Professional Documents
Culture Documents
Organ Donation: From Diagnosis To Transplant: Review
Organ Donation: From Diagnosis To Transplant: Review
Organ Donation: From Diagnosis To Transplant: Review
CURRENT
OPINION Organ donation: from diagnosis to transplant
Chiara Robba a, Francesca Fossi b, and Giuseppe Citerio b,c
Purpose of review
Organ transplantation has largely expanded over the last decades and despite several improvements have
been made in the complex process occurring between the identification of organ donors and organ
transplant, there is still a chronic inability to meet the needs of patients. Consequently, the optimization of
the transplant process through its different steps is crucial, and the role of the intensivists is fundamental as
it requires clinical, managerial and communication skills to avoid the loss of potential donors. The purpose
of this review is to provide an update on the transplant process from the early identification of the donor, to
Downloaded from https://journals.lww.com/co-anesthesiology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3hIW04IhZ9AvNyXiDskTJpGAYXztNG71dMzsxvxmZhgI= on 04/12/2020
transplant. The two main pathways of organ donation will be discussed: donation after death by
neurologic criteria and the donation after cardiac death (DCD).
Recent findings
Recent evidence demonstrates that appropriate intensive care management is fundamental to increase organ
availability for transplantation. The expansion of pool donation requires a strong legal framework supporting
ethical and organizational considerations in each country, together with the implementation of physicians’
technical expertise and communication skills for family involvement and satisfaction. New evidence is available
regarding organ donor’s management and pathway. The importance of checklists is gaining particular interest
according to recent literature. Recent clinical trials including the use of naloxone, simvastatin and goal directed
hemodynamic therapies were not able to demonstrate a clear benefit in improving quality and number of
transplanted organs. Ethical concerns about DCD are recently being raised, and these will be discussed
focusing on the differences of outcome between controlled and uncontrolled procedure.
Summary
The major change in the process of organ donation has been to implement parallel DCD and donation
after brain death pathways. However, more research is needed for improving quality and number of
transplanted organs.
Keywords
brain death, healthcare organization, organ donation, transplant
FIGURE 1. The process from the determination of brain death or cardiac death to organ retrieval.
0952-7907 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-anesthesiology.com 147
Table 1. Pathophysiology, clinical manifestations and treatment goals for each organ damaged after brain death
Level of
Pathophysiology of injury Clinical manifestation Treatment goals evidence
Heart
Vagal and cardiomotor nuclei Hemodynamic instability Normotensive, euvolemic state (no high-level II.1
become ischemic Intense vasoconstriction: evidence regarding the use of monitoring and
Unopposed sympathetic hypertension, tachycardia, and a treatment goals, as well as of the use of fluids
stimulation secondary increase in myocardial and vasopressors/inotropes)
Loss of spinal sympathetic oxygen demand (subendocardial
pathways ischemia)
Total sympathetic denervation vasoplegia and hypotension;
electrocardiographic abnormalities
and arrhythmias
Hypothalamus and electrolyte imbalance
Loss of hypothalamic control Central diabetes insipidus (86% of Volume replacement III
cases): depletion of antidiuretic Aggressive fluids administration may have
hormone causes large loss of water detrimental effects
and diluited urine, hypernatremia Desmopressin or vasopressin is often required
and high plasma hyperosmolarity
Thyroid
Anterior and posterior pituitary Thyroid abnormalities (es. ‘sick Corticosteroids treatment may improve III
failure euthyroid syndrome’): generally hemodynamic instability and graft and recipient
low T3 levels and normal T4 levels survival
Hormones replacement suggested just when
hemodynamically unstability occurs
Thermal homeostasis
Anterior and posterior pituitary Temperature dysregulation: Reasonable to maintain core temperature at least III
failure consequence of loss of above 35 degrees
hypothalamic control and Normothermia should be maintained through
increased peripheral vasoplegia invasive or non invasive devices (including warm
Cardiovascular consequences air or water blankets and warmed intravenous
coagulopathy fluids)
Lung
Catecholamines surge Increased pressure in the pulmonary Ventilator management: lung protective ventilation II.1
Peripheral and pulmonary endothelial damage (neurogenic strategies avoiding actelectasis
vasoconstriction pulmonary edema and lung injury)
Increase pulmonary capillary
pressure
Neurogenic pulmonary edema
Coagulation and hemostasis
Release of thromboplastin from Coagulopathy, with increased risk of A threshold of 50 000/ml platelets has been III
the ischemic brain (general disseminated intravascular suggested as trigger for transfusion
prothrombotic state) coagulation and piastrinopenia International normalized ratio <1.5 before surgery
The suggested threshold for red blood cell
transfusion is similar to the targets in the general
population (specific RCTs are lacking)
Level of evidence adapted from Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 1979.
