Non-heart beating donation
Encyclopedia
Prior to the introduction of brain-stem death
into law in the mid to late 1970s, all organ transplant
s from cadaveric donors came from non-heart beating donors (NHBD).
Brain-stem dead donors (beating heart cadaver
s), however, led to better results as the organs were perfused with oxygenated blood until the point of perfusion and cooling at organ retrieval, and so non-heart beating donors were generally no longer used except in Japan, where brain-stem death was not legally (until very recently) or culturally (still) recognized.
However, a growing discrepancy between demand for organs and their availability from brain-stem dead donors has led to a re-examination of using non-heart beating donors, and many centres are now using such donors to expand their potential pool of organs.
Tissue donation (cornea
s, heart valve
s, skin
, bone
) has always been possible for non-heart beating donors, and many centres now have established programmes for kidney
transplants from such donors. A few centres have also moved into NHBD liver
and lung
transplants. Many lessons have been learnt since the 1970s, and results from current NHBD transplants are comparable to transplants from brain-stem dead donors.
Categories I, II and V are termed uncontrolled and categories III and IV are controlled. Only tissues such as heart valves and corneas can be taken from category I donors. Category II donors are patients who have had a witnessed cardiac arrest outside hospital, have cardiopulmonary resuscitation by CPR-trained providers commenced within 10 minutes but who cannot be successfully resuscitated. Category III donors are patients on intensive care
units with non-survivable injuries who have treatment withdrawn; where such patients wished in life to be organ donors, the transplant team can attend at the time of treatment withdrawal and retrieve organs after cardiac arrest has occurred.
can potentially be used from category III, IV and V donors. An unsuccessful kidney recipient can remain on dialysis
, unlike recipients of some other organs, meaning that a failure will not result in death.
Kidneys from uncontrolled (category II) donors must be assessed with care as there is otherwise a high rate of failure. Many centres have protocols for formal viability assessment. Relatively few centres worldwide retrieve such kidneys, and leaders in this field include the transplant units in Maastricht
(the Netherlands
), Newcastle upon Tyne
and Leicester
(United Kingdom
), Madrid
and Barcelona
(Spain
), Pavia
(Italy
) and Washington, DC (United States
).
Livers and lungs for transplant can only be taken from controlled donors, and are still somewhat experimental as they have only been performed successfully in relatively few centres. In the United Kingdom
, NHBD liver transplants are currently performed in Addenbrooke's Hospital
Cambridge
, Queen Elizabeth Hospital
Birmingham
, King's College Hospital
London
, Leeds
, Newcastle upon Tyne
and the Scottish Liver Transplant Unit in Edinburgh. The International Meeting on Transplantation from Non-Heart Beating Donors is organised in the UK every 2 years and brings together specialists in transplantation including transplant physicians, surgeons, fellows, nurses, coordinators, intensive care physicians, perfusion technicians, ethicists, and researchers interested in the aspects of retrieval, preservation and transplantation of DCD thoracic and abdominal organs and cells.
Lectures are held by experts on the most challenging themes such as clinical outcomes of transplantation of controlled and uncontrolled
DCD organs, progress made on machine perfusion of kidneys, livers, lungs and hearts and ethics and legal issues regarding donation after cardiac death.
Once the stand-off period has elapsed, a cut down is performed over the femoral artery, and a double-balloon triple-lumen (DBTL) catheter is inserted into the femoral artery
and passed into the aorta
. The balloons are inflated to occlude the aorta above and below the renal arteries (any donor blood specimens required can be taken before the top balloon is inflated). A pre-flush with streptokinase
or another thrombolytic
is given through the catheter, followed by 20 litres of cold kidney perfusion fluid; the opening of the lumen is between the balloons so that most of the flush and perfusion fluid goes into the kidneys. Another catheter is inserted into the femoral vein to allow venting of the fluid.
Once full formal consent for organ donation has been obtained from relatives, and other necessary formalities such as identification of the deceased by the police and informing the Coroner
(in the UK
), the donor is taken to the operating room, and the kidneys and heart valves retrieved.
