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1.
Can J Surg ; 63(6): E581-E593, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33278908

RESUMO

Humans are destined to explore space, yet critical illness and injury may be catastrophically limiting for extraterrestrial travel. Humans are superorganisms living in symbiosis with their microbiomes, whose genetic diversity dwarfs that of humans. Symbiosis is critical and imbalances are associated with disease, occurring within hours of serious illness and injury. There are many characteristics of space flight that negatively influence the microbiome, especially deep space itself, with its increased radiation and absence of gravity. Prolonged weightlessness causes many physiologic changes that are detrimental; some resemble aging and will adversely affect the ability to tolerate critical illness or injury and subsequent treatment. Critical illness-induced intra-abdominal hypertension (IAH) may induce malperfusion of both the viscera and microbiome, with potentially catastrophic effects. Evidence from animal models confirms profound IAH effects on the gut, namely ischemia and disruption of barrier function, mechanistically linking IAH to resultant organ dysfunction. Therefore, a pathologic dysbiome, space-induced immune dysfunction and a diminished cardiorespiratory reserve with exacerbated susceptibility to IAH, imply that a space-deconditioned astronaut will be vulnerable to IAH-induced gut malperfusion. This sets the stage for severe gut ischemia and massive biomediator generation in an astronaut with reduced cardiorespiratory/immunological capacity. Fortunately, experiments in weightless analogue environments suggest that IAH may be ameliorated by conformational abdominal wall changes and a resetting of thoracoabdominal mechanics. Thus, review of the interactions of physiologic changes with prolonged weightlessness and IAH is required to identify appropriate questions for planning exploration class space surgical care.


L'humanité est à l'aube d'une nouvelle ère d'exploration spatiale, mais le risque de maladies et blessures graves pourrait restreindre de manière catastrophique le potentiel des voyages dans l'espace. L'être humain est un superorganisme vivant en symbiose avec son microbiote, dont la diversité génétique éclipse celle de l'hôte. Cette symbiose est essentielle : tout déséquilibre est associé à une dégradation de l'état de santé dans les heures suivant l'occurrence d'une blessure ou d'une maladie grave. Bon nombre de caractéristiques propres au vol spatial ont des répercussions négatives sur le microbiote; l'espace lointain présente des dangers particuliers en raison de l'exposition accrue au rayonnement et de l'absence de gravité. L'exposition prolongée à l'apesanteur cause une myriade de changements physiologiques nuisant à la santé. Certains ressemblent à des processus de vieillissement et réduiront la capacité à tolérer une blessure ou une maladie grave et son traitement. L'hypertension intra-abdominale (HIA) causée par une maladie grave peut réduire la perfusion des viscères et du microbiote, ce qui peut avoir des conséquences catastrophiques. Des études sur modèle animal ont confirmé les effets profondément délétères de l'HIA sur les intestins par l'apparition d'une ischémie et une altération de la barrière intestinale; cette découverte permettrait d'établir un lien mécanistique entre l'HIA et la défaillance d'organes résultante. Par conséquent, une dysbiose pathologique, associée à un dysfonctionnement immunitaire en apesanteur et à une réduction de la réserve cardiorespiratoire accompagnée d'une exacerbation de la susceptibilité à l'HIA, pourrait signifier qu'un astronaute exposé à l'effet déconditionnant de l'apesanteur serait vulnérable aux problèmes de perfusion de l'intestin découlant de l'HIA. Ce problème pourrait à son tour mener à une ischémie intestinale grave et à une production massive de biomédiateurs chez un astronaute présentant déjà une capacité cardiorespiratoire et immunitaire réduite. Heureusement, des expériences dans des environnements simulant l'apesanteur semblent indiquer que les effets de l'HIA pourraient être contrés par des changements conformationnels de la paroi abdominale et un rétablissement de la mécanique thoracoabdominale. Par conséquent, un examen des interactions des changements physiologiques associés à un état d'apesanteur prolongé et à l'HIA est requis pour déterminer les questions à poser afin de planifier adéquatement les soins chirurgicaux en contexte d'exploration spatiale.


Assuntos
Disbiose/fisiopatologia , Hipertensão Intra-Abdominal/fisiopatologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Voo Espacial , Ausência de Peso/efeitos adversos , Abdome/fisiopatologia , Animais , Estado Terminal , Disbiose/etiologia , Disbiose/prevenção & controle , Microbioma Gastrointestinal/fisiologia , Humanos , Hipertensão Intra-Abdominal/etiologia , Hipertensão Intra-Abdominal/prevenção & controle , Modelos Animais , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controle
2.
World J Emerg Surg ; 14: 39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31404221

RESUMO

Background: Severe complicated intra-abdominal sepsis (SCIAS) has high mortality, thought due in part to progressive bio-mediator generation, systemic inflammation, and multiple organ failure. Treatment includes early antibiotics and operative source control. At surgery, open abdomen management with negative-peritoneal-pressure therapy (NPPT) has been hypothesized to mitigate MOF and death, although clinical equipoise for this operative approach exists. The Closed or Open after Laparotomy (COOL) study (https://clinicaltrials.gov/ct2/show/NCT03163095) will prospectively randomize eligible patients intra-operatively to formal abdominal closure or OA with NPTT. We review the ethical basis for conducting research in SCIAS. Main body: Research in critically ill incapacitated patients is important to advance care. Conducting research among SCIAS is complicated due to the severity of illness including delirium, need for emergent interventions, diagnostic criteria confirmed only at laparotomy, and obtundation from anaesthesia. In other circumstances involving critically ill patients, clinical experts have worked closely with ethicists to apply principles that balance the rights of patients whilst simultaneously permitting inclusion in research. In Canada, the Tri-Council Policy Statement-2 (TCPS-2) describes six criteria that permit study enrollment and randomization in such situations: (a) serious threat to the prospective participant requires immediate intervention; (b) either no standard efficacious care exists or the research offers realistic possibility of direct benefit; (c) risks are not greater than that involved in standard care or are clearly justified by prospect for direct benefits; (d) prospective participant is unconscious or lacks capacity to understand the complexities of the research; (e) third-party authorization cannot be secured in sufficient time; and (f) no relevant prior directives are known to exist that preclude participation. TCPS-2 criteria are in principle not dissimilar to other (inter)national criteria. The COOL study will use waiver of consent to initiate enrollment and randomization, followed by surrogate or proxy consent, and finally delayed informed consent in subjects that survive and regain capacity. Conclusions: A delayed consent mechanism is a practical and ethical solution to challenges in research in SCIAS. The ultimate goal of consent is to balance respect for patient participants and to permit participation in new trials with a reasonable opportunity for improved outcome and minimal risk of harm.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/educação , Procedimentos Cirúrgicos do Sistema Digestório/ética , Sepse/cirurgia , Humanos , Consentimento Livre e Esclarecido/ética , Consentimento Livre e Esclarecido/normas , Estudos Prospectivos , Projetos de Pesquisa/normas
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