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1.
Pediatrics ; 146(Suppl 1): S75-S80, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32737237

RESUMO

Death is defined biologically as the irreversible loss of the functioning of the organism as a whole, which typically occurs after the loss of cardiorespiratory function. In 1968, a Harvard committee proposed that death could also be defined neurologically as the irreversible loss of brain function. Brain death has been considered to be equivalent to cardiorespiratory arrest on the basis of the belief that the brain is required to maintain functioning of the organism as a whole and that without the brain, cardiorespiratory arrest and biological death are both rapid and certain. Over the past 20 years, however, this equivalence has been shown to be false on the basis of numerous cases of patients correctly diagnosed as brain-dead who nevertheless continued to survive for many years. The issue reached national attention with the case of Jahi McMath, a young woman diagnosed as brain-dead after a surgical accident, who survived for almost 5 years, mostly at home, supported with a ventilator and tube feedings. The fact that brain death is not biological death has many implications, notably including the concern that procurement of organs from brain-dead donors may not comply with the so-called dead donor rule, which requires that vital organs be procured from patients only after they are dead. In this article, I conclude with an analysis of options for moving forward and among them advocate for reframing brain death as a "social construct," with implicit societal acceptance that patients diagnosed as brain-dead may be treated legally and ethically the same as if they were biologically dead.


Assuntos
Morte Encefálica , Morte , Parada Cardíaca , Adolescente , Atitude Frente a Morte , Morte Encefálica/diagnóstico , Morte Encefálica/legislação & jurisprudência , Morte Encefálica/fisiopatologia , Feminino , Parada Cardíaca/diagnóstico , Parada Cardíaca/etiologia , Parada Cardíaca/fisiopatologia , História do Século XXI , Humanos , Neuroimagem/métodos , Neurologia/normas , Hemorragia Pós-Operatória/complicações , Guias de Prática Clínica como Assunto , Respiração Artificial , Sobrevivência , Fatores de Tempo , Inconsciência , Estados Unidos
2.
J Stroke Cerebrovasc Dis ; 29(9): 104913, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807410

RESUMO

Introduction and Case Presentation: Brain death can be associated with limb movements that are attributed to spinal reflexes. Although head/face movements have been rarely reported, no case of overt eye movements in brain death has been documented. We report a case of a patient with subtle eye movements whose exam was otherwise consistent with brain death. The presence of eye movements delayed pronouncing the patient as brain dead and delayed organ donation. We agree with American Academy of Neurology Position statement from 2019 that brain death does not mean demise of every neuron. Discussion: This case raises important questions about the types of movements that should be "allowed" during the determination of brain death to avoid delays in diagnosis.


Assuntos
Morte Encefálica/fisiopatologia , Morte Súbita Cardíaca/etiologia , Movimentos Oculares , Morte Encefálica/diagnóstico , Diagnóstico Tardio , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Tempo , Doadores de Tecidos , Coleta de Tecidos e Órgãos
3.
JAMA ; 324(11): 1078-1097, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32761206

RESUMO

Importance: There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries. Objective: To formulate a consensus statement of recommendations on determination of BD/DNC based on review of the literature and expert opinion of a large multidisciplinary, international panel. Process: Relevant international professional societies were recruited to develop recommendations regarding determination of BD/DNC. Literature searches of the Cochrane, Embase, and MEDLINE databases included January 1, 1992, through April 2020 identified pertinent articles for review. Because of the lack of high-quality data from randomized clinical trials or large observational studies, recommendations were formulated based on consensus of contributors and medical societies that represented relevant disciplines, including critical care, neurology, and neurosurgery. Evidence Synthesis: Based on review of the literature and consensus from a large multidisciplinary, international panel, minimum clinical criteria needed to determine BD/DNC in various circumstances were developed. Recommendations: Prior to evaluating a patient for BD/DNC, the patient should have an established neurologic diagnosis that can lead to the complete and irreversible loss of all brain function, and conditions that may confound the clinical examination and diseases that may mimic BD/DNC should be excluded. Determination of BD/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there is no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation; (2) pupils are fixed in a midsize or dilated position and are nonreactive to light; (3) corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is no facial movement to noxious stimulation; (5) the gag reflex is absent to bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to deep tracheal suctioning; (7) there is no brain-mediated motor response to noxious stimulation of the limbs; and (8) spontaneous respirations are not observed when apnea test targets reach pH <7.30 and Paco2 ≥60 mm Hg. If the clinical examination cannot be completed, ancillary testing may be considered with blood flow studies or electrophysiologic testing. Special consideration is needed for children, for persons receiving extracorporeal membrane oxygenation, and for those receiving therapeutic hypothermia, as well as for factors such as religious, societal, and cultural perspectives; legal requirements; and resource availability. Conclusions and Relevance: This report provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries.


