Brain Stem Dead Donors Research Articles

Heart transplantation and alternative surgery

Heart failure is a common source of morbidity and mortality with a poor survival for patients with NYHA class III/IV symptoms. Despite the advent of medical treatments some patients may benefit from surgical treatments. The mainstay of surgical treatment is heart transplantation to which the others are compared. For carefully selected recipients, transplantation improves survival and quality of life. Selection includes a serial assessment of severity of heart failure, risk of surgery, social support and the presence of contraindications to surgery. The selection and management of brainstem dead potential donors is important in optimizing the yield of hearts suitable for patients awaiting transplantation. Postoperatively, the risk of cellular rejection is reduced by the use of ciclosporin, azathioprine and prednisolone immunosupression while the risk of infection with pneumocystis carinii, toxoplasmosis and cytomegalovirus can be reduced by co-trimazole, pyrimethamine and ganciclovir, respectively. New immunosupression drugs such as tacrolimus or mycophenolate mofetil may improve on this while pravastatin and diltiazem may reduce allograft vasculopathy. Alternative surgical treatments include revascularization, mitral valve surgery, biventricular pacing, ventricular assist devices and ventricular geometrical surgery. Revascularization may reverse dysfunction in hibernating myocardium. Mitral valve surgery may restore mitral valve function secondary to left ventricular dilation while surgical geometrical surgery restores the shape of the ventricle. Biventricular pacing may resynchronize the heart and improve LV function while long term ventricular assist devices may enable patients to survive until transplantation or even allow a bridge to permanent recovery. Total artificial heart replacement, xeno or cellular transplantation are still at the experimental and/or early clinical trial stage and their potential as a treatment for heart failure remains uncertain.

Variation in Organ Donation in Northeastern England 1986 to 2003

Renal transplantation is established as the best form of renal replacement therapy, but demand for kidneys exceeds supply from cadaveric donations. It is therefore important to make the best use of the pool of potential cadaveric organ donors. Donation rates are to a large extent dependent on public opinions, which may be influenced by external events. In northeast England from 1986 to 2003, there was a potential pool of 1170 brain stem–dead donors, of whom 190 (16%) could not be retrieved due to relatives’ objections. From 1998 to 2003 we were referred 90 potential non–heart-beating donors, of whom relatives refused donation in 10 (11%). A major reason for not retrieving organs from a potential donor has been lack of consent from the relatives. Refusals appear to vary year by year and are consistently lower for non–heart-beating donors. This therefore raises the possibility that negative or positive media publicity plays a role in this variation.

Management of the brainstem dead organ donor: Pathophysiology and donor optimization

Transplantation of vital human organs is a life saving therapy for patients with end-stage organ failure. However, donor management remains one of the most neglected areas in transplantation medicine. Brainstem death leads to heamodynamic, metabolic and immune perturbations. Failure to provide adequate physiological support during this time accounts for at least 25% of lost donor organs. Donor optimization leads to increased organ procurement and contributes to improved organ function in the recipient. This article reviews the management of the brainstem dead donor from intensive care through organ procurement whilst highlighting advances and controversies in donor care.

Management of the brainstem dead organ donor: Pathophysiology and donor optimization

AbstractTransplantation of vital human organs is a life saving therapy for patients with end-stage organ failure. However, donor management remains one of the most neglected areas in transplantation medicine. Brainstem death leads to heamodynamic, metabolic and immune perturbations. Failure to provide adequate physiological support during this time accounts for at least 25% of lost donor organs. Donor optimization leads to increased organ procurement and contributes to improved organ function in the recipient. This article reviews the management of the brainstem dead donor from intensive care through organ procurement whilst highlighting advances and controversies in donor care.

Use of Elderly Donors (> 60 Years) for Liver Transplantation

As the demand for liver transplantation has become greater than the availability of donor livers, the criteria for donor selection or rejection are more important than ever before. In view of an increasing number of patients on the waiting list, some centres are expanding their donor pool by relaxing the criteria, such as by using organs from elderly (> 60 years) brainstem-dead donors. In this study, we reviewed our experience of using elderly brain-dead donor livers, investigating the potential prognostic factors of the donor, and analysing the influence of donor age on early graft function and graft survival. We retrospectively evaluated 106 cadaveric donor liver transplantations in 98 patients. Seven patients (6.6%, 7 vs 106) received livers from donors older than 60 years. Pre-transplantation characteristics of donors and the outcome of recipients were evaluated. Donor prognostic factors were analysed using Cox univariate analysis and confirmed by a multivariate forward stepwise Cox model. Early graft function was compared between recipients of grafts from donors older and younger than 60 years. There were no primary non-functions or re-transplants in the group receiving elderly grafts. Early graft function was similar in patients with grafts from elderly and younger donors. Univariate analysis demonstrated that prognostic factors had no relationship with long-term recipient survival. The 3-month and 1-year cumulative graft survival rates were 100% and 82% in the elderly graft group and 84% and 83% in the younger graft group, respectively. Kaplan-Meier curves and the log-rank test indicated that there was no difference in graft and patient survival rates between the two groups. Old age is not a contraindication for liver donation. Liver grafts from donors older than 60 years can be used safely.

