Transcranial Doppler for early identification of potential organ transplant donors

BACKGROUND: Encouraging results in transplant medicine create a growing demand for organ transplant donors. Transcranial Doppler (TCD) has been used by several investigators to assess arrest of the cerebral circulation in brain dead patients. We report on TCD as a monitoring tool for early identification of potential organ transplant donors. DESIGN: A prospective clinical study. SETTING: Intensive care unit (ICU) of a 900-bed community hospital (primary and tertiary care center) in Vienna, Austria. SUBJECTS AND METHODS: All patients with acute intracranial lesions admitted to our intensive care unit underwent TCD examination at least once daily. In patients with Glasgow Coma Scores < 7, TCD waveforms with high resistance profiles unchanged by therapeutic attempts to lower intracranial pressure indicated the need for repeated TCD up to four times a day. TCD waveform abnormality consisting of absent or reversed diastolic flow or small early systolic spikes in at least two intracranial arteries was considered to constitute intracranial circulatory arrest. Brain death was confirmed by clinical criteria, an isoelectric electroencephalography (EEG) or non filling of the intracerebral arteries on arteriography. RESULTS: From January 1994 to July 1996 we identified 11 comatose patients as potential organ transplant donors with typical TCD findings indicating intracranial circulatory arrest. Diagnosis was subarachnoid hemorrhage in 7 and intracerebral hemorrhage in 4 patients. Brain death diagnosis according to the criteria of Austrian law was initiated immediately after the TCD findings suggested intracranial circulatory arrest. Confirmation of brain death was obtained by clinical criteria and either EEG (6 patients) or cerebral angiography (5 patients). CONCLUSION: TCD examinations on a daily routine basis offer a noninvasive monitoring method for early assessment of intracranial circulatory arrest. TCD enables quick identification and further diagnosis of candidates for organ transplant donation.     

Warm ischemic tolerance in collapsed pulmonary grafts is limited to 1 hour

OBJECTIVE: To determine the length of warm ischemic tolerance in pulmonary grafts from non-heart-beating donors. SUMMARY BACKGROUND DATA: If lungs could be retrieved for transplant after circulatory arrest, the shortage of donors might be significantly alleviated. Great concern, however, exists about the length of tolerable warm ischemia before cold preservation of pulmonary grafts retrieved from such non-heart-beating donors. METHODS: The authors compared the influence of an increasing postmortem interval on graft function in an isolated, room air-ventilated rabbit lung model during blood reperfusion up to 4 hours. Four groups of cadavers (four animals per group) were studied. In group 1, lungs were immediately reperfused. In the other groups, cadavers with lungs deflated were left at room temperature for 1 hour (group 2), 2 hours (group 3), or 4 hours (group 4). RESULTS: Pulmonary vascular resistance was enhanced in all ischemic groups compared with the control group. An increase was noted with longer postmortem intervals in peak airway pressure and in weight gain. A concomitant decline was observed in the venoarterial oxygen pressure gradient caused by progressive edema formation, as reflected by the wet-to-dry weight ratio at the end of reperfusion. CONCLUSIONS: Warm ischemia resulted in increased pulmonary vascular resistance. Graft function in lungs retrieved 1 hour after death was not significantly worse than in nonischemic lungs. Therefore, 60 minutes of warm ischemia with the lung collapsed may be tolerated before cold storage. Further studies are necessary to investigate whether lungs retrieved from non-heart-beating donors will become a realistic alternative for transplant.     

The feasibility of organ salvage from non-heart-beating trauma donors

BACKGROUND: Blunt trauma patients without vital signs on admission are potential non-heart-beating donors. OBJECTIVE: To review the feasibility of postmortem visceral perfusion and organ donation in blunt trauma patients without vital signs. DESIGN: A retrospective case series of blunt trauma victims who were declared dead in the emergency department. SETTING: A level I trauma center. MAIN OUTCOME MEASURES: Factors potentially precluding donation and potential donor yield. RESULTS: The mean trauma-to-death interval was 71 minutes (< 60 minutes in 57% of the cases). Injuries likely to interfere with in situ perfusion were present in 41% of the cases. The tissue donation consent rate was 45%. Assuming a similar organ donation consent rate, the potential donor yield was 9% after excluding victims who were younger than 60 years of age, warm ischemia times that were less than 60 minutes, and patients who had injuries precluding perfusion. CONCLUSIONS: The potential organ yield from non-heart-beating, blunt trauma victims is low, which highlights the ethical and legal problems of this approach.     

