|Year : 2022 | Volume
| Issue : 1 | Page : 26-41
Organ donation after circulatory determination of death in India: A joint position paper
Avnish Kumar Seth1, Ravi Mohanka2, Sumana Navin3, Alla Gopala Krishna Gokhale4, Ashish Sharma5, Anil Kumar6, Bala Ramachandran7, KR Balakrishnan8, Darius F Mirza9, Dhvani Mehta10, Kapil G Zirpe11, Kumud Dhital12, Manisha Sahay13, Srinagesh Simha14, Radha Sundaram15, Rahul Anil Pandit16, Raj Kumar Mani17, Roop Gursahani18, Subhash Gupta19, Vivek Kute20, Sunil Shroff21
1 Manipal Organ Sharing and Transplant (MOST), Manipal Hospital, New Delhi, India
2 HN Reliance Foundation Hospital, Mumbai; Liver Transplant Society of India, India
3 Division of Training and Education, MOHAN Foundation, Chennai, Tamil Nadu, India
4 Department of Intensive Care and Emergency Medicine, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, Tamil Nadu, India
5 Department of Renal Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
6 Ministry of Health and Family Welfare, Government of India, Delhi, India
7 Department of Cardio-thoracic Surgery, Apollo Hospitals, Chennai, Tamil Nadu, India
8 Department of Cardio-thoracic Surgery, MGM Healthcare, Chennai, Tamil Nadu, India
9 Department of Hepato-biliary Surgery, Apollo Hospital, Navi Mumbai, Maharashtra, India
10 Vidhi Centre for Legal Policy, Delhi, India
11 Department of Neuro Trauma Unit, Grant Medical Foundation, Ruby Hall Clinic, Pune, Maharashtra, India
12 Department Heart and Lung Transplantation, SPARSH Hospitals, Bengaluru, Karnataka, India
13 Department of Nephrology, Osmania Medical College and General Hospital, Hyderabad, Telangana, India
14 Karunashraya Hospice, Bengaluru, Karnataka, India
15 NHS Blood and Transplant, Scotland, UK
16 Department of Intensive Care, Fortis Hospital, Mumbai, Maharashtra, India
17 Department of Critical Care and Pulmonology, Yashoda Super Specialty Hospital, Kaushambi, Ghaziabad, Uttar Pradesh, India
18 Department of Neurology, P.D. Hinduja National Hospital, Mumbai, Maharashtra, India
19 Max Centre for Liver and Biliary Sciences, Max Saket Hospital, New Delhi, India
20 Department of Nephrology, Institute of Kidney Diseases and Research Center, Dr H.L. Trivedi Institute of Transplantation Sciences (IKDRCITS), Ahmedabad, Gujarat, India
21 MOHAN Foundation, Chennai, Tamil Nadu; Indian Society of Organ Transplantation, India
|Date of Submission||16-Jun-2021|
|Date of Acceptance||19-Jan-2022|
|Date of Web Publication||31-Mar-2022|
MOHAN Foundation, 3rd Floor, Toshniwal Building, 267, Kilpauk Garden Road, Chennai - 600 010, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Organ donation following circulatory determination of death (DCDD) has contributed significantly to the donor pool in several countries, without compromising the outcomes of transplantation or the number of donations following brain death (BD). In India, majority of deceased donations happen following BD. While existing legislation allows for DCDD, there have been only a few reports of kidney transplantation following DCDD from the country. This document, prepared by a multi-disciplinary group of experts, reviews the international best practices in DCDD and outlines the path for furthering the same in India. The ethical, medical, legal, economic, procedural, and logistic challenges unique to India for all types of DCDD based on the Modified Maastricht Criteria have been addressed. India follows an opt-in system for organ donation that does not allow much scope for uncontrolled DCDD categories I and II. The practice of withdrawal of life-sustaining treatment (WLST) in India is in its infancy. The process of WLST, laid down by the Supreme Court of India, is considered time-consuming, possible only in patients in a permanent vegetative state, and considered too cumbersome for day-to-day practice. In patients where continued medical care is determined to be futile following detailed and repeated assessment, the procedure for WLST, as laid down and published by Vidhi Centre for Legal Policy in conjunction with leading medical experts is described. In controlled DCDD (category-III), the decision for WLST is independent of and delinked from the subsequent possibility of organ donation. Once families are inclined toward organ donation, they are explained the procedure including the timing and location of WLST, consent for antemortem measures, no-touch period, and the possibility of stand down and return to the intensive care unit without donation. While donation following neurologic determination of death (DNDD) is being increasingly practiced in the country, there are instances where the cardiac arrest occurs during the process of declaration of BD, before organ retrieval has been done. Protocol for DCDD category-IV deals with such situations and is described in detail. In DCDD category V, organ donation may be possible following unsuccessful cardiopulmonary resuscitation of cardiac arrest in the intensive care. An outline of organ-specific requisites for kidney, liver, heart, and lung transplantation following DCDD and the use of techniques such as normothermic regional perfusion and ex vivo machine perfusion has been provided. With increasing experience, the outcomes of transplantation following DCDD are comparable to those following DBDD or living donor transplantation. Documents and checklists necessary for the successful execution of DCDD in India are described.
