Donor identification and consent for deceased organ donation: summary of NICE guidance

Transcription

1 GUIDELINES Donor identification and consent for deceased organ donation: summary of NICE guidance K Chamberlain, 1 M R Baker, 1 P Kandaswamy, 1 E J Shaw, 1 G McVeigh, 2 F Siddiqui, 1 on behalf of the Guideline Development Group 1 National Institute for Health and Clinical Excellence, Manchester M1 4BD, UK 2 Department of Therapeutics and Pharmacology, Belfast BT9 7BL, UK Correspondence to: Professor G McVeigh g.mcveigh@qub.ac.uk Cite this as: BMJ 2012;344:e341 doi: /bmj.e341 This is one of a series of BMJ summaries of new guidelines based on the best available evidence; they highlight important recommendations for clinical practice, especially where uncertainty or controversy exists. bmj.com Previous articles in this series ЖЖAssessment and referral after emergency treatment of a suspected anaphylactic episode (BMJ 2011;343:d7595) ЖЖLonger term management of self harm (BMJ 2011;343:d7073) ЖЖCaesarean section: summary of updated NICE guidance (BMJ 2011;343:d7108) ЖЖDiagnosis and management of colorectal cancer (BMJ 2011;343:d6751) Organ donation plays a major role in the management of patients with single organ failure of the kidneys, liver, pancreas, heart, or lung, or with combined organ failure of heart and lung (such as in cystic fibrosis) or of kidney and pancreas (such as in diabetes). A shortage of transplant organs has resulted in long waits for transplantation. Currently about 500 people in the United Kingdom die each year because of a shortage of donated organs, 1 and at 31 March 2011 almost 7000 patients were waiting for a kidney transplant 1 and would be having costly dialysis with serious morbidity and impact on quality of life. This shortage of organs is partly the result of relatively low numbers of road traffic deaths (lower than in many countries) but is also the result of inefficiencies in the donor identification and consent processes. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on improving donor identification and consent rates for deceased organ donation. 2 Recommendations NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. Identifying patients who are potential donors Consider organ donation as a usual part of planning for end of life care. Identify all patients who are potentially suitable donors as early as possible, through a systematic approach. While recognising that clinical situations vary, base this identification on either of the following criteria: Defined clinical trigger factors in patients who have had a catastrophic brain injury (namely (a) the absence of one or more cranial nerve reflexes and (b) a Glasgow coma scale score of 4) unless there is a clear reason why these triggers are not met (for example, because of sedation) and/or a decision has been made to perform brainstem death tests, whichever is the earlier; or The intention to withdraw life sustaining treatment in patients with a life threatening or life limiting condition that will, or is expected to, result in circulatory death. Assessing best interests While assessing the patient s best interests clinically stabilise the patient in an appropriate critical care setting while the assessment for donation is performed for example, in an adult intensive care unit or discussed with a regional paediatric intensive care unit. Provided that delay is in the patient s overall best interests, life sustaining treatments should not be withdrawn or limited until the patient s wishes around organ donation have been explored and the clinical potential for the patient to donate has been assessed in accordance with legal and professional guidance. 3 4 studies and on the experience and opinion of the Guideline Development Group (GDG)] Seeking consent for organ donation If a patient lacks the capacity to consent to organ donation, seek to establish whether the patient has given prior consent by: Referring to an advance care statement if available Establishing whether the patient has registered and recorded their consent to donate on the NHS organ donor register, and Exploring with those close to the patient whether the patient had expressed any views about organ donation. If it has not been possible to ascertain whether the patient gave prior consent, and in the absence of a person(s) having been appointed as nominated representative(s), seek consent for organ donation from those in a qualifying relationship with the patient (a qualifying relationship ranks those from a spouse or partner (including civil or same sex partner); parent or child; brother or sister and other relatives; through to a friend of long standing). Where a nominated representative has been appointed and the person had not already made a decision about donation before their death, then seek consent after death from the said nominated representative(s). Approaching those close to the patient The multidisciplinary team should be responsible for planning the approach and discussing organ donation with those close to the patient. The multidisciplinary team should include: The medical and nursing staff involved in the care of the patient, led throughout the process by an identifiable consultant and The specialist nurse for organ donation and Local faith representative(s) where relevant. Before approaching those close to the patient, try to seek information on all of the following: BMJ 21 JANUARY 2012 VOLUME

