Brain stem death and organ donation.

Organs for donation are in short supply in the United Kingdom, resulting in allegations that relatives of potential donors are not being asked for consent. Legislation on "required request" has been proposed to overcome this. The incidence, causes, complications, and patterns of organ donation in brain stem dead patients in one referral centre were studied over 12 months. Data were collected on all patients fulfilling criteria for brain stem death or considered suitable for donating organs after circulatory arrest. Forty two patients fulfilled the criteria for brain stem death, and in 10 further patients circulatory arrest occurred before formal testing was finished. The major causes of brain stem death were head injury (28) and intracranial haemorrhage (17). Consent to organ donation was obtained for 24 potential donors, and organs were donated by 23 of them. Twenty nine patients did not donate organs. The commonest reasons for failure to donate were medical unsuitability (13) and the coroner not releasing the body (eight). Consent was not sought in three cases, and the relatives refused consent in the remaining five. This study suggests that required request will not considerably increase the supply of donor organs.     

Diagnosis and management of brain death.

Finland was the first country in which brain death was legally accepted. Since 1975, 37 cases of brain death had been recorded in a university hospital in Finland, and these were reviewed. The cause for brain death was intracranial bleeding in 32 cases, other cerebrovascular disorder in two, and intracranial neoplasm in three. In 21 brain death was diagnosed clinically. In 16 cases confirmatory investigations (electroencephalography, cerebral angiography) were needed. After brain death had been established artificial support was withdrawn in 15 patients and organ transplantation was carried out in 10. In 12 patients, however, diagnosis of brain death did not influence management, though the heart stopped beating on average 25 hours after diagnosis. The Finnish criteria for brain death seem to be reliable and suitable for routine use.     

SEP testing in deeply comatose and brain dead patients: the role of nasopharyngeal,scalp and earlobe derivations in recording the P14 potential

Median nerve somatosensory evoked potentials (SEPs) were tested in 50 patients (20 brain dead, 18 comatose and in 12 progessing from coma to brain death, i.e., 32 cases with brain death and 30 cases with coma were recorded).Derivations were taken from nasopharynx, earlobes, scalp, and neck using cephalic and non-cephalic references. Cortical and subcortical SEP components were evaluated, focussing on the P14 potential. There is evidence that rostral and caudal parts of the P14 generator (lemniscus medialis) are differently affected in brain death, resulting in an abolition of the rostral part, while occassionally leaving intact for some time the caudal part. Non-cephalic referenced scalp records pick up the whole P14 dipole, whereas nasopharyngeal and earlobe derivations pick up different parts of P14, depending on the reference used. Scalp-to-nasopharynx records derive the most rostral part of P14; this “rostral P14” was bilaterally lost in all brain dead patients, but preserved in all deeply comatose patients with diffuse brain-sttem injuries. Scalp-to-earlobe records in contrast, picked up a P14 dipole segment reaching more caudally, resulting in a P14 potential also in brain dead patients. It is concluded that midfrontal scalp-to-nasopharynx derivations give the moset valuable contribution to the electrophysiological assessment of brain death versus deep coma.     

Brain death and organ donation in a neurosurgical unit: audit of recent practice.

OBJECTIVE--To assess the potential for increasing the yield of donors by comparing the current pattern of brain death and organ donation in a neurosurgical unit with that reported in 1981 and with a recent national audit. DESIGN--Retrospective review of all deaths for 1986, 1987, and 1988 and prospective data for 1989. SETTING--A regional neurosurgical unit serving 2.7 million population. RESULTS--Of 553 deaths, 35% (191) patients died while on a ventilator and 17% (92) after discontinuation of ventilation. Medical contraindications to donation were found in 23% (32) of 141 patients tested for brain death, in 38% (19) of 50 patients who died while being ventilated who were not tested, and in 12% (11) of 92 patients no longer being ventilated. Consent for donation was sought in 88% (96) of 109 medically suitable brain dead patients and granted in 70% (67) of these. Half those with permission for multiorgan donation had only the kidneys removed. CONCLUSIONS--More organs may be lost owing to transplant team logistics than by failure to seek consent from relatives of brain dead patients. The estimated size of the pool of potential donors depends on what types of patients might be considered. Ensuring that all who die while being ventilated are tested for brain death and considering the potential for donation before withdrawing ventilation could yield more donors. Ventilating more patients who are hopelessly brain damaged to secure more donors raises ethical and economic issues.     