Keywords: Deceased donations, donation after circulatory determination of death, donation after neurologic determination of death, living donor transplantation
|How to cite this article:|
Seth AK, Mohanka R, Navin S, Gokhale AG, Sharma A, Kumar A, Ramachandran B, Balakrishnan K R, Mirza DF, Mehta D, Zirpe KG, Dhital K, Sahay M, Simha S, Sundaram R, Pandit RA, Mani RK, Gursahani R, Gupta S, Kute V, Shroff S. Organ donation after circulatory determination of death in India: A joint position paper. Indian J Transplant 2022;16:26-41
|How to cite this URL:|
Seth AK, Mohanka R, Navin S, Gokhale AG, Sharma A, Kumar A, Ramachandran B, Balakrishnan K R, Mirza DF, Mehta D, Zirpe KG, Dhital K, Sahay M, Simha S, Sundaram R, Pandit RA, Mani RK, Gursahani R, Gupta S, Kute V, Shroff S. Organ donation after circulatory determination of death in India: A joint position paper. Indian J Transplant [serial online] 2022 [cited 2022 Dec 8];16:26-41. Available from: https://www.ijtonline.in/text.asp?2022/16/1/26/342440
| Introduction|| |
The Global Observatory on Organ Donation and Transplantation data indicates that 12,666 organ transplants were carried out in India in 2019, next only to the United States and China [Figure 1]. Despite the rising numbers, this accounts for <10 transplants per million population (PMP) compared to more than 100 transplants PMP in the USA. Majority of transplants in India were done from living kidney and liver donors and less than one-fifth from deceased donors. Most deceased donor transplants were from donation after brain stem death, hereafter referred to as brain death (BD) and recently called donation after neurologic determination of death (DNDD)., In India, the process for DNDD is well established with 715 DNDDsin 2019 but the donation rate remains low at <1PMP. The World Health Organization has called upon all countries to pursue self-sufficiency in organ transplantation, both by decreasing disease burden and increasing the availability of organs., Organ donation after circulatory death (DCD), more recently called donation after circulatory determination of death (DCDD), has successfully expanded the donor pool in many countries, accounting for 20%–50% of deceased donors., In India, where the concept of circulatory death is universally understood, DCDD may be an acceptable pathway to increase organ donation. The Transplantation of Human Organs Act, 1994 defines a 'deceased person' as one in whom permanent disappearance of all evidence of life occurs, by reason of brain stem death or in a cardio-pulmonary sense at any time after live birth has taken place.
This group with multi-disciplinary expertise in all aspects of intensive care, organ donation, and transplantation has compiled this document to serve as a joint position statement and guidelines for furthering DCD in India, keeping in mind the existing international best practices. Written inputs and writeups by all authors were compiled, edited, and finalized over several rounds of interactions, consultations, and deliberations. Due to restrictions imposed by the COVID-19 pandemic, interactions were held on virtual platforms. The professional bodies represented by the group include the following:
- Indian Society of Organ Transplantation
- Indian Society of Critical Care Medicine
- Society of Neuro-Critical Care
- Indian Academy of Neurology
- Indian Association of Palliative Care
- Liver Transplantation Society of India
- Indian Society for Heart and Lung Transplantation
- Indian Academy of Paediatrics, Critical Care Chapter.
A patient with devastating brain injury (DBI), most commonly due to trauma, stroke, or hypoxia may have circulatory death before or on reaching the hospital. Once in the hospital, most patients would require ventilatory support and may either recover or progress to BD or circulatory death [Figure 2]. BD can be diagnosed in 30% of patients with DBI before the heart stops. On the other hand, BD only accounts for about 2% of all deaths. While in DNDD, organ donation is authorized/planned after BD, in DCDD the donation needs to be authorized when death is anticipated, before death or after death, which poses new ethical, medical, legal, economic, procedural, and logistic challenges. The Maastricht system classifies DCDD based on the circumstances of death and has been widely used and modified. We chose the modified Maastricht classification that is simple and relevant to India [Table 1].
