachycardia [2]. This clinical picture is known as the “catecholamine storm,” and these features are also associated with central redistribution of blood volume, increased afterload, and visceral ischemia [2].
The level of increase in catecholamines is dependent upon the rate of increasing ICP and may even elevate as much as 1,000-fold from baseline if the ICP rises very rapidly [21]. The effects of the catecholamine surge on the myocardium results in an altered metabolism associated with depletion of adenosine triphosphate in the cardiac myocyte. This is evidenced by the fact that 20%–25% of brain-dead donors show evidence of myocardial ischemia with 40% showing echocardiographic evidence of myocardial dysfunction [21]. Acute myocardial injury occurring around the time of brain death has been identified in both animal and human studies [2].
As ischemia progress down the spinal cord, it may cause loss of function in the thoracic sympathetic chain with severe hypotension resulting from a reduction in afterload. As the aortic diastolic pressure decreases, it may compromise the coronary perfusion pressure to critical levels, resulting in myocardial ischemia [20]. The resulting hypotension may lead to hypoperfusion of all organs, including the heart, if not properly and timely treated, and may contribute to rapid donor loss [22]. Additional factors may contribute to hypotension, including diuretics (mannitol), hyperglycemia-induced osmotic diuresis, diabetes insipidus (DI), hypothermic “cold” diuresis, inadequate fluid resuscitation and decreased oncotic pressure after crystalloid resuscitation, ongoing blood loss, rewarming of the patient, and relative adrenal insufficiency as a result of trauma, and critical illnesses [5].

Respiratory Changes

The lungs are the organs most often assumed to be medically unsuitable for transplants, with only 10%–20% of lungs eligible for transplantation [23]. Neurogenic pulmonary edema (NPE) and inflammatory acute lung injury are the two main factors related to brain-death-induced lung injury and dysfunction [24]. In a brain-dead person, the NPE is related to a sympathetic storm caused by hemodynamic and sympathetic mechanisms. NPE can occur immediately after a neurological insult, but it may also occur earlier, before the patient is distinguished as a potential organ donor [25]. The sympathetic storm leads to systemic vasoconstriction and an increase in cardiac afterload, thus increasing left ventricle and left atrial pressures. The blood is shifted from the periphery to the central compartment, causing an increase in both pulmonary blood volume and pulmonary artery pressure. Increased left atrial and pulmonary artery pressures may lead to a massive increase in pulmonary capillary pressure and pulmonary edema. This elevated hydrostatic pressure would ultimately lead to structural damage to the capillary endothelium [25]. Respiratory arrhythmias may progress to apnea and cardiac arrest if there is no supporting mechanical ventilation [2].
In addition, proinflammatory mediators that are released following brain death may further contribute toward lung injury by promoting infiltration of activated neutrophils into the lungs [26]. Other contributing factors for lung dysfunction include chest trauma, aspiration, and atelectasis [17]. Moreover, long-term dependency on mechanical ventilation also creates a predisposition toward nosocomial chest infections [20].

Renal Changes

Experimental models have demonstrated that biomarkers for renal tubular injuries may be elevated as early as 30 minutes after the onset of brain death [20]. Both proinflammatory and procoagulant effects caused by brain death have been identified as main contributing factors [20]. Pretransplant kidney biopsies of a brain-dead donor found that the kidneys contain more infiltrating T lymphocytes and macrophages compared to those from living and cardiac-dead donors. There is also compelling evidence showing a greater release of inflammatory cytokines during reperfusions in brain-dead donor kidneys [27].

Endocrine Changes

Brain death may cause significant endocrine changes that vary in timing and severity, resulting in anterior and posterior pituitary failure [28]. Animal studies have shown that in baboons with acute increases in ICP, posterior and anterior pituitary function is rapidly lost after brain death [29], which is associated with deterioration in cardiac function and a shift to an anaerobic metabolism. However, the profile is less consistent in the case of human donors [2].
Function of the posterior pituitary gland becomes clinically lost in as many as 80% of brain-dead organ donors, which results in the development of DI with electrolyte imbalances, hypovolemia, and circulatory instability, and can create major problems in organ donor management [30,31]. DI develops because of a lack of anti-diuretic hormones released from the posterior pituitary gland, and if left untreated, can causes polyuria and result in hypovolemic shock and hypernatremia. Other causes of polyuria, such as hyperglycemia or the use of a diuretic or osmotherapy, should be excluded before considering a diagnosis of DI [20].
Usually, anterior pituitary function appears to be preserved or partially affected due to preserved pituitary blood flow [32]. Most donors show normal values of thyroid-stimulating hormones (TSH), adrenocorticotropic hormones, and human growth hormones, which indicate there is some residual function and, thus, perfusion of the hypothalamic pituitary neuroendocrine system [28]. Thyroid hormones and TSH levels show the typical picture of “sick euthyroid syndrome” that actually accompanies severe brain injury, rather than as a result of TSH deficiency [28].
Hyperglycemia is also a common endocrine change in brainstem-dead patients due to reduced insulin concentrations and insulin resistance [2]. In addition, hyperglycemia may worsen with stress, alterations in carbohydrate metabolism and the use of glucose solutions; however, as C-peptide levels increase over time, insulin levels will subsequently normalize [21]. If untreated, hyperglycemia may cause pancreatic cell damage, which may affect pancreatic graft; therefore, measures should be taken to maintain strict euglycemia to minimize this risk [21]. Untreated hyperglycemia may also affect outcomes after a renal transplantation [33].

Systemic Inflammatory Response

An active systemic inflammatory response is a common and typical picture of all brainstem-dead donors [34] and can be quite severe. Although inflammation may be associated with trauma and other critical illnesses, it can be particularly severe in a brain-dead donor as mediators are released from the damaged brain. Additionally, generalized ischemia-reperfusion injury, metabolic changes at the time of the catecholamine storm, or failure to adequately restore to the normal cardiovascular state further complicate matters [2]. Plasma levels of interleukin-6 also increase in the donor and may lead to poorer graft utilization and subsequent graft dysfunction [35].

Hematological Changes

Anemia is commonly found in brain-dead patients when traumatic bleeding occurs, with coagulopathy and fluid administration further exacerbating the condition [36]. Isolated head injuries are present with coagulopathy in 34% of cases [37]. Necrotic brains release tissue thromboplastin [38] and plasminogen activators, which are also released from cerebral injuries, and result in disseminated intravascular coagulation [20]. Bleeding complications may occur due to a deranged coagulation profile (prothrombin and activated partial thromboplastin time) and thrombocytopenia [20]. Leukocyte count may be elevated from the cerebral insult, with a systemic inflammatory state or nosocomial infection possibly occurring in the later stages [20].

Hypothermia, Stress, and Metabolic Responses

Hypothermia is a common feature in brain-dead organ donors due to the loss of thermoregulatory control, exposure to cold ambient temperatures, or massive infusions of cold intravenous (IV) fluids or blood products [39]. It may also occur due to a reduced metabolic rate, excessive heat loss, or loss of protective mechanisms such as vasoconstriction or shivering [2]. Preventing hypothermia is preferred rather than attempting to treat it. Once hypothermia develops, it is difficult to warm patients and may directly affect cardiac function, induce arrhythmias, coagulation cascades, and interfere with oxygen delivery to tissues [36].