If only the kidneys are suitable for retrieval, either rapid retrieval or cannulation with DBTL catheter can be used. Use of a DBTL catheter allows relatives of the deceased to see them after death, but the donor must be taken to the operating room as soon as possible.
The formalities necessary for donation can usually be carried out prior to treatment withdrawal in controlled donation, so early retrieval should be possible.
Category IV donors (who are already brain-stem dead), should either proceed as for a normal multi-organ retrieval – if this has already started – or should be managed as a category II or III as appropriate to the circumstances of cardiac arrest.
There is not as much long-term data for NHBD liver transplants, but published results are promising. Unlike in kidneys, where delayed graft function simply means a need for dialysis
, delayed graft function in livers can be fatal, which is why only controlled donors are used for livers. Intra-hepatic biliary strictures are a complication more common in NHBD livers than in brain-stem dead donors. Many transplant surgeons feel that NHBD livers should not be used to transplant acutely sick patients with acute liver failure.
Long-term data on NHBD lung transplants is not yet available.
The latest results of transplants of NHBD/DCD organs are presented every 2 years at the International Meeting on Transplantation from Non-Heart Beating Donors, which is held in London since 2002.
In 2010 the 5th International Meeting on Transplantation from Non-Heart Beating Donors (NHBD2010) will be held in London on the 13-15 May in conjunction with the European Liver and Intestine Transplant Association (ELITA) Annual Meeting.
In category II uncontrolled donors, the donor may die and the transplant team arrive before the donor's next-of-kin can be contacted. It is controversial whether cannulation and perfusion can be started in these circumstances. On one hand, it can be considered a violation of the potential donor's autonomy to cannulate before their in-life wishes are known. On the other hand, delay in cannulation may mean that a patient's strongly held wish to be donor cannot be respected. Many ethicists also feel that a doctor's duty of care to the still living outweighs any duty of care to the dead. The compromise reached is usually to cannulate if there is any evidence of a wish to donate (such as a donor card or registration as a donor) even in the absence of next-of-kin.
For category III donors, treatment is being withdrawn from a living person, who will then die and become a donor. It is important that the decisions that injuries are non-survivable, continued treatment is futile and that withdrawal is in the patient's best interests be made completely independently of any consideration of suitability as an organ donor. Only after such decisions have been firmly made should a patient be considered as a potential organ donor. Although such treatment can be continued until the transplant team arrive, no additional treatment should be started to improve the organs – until the point of death, the patient should be treated exactly as any other dying patient.
In recent years this has been termed Donation after Cardiac Death (DCD) or Donation after Cardiac Determination of Death (DCDD) in the United States, although Non-Heart Beating Donation is the more widely used term internationally.
Brain death
Brain death is the irreversible end of all brain activity due to total necrosis of the cerebral neurons following loss of brain oxygenation. It should not be confused with a persistent vegetative state...
into law in the mid to late 1970s, all organ transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
s from cadaveric donors came from non-heart beating donors (NHBD).
Brain-stem dead donors (beating heart cadaver
Beating heart cadaver
A beating heart cadaver is a human body that though dead in all medical and legal definitions is attached to a medical ventilator and retains cardio-pulmonary functions. This will keep the organs of the dead body, including the heart, functioning and alive for a few days...
s), however, led to better results as the organs were perfused with oxygenated blood until the point of perfusion and cooling at organ retrieval, and so non-heart beating donors were generally no longer used except in Japan, where brain-stem death was not legally (until very recently) or culturally (still) recognized.
However, a growing discrepancy between demand for organs and their availability from brain-stem dead donors has led to a re-examination of using non-heart beating donors, and many centres are now using such donors to expand their potential pool of organs.
Tissue donation (cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
s, heart valve
Heart valve
A heart valve normally allows blood flow in only one direction through the heart. The four valves commonly represented in a mammalian heart determine the pathway of blood flow through the heart...
s, skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
) has always been possible for non-heart beating donors, and many centres now have established programmes for kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
transplants from such donors. A few centres have also moved into NHBD liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
transplants. Many lessons have been learnt since the 1970s, and results from current NHBD transplants are comparable to transplants from brain-stem dead donors.