Assuntos
Apneia/diagnóstico , Morte Encefálica/diagnóstico , Coma/diagnóstico , Fenômenos Fisiológicos do Sistema Nervoso , Pesquisa Biomédica , Morte Encefálica/fisiopatologia , Tronco Encefálico/fisiopatologia , Diagnóstico Diferencial , Humanos
5.
J Vis Exp ; (158)2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32364540

RESUMO

While both living donation and donation after circulatory death provide alternative opportunities for organ transplantation, donation after donor brain death (BD) still represents the major source for solid transplants. Unfortunately, the irreversible loss of brain function is known to induce multiple pathophysiological changes, including hemodynamic as well as hormonal modifications, finally leading to a systemic inflammatory response. Models that allow a systematic investigation of these effects in vivo are scarce. We present a murine model of BD induction, which could aid investigations into the devastating effects of BD on allograft quality. After implementing intra-arterial blood pressure measurement via the common carotid artery and reliable ventilation via a tracheostomy, BD is induced by steadily increasing intracranial pressure using a balloon catheter. Four hours after BD induction, organs may be harvested for analysis or for further transplantation procedures. Our strategy enables the comprehensive analysis of donor BD in a murine model, therefore allowing an in-depth understanding of BD-related effects in solid organ transplantation and potentially paving the way to optimized organ preconditioning.


Assuntos
Artérias/fisiopatologia , Determinação da Pressão Arterial , Morte Encefálica/fisiopatologia , Monitorização Fisiológica , Respiração Artificial , Traqueostomia , Animais , Pressão Sanguínea , Encéfalo/fisiopatologia , Morte Encefálica/sangue , Morte Encefálica/imunologia , Humanos , Sistema Imunitário/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante de Órgãos/métodos , Transplante Homólogo
7.
Clin Exp Metastasis ; 37(3): 435-444, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32377943

RESUMO

Brain metastasis (BM) affects up to one-third of adults with cancer and carries a historically bleak prognosis. Despite advances in stereotactic radiosurgery (SRS), rates of in-field recurrence (IFR) after SRS range from 10 to 25%. High rates of neurologic death have been reported after SRS failure, particularly for recurrences deep in the brain and surgically inaccessible. Laser interstitial thermal therapy (LITT) is an emerging option in this setting, but its ability to prevent a neurologic death is unknown. In this study, we investigate the causes of death among patients with BM who undergo LITT for IFR after SRS. We conducted a single institution retrospective case series of patients with BM who underwent LITT for IFR after SRS. Clinical and demographic data were collected via chart review. The primary endpoint was cause of death. Between 2010 and 2018, 70 patients with BM underwent LITT for IFR after SRS. Median follow-up after LITT was 12.0 months. At analysis, 49 patients died; a cause was determined in 44. Death was neurologic in 20 patients and non-neurologic in 24. The 24-month cumulative incidence of neurologic and non-neurologic death was 35.1% and 38.6%, respectively. Etiologies of neurologic death included local recurrence (n = 7), recovery failure (n = 7), distant progression (n = 5), and other (n = 1). Among our patient population, LITT provided the ability to stabilize neurologic disease in up to 2/3 of patients. For IFR after SRS, LITT may represent a reasonable treatment strategy for select patients. Additional work is necessary to determine the extent to which LITT can prevent neurologic death after recurrence of BM.


Assuntos
Morte Encefálica/diagnóstico , Neoplasias Encefálicas/terapia , Hipertermia Induzida , Recidiva Local de Neoplasia/terapia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/efeitos da radiação , Morte Encefálica/patologia , Morte Encefálica/fisiopatologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/secundário , Causas de Morte , Progressão da Doença , Feminino , Seguimentos , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/fisiopatologia , Seleção de Pacientes , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
8.
Curr Opin Organ Transplant ; 25(3): 241-247, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374575