The fundamental principles of organ donor management in intensive care units (ICU) are based on monitoring programs and therapies. These include confirmation of therapeutic goals, regular review of the donor patient’s state, and prompt changes in therapy when required [2]. The medical management of the potential brain-dead organ donor is often dependent on the discretion of the primary critical care team with considerable variation in practices between ICUs [20].
The target of management is to maintain physiological homeostasis in order to continue optimal organ function and to maximize graft viability in the organ recipient [20]. Given the variation in management protocols, donor goals were developed to establish a standard protocol aimed at maintaining the physiology close to normal values based on routine monitoring of ICU patients [2]. An early and easy-to-remember series of goals were established known as the “rule of 100” [40]: systolic arterial pressure >100 mmHg, urine output >100 ml/hr, arterial partial pressure of oxygen (PaO2) >100 mmHg, and hemoglobin concentration >100 g/L. Later, an additional goal was included: “blood sugar 100% normal” (Gelb AW, personal communication; 2011).
Although there is still considerable variation in treatment protocols, application of management techniques, donor acceptance, and achievement of donor goals [41,42], a higher number of transplantable organs is possible using protocols or systems that can easily and reliably promote achievement of management goals [43].

Temperature Management

Prevention of hypothermia should be preferred compared with its reversal. It is easier to prevent hypothermia by actively warming the donor body, and bodies with temperatures <34°C should be subjected to core warming [36]. Surface warming should be performed for all patients with hypothermia and should be continued to maintain a temperature over 35.8°C before and during the retrieval operation [28,44]. Active warming can be achieved using warm blankets, fluid warmers, and heated humidifiers in ventilator circuits [39], as well as by adjusting the ambient temperature.

Cardiovascular Management

Hemodynamic goals

Goals for the management of hemodynamic status in donors are as follows [5]: (1) to maintain normovolemia; (2) to control blood pressure (BP); (3) to optimize cardiac output (CO) to maintain perfusion pressure of all organs; and (4) to minimize use of vasoactive agents. Although some consensus recommendations have been made (Table 2) [20,45], currently, there is still a lack of clear evidence for recommendations on ideal hemodynamic goals in organ donor management. Logically, recommendations on BP values should be individualized; for example, higher BP targets for potential organ donors with known hypertension [20].


Anti-hypertensive drugs are typically not required after brain death due to the transient nature of the autonomic storm [36]. Hypertension is very unlikely to occur after brain death, and as donor organs tend to be at higher risk of hypotension rather than hypertension, a conservative treatment plan is recommended [14]. In the case of a hypertensive donor, the goal for mean arterial BP is <90 mmHg, but it should always be kept above 65–70 mmHg [14]. If necessary, short-acting anti-hypertensive drugs, such as esmolol, sodium nitroprusside, hydralazine, labetalol, or nitroglycerine, are preferred as long-term use of anti-hypertensive drugs are usually not required [36].


Systemic hypotension is very common in brain-dead donors and may occur in up to 97% of cases [46]. Signs of continuing hemorrhage (external, gastrointestinal, urinary, abdominal, etc.) should be checked, and medications that may contribute towards hypotension (e.g., anti-hypertensive drugs, β-blockers) should be avoided [36]. Three management strategies are commonly adopted, and the direction of treatment depends on the clinical response. These strategies include volume expansion, vasopressors and inotropes, and hormonal replacement as described below [5].

Volume expansion and fluid management

Hypovolemia is a common scenario in brain-dead donors and appropriate fluid resuscitation is usually considered the first step in correcting hypotension [28]. There is debate on the selection of fluid, with no consensus on which type of fluid is more appropriate. At different centers, both crystalloids and colloids are used and often in combination [28]. However, the decision for fluid selection should be considered based on serum electrolytes, sugar levels, hemodynamics of the patient, estimated volume deficiency, and polyuria from DI [36].
(1) Fluid
The recommendations are as follows [5,36]. (1) Crystalloids with balanced salt content should be used to avoid hypernatremia (concurrent DI). Lactated Ringer’s solution and halfnormal saline (0.45%) are frequently used [36]. A solution of 0.9% normal saline may cause hyperchloremic acidosis, which increases renal vascular resistance and confounds base excess when used as a resuscitation fluid. Excessive IV fluids containing 5% dextrose may worsen hyperglycemia and hypothermia [36]. (2) Colloids, such as hydroxyethyl starches, need to be avoided in organ donors as they can damage renal epithelial cells and cause early graft dysfunction in the transplanted kidneys [36]. (3) Albumin solutions (4% and 20%) can be used to reduce the amount of fluid volume administered. However, it is usually only moderately effective, and the high sodium content of albumin-based solutions should also be considered [36]. (4) Lactated Ringer’s solution or half-normal saline solution (0.45%), with the addition of sodium bicarbonate at 50 mmol/L, can be given if the donor has acidosis to reduce the incidence of hypernatremia (i.e., sodium levels ≥150 mmol/L) in donors [5].
(2) Monitoring
Hemodynamic monitoring tools are used in the assessment of volume status and responses to therapy [12]. Pulmonary artery or central venous catheter insertion, as well as noninvasive monitoring techniques, should be considered. Serial or continuous measurements of central venous pressure or pulmonary arterial obstructive pressure are necessary. Stroke volume, CO, cardiac index, and mixed venous oxygen saturation should also be monitored continuously [12].

Vasoactive agents

Patients require additional vasoactive agents when adequate fluid resuscitation is not sufficient to restore BP and CO. It has been estimated that approximately 80%–90% of donors require inotropic and/or vasopressor support [47]. There are widely divergent opinions concerning the use of vasoactive medication, with no consensus or randomized controlled trials (RCTs) to determine which drugs to use and which to avoid [28]. Depending on local practices and protocols, noradrenaline, adrenaline, vasopressin, dopamine, and/or dobutamine are commonly used solely or in combination. Animal models have shown that high doses of catecholamines may cause cardiomyopathy [48]. Although no RCTs in humans currently exist, animal models have demonstrated a reduced inflammatory response and improved oxygenation when using noradrenaline [49].
Very few retrospective studies currently exist examining the selection of catecholamines for use in organ-protective intensive care [50-52]. In Germany, norepinephrine is most often used to target parameters at low dosages, whereas in the Anglo-American arena, vasopressin is often preferred over norepinephrine. The recommended dose of noradrenaline is 0.5–4 U/hr [50-52]. In some centers, if the CO is lowered, dobutamine is also used.
Vasopressin is highly effective in DI management and reduces the hemodynamic need for using different catecholamines [53,54]. However, other studies have shown that norepinephrine increased both coronary and renal blood flow in the normal mammalian circulation [55], whereas vasopressin had no effect [56]. At present, there are no convincing studies or consensus to demonstrate that one vasopressor is superior to another [28].
Although dopamine is used frequently by some centers, other transplant teams prefer not to use it as dopamine causes presynaptic modulation of norepinephrine release. Therefore, prolonged dopamine infusions may cause depletion of norepinephrine stores in the heart, possibly resulting in myocardial dysfunction after transplantation [57,58]. Some studies have found that combining 1-deamino-8-D-arginine vasopressin with a low dose of epinephrine may produce prolonged hemodynamic stability in brain-dead patients without causing worsening of liver or renal functions [59], although such approaches are still considered experimental.