RCTs, randomized controlled trials.
careful neurological assessment, which includes the transcranial doppler. The choice should be made
evaluation of coma, and the absence of voluntary based on local and legal protocols and the specific
&&
movements and motor response to pain [6,7 ,8– characteristics of each patient (such as patients under
10,12]. The absence of brainstem activity is a core ECMO with difficulties in the transportation) [25].
component of neurological assessment. The DNC Recent evidence show promising results for CT
patient is unable to breathe and ventilation is replac- perfusion, demonstrating increased sensitivity com-
ing this function. The apnea test [13,14] is a key pared with Angio-CT [26,27]. So, CT perfusion, in
component of the DNC determination and it is addition to Angio-CT might be useful as an additional
&&
required in all countries, with some minor differ- ancillary test [28 ], especially in children [29].
ences according to individual laws. The test is con-
sidered valid and positive when the increase of
arterial partial pressure carbon dioxide (PaCO2) does Organ donation after circulatory death
not result in the activation of the respiratory centers. Organ donation after a circulatory arrest is an
The PaCO2 target of 60 mmHg, that is an increase of increasingly used strategy especially in the context
at least 20 mmHg from the baseline, is considered of a continuing shortage of DNC organ donors, and
the threshold to achieve in most countries, with the high request and need for organs to be trans-
possibly normocapnia (PaCO2 of 35–45 mmHg), planted [30]; also, it does not imply the need for
normoxia and hemodynamic stability before start- fulfilling DNC criteria. DCD can be considered
ing the test. either in cases when a cardiopulmonary resuscita-
In specific situations, these prerequisites can tion has failed or withdrawal of care is planned; in
be challenging to achieve, in particular in patient the first case, related to an unexpected cardiac arrest,
under extracorporeal membrane oxygenation it is defined as uncontrolled DCD, whereas in the
&&
(ECMO) [15 ,16], even though recent evidence sug- latter case, it is called controlled DCD.
gests that it is feasible with a low incidence of Controlled DCD includes a series of steps to
&&
complications [16,17 ]. The worldwide increasing guide the pathway to the organ donation. The first
use of ECMO for cardiac or respiratory support, and step, once end of life decision has been taken (inde-
the consequent increase of brain-dead ECMO sup- pendently from organ donation), the patient is
ported patients, is posing questions regarding the evaluated as a potential candidate. Then, according
DNC diagnosis in this group of patients. ECMO can to the local legislation, the authorization for dona-
have consequences upon the testing of brainstem tion should be obtained from the patient, who could
and in particular on apnea reflexes: pharmacoki- have previously authorized donation in case of
netic alterations can occur because of membrane death, or from the family. Then, a careful revision
sequestration and of decarboxylation that may of the patient’s medical history and conditions for
affect the performance of the apnea test. Moreover, DCD potential should be made, including donor
hemodynamic instability can result in an additional screening for compatibility and organ allocation.
difficulty in meeting the prerequisites [18]. Then end-of-life care plan is decided and withdrawal
Hemodynamic stability can be difficult to of care is planned and diagnosis of death is made
achieve and maintain during apnea test [16]; to per- with a variable ‘no-touch’ observation period of
form an apnea test under ECMO support, the fraction 5–20 min (accordingly to each country law) before
&&
of inspired oxygen to the membrane should be transferring the patient to the operating room [31 ].
increased up to 100%, and gas flow progressively In some countries, as Italy, with very long no-touch
sweeped to 1 l/min, reducing elimination of carbon period the prolongation of warm ischemia will
dioxide and allowing a typical apnea test. Apnea can require ex-vivo perfusion for a better organ function
be confirmed as absence of breathing after mechani- evaluation.