2 FURTHER INFORMATION ON THE GUIDANCE This guidance was developed by the Short Clinical Guidelines team at NICE in accordance with NICE guideline development method ( aboutnice/howwework/developingniceclinicalguidelines/ clinicalguidelinedevelopmentmethods). A Guideline Development Group was established by Short Clinical Guidelines, which incorporated two patient/carer members and healthcare professionals working in clinical areas relating to organ donation for transplantation, including intensive care units, organ donation committees, regional transplant organisations, and ethics and diversity. The group examined five key clinical questions and analysed and appraised the evidence using GRADE methods where appropriate. The draft guideline underwent a rigorous validation process, which included inviting stakeholder organisations to comment. All comments were taken into consideration when the final version of the guideline was produced. NICE produces three versions of its short clinical guidelines: a full version (with all the recommendations plus details of the methods used and the underpinning evidence); a quick reference guide (with recommendations in a suitable format for health professionals); and a version known as Understanding NICE guidance (written for people without specialist medical knowledge). All these versions are available on the NICE website (in this case at The guideline will be reviewed for an update in three years as part of the NICE guideline development programme. Future research The guideline recommends the following topics for future research: Reasons why people join the NHS organ donation register Reasons for refusal for consent How to improve rates of identification and referral of potential donors How to improve consent rates for donation Understanding the experience of consenting for organ donation Knowledge of the clinical history of the patient who is a potential donor Identification of key family members Assessment of whether family support is needed for example, local faith representative, family liaison officer, bereavement service, trained interpreter, advocate Identification of other key family concerns Identification of cultural and religious concerns that may affect consent. Every approach to those close to the patient should be planned with the multidisciplinary team and at a time that suits the family s circumstances. When approaching those close to the patient: Discuss with them that donation is a usual part of the end of life care Use open ended questions for example, How do you think your relative would feel about organ donation? Use positive ways to describe organ donation, especially when patients are on the NHS organ donor register or they have expressed a wish to donate during their lifetime for example, By becoming a donor, your relative has a chance to save and transform the lives of many others Avoid using apologetic or negative language such as, I am asking you because it is policy or I am sorry to have to ask you. The healthcare team providing care for the patient should provide those close to the patient who is a potential donor with the following, as appropriate: Assurance that the primary focus is on the care and dignity of the patient (whether the donation occurs or not) Explicit confirmation and reassurance that the standard of care received will be the same whether they consider giving consent for organ donation or not The rationale behind the decision to withdraw or withhold life sustaining treatment and how the timing will be coordinated to support organ donation A clear explanation of and information on: the process of organ donation and retrieval, including post-retrieval arrangements; what interventions may be required between consent and organ retrieval; where and when organ retrieval is likely to occur; how current legislation applies to their situation, 5 6 including the status of being on the NHS organ donor register or any advance care directive; how the requirements for coronial referral apply to their situation Consent documentation Reasons why organ donation may not take place, even if consent is granted. studies and on the experience and opinion of the