Combined hormonal therapy

Although “triple-therapy” (the combination methylprednisolone, vasopressin, and triiodothyronine [T3]) remains controversial, some studies have reported that it may improve both hemodynamic stability in brain-dead patients, as well as the quality of the procured organs [60]. Some centers use triple therapy according to their local protocol with the decision of initiating hormonal therapy undertaken in discussion with the organ retrieval teams [60].
The United Network for Organ Sharing has conducted an analysis on 10 years of data covering several hormone replacement modalities and showed that the combination of a thyroid hormone, corticosteroid, insulin, and an antidiuretic hormone was the most promising in multiple organ procurement [61]. Combined hormonal therapy is particularly indicated in patients in which volume loading and vasoactive medications have not produced hemodynamic instability [39]. Hormone replacement therapy may be initiated if hemodynamic goals are not met and/or the left ventricular ejection fraction remains less than 45% [12]. The recommended replacements are [2,5,14,36]: (1) vasopressin: 1 U bolus followed by an infusion of 0.5–4.0 U/hr, (2) methylprednisolone: 15 mg/kg immediately after the diagnosis of brain death and every 24 hours afterwards. Alternatively, 250 mg followed by 100 mg/hr until organ retrieval, (3) insulin infusion to maintain blood glucose levels between 80 and 150 mg, (4) thyroxine (T4; 20 μg bolus) followed by infusions of 10 μg/hr. T3, administered as a 4 μg bolus, followed by infusion of 3 μg/hr. T4 improves hemodynamic status and prevents cardiovascular collapse in hemodynamically unstable organ donors.


Atrial and ventricular arrhythmias, as well as conduction defects, occur frequently in brain-dead organ donors and are more commonly seen in cases with a longer lag between brain death and organ removal [36,62]. Additionally, electrolyte and arterial blood gas (ABG) disorders, hypotension with myocardial ischemia, hypothermia, inotropes infusion, myocardial contusions, and increased ICP are important contributing factors to the development of arrhythmias [40]. Special attention should be paid to treat arrhythmias promptly, as severe problems are associated with them.

Prevention of arrhythmia

To prevent and reduce the risk of developing cardiac arrhythmias, electrolytes, BP, fluid volume, and body temperature should all be carefully monitored and maintained within the normal range [36].

Treatment of tachyarrhythmia

Standard therapies, such as amiodarone or cardioversion, can be used to treat arrhythmias [36]. While atropine is not useful in the management of bradycardia, adrenaline, isoprenaline, or pacing, may be effective in such cases [63]. Ultimately, all brain-dead individuals undergo terminal arrhythmias that are resistant to therapy [62]. In such cases, cardiopulmonary resuscitation should be performed for at least a limited period and especially if the donor is already in the operating room [40].

Respiratory Management

Currently, there are a limited number of RCTs examining optimal management strategies for respiratory function in braindead donors [28]. An RCT involving 118 potential donors reported that lung protective ventilation (i.e., lowest possible plateau pressure, tidal volumes of 6 ml/kg of ideal body weight, and moderate positive end expiratory pressure [PEEP] of 5–10 cmH2O to achieve an oxygen saturation of >92%) doubled the lung transplant rate from 27% to 54% [64].
In the majority of circumstances, volume-limited controlled mechanical ventilation is typically used during organ donor care. The goals of mechanical ventilation include maintaining [14]: (1) peak airway pressure: <40 cmH2O, (2) plateau airway pressure: <35 cmH2O, (3) fraction of inspired oxygen (FiO2): lowest possible to maintain peripheral arterial oxygen saturation (SpO2) >92% and PaO2 >70 mmHg, (4) PEEP: minimum 5 cmH2O, adjust to maintain PaO2 >70 mmHg, (5) auto-PEEP <5 cmH2O, (6) ABG values: pH 7.35–7.45; arterial partial pressure of carbon dioxide (PaCO2) >16 mmHg, <60 mmHg to maintain pH within goal range; PaO2 >70 mmHg; HCO3 not independently adjusted.
The respiratory passage must be kept clear of any obstruction with routine measures, such as suctioning, positioning, and turning, continued to achieve this [36]. Although atelectasis and excessive fluid resuscitation are two major causes of hypoxemia that often preclude the use of lungs in transplantation, these factors can be corrected [5]. Recently, it has been recognized that lung injury and inflammation may occur due to the use of prolonged mechanical ventilation. It has been suggested that the strategies for alveolar recruitment to treat atelectasis should be applied judiciously, with the end inspiratory plateau pressure limited to less than 30 cmH2O [5]. Strategies (e.g., PEEP to maintain oxygen delivery to the organs due to reduction in atelectasis, avoidance of interstitial fluid overload, and maintenance of oxygen saturations within normal limits) should be undertaken and normocapnia should be maintained [36].

Endocrine Management

Thyroid hormone replacement

Positive effects on the routine administration of thyroid hormones as a part of the brain-dead organ donor management protocol have not been reported in many studies [65,66]. This has created considerable debate within the transplant field. Animal studies have demonstrated that deterioration in cardiac function could be reversed with T3 supplementation [67,68], although no such correlation was found in human studies [45,66,69].
Although T3 levels decrease in roughly 75% of patients, very few brain-dead donor patients actually reach significantly low T3 levels, while free T4, conversely, seems to be less affected with only one-third presenting subnormal values [20]. Actually, abnormal thyroid function values seen after brain death are more consistent with “sick euthyroid syndrome” rather than true hypothyroidism [45,66]. Thus, routine replacement of thyroid hormones is not recommended for all organ donors [20]. Some guidelines suggest thyroid hormone supplementation only if impaired cardiac performance is documented despite overall good general management [70,71]. Thyroid hormone supplementation may be safe if over dosing is avoided [72,73]. Perhaps only patients with true hypothyroidism will actually benefit from thyroid hormone replacement since not all brain-dead donors exhibit a total absence of anterior pituitary gland function [12].


High doses of corticosteroids may reduce brain death-induced inflammation and help to modulate immune function, thereby improving donor organ quality and post-transplant graft function [12]. Therefore, treating brain-dead donors with corticosteroids is often recommended [5,74]. The main purpose of using corticosteroids is not to treat adrenocortical failure, but rather to attenuate the immune responses and reduce the catecholamine requirement for maintaining BP [20].
The use of methylprednisolone in brain-dead donors leads to improved short- and long-term outcomes for most transplanted organs [28], along with improved oxygenation, reduction of extravascular lung water [23], and increased lung yield. It also reduces inflammation in the liver [75], heart [76], and kidney [77]. Administration of methylprednisolone to the organ donor reduces inflammation in the kidney after transplantation [77]; however, there is no evidence of reduction of the incidence or duration of primary graft failure. Methylprednisolone should be administered as soon as possible as its use is associated with increased organ retrieval [78].