Maastricht classification
NHBDs are grouped by the Maastricht classification:| I | Brought in dead |  |
uncontrolled |
| II | Unsuccessful resuscitation | ||
| III | Awaiting cardiac arrest |  |
controlled |
| IV | Cardiac arrest after brain-stem death | ||
| V | Cardiac arrest in a hospital inpatient | uncontrolled (added in 2000) | |
Categories I, II and V are termed uncontrolled and categories III and IV are controlled. Only tissues such as heart valves and corneas can be taken from category I donors. Category II donors are patients who have had a witnessed cardiac arrest outside hospital, have cardiopulmonary resuscitation by CPR-trained providers commenced within 10 minutes but who cannot be successfully resuscitated. Category III donors are patients on intensive care
Intensive care medicine
Intensive-care medicine or critical-care medicine is a branch of medicine concerned with the diagnosis and management of life threatening conditions requiring sophisticated organ support and invasive monitoring.- Overview :...
units with non-survivable injuries who have treatment withdrawn; where such patients wished in life to be organ donors, the transplant team can attend at the time of treatment withdrawal and retrieve organs after cardiac arrest has occurred.
Organs that can be used
Kidneys can be used from category II donors, and all organs except the heartHeart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
can potentially be used from category III, IV and V donors. An unsuccessful kidney recipient can remain on dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
, unlike recipients of some other organs, meaning that a failure will not result in death.
Kidneys from uncontrolled (category II) donors must be assessed with care as there is otherwise a high rate of failure. Many centres have protocols for formal viability assessment. Relatively few centres worldwide retrieve such kidneys, and leaders in this field include the transplant units in Maastricht
Maastricht
Maastricht is situated on both sides of the Meuse river in the south-eastern part of the Netherlands, on the Belgian border and near the German border...
(the Netherlands
Netherlands
The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
), Newcastle upon Tyne
Newcastle upon Tyne
Newcastle upon Tyne is a city and metropolitan borough of Tyne and Wear, in North East England. Historically a part of Northumberland, it is situated on the north bank of the River Tyne...
and Leicester
Leicester
Leicester is a city and unitary authority in the East Midlands of England, and the county town of Leicestershire. The city lies on the River Soar and at the edge of the National Forest...
(United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
), Madrid
Madrid
Madrid is the capital and largest city of Spain. The population of the city is roughly 3.3 million and the entire population of the Madrid metropolitan area is calculated to be 6.271 million. It is the third largest city in the European Union, after London and Berlin, and its metropolitan...
and Barcelona
Barcelona
Barcelona is the second largest city in Spain after Madrid, and the capital of Catalonia, with a population of 1,621,537 within its administrative limits on a land area of...
(Spain
Spain
Spain , officially the Kingdom of Spain languages]] under the European Charter for Regional or Minority Languages. In each of these, Spain's official name is as follows:;;;;;;), is a country and member state of the European Union located in southwestern Europe on the Iberian Peninsula...
), Pavia
Pavia
Pavia , the ancient Ticinum, is a town and comune of south-western Lombardy, northern Italy, 35 km south of Milan on the lower Ticino river near its confluence with the Po. It is the capital of the province of Pavia. It has a population of c. 71,000...
(Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
) and Washington, DC (United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
).
Livers and lungs for transplant can only be taken from controlled donors, and are still somewhat experimental as they have only been performed successfully in relatively few centres. In the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, NHBD liver transplants are currently performed in Addenbrooke's Hospital
Addenbrooke's Hospital
Addenbrooke's Hospital is an internationally renowned teaching hospital in Cambridge, England, with strong links to the University of Cambridge. It was founded in 1766 on Trumpington Street with £4,500 from the will of Dr John Addenbrooke, a fellow of St Catharine's College...