GDG] Organising identification, referral, and consent processes The skills and competencies required of the individual members of the team will depend on their role in the process. However, all healthcare professionals involved in identification, referral to a specialist nurse for organ donation, and consent processes should: Have knowledge of the basic principles and the relative benefits of donation after circulatory death versus donation after brainstem death. For example, the benefits of donation after brainstem death are that heart and lungs are usable, all retrieved organs are likely to be in a better condition, and failure rates are lower (especially for liver and kidney) Understand the principles of the diagnosis of death using neurological or cardiorespiratory criteria and how this relates to the organ donation process 3 Be able to explain neurological death clearly to families. For example, they need to be able to explain that death is diagnosed after the brainstem (the part of the brain responsible for maintaining life) stops functioning and is confirmed using specific criteria. This signifies there is no prospect for recovery of brain function and that death is confirmed while the body of the person is attached to an artificial ventilator and the heart is still beating Understand the use of clinical triggers to identify patients who may be potential organ donors Understand the processes, policies, and protocols relating to donor management 46 BMJ 21 JANUARY 2012 VOLUME 344

3 Adhere to relevant professional standards of practice for organ donation and end of life care. 3 Consultant staff should have specific knowledge and skills in: The law surrounding organ donation 7 Medical ethics as applied to organ donation 4 The diagnosis and confirmation of death using neurological or cardiorespiratory criteria The greater potential for transplantation of organs retrieved from donation after brainstem death compared with organs from donation after circulatory death Legally and ethically appropriate clinical techniques to secure physiological optimisation in patients who are potential organ donors Communication and knowledge necessary to improve consent ratios for organ donation. studies and on the experience and opinion of the GDG] Overcoming barriers The process of identification of potential donors and gaining consent for organ donation, including whether families are asked to consider organ donation, varies widely across the UK ( ukt/statistics/potential_donor_audit/potential_donor_ audit.jsp). This guideline aims to resolve current inequalities by helping to make organ donation a usual part of end of life care, so that families of all potential organ donors are approached and supported, irrespective of factors such as ethnicity and religion. The guidance also aims to overcome barriers through increasing clinicians skills and competencies in identifying potential organ donors and approaching families for consent, with the support of the specialist nurse for organ donation. The Guideline Development Group comprised Gary McVeigh (chair), Tim Collins, James Fraser, Karen Morgan, Paul Murphy, Jane Nix, Ronan O Carroll, Gurch Randhawa, Angus Vincent, Huw Twamley, Barry Williams, and Simon Bramhall (co-opted member). The NICE Short Clinical Guideline Technical Team comprised Mark Baker, Emma Banks, Kathryn Chamberlain, Nicole Elliott, Michael Heath, Prashanth Kandaswamy, Hanna Lewin, Beth Shaw, Faisal Siddiqui, and Sheryl Warttig. Contributors: All authors contributed to the conception and drafting of this article and revising it critically. They have all approved this version. Competing interests: None declared. Provenance and peer review: Commissioned; not externally peer reviewed. 1 NHS Blood and Transplant. Transplant activity in the UK. Activity report 2010/ activity_report/current_activity_reports/ukt/activity_report_2010_11.pdf. 2 National Institute for Health and Clinical Excellence. Organ donation: improving donor identification and consent rates for cadaveric organ donation. (Clinical guideline 135.) CG Intensive Care Society. Donation after circulatory death ac.uk/intensive_care_professional/standards_and_guidelines/dcd. 4 General Medical Council. Treatment and care towards the end of life: good practice in decision making guidance/6858.asp. 5 Mental Capacity Act contents. 6 Human Tissue Act contents. 