Major hormonal alterations caused by brain death may result in insulin resistance and gluconeogenesis. Moreover, the practice of administering solutions containing dextrose and the use of corticosteroids may further worsen glucose homeostasis [12]. Hyperglycemia is closely associated with reduced host immune responses that result in an increased risk of infection, worsening of renal function in renal transplant recipients, as well as osmotic diuresis [20]. A retrospective study on deceased organ donors showed that higher glucose levels with greater fluctuating levels were associated with reduced pre-recovery of renal function [33].
It is generally accepted that uncontrolled hyperglycemia should be treated and deceased hyperglycemic organ donors should be treated as other critically ill patients. However, there still remains considerable debate regarding target glucose levels for intensive insulin therapy in critically ill patients [12]. Hyperglycemic organ donor patients should be treated according to the local institutional guidelines used for other critically ill patients. Routine use of IV fluids containing dextrose should be avoided [12].

Anti-diuretic hormone

If the patient develops DI, electrolytes should be monitored frequently and corrected accordingly [20]. If left untreated, this may result in hypovolemia, hyperosmolality, hypernatremia, hypermagnesemia, hypokalemia, hypophosphatemia, and hypocalcemia [40]. IV fluids should be given to replace fluid loss through urine and a balanced salt solution or fluids with low-sodium content (5% dextrose or 0.45% saline) should be used to maintain sodium levels between 135 and 145 mEq/L [36].
Treatment for arginine vasopressor or antidiuretic hormone deficiency should be considered if hypotension persists despite adequate volume resuscitation and if one or more of the following criteria are identified in the absence of other causes [12]: polyuria (urine output >3–4 L/day or 2.5–3.0 ml/kg/hr), normal or increased serum osmolality, (3) inappropriately diluted urine (specific gravity <1.005, urine osmolality <200 mOsm/kg H2O), (4) hypernatremia (Na+ >145 mmol/L). DI can be treated by replacement of fluid with adequate crystalloid solutions and by administration of desmopressin. Vasopressin can also be used as an alternative to desmopressin [2,46].

Renal Management

As shown in experimental animal models and historical databases, kidneys are at high risk for developing ischemia because of increased levels of catecholamines at the time of brain death. Subsequent hypoperfusion is also possible if donor management is inadequate and is not appropriately treated [3]. Effective donor management is associated with good renal graft function, even if liberal fluid therapy is avoided [2]. Renal management should be achieved by appropriate fluid management and judicial use of vasopressor drugs.

Hematological Management


The most likely causes of anemia during donor care management are continued blood loss or excessive blood draws performed for laboratory testing, with hemolysis very unlikely to occur [14]. The target is to maintain the hematocrit (Hct) above 30%. If the Hct drops below 30%, two units of packed red blood cells (PRBCs) should be transfused rapidly. Hct levels should be reassessed 1 hour after every PRBC infusion, with repeated transfusions necessary if Hct levels remain below 30% [14].


Coagulopathy should be treated promptly with management including the administration of red blood cells, clotting factors, and platelets [40]. However, the transfusion of blood or blood products should be given only when necessary [36]. In certain cases, the onset of severe coagulopathy may necessitate the rapid transfer of the donor from the ICU to the operating room for organ retrieval [40].

Infectious Disease Protection

The diagnosis of sepsis may be difficult in brain death as elevated leukocyte count and tachycardia are non-specific for infectious processes. Additionally, fever may not be clinically evident in some patients due to hypothalamic dysfunction [20]. The principles of antimicrobial therapy are similar to other critical non-organ donor patients. Antimicrobial therapy should be given based on the results of gram staining or cultures; empirical therapy can be started if recommended by the transplant team to treat suspected pathogens causing infection [39]. Nephrotoxic antimicrobials should be avoided if possible and the use of prophylactic antimicrobials are not routinely recommended [39]. Preventive measures include maintaining pulmonary hygiene with regular tracheal suctioning and oral care, keeping the head of the bed elevated, as well as aseptic management of invasive lines or catheters that should be removed as soon as they are no longer needed [20].

Management of Nutrition

Nutrition should be continued based on standard ICU protocols in patients waiting for consent for organ donation from family members [79]. Continuing enteral feeding to maintain adequate nutrition in potential donors may help to provide beneficial effects on organ functioning [80].


In this review, we have thoroughly mentioned and identified the physiological effects of irreversible total loss of brain function in brain death. We have also mentioned the practical aspects of brain-death management and the care of potential organ donors. We have reviewed in detail different guidelines and protocols used in brain-dead donor management and found that each transplant center follows their own protocol.
Although there is considerable variation in treatment protocols for different centers with no authentic guidelines in the management of potential brain-dead organ donors, herein, we propose a guideline for consideration. Our proposed treatment protocol, based primarily on the Korea University Anam Hospital (Seoul, Korea) management protocol for brain-dead organ donors, has been prepared for centers or countries, such as Bangladesh, where no management guidelines are currently available. Our proposed guideline (shown below) will help other centers to prepare their own management protocols for proper management of potential organ donors. This will increase chances of successful transplantations in the future.

Protocol for the Management of Brain-Dead Organ Donors

Main protocols are summarized in Table 3. The oxygen challenge test is a major criterion for lung donor selection. The ratio of PaO2/FiO2 is recorded to determine the predictive variables of the donor lung PaO2/FiO2 ratio [81]. Good oxygenation is considered a good indicator for determining the functional quality of the lung [82]. During the oxygen test, lung compliance is tested under direct vision by disconnecting the endotracheal tube from the ventilator; if the lungs remain inflated or only slowly collapse, this indicates interstitial fluid accumulation, pneumonia, or small airway obstructive disease (emphysema), or major airway plugging. After removing all atelectatic zones by squeezing, the lungs will gently reinflate. A blood gas sample is then drawn from the left and right pulmonary veins to reassess the oxygenation capacity of both lungs separately [82].
Although most studies demonstrate that the results of the oxygen challenge test predict the outcome of lung transplantations, in other studies, it is considered a categorical variable. Some studies suggest different cutoff points for the oxygen challenge test [81]. For example, based on the international criteria for lung donation, an oxygen challenge test with a result <400 mmHg is usually considered ideal and a result <200 mmHg as not acceptable [81]. It is recommended that the donor PaO2 should be <300 mmHg. If the result of the donor oxygen test is <300 mmHg after transplantation, pulmonary function may have deteriorated [83]. Donors with suboptimal oxygen challenge test results should not be excluded immediately, however. Instead, more aggressive donor management strategies should be undertaken to decrease the percentage of unusable donor lungs and to maximize transplantation opportunities [81].
Medication protocols for brain-dead organ donors are summarized in Table 4.


