Management of the deceased organ donor

INTRODUCTION — Organ transplantation has saved or enhanced the lives of hundreds of thousands of recipients worldwide over the past 50 years. Optimal donor management is essential in both the intensive care unit and the operating room to maximize the function of transplanted organs and the quality of life and survival benefits conveyed to the recipients.

The management of deceased adult organ donors prior to organ procurement will be reviewed here. The evaluation of potential deceased adult organ donors and the evaluation and management of potential deceased pediatric organ donors are discussed separately. (See "Evaluation of the potential deceased organ donor (adult)" and "Assessment of the pediatric patient for potential organ donation" and "Management of the potential pediatric organ donor following neurologic death".)

GENERAL CONSIDERATIONS — Management of the potential organ donor primarily involves the use of conventional therapeutic and supportive measures to reverse or mitigate the physiologic changes that occur after brain death, including potentially severe autonomic and inflammatory responses. The mechanisms of these changes are not well understood, not easily studied, and potentially harmful to the function of transplantable organs [1,2]. The intensive care unit (ICU) team and an Organ Procurement Organization (OPO) coordinator work together to optimize the cardiopulmonary and endocrine systems by restoring optimal circulating intravascular volume, normalizing electrolyte and metabolic imbalances, and maintaining hemodynamics to promote adequate perfusion and oxygenation of donor organs, thus maximizing the viability and function of procured organs [3-5]. (See "Evaluation of the potential deceased organ donor (adult)", section on 'Responsibilities of the organ procurement organization'.)

This process requires balancing the interventions needed for the successful preservation of multiple organs. Interventions that improve the function of one organ may be detrimental to the function of other organs [4]. As an example, although the renal transplant team prefers an extremely well-hydrated donor with excellent diuresis, aggressive hydration may cause edema that may jeopardize the transplantability of the heart, lungs, liver, and pancreas. However, data suggest that restrictive fluid balance, which is intended to improve lung procurement and viability, has no substantial detrimental effect on rates of kidney procurement or function after transplant [6].

Other important general considerations include the following:

●Proper ventilatory support, good pulmonary toilet, and appropriate infection prophylaxis and/or treatment [1,4].

●Mild therapeutic hypothermia versus maintenance of normothermia.

Normothermia may be maintained passively with blankets or with active rewarming (eg, forced air blankets) if necessary. With the loss of hypothalamic temperature regulation, the brain-dead donor tends to be hypothermic. A target temperature range of 36.5 to 37.5°C is reasonable, unless therapeutic hypothermia (34 to 35°C) is used to reduce delayed graft function of the kidneys. (See 'Therapeutic hypothermia' below.)

STEPS TO OPTIMIZE ORGAN FUNCTION — Care of the potential organ donor should continue the support that started before the declaration of brain death and should compensate for the associated physiologic deterioration. While evidence from randomized trials for optimal donor management [7] is lacking, active donor management is believed to (and almost certainly does) improve the retrieval rate [8]. The Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations (SCCM/ACCP/AOPO) have published guidelines for donor management [4]. The Donation after Brain Death Study Group reported on development of key interventions and quality indicators for the management of the donor after brain death using modified Delphi method [9]. Our approach is consistent with these guidelines (table 1).

Monitoring — The primary goal for monitoring of the potential organ donor is to optimize the number and long-term function of transplanted organs. While practices vary among institutions, monitoring potential organ donors commonly involves the following [4]:

●The usual hemodynamic and respiratory monitoring for critically ill patients, such as serial or continuous monitoring of temperature, blood pressure, heart rate and rhythm, pulse oxygen saturation, and urine output.

●An arterial line is typically placed for continuous blood pressure monitoring, assessment of pulse pressure variation (PPV) and/or systolic pressure variation (SPV), and access for drawing blood, although this practice varies among institutions. (See "Intraoperative fluid management", section on 'Monitoring intravascular volume status' and "Novel tools for hemodynamic monitoring in critically ill patients with shock", section on 'Volume tolerance and fluid responsiveness'.)

●A central venous catheter is usually placed to enable serial or continuous measurements of parameters such as central venous pressure (CVP) and central venous oxygen saturation (CVO₂) [4]. Caution must be used in interpreting the CVO2 from an internal jugular or subclavian central line due to the absence of deoxygenated blood from the brain. The CVP catheter also facilitates administration of vasopressor and other medications and enables sampling of central venous blood.

●A pulmonary artery catheter (PAC) may be placed in selected patients when measurement of pulmonary artery occlusion pressure (PAOP, also known as the pulmonary capillary wedge pressure), stroke volume, cardiac output (CO), and cardiac index is needed. Serial mixed venous oxygen saturation measurements can be made via PAC.

●Hemodynamic parameters can also be measured with pulse contour analysis, esophageal doppler, or noninvasively with bioreactance monitors [10-12].

●Laboratory monitoring includes renal function, electrolytes, acid-base status, serum lactate, liver function tests, and sometimes troponins and brain natriuretic peptide. Bacterial cultures of blood, urine, and sputum are routinely obtained. Upper airway testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is frequently performed, and lower airway testing is required for all lung donors.

Hemodynamic support and electrolyte management — Hemodynamic support is an essential component of optimizing future allograft function (table 1).

Goal blood pressure — Control of extremes of blood pressure is one of the donor management goals (DMG) that were developed to improve organ donation outcomes [13]. The DMG for blood pressure is a mean arterial pressure (MAP) of 60 to 110 mmHg [13]. We agree with guidelines that recommend targeting a MAP of at least 60 to 65 mmHg in potential organ donors [4,14].

Hypertensive autonomic storm — Brain death often results in an initial hypertensive crisis followed by hypotension [15]. The hypertensive crisis (also known as an autonomic storm) is attributed to a massive sympathetic discharge following brain death. For patients who manifest the cardiovascular effects of autonomic storm (eg, tachycardia, increased myocardial oxygen consumption, hypertension), any intervention should be easily reversible as this phase tends to be followed by hypotension. Beta-adrenergic antagonists such as esmolol may ameliorate the cardiovascular effects and preserve myocardial function [4,16-18].