Leadership: as my father used to say

From 1983 to August 1995, the University of Miami Organ Procurement Organization evaluated 41 candidates for non-heart-beating cadaveric donation and determined that 34 patients met the criteria. All patients had irreversible brain injury incompatible with survival. All families gave permission for withdrawal of life support and for tissue and organ donation after cardiac arrest. Thirteen donors died in the operating room, and 9 died in the ICU or emergency department. Four of the 9 patients who died in the ICU had undergone femoral cannulation. The remaining 12 donors were brain-dead but had an unpredicted cardiac arrest before laparotomy. All kidneys were preserved by using machine pulsatile perfusion, and 21 kidneys were transported to other centers. Of the 35 transplanted kidneys, 26 (74%) had immediate function, 6 (17%) had delayed graft function, and 3 (9%) were not used for other reasons. Five of the six transplanted livers had immediate function.     

Real-time X-ray diffraction study at different scan rates of phase transitions for dipalmitoylphosphatidylcholine in KSCN

A questionnaire survey was carried out to examine the attitudes and practices of Australian and New Zealand intensivists with regard to brain death and organ donation. A return rate of 82.5% was achieved. Fifty-eight per cent had written evidence of their own wishes to donate organs and 94% would agree to donation from a dependent. At least one intensivist is involved in certifying brain death on 95% of occasions. Intensivists are involved in the request for organ donation over 90% of the time although one-third do not believe that it is their role to request organ donation. Although two-thirds believe that the family should always be approached for organ donation, another 52 out of 254 indicated that it was their (the intensivist's) role to decide if families should be asked for organ donation. Possible reasons for not requesting are language or other communication problems, perceptions of cultural differences and degrees of family distress. Twenty per cent of respondents do not provide haemodynamic support before brain death confirmation. Australian and New Zealand intensivists overwhelmingly support the concept of brain death, current methods of confirmation of brain death, organ donation and transplantation. Possible reasons behind loss of potential donors include decisions not to resuscitate both before and after brain death is confirmed. Perceptions of family grief and cultural differences clearly inhibit requests for organ donation. A very few units have an effective policy on approaching families about organ donation. Intensivists have almost exclusive control over requests for organ donation and thus bear a full professional responsibility for this element of hospital practice.     

The “ick” factor, anticipated regret, and willingness to become an organ donor.

Objective: This research tested the role of traditional rational-cognitive factors and emotional barriers to posthumous organ donation. An example of an emotional barrier is the “ick” factor, a basic disgust reaction to the idea of organ donation. We also tested the potential role of manipulating anticipated regret to increase intention to donate in people who are not yet registered organ donors. Design: In three experiments involving 621 members of the United Kingdom general public, participants were invited to complete questionnaire measures tapping potential emotional affective attitude barriers such as the “ick” factor, the desire to retain bodily integrity after death, and medical mistrust. Registered posthumous organ donors were compared with nondonors. In Experiments 2 and 3, nondonors were then allocated to a simple anticipated regret manipulation versus a control condition, and the impact on intention to donate was tested. Main Outcome Measures: Self-reported emotional barriers and intention to donate in the future. Results: Traditional rational-cognitive factors such as knowledge, attitude, and subjective norm failed to distinguish donors from nondonors. However, in all three experiments, nondonors scored significantly higher than donors on the emotional “ick” factor and bodily integrity scales. A simple anticipated regret manipulation led to a significant increase in intention to register as an organ donor in future. Conclusions: Negative affective attitudes are thus crucial barriers to people registering as organ donors. A simple anticipated regret manipulation has the potential to significantly increase organ donation rates. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Analysis of donor versus nondonor demographics

A retrospective analysis of the demographic features of all potential organ donors over a 3-year period (1994-1996) at one organ procurement organization was conducted. The potential donor pool of 495 people was 42% female and 58% male, with a slight difference in consent by gender. The mean income difference between donors and nondonors was less than $3000 per year (obtained from zip code census data). Educational achievement affected donation at the lowest educational levels. Cause of death influenced donation, with motor vehicle crash victims donating more often. The strongest factor in consent for donation was ethnicity; whites were more likely to donate than were other ethnic groups. The combination of gender, ethnicity, and cause of death improved the probability of determining a positive outcome to 63%. Demographic information on donors and nondonors can increase public and professional understanding as well as influence decision making to improve donation.     