The Establishment of the UK Human Tissue Bank

The UK Human Tissue Bank (UKHTB) was established in 1998, to provide biomedical researchers with an effective, transparent and ethical supply of human tissues. The UKHTB collects and processes non-transplantable human tissue from cadaveric brain stem dead donors and surgical tissues surplus to diagnostic requirements, and distributes to researchers working in UK universities, medical institutions and the pharmaceutical industry. The UKHTB has gained approval from UK National Health Service Ethical Committees for the receipt of human tissues and transfers donated tissues to researchers with allied approval, who additionally agree to the scrutiny of the end-use of tissue by the UKHTB. All donations are made with the informed consent of the donor family or patient. In this way, all donations are traced from source to end-use. The UKHTB operates under a not-for-profit policy and employs a method of cost recovery to recoup processing, staff and transport costs; the tissue itself is not subject to a charge. We are confident that improved access to human tissue models results in more relevant results being ultimately available for clinical practice.

Use of two biomarkers of renal ischemia to assess machine-perfused non-heart-beating donor kidneys.

Renal transplantation is a recognized treatment for end-stage renal failure, offering a better quality of life, independence from dialysis, better survival rates, and decreased cardiovascular complications compared with renal replacement therapy (1). Recently, continued increases in the prevalence of end-stage renal failure and the length of transplantation waiting lists have not been matched by an increased supply of donors from the traditional brainstem dead donors and living donors. Non-heart-beating donor (NHBD) kidneys are regaining importance to substantially increase the kidney donor pool, with estimates indicating a potential increase of 20–40% (2)(3). The use of NHBD kidneys is associated with the development of two adverse conditions, primary nonfunction (PNF) and delayed graft function (DGF), which are caused by the ischemic injury that occurs after cardio-respiratory arrest. Therefore, in centers with NHBD programs, it has become necessary to screen-out damaged kidneys that will never work. Machine preservation using continuous hypothermic pulsatile perfusion has been adopted in NHBD kidney screening initiatives, and perfusion characteristics (flow, pressure, resistance, temperature, weight gain) with enzyme analysis of kidney effluents are used to assess viability. Since its isolation and identification as ligandin, glutathione S -transferase (GST) has evolved as a suitable biomarker in the pretransplantation assessment of machine-perfused NHBD kidneys. Different isoforms have been identified from the distal and proximal renal tubules, and the commonest isoform, α-GST, has previously been used as a biomarker of renal ischemia as assessed by ELISA (4). However, we have previously demonstrated that a spectrophotometric assay for total GST activity (tGST) could reliably be substituted for α-GST (5). Original work by the Maastricht NHBD group has established threshold limits for tGST activity in kidney perfusates for the selection of “viable” kidneys for transplantation (6). This criterion has been introduced in Newcastle, England, where 69 NHBD renal transplants have …

Transplantation using lung lobes from living donors

At present, in the UK, live lobe donation of the lung is generally considered in the context of patients with cystic fibrosis (CF) which is a life-threatening, inherited disease.1 However,...

Donor thyroid function does not affect outcome in orthotopic liver transplantation.

Brainstem death is associated with endocrine and metabolic alterations that can result in donor hemodynamic instability. It has been suggested that these changes can be reversed through hormonal manipulation of the donor. We measured thyroid hormone levels (free triiodothyronine [fT3], free tetraiodothyronine [fT4], reverse triiodothyronine) and thyroid-stimulating hormone (TSH) in 50 consecutive adult brain dead multiorgan donors. Recipient graft function was assessed using peak and day 5 aspartate aminotransferase, peak serum bilirubin, and minimum prothrombin time during the first week after OLT. Free T3 was low in 32/50 donors and was associated with a low fT4 in 24 cases. TSH was normal in 35 donors and we found no correlation between TSH levels and fT3 or fT4. Reverse triiodothyronine was normal or high in 96% of donors. Patient and graft survival were 96% for both the low and high fT3 groups. These data suggest that euthyroid sick syndrome is the most likely cause for the endocrine and metabolic alterations seen in brainstem-dead donors. This does not appear to influence liver recipient or graft survival.

Availability of transplantable organs from brain stem dead donors in intensive care units.