Initial management of hypotension — Following the initial hypertensive storm, a hypotensive period often ensues and is attributed to multiple potential factors, including hypovolemia, cardiac dysfunction, and vasodilation [1]. The initial management requires fluid administration to maintain an adequate, typically near-normal circulating volume. Administration of vasoconstrictors may be needed to compensate for the loss of vascular tone (vasoplegia) that often accompanies brain death. Inadequate fluid resuscitation may require excessive vasoconstrictor administration, which can be deleterious to the organs to be procured. In contrast, aggressive fluid administration can cause edema in the lungs, liver, and heart, which can be detrimental to their function in recipients.

●For hypotensive patients with a PPV greater than 15, intravenous fluids are administered to replete the circulating volume, aiming to bring the MAP to >60 to 65 mmHg and urine output to 0.5 to 1 mL/kg per hour [4,13,19].

●Patients with a high urine output may have brain-death-associated diabetes insipidus (DI), which will need specific treatment to avoid hypernatremia and ongoing fluid losses. (See 'Vasopressin and desmopressin' below.)

●The optimal methods to assess euvolemia and exact targets have not been determined. Traditional measures include achieving the MAP and urine output targets noted above, CVP 4 to 10 mmHg, or PAOP 8 to 12 mmHg. However, these measures can be misleading, so there is a growing use of noninvasive dynamic measures such as PPV or SPV, which are described separately. (See 'Monitoring' above and "Novel tools for hemodynamic monitoring in critically ill patients with shock", section on 'Pulse contour analysis (fluid responsiveness)'.)

●When the PPV or SPV indicates that the patient is no longer volume responsive (figure 1), it is appropriate to start either a vasoconstrictor (wide pulse pressure) or a positive inotrope (narrow pulse pressure), regardless of whether the conventional targets for CVP (4 to 10 mmHg) or PAOP (8 to 12 mmHg) have been met, as discussed below. (See 'Hypotension despite fluid repletion' below and "Definition, classification, etiology, and pathophysiology of shock in adults" and "Treatment of severe hypovolemia or hypovolemic shock in adults".)

●A prospective study utilizing an early stroke-volume-based fluid resuscitation protocol for four hours in brain-dead organ donors was associated with a significant increase in fluid infused (1937 mL versus 1323 mL) and a decrease in time on vasopressors (2.9 hours versus 16 hours) compared with a control group. Stroke volume was assessed by pulse contour analysis or esophageal Doppler with equal efficacy [20]. Donors in the protocol group were more likely to donate four or more organs than donors in the control group [10].

Choices for fluid and electrolyte replacement — The optimal choice for fluid replacement has not been determined. Guidelines advocate use of isotonic crystalloids, such as lactated Ringer solution, PlasmaLyte, Normosol, or 0.9 percent saline [4]. The presence of a hyperchloremic acidosis may prompt selection of lactated Ringer solution or other bicarbonate-containing solutions, while the presence of hypernatremia may prompt the use of more hypotonic solutions until the underlying cause has responded to treatment. Some experts prefer colloids, such as albumin (5 percent) [21], but hydroxyethyl starch has been associated with acute kidney injury and is not recommended [4,22]. (See "Treatment of severe hypovolemia or hypovolemic shock in adults", section on 'Nonhemorrhagic shock'.)

The optimal hemoglobin level for organ procurement/preservation is not known. Intraoperative red cell transfusion is often necessary in patients with prior abdominal surgery, in whom the dissection of the liver and kidneys for organ procurement might be difficult, or in patients whose blood vessels are difficult to cannulate. Based on the success of restrictive transfusion policies, transfusion to a target hemoglobin level >7 g/dL is suggested by guidelines, but a trigger of 7 to 10 g/dL may be requested by one of the procuring surgical teams [4]. (See "Indications and hemoglobin thresholds for RBC transfusion in adults".)

Careful attention should be paid to maintaining normal electrolyte levels. According to current guidelines, serum sodium should be maintained below 155 mEq/dL and potassium between 4 and 5 mEq/dL (table 1) [9,23]. If serum sodium is elevated, the patient should be evaluated for central DI, which may result from posterior pituitary infarction. (See 'Vasopressin and desmopressin' below.)

Hypotension despite fluid repletion — For patients who remain hypotensive (MAP <60 mmHg) despite appropriate fluid replacement, we initiate infusion of low-dose vasopressin, which is effective in treating vasodilatory shock and reducing the need for catecholamines for blood pressure support [24], in addition to treating DI, if present. In addition, use of vasopressin is associated with an increased rate of organ recovery, based on a large retrospective analysis described below. (See 'Vasopressin and desmopressin' below.)

For persistent hypotension, the next step is to determine whether it is due to low systemic vascular resistance or myocardial dysfunction. Assessment of PPV and SPV can help with this differentiation (figure 1) (see 'Monitoring' above). Transthoracic echocardiography is also used to assess left ventricular ejection fraction and determine the need for additional invasive hemodynamic monitoring or support. Myocardial dysfunction may be due to underlying cardiac disease, cardiac injury from chest trauma, or stress cardiomyopathy.

●Vasodilatory shock – The optimal vasopressor for deceased organ donors with intact myocardial function has not been determined [4]. Traditionally, dopamine has been the first choice for donors who are hemodynamically unstable despite vasopressin, and some evidence supports a benefit in improving post-transplant kidney allograft function [25]. However, comparative trial data are lacking, and practice patterns have shifted in favor of using norepinephrine or phenylephrine for severe vasoplegia [4,26,27].

●Reduced myocardial function – If the left ventricular ejection fraction is estimated at less than 45 percent, an inotropic agent, such as dopamine, dobutamine, or epinephrine, is used. The response to treatment is assessed by serial echocardiography, or placement of a pulmonary artery catheter. All echocardiograms should be interpreted in the context of vasopressor(s) support that the donor was receiving at the time of the study [26]. Most heart transplant centers prefer the donor to be on minimal or no vasopressors or inotropes during the last echocardiogram prior to a heart offer.