RESUMO

PURPOSE OF REVIEW: Increasing number of patients with end-stage heart failure and those with improved survivorship from selective utilization of implantable mechanical circulatory support devices have added further burden and complexity to the transplant waitlist and on the rate-limiting availability of donor hearts from the standard pathway of donation after brain death. Unlike this conventional route, the increasing clinical use of donation after circulatory death (DCD) donor hearts necessitates a closer understanding of the logistics involved in the DCD process as well as of the risks associated with the unique pathophysiological consequences in this setting. RECENT FINDINGS: Notwithstanding a higher incidence of delayed graft function, the clinical utilization of DCD hearts for cardiac transplantation over the past five years has demonstrated this to be a well-tolerated and strategic alternative with excellent medium-term clinical outcomes. SUMMARY: The uptake of DCD heart transplantation remains selective and currently confined to Australia, the United Kingdom, Belgium, and more recently the USA. A more significant adoption will only come about through: a concerted effort to resolve the ethical and clinical controversies; a better understanding of postconditioning strategies; continued resolve to reduce the obligatory period of warm ischemia; and from better extracorporeal platforms that permit functional viability assessment of the DCD donor heart.


Assuntos
Morte Encefálica/fisiopatologia , Transplante de Coração/métodos , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
J Trauma Acute Care Surg ; 88(6): 783-788, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32459446

RESUMO

BACKGROUND: Delayed graft function (DGF), the need for dialysis in the first week following kidney transplant, affects approximately one quarter of deceased-donor kidney transplant recipients. Donor demographics, donor serum creatinine, and graft cold ischemia time are associated with DGF. However, there is no consensus on the optimal management of hemodynamic instability in organ donors after brain death (DBDs). Our objective was to determine the relationship between vasopressor selection during donor management and the development of DGF. METHODS: Prospective observational data, including demographic and critical care parameters, were collected for all DBDs managed by 17 organ procurement organizations from nine Organ Procurement and Transplantation Network Regions between 2012 and 2018. Recipient outcome data were linked with donor data through donor identification numbers. Donor critical care parameters, including type of vasopressor and doses, were recorded at three standardized time points during donor management. The analysis included only donors who received at least one vasopressor at all three time points. Vasopressor doses were converted to norepinephrine equivalent doses and analyzed as continuous variables. Univariate analyses were conducted to determine the association between donor variables and DGF. Results were adjusted for known predictors of DGF using binary logistic regression. RESULTS: Complete data were available for 5,554 kidney transplant recipients and 2,985 DBDs. On univariate analysis, donor serum creatinine, donor age, donor subtype, kidney donor profile index, graft cold ischemia time, phenylephrine dose, and dopamine dose were associated with DGF. After multivariable analysis, increased donor serum creatinine, donor age, kidney donor profile index, graft cold ischemia time, and phenylephrine dose remained independent predictors of DGF. CONCLUSION: Higher doses of phenylephrine were an independent predictor of DGF. With the exception of phenylephrine, the selection and dose of vasopressor during donor management did not predict the development of DGF. LEVEL OF EVIDENCE: Prognostic study, Level III.


Assuntos
Morte Encefálica/fisiopatologia , Cuidados Críticos/estatística & dados numéricos , Função Retardada do Enxerto/epidemiologia , Transplante de Rim/efeitos adversos , Rim/efeitos dos fármacos , Vasoconstritores/efeitos adversos , Adulto , Fatores Etários , Isquemia Fria/efeitos adversos , Cuidados Críticos/métodos , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/prevenção & controle , Relação Dose-Resposta a Droga , Feminino , Humanos , Rim/irrigação sanguínea , Rim/fisiopatologia , Transplante de Rim/métodos , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Fenilefrina/administração & dosagem , Fenilefrina/efeitos adversos , Estudos Prospectivos , Medição de Risco , Obtenção de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Vasoconstritores/administração & dosagem , Adulto Jovem
10.
Transplantation ; 104(9): 1862-1868, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32345867