cal ventilation being discontinued; to avoid hypoxia Uncontrolled DCD is slowly gaining popularity
and derecruitment, positive end-expiratory pressure for the potential of the increasing donor pool, but at
and recruitment manoeuvres can be applied. New present not many centers in Europe have established
&& &
protocols have being developed [19 ,20 ]. specific programs, with several legal and ethical
Ancillary tests are not mandatory in all countries issues. The pathway for uncontrolled DCD starts
[21–24]. When facultative, these should be reserved with patients with certain characteristics and cardiac
for the cases when the confounding factors or seda- arrest with unsuccessful cardiopulmonary resuscita-
tion cannot be excluded, or clinical examination tion. The patient is then considered as a potential
cannot be performed appropriately or in cases of donor and is transferred to the hospital maintaining
any doubts in the tests. Several exams are available ventilation and cardiac compression. At the hospital,
including Angio-computed tomography (CT) with/ declaration of death is made and the ‘no-touch’
without CT perfusion, electroencephalography and period starts; following the determination of death,
0952-7907 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-anesthesiology.com 149
extracorporeal support is restored to maintain organ to process the bad news before even asking about the
perfusion. ECMO or other modalities of organ pres- patient consent or denial to be an organ donor.
ervation (such as ex-vivo perfusion) can be taken into The first and strongest predictor of donation
consideration as an organ preservation measure. For consent is the knowledge of the patients’ wishes
lung donation, some centers were able to transplant [45]; however, families are often not aware of the
organs without ECMO, only keeping the lung venti- patient’s wishes [46]. In these situations, communi-
lated without circulation, using a careful ex-vivo lung cation and accurate information about organ dona-
perfusion phase [32]. tion aid the decision-making; in a recent survey,
Outcomes after DCD appear controversial from among more than 100 families, only 32% could
current literature. Many previous studies show that answer questions about organ donation [47].
uncontrolled DCD has poorer outcomes than con- Also, to use the patient’s name, communication
&&
trolled DCD or death by neurological criteria [33 ]. of the news in a comfortable environment, leave
By contrary, recent publications demonstrate that room for questions, patience, kindness and atten-
function of grafts preserved by normothermic recir- tion (event just by turning off electronic devices
culation in uncontrolled DCD is better according to such as phones or pagers) will improve the chances
&& &&
long-term outcomes [34 ,35 ]. The potential of of clarity and the likeliness of a donation.
this technique is huge, with a possible increase of It is common practice in some countries to
donor by 220 007 per year in the USA [36]. separate the organ donor manager from the clini-
cian that takes care of the diagnostic process: having
two different figures can help in the process.
Family involvement: communication of death
by neurologic criteria and organ donation
Communicate DNC to families [37,38] is a compli- Management of the donor in death by
cated matter, regardless of the family’s medical neurologic criteria
background or experience. Moreover, even the Because mortality in the waiting list remains high
most informed relative can object to the diagnosis [48], a fundamental step of organ donation, once
due to moral or religious issues, or even refuse it. the potential donor has been identified and a diag-
Popular culture and the media, in general, are often nosis of death has been made, is to ensure the
imprecise and confusing [39,40]. Family members highest quality of transplantable organs, to maxi-
have the critical role in the decision process and mize the number of organs potentially available for
often can experience posttraumatic stress, anxiety donation. However, this can be challenging because
and depression. The prerequisite for organ donation of the pathophysiology of DNC and the systemic
is to obtain valid informed consent. There are changes triggered by the neurological dying
mainly two legal different consent systems, an sequence. Brainstem death leads to the so-called
opt-in (or explicit consent of the patients when sympathetic storm, with an extensive increase in
alive), and opt-out (where everybody is considered circulating catecholamine levels and systemic vaso-
a potential donor and the consent is assumed unless constriction, affecting all the organs [49].
&
otherwise specified) [41 ]. However, self-determina- Hemodynamic instability with initial hyperten-
tion is at the heart of the process and discussion, sion, tachycardia, and following vasoplegia and
&&
consisting in the knowledge and respect of the hypotension often occur [31 ], as well as electro-
patient’s wishes. cardiographic abnormalities and arrhythmias. The
The dialogue should be carefully conducted, goal of treatment is to achieve a normotensive,
clear and honest. The clinician should be well euvolemic state, but the maintenance of hemody-
informed and have clear all the steps of the diag- namic stability is challenging, and no high-level
nostic process, while also being trained to use the evidence are available regarding the use of monitor-
right words not to be misunderstood [42]. Being ing and treatment goals, as well as of the use of fluids
capable to recognize different backgrounds while and vasopressors/inotropes. Dopamine has been
being scientifically prepared will also help the prac- suggested as the catecholamine of first choice and
titioner himself to face the inevitable distress of its use may result in a lower need for dialysis [10,11];
facing the other’s grief. norepinephrine may result in increased pulmonary
Even though the process of organ donation permeability and cardiac afterload, synthetic col-
differs in each country, there are some common loids should be avoided as they may induce delayed
‘good practices’ that we can follow [30,43,44]. graft failure after renal transplantation [50].