Hemodynamic or electrolyte disturbances due to acute kidney injury — For deceased potential organ donors who develop diuretic-refractory oliguric or anuric acute kidney injury with severe volume overload, metabolic acidosis, or hyperkalemia, we suggest initiation of continuous renal replacement therapy (CRRT) to facilitate optimization of organs for transplant.

Acute kidney injury (AKI) in deceased potential organ donors is increasing due to the increased frequency of anoxia as a cause of brain death. In this setting, kidney function usually returns to baseline with adequate hydration, restoration of perfusion, and time. However, oliguric or anuric kidney injury can cause electrolyte disturbances and circulatory overload that prevent the achievement of standard hemodynamic and electrolyte support during transplant evaluation. Some organ procurement organizations have begun using continuous renal replacement therapy to facilitate organ optimization in these patients.

●In one observational study, 27 deceased potential donors with oliguric or anuric AKI treated with CRRT after the diagnosis of brain death were compared with historical controls that were treated medically [28]. The patients who received CRRT stabilization were managed for longer pre-explant time (62.8 versus 37.1 hours), and had more organs successfully transplanted per donor (2.9 versus 1.4). This difference was due in large part to an increase in thoracic organs transplanted (1.4 versus 0.6). Notably, thirty-seven percent of the kidneys treated with CRRT were successfully transplanted with a mean serum creatinine of 1.4 mg/dL at six months.

Ventilation and oxygenation — The goals of mechanical ventilation are to maintain tissue oxygenation and protect the lungs for transplantation.

Ventilator settings — The optimal strategy for mechanical ventilation of the donor has not been determined, but the trend is to use low tidal volume ventilation (LTVV, also known as lung protective ventilation), and this is the strategy used by the authors (table 1) [4,29,30]. This is in contrast with the traditional use of tidal volumes of 8 to 15 mL/kg and a positive end-expiratory pressure (PEEP) of 5 cm H₂O [31]. (See "Acute respiratory distress syndrome: Ventilator management strategies for adults", section on 'Low tidal volume ventilation: Initial settings' and "Ventilator-induced lung injury", section on 'Mechanisms'.)

●Low tidal volume ventilation – Implementation of LTVV is described in the table (table 2) and in more detail separately. (See "Acute respiratory distress syndrome: Ventilator management strategies for adults", section on 'Application and titration'.)

While data in support of LTVV for potential organ donors are limited, LTVV has demonstrated benefits in patients with acute respiratory distress syndrome and in a multicenter, randomized trial that assessed the effect of LTVV on the number of lungs eligible for transplantation [29]. Potential donors were assigned to conventional ventilation (tidal volumes 10 to 12 mL/kg of predicted body weight and PEEP of 3 to 5 cm H₂O) or protective ventilation (tidal volume 6 to 8 mL/kg of predicted body weight and PEEP of 8 to 10 cm H₂O) for a six-hour observation period. In both groups, the respiratory rate was adjusted to obtain an arterial partial pressure of carbon dioxide (PaCO₂) of 40 to 45 mmHg. Lungs were procured from 16 (27 percent) donors in the conventional strategy group versus 32 (54 percent) in the protective strategy group (p = 0.004). Six-month survival rates of lung transplant recipients did not differ between the two groups. Thus, if overall hemodynamic and acid-base status will allow, the LTVV strategy for potential lung donors appears to substantially increase the proportion of lungs that are acceptable for transplantation.

●Peak and plateau airway pressures – The critical care literature supports keeping the plateau (static) airway pressure below 25 to 30 cm water pressure to reduce lung injury. If plateau pressures are difficult to obtain, the peak pressure can be followed. (See "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit".)

●Preventing ventilator-associated pneumonia – Measures to prevent ventilator-associated pneumonia should be employed, including elevation of the head of the bed to 30 degrees, if blood pressure is adequate. Additional measures to prevent ventilator-associated pneumonia are discussed separately (table 3). (See "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Prevention'.)

●Fraction of inspired oxygen and PEEP – Initial ventilator settings include PEEP 5 to 10 cm H₂O and a fraction of inspired oxygen (FiO₂) of 100 percent. Subsequently, FiO₂ and PEEP are titrated in tandem (table 2), similar to the method used for acute respiratory distress syndrome (ARDS). Some experts advise an initial PEEP ≥8 cm H₂O to enhance lung procurement [14,30], but we prefer to titrate as needed. PEEP has the potential to decrease venous return and contribute to hypotension. To avoid hypotension, it is crucial that the donor be adequately volume resuscitated before increasing PEEP or using lung recruitment maneuvers.

To optimize lung procurement, most experts aim for the lowest FiO₂, preferably 25 to 40 percent, that provides adequate oxygenation (eg, arterial oxygen saturation [SpO₂] >95 percent; arterial oxygen tension [PaO₂] >90 mmHg).

Lung recruitment maneuvers may be used when oxygenation does not meet acceptable parameters for donation. (See "Mechanical ventilation during anesthesia in adults", section on 'Recruitment maneuvers'.)

Measurement of oxygen saturation — Per Organ Procurement and Transplant Network (OPTN) policy, lung donor blood gases are measured on FiO₂ 1.0 and PEEP 5 cm H₂O, and a PaO₂ >300 mmHg is generally required for lung transplantation. This requires that blood gas analyzers are accurate in the high PO₂ range, which is not usually a clinically relevant range in the intensive care unit (ICU). One study demonstrated that a point-of-care (POC) blood gas analyzer underestimated the PaO₂ above 300 mmHg, on average, by 54 mmHg, which was associated with fewer lungs transplanted compared with a benchtop analyzer (35 versus 48 percent) [32]. If a POC analyzer is used for donor management, the accuracy of the PO₂ measurement above 300 mmHg should be verified.