As brain stem death leads to an expected pattern of complex multiple organ failure, appropriate management and adequate care of the potential organ donor before and after brain death can increase the number and quality of donor organs [36]. The management of a brain-dead organ donor is very challenging. To achieve this goal, adequate fluid resuscitation, intense vasoactive medication, immunosuppressive therapy, and sufficient hemodynamic, and physiological monitoring are required [28]. The current protocols are based on expert opinions, and mostly recommend extended hemodynamic monitoring, early-differentiated volume, and vasopressor or catecholamine therapy [13]. The protocol we have proposed and provided in the checklist may help intensivists manage brain-dead organ donors to promote successful organ and tissue donations.


▪ Intensivists need to play a vital role in the management of potential organ donors through identification of potential donors, declaration of brain death, and proper medical care, all of which can improve the rates of graft survival.
▪ The protocol we have proposed and provided in the checklist may help intensivists in managing brain-dead organ donors to promote successful organ and tissue donation.


CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported.


First of all, I express my ever gratitude to almighty Allah who has given me the enough strength, spirit, and fortitude to carry out this laborious job. With upmost regards, I owe my heartiest gratitude and indebtedness to my honorable teacher and guide Dr. Jae Myeong Lee (Assistant Professor of Department of Acute Care Surgery, Korea University Anam Hospital, Seoul, Korea) who is the corresponding author of this article, for her constant courage, close supervision and scholarly support throughout this work. I also give thanks to Korea University Anam Hospital authority to give me the opportunity of working in this hospital and provide all the supports to complete this research work successfully. I owe a deep debt gratitude to Dr. Harun Ur Rashid, Professor and Chairman of the Kidney Foundation, Dhaka, Bangladesh, who arranged my fellowship training on brain-dead donor management in Korea University Anam Hospital, Seoul, Korea and I am also grateful to Dr. Md. Nizamuddin Chowdhury, Professor and Head, Department of Nephrology, Dhaka Medical College Hospital, for his encouragement, invaluable skillful advice and suggestion which have been instrumental for me throughout the period of this work. I am indebted to my parents and family members for their sacrifice, wholehearted support, and continuous inspiration.



Conceptualization: JML. Project administration: all. Visualization: JML. Writing - original draft: all. Writing - review & editing: all.

Table 1.
Frequency of pathophysiological changes in irreversible loss of brain function
Variable Cause Frequency (%)
Hypothermia Hypothalamic dysfunction, vasoplegia 100
Hypotension Vasoplegia, hypovolemia, myocardial dysfunction 80–97
Diabetes insipidus Hypothalamic/pituitary dysfunction 65–90
Arrhythmias Catecholamine release, myocardial injury 25–32
Pulmonary edema Injury to vascular endothelium 15–20
Cardiac arrest Prolonged hypotension, arrhythmia 5–10

Adapted from Hahnenkamp et al. Dtsch Arztebl Int 2016;113:552-8 [13].

Table 2.
Consensus recommendations [20]
Variable Crystal City consensus Shemie et al. (2006) [45] ACCP/SCCM consensus [12]
Heart rate (beats/min) 60–120
Arterial systolic pressure (mmHg) >100
Mean arterial pressure (mmHg) >60 ≥70 >60
Central venous pressure (mmHg) 4–12 6–10
Urine output (ml/kg/hr) 0.5–3 >1
Pulse oximetry (%) ≥95
Pulmonary capillary wedge pressure (mmHg) 8–12 6–10
Cardiac index (L/min/m2) 2.4 2.4
Systemic vascular resistance (dyn-s/cm5) 800–1,200 800–1,200

ACCP/SCCM: American College of Chest Physicians/Society of Critical Care Medicine Consensus.

Table 3.
Protocols for the management of brain-dead organ donors
Category Recommendation
General management Central line insertion and monitoring
Arterial line insertion and monitoring
Nasogastric tube insertion
Foley’s catheter insertion
Care lines, intubation tube, Foley’s catheter; consider changing when necessary
Maintain the head of the bed at 30°–40° elevation
Continue side-to-side body positioning
Warming blankets to maintain body temperature around 36.5°C
Maintain pneumatic compression device for preventing deep vein thrombosis
Eye protection
Frequent airway suctioning
Ulcer prophylaxis
Broad spectrum antibiotics
Monitoring Vital signs check every 1 hour
Urine output check every 1 hour
Arterial blood pressure with continuous monitoring
ABG analysis every 6 hours
Body temperature check every 1 hour
Therapeutic target Mean arterial pressure: >65 mmHg
Hemoglobin: >10 g/dl
Sodium: <160 mmol/L
Potassium: 3.5–5 mmol/L
Central venous or mixed venous oxygen saturation: >70%
SpO2: >92%
Arterial blood gases within the normal range (with the exception of permissive hypercapnia)
Lactate: <3 mmol/L
PCO2: 35–45 mmHg
Blood sugar: 140–180 mg/dl
Hourly urine output: 100–300 ml
Central body temperature: >36.0°C
Investigations-lab Routine complete blood count, serum electrolyte panel including total CO2
Blood urea nitrogen
Serum creatinine
Total calcium (Ca), ionized Ca, magnesium (Mg), phosphate (P)
Total bilirubin, direct bilirubin
Aspartate aminotransferase, alanine transaminase
Alkaline phosphatase, gamma-glutamyl transpeptidase
Protein, albumin
Amylase, lipase
Total cholesterol, triglyceride, cholesterol (low density lipoprotein and high density lipoprotein)
Uric acid
C-reactive protein, erythrocyte sedimentation rate
Creatinine phosphokinase
Creatinine kinase-muscle/brain, troponin I
N-terminal pro B-type natriuretic peptide
Carcinoembryonic antigen, prostate-specific antigen
CA 19-9, CA 125, alpha-fetoprotein
T3, T4, thyroid stimulating hormone
aPTT and prothrombin time
Hemoglobin A1c
Typing, antibody
Urine analysis
ABG study
Hepatitis A virus (HAV) antibody testing: HAV Ab IgM, HAV Ab IgG
Hepatitis B virus antigen and antibody testing: HBcAb, HBcAb IgM (enzyme-linked immunosorbent assay),
HBsAg, HBsAb, HBeAg, HBeAb; HBsAg confirmatory test (reverse transcription polymerase chain reaction)
Hepatitis C virus Ab confirmatory test (RT-PCR)
Human immunodeficiency virus testing: HIV Ag and Ab combination (screening)screening test
Cytomegalovirus (CMV) antibody test: CMV IgM, CMV IgG
Epstein-Barr virus antibody (EBV) test: EBV EA DR IgG, EBV EA DR IgM
Venereal disease research laboratory test: if positive then, treponema pallidum latex agglutination test or treponema pallidum hemagglutination assay HLA A DNA, HLA B DNA, HLA DR DNA, HLA DQ DNA
HLA crossmatch B test
Culture and sensitivity (urine), gram stain (urine)
Culture and sensitivity (sputum), Gram stain (sputum)
Culture and sensitivity (blood), aerobic
Culture and sensitivity (blood), anaerobic
24-Hour urine: glucose, K, Cl, Ca, total, urea nitrogen, creatinine, uric acid, protein
Investigation-imaging Chest X-ray posteroanterior view
Hepatobiliary and kidney ultrasonogram
Abdomen and pelvis CT scan (non-contrast enhanced)
Brain CT scan (non-contrast enhanced)

ABG: arterial blood gas; SpO2: peripheral arterial oxygen saturation; PCO2: partial pressure of carbon dioxide; CA: carbohydrate antigen; T3: triiodothyronine; T4: thyroxine; aPTT: activated partial thromboplastin time; Ab: antibody; Ig: immunoglobulin; HBc: hepatitis B core; HBs: hepatitis B surface; Ag: antigen; HBe: hepatitis B virus e antigen; RT-PCR: reverse transcription polymerase chain reaction; HIV: human immunodeficiency virus; CMV: cytpmegalovirus; EBV: Ebstein-Barr virus; EA: early antigen; DR: diffuse and restricted; HLA: human leukocyte antigen; CT: computed tomography.