As clinicians, we must be certain that the gravity Central diabetes insipidus is the most common
of the patient’s condition is clear from the very endocrine problem in brain-dead donors, occurring
beginning and to leave the right amount of time in up to the 86% of cases [51] and it is characterized
by a large loss of water and diluted urine, hyper- before surgery. The suggested threshold for red
natremia and high plasma hyperosmolarity, as a blood cell transfusion is similar to the targets in
consequence of depletion of antidiuretic hormone. the general population as specific RCTs are lacking
Volume replacement is suggested to ensure euvole- in this population.
mia, but aggressive fluids administration may have Finally, an extensive infection screening should
detrimental effects, and administration of desmo- be performed; bacteraemia and sepsis are not contra-
pressin or vasopressin is often required. indications to transplant, provided that an appropri-
Thyroid abnormalities, including the ‘sick ate antibiotics therapy has been initiated for 48 h [11].
euthyroid syndrome’ may occur, with generally
low T3 levels and normal T4 levels; however, the
role of hormones replacement has still to be estab- Management of the donation after cardiac
lished and it is suggested just when hemodynami- death donor
cally instability occurs [11]. In DCD we can distinguish between acceptable and
Similarly, corticosteroids treatment may improve nonacceptable interventions according to WHO [5].
hemodynamic instability and graft and recipient Blood samples, life-sustaining treatment and altering
survival, but high-quality randomized controlled the time and place of treatment withdrawal are con-
trials (RCTs) are lacking [52]. sidered as acceptable, because they are in the patient’s
Experimental studies showed that simvastatin best interests if they wished to be an organ donor
administered in the donor can be vasculoprotective without inducing any harm. On contrary, systemic
and inhibiting cardiac allograft ischemia-reperfu- heparinization, CPR and femoral cannulation can
sion injury. A recent research analyzed 84 multi- inflict distress to a patient or family and accelerate
organ donors randomly assigned to receive 80 mg of death and therefore considered non acceptable.
simvastatin and it was proved that donor simva-
statin treatment can safely and inexpensively reduce
biomarkers of myocardial injury after heart trans- Organization of the process to an organ
plantation [53 ].
&&
transplant: summary of recent evidence
Temperature dysregulation as a consequence of The success of organ donation depends on the orga-
loss of hypothalamic control and increased peripheral nization of every single step of a process that involves
vasoplegia can result in profound hypothermia with many healthcare professionals. Once the potential
consequent cardiovascular consequences and coagul- donor has been identified, several tasks have to be
opathy. However, mild hypothermia (34–358) com- quickly completed to get to the transplanting phase,
pared with normothermia (36.5–37.58) is associated and each one of these steps requires an appropriate
with improved renal function in transplanted patients training and professional development program.
[54] and it seems to be reasonable to maintain core As described above, early identification and
temperature between 35 and 37.58 [48]. Normother- management of potential donor is fundamental;
mia should be maintained through invasive or non- however, suboptimal identification and referral of
invasive devices, including warm air or water blankets potential donors can be related to several factors
&&
and warmed intravenous fluids [55 ]. including the lack of specific training; the use of
The elevation of left atrial pressure, raised checklists has shown to be useful and easy tools for
hydrostatic pressure increase in pulmonary capillary diagnosis approach (such as the ABC approach:
permeability cause increased pressure in the pulmo- Aetiology of Brain Injury, Brain death alerts, Contra-
&&
nary endothelial damage, with increasing risk of indications to donation [3 ]). Patients potentially
neurogenic pulmonary edema and lung injury eligible for donation are those with devastating
&&
[56 ]. Respiratory targets and ventilator manage- brain injury, with the suspect of DNC, as well as
ment are not clear, but the use of lung-protective patients in whom withdrawal of care has been
ventilation strategies avoiding atelectasis seems to planned or with cardiac arrest not responsive to
be a reasonable approach, especially in patients cardiopulmonary resuscitation.