Additional interventions to improve lung function

●Donor management protocol – A comprehensive lung-protective donor management protocol at one OPO's organ recovery center demonstrated a significant increase in lung procurement rate (lungs donors/all brain-dead donors) from 19.8 percent (prior to 2008) to 33.9 percent (after the protocol was started, 2009 to 2016) [33]. The national average of lungs procured/brain-dead donor is 22 percent. The protocol included low tidal volume (6 to 8 mL/kg ideal body weight), low flow rates (25 to 30 L/min), inspiratory:expiratory ratio (I:E) 1:1, peak pressures <30 mmHg, and PEEP 8 to 10 cm H₂O. It also included intrapulmonary percussive ventilation every four hours, frequent bronchoscopy to remove secretions, recruitment maneuvers (PEEP up to 15 cm H₂O), and pulmonary ultrasound to evaluate for pulmonary edema. Further study is needed to confirm these results.

●Prone ventilation – Basilar atelectasis is very common in the brain-dead donor due to the absence of spontaneous diaphragmatic movement and the cough reflex, loss of positive airway pressure with the apnea test, and lack of suctioning, since the patient is not demonstrating any distress. Atelectasis was the most common finding (45 percent) in a study of 445 chest computed tomography (CT) scans in brain-dead donors [34]. A prospective study of prone ventilation in the hypoxemic brain-dead donor with basilar atelectasis demonstrated an improvement in oxygenation, decrease in atelectasis, and an increase in lungs transplanted from 24 to 45 percent [35]. After four hours of prone ventilation, the PaO₂ increased an average of 113 versus 54 mmHg in the supine group and remained 74 mmHg higher at 12 hours. Basilar opacities and/or atelectasis was present in 75 percent of the donors, and significantly decreased in the donors after prone ventilation (image 1). Prone ventilation should be considered in the hypoxemic donor with basilar opacities on a chest radiograph or CT scan.

●Nebulized albuterol – Nebulized albuterol is frequently used on mechanically ventilated patients as part of a ventilator protocol. A randomized trial of aerosolized high-dose albuterol (5 mg every four hours) versus saline was performed to decrease pulmonary edema and improve alveolar fluid clearance in organ donors with the hope of improving oxygenation and number of lungs transplanted [36]. The change in PaO₂/FiO₂ from enrollment to organ procurement did not differ between treatment groups nor did donor lung utilization (albuterol 29 versus placebo 32 percent). In the albuterol group, study drug was more likely to be decreased or stopped due to tachycardia. Albuterol should be used in organ donors with an indication for bronchodilatation (eg, asthma) and not routinely to improve oxygenation.

●Lack of benefit to naloxone – We do not use naloxone in the brain-dead donor to attenuate neurogenic pulmonary edema. Despite preliminary animal data suggesting improvement in oxygenation, a multi-OPO randomized trial of naloxone (8 mg) versus saline in 199 hypoxemic brain-dead donors revealed no difference in the increase in PaO₂ (81 versus 80 mmHg) nor number of lungs transplanted (19 versus 19 percent) between the naloxone and control group [37].

●Ex-vivo lung perfusion (EVLP) – If the arterial oxygen tension/fraction of inspired oxygen (PaO₂/FiO₂) ratio remains below 300 after intensive lung donor management, EVLP may be an option after lung procurement to recondition lungs, improve oxygenation, and decrease pulmonary compliance, thus improving acceptability of otherwise unacceptable lung allografts, as discussed separately. (See "Lung transplantation: Donor lung procurement and preservation", section on 'New approaches to organ preservation'.)

Hormonal therapy — Brain death is associated with endocrine and metabolic dysfunction, and it is hypothesized that these changes may affect graft survival. Interventions to address these abnormalities include vasopressin, glucocorticoids, thyroid hormone, and insulin (table 1) [16,38,39].

There is a lack of consensus about when hormonal therapies should be initiated. Some experts recommend using them only in hemodynamically compromised donors, while others recommend broad use in most donors [31].

Vasopressin and desmopressin — In a substantial majority of potential organ donors, the pituitary gland is compressed at the time of brain herniation, potentially leading to development of central DI, manifest by high urinary output >1000 mL/hour and the evolution of hypernatremia and hypotension [40]. We suggest initiation of vasopressin (also called arginine vasopressin or AVP) in donors with hypotension despite adequate fluid resuscitation or with excessive urinary output [26,41], while desmopressin can be used for hypernatremia without hypotension. (See "Arginine vasopressin deficiency (central diabetes insipidus): Treatment".)

Vasopressin is often used as part of hormonal therapy for deceased organ donors with hypotension, but without frank DI, although this is off-label [41]. A typical dosing regimen is an initial bolus infusion of 1 unit, followed by a continuous infusion of 0.01 to 0.1 units/minute (typical doses are 0.01 to 0.04 units/minute), titrating to a mean arterial pressure (MAP) >60 mm Hg and systemic vascular resistance of 800 to 1200 dynes-sec/cm⁵ [4,26]. Doses >0.04 units/minute have been associated with adverse cardiac effects [4,26].

In a retrospective analysis of 10,431 donors in the OPTN database, use of AVP was associated with an increased rate of organ recovery, 50.5 percent from those receiving AVP versus 35.6 percent from those without [41]. In a separate study of 12,322 donors from the same database, 63 percent of donors received AVP, which was associated with higher rates of organ recovery (mean 3.75 versus 3.33, p<0.001) and successful lung recovery (26.3 versus 20.5 percent, p<0.001) [42]. However, it is unclear in these studies whether AVP was used for DI or hypotension, or both. Also, the group that received AVP was significantly younger, had less bacteremia, and had more traumatic brain injury as a cause of death, which could contribute to more transplantable organs [27].

Desmopressin is an analog of vasopressin with greater antidiuretic effect and substantially less vasopressor effect. Thus, this agent is used for patients with DI who are not hypotensive. For patients with hypernatremia (serum sodium >145 to 150 mmol/L) and urine output >2.5 to 3.0 mL/kg/hour, an initial dose of 1 to 4 micrograms is given intravenously. The urine output, urine osmolality, and serum sodium are monitored and the dose adjusted to achieve a urine volume <4 mL/kg/hour [4]. A typical dose is 1 to 2 micrograms intravenously every six hours. Desmopressin can be used concurrently with vasopressin in patients with severe hypernatremia and hypotension.