Table 4.
Medication protocols for brain-dead organ donors
Category Recommendation
 Hypertension Short acting anti-hypertensive drugs can be used.
 Hypotension Restore circulatory volume and use vasoactive agents.
 Fluids Balanced crystalloid solution should be used.
Avoid synthetic starch solutions.
Avoid excess volume.
 Vasopressors Norepinephrine 20 mg in 5% dextrose water 500 ml
 Transfusion Consider need for blood products, platelets, or filters coagulopathy should be corrected if there is active bleeding.
 Sodium (Na) Na >180 mmol/L: 0.45% saline 300 ml/hr or 5% DW 300 ml/hr IV
Na >160 mmol/L: 0.45% saline 200 ml/hr or 5% DW 200 ml/hr IV
Na >140 mmol/L: 0.45% saline 200 ml/hr or 5% DW 200 ml/hr IV
Na <140 mmol/L: ballanced crystalloid and total parenteral nutrition
 Potassium (K) K 3.5–4.5 mmol/L (target)
Endocrine RI 100 IU in 0.9% saline 100 ml mix
 Hyperglycemia Initial starting dose
BST 200–300 mg/dl → RI 1 U/hr
BST 300–400 mg/dl → RI 2 U/hr
BST >400 mg/dl → RI 3 U/hr
Maintenance dose
BST 200–300 mg/dl → add RI 1U/hr
BST 300–400 mg/dl → add RI 2 U/hr
BST 400–500 mg/dl → add RI 3 U/hr
BST 100–200 mg/dl → continue and maintain the dose
BST 80–100 mg/dl → reduce RI 1 U/hr
 Hypoglycemia BST 50–80 mg/dl → 50% DW 10 ml IV infusion and notify
BST < 50 mg/dl → 50% DW 20 ml IV infusion first and then notify
 Steroid replacement Methylprednisolone 200 mg in 0.9% saline 100 ml IV, infusion rate 4 ml/hr
 Diabetes insipidus control Vasopressin 20 U in 5% DW 500 ml mix
HUO >300 ml: IV infusion rate 3 ml/hr
HUO 100–200 ml: keep the dose and maintain with 0.5–1 ml/hr and HUO monitoring
 Thyroid supply Ideal is to check T3, T4 first but in this context we should start with levothyroxine 150 μg daily
 Mucolytic agents IV mucolytics (N-acetylcysteine) 300 mg every 8 hours
 Anti-ulcer agents IV proton pump inhibitor or IV H2 blocker
 Antimicrobials Fever (−): 3rd generation cephalosporin
Fever (+): empiric antibiotics as below then consult with infectious disease specialist
Vancomycin 1 g every 12 hours+piperacillin/tazobactam 4.5 g every 8 hours or
Vancomycin 1 g every 12 hours+meropenem 1 g every 8 hours

DW: dextrose water; RI: regular human insulin; BST: blood sugar test; HUO: hourly urine output; IV: intravenous.


1. Kutsogiannis DJ, Pagliarello G, Doig C, Ross H, Shemie SD. Medical management to optimize donor organ potential: review of the literature. Can J Anaesth 2006; 53: 820–30.
crossref pmid
2. McKeown DW, Bonser RS, Kellum JA. Management of the heartbeating brain-dead organ donor. Br J Anaesth 2012; 108 Suppl 1: i96–107.
crossref pmid pdf
3. Bos EM, Leuvenink HG, van Goor H, Ploeg RJ. Kidney grafts from brain dead donors: inferior quality or opportunity for improvement? Kidney Int 2007; 72: 797–805.
crossref pmid
4. Rodrigues Sde L, Ferraz Neto JB, Sardinha LA, Araujo S, Zambelli HJ, Boin Ide F, et al. Profile of effective donors from organ and tissue procurement services. Rev Bras Ter Intensiva 2014; 26: 21–7.
crossref pmid pmc
5. Wood KE, Becker BN, McCartney JG, D’Alessandro AM, Coursin DB. Care of the potential organ donor. N Engl J Med 2004; 351: 2730–9.
crossref pmid
6. Goila AK, Pawar M. The diagnosis of brain death. Indian J Crit Care Med 2009; 13: 7–11.
crossref pmid pmc
7. de Groot YJ, Jansen NE, Bakker J, Kuiper MA, Aerdts S, Maas AI, et al. Imminent brain death: point of departure for potential heart-beating organ donor recognition. Intensive Care Med 2010; 36: 1488–94.
crossref pmid pmc
8. Dhanwate AD. Brainstem death: a comprehensive review in Indian perspective. Indian J Crit Care Med 2014; 18: 596–605.
crossref pmid pmc
9. Wikipedia contributors. Brain death [Internet]. San Francisco (CA), Wikimedia Foundation. [cited 2019 Feb 20]. Available from: https://en.wikipedia.org/wiki/Brain_death.

10. Karasawa H, Sakaida K, Noguchi S, Hatayama K, Naito H, Hirota N, et al. Intracranial electroencephalographic changes in deep anesthesia. Clin Neurophysiol 2001; 112: 25–30.
crossref pmid
11. Young GB. Diagnosis of brain death [Internet]. Waltham (MA), UpToDate. 2018; [cited 2019 Feb 20]. Available from: https://www.uptodate.com/contents/diagnosis-of-brain-death.