|Table 1: Modified maastricht classification of donation after circulatory determination of death|
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| Donation After Circulatory Determination of Death Worldwide|| |
Although the first kidney transplant between twin brothers was a living donor transplant, the first liver, lung, and heart were transplanted following cardiac death, as understood at that time.,,, The growth in transplant activity was primarily driven by DNDD. However, it was soon realized that DNDD and living donations were unable to fulfill the ever-increasing demand for transplants. This led to a resurgence of DCDD transplants. In the last two decades, a large number of DCDD kidney, liver, lung, and heart transplants have been successfully performed all over the world using rapid retrieval techniques in carefully selected donors. Recent DCDD protocols incorporate novel innovations such as hypothermic and normothermic, in situ and ex vivo perfusion, with nonoxygenated or oxygenated preservative solutions that are either acellular or contain blood. These technologies not only enable longer preservation time, allow organ viability assessment and reduce the urgency of the logistic challenges, but also have the potential for organ reconditioning.
DCDD donations worldwide are increasing every year [Figure 3], with significant contributions from many European and some non-European countries [Figure 4]a and [Figure 4]b. The terminology used in DCDD is summarized in [Table 2]. Legislations, guidelines, procedures, protocols for declaration of death, consent, no-touch period, antemortem interventions, and organ preservation methods are based on unique local ethical, social, cultural, legal, and economic factors in each country [Table 3].,,,,,,,,,,,, Opt-out consent system, coupled with robust emergency and resuscitation services, favorably influences DCDD categories I and II. No-touch period of 5 min is most commonly used worldwide, including in the published literature from India, as it is well proven that lack of blood supply to the brain for 5 min results in irreversible and permanent brain injury.
|Table 2: Terminology and definitions relevant for donation after circulatory determination of death|
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|Table 3: Comparison of regulations and donation after circulatory determination of death practices in different countries|
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|Figure 3: Worldwide total number of actual donors after circulatory determination of death|
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|Figure 4: (a) Donation after circulatory determination of death in non-European countries in 2019. (b) donation after circulatory determination of death in European countries in 2019|
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DCDD from pediatric donors is also possible using similar protocols., The ethical principles that apply to consent, withdrawal of support, death declaration, and end-of-life care in pediatric DCD (pDCD) are similar to those in adults. Rates of graft and patient survival after transplantation of liver and kidneys obtained by pDCD are similar to those after DNDD. Although there is limited experience with recovering and transplanting hearts after pDCD, it is technically feasible.,
| Donation After Circulatory Determination of Death in India: Published Reports, Status and Potential|| |
Although a few DCDD transplants have been reported from India, unlike DNDD, it is not common across the country and is not a national program. Two DCDD kidney transplant series have been published. A few unpublished DCDD liver transplants have been done but there have been no heart or lung transplants.
The Institute of Kidney Diseases and Research Centre (IKDRC), Ahmedabad performed 33 cDCDD kidney transplants between January 1999 and January 2012, constituting 10% of their total deceased donor transplants during that period. WLST was done in the operating room with 5–10 min of the no-touch period followed by heparinization, femoral artery cannulation, and rapid retrieval. With standard immunosuppression, patient survival at 1 and 10 years was 87.3% and 72.8%, respectively, and graft survival was 90.9% when donors were younger than 70 years, with an acceptable delayed graft function (DGF) rate of 31%.
The Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh published their initial experience with 9 uDCDD kidney transplants (out of 26 performed till December 31, 2020) from 5 donors with a mean age (±standard deviation) of 29.6 ± 16.3 years, when the cardiac arrest was unrecoverable. Cardiopulmonary resuscitation (CPR) was continued while shifting the donor into the operation theater in three patients. After 5 min of the no-touch period, without any antemortem interventions, super rapid retrieval was performed. Warm ischemic time was 68 ± 15.16 min and cold ischemic time ranged from 3.5 to 13.1 h. One patient had primary graft nonfunction. DGF was observed in 80% of patients, with subsequent good graft function. Recovery was earlier in grafts from donors who underwent CPR.
In India, there is a significant lack of awareness about end-of-life care (EOLC), palliative care, WLST, and general understanding of organ donation and its altruistic value to society. This forces the majority of families to demand Discharge or Leave (or transfer) Against Medical Advice (DAMA/LAMA). This often results in the death of the patient during transportation or at home, amounting to WLST without organ donation. This practice deprives the terminal patient of dignity in death and denies the family an opportunity to donate organs. A similar dilemma exists in BD patients whose families do not wish to donate organs. Since BD is defined under the Transplantation of Human Organs Act, 1994, intensive care unit (ICU) doctors may be uncomfortable discontinuing life support even after BD declaration. Thus, delinking BD from organ donation is also essential, which may be achieved by including both BD and circulatory death in The Registration of Births and Deaths Act, 1969. In some states like Kerala, the procedure for BD declaration and removal of life support have been delinked by passing a government order (GO 7/2020). Some of the relevant legislation, rules, recommendations by professional bodies, government notifications, court judgments, and events relevant to DCDD are listed in [Table 4].,,,,,,,,,,,,,
|Table 4: Landmarks in transplants in India, relevant to end of life care, palliative care, withdrawal of life-sustaining treatment and donation after circulatory determination of death|
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| Donation after Circulatory Determination Of Death: Procedures and Prot Csocols|| |
Procedures and protocols for various DCDD categories, as applicable in India are described.