eligible for transplanted lungs [57]. Once the diagnosis has been made, the following
Other systemic derangements include coagulop- step is the family approach and to obtain consent for
athy due to release of thromboplastin from the organ donation. Thereafter, donor clinical manage-
ischemic brain, with a general prothrombotic state ment to optimize donated organs becomes a priority;
which can lead do microemboli and increased risk of strategies to optimize donated organs include the use
disseminated intravascular coagulation and throm- of checklists, continuous organs evaluation, before
&&
bocytopenia [56 ]. A threshold of 50 000/ml plate- organ retrieval, ex-situ organ preservation, recondi-
lets has been suggested as a trigger for transfusion, tioning and before transplantation [58]. Some organs
and international normalized ratio less than 1.5 such as lung and hearth may not be used for
0952-7907 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-anesthesiology.com 151
NCT01974206 A Study to Evaluate the Efficacy and Safety of a Vaccine, ASP0113, Active, not Kidney transplantation cytomegalovirus 150
in Cytomegalovirus (CMV)-Seronegative Kidney Transplant recruiting (CMV) negative recipients
Recipients Receiving an Organ From a CMV-Seropositive Donor
NCT03213171 Promoting Organ Donor Registration in Family Physician Offices Active, not Organ donationjRegistration for 6
recruiting deceased organ donation
NCT03600285 Prospective, Single-Arm, Study to Assess the Safety and Performance Active, not Kidney preservation and transportation 32
of the TB1-K Device for Organ Preservation in Donor Kidneys for recruiting
Transplantation
Intensive care and resuscitation
NCT04127266 Expanding Pancreas Donor Pool by Evaluation of Unallocated Not yet Unallocated pancreas organs 100
Organs After Brain Death (EXPLORE) recruiting
www.co-anesthesiology.com
NCT03089489 Lung PGD Biomarkers in Organ Donors Not yet Lung transplant failure 50
recruiting
NCT02836301 RCT- Comparing Testimonial Versus Documentary Organ Donation Not yet Organ donation 1716
Video Education recruiting
NCT03861962 Re-evaluation of Donor-specific Anti-HLA Alloantibodies Not yet Organ transplantation 20 000
Immunoassay After Organ Transplantation, From Antigen Level to recruiting
Epitope Level
NCT03995901 A Safety and Efficacy Study of FCR001 vs. Standard of Care in de Recruiting Transplanted organ rejection 120
Novo Living Donor Kidney Transplantation
NCT02162511 CD34þ Cell Enriched and T Cell Depleted Allogeneic Stem Cell Recruiting Malignant diseasesjNonmalignant 30
Transplantation for Patients With Mismatched Related Donors or diseases
Borderline Organ Function
NCT02525510 Deceased Organ Donor Interventions to Protect Kidney Graft Recruiting Brain deathjOrgan donationjOrgan 2800
Function transplant failure or rejectionjDelayed
graft function
NCT03803423 Dissemination of the Donor Application: Utilizing Social Media to Recruiting End stage renal diseasejEnd stage liver 1000
Identify Potential Live Organ Donors disease
NCT03179020 Donation Network to Optimize Organ Recovery Study Recruiting Brain deathjOrgan donation 1200
NCT03665675 Donor CMV Specific CTLs in Treating CMV Reactivation or Infection Recruiting Allogeneic hematopoietic stem cell 20
in Participants Who Have Undergone Stem Cell Transplant or transplantation
Solid Organ Transplant recipientjCytomegalovirusjDonorjSolid
organ transplantation recipient
NCT03786991 EPI-STORM: Cytokine Storm in Organ Donors Recruiting Organ donationjLiver transplantation 105
NCT03439995 Goal of Open Lung Ventilation in Donors Recruiting Brain deathjOrgan donationjOrgan 400
NCT02109575 Quantitative Detection of Circulating Donor-Specific DNA in Organ Recruiting Cardiovascular diseasejAcute rejection 480
Transplant Recipients (DTRT-Multi-Center Study) of cardiac transplantjCardiac
transplant rejectionjHeart transplant
failure and rejection
NCT02469207 Regenerative Cellular Therapies, Physiology, Pathology and Recruiting Graft rejectionjTransplantationjDiabetes 50
Developmental Biology mellitus
NCT03984747 Study for the Prediction of Active Rejection in Organs Using Donor- Recruiting Kidney transplant rejectionjAllograft 500
derived Cell-free DNA Detection rejectionjKidney transplant;
complications
NCT03098706 Therapeutic Hypothermia in ‘Expanded Criteria’ Brain-dead Donors Recruiting Organ donorjBrain deathjKidney 516
and Kidney-graft Function transplant; complicationsjCritical
illnessjHypothermia
NCT03086044 Transplanting Hepatitis C Positive Thoracic Organs Recruiting Hepatitis CjAwaiting organ transplant 100
0952-7907 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved.