RESUMO

BACKGROUND: Intestine graft viability compromises retrieval in most brain-dead donors. Small bowel transplantation is a complex procedure with worse outcomes than transplantation of other abdominal organs. The hormone 17ß-estradiol (E2) has shown vascular protective effects in lung tissue of brain death (BD) male rats. Thus, estradiol might be a treatment option to improve the quality of intestinal grafts. METHODS: Male Wistar rats were divided into 3 groups (n = 10/group): rats that were trepanned only (sham-operated), rats subjected to rapid-onset BD, and brain-dead rats treated with E2 (280 µg/kg, intravenous) (BD-E2). Experiments performed for 180 minutes thereafter are included: (a) laser-Doppler flowmetry and intravital microscopy to evaluate mesenteric perfusion; (b) histopathological analysis; (c) real-time polymerase chain reaction of endothelial nitric oxide synthase (eNOS) and endothelin-1; (d) immunohistochemistry of eNOS, endothelin-1, P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 expression; and (e) ELISA for cytokines and chemokines measurement. RESULTS: 17ß-Estradiol improved microcirculatory perfusion and reduced intestinal edema and hemorrhage after BD. The proportions of perfused small vessels were (mean ± scanning electron microscope) BD rats (40% ± 6%), sham-operated rats (75% ± 8%), and BD-E2 rats (67% ± 5%) (P = 0.011). 17ß-Estradiol treatment was associated with 2-fold increase in eNOS protein (P < 0.0001) and gene (P = 0.0009) expression, with no differences in endothelin-1 expression. BD-E2 rats exhibited a reduction in vascular cell adhesion molecule 1 expression and reduced cytokine-induced neutrophil chemoattractant 1 and interleukina-10 serum levels. CONCLUSIONS: 17ß-Estradiol was effective in improving mesenteric perfusion and reducing intestinal edema and hemorrhage associated with BD. The suggestion is that E2 might be considered a therapy to mitigate, at least in part, the deleterious effects of BD in small bowel donors.


Assuntos
Morte Encefálica/fisiopatologia , Estradiol/farmacologia , Intestino Delgado/transplante , Microcirculação/efeitos dos fármacos , Perfusão , Doadores de Tecidos , Animais , Citocinas/sangue , Hemorragia Gastrointestinal/prevenção & controle , Intestino Delgado/patologia , Masculino , Ratos , Ratos Wistar , Circulação Esplâncnica/efeitos dos fármacos
11.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32220905

RESUMO

The American Academy of Neurology believes that doctors have the right to do tests to evaluate whether a patient is brain dead even if the family does not consent. They argue that physicians have "both the moral authority and professional responsibility" to do such evaluations, just as they have the authority and responsibility to declare someone dead by circulatory criteria. Not everyone agrees. Truog and Tasker argue that apnea testing to confirm brain death has risks and that, for some families, those risks may outweigh the benefits. So, what should doctors do when caring for a patient whom they believe to be brain dead but whose parents refuse to allow testing to confirm that the patient meets neurologic criteria for death? In this article, we analyze the issues that arise when parents refuse such testing.


Assuntos
Morte Encefálica/diagnóstico , Exame Neurológico/psicologia , Consentimento dos Pais , Adolescente , Atitude Frente a Morte , Temas Bioéticos , Morte Encefálica/fisiopatologia , Tomada de Decisão Clínica , Humanos , Masculino , Futilidade Médica/legislação & jurisprudência , Futilidade Médica/psicologia , Exame Neurológico/ética , Consentimento dos Pais/ética , Consentimento dos Pais/legislação & jurisprudência , Pais , Religião e Psicologia , Suicídio
12.
J Bras Pneumol ; 46(2): e20180299, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32130341

RESUMO

OBJECTIVE: Brain death (BD) triggers important hemodynamic and inflammatory alterations, compromising the viability of organs suitable for transplantation. To better understand the microcirculatory alterations in donor lungs caused by BD. The present study investigated the pulmonary microcirculation in a rodent model of BD via intravital microscopy. METHODS: Male Wistar rats were anaesthetized and mechanically ventilated. They were trepanned and BD was induced through the increase in intracranial pressure. As control group, sham-operated (SH) rats were trepanned only. In both groups, expiratory O2 and CO2 were monitored and after three hours, a thoracotomy was performed, and a window was created to observe the lung surface using an epi-fluorescence intravital microscopy. Lung expression of intercellular adhesion molecule (ICAM)-1 and endothelial nitric oxide synthase (eNOS) was evaluated by immunohistochemistry, and cytokines were measured in lung samples. RESULTS: Three hours after the surgical procedures, pulmonary perfusion was 73% in the SH group. On the other hand, BD animals showed an important decrease in organ perfusion to 28% (p = 0.036). Lung microcirculatory compromise after BD induction was associated with an augmentation of the number of leukocytes recruited to lung tissue, and with a reduction in eNOS expression and an increase in ICAM-1 expression on lung endothelial cells. BD rats showed higher values of expiratory O2 and lower values of CO2 in comparison with SH animals after three hours of monitoring. CONCLUSION: Data presented showed that BD triggers an important hypoperfusion and inflammation in the lungs, compromising the donor pulmonary microcirculation.