| Controlled Donation after Circulatory Determination Of Death: Maastricht Category III: Expected Circulatory Death in Intensive Care Unit|| |
In patients where all curative treatment options have been exhausted and ongoing treatment is considered futile, the process of WLST or EOLC may be initiated. Determination of futility of care is independently made by the primary doctor, ICU doctor, and other specialists involved in the care, following early, open, transparent, empathetic, complete, effective, and multiple communications between them. Independent evaluations, revisits, second opinions, and treatment response evaluations for 72 h may be required before a consensus can be reached. Multiple sessions of detailed discussions about WLST are then held with the family by the treating unit, intensivist, and hospital administrator. Family dynamics are understood and key stakeholders in the family identified. Discussion sessions with the family are structured to progressively include more information about the disease, prognosis, futility, DNAR, WLST, EOLC, and palliative care. This is primarily a medical decision to which the family consents and must be scrupulously delinked from the subsequent possibility of organ donation to avoid any perceptions of conflict of interest and loss of public trust.
Once the family has consented to WLST, the critical care team should notify the hospital transplant coordinator/trained counselor to broach the topic of opportunity for organ donation with the family. This group suggests a combined approach, depending upon the dynamics and level of training at each hospital, by transplant coordinator, social worker, treating neurologist/neurosurgeon, critical care specialist, or specialist nurse. Once these procedures become a routine a team led by the transplant procurement manager may help streamline the process better. The counseling process is likely to be a lot easier if the patient had already agreed for donation through either speaking to the next of kin or had carried an organ donor card or expressed the wishes through the driving license. Multiple sessions of counseling may be required to build on the rapport with the family. Occasionally direct conversation with a conscious and competent patient may be possible. If the family/patient does not wish to donate organs, the process of WLST/EOLC/palliative care is initiated in the ICU. If there is the initial inclination for organ donation by the family, the process should be discussed in detail, including timing and location of WLST, consent for antemortem measures, a realistic timescale, and the possibility of stand down (20% chance of lack of cessation of circulation within 120 min and return to ICU for EOLC). Organ allocation authority is informed by the transplant coordinator, potential recipients identified, retrieval teams, alerted, and cross-match tests ordered for identified recipients. No member of the transplant team is involved in the determination of futility of care or any discussions with the patient's family. Ongoing communication with the family and providing constant information and emotional support is the key.
The process of WLSTleading to organ donation is coordinated between ICU doctors, anesthetists, and the transplant coordinator. All important steps and timings are recorded [Figure 5]. The agonal phase starts with WLST. The no-flow state starts and the agonal phase ends with circulatory arrest. Cessation of circulation can be confirmed by the absence of pulse and blood pressure by an indwelling arterial line or doppler, or absence of cardiac activity on ECG or absent cardiac forward flow on echocardiography. This is followed by a no-touch period to allow time for auto resuscitation/restoration of spontaneous circulation (ROSC), which is also a no-flow state. After this period, if there is no sign of cardiac activity, death is certified and written consent for organ donation is obtained by the transplant coordinator. A checklist for actions by the transplant coordinator is shown in [Table 5].
|Figure 5: Pathway for controlled donation after circulatory determination of death – Category III|
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|Table 5: Checklist for transplant coordinators' for donation after circulatory determination of death|
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If normothermic regional perfusion (nRP) is planned, these steps may be performed in the ICU. Heparinization and rapid femoral cannulation is performed, and extracorporeal perfusion is initiated. If lung retrieval is planned, bilateral pleural cold perfusion is also initiated. Donor's pump flow and laboratory parameters such as lactate and hepatic transaminases are observed for 4 h or more. If these are acceptable, the donor is shifted to the OR for retrieval. If nRP is not planned, WLST may be performed in the OR rather than the ICU to minimize warm ischemia time (WIT). Organ preservation is started using cold University of Wisconsin/Histidine-tryptophan-ketoglutarate or other preservative solutions, which marks the end of WIT and the beginning of cold ischemia time (CIT). The retrieved organ may be further subjected to ex vivo hypothermic/normothermic preservation before transplantation.