DI increases urinary losses of magnesium, phosphate, and potassium, so serum levels of these electrolytes should be monitored and replaced as needed.

Glucocorticoids — Glucocorticoids are often given prior to organ retrieval to optimize donor lung function, based on a widespread belief in a benefit from glucocorticoids as a treatment for the inflammatory state that can sometimes be present in brain-dead donors, even if other hormonal agents are not used [4,39,43]. In addition, adrenal insufficiency after brain death has been reported [44]. When administering glucocorticoids for donor hypotension, we typically use a relatively low dose (hydrocortisone 300 mg IV once, then 100 mg every eight hours) [26,45]. Higher doses, such as methylprednisolone (15 mg/kg, as an intravenous infusion, or 250 mg as an intravenous bolus followed by an infusion of 100 mg/hour) were used in the past [4], but are associated with more adverse effects.

Glucocorticoids should not be given until after blood has been collected for tissue typing [4]. Glucocorticoid administration is supported by current guidelines despite conflicting evidence regarding benefit [4,45,46].

Several studies suggest a benefit to using intravenous hydrocortisone in organ donor management [47,48]. Hydrocortisone has mineralocorticoid as well as glucocorticoid activity, which is beneficial in the volume depleted hypotensive organ donor. In a prospective multicenter cluster study of 259 organ donors, the probability of weaning norepinephrine was 4.67 times higher in the low-dose hydrocortisone group (50 mg IV, then 10 mg/hr IV continuously) compared with the control group [47]. Another study of 31 hypotensive donors who received 50 mg IV hydrocortisone demonstrated a significant decrease in norepinephrine dose within three hours, particularly in donors who did not respond to an adrenocorticotropic hormone stimulation test (true adrenal non-function) [48]. A comparison study of high-dose methylprednisolone (15 mg/kg daily) to low-dose hydrocortisone (300 mg once, then 100 mg every eight hours) in 132 brain-dead donors demonstrated similar improvements in hemodynamic stability and oxygenation, with no difference in the number of hearts or lungs transplanted. The low-dose group had less hyperglycemia, and more donors were off insulin compared with the high-dose group (74 versus 53 percent, p = 0.02) [49].

Thyroid hormone — Since the publication of the SCCM/ACCP/AOPO guidelines in 2015 [4], clinical trials have demonstrated that thyroid hormone administration has little to no positive or negative impact on important transplant outcomes. Given this lack of benefit and the modestly increased cost and complexity associated with thyroid hormone administration, we suggest against its use in brain-dead donors, including those who are hemodynamically unstable.

The best data come from a trial of 838 hemodynamically unstable brain-dead donors who were randomly assigned 1:1 to receive levothyroxine 30 mcg/hr for at least 12 hours or saline placebo [50]. Major outcomes included the following:

●The number of hearts transplanted in the levothyroxine group and the saline group were similar (54.9 versus 53.2 percent of donors, respectively, adjusted risk ratio 1.01; 95% CI, 0.97-1.07). Donors with low ejection fraction or higher than median vasopressor use were not more likely to benefit from levothyroxine than the rest of the group.

●Similar numbers of lungs, livers, or kidneys were transplanted between the two groups.

●The groups demonstrated similar median time to weaning off vasopressors (22 hours in the levothyroxine group and 25 hours in the placebo group), accompanied by nearly identical ejection fractions.

●There was similar 30-day cardiac graft survival, with 97.4 percent survival from donors assigned to receive levothyroxine compared with 95.5 percent survival in those from donors who received saline (difference, 1.9 percentage points; 95% CI, -2.3 to 6.0).

●Increased adverse hemodynamic effects were seen with levothyroxine, as evidenced by higher rates of severe hypertension and tachycardia (6 and 4 percent, respectively) in donors who received levothyroxine than in those who received saline (approximately 1 percent for each adverse effect).

A separate randomized trial of T3 versus T4 in vasopressor-dependent organ donors after fluid resuscitation did not demonstrate any benefit of T3 over T4 in terms of norepinephrine weaning, improvement in cardiac ejection fraction, nor number of hearts transplanted [51].

Additional placebo-controlled trials also have also suggested lack of benefit to T3 or T4 supplementation based on hemodynamic outcomes [52,53].

Based on the above data, the lack of any benefit of T4, and the increased adverse events with T4, we do not recommend using T4 nor T3 in brain-dead organ donors.

Glycemic control — For patients with hyperglycemia, we suggest maintaining glycemic control with an insulin infusion, typically aiming for a blood glucose of 120 to 180 mg/dL (6.7 to 10 mmol/L) [31]. Hyperglycemia can cause an osmotic diuresis and hypovolemia and may mislead the care team about the adequacy of the circulation in the donor.

Therapeutic hypothermia — Traditionally, a normothermic body temperature (36.5 to 37.5°C), which may require active warming, has been used for organ donors. A few studies suggest that mild donor hypothermia may improve subsequent kidney allograft function [54-57]. In a trial that compared two targeted temperature ranges (34 to 35°C and 36.5 to 37.5°C), hypothermia reduced the frequency of delayed graft function after kidney transplant, defined as a requirement for hemodialysis in the first post-transplant week (OR 0.62; 95% CI 0.43-0.92) without any apparent risk to other organs that may be transplanted [54]. In a separate trial, hypothermia reduced the odds of graft failure at one year in standard criteria donors (0.3; 95% CI 0.15-0.99) but not in the extended criteria donors (older with more comorbidities) [55].

Venous thromboembolism and stress ulcer prophylaxis — Deceased organ donors are at high risk for venous thromboembolism. As with critically ill patients in general, we use thromboprophylaxis rather than mechanical methods and prefer low molecular weight heparin (eg, enoxaparin 40 mg every 12 hours) for patients with normal kidney function. Unfractionated heparin is an alternative for those with kidney failure or in whom cost is an issue. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'High-risk patients'.)