NCT03343535 Trial to Evaluate the Safety and Effectiveness of the Portable Organ Recruiting Lung transplantation 90
Care System (OCS, Ѣ) Lung System for Recruiting, Preserving
and Assessing Non-Ideal Donor Lungs for Transplantation
NCT03252795 Uterus Transplantation From a Multiorgan Donor Recruiting Infertility, femalejMayer Rokitansky 20
Kuster Hauser syndrome
153
Intensive care and resuscitation
Future directions 1. Niemann CU, Matthay MA, Ware LB. The continued need for clinical
& trials in deceased organ donor management. Transplantation 2019;
Ongoing RCTs are mainly directed toward optimiz- 103:1298–1299.
The authors describe the results of a study that compared naloxone with placebo in
ing the process of organ donation. Table 2 summa- deceased organ donors with the goal to improve oxygenation without beneficial
rized the most interesting ongoing researches effects proved.
2. Manara A, Procaccio F, Domı́nguez-Gil B. Expanding the pool of deceased
retrieved from ClinicalTrials.gov (search on 14 && organ donors: the ICU and beyond. Intensive Care Med 2019; 45:357–360.
November 2019). It is fundamental to expand the pool of organ donors trough the engagement of the
intensive and emergency care communities and an understanding of physicians’
responsibility to attempt to meet the transplantation needs of their citizens.
3. Martin-Loeches I, Sandiumenge A, Charpentier J, et al. Management of
CONCLUSION && donation after brain death (DBD) in the ICU: the potential donor is identified,
what’s next? Intensive Care Med 2019; 45:322–330.
There is still the current inability to meet the trans- The article underlines the main steps of organ donation from early identification to organ
donor management, remarking the importance of developing research in this field.
plant needs of patients. The intensivist plays a 4. Robba C, Iaquaniello C, Citerio G. Death by neurologic criteria: pathophy-
crucial role in the pathway leading to organ donation & siology, definition, diagnostic criteria and tests. Minerva Anestesiol 2019;
85:774–781.
and its steps, which are often challenging and The authors discuss the pathophysiology and definition of death by neurological
complex. From potential donor identification to criteria with a particular attention on ancillary testing.
5. WHO j Human organ transplantation [Internet]. WHO. Available from: https://
the diagnosis of death, organ preservation and the www.who.int/transplantation/organ/en/. [Cited 1 November 2019].
activation of the process leading to transplant, 6. Carmona M. Newsletter transplant 2019 [Internet]. GODT. Available from:
http://www.transplant-observatory.org/download/newsletter-transplant-
clinical communicational and managerial skills are 2019/. [Cited 2 November 2019].
required. Maintenance of organ preservation and 7. Westphal GA, Robinson CC, Biasi A, et al. DONORS (Donation Network to
Optimise Organ Recovery Study): study protocol to evaluate the implementa-
clinical management of patients with DNC is funda- &&
16. Giani M, Scaravilli V, Colombo SM, et al. Apnea test during brain death 38. Bocci MG, D’Alò C, Barelli R, et al. Taking care of relationships in the intensive
assessment in mechanically ventilated and ECMO patients. Intensive Care care unit: positive impact on family consent for organ donation. Transplant
Med 2016; 42:72–81. Proc 2016; 48:3245–3250.
17. Ihle J, Burrell A. Confirmation of brain death on VA-ECMO should mandate 39. Daoust A, Racine E. Depictions of ‘brain death’ in the media: medical and
&& simultaneous distal arterial and postoxygenator blood gas sampling. Intensive ethical implications. J Med Ethics 2014; 40:253–259.