Organs for transplantation. The demand increases--but not the supply

The supply of organs is the only factor which limits the scope of transplantation to help the severely ill. As the number of donors can not be appreciably increased, the functional and medical criteria for donors are reduced instead. Although the already positive attitude of the public to cadaveric organ donation is unlikely to improve further, intensified information campaigns might result in more people discussing organ donation with their relatives and informing them of their views, which would help surviving relatives to decide for or against organ donation. It should also be possible to improve access to organs by educating health care personnel.     

Fatal cerebral gunshot wounds: factors influencing organ donation

Patients with clinical brain death following head injury are important potential cadaveric organ donors. We analyzed our series of cranial gunshot wounds with particular attention to the frequency and patterns of organ donation after fatal injuries. Sixty-six patients with gunshot wounds to the head, including 59 with intracranial involvement (43 male, average age 26 years) were seen during a 4-year period. Injuries were limited to the head in 50 of 59 patients. Overall mortality was 66 per cent. Predictors of mortality included Glasgow Coma Scale (GCS) of six or less (93%), self-inflicted gunshot wounds (75%), and computed tomography (CT) findings of bihemispheric injury (87%) or ventricular injury (82%). Of the 39 patients who died, 28 met standard criteria for brain death, and nine of these went on to organ procurement. Thirteen families refused donation, and six patients were not harvested for reasons including old age, pregnancy, suspicion of AIDS, coroner refusal, and failure to pursue consent. Principles essential to maximal organ retrieval include: 1) Recognition that patients suffering cerebral gunshot wounds represent potential organ donors and that certain factors are predictive of mortality; 2) Critical care/trauma team approach with standardized management and timely declaration of brain death; 3) Early search for family members and prompt notification of organ procurement agencies; 4) Sensitivity to cultural issues influencing donation; and 5) Programs to increase public awareness of organ donation.     

A rapid organ recovery program for non-heart-beating donors

We report a successful method for rapid organ recovery from the non-heart-beating donor, which can open a new resource of organs for transplantation. The RORP is not controversial, is simple in design and execution, and results in kidneys that are viable for transplantation. Special personnel and equipment are needed but are easily incorporated in the overall budget of an OPO or donor hospital. Clearly more research is needed to rebuild ischemically damaged cells ex vivo and to develop new agents/methods to minimize the reperfusion response. When these processes are better understood and managed, the full potential of the NHBD as a donor resource will be fully achieved. We agree with others that the donor shortage could be entirely relieved by routine organ recovery from NHBD trauma victims.     

The echocardiographic findings in patients with brain death. The implications for their selection as heart transplant donors

INTRODUCTION AND AIMS: Brain death causes myocardial impairment by some mechanisms not yet well understood. The aim of this work was to assess the echocardiographic features found in these patients and their implication in donor selection for heart transplantation. METHODS: With this aim, we have studied 38 consecutive patients with brain death assessed as possible donors for heart transplant in our hospital in the last 3 years. Age was 23 +/- 13 years; 77% were male. No history of cardiac disease was present in any patient. An adequate transthoracic echocardiogram was obtained in 74% of patients; transesophageal view was used in the remaining 26%. RESULTS: Echocardiogram was strictly normal in only 14 patients (37%). Mild valvular alterations were found in 5 patients (13%); a dilated aortic root in 1 (3%); moderate concentric left ventricular hypertrophy in 5 (14%); mild pericardial effusion in 1 (3%); mild septal hypokinesia with normal left ventricular ejection fraction in 4 (10%); abnormal left ventricular diastolic function in 7 (18%); and diffuse hypokinesia with ejection fraction less than 60% in 14 (37%). In 7 patients (18%) ejection fraction was lower than 40% (one of them was cocaine-addict). Mean ejection fraction was 59 +/- 15% (23 to 83%). Only 2 of the 19 (10%) donor hearts implanted in our hospital showed early dysfunction after transplant, but no relation to pretransplant ejection fraction was found. Ejection fraction increased from 62% pretransplant to 73% at one week after transplant in the other 17 cases. CONCLUSIONS: Brain death commonly causes alterations of left ventricular function, and this impairment is severe in almost 20% of cases. These echocardiographic features must be known when selection of donors for heart transplantation is concerned.     