Organ donation from intensive care units in England.

OBJECTIVE--To audit all deaths in intensive care units (excepting coronary care only and neonatal intensive care units) in England to assess potential for organ procurement. DESIGN--An audit in which 14 regional health authorities and London special health authorities each designated a regional liaison officer to identify intensive care units and liaise with Department of Health and the Medical Research Council''s biostatistics unit in distribution, return, and checking of audit forms. Audit took place from 1 January to 31 March 1989 and will continue to 31 December 1990. SETTING--278 Intensive care units in England. PARTICIPANTS--Colleagues in intensive care units (doctors, nurses, coordinators, and others), who completed serially numbered audit forms for all patients who died in intensive care. RESULTS--The estimated number of deaths in intensive care units was 3085, and validated audit forms were received for 2853 deaths (92%). Brain stem death was a possible diagnosis in only 407 (14%) patients (about 1700 cases a year) and was confirmed in 282 (10%) patients (an estimated 1200 cases a year). Half the patients (95% confidence interval 45% to 57%) in whom brain stem death was confirmed became actual donors of solid organs. Tests for brain stem death were not performed in 106 (26%) of 407 patients with brain stem death as a possible diagnosis, and general medical contraindication to organ donation was recorded for 48 (17%) of 282 patients who fulfilled brain stem death criteria before cessation of heart beat. The criteria were fulfilled before cessation of heart beat and in the absence of any general medical contraindication to organ donation in 234 patients, 8% of those dying in intensive care (an estimated 1000 cases a year). Consent for organ donation was given in 152 (70%) of 218 cases (64% to 76%) when the possibility of organ donation was suggested to relatives. In only 14 out of 232 families (6%; 3% to 9%) was there no discussion of organ donation with relatives. Corneal suitability was recorded as "not known" in a high proportion (1271; 45%) of all deaths and intensive care units reported only 123 corneal donors (4% of all audited deaths). CONCLUSION--When brain stem death is a possible diagnosis tests should always be carried out for confirmation. Early referral to the transplant team or coordinator should occur in all cases of brain stem death to check contraindications to organ donation. There should be increased use of asystolic kidney donation, and patients should be routinely assessed for suitability for corneal donation. Finally, more publicity and education are necessary to promote consent.     

CHOLEDOCHOLITHIASIS-Correlation of Preoperative with Operative and Postoperative Data to Enhance Diagnostic Insight

One hundred cases of common bile duct explorations were reviewed in an attempt to obtain information that might give insight into the diagnosis and definitive treatment of choledocholithiasis. Fifty of the hundred patients had common duct stones. Correlations were made between the incidence of choledocholithiasis as proved at operation, and the following factors: Kind and number of choledochal exploratory criteria used, the clinical diagnosis of common duct stones, and the pathologic features of gallbladders removed. The incidence of stones was statistically related to aging. The most frequent choledochal exploratory criteria were common duct dilatation or thickening (63 cases) and history of jaundice (50 cases). The most reliable single criterion in "diagnosing" common duct stones was palpable common or hepatic duct stones, the diagnosis having been correct in 15 of 17 such cases. The most reliable combination of criteria was a history of jaundice, plus palpable stones, with correct diagnosis in all such cases. The clinical diagnosis of choledocholithiasis was correct in only 17 per cent of cases. The correlation of the incidence of common duct stones with the degree of gallbladder disease-that is, acute or chronic-did not provide information that might be helpful in diagnosing choledocholithiasis. The incidence of proven retained common duct stones was 3 per cent, the non-fatal postoperative complication rate was 21 per cent and operative mortality was 1 per cent.     