Cambridge
Cambridge
The city of Cambridge is a university town and the administrative centre of the county of Cambridgeshire, England. It lies in East Anglia about north of London. Cambridge is at the heart of the high-technology centre known as Silicon Fen – a play on Silicon Valley and the fens surrounding the...
, Queen Elizabeth Hospital
Queen Elizabeth Hospital
Queen Elizabeth Hospital or Queen Elizabeth's Hospital can refer to one of several institutions named after Queen Elizabeth I, Queen Elizabeth II or Queen Elizabeth the Queen Mother:Australia*Queen Elizabeth Hospital, AdelaideBarbados...
Birmingham
Birmingham
Birmingham is a city and metropolitan borough in the West Midlands of England. It is the most populous British city outside the capital London, with a population of 1,036,900 , and lies at the heart of the West Midlands conurbation, the second most populous urban area in the United Kingdom with a...
, King's College Hospital
King's College Hospital
King's College Hospital is an acute care facility in the London Borough of Lambeth, referred to locally and by staff simply as "King's" or abbreviated internally to "KCH"...
London
London
London is the capital city of :England and the :United Kingdom, the largest metropolitan area in the United Kingdom, and the largest urban zone in the European Union by most measures. Located on the River Thames, London has been a major settlement for two millennia, its history going back to its...
, Leeds
Leeds
Leeds is a city and metropolitan borough in West Yorkshire, England. In 2001 Leeds' main urban subdivision had a population of 443,247, while the entire city has a population of 798,800 , making it the 30th-most populous city in the European Union.Leeds is the cultural, financial and commercial...
, Newcastle upon Tyne
Newcastle upon Tyne
Newcastle upon Tyne is a city and metropolitan borough of Tyne and Wear, in North East England. Historically a part of Northumberland, it is situated on the north bank of the River Tyne...
and the Scottish Liver Transplant Unit in Edinburgh. The International Meeting on Transplantation from Non-Heart Beating Donors is organised in the UK every 2 years and brings together specialists in transplantation including transplant physicians, surgeons, fellows, nurses, coordinators, intensive care physicians, perfusion technicians, ethicists, and researchers interested in the aspects of retrieval, preservation and transplantation of DCD thoracic and abdominal organs and cells.
Lectures are held by experts on the most challenging themes such as clinical outcomes of transplantation of controlled and uncontrolled
DCD organs, progress made on machine perfusion of kidneys, livers, lungs and hearts and ethics and legal issues regarding donation after cardiac death.
Procedure for uncontrolled donors
Following declaration of death, cardiopulmonary resusciation (CPR) is continued until the transplant team arrive. A stand-off period is observed after cessation of CPR to ensure that death has occurred; this is usually from 5 to 10 minutes in length and varies according to local protocols.Once the stand-off period has elapsed, a cut down is performed over the femoral artery, and a double-balloon triple-lumen (DBTL) catheter is inserted into the femoral artery
Femoral artery
The femoral artery is a general term comprising a few large arteries in the thigh. They begin at the inguinal ligament and end just above the knee at adductor canal or Hunter's canal traversing the extent of the femur bone....
and passed into the aorta
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
. The balloons are inflated to occlude the aorta above and below the renal arteries (any donor blood specimens required can be taken before the top balloon is inflated). A pre-flush with streptokinase
Streptokinase
Streptokinase , a protein secreted by several species of streptococci can bind and activate human plasminogen. SK is used as an effective and inexpensive thrombolysis medication in some cases of myocardial infarction and pulmonary embolism...
or another thrombolytic
Thrombolysis
Thrombolysis is the breakdown of blood clots by pharmacological means. It is colloquially referred to as clot busting for this reason...
is given through the catheter, followed by 20 litres of cold kidney perfusion fluid; the opening of the lumen is between the balloons so that most of the flush and perfusion fluid goes into the kidneys. Another catheter is inserted into the femoral vein to allow venting of the fluid.
Once full formal consent for organ donation has been obtained from relatives, and other necessary formalities such as identification of the deceased by the police and informing the Coroner
Coroner
A coroner is a government official who* Investigates human deaths* Determines cause of death* Issues death certificates* Maintains death records* Responds to deaths in mass disasters* Identifies unknown dead* Other functions depending on local laws...