7 Department of Health. Legal issues relevant to non-heartbeating organ donation Publications/PublicationsPolicyAndGuidance/DH_ EASILY MISSED? Multiple myeloma Danny C Hsu, 1 2 Peter Wilkenfeld, 3 Douglas E Joshua University of Sydney, Sydney, NSW 2050, Australia 2 Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia 3 Bondi Junction, Sydney, NSW 2022, Australia Correspondence to: D C Hsu danny. hsu@tpg.com.au Cite this as: BMJ 2012;344:d7953 doi: /bmj.d7953 This is one of a series of occasional articles highlighting conditions that may be more common than many doctors realise or may be missed at first presentation. The series advisers are Anthony Harnden, university lecturer in general practice, Department of Primary Health Care, University of Oxford, and Richard Lehman, general practitioner, Banbury. To suggest a topic for this series, please us at easilymissed@ bmj.com. A 62 year old man presents to his general practitioner with new onset lower back pain and fatigue for the past few weeks. The patient denies any recent trauma and has otherwise been in good health except for a chest infection treated with oral amoxicillin three months ago. On examination there is midline tenderness over the L5 vertebra with no evidence of neurological signs. The general practitioner requests a full blood count, liver function tests, and a biochemistry panel, which showed mild normocytic normochromic anaemia with rouleaux in the blood film, mild renal impairment, and a raised total protein concentration. Serum electrophoresis confirms the presence of a monoclonal paraprotein. The general practitioner refers the patient to the haematology unit, where myeloma is diagnosed after further investigation and management. What is multiple myeloma? Multiple myeloma is a neoplasm of plasma cells characterised by the production of monoclonal immunoglobulin by the malignant cells. This disease predominantly affects older adults, and because of the protean manifestations of the disease patients can initially present to their primary care physicians with vague and confusing symptoms. Why is multiple myeloma missed? In a small retrospective UK case review more than half of symptomatic patients who had initially presented to their general practitioners had a delay of more than six months (>12 months in 33% of cases) before specialist referral. 6 A large retrospective review of data from a US cancer registry also confirmed that considerable delays occur in diagnosis, with the median time from onset of symptoms or signs to the diagnosis of myeloma being 99 days. 7 As most patients with myeloma are in their HOW COMMON IS MULTIPLE MYELOMA? In the United Kingdom and the United States myeloma accounts for about 10% of all haematological malignancies 1 2 The reported annual incidence of myeloma in the UK and the US is about 3-4 per The incidence of myeloma varies across different ethnic groups; in the US the incidence is twice as high in African Americans as in white people 4 but in ethnic Chinese people in Taiwan it is as low as 0.75 per BMJ 21 JANUARY 2012 VOLUME

4 Most common presenting symptoms or signs 8 Normochromic, normocytic anaemia about 70% of patients Bone pain about 60% Renal impairment about 50% Fatigue about 30% Weight loss about 25% Hypercalcaemia about 15% Hyperviscosity symptoms* <7% Paraesthesia 5% Spinal cord compression 5% Hepatomegaly 4% Splenomegaly 1% Lymphadenopathy 1% Fever <1% *Such as headache, visual disturbance, cognitive impairment late 60s, they may accept symptoms such as diminished energy, various aches and pains, and slight weight loss as normal for their age, especially if symptom onset was gradual. The protean presentations of myeloma may not initially suggest a haematological diagnosis, especially as non-specific early symptoms such as fatigue, bone pain, and weight loss may overlap with those of more common conditions such as depression, osteoarthritis, and diabetes. In the absence of trauma or neurological symptoms ( red flags ), routine radiography of the back is usually not indicated in the investigation of non-specific back pains. Although no single, specific finding is diagnostic of myeloma, one of the key features of the disease that is often clinically silent is the presence of monoclonal paraproteinaemia in blood or urine. The findings of rouleaux (stacks of red cells) in the peripheral blood film or a raised erythrocyte sedimentation rate may be the only indications of underlying paraproteinaemia. Therefore, the findings of bone pain associated with renal disease or anaemia with rouleaux may suggest that a haematologist s opinion is necessary. Why does this matter? Patients with untreated myeloma can develop debilitating complications such as pathological fractures from lytic lesions, irreversible renal failure requiring long term haemodialysis, or more rarely spinal cord compression from extramedullary plasmacytomas. Delays in diagnosis are associated with a higher rate of complications and reduced disease-free survival. 