Materiały źródłowe

• #1 Brain Death – EMCrit Project

  https://emcrit.org/ibcc/brain-death/

  Defined as irreversible cessation of all cerebral and brainstem functioning. […] Brain death is defined by a strict set of criteria that, once met, confers zero likelihood of awakening from coma. […] Regardless of the initial injury, eventually brain death occurs via a spiral of progressive intracranial hypertension, tissue damage, and edema. This is essentially an intracranial compartment syndrome. […] Complete brain death occurs when there is complete circulatory arrest of the brain no blood is entering the brain.

• #2

  https://journals.lww.com/amjm/fulltext/2020/16020/pathophysiology_of_brain_stem_death.4.aspx

  Brain stem death (BD) is a pathological process which has a profound effect on hemodynamic balance, hormone levels and functioning of other organ systems. It also triggers a systemic inflammatory response. Knowledge about the changes that occur during brain stem death is necessary for subsequent management. This article discusses the pathophysiological changes in the body after brain stem death. […] Brain stem death (BD) is a pathological process which is characterized by hormonal impairment, hemodynamic imbalance, and a systemic inflammatory response. Knowledge about these changes is important in managing a BD donor. […] The American Academy of Neurology defines BD as the irreversible loss of brain and brain stem function, usually caused by major hemorrhage, hypoxia, or metabolic dysregulation.

• #3 Brain Death – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538159/

  Brain death, both a legal and clinical term, has been present in medical literature and texts for many years and was defined by the Uniform Determination of Death Act (UDDA) in 1981. […] The course primarily focuses on three core areas: the etiology and progression to brain death, distinguishing brain death from other states such as coma or vegetative state, and the comprehensive criteria and protocols for the diagnosis of brain death. […] Brain death occurs as a result of an acute catastrophic brain injury. Abrupt loss of cerebral perfusion occurs if a concomitant elevation of intracranial pressure exceeds the mean arterial pressure. […] Inadequate tissue oxygenation leads to a progressive cascade of further edema, increasing intracranial pressure (ICP), a further decrease in cerebral perfusion and eventual herniation, or complete cessation of blood flow and aseptic necrosis of brain tissue.

• #4 Brain death: a clinical overview | Journal of Intensive Care | Full Text

  https://jintensivecare.biomedcentral.com/articles/10.1186/s40560-022-00609-4

  Brain death, also commonly referred to as death by neurologic criteria, has been considered a legal definition of death for decades. Its determination involves many considerations and subtleties. […] In 1959, the concept of brain death/death by neurologic criteria (BD/DNC) was first theorized as le coma dpass, by Mollaret and Goulon, who described an apneic, comatose patient without brainstem reflexes or electroencephalographic (EEG) activity. Neurologists began to postulate that neurologic function was equally or more vital than cardiopulmonary function, and began a process to define death neurologically, independent of other essential organ functions. […] The first and most widely accepted is the whole brain formulation which asserts that brain death is equivalent to catastrophic injury to all the major structures of the brain including the hemispheres, diencephalon, brainstem, and cerebellum. In this view, confirmation of complete and permanent damage to the whole brain should be confirmed before BD/DNC is ultimately declared.

• #5 Brain death diagnosis | STROKE MANUAL

  https://www.stroke-manual.com/brain-death-diagnosis/

  brain death (BD)/death by neurologic criteria (DNC) is defined as the permanent (irreversible) loss of all functions of the entire brain (including the brainstem), regardless of the continued function of the cardiovascular system and other organs […] These conditions lead to intracranial hypertension (with brain herniation) and a decrease and subsequent disappearance of cerebral perfusion. This results in necrosis of brain cells and loss of function. […] there must be no doubt about the cause of BD/DNC and the irreversibility of brain damage […] death may be caused by a primary structural brain lesion or a secondary metabolic or hypoxic lesion causing brain edema […] when a patient is comatose, apneic, and has absent brainstem reflexes but there is not an identified mechanism of brain injury, there is a risk that the clinical findings may be caused by a reversible process […] the effects of drugs altering the central nervous system function (sedatives, hypnotics, and opioids) […] hypothermia may reduce the metabolic demands of brain cells and lead to a clinical image of brain death […] cerebral perfusion arrest occurs when ICP MAP.

• #6 Brain death: a review | Egyptian Journal of Neurosurgery | Full Text

  https://ejns.springeropen.com/articles/10.1186/s41984-024-00269-6

  To date, the recognized medical criteria for BD/DNC (brain death/death according to neurological criteria) in the USA (United States of America) are the 2010 AAN (American Academy of Neurology) standards for identification of the BD/DNC for adult age and the 2011 Society of Critical Care Medicine/Child Neurology Society/American Academy of Pediatrics standards for identification of BD/DNC in Pediatrics. […] This review defines the essential requirements of BD/DNC, its assessment (including apnea test) on a clinical basis, usage of additional examinations, and the arguments for its definition worldwide. […] The pathophysiology of brain death is analogous irrespective of the cause. Tissue hypoxia leads to a continuous gush of excess edema (due to liberation of cytotoxic materials), elevated intracranial pressure (which in turn impairs more the brain tissue oxygenation), marked reduction of cerebral perfusion and brain herniation, or complete stop of cerebral blood flow and a subsequent brain tissue aseptic necrosis.