Assuntos
Morte Encefálica/fisiopatologia , Células Endoteliais , Pulmão/irrigação sanguínea , Microcirculação/fisiologia , Doadores de Tecidos , Animais , Masculino , Microvasos , Modelos Teóricos , Ratos , Ratos Wistar
13.
Clin Exp Metastasis ; 37(2): 353-363, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32008137

RESUMO

The role of radiosurgery has become further accentuated in the era of targeted agents (TA). Thus, the neurologic outcome of radiosurgery in brain metastasis (BM) of non-small cell lung cancer (NSCLC) was reviewed. We analyzed 135 patients with BM of NSCLC who were administered Cyberknife radiosurgery (CKRS) as either initial or salvage therapy. We evaluated local failure (LF), intracranial failure (IF), and neurological death (ND) due to BM. Primary outcome was neurological death-free survival (NDFS). Median follow-up was 16.2 months. Median CKRS dose of 22 Gy was administered to median 2 targets per patient. Among 99 deaths, 14 (14%) were ND. Upfront treatment for BM included CKRS alone in 85 patients (63%), CKRS + TA in 26 patients (19%), and WBRT in 24 patients (18%). No patients or tumor related factors were associated with ND. However, the type of upfront treatment for BM was significantly associated with ND [HR 0.07 (95% CI 0.01-0.57) for CKRS + TA, HR 0.56 (95% CI 0.19-1.68) for CKRS alone] compared with the WBRT group (P = 0.01). The 2-year NDFS rates for the CKRS + TA, CRKS alone, and WBRT groups were 94%, 87%, and 78%, respectively (P = 0.03). Upfront CKRS showed significantly higher 2-year LF-free survival rate (P < 0.01). IF rate was insignificantly lower in the WBRT group compared with CKRS group (P = 0.38). Upfront CKRS + TA was associated with the best neurological outcome with high NDFS. Active brain control by early delivery of radiosurgery could achieve better neurological outcome in NSCLC with BM.


Assuntos
Morte Encefálica/diagnóstico , Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/patologia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Encéfalo/efeitos da radiação , Morte Encefálica/fisiopatologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação/métodos , Fatores de Tempo
14.
Am J Nurs ; 120(3): 32-38, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32049689

RESUMO

In 1968, the criteria for brain death were established by the Harvard Ad Hoc Committee. Despite what may appear to be unambiguous definitions, clinicians, ethicists, and the public have grappled with the concept of brain death since its inception. In light of recent public discourse on the topic, Harvard Medical School convened a conference to examine research and ethical inquiry conducted over the past 50 years related to death as defined by neurologic criteria. Drawing on the report produced by this conference, this article provides an overview of the development of brain death criteria, describes recent controversies and updates, and discusses implications of these criteria for nurses.


Assuntos
Bioética/história , Morte Encefálica/diagnóstico , Morte Encefálica/fisiopatologia , Família/psicologia , História do Século XX , História do Século XXI , Humanos , Enfermeiras e Enfermeiros/psicologia , Guias de Prática Clínica como Assunto
15.
Curr Opin Organ Transplant ; 25(2): 144-150, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32073483

RESUMO

PURPOSE OF REVIEW: The identification and utilization of kidneys from uncontrolled donation after circulatory death (uDCD) donors for transplantation may increase transplantation rates markedly. This article summarizes the latest international results from successful uDCD kidney transplant programmes and considers how such programmes may impact on the transplant waiting list. RECENT FINDINGS: The results of more than 1000 uDCD donor kidney transplants have been reported since 2007 from France and Spain. Estimates from France, Spain and Sweden suggest that effective utilization of the potential uDCD donor pool might increase donation rates by 25%. The main concern relating to uDCD kidney transplantation is the high incidence of primary nonfunction with the incidence of primary nonfunction reported as 7-8% even with careful donor selection and the use of normothermic regional perfusion at the time of organ recovery. Notwithstanding, reported 1- year graft survival figures are equivalent to those from expanded criteria donors (ECD) and 10-year graft survival of between 72 and 82% was reported in the two single-centre series with longest reported follow-up period. SUMMARY: Uncontrolled DCD kidney transplantation has been successfully implemented in several regions in France and Spain. Wider implementation of uDCD programmes would increase substantially the number of kidneys for transplantation, while maintaining acceptable transplant outcomes.