6 Timely diagnosis of myeloma may prevent the potentially serious complications of the disease. How is myeloma diagnosed? Clinical features The symptoms and signs of myeloma result from malignant plasma cells infiltrating the bones or other organs (such as myelosuppression from marrow infiltration, hepatosplenomegaly), as well as from an increased amount of paraprotein (which causes, for example, hyperviscosity symptoms or paraesthesia from peripheral neuropathy) or light chains in the serum (which result, for example, in renal failure from light chain nephropathy). Patients with early stage disease may remain completely asymptomatic until complications arise. The box lists the most common presenting symptoms or signs, according to a large, single centre retrospective analysis. 8 Investigations When myeloma is suspected in a patient, the baseline screening investigations should include: A full blood count to detect cytopenias resulting from marrow infiltration Inspection of the peripheral blood film to look for rouleaux, which may suggest underlying paraproteinaemia Serum biochemistry to detect the presence of renal impairment, hypercalcaemia (from widespread bony destruction, as cytokine expression by myeloma cells results in osteoclastic bone resorption), and raised uric acid (from increased tumour cell turnover) Liver function tests to look at the total protein concentration. At times, the only clue to underlying paraproteinaemia may be an unexpectedly raised total protein concentration, which is brought to the clinician s attention by the clinical chemistry laboratory. A markedly raised erythrocyte sedimentation rate may also suggest the diagnosis of myeloma, with one study showing an average rate of 85 mm/h in newly diagnosed patients. 9 We have to be aware that in patients aged over 50 with a raised erythrocyte sedimentation rate and systemic symptoms, polymyalgia rheumatica is a reasonable differential diagnosis, but treatment with steroids should not be started before further investigations to exclude myeloma are considered. The C reactive protein concentration can also be mildly raised in patients with myeloma, but typically it is about 1 mg/dl (9.52 nmol/l) and is not as useful as the erythrocyte sedimentation rate as a screening test. To confirm the presence of monoclonal paraproteins, general practitioners may order serum protein electrophoresis and immunofixation, and serum-free light chains (if available). As part of the diagnostic investigations after haematology referral, most haematologists would arrange for a bone marrow biopsy to assess the presence of atypical, clonal plasma cells and a 24 hour urine collection for electrophoresis and immunofixation (to detect urinary light chain excretion). Once the diagnosis is confirmed, other tests would include serum immunoglobulin concentrations (to exclude secondary hypogammaglobulinaemia, which may cause recurrent infections) and a radiological skeletal survey (to look for lytic bone lesions). In 97% of patients with myeloma, the combination of serum and urine electrophoresis and immunofixation can detect a monoclonal paraprotein (M protein). Serum or urine electrophoresis is used to quantitate the amount of detectable paraprotein, whereas immunofixation is used to confirm the monoclonal nature of the protein as well as characterise the specific immunoglobulin subclass. It is important to note that other plasma cell disorders (such as plasmacytomas) and lymphoproliferative 48 BMJ 21 JANUARY 2012 VOLUME 344

5 bmj.com Previous articles in this series ЖЖFemoral hernias (BMJ 2011;343:d7668) ЖЖAppendicitis (BMJ 2011;343:d5976) ЖЖPVL positive Staphylococcus aureus skin infections (BMJ 2011;343:d5343) ЖЖAcute aortic dissection (BMJ 2011;343:d4487) disorders (such as chronic lymphocytic leukaemia and non-hodgkin s lymphoma) can also be associated with an M protein. To diagnose symptomatic myeloma, three diagnostic criteria must be fulfilled 10 : 1. The presence of an M protein in serum or urine (no specific cut-off as 40% of symptomatic patients with myeloma will have a level <30 g/l) 2. The presence of >10% clonal plasma cells in the bone marrow aspirate 3. Evidence of end organ damage (the so called CRAB features of hypercalcaemia from bone destruction, Renal impairment, Anaemia, and lytic Bone lesions on imaging). Patients who meet criteria 1 and 2 without evidence of the CRAB features are said to have smouldering myeloma. An asymptomatic patient (without CRAB features) whose bone marrow biopsy shows <10% plasma cells or whose serum or urinary M protein concentrations are <30 g/l has monoclonal gammopathy of undetermined significance. This condition is much more common than myeloma, with an estimated prevalence of 3% in the general population aged over 50 years. 