Liver splitting and living donor techniques

Split liver transplantation (SLT) and living related transplantation (LRT) have been developed following advancements in liver surgery. In experienced hands they can yield results comparable to full organ liver transplantation. They are today a reality which has to be implemented and used more widely. LRT is the best procedure available and should be the method of choice despite the high success of SLT. Any method safely enlarging the pool of donors has to be utilized, especially in view of the possible future application for adults. The procedures should be initially performed and tested in centres specialized in liver transplantation and liver surgery, with the aim of making the techniques more widely available in the future. High ethical standards are required to perform LRT. In the short term, SLT and LRT are the methods more apt to increase the organ pool and thus decrease pre-transplant mortality both in children and adults.     

Right ventricular arrhythmogenic dysplasia

The influence of donor age and recipient age on outcome after renal transplantation has been investigated in numerous studies. There is some evidence that patient survival in elderly patients who receive a transplant is significantly higher compared with those, who remain on dialysis. In general, patient survival after renal transplantation is mainly dependent on recipient age and on comorbid conditions. Concerning graft survival, most studies conclude that the survival of kidneys taken from older donors (> 50 years) and very young donors (< 5 years) is reduced. Graft survival was also found to be reduced in very young recipients (< 5 years). Functional graft survival proved to be better in older recipients (> 50 years) as compared to younger recipients, due to a reduced immunologic response capability. Actual graft survival however, where cases of death with functioning graft are included, is fairly equal in both populations. The question, whether the age difference between donor and recipient has an influence on graft survival, needs to be further investigated. In conclusion, donor and recipient age are important risk factors, which may influence outcome after renal transplantation and therefore should be considered carefully.     

Granulocytic Ehrlichia infection in ixodid ticks and mammals in woodlands and uplands of the U.K

BACKGROUND: The number of patients waiting lung transplantation greatly exceeds the supply of donors. This study was conducted to determine the effect of high-dose steroid administration on oxygenation and donor lung recovery after brain death. METHODS: A retrospective analysis was conducted on 118 consecutive organ donors from January 1 through December 31, 1995. Eighty donors received high-dose steroids (methylprednisolone, mean 14.5+/-0.06 mg/kg) after organ procurement organization management began; a second group was composed of 38 patients who received no steroids. PaO2/FiO2 ratios were used to evaluate oxygenation. The number of single and double lungs transplanted served as the endpoint. RESULTS: No differences were noted in hemodynamics, most clinical or demographic variables and initial values of PaO2/FiO2 between groups. However, nonsteroid-treated donors showed an overall decrease in oxygenation (mean decrease in PaO2/FiO2 -34.2+/-14), whereas steroid-treated donors had a significant and progressive increase in oxygenation (mean increase in PaO2/FiO2: 16+/-14) before aortic cross-clamping (p = 0.01). Time before cross-clamping was longer in the steroid-treated patients (p = 0.003). The number of procured lungs was markedly greater in steroid-treated than nonsteroid-treated donors (25/80 patients vs 3/38; p < 0.01). CONCLUSIONS: High-dose methylprednisolone given during donor management results in improved oxygenation at organ recovery. This treatment resulted in a significant increase in the number of lungs transplanted and may have enabled donors to be treated longer.     