By audit from January to June 1989 to quantify, separately for hearts, kidneys, liver, lungs and corneas, the possible increases in transplantable organs from brain stem dead potential donors in intensive care units and to compare them with the increases achieved in October-November 1989, during intense, national publicity about transplantation. Prospective audit of all deaths in intensive care units in England from 1 January to 30 June 1989 and subsequent case study of the impact of publicity on offers and donations during October-November 1989. 15 regional and special health authorities in England. 5803 patients dying in intensive care units, of whom 497 were confirmed as brain stem dead and had no general medical contraindication to organ donation. Organ specific suitability for transplantation (as reported by intensive care units); consent for donation of specific suitable organs; and procurement of specific organs reported as suitable for transplantation and offered. In the 497 (8.6%) brain stem dead potential donors were estimated the organ specific suitability for heart as 63%, kidneys 95%, liver 70%, lungs 29%, and corneas 91%. Refusal of relatives (30%) accounted for major losses of suitable organs of all types. For kidneys the loss was equivalent to 44% of brain stem dead actual kidney donors. No discussion of organ donation was the second most important reason for missed kidney donors, the loss being equivalent to 10% of brain stem dead actual donors. Non-procurement or difficulties with allocating organs was the second most notable cause of missed suitable liver and lung donors; 29% (55) of the offered total of 189 liver donors and 27% (21) of 78 offered suitable lung donors in six months. Non-procurement of suitable, offered organs was rare for kidneys and modest, of the order of 13% and 10% respectively, for heart and corneas. Corneal donation from brain stem dead potential donors might be improved nearly as much (that is, a 78% increase in brain stem dead actual corneal donors) by specific measures to promote corneal donation when other organs are offered as by reducing the overall refusal rate. Restricted offers, non-procurement, and no discussion of donation accounted for nearly equal numbers of lost donations of hearts (each equivalent to 15% of donated hearts). During October-November 1989 when there was intense, positive publicity about transplantation the rates of refusal and non-discussion fell compared with during January-June (22%, 36/163 v 30%, 138/460; 7%, 33/497 v 2%, 4/167 respectively). Offers of suitable donors increased significantly (p less than 0.02) compared with the first six months of 1989, most notably for heart donors (80 v 60.1 expected) and kidney donors (122 v 102.1 expected) but only for kidneys was there a noticeable 17% increase in actual donors (118 actual audited donors v 100.8 expected donors; p = 0.09). Four strategies to increase the supply of transplantable organs from brain stem dead potential donors in intensive care units were identified: (a) reducing refusal of relatives (b) avoiding non-procurement of actually suitable organs (by logistical initiatives) and deterioration of initially suitable organs (by donor care initiatives); (c) converting restricted offers to unrestricted offers; and (d) ensuring discussion with families. Early referral to the transplant team or coordinator gives time for discussion about donor care and agreement on medical suitability for donation of specific organs. Solving some of the logistical problems of non-procurement may be a prerequisite for increased offers to be translated into increased donations. The impact of publicity therefore needs to be measured on offers of suitable donors as well as by actual donations.

Anterior and posterior pituitary function in brain-stem-dead donors. A possible role for hormonal replacement therapy.

Blood samples were obtained, at the time of organ donation, from 31 consecutive brain-stem-dead (BSD) donors referred to one transplant coordinator during a 9-month period. Twenty-four cases (77%) had clinical diabetes insipidus (DI), which was poorly controlled with marked dehydration in a majority of cases (serum osmolality range 268-357; median 302 mOSM/kg). Serum triiodothyronine (T3) was subnormal in 25 (81%); all had normal or high serum reverse T3; and the serum free thyroxine (T4) index was subnormal in 9 (29%), and TSH was subnormal in 7 (23%). In no case were T4 and TSH both subnormal and results were typical of the sick euthyroid syndrome rather than TSH deficiency. Of 21 cases not receiving corticosteroids, 5 (24%) had a serum cortisol above 550 nmol/L (20 micrograms/dl), excluding ACTH deficiency, and only 1 had undetectable cortisol levels. Those with severe hypotension did not have significantly lower serum cortisol (mean 354 vs. 416; P greater than 0.5). Levels of prolactin, growth hormone, gonadotrophins, and gonadal steroids were variable, but only a minority were frankly deficient in these hormones. BSD donors frequently have DI, which is often managed poorly by nonspecialists and requires appropriate replacement therapy. In contrast most patients are not totally deficient in anterior pituitary hormones. Routine hormonal therapy with cortisol and T3 cannot, therefore, be justified on endocrinological grounds. Widespread introduction of such treatment should only follow controlled trials that clearly demonstrate clinically significant improvement in the transplanted organ function, without detriment to the donor.