11 This premalignant condition confers a risk of progression into myeloma (or into related lymphoproliferative disorders) of 1% a year. KEY POINTS The common manifestations of multiple myeloma, such as bone pain, fatigue, and weight loss, may be non-specific and are often initially ignored or missed by patients and medical practitioners Early diagnosis of myeloma may prevent debilitating complications such as pathological fractures, irreversible renal impairment, or spinal cord compression The finding of rouleaux in the blood film and/or a raised total protein concentration may suggest an underlying paraproteinaemia, especially in a patient with anaemia and bone pain, and would therefore warrant consultation with a haematology specialist How is myeloma managed? Refer patients with suspected myeloma to a specialist haematology unit for further investigation and management. Conventionally, after confirmation of the diagnosis with tests including a diagnostic bone marrow biopsy and skeletal survey, patients with evidence of end organ damage need treatment. Patients with smouldering myeloma are generally monitored closely as historically there has been no evidence that early treatment of these patients confers a superior long term outcome. However, with the development of new therapeutic agents with more favourable toxicity profiles, there are now phase III trials challenging this dogma and looking at the outcomes of early treatment of patients with monoclonal gammopathy of undetermined significance or smouldering myeloma. Patients with myeloma are broadly divided into two main groups: those who are or are not eligible for an autologous stem cell transplant. This division is important as cytotoxic agents form the backbone of modern treatment for myeloma, and in patients eligible for transplantation the excessive use of alkylating agents may jeopardise a successful stem cell collection. Patients often receive repeated cycles of induction chemotherapy usually in combination with thalidomide, lenalidomide, or bortezomib before stem cell mobilisation and autologous transplantation. Patients who are not eligible for transplantation are typically treated with combination chemotherapy until resolution of end organ damage and absence of detectable paraprotein. All patients with myeloma require bisphosphonates, which reduce pathological fractures and skeletal related events in myeloma. 12 A recent randomised controlled trial suggests that zoledronic acid may be the bisphosphonate of choice. 13 Adjuvant treatments in the form of localised radiotherapy may also be used for patients with symptomatic lytic lesions. Patients with recurrent infections resulting from secondary hypogammaglobulinaemia may benefit from regular intravenous immunoglobulin replacement. Contributors: DEJ proposed the overall concept of the article and is the guarantor. DCH did the literature search. All authors contributed to writing the article. Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Provenance and peer review: Commissioned; externally peer reviewed. Patient consent not required (patient anonymised, dead, or hypothetical). 1 Office for National Statistics. Cancer Statistics registrations: registrations of cancer diagnosed in 2008, England. (Series MB1 no 39.) National Statistics. 2 Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, CA Cancer J Clin 2009;59: Phekoo KJ, Schey SA, Richards MA, Bevan DH, Bell S, Gillett D, et al. A population study to define the incidence and survival of multiple myeloma in a National Health Service region in UK. Br J Haematol 2004;127: Waxman AJ, Mink PJ, Devesa SS, Anderson WF, Weiss BM, Kristinsson SY, et al. Racial disparities in incidence and outcome in multiple myeloma: a population-based study. Blood 2010;116: Huang SY, Yao M, Tang JL, Lee WC, Tsay W, Cheng AL, et al. Epidemiology of multiple myeloma in Taiwan: increasing incidence for the past 25 years and higher prevalence of extramedullary myeloma in patients younger than 55 years. Cancer 2007;110: Kariyawasan CC, Hughes DA, Jayatillake MM, Mehta AB. Multiple myeloma: causes and consequences of delay in diagnosis. QJM 2007;100: Friese CR, Abel GA, Magazu LS, Neville BA, Richardson LS, Earle CC. Diagnostic delay and complications for older adults with multiple myeloma. Leuk Lymphoma 2009;50: Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78: Alexandrakis MG, Passam FH, Ganotakis ES, Sfiridaki K, Xilouri I, Perisinakis K, et al. The clinical and prognostic significance of erythrocyte sedimentation rate (ESR), serum interleukin-6 (IL-6) and acute phase protein levels in multiple myeloma. Clin Lab Haem 2003;25: International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121: Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: emphasis on risk factors for progression. Br J Haematol 2007;139: Mhaskar R, Redzepovic J, Wheatley K, Clark OA, Miladinovic B, Glasmacher A, et al. Bisphosphonates in multiple myeloma. Cochrane Database Syst Rev 2010;3:CD Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet 2010;376: BMJ 21 JANUARY 2012 VOLUME