We follow guidance for stress ulcer prophylaxis in critically ill patients. (See "Stress ulcers in the intensive care unit: Diagnosis, management, and prevention", section on 'Prophylaxis'.)

Empiric antibiotics — Empiric antibiotics may be administered based on the organ(s) being transplanted. For lung donors, who typically have lower respiratory tract colonization with nosocomial pathogens, the regimen is designed to cover methicillin-resistant S. aureus (MRSA) and gram-negative pathogens with adjustment, as needed, based on microbiology data. The regimen is continued up to procurement.

SUPPORT FOR FAMILY AND LOVED ONES — The death of a loved one can be intense and emotionally painful, regardless of the manner of death. However, loss from a sudden catastrophic illness, violence, or accident is likely to produce intense acute grief. (See "Communication in the ICU: Holding a meeting with families and caregivers".)

The process of acceptance of the diagnosis of death by neurologic criteria (brain death) or anticipated death by circulatory-respiratory criteria requires patience and empathy on the part of the caregivers [58]. After brain death has been determined and authorization has been provided for organ donation, family members and loved ones may or may not wish to stay with the deceased for some period of time, including until transfer to the operating room for organ retrieval.

Family members may have questions about the procurement procedure, anesthesia during procurement, and eventual transfer of the remains of their loved one to a funeral home. Anesthesia is used to decrease the remaining physiologic response to the procedures involved in procurement.

Specific grief counseling is generally not indicated. Most bereaved individuals are resilient, and acute grief is integrated during a natural adaptive process that typically unfolds with the support and encouragement of close family and friends, as well as clergy. Bereaved individuals, especially those who have lost children, often find it very difficult to speak about the loss. However, grief counseling can be helpful for bereaved individuals who request it. (See "Bereavement and grief in adults: Clinical features" and "Bereavement and grief in adults: Management".)

DETERMINING WHICH ORGANS WILL BE RETRIEVED — The assessment of organs for transplant is generally guided by the Organ Procurement and Transplant Network (OPTN) guidelines and are implemented by the Organ Procurement Organization (OPO) for the geographical territory. Specific requirements vary somewhat from one organ to another [4]. Organs are allocated based on United Network for Organ Sharing (UNOS) or the national guidelines for that country. The OPO will communicate with the transplant team which organs will be retrieved.

●Lung – Determination of lung acceptability has multiple components (eg, gas transfer, chest radiograph, bronchoscopic airway survey, review of prior lung disease or cardiothoracic surgery), which are discussed separately [4]. (See "Lung transplantation: Deceased donor evaluation" and "Heart-lung transplantation in adults", section on 'Donor evaluation'.)

●Heart – A decreased ejection fraction can occur after brain death due to a stunned myocardium from excessive norepinephrine release from the sympathetic storm [59]. Approximately 50 percent of the donors with a decreased ejection fraction will improve over 24 to 48 hours. The left ventricular hypokinesis follows the sympathetic innervation and involves the base and walls with apical sparing. This is the opposite of Takotsubo cardiomyopathy with apical ballooning and basilar sparing. If the ejection fraction returns to ≥55 percent, then the heart can be considered for transplantation [60].

Echocardiography should be performed for all potential donors. If the ejection fraction is estimated at less than 55 percent, or the patient is on high-dose inotropic support, serial echocardiography may be required to assess changes in cardiac function. The precise timing of echocardiography is controversial. The most important echocardiographic information is obtained once normovolemia has been achieved [4]. Therefore, it is reasonable to repeat echocardiogram after volume repletion, if the first study was performed when the donor was hypovolemic.

Coronary angiography may be indicated for older donors (>40 years old) or for younger donors with risk factors for premature coronary artery disease [4]. (See "Heart-lung transplantation in adults", section on 'Donor evaluation'.)

●Liver – (See "Liver transplantation in adults: Deceased donor evaluation and selection".)

●Kidney – Potential kidney donors are assessed based on the kidney donor profile index (table 4). (See "Kidney transplantation in adults: Risk factors for graft failure".)

●Kidney-pancreas – (See "Pancreas-kidney transplantation in diabetes mellitus: Benefits and complications", section on 'Donor factors'.)

●Intestine – (See "Overview of intestinal and multivisceral transplantation", section on 'Donor selection/operation'.)

MANAGEMENT DURING ORGAN PROCUREMENT

Preparation — The supportive measures outlined above (eg, monitoring, central venous access, arterial line, mechanical ventilation, vasopressors/inotropic agents) should be continued when the donor is brought to the operating room, or instituted as necessary in the operating room. Antibiotics that were initiated in the intensive care unit (ICU) should be continued as scheduled up until procurement. (See 'Empiric antibiotics' above.)

In anticipation of organ procurement, the following issues should be discussed between the surgical team and the clinicians who will be monitoring and supporting the donor during the procedure:

●The amount of cross-matched blood that should be available

●The required doses of heparin and glucocorticoids

●For lung procurement, the need to change/upsize the existing endotracheal tube, typically to size 8.0 or 8.5 mm

Control of spinal reflexes — The brain-dead organ donor usually has a functioning spinal cord, and thus may exhibit unregulated sympathetic and motor spinal reflexes in response to stimulation.

●Motor reflexes – Neuromuscular blocking agents (NMBAs) are typically administered to prevent uninhibited motor responses to surgery. NMBAs should be administered in doses that result in deep neuromuscular blockade (ie, zero twitches using a train of four peripheral nerve stimulation monitor). (See "Clinical use of neuromuscular blocking agents in anesthesia".)

●Sympathetic reflexes – Reflex sympathetic responses (ie, hypertension and tachycardia) can be controlled with vasoactive drugs, or with inhaled anesthetics (eg, isoflurane, desflurane, sevoflurane) if available.

Temperature regulation — Forced air and fluid warming should be used intraoperatively to maintain a temperature of 35 to 37°C. (See 'General considerations' above and 'Therapeutic hypothermia' above.)