Several models, like the COMFRT tool in the UK, may be used to encompass all aspects of DCDD-III:
- C-Consensus decision regarding futility. All members of the team need to agree
- O-Organ donation to be considered (both solid/tissues)
- M-Medical documentation to be completed (DNAR and EOLC)
- F-Family: privacy
- R-Religion and spiritual needs
- T-Tasks: keepsakes, fingerprints.
The Clinical Ethics Committee (CEC) should be in place in the hospital for audits, carried out from time to time. This five-member Committee is appointed by the chief administrator of the medical facility and no external approvals are required. Members include the head of the ICU, chief medical administrator, an invited senior physician with relevant experience not employed by the medical facility, a legal expert, and a layperson preferably involved in social service. This group recommends that all hospitals should constitute the CEC and decisions on WLST be increasingly incorporated into day-to-day practice, following the spirit of the law rather than the letter.
Documentation: following documents should be maintained in a cDCDD setting:
- Counseling form including diagnosis, daily assessments/progress notes with prognosis (life expectancy and quality of life), details of family meetings including individuals present in each and outcomes if any [Appendix 1]
- Documentation of WLST [Appendix 2]
- Medical Certificate of Cause of Death in Form 4, Registration of Births and Deaths Act, 1969
- Consent for organ donation in Form 8, Transplantation of Human Organs and Tissues Act, 1994 [Appendix 3].
| Uncontrolled DCDD: Modified Maastricht Category I, II, and V|| |
In the case where an unexpected cardiac arrest happens either in the community (Category I), in the emergency room (Category II) or in the ICU (Category V) CPR is initiated. However, if CPR is unsuccessful after 30 min, death is certified. In cases where cardiac arrest is anticipated in ICU, the family may express wishes for organ donation [Figure 6]. In such a situation, the procedure for organ donation after death is discussed with the family, including “no-touch” period, ante-mortem measures, the process of certification of death, and nRP or organ retrieval may be discussed with the family by a team that may include transplant coordinator, transplant procurement manager, social worker, treating neurologist/neurosurgeon, critical care specialist or specialist nurse. Measures to minimize warm ischemic injury are critical to the success of uDCDD transplant and must go hand-in-hand with the assessment of donation potential, whilst approaching the family for consent and mobilizing multiple retrieval services.
|Figure 6: Pathway for uncontrolled donation after circulatory determination of death – Category I, II, and V|
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In case of unexpected cardiac arrest, if the family is strongly inclined towards organ donation or the deceased had expressed wishes to donate his/her organs through a donor card or driving license, counseling for organ donation may be initiated even while resuscitation attempts are ongoing. This should be handled very sensitively by an experienced team of ICU doctors, treating team, and transplant coordinators.
After certification of death chest compressions may be re-initiated after observing no-touch period for maintaining organ circulation. Heparinization and femoral cannulation are done rapidly and nRP initiated. Donor's pump flow and laboratory parameters are monitored on nRP for a minimum of 4 h. The organ allocation body is informed for organ allocation. If nRP parameters are favorable, the donor is shifted to the OR for retrieval.
| Documentation|| |
- Documentation of all communication with the family
- Medical Certificate of Cause of Death in Form 4, Registration of Births and Deaths Act, 1969
- Consent for organ donation in Form 8, Transplantation of Human Organs and Tissues Act, 1994.
| Modified Maastricht Category IV: Cardiac Arrest Happens in a Brain-Dead Donor|| |
In India, the occurrence of cardiac arrest during the process of brain-death declaration is not uncommon. In eligible donors, where BD has been certified after both sets of tests, CPR and no-touch period are not required and donation can be performed as Category IV. In potential donors were no formal testing or only one set of brainstem death tests have confirmed BD, CPR should be performed for 30 min. However, if DNAR has been signed, CPR is not required, but 5-min no-touch period is required [Table 6].
|Table 6: Protocol for modified Maastricht category IV: Cardiac arrest in a brain-dead donor|
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| Documentation|| |
- DNAR consent, Indian Council of Medical Research Consensus Guidelines [Appendix 4]
- Form 10, Transplantation of Human Organs and Tissues Act, 1994: Certification of brain stem death
- Form 8, Transplantation of Human Organs and Tissues Act, 1994: Consent for organ donation
- Form 4, Registration of Births and Deaths Act, 1969: Medical Certificate of Cause of Death.
| Organ Specific Considerations|| |
Although DCDD kidney and liver transplants are common, increasing number of centers are also performing DCDD heart and lung transplants. Outcomes equivalent to DNDD transplants, and consistently superior to waiting list mortality for most organs have been reported.,,,
| Heart|| |
The limited myocardial tolerance to either cold or warm ischemia necessitated the introduction of ex-situ donor heart perfusion technology and pharmacological postconditioning strategy to permit the late, but the successful introduction of DCDD heart transplantation as recently as 2014. DCDD heart transplants are generally from Category III donors with some unpublished and anecdotal accounts of successful transplants utilizing Category IV donors also. DCDD hearts are accepted from hemodynamically stable donors up to 40 years of age without cardiac disease, cardiac surgery, significant thoracic trauma and a satisfactory echocardiographic evaluation of the heart. In experienced centers, hearts from donors up to 50 years of age with satisfactory coronary angiography may be accepted.