Care Med 2019; 45:1165–1166. 40. Lewis A, Lord AS, Czeisler BM, Caplan A. Public education and misinforma-
Authors explain protocols for diagnosis of brain death on venous arterial (VA)-ECMO. tion on brain death in mainstream media. Clin Transplant 2016;
18. Saucha W, Sołek-Pastuszka J, Bohatyrewicz R, Knapik P. Apnea test in 30:1082–1089.
the determination of brain death in patients treated with extracorporeal mem- 41. Kentish-Barnes N, Siminoff LA, Walker W, et al. A narrative review of family
brane oxygenation (ECMO). Anaesthesiol Intensive Ther 2015; 47:368–371. & members’ experience of organ donation request after brain death in the critical
19. Ihle JF, Burrell AJC, Philpot SJ, et al. A protocol that mandates postoxygenator care setting. Intensive Care Med 2019; 45:331–342.
&& and arterial blood gases to confirm brain death on venoarterial extracorporeal In this review, clinicians, and researchers describe the legal systems regarding
membrane oxygenation. ASAIO J 2019. [Epub ahead of print] family implication in organ donation decisions and factors influencing the decision-
Authors explain a new protocol to assess brain death on patients supported by VA- making process. Finally, they suggest communication skills and support to be
ECMO. developed.
20. Lie SA, Hwang NC. Challenges of brain death and apnea testing in adult 42. Youngner SJ. How to communicate clearly about brain death and first-person
& patients on extracorporeal membrane oxygenation-a review. J Cardiothorac consent to donate. AMA J Ethics 2016; 18:108–114.
Vasc Anesth 2019; 33:2266–2272. 43. Ghorbani F, Khoddami-Vishteh HR, Ghobadi O, et al. Causes of family refusal
This is a review about recent evidence on apnea testing in patients supported by for organ donation. Transplant Proc 2011; 43:405–406.
VA ECMO. 44. Procaccio F, Rizzato L, Ricci A, et al. Do ‘silent’ brain deaths affect potential
21. Haupt WF, Rudolf J. European brain death codes: a comparison of national organ donation? Transplant Proc 2010; 42:2190–2191.
guidelines. J Neurol 1999; 246:432–437. 45. Frutos MA, Blanca MJ, Mansilla JJ, et al. Organ donation: a comparison of
22. Chua HC, Kwek TK, Morihara H, Gao D. Brain death: the Asian perspective. donating and nondonating families. Transplant Proc 2005; 37:1557–1559.
Semin Neurol 2015; 35:152–161. 46. Organ donation statistics j organ donor [Internet]. Available from: http://
23. Citerio G, Murphy PG. Brain death: the European perspective. Semin Neurol www.organdonor.gov/statistics-stories/statistics.html. [Cited 18 September
2015; 35:139–144. 18 2019].
24. Shemie SD, Baker A. Uniformity in brain death criteria. Semin Neurol 2015; 47. Michetti CP, Newcomb A, Thota V, Liu C. Organ donation education in the
35:162–168. ICU setting: a qualitative and quantitative analysis of family preferences. J Crit
25. Greer DM, Wang HH, Robinson JD, et al. Variability of brain death policies in Care 2018; 48:135–139.
the United States. JAMA Neurol 2016; 73:213–218. 48. Tullius SG, Rabb H. Improving the supply and quality of deceased-donor
26. Shankar JJS, Vandorpe R. CT perfusion for confirmation of brain death. AJNR organs for transplantation. N Engl J Med 2018; 378:1920–1929.
Am J Neuroradiol 2013; 34:1175–1179. 49. Lee VH, Oh JK, Mulvagh SL, Wijdicks EFM. Mechanisms in neurogenic stress
27. Escudero D, Otero J, Marqués L, et al. Diagnosing brain death by CT perfusion cardiomyopathy after aneurysmal subarachnoid hemorrhage. Neurocrit Care
and multislice CT angiography. Neurocrit Care 2009; 11:261–271. 2006; 5:243–249.
28. Gastala J, Fattal D, Kirby PA, et al. Brain death: radiologic signs of a 50. Patel MS, Niemann CU, Sally MB, et al. The impact of hydroxyethyl starch use
&& nonradiologic diagnosis. Clin Neurol Neurosurg 2019; 185:105465. in deceased organ donors on the development of delayed graft function in
Authors trace all the radiologic evaluations either mandatory or helpful as ancillary kidney transplant recipients: a propensity-adjusted analysis. Am J Transplant
testing to diagnose brain death. 2015; 15:2152–2158.