Assuntos
Morte Encefálica/fisiopatologia , Transplante de Rim/métodos , Humanos , Doadores de Tecidos , Resultado do Tratamento
16.
Acta Cir Bras ; 34(11): e201901107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939503

RESUMO

PURPOSE: To establish a hypotensive brain death pig model and observe the effects of hypotension on small bowel donors. METHODS: The hypotensive brain death model was produced using the modified intracranial water sac inflation method in ten domestic crossbred pigs. Effects of hypotensive brain death on small bowel tissue morphology were evaluated through changes in intestinal tissue pathology, tight junction protein of the intestinal mucosa and plasma intestinal fatty acid-binding protein (i-FABP) levels. The pathophysiological mechanism was examined based on changes in superior mesenteric artery (SMA) blood flow and systemic hemodynamics. RESULTS: After model establishment, SMA blood flow, and the mean arterial pressure (MAP) significantly decreased, while heart rate increased rapidly and fluctuated significantly. Small bowel tissue morphology and levels of tight junction protein of the intestinal mucosa showed that after model establishment, small bowel tissue injury was gradually aggravated over time (P<0.05). Plasma i-FABP levels significantly increased after brain death (P<0.05). CONCLUSIONS: A hypotensive brain death pig model was successfully established using an improved intracranial water sac inflation method. This method offers a possibility of describing the injury mechanisms more clearly during and after brain death.


Assuntos
Morte Encefálica/fisiopatologia , Modelos Animais de Doenças , Hipotensão/fisiopatologia , Intestino Delgado/patologia , Intestino Delgado/transplante , Animais , Biópsia , Western Blotting , Ensaio de Imunoadsorção Enzimática , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Hemodinâmica , Intestino Delgado/irrigação sanguínea , Masculino , Microscopia Eletrônica de Transmissão , Reprodutibilidade dos Testes , Suínos , Fatores de Tempo , Proteína da Zônula de Oclusão-1/análise
17.
Clin Neurophysiol ; 131(3): 676-693, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31978852

RESUMO

Heart rate variability (HRV) has been associated with various diseases and reflects autonomic cardiac control sensitive to central nervous system function. Examples of the heart-brain interaction are illustrated by extreme clinical conditions such as brain death, orthotopic heart transplantation, weaning from respirator support, and brain maturation in preterm infants. Interactions with the immune system document the importance of HRV for tumor growth and prognosis. Research linking HRV to the regulation of negative emotions including depression and anxiety document the sensitive influence of central commands on cardiac activity. Moreover, 0.1 Hz oscillations in the heart and the brain seem to be coupled, thus indicating central pacemakers on the heart rhythm. Moreover, low frequency oscillations in heart rate seem to be composed of two subcomponents presumably signaling different central-autonomic functions. We conclude by showing that breathing at 6 breaths/minute could induce coherence of the 0.1 Hz oscillations, thus facilitating physical and psychological function. The reviewed findings impressively demonstrate that central nervous system function modifies the rhythm of the heart and vice versa, suggesting that HRV could be a useful indicator of central-autonomic integration and that 0.1 Hz oscillations play a major role in physical and mental health via optimizing energy supply.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Morte Encefálica/fisiopatologia , Frequência Cardíaca/fisiologia , Respiração , Cuidados Críticos , Humanos
18.
Br J Surg ; 107(1): 87-95, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573084

RESUMO

BACKGROUND: When the blood supply ceases in a deceased organ donor, ischaemic injury starts. Kidneys are cooled to reduce cellular metabolism and minimize ischaemic injury. This cooling is slow and kidneys are lukewarm during nephrectomy. Smaller single-centre studies have shown that prolonged donor nephrectomy time decreases early kidney transplant function, but the effect on long-term outcome has never been investigated in large multicentre cohort studies. METHODS: The relationship between donor nephrectomy time and death-censored graft survival was evaluated in recipients of single adult-to-adult, first-time deceased-donor kidneys transplanted in the Eurotransplant region between 2004 and 2013. RESULTS: A total of 13 914 recipients were included. Median donor nephrectomy time was 51 (i.q.r. 39-65) min. Kidneys donated after circulatory death had longer nephrectomy times than those from brain-dead donors: median 57 (43-78) versus 50 (39-64) min respectively (P < 0·001). Donor nephrectomy time was independently associated with graft loss when kidneys were donated after circulatory death: adjusted hazard ratio (HR) 1·05 (95 per cent c.i. 1·01 to 1·09) per 10-min increase (P = 0·026). The magnitude of this effect was comparable to the effect of each hour of additional cold ischaemia: HR 1·04 (1·01 to 1·07) per h (P = 0·004). For kidneys donated after brain death, there was no effect of nephrectomy time on graft survival: adjusted HR 1·01 (0·98 to 1·04) per 10 min (P = 0·464). CONCLUSION: Prolonged donor nephrectomy time impairs graft outcome in kidneys donated after circulatory death. Keeping this short, together with efficient cooling during nephrectomy, might improve outcome.