(in the UK
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
), the donor is taken to the operating room, and the kidneys and heart valves retrieved.
Procedure for controlled donors
If the liver or lungs are felt to be suitable for transplantation, then the donor is usually taken directly to the operating room after cardiac arrest, and a rapid retrieval operation is performed once a 10 minute stand-off period has elapsed. It seems this stand-off period has been reduced to as short as 75 seconds based on a recent article by the CBC. http://www.cbc.ca/health/story/2008/08/13/cardiac-death-donations.html. This is now causing an ethical debate as to whether physicians will declare death sooner than is currently required. This is similar to a normal multi-organ retrieval, but prioritises rapid cannulation, perfusion and cooling with ice, with dissection following later.If only the kidneys are suitable for retrieval, either rapid retrieval or cannulation with DBTL catheter can be used. Use of a DBTL catheter allows relatives of the deceased to see them after death, but the donor must be taken to the operating room as soon as possible.
The formalities necessary for donation can usually be carried out prior to treatment withdrawal in controlled donation, so early retrieval should be possible.
Category IV donors (who are already brain-stem dead), should either proceed as for a normal multi-organ retrieval – if this has already started – or should be managed as a category II or III as appropriate to the circumstances of cardiac arrest.
Results of NHBD transplantation
NHBD kidney transplantation, from both controlled and uncontrolled donors, has been shown to have almost identical graft survival times and long-term function as kidneys from brain-stem dead donors. In the short-term they are prone to delayed graft function of around 7–14 days (this does not affect long term function in NHBD kidneys) and have a failure rate of around 5-10% (compared to 3-5% for kidneys from brain-stem dead donors).There is not as much long-term data for NHBD liver transplants, but published results are promising. Unlike in kidneys, where delayed graft function simply means a need for dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
, delayed graft function in livers can be fatal, which is why only controlled donors are used for livers. Intra-hepatic biliary strictures are a complication more common in NHBD livers than in brain-stem dead donors. Many transplant surgeons feel that NHBD livers should not be used to transplant acutely sick patients with acute liver failure.
Long-term data on NHBD lung transplants is not yet available.
The latest results of transplants of NHBD/DCD organs are presented every 2 years at the International Meeting on Transplantation from Non-Heart Beating Donors, which is held in London since 2002.
In 2010 the 5th International Meeting on Transplantation from Non-Heart Beating Donors (NHBD2010) will be held in London on the 13-15 May in conjunction with the European Liver and Intestine Transplant Association (ELITA) Annual Meeting.
Ethical issues
Certain ethical issues are raised by NHBD transplantation, and require due sensitivity to ensure that ethical standards are maintained.In category II uncontrolled donors, the donor may die and the transplant team arrive before the donor's next-of-kin can be contacted. It is controversial whether cannulation and perfusion can be started in these circumstances. On one hand, it can be considered a violation of the potential donor's autonomy to cannulate before their in-life wishes are known. On the other hand, delay in cannulation may mean that a patient's strongly held wish to be donor cannot be respected. Many ethicists also feel that a doctor's duty of care to the still living outweighs any duty of care to the dead. The compromise reached is usually to cannulate if there is any evidence of a wish to donate (such as a donor card or registration as a donor) even in the absence of next-of-kin.
For category III donors, treatment is being withdrawn from a living person, who will then die and become a donor. It is important that the decisions that injuries are non-survivable, continued treatment is futile and that withdrawal is in the patient's best interests be made completely independently of any consideration of suitability as an organ donor. Only after such decisions have been firmly made should a patient be considered as a potential organ donor. Although such treatment can be continued until the transplant team arrive, no additional treatment should be started to improve the organs – until the point of death, the patient should be treated exactly as any other dying patient.
In recent years this has been termed Donation after Cardiac Death (DCD) or Donation after Cardiac Determination of Death (DCDD) in the United States, although Non-Heart Beating Donation is the more widely used term internationally.