29. Pellón R, de Lucas EM, Fernández CG, et al. Usefulness of addition of CT 51. Maciel CB, Greer DM. ICU management of the potential organ donor: state of
perfusion to CT angiography for brain death diagnosis in a child. Neurope- the art. Curr Neurol Neurosci Rep 2016; 16:86.
diatrics 2010; 41:189–192. 52. Dupuis S, Amiel J-A, Desgroseilliers M, et al. Corticosteroids in the manage-
30. Sandroni C, D’Arrigo S, Callaway CW, et al. The rate of brain death and organ ment of brain-dead potential organ donors: a systematic review. Br J Anaesth
donation in patients resuscitated from cardiac arrest: a systematic review and 2014; 113:346–359.
meta-analysis. Intensive Care Med 2016; 42:1661–1671. 53. Nykänen AI, Holmström EJ, Tuuminen R, et al. Donor simvastatin treatment in
31. Smith M, Dominguez-Gil B, Greer DM, et al. Organ donation after circulatory && heart transplantation. Circulation 2019; 140:627–640.
&& death: current status and future potential. Intensive Care Med 2019; The trial show the potential beneficial effect of simvastatin administered in the
45:310–321. donor, without risky effects but with important beneficial effects in reducing
The review explain the two pathways of controlled and uncontrolled donation after biomarker of myocardial inflammation after heart transplantation.
cardiac death (DCD), with considerations to minimize warm and cold ischemia 54. Niemann CU, Broglio K, Malinoski D. Comments on ‘Impact of spontaneous
times. Finally authors address the potential ethical concerns of this procedure. donor hypothermia on graft outcomes after kidney transplantation’. Am J
32. Valenza F, Citerio G, Palleschi A, et al. Successful transplantation of lungs Transplant 2018; 18:763.
from an uncontrolled donor after circulatory death preserved in situ by alveolar 55. Malinoski D, Patel MS, Axelrod DA, et al. Therapeutic hypothermia in
recruitment maneuvers and assessed by ex vivo lung perfusion. Am J Trans- && organ donors: follow-up and safety analysis. Transplantation 2019;
plant 2016; 16:1312–1318. 103:e365–e368.
33. Lomero M, Gardiner D, Coll E, et al. Donation after circulatory death today: an Mild hypothermia in the donor safely reduced the rate of delayed graft function in
&& updated overview of the European landscape. Transpl Int 2019. [Epub ahead kidney transplant recipients without adversely affecting donor physiology or
of print] extrarenal graft survival.
The article describes the updated state of art about DCD in Europe, in particular 56. Meyfroidt G, Gunst J, Martin-Loeches I, et al. Management of the brain-dead
author outline the contribution of DCD to increase the number of organs available. && donor in the ICU: general and specific therapy to improve transplantable
34. Delsuc C, Faure A, Berthiller J, et al. Uncontrolled donation after circulatory organ quality. Intensive Care Med 2019; 45:343–353.
&& death: comparison of two kidney preservation protocols on graft outcomes. The article provides an overview about the management of the potential organ
BMC Nephrol 2018; 19:3. donor in ICU. The authors speak about how to deal with cardiorespiratory
Function of kidney-grafts preserved by normothermic recirculation resulted better management, electrolites’ derangements, anemia, coagulopathy, temperature
in long-term outcomes. management and infections.
35. Sánchez-Fructuoso AI, Pérez-Flores I, Del Rı́o F, et al. Uncontrolled donation 57. Mascia L, Pasero D, Slutsky AS, et al. Effect of a lung protective strategy for
&& after circulatory death: a cohort study of data from a long-standing deceased- organ donors on eligibility and availability of lungs for transplantation: a
donor kidney transplantation program. Am J Transplant 2019; 19:1693–1707. randomized controlled trial. JAMA 2010; 304:2620–2627.
The study confirms that in uncontrolled donation after circulatory death can expand 58. Hunter JP, Ploeg RJ. An exciting new era in donor organ preservation and
the kidney donor pool. transplantation: assess, condition, and repair! Transplantation 2016;
36. Medicine I of organ donation: opportunities for action [Internet]. 2006. 100:1801–1802.
Available from: https://www.nap.edu/catalog/11643/organ-donation-oppor- 59. Domı́nguez-Gil B, Murphy P, Procaccio F. Ten changes that could improve
tunities-for-action. [Cited 18 September 2019]. organ donation in the intensive care unit. Intensive Care Med 2016;
37. Kompanje EJO. Families and brain death. Semin Neurol 2015; 35:169–173. 42:264–267.
0952-7907 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-anesthesiology.com 155