The majority of the DCDD heart transplants have been performed using the Sydney protocol involving a rapid retrieval technique with in situ cardioplegia delivery, cardiac explant and subsequent reanimation on an ex-situ organ perfusion device (OCS Heart, TransMedics Inc, Andover, USA). The alternative method has been the Papworth protocol which involves the institution of normothermic regional perfusion (nRP) and in situ assessment of the reanimated heart before it is explanted and placed on the extra-corporeal perfusion device for transportation. Cardiac preservation of DCD hearts with standard static cold storage has been described in a limited number of cases where donors and recipients have been co-located in the same hospital.
The medium-term outcomes of DCDD heart transplants have been excellent with 1- and 5-year survival of 98% and 95%, respectively,,, and noninferior to outcomes from utilizing donor hearts from the standard DNDD pathway. The recent introduction of continuous cold oxygenated perfusion devices (Paragonix Sherpa Pak and XVIVO) for preservation and transportation is being successfully validated in clinical trials. While these devices should simplify logistical challenges for organ retrieval teams, they still require an additional platform to enable cardiac reanimation when pretransplant functional evaluation is necessary.
At present, the cost of the ex situ normothermic beating heart perfusion technology is a major obstacle to its adoption in India where the patient is responsible for all such expenses including ambulance and air transportation. The Papworth method of thoracoabdominal perfusion using either central cardio-pulmonary bypass or femoro-femoral ECMO, with the exclusion of cerebral reperfusion, would permit cardiac reanimation, full in situ functional assessment, potentially a longer WIT of up to 60 min and also facilitate safe recovery of abdominal organs. This could be applied to both controlled Maastricht III and IV category donors ideally with co-located recipients. In the absence of ex situ perfusion devices, the use of DCDD donor hearts that have had in situ reanimations with extracorporeal support and subsequently transported under cold static preservation needs further controlled evaluation.
| Lungs|| |
Lungs are uniquely privileged in their tolerance to warm ischemia by virtue of trapped alveolar air allowing continued aerobic respiration and metabolic activity. There is significant clinical data for the safety and excellent outcomes with the use of Category III DCDD lungs using static cold storage preservation and without the need for ex situ organ perfusion. Donors <65 years without significant preexisting lung disease, smoking history, or lung injury with a tidal volume of 6–8 ml/kg, PaO2/FiO2 ratio >300 mmHg or >40 KPa at 100% FiO2 and PEEP of 5–8 cm H2O and a clear chest X-ray are acceptable for DCDD lung donation. Bronchoscopy is useful for mucosal assessment, bronchial toilet, and lower respiratory samples for microbiology, such as the bronchoalveolar lavage samples that currently permit a more accurate reverse transcription-polymerase chain reaction assessment of SARS CoV-2 infection. Typically, agonal phase of 90 min is considered acceptable. Ante-mortem Heparin administration is preferred with rapid sternotomy and pneumoplegia delivery. Retrograde pneumoplegia flush on the back-bench is done to complete the process of pulmonary preservation and also to ensure the absence of visible emboli or clots returning from the pulmonary artery. DCDD lungs may be offered to all wait-listed patients as the allocation criteria and outcomes are similar to DNDD transplants.,, In India it would be possible to safely utilize controlled category IV lungs. Furthermore, encouraging results from championing centers in Spain and North America would also suggest the potential of using uncontrolled category II and V DCDD lungs in India. However, it is likely that the necessary assessment of these very extended criteria lungs will require ex-situ machine perfusion technology.