Fine needle aspiration cytodiagnosis of clinically suspected tuberculosis in tissue enlargements

A retrospective study of the use of fine needle aspiration (FNA) cytology to confirm a clinical suspicion of tuberculosis in tissue enlargements was performed, using 70 cases. The criteria required to make an FNA cytodiagnosis of tuberculosis were reassessed, and the sensitivity and predictive value of cytology for diagnosing such aspirates was determined. All but 2 of the 70 aspirates contained adequate cellularity. The adequate samples were diagnosed as 40 cases of caseating tuberculosis, 11 cases of noncaseating tuberculosis and 17 cases of acute necrotizing granulomatous inflammation suspicious for tuberculosis. Subsequent histologic study verified the cytologic diagnosis in 27 of 27 biopsied caseating lesions, 4 of 7 biopsied noncaseating cases and 5 of 8 necrotizing cases. The six cases with a false-positive cytodiagnosis of tuberculosis were histologically diagnosed as one Lennert's lymphoma, two reactive lymph nodes and three necrotizing metastatic carcinomas. The sensitivity of FNA cytology for the diagnosis of tuberculosis was 100%, with the predictive value of a positive result being 88%. The findings in this study emphasize that all criteria for the diagnosis of tuberculosis in FNA samples must be utilized and that particular caution should be exercised in making a diagnosis of acute necrotizing tuberculosis.     

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

The Qatari law, as in many other countries, uses brain death as the main criteria for organ donation and cessation of medical support. By contrast, most of the public in Qatar do not agree with the limitation or withdrawal of medical care until the time of cardiac death. The current study aims to examine the duration of somatic survival after brain death, organ donation rate in brain-dead patients as well as review the underlying etiologies and level of support provided in the state of Qatar. This is a retrospective study of all patients diagnosed with brain death over a 10-year period conducted at the largest tertiary center in Qatar (Hamad General Hospital). Among the 53 patients who were diagnosed with brain death during the study period, the median and mean somatic survivals of brain-dead patients in the current study were 3 and 4.5 days respectively. The most common etiology was intracranial hemorrhage (45.3%) followed by ischemic stroke (17%). Ischemic stroke patients had a median survival of 11 days. Organ donation was accepted by only two families (6.6%) of the 30 brain dead patients deemed suitable for organ donation. The average somatic survival of brain-dead patients is less than one week irrespective of supportive measures provided. Organ donation rate was extremely low among brain-dead patients in Qatar. Improved public education may lead to significant improvement in resource utilization as well as organ transplant donors and should be a major target area of future health care policies.     

Clinical Analysis of Brain Trauma-Associated SIADH

The objective of this study was to analyze the clinical features of brain trauma associated syndrome of inappropriate antidiuretic hormone secretion. A retrospective analysis was performed for the electrolytes and osmolality of blood and urine samples of brain injury patients, which have been collected in our department since last 20 years. Four cases of brain injury patients met the criteria of SIADH, and three of them were cured but one patient died. In conclusion, the pathogenesis and treatment of SIADH associated with brain injury are different from hyponatremia. Early diagnosis and treatment can reduce the morbidity and mortality of patients with traumatic brain injury.     

Potential availability of cadaver organs for transplantation.

OBJECTIVE--To determine the potential number of cadaver kidney donors by applying defined donor criteria to people dying in hospital. DESIGN--Prospective study of all deaths occurring in 21 hospitals from 1 September 1988 to 31 August 1989. Questionnaires were administered to medical and nursing staff and families of potential donors aged 1-69. SETTING--Acute care hospitals in Gwent, South Glamorgan, Mid Glamorgan, West Glamorgan, Pembrokeshire, and East Dyfed health authorities, serving a population of 2.2 million. MAIN OUTCOME MEASURES--Cause of death, age, ventilation at time of death, diagnosis of brain death, and consideration of consent. RESULTS--Adequate data were available for 9840 of 10,095 hospital deaths (97.5% coverage). 188 patients aged 0-69 were identified as potential organ donors (widest definition), and of these 108 died without being ventilated at the time of death. Tests of brain stem death were formally completed in 57 cases, and organ donation was considered by the families of 47 of these potential donors. 26 patients became organ donors. Patients aged 50-69 with stroke were less likely to be ventilated than those aged less than or equal to 49 (21/96 v 24/34). Families of potential donors aged 20-39 were least likely to give permission. CONCLUSIONS--The supply of donor organs (specifically kidneys) could be increased by altering the management of patients aged 50-69 dying of severe cerebrovascular disease in general medical wards, in particular by increasing the proportion ventilated. The ethics of elective ventilation for the purposes of organ donation require discussion.     