Anticoagulation — The anesthesia clinician will be asked to administer the agreed-upon dose of heparin several minutes before aortic cross-clamp, which is performed to prepare for infusion of preservative solution into the organs to be procured. A typical dose for an adult is 30,000 units of heparin, or 300 units/kg. Adequate anticoagulation is essential for organ procurement, so heparin should be administered via a central venous catheter if one is in place. Once the heparin has had time to circulate (longer time may be allowed in a hemodynamically unstable donor) the aorta is cross-clamped, and the transplant teams will proceed with procurement.

Multiorgan retrieval — As multiple organs are retrieved from most deceased donors, more than one procurement team may be accessing the patient. There is no one correct way to procure organs for transplantation. If thoracic organs are to be procured in addition to abdominal organs, a single incision is made from the supraclavicular notch to the symphysis pubis. The remainder of the operation involves clamping and cannulating the major blood vessels associated with the organs to be procured. When the lungs are being procured, the trachea will be dissected and ultimately divided. (See "Lung transplantation: Procedure and postoperative management".)

The specifics of procurement for the individual organs are beyond the scope of this topic.

Organ procurement setting — Traditionally, donor management and organ procurement occur at the donor hospital where brain death was declared. Another alternative is to transfer the donor to an organ recovery center (ORC) after the declaration of brain death. The ORC is managed by the local Organ Procurement Organization (OPO) and can be an independent facility or part of a transplant center or donor hospital. The ORC usually has an equipped ICU, surgical suite, and radiology facilities, including a computed tomography (CT) scanner and ultrasound. Some ORCs have cardiac catheterization suites, laboratory facilities (including human leukocyte antigen, serology, and nucleic acid amplification testing) and dialysis capabilities. The donors are managed by the OPO coordinators under the direction of a medical director. Approximately 40 percent of OPOs have an ORC.

The ORC is usually located in cities with transplant centers, and therefore the benefit to the local transplant surgeon is decreased travel time, decreased organ cold ischemic time, and more frequent procurements in daytime hours. Because of these benefits, more OPOs are transitioning to the ORC model of donor management.

DONATION AFTER CIRCULATORY DEATH — Donation after circulatory death (DCD, also referred to as donation after circulatory determination of death [DCDD]) can be considered when organ donation is desired for a patient who does not meet neurologic criteria for brain death but has no hope of viable recovery (eg, stroke, cardiac arrest, multiple trauma), and the decision has been made to withdraw life-sustaining treatment [4,61]. Potential donors are ordinarily expected to expire within a short amount of time after discontinuation of life support (eg, 60 minutes).

Withdrawal of life support — Withdrawal of life support is best performed in or near the operating room (eg, in an isolation bay in the recovery room) with the transplant teams ready nearby to minimize warm ischemic time. As family and friends may wish to be present at the time life support is withdrawn, it is imperative that the procuring teams be kept completely separate from the patient and their family/friends and out of the room where support is being withdrawn, until after the patient has been pronounced dead and the family has left.

The patient's primary team withdraws life support (eg, mechanical ventilation, intraaortic balloon pump, pacemaker, mechanical circulatory support, and vasopressor/inotrope agents). Systemic heparin is usually administered at the time of withdrawal of life support to prevent thrombosis in the transplanted organs. Determination of death is made using standard cardiopulmonary criteria (permanent absence of respiration, circulation, and responsiveness) [4,61-65]. Initiation of recovery of the organs to be donated (eg, kidneys, liver, lungs, pancreas, sometimes heart) can proceed no sooner than two minutes, and no later than five minutes after the patient has been determined to be dead [62]. If the lungs are to be procured, the donor is reintubated and the lungs are inflated with positive pressure.

The longer the time between withdrawal of life support and declaration of death, the greater the warm ischemic injury to the organs to be procured. Warm ischemic time can be calculated from the time of onset of hypotension or hypoxemia until the time the organs have been cooled, although some centers advocate calculating the time from when the support is withdrawn until the time the organs are cooled [66]. Ideally, warm ischemic time should be no longer than 30 minutes for livers and 60 minutes for kidneys and lungs [4]. If the patient does not expire after 60 minutes, the patient may be returned to the intensive care unit (ICU). Parameters used to predict whether death is likely to occur within 60 minutes of withdrawal of life-sustaining therapies are discussed separately.

Results of transplantation after DCD — Despite an increased incidence of poor initial allograft function, some centers have reported long-term survival rates of kidneys from DCD comparable to those observed with kidneys recovered from heart-beating and living donors [63,67-72]. In a single-center study, for example, the one- and five-year renal allograft survival rates were 87 and 82 percent for transplants from non-heart-beating donors, 91 and 86 for transplants from heart-beating donors less than 60 years of age, and 80 and 73 percent for transplants from heart-beating donors greater than 60 years of age, respectively [70]. Perfusing these kidneys with a pulsatile preservation system may help reduce the rate of delayed graft function in DCD kidneys (this is well-established with traditional brain-dead donor kidneys). (See "Deceased- and living-donor kidney allograft recovery", section on 'Technique'.)

Initial experience suggested that this approach can also be used for liver and lung transplantation, provided that the warm ischemic time is minimized [73-75]. Survival after lung transplantation from DCD was comparable to that of donation after brain death in observational cohort studies, including a large international registry consisting of 306 recipients among 10 centers worldwide [64,76,77]. However, there continues to be debate whether liver transplantation from DCD donors leads to higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of retransplantation, and lower graft survival [78-80].

Role of ECMO in DCD — The use of extracorporeal membrane oxygenation (ECMO) to provide regional perfusion to organs that will be transplanted after DCD has shown promise in preliminary studies, but further study of the ethical issues and effects on organ retrieval outcomes is needed [4,81,82]. (See "Lung transplantation: Donor lung procurement and preservation", section on 'Donation after circulatory death' and "Heart transplantation in adults: Donor selection and organ allocation", section on 'Donation after circulatory death' and "Lung transplantation: Deceased donor evaluation", section on 'Protocol'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of potential deceased organ donors" and "Society guideline links: Lung transplantation".)