| Liver|| |
The liver is also tolerant of some warm ischemia and the world's first liver transplants in the 1960s used cDCDD donors. DCDD liver grafts are usually retrieved from category III donors (but also from all other Maastricht groups) have a slightly higher risk of primary nonfunction (PNF), delayed graft function, and ischemic biliary strictures. Donor selection and recipient selection are crucial and variable depending on center experience aiming to keep cold ischemia short. Super-rapid retrieval and static cold storage (SCS) are currently used with 5-10 min of no-touch. Ante-mortem measures such as iliac vessel cannulation and heparinization, if permitted, may reduce ischemia times. Factors influencing outcomes are well summated in the DCD risk score analysis which includes donor and recipient age, donor BMI, functional WIT, MELD score, CIT, and previous liver transplantation. Current outcomes of DCDD and DNDD liver transplantation are very similar, with 85%–95% and 70%–85% 1-year and 5-year patient and graft survival respectively, albeit with a higher risk of late re-transplantation in DCDD recipients.,,, Modern perfusion and preservation techniques have reduced the risks of primary non function and biliary complications. The technique of trans-arterial normothermic regional perfusion using a portable ECMO device permits early blood perfusion and oxygenation, resulting in mitochondrial replenishment before SCS. Normothermic machine liver perfusion (NMLP) is associated with lesser hepatocellular injury and acceptable biliary complications. Post SCS NMLP at the recipient hospital (”back-to-base”) approach overcomes logistic and cold ischemia pressures but may not prevent ischemic biliary complications. Hypothermic machine perfusion (dual arterial and portal venous or portal venous alone) also reduces the risk of PNF and ischemic cholangiopathy. SCS may give way to the routine use of these novel emerging techniques for better long-term outcomes in the future although they need further evaluation. For India, a logical place to start DDCD liver transplantation would be for Category V, while the other legal and logistical challenges are addressed.
| Kidneys|| |
Kidneys are capable of tolerating ischemic insult the most and a period of delayed graft function can be easily managed with dialysis as compared to other organs. Therefore, these remain the most widely used organs amongst DCDD donors. Majority of the DCDD donations across the globe are from Category III/IV (controlled) donors whereas uncontrolled donations especially category I happen only in a few European countries such as Spain, France, the Czech Republic, and Switzerland. Donors with acute kidney injury requiring dialysis, older (>60 years) ones with hypertension and/or cardiovascular death and/or substantial arterial disease or glomerulosclerosis on preimplantation biopsy may be excluded. For uDCDD a witnessed cardiac arrest, age <60 years and fWIT <30 min and WIT <180 min without a history of diabetes mellitus, uncontrolled hypertension is acceptable. Rapid retrieval techniques including the use of double-balloon triple lumen catheters can help in minimizing WIT. SCS is the current standard, with organ perfusion systems increasingly being used in research settings. The use of ex vivo cold perfusion for graft selection may reduce the risk of DGF. The use of ex vivo normothermic oxygenated perfusion may permit better recovery of graft function. Perfusion pressures on these systems, perfusate effluent biochemical analysis, or preimplant biopsy/scoring systems may not accurately predict the risk of primary nonfunction, although complete acute cortical necrosis on preimplantation kidney biopsy should be excluded. DCDD kidneys may be offered to all recipients on the waiting list, either as a single or dual kidney. Long term (10-year) DCDD outcomes using conventional techniques are similar to DNDD. Graft outcome is more closely related to whether graft is from expanded criteria donor versus standard criteria donor. Ten-year graft survivals of >80% in both controlled and uncontrolled DCDD are reported.,, Category IV donors should be the easiest to start in India as the family is aware of the irreversible situation and consent would already be there from some of them. Experienced centers can also proceed with Category V although obtaining consent at a very short interval will have challenges but might be possible in those who have shown their desire on driving license or have an organ donor card. Category III would only be possible in centers where withdrawal of care is being practiced as per the law. Neonates with conditions not compatible with life are another potential category although surgical complications remain high in these situations.
| Summary|| |
DCDD is feasible in India. Standard operating procedures and protocols considering local ethical, social and cultural sensitivities will ensure its success in expanding the donor pool. Initial pilot DCDD programs at well-established transplant centers will help minimize ischemia time, logistic difficulties, and cost due to donor-recipient co-location. The key elements for the success of the DCDD program are careful donor selection, support to the family, early determination of impending death/death, optimal “no-touch” period to minimize ischemic injury, and use of techniques and technologies to facilitate organ preservation and repair. The use of ex situ perfusion systems may be limited in India for now, due to prohibitive cost. Development of indigenous organ care systems and preservative solutions, data submission, audit, and outcome analysis will inspire confidence among professionals and generate much-needed public assurance.
This guideline article is being published simultaneously in the Indian Journal of Transplantation and the Indian Journal of Critical care medicine as per the decision of Editor-In-Chiefs as it is a joint position paper.
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Conflicts of interest
There are no conflicts of interest.
| Appendix|| |
Patient name : Age/Gender:
Hospital ID : Ward/Bed No.: Date/Time:
Summary of the present condition conveyed to the legally appointed healthcare proxy/next-of-kin(s)/surrogate decision maker(s):
Decision on the goal of care: Full treatment/comfort care/decision pending valid until …………………
Members of family present (any one signature):
Members of treating team present (any one signature)
Directive for Withdrawal of Life Support (WLST)
Part I (to be filled-in at the time of WLST discussion and consent)
Patient name: Age/Gender:
Hospital ID: Ward/Bed No.: Date/Time:
□ Patient has an appropriate Advance Medical Directive and has named -_________________________________________ as his/her health care proxy/surrogate decision maker.