AN EXPERIMENTAL COMPARISON OF DIFFERENT CRITERIA OF DEATH IN YEAST

Different criteria of death have been compared experimentally and quantitatively. Pure cultures of a yeast have been subjected to adverse conditions, and the number of dead cells, judged by different tests, has been determined in successive time intervals. The yeast cultures were exposed to heat, to HgCl₂, to ultraviolet light, and to x-rays. In each case, the cells lost the power of reproduction (measured by the plate count) most rapidly. The loss of fermentation (measured by the CO₂ pressure) was less rapid. Still slower was the change in staining reaction with methylene blue, and the loss of selective permeability of the plasma membrane (measured by the percentage of cells staining with Congo red). Slowest of all was the coagulation of protoplasm as observed in the dark-field. In the case of death by heat or by HgCl₂, the rate of loss of reproduction was about twice as rapid as that of the loss of fermentation, about three times that of the loss of semipermeability, and about forty times as large as the rate of coagulation. With ultraviolet light and with x-rays, these ratios were decidedly different. The technique employed does not permit the conclusion that any one criterion of death is the prerequisite for other criteria. It does not appear probable that loss of reproduction is the prerequisite for loss of fermentation or of semipermeability because the ratios of the velocities of these processes are not the same with all causes of death. There is no evidence that cells may show certain criteria of death immediately after exposure, and recover later.     

Accuracy of clinical diagnosis in a Canadian teaching hospital.

Two hundred autopsies were investigated to determine the correlation between the clinical and pathological diagnoses in three categories--major underlying disease, cause of death and significant incidental pulmonary findings. There was concurrence in diagnosis of the major underlying disease in 76% of cases, with 12% of disagreements being considered minor and 12% major. In only three cases might different management have affected the outcome had the correct diagnosis of the major underlying disease been made during life. There was concurrence of the diagnosis of the cause of death (which was often different from the underlying disease) in 64% of cases, and in 10% of cases the outcome might have been different had the clinical diagnosis been accurate. The clinical opinion that lung disease was the cause of death was confirmed at autopsy in 54% of cases, and 45% of the pulmonary causes of death as determined at autopsy had been recognized clinically. Major incidental pulmonary findings diagnosed clinically were confirmed in 76% of cases, and major pulmonary findings diagnosed at autopsy had been recognized clinically in 83%. The major sources of these discrepancies were pulmonary embolism and pneumonia. If autopsies are to play a role in patient management, clinicians will have to be made aware of discrepancies between clinical and autopsy diagnosis. The real test of efficacy would be modification of patient management for the good.     

Age at time of first intercourse v. chronologic age as a basis for Pap smear screening.

The Walton Report on cervical cancer screening programs recently recommended a new program for screening for cervical cancer based on chronologic age, calling for 3- and 5-year intervals between examinations. It recommended that such examinations be discontinued after 60 years of age. In a group of 232 routinely examined women (aged 18 to 47 years) in whom cervical intraepithelial neoplasia developed the timing of onset of the disease and the implications for screening were studied. The average age at the time of diagnosis was 30 years; in 20% of the patients the diagnosis had been made after age 35. The screening program recommended in the Walton Report would have been effective in diagnosing most cases (80%) in this sample by age 35 and all by age 60. However, when the patients were grouped according to age at the time of first intercourse, the diagnosis had been made after age 35 in only 13% of those who started having intercourse at age 15 to 17 years, 20% of those who started at age 18 to 19 years and 33% of those who started at age 20 years of later. When the times of diagnosis were expressed by number of years of intercourse the distributions became uniform in the same three groups; in 72% of all the patients the diagnosis had been made within the first 15 years of intercourse, in 88% it had been made within 20 years and in 100% it had been made by 30 years. These data suggest that a program based on number of years of intercourse may be more uniform and more efficient than one based on chronologic age, and that cytologic examinations should be concentrated during the time when most cases develop -- 6 to 20 years after the time of first intercourse.     