12. Kotloff RM, Blosser S, Fulda GJ, Malinoski D, Ahya VN, Angel L, et al. Management of the potential organ donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med 2015; 43: 1291–325.
crossref pmid
13. Hahnenkamp K, Böhler K, Wolters H, Wiebe K, Schneider D, Schmidt HH. Organ-protective intensive care in organ donors. Dtsch Arztebl Int 2016; 113: 552–8.
crossref pmid pmc
14. Powner DJ, Darby JM, Kellum JA. Proposed treatment guidelines for donor care. Prog Transplant 2004; 14: 16–26.
crossref pmid
15. Smith M. Physiologic changes during brain stem death: lessons for management of the organ donor. J Heart Lung Transplant 2004; 23(9 Suppl):S217–22.
crossref pmid
16. Amado JA, López-Espadas F, Vázquez-Barquero A, Salas E, Riancho JA, López-Cordovilla JJ, et al. Blood levels of cytokines in brain-dead patients: relationship with circulating hormones and acute-phase reactants. Metabolism 1995; 44: 812–6.
crossref pmid
17. Mascia L, Mastromauro I, Viberti S, Vincenzi M, Zanello M. Management to optimize organ procurement in brain dead donors. Minerva Anestesiol 2009; 75: 125–33.
18. Rey JW, Ott T, Bösebeck D, Welschehold S, Galle PR, Werner C. Organ protective intensive care treatment and simulationbased training. Anaesthesist 2012; 61: 242–8.
crossref pmid
19. Rech TH, Moraes RB, Crispim D, Czepielewski MA, Leitão CB. Management of the brain-dead organ donor: a systematic review and meta-analysis. Transplantation 2013; 95: 966–74.
crossref pmid
20. Wong J, Tan HL, Goh JP. Management of the brain dead organ donor. Trends Anaesth Crit Care 2017; 13: 6–12.
21. Kumar L. Brain death and care of the organ donor. J Anaesthesiol Clin Pharmacol 2016; 32: 146–52.
crossref pmid pmc
22. Szabó G, Hackert T, Sebening C, Vahl CF, Hagl S. Modulation of coronary perfusion pressure can reverse cardiac dysfunction after brain death. Ann Thorac Surg 1999; 67: 18–25.
crossref pmid
23. Venkateswaran RV, Patchell VB, Wilson IC, Mascaro JG, Thompson RD, Quinn DW, et al. Early donor management increases the retrieval rate of lungs for transplantation. Ann Thorac Surg 2008; 85: 278–86.
crossref pmid
24. Avlonitis VS, Fisher AJ, Kirby JA, Dark JH. Pulmonary transplantation: the role of brain death in donor lung injury. Transplantation 2003; 75: 1928–33.
crossref pmid
25. 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.
crossref pmid
26. Strieter RM, Kunkel SL. Acute lung injury: the role of cytokines in the elicitation of neutrophils. J Investig Med 1994; 42: 640–51.
27. de Vries DK, Lindeman JH, Ringers J, Reinders ME, Rabelink TJ, Schaapherder AF. Donor brain death predisposes human kidney grafts to a proinflammatory reaction after transplantation. Am J Transplant 2011; 11: 1064–70.
crossref pmid
28. Bugge JF. Brain death and its implications for management of the potential organ donor. Acta Anaesthesiol Scand 2009; 53: 1239–50.
crossref pmid
29. 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.
crossref pmid
30. Gramm HJ, Meinhold H, Bickel U, Zimmermann J, von Hammerstein B, Keller F, et al. Acute endocrine failure after brain death? Transplantation 1992; 54: 851–7.
crossref pmid
31. Howlett TA, Keogh AM, Perry L, Touzel R, Rees LH. Anterior and posterior pituitary function in brain-stem-dead donors: a possible role for hormonal replacement therapy. Transplantation 1989; 47: 828–34.
crossref pmid
32. Tien RD. Sequence of enhancement of various portions of the pituitary gland on gadolinium-enhanced MR images: correlation with regional blood supply. AJR Am J Roentgenol 1992; 158: 651–4.
crossref pmid
33. Blasi-Ibanez A, Hirose R, Feiner J, Freise C, Stock PG, Roberts JP, et al. Predictors associated with terminal renal function in deceased organ donors in the intensive care unit. Anesthesiology 2009; 110: 333–41.
crossref pmid
34. Barklin A. Systemic inflammation in the brain-dead organ donor. Acta Anaesthesiol Scand 2009; 53: 425–35.
crossref pmid
35. Murugan R, Venkataraman R, Wahed AS, Elder M, Hergenroeder G, Carter M, et al. Increased plasma interleukin-6 in donors is associated with lower recipient hospital-free survival after cadaveric organ transplantation. Crit Care Med 2008; 36: 1810–6.
crossref pmid
36. 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.
crossref pmid pmc
37. Talving P, Benfield R, Hadjizacharia P, Inaba K, Chan LS, Demetriades D. Coagulopathy in severe traumatic brain injury: a prospective study. J Trauma 2009; 66: 55–61.
crossref pmid
38. Barklin A, Tønnesen E, Ingerslev J, Sørensen B, Fenger-Eriksen C. Coagulopathy during induced severe intracranial hypertension in a porcine donor model. Anesthesiology 2009; 110: 1287–92.
crossref pmid
39. Intensive Care Society of Ireland. Diagnosis of brain death & medical management of the organ donor: guidelines for adult patients [Internet]. Intensive Care Society of Ireland. 2010; [cited 2019 Feb 20]. Available from: https://www.anaesthesia.ie/archive/ICSI/ICSI%20Guidelines%20MAY10.pdf.

40. Gelb AW, Robertson KM. Anaesthetic management of the brain dead for organ donation. Can J Anaesth 1990; 37: 806–12.
crossref pmid
41. Franklin GA, Santos AP, Smith JW, Galbraith S, Harbrecht BG, Garrison RN. Optimization of donor management goals yields increased organ use. Am Surg 2010; 76: 587–94.
42. Selck FW, Deb P, Grossman EB. Deceased organ donor characteristics and clinical interventions associated with organ yield. Am J Transplant 2008; 8: 965–74.
crossref pmid
43. Klein AS, Messersmith EE, Ratner LE, Kochik R, Baliga PK, Ojo AO. Organ donation and utilization in the United States, 1999-2008. Am J Transplant 2010; 10(4 Pt 2):973–86.
crossref pmid
44. Wood KE, McCartney J. Management of the potential organ donor. Transplant Rev 2007; 21: 204–18.
45. Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, Brand T, et al. Organ donor management in Canada: recommendations of the forum on Medical Management to Optimize Donor Organ Potential. CMAJ 2006; 174: S13–32.
crossref pmid pmc
46. 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.
crossref pmid
47. Wood KE, Coursin DB. Intensivists and organ donor management. Curr Opin Anaesthesiol 2007; 20: 97–9.
crossref pmid
48. Rona G. Catecholamine cardiotoxicity. J Mol Cell Cardiol 1985; 17: 291–306.
crossref pmid
49. Avlonitis VS, Wigfield CH, Kirby JA, Dark JH. The hemodynamic mechanisms of lung injury and systemic inflammatory response following brain death in the transplant donor. Am J Transplant 2005; 5(4 Pt 1):684–93.
crossref pmid
50. Plurad DS, Bricker S, Falor A, Neville A, Bongard F, Putnam B. Donor hormone and vasopressor therapy: closing the gap in a transplant organ shortage. J Trauma Acute Care Surg 2012; 73: 689–94.
crossref pmid
51. Plurad DS, Bricker S, Neville A, Bongard F, Putnam B. Arginine vasopressin significantly increases the rate of successful organ procurement in potential donors. Am J Surg 2012; 204: 856–60.
crossref pmid
52. Callahan DS, Neville A, Bricker S, Kim D, Putnam B, Bongard F, et al. The effect of arginine vasopressin on organ donor procurement and lung function. J Surg Res 2014; 186: 452–7.
crossref pmid
53. Pennefather SH, Bullock RE, Mantle D, Dark JH. Use of low dose arginine vasopressin to support brain-dead organ donors. Transplantation 1995; 59: 58–62.
crossref pmid
54. Chen JM, Cullinane S, Spanier TB, Artrip JH, John R, Edwards NM, et al. Vasopressin deficiency and pressor hypersensitivity in hemodynamically unstable organ donors. Circulation 1999; 100(19 Suppl):II244-6.
crossref pmid
55. Di Giantomasso D, May CN, Bellomo R. Norepinephrine and vital organ blood flow. Intensive Care Med 2002; 28: 1804–9.
crossref pmid
56. Di Giantomasso D, Morimatsu H, Bellomo R, May CN. Effect of low-dose vasopressin infusion on vital organ blood flow in the conscious normal and septic sheep. Anaesth Intensive Care 2006; 34: 427–33.
crossref pmid
57. Weiner N. Norepinephrine, epinephrine, and sympathomimetic amines. In: Gilman AC, , Goodman LS, , Rall TW, , Murad F. In: Goodman and Gilman’s the pharmacological basis of therapeutics. 6th ed. New York, MacMillan. 1985, pp 145–80.