Human cytomegalovirus infection: new methods for virological diagnosis

Recently developed methods have greatly increased the sensitivity and speed of virological diagnosis of cytomegalovirus infection. Virus can be detected in infected cell cultures within 24 or 48 hours of specimen inoculation by using monoclonal antibodies to immediate-early antigens in immunocytochemistry procedures or DNA sequences in hybridisation in situ assays. CMV antigens can also be detected directly in infected cells within clinical specimens. An early antigen can be visualized in nuclei of circulating leukocytes from viremic patients. DNA hybridization is used for CMV analysis in Dot-blot, Southern-blot and in situ hybridization assays. DNA amplification, by polymerase chain reaction (PCR), has proven to be a very sensitive method for diagnosis of CMV infection and should be useful for investigation of CMV pathogenesis and latency. Serologic assays such as ELISA and latex agglutination assays are accurate for screening donors and recipients of blood and organ or marrow graft. Studies of viral protein epitopes recognized by human sera are in progress.     

C-13 Methanol Far-Infrared Laser: Newly Discovered Lines, Predictions, and Assignments

Autologous blood donation before elective surgery is generally believed to be a safe procedure for patients with a variety of underlying medical conditions, but the accumulation of additional data continues to define its safety in unique patient groups. Patients who have received a solid organ transplant may also undergo various elective surgical procedures after transplantation, and the question of safety of autologous blood donation for these patients is raised. In one hospital-based blood collection program, we identified 4 patients who had received solid organ transplants and subsequently made autologous blood donations for elective operations unrelated to the transplantation. Two patients had received heart transplants and 2 received liver transplants. A total of 10 autologous donations were made by these 4 patients without adverse effects or complications. A low hemoglobin concentration was the only reason for temporary deferral from autologous donation. Despite having complicated clinical situations, recipients of solid organ transplants can safely donate autologous blood and should not be automatically excluded from making such donations.     

Diagnosis of death in comatose patients under resuscitation treatment: a critical review of the Harvard report

In this Article, which draws primarily on continental West European views on death and dying, the author contends that the Harvard criteria for irreversible coma (1968) are not reliable for diagnosing death in comatose patients under resuscitation treatment. The Article suggests that use of the Harvard Criteria to diagnose death leaves such patients legally unprotected against surgical assaults such as organ removal and biomedical experiments while they still may be living and capable of perception, possibly including the perception of pain and the spoken word. An alternative to the Harvard Criteria--angiography--is offered, and several additional issues related to the definition and diagnosis of death are discussed. Finally, the author suggests that even prior to death, termination of resuscitation treatment of irreversibly comatose patients, though followed by death, should be lawful.     

Viral hepatitis and kidney transplantation

Many etiologic factors can cause hepatic dysfunction in renal transplant recipients. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the major causes of hepatitis in such patients. Taiwan is an endemic area for HBV infection, and HCV infection is also quite common among Taiwanese patients with end-stage renal disease. Whether renal transplantation can be safely performed in these patients is controversial. Advances in understanding of the natural course and improved treatment results in viral hepatitis patients in recent years have gradually improved the outlook for renal transplantation in such patients. Because of the severe shortage of organ donors worldwide, research efforts have also been directed at studying the safety and feasibility of using kidneys from donors infected with HBV or HCV. Short-term results are good for renal transplantation in HBV- or HCV- infected recipients, as well as for recipients who receive HBV- or HCV- infected kidneys. Long-term results show that these patients are at greater risk for hepatic disorders and have poorer outcomes than cohorts without infection, although their survival is better than that of patients with HBV or HCV infection who remain on dialysis. To plan effective treatment strategies, renal transplant physicians should be alert to the occurrence of hepatitis among these patients and realize its impact on renal transplant recipients in terms of increased morbidity/mortality and altered pharmacokinetics of immunosuppressive drugs. Hepatitis in renal transplant recipients is a great challenge for both transplant physicians and hepatologists. Many unresolved issues need further investigation.     

Injury prevention programmes in primary care: a high risk group or a whole population approach?

Assessments of the acceptability of new transplantation practices require a pinpointing of not only the meaning of death, but also the timing of death. They typically perceive elective ventilation as occurring just prior to death and non-heart-beating donor protocols as operative just after death. However, such practices in fact highlight the general vagueness and ambiguity surrounding these issues in both law and ethics. Supply-side dilemmas in transplantation lend real urgency to this "life or death" debate.