ARGUMENTS AGAINST PROMOTING ORGAN TRANSPLANTS FROM BRAIN‐DEAD DONORS,AND VIEWS OF CONTEMPORARY JAPANESE ON LIFE AND DEATH

As of 2009, the number of donors in Japan is the lowest among developed countries. On July 13, 2009, Japan's Organ Transplant Law was revised for the first time in 12 years. The revised and old laws differ greatly on four primary points: the definition of death, age requirements for donors, requirements for brain‐death determination and organ extraction, and the appropriateness of priority transplants for relatives. In the four months of deliberations in the National Diet before the new law was established, various arguments regarding brain death and organ transplantation were offered. An amazing variety of opinions continue to be offered, even after more than 40 years have elapsed since the first heart organ transplant in Japan. Some are of the opinion that with the passage of the revised law, Japan will finally become capable of performing transplants according to global standards. Contrarily, there are assertions that organ transplants from brain‐dead donors are unacceptable because they result in organs being taken from living human beings. Considering the current conditions, we will organize and introduce the arguments for and against organ transplants from brain‐dead donors in contemporary Japan. Subsequently, we will discuss the primary arguments against organ transplants from brain‐dead donors from the perspective of contemporary Japanese views on life and death. After introducing the recent view that brain death should not be regarded as equivalent to the death of a human being, we would like to probe the deeply‐rooted views on life and death upon which it is based.     

Clinical characteristics of patients with spondyloarthritides and HLA-B27 positive antigen

The aim of this study was to present our experiences in diagnosing spondyloarthritides (SpA), and to list the most common clinical features of HLA-B27 positive patients. The study included 65 HLA-B27 positive patients with confirmed diagnosis of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) who were analyzed between 2009 and 2010 in Clinic of Internal Medicine in Osijek. The diagnosis of seronegative spondyloarthritides was based on the ASAS (Assessment in AS Working Group) classification criteria for axial and then supplemented with ASAS criteria for peripheral SpA and was confirmed by radiological techniques. For diagnosing the ankylosing spondylitis (AS), there have been applied the modified New York criteria. Radiological criteria for definite sacroiliitis according to the modified New York criteria is bilateral sacroiliitis, grade 2-4 (> or = 2) or unilateral sacroiliitis, grade 3-4. For diagnosing the psoriatic arthritis (PsA), there were used CASPAR diagnostic criteria. Other features of SpA are defined within the existing classification criteria. HLA-B27 antigen was determined by direct immune-fluorescence technique using flow cytometer. The average age of patients was 50.34 years, of whom 27 female (41.53%), 38 male (58.46%). Duration of illness was 15.79 years on average. With 75.38% of patients, there had been determined the diagnosis of AS; 24.62% of patients had the diagnosis of PsA. The most common clinical characteristics that patients had were: inflammatory back pain (pain Inflammation along the lumbosacral spine), peripheral arthritis, intermittent pain in the gluteus, sacroiliitis, enthesitis, uveitis, dactilitis.     

CHOLEDOCHOLITHIASIS—Correlation of Preoperative with Operative and Postoperative Data to Enhance Diagnostic Insight

One hundred cases of common bile duct explorations were reviewed in an attempt to obtain information that might give insight into the diagnosis and definitive treatment of choledocholithiasis. Fifty of the hundred patients had common duct stones. Correlations were made between the incidence of choledocholithiasis as proved at operation, and the following factors: Kind and number of choledochal exploratory criteria used, the clinical diagnosis of common duct stones, and the pathologic features of gallbladders removed.The incidence of stones was statistically related to aging.The most frequent choledochal exploratory criteria were common duct dilatation or thickening (63 cases) and history of jaundice (50 cases).The most reliable single criterion in “diagnosing” common duct stones was palpable common or hepatic duct stones, the diagnosis having been correct in 15 of 17 such cases.The most reliable combination of criteria was a history of jaundice, plus palpable stones, with correct diagnosis in all such cases.The clinical diagnosis of choledocholithiasis was correct in only 17 per cent of cases.The correlation of the incidence of common duct stones with the degree of gallbladder disease—that is, acute or chronic—did not provide information that might be helpful in diagnosing choledocholithiasis.The incidence of proven retained common duct stones was 3 per cent, the non-fatal postoperative complication rate was 21 per cent and operative mortality was 1 per cent.     