□ Patient does not have Advance Medical Directive/legally appointed healthcare proxy and his/her surrogate decision maker (s) are:
I/We, the Health Care Proxy/surrogate decision-maker (s) (names as above) have been informed by Dr. ___________________________________________________that my/our patient is suffering from a terminal illness.
After extensive discussion with the treating doctors, I/We understand that any life-sustaining treatment is not in the patient's best interest, may be inappropriate for the above condition and/or is likely to prolong his/her suffering.
Bearing this in mind I/we request doctors the following on behalf of the patient:
□ Allow natural death in the event of cardio-pulmonary arrest (DNAR) i.e., (no external chest compressions, no intubation, no chemical or electrical cardioversion)
I/We refuse the continuation of the following Life Support that are inappropriate for my patient (Please tick)
□ Artificial breathing support and airway
□ Artificial cardiac support including medications for maintaining blood pressure, rhythm
□ Artificial nutrition
□ Other invasive investigations or therapies (including Extracorporeal Membrane Oxygenation, Left Ventricular Assist Devices, Implantable Cardiovertor-Defibrillators etc)
In case of the survival of my patient after WLST, I/We further request that his/her treatment/care be carried out at ___________________________________________(hospital or home after terminal discharge).
I/We fully understand that I am at full liberty to revoke the above decisions at any time.
We hereby certify that the Health Care Proxy/surrogate decision-maker (s) of the patient suffering from terminal illness _____________________________________________________________has opted for WLST including DNAR.
He/she/they has/have further requested for appropriate palliative care for the patient in the form of pain medications and other therapies for providing relief from symptoms.
Part II (To be completed during quarterly Audit by the Clinical Ethics Committee)
We hereby certify that we have reviewed the process for WLST for the patient Mr./Mrs./Ms.______________________________________________________________________________________suffering from terminal illness_________________________________
The Directive for WLST and the endorsement of the same by the treating consultants have been checked and were found to be in order.
FOR DECLARATION CUM CONSENT
(To be filled by near relative or lawful possessor of brain-stem dead person)
[Refer rules 5 (1)(b), 5 (4)(b) and 5 (4)(d)]
DECLARATION AND CONSENT FORM
I.,________________________________S/o, D/o, W/o____________________________________aged______________________________resident of_________________________________in the presence of persons mentioned below, hereby declare that:
1. I have been informed that my relative (specify relation). _____________________________________________S/o, D/o, W/o______________________________________aged_________________________has been declared brain-stem dead/dead.
2. To the best of my knowledge (Strike off whichever is not applicable):
. (a) He/She (Name of the deceased)__________________had/had not, authorised before his/her death, the removal of__________________________(Name of organ/tissue/both) of his/her body after his/her death for therapeutic purpose. The documentary proof of such authorisation is enclosed/not available.
. (b) He/She (Name of the deceased)_________had not revoked the authority as at No. 2 (a) above (If applicable).
. (c) There are reasons to believe that no near relative of the said deceased person has objection to any of his/her organs/tissue being used for therapeutic purposes.
3. I have been informed that in the absence of such authorization, I have the option to either authorize or decline donation of organ/tissue/both including eye/cornea of_______________(Name of the deceased) for therapeutic purposes. I also understand that if corneas/eyes are not found suitable for therapeutic purposes, then maybe used for education/research.
4. I hereby authorize/do not authorize the removal of his/her body organ(s) and/or tissue(s), namely (Any organ and tissue/Kidney/Liver/Heart/Lungs/Intestine/Cornea/Skin/Bone/Heart Valve/Any other; please specify)______________________for therapeutic purposes. I also give permission for drawing of a blood sample for serology testing and am willing to share social/behavioral and medical history to facilitate proper screening of the donor for safe transplantation of the organs/tissues.
Date______________Signature of near relative/person in lawful possession of the dead body, and address for correspondence*
Place_____________ Telephone No_________________ Email_________________________
*in case of the minor the declaration shall be signed by one of the parent of the minor or any near relative authorized by the parent. In case the near relative or person in lawful possession of the body refuses to sign this form, the same shall be recorded in writing by the Registered Medical Practitioner on this Form.
(Signature of Witness 1)
1. Shri/Smt./Km_____________________S/o, D/o, W/o______________________aged_________________resident of_____________ Telephone No__________________________Email___________________________________
(Signature of Witness 2)
2. Shri/Smt./Km_________________________________S/o, D/o, W/o__________________________aged_________________resident of______________________Telephone No_________________________Email__________________________
(From ICMR, Indian J Med Res, April 2020)
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]