SUMMARY AND RECOMMENDATIONS

●Overview – Management of the potential organ donor in the intensive care unit (ICU) primarily involves the use of conventional therapeutic and supportive measures to reverse or mitigate the changes in physiology that occur after brain death (table 1). (See 'General considerations' above.)

●Management of hypertensive autonomic storm – Brain death often results in an initial hypertensive crisis, due to a massive sympathetic discharge. For patients who manifest the cardiovascular effects (eg, tachycardia, increased myocardial oxygen consumption, hypertension) of autonomic storm, we suggest using a short-acting beta-adrenergic antagonist (eg, esmolol) (Grade 2C), rather than a longer acting agent or an alpha-antagonist. (See 'Hypertensive autonomic storm' above.)

●Initial management of hypotension – After initial hypertension, deceased potential donors often become hypotensive.

•We suggest using isotonic intravenous crystalloid fluids (eg, lactated Ringer solution, Plasma-Lyte, Normosol, or 0.9 percent saline) to replete circulating volume (Grade 2C). Albumin (5 percent) is a reasonable alternative to isotonic crystalloid. We suggest avoiding hydroxyethyl starch due to potential adverse effects on the kidneys (Grade 2C). (See 'Initial management of hypotension' above.)

•Fluids are administered until the circulating volume is adequate, based on a central venous pressure (CVP) of 4 to 10 mmHg, pulse pressure variation (PPV) <12 percent, systolic pressure variation (SPV) <10 to 15 percent, and/or maximized stroke volume (ie, stroke volume no longer increases with fluid bolus) (figure 1). (See 'Hemodynamic support and electrolyte management' above.)

•We aim for a target mean arterial pressure (MAP) of 60 to 110 mmHg and target urine output of 0.5 to 1 mL/kg per hour. (See 'Goal blood pressure' above.)

●Hypotension despite adequate circulatory volume – For patients with vasoplegia (low systemic vascular resistance with normal cardiac output), we suggest initiation of vasopressin first rather than other vasopressors (Grade 2C); usually a one-unit bolus is given, followed by an infusion of 0.01 to 0.04 units/minute titrated to maintain mean arterial pressure (MAP) >60 mmHg. Severe vasoplegia may require the addition of norepinephrine, phenylephrine, or another vasopressor. (See 'Hypotension despite fluid repletion' above and 'Vasopressin and desmopressin' above.)

•Patients who are hypotensive in spite of adequate volume resuscitation and treatment of vasoplegia should be evaluated with echocardiography. Myocardial dysfunction can be treated with dobutamine, epinephrine, or dopamine. (See 'Hypotension despite fluid repletion' above.)

●Hemodynamic or electrolyte disturbances due to acute kidney injury – We typically support deceased potential donors with fluids and diuretics to correct metabolic acidosis (goal pH 7.35 to 7.45), electrolyte disturbances (goal sodium 135 to 155 mEq / dL, goal potassium 4 to 5 mEq / dL), and oliguria (goal urine output 0.5 to 1mL/kg per hour) (table 1). For deceased potential organ donors who develop diuretic-refractory oliguric or anuric acute kidney injury with severe volume overload, metabolic acidosis, or hyperkalemia, we suggest initiation of continuous renal replacement therapy (Grade 2C) to facilitate optimization of organs for transplant. (See 'Hemodynamic or electrolyte disturbances due to acute kidney injury' above.)

●Mechanical ventilation – The goals of mechanical ventilation are to maintain tissue oxygenation and protect the lungs for transplantation. The optimal strategy for mechanical ventilation of the donor has not been determined; however, we suggest low tidal volume ventilation (LTVV) rather than conventional ventilation (Grade 2B), based on an apparent protective effect on lung allografts and experience in other settings. The target arterial tension of carbon dioxide (PaCO₂) is 35 to 45 mmHg, and the target arterial oxygen saturation (SpO₂) is >95 percent. (See 'Ventilation and oxygenation' above.)

●Endocrine dysfunction – Brain death is associated with metabolic and endocrine dysfunction. While the exact role of hormone therapy in the management of organ donors is not well-established, hormone therapy is common (table 1). Diabetes insipidus (DI) is treated with vasopressin and/or desmopressin. Hyperglycemia is managed with avoidance of glucose-containing intravenous solutions and an insulin drip, if needed. Glucocorticoids are often administered to prevent inflammation. (See 'Hormonal therapy' above.)

For brain-dead donors, including those who are hemodynamically unstable, we suggest against the use of thyroid hormone (Grade 2C). Thyroid hormone supplementation has little to no effect on organ procurement or graft outcomes, but it increases the rates of hypertension and tachycardia in deceased donors. (See 'Hormonal therapy' above.)

●Management during organ procurement – Support during the organ procurement procedures includes continuing or adjusting mechanical ventilation, vasopressor agents, hormonal therapy, and temperature control as needed. Anticoagulation, which is required for organ procurement, is administered as per the surgical team. Antibiotics that were initiated in the ICU should be continued as scheduled up until procurement. (See 'Management during organ procurement' above.)

●Control of spinal reflexes – After brain death, the spinal cord usually continues to function, and thus unregulated motor and sympathetic reflexes may occur in response to stimulation. Neuromuscular blocking agents are used to prevent motor reflexes, and if necessary, vasoactive drugs or inhaled anesthetics can be used to manage sympathetic reflexes. (See 'Control of spinal reflexes' above.)

●Donation after circulatory death – For organ donation after circulatory death (DCD; also known as donation after circulatory determination of death), the donor is typically transferred to a location in or near the operating room for withdrawal of life support. Heparin is usually administered at the time of extubation or withdrawal of life support. After meeting criteria for determination of death, a two- to five-minute stand-off observation period for auto-resuscitation occurs prior to organ procurement. If lung procurement is planned, then the donor is re-intubated and the lungs inflated with positive pressure. (See 'Donation after circulatory death' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Edward Garrity, MD, MBA, who contributed to earlier versions of this topic review.