Assuntos
Rejeição de Enxerto/etiologia , Transplante de Rim/métodos , Nefrectomia/estatística & dados numéricos , Doadores de Tecidos , Coleta de Tecidos e Órgãos/métodos , Idoso , Morte Encefálica/fisiopatologia , Isquemia Fria/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
19.
Acta cir. bras ; 34(11): e201901107, Nov. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1054678

RESUMO

Abstract Purpose: To establish a hypotensive brain death pig model and observe the effects of hypotension on small bowel donors. Methods: The hypotensive brain death model was produced using the modified intracranial water sac inflation method in ten domestic crossbred pigs. Effects of hypotensive brain death on small bowel tissue morphology were evaluated through changes in intestinal tissue pathology, tight junction protein of the intestinal mucosa and plasma intestinal fatty acid-binding protein (i-FABP) levels. The pathophysiological mechanism was examined based on changes in superior mesenteric artery (SMA) blood flow and systemic hemodynamics. Results: After model establishment, SMA blood flow, and the mean arterial pressure (MAP) significantly decreased, while heart rate increased rapidly and fluctuated significantly. Small bowel tissue morphology and levels of tight junction protein of the intestinal mucosa showed that after model establishment, small bowel tissue injury was gradually aggravated over time (P<0.05). Plasma i-FABP levels significantly increased after brain death (P<0.05). Conclusions: A hypotensive brain death pig model was successfully established using an improved intracranial water sac inflation method. This method offers a possibility of describing the injury mechanisms more clearly during and after brain death.


Assuntos
Animais , Masculino , Feminino , Morte Encefálica/fisiopatologia , Modelos Animais de Doenças , Hipotensão/fisiopatologia , Intestino Delgado/patologia , Intestino Delgado/transplante , Suínos , Fatores de Tempo , Biópsia , Ensaio de Imunoadsorção Enzimática , Western Blotting , Reprodutibilidade dos Testes , Microscopia Eletrônica de Transmissão , Proteínas de Ligação a Ácido Graxo/sangue , Proteína da Zônula de Oclusão-1/análise , Hemodinâmica , Intestino Delgado/irrigação sanguínea
20.
Biomed Res Int ; 2019: 5924101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565655

RESUMO

Deceased after circulatory death (DCD) donors offer a viable solution to the current organ shortage, particularly the Maastricht Class III (arrest subsequent to cessation of life support in the hospital). Although current results from these donors are very satisfactory, the number of included donors is too low and future expansion of inclusion criteria will likely decrease organ quality, with negative consequences on the complication rate. This donor type thus represents a priority in terms of scientific exploration, so as to study it in controlled settings and prepare for future challenges. Hence, we mimicked the DCD Class III clinical conditions a Large White pig model. Herein, we detail the different strategies attempted to attain our objectives, including technical approaches such as animal positioning and ventilator settings, as well as pharmacological intervention to modulate blood pressure and heart rate. We highlight the best combination of factors to successfully reproduce DCD Class III conditions, with perfusion pressures and functional warm ischemia (hypoperfusion) closely resembling clinical situations. Finally, we detail the functional and histological impacts of these conditions. Such a model could be of critical value to explore novel management alternative for these donors, presenting a uniquely adapted platform for such therapeutics as normothermic regional circulation and/or pharmacological intervention.


Assuntos
Morte Encefálica/fisiopatologia , Rejeição de Enxerto/fisiopatologia , Sobrevivência de Enxerto/fisiologia , Doadores de Tecidos , Animais , Morte , Humanos , Transplante de Fígado/métodos , Masculino , Suínos/fisiologia , Obtenção de Tecidos e Órgãos
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