58. Novitzky D, Cooper DK, Wicomb WM, Reichert B. Haemodynamic changes, myocardial injury, and pulmonary oedema induced by sympathetic activity during the development of brain death in the baboon. Transplant Proc 1986; 13: 609–12.

59. Yoshioka T, Sugimoto H, Uenishi M, Sakamoto T, Sadamitsu D, Sakano T, et al. Prolonged hemodynamic maintenance by the combined administration of vasopressin and epinephrine in brain death: a clinical study. Neurosurgery 1986; 18: 565–7.
crossref pmid
60. Findlater C, Thomson EM. Organ donation and management of the potential organ donor. Anaesth Intensive Care Med 2015; 16: 315–20.
61. 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 2014; 7: 17–27.
crossref pmid pmc
62. Logigian EL, Ropper AH. Terminal electrocardiographic changes in brain-dead patients. Neurology 1985; 35: 915–8.
crossref pmid
63. Vaghadia H. Atropine resistance in brain-dead organ donors. Anesthesiology 1986; 65: 711–2.
crossref pmid
64. 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.
crossref pmid
65. Rosendale JD, Kauffman HM, McBride MA, Chabalewski FL, Zaroff JG, Garrity ER, et al. Aggressive pharmacologic donor management results in more transplanted organs. Transplantation 2003; 75: 482–7.
crossref pmid
66. Goarin JP, Cohen S, Riou B, Jacquens Y, Guesde R, Le Bret F, et al. The effects of triiodothyronine on hemodynamic status and cardiac function in potential heart donors. Anesth Analg 1996; 83: 41–7.
crossref pmid
67. Novitzky D, Cooper DK, Morrell D, Isaacs S. Change from aerobic to anaerobic metabolism after brain death, and reversal following triiodothyronine therapy. Transplantation 1988; 45: 32–6.
crossref pmid
68. Novitzky D, Wicomb WN, Cooper DK, Tjaalgard MA. Improved cardiac function following hormonal therapy in brain dead pigs: relevance to organ donation. Cryobiology 1987; 24: 1–10.
crossref pmid
69. Randell TT, Höckerstedt KA. Triiodothyronine treatment is not indicated in brain-dead multiorgan donors: a controlled study. Transplant Proc 1993; 25(1 Pt 2):1552–3.
70. Masson F, Thicoïpe M, Latapie MJ, Maurette P. Thyroid function in brain-dead donors. Transpl Int 1990; 3: 226–33.
crossref pmid
71. Zaroff JG, Rosengard BR, Armstrong WF, Babcock WD, D’Alessandro A, Dec GW, et al. Consensus conference report: maximizing use of organs recovered from the cadaver donor: cardiac recommendations, March 28-29, 2001, Crystal City, Va. Circulation 2002; 106: 836–41.
crossref pmid
72. 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.
crossref pmid
73. Novitzky D, Cooper DK, Reichart B. Hemodynamic and metabolic responses to hormonal therapy in brain-dead potential organ donors. Transplantation 1987; 43: 852–4.
crossref pmid
74. Rosendale JD, Chabalewski FL, McBride MA, Garrity ER, Rosengard BR, Delmonico FL, et al. Increased transplanted organs from the use of a standardized donor management protocol. Am J Transplant 2002; 2: 761–8.
crossref pmid
75. 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.
crossref pmid
76. McLean KM, Duffy JY, Pandalai PK, Lyons JM, Bulcao CF, Wagner CJ, et al. Glucocorticoids alter the balance between proand anti-inflammatory mediators in the myocardium in a porcine model of brain death. J Heart Lung Transplant 2007; 26: 78–84.
crossref pmid
77. Kainz A, Wilflingseder J, Mitterbauer C, Haller M, Burghuber C, Perco P, et al. Steroid pretreatment of organ donors to prevent postischemic renal allograft failure: a randomized, controlled trial. Ann Intern Med 2010; 153: 222–30.
crossref pmid
78. Chamorro C, Falcón JA, Michelena JC. Controversial points in organ donor management. Transplant Proc 2009; 41: 3473–5.
crossref pmid
79. Singer P, Cohen J, Cynober L. Effect of nutritional state of braindead organ donor on transplantation. Nutrition 2001; 17: 948–52.
crossref pmid
80. Singer P, Shapiro H, Cohen J. Brain death and organ damage: the modulating effects of nutrition. Transplantation 2005; 80: 1363–8.
crossref pmid
81. Najafizadeh K, Arab M, Radpei B, Pojhan S, Abbasi-Dezfuli A, Deneshvar A, et al. Age and sex predict PaO2/FiO2 ratio in brain-dead donor lungs. Transplant Proc 2009; 41: 2720–2.
crossref pmid
82. Van Raemdonck D, Neyrinck A, Verleden GM, Dupont L, Coosemans W, Decaluwé H, et al. Lung donor selection and management. Proc Am Thorac Soc 2009; 6: 28–38.
crossref pmid
83. Zafar F, Khan MS, Heinle JS, Adachi I, McKenzie ED, Schecter MG, et al. Does donor arterial partial pressure of oxygen affect outcomes after lung transplantation? A review of more than 12,000 lung transplants. J Thorac Cardiovasc Surg 2012; 143: 919–25.
crossref pmid
Editorial Office
#805-806, Yongseong Biztel, 109 Hangang-daero, Yongsan-gu, Seoul 04376, Korea
TEL: +82-2-2077-1533   FAX: +82-2-2077-1535   E-mail: acc@accjournal.org
About |  Browse Articles |  Current Issue |  For Authors and Reviewers
Copyright © The Korean Society of Critical Care Medicine. All rights reserved.                 developed in m2community
Close layer
prev next