When is pneumonia not pneumonia: a clinicopathologic study of the utility of lung tissue biopsies in determining the suitability of cadaveric tissue for donation

Healthcare-associated pneumonia (HCAP) represents a major diagnostic challenge because of the relatively low sensitivity and specificity of clinical criteria, radiological findings, and microbiologic culture results. It is often difficult to distinguish between pneumonia, underlying pulmonary disease, or conditions with pulmonary complications; this is compounded by the often-subjective clinical diagnosis of pneumonia. We conducted this study to determine the utility of post-mortem lung biopsies for diagnosing pneumonia in tissue donors diagnosed with pneumonia prior to death. Subjects were deceased patients who had been hospitalized at death and diagnosed with pneumonia. Post-mortem lung biopsies were obtained from the anatomic portion of the cadaveric lung corresponding to chest radiograph abnormalities. Specimens were fixed, stained with hematoxylin and eosin, and read by a single board-certified pathologist. Histological criteria for acute pneumonia included intense neutrophilic infiltration, fibrinous exudates, cellular debris, necrosis, or bacteria in the interstitium and intra-alveolar spaces. Of 143 subjects with a diagnosis of pneumonia at time of death, 14 (9.8 %) had histological evidence consistent with acute pneumonia. The most common histological diagnoses were emphysema (53 %), interstitial fibrosis (40 %), chronic atelectasis (36 %), acute and chronic passive congestion consistent with underlying cardiomyopathy (25 %), fibro-bullous disease (12 %), and acute bronchitis (11 %). HCAP represents a major diagnostic challenge because of the relatively low sensitivity and specificity of clinical criteria, radiological findings, and microbiologic testing. We found that attending physician-diagnosed pneumonia did not correlate with post-mortem pathological diagnosis. We conclude that histological examination of cadaveric lung tissue biopsies enables ascertainment or rule out of underlying pneumonia and prevents erroneous donor deferrals.     

The problematic role of 'irreversibility' in the definition of death

Most definitions of death – whether cardiopulmonary, whole brain and brain stem, or just upper brain – include an irreversibility condition. Cessation of function is not enough to declare death. Irreversibility should be limited to an organism's ability to 'restart' itself after vital organs have ceased to function. However, this would mean that every hour people who cannot be revived without the intervention of medical personnel and their technology are coming back from the dead. However, the alternative of irreversibility being dependent upon technology will lead to even more counterintuitive results such as: some people are dead at a particular time and place, but others in more technologically advanced eras and locations are alive despite their being in identical physical states; in the future, millions of cryogenically frozen human beings could spend centuries in a non–dead state because of the future technological breakthroughs; or large numbers of 'frozen' people are dead for aeons but coroners are not able to declare them so because they are unaware of what biological conditions science will never be able to reverse. So death should be defined only in non–relational biological terms with a self–starting condition similar to that once advocated by Lawrence Becker.     

The debate about death: an imperishable discussion?

In this concise review we discuss some of the complex edges of the concept of death that arose after the notorious advances in science and medicine over the last 50 years, in which the classical cardio-pulmonary criteria have led to the neurological criteria of death. New complicated questions like the definition of death and the operational criteria for diagnosing it have arisen and we think that they are far from being adequately and satisfactorily solved. A number of important issues--like the reliability and differences between cardio-pulmonary versus brain based criteria of death, if death is an event or a process, the meaning of integration and irreversibility--have not yet received sufficient attention. Here we have approached the death problem from two (biological) complex system perspectives: the organism level and the cellular-molecular level. We also discuss issues from a third systemic approach, that is, the entire society, thus involving legal, religious, bioethical and political aspects of death. Our aim is to integrate new perspectives in order to promote further discussion on these critical yet frequently neglected issues.     

36 例心源性猝死尸检的临床病理学研究*

目的:分析心源性猝死的临床病理学特征,为心源性猝死的诊断和预防提供理论依据。方法:收集36例心源性猝死病例的尸检解剖资料,进行病理组织学检查。结果:36例心源性猝死者中,冠心病21例,占心源性猝死者总数的58.33%;心律失常性右心室心肌病猝死者3例,占心源性猝死者总数的8.33%。结论:科学系统的尸检可以明确猝死原因,为医疗纠纷鉴定提供可靠依据,同时,对提高医疗质量,早期诊断、治疗心血管系统疾病和减少猝死发生起有重要作用。