• #7 Brain death: a review | Egyptian Journal of Neurosurgery | Full Text

  https://ejns.springeropen.com/articles/10.1186/s41984-024-00269-6

  It is noted that the mechanism of cerebral edema during hypoxia is the influx of sodium ions across a pre-existing electrochemical gradient due to ATP (adenosine triphosphate) depletion and a defect in the Na+-K+ATPase pump; Besides disrupting the bloodbrain barrier (damaged by reactive oxygen species), it contributes to increased fluid leakage and brain edema. […] In all age categories, a known extracranial or intracranial etiology may be responsible for brain death which happens next to significant damage of the brain neuronal cells resulting in permanent coma (loss of consciousness), absent brainstem reflexes, and apnea.

• #8

  https://journals.lww.com/amjm/fulltext/2020/16020/pathophysiology_of_brain_stem_death.4.aspx

  Cushing reflex is characterized by bradycardia and systemic arterial hypertension and can be seen in a BD patient due to rise in intracranial pressure (ICP). […] High intracranial pressure causes cerebral and brain stem herniation which leads to sympathetic stimulation and dysfunction of the hypothalamo-pituitary axis. This in turn causes hypotension and also reduces levels of circulating ADH, thyroid hormones and cortisol. […] Ischemia leads to metabolic acidosis which stimulates the releases of cytokines and activates coagulation factors and promotes leukocytic proliferation, causing systemic inflammatory pathway activation and tissue damage. […] Brain stem failure leads to initial hypertension and bradycardia followed by an intense sympathetic storm which remains unopposed due to ischemia of the parasympathetic vagal nucleus and occurs in a rostrocaudal direction.

• #9 Pathophysiology of brain stem death. – Document – Gale OneFile: Health and Medicine

  https://go.gale.com/ps/i.do?id=GALE%7CA633601349&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=09759662&p=HRCA&sw=w

  Ischemia leads to metabolic acidosis which stimulates the releases of cytokines and activates coagulation factors and promotes leukocytic proliferation, causing systemic inflammatory pathway activation and tissue damage. […] Brain stem failure leads to initial hypertension and bradycardia followed by an intense 'sympathetic storm’ which remains unopposed due to ischemia of the parasympathetic vagal nucleus and occurs in a rostrocaudal direction.

• #9 Pathophysiology of brain stem death. – Document – Gale OneFile: Health and Medicine

  https://go.gale.com/ps/i.do?id=GALE%7CA633601349&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=09759662&p=HRCA&sw=w

  Brain stem death (BD) is a pathological process which has a profound effect on hemodynamic balance, hormone levels and functioning of other organ systems. […] Brain stem death (BD) is a pathological process which is characterized by hormonal impairment, hemodynamic imbalance, and a systemic inflammatory response. […] The American Academy of Neurology defines BD as the irreversible loss of brain and brain stem function, usually caused by major hemorrhage, hypoxia, or metabolic dysregulation. […] Cushing reflex is characterized by bradycardia and systemic arterial hypertension and can be seen in a BD patient due to rise in intracranial pressure (ICP). […] High intracranial pressure causes cerebral and brain stem herniation which leads to sympathetic stimulation and dysfunction of the hypothalamo-pituitary axis.

• #10

  https://journals.lww.com/amjm/fulltext/2020/16020/pathophysiology_of_brain_stem_death.4.aspx

  The massive increase in sympathetic tone results in widespread vasoconstriction and microthrombus formation, which in turn impairs organ and tissue perfusion. […] The pathophysiology of cardiac dysfunction after BD remains controversial. […] BD is frequently accompanied by massive release of endogenous catecholamines (catecholamine storm). […] High levels of norepinephrine in the myocardial interstitium lead to myocyte necrosis and contractile dysfunction and damage the sympathetic nerve terminals themselves. […] The reduction in calcium ATPase activity leads to myocyte calcium overload and cell death, which occurs due to the high interstitial concentration of norepinephrine. […] The inflammatory response is accelerated with rapid expression of cytokines, chemokines, and adhesion molecules and leukocyte infiltration.

• #11

  https://journals.lww.com/amjm/fulltext/2020/16020/pathophysiology_of_brain_stem_death.4.aspx

  BD causes cessation of the hypothalamic-pituitary axis and affects hormone regulation. […] Nonthyroidal illness syndrome (NTIS) can be seen in BD donors, which may confound the metabolic state. […] The biological processes related with transcription and metabolic process were dysregulated in the liver after BD. […] BD is associated with increased complement activation, apoptosis, and pro-inflammatory cytokine and plays an important role in graft rejection. […] Newer studies showed that the association between resistin and MCP-1 in the brain stem dead organ donors seems to indicate a causative relationship between these two and may suggest a role for resistin in the initiation of the inflammatory response after brain death. […] The increased VWF propeptide levels in the brain stem dead organ donors are due to an acute activation of the endothelium.

• #12 The intractable problems with brain death and possible solutions | Philosophy, Ethics, and Humanities in Medicine | Full Text

  https://peh-med.biomedcentral.com/articles/10.1186/s13010-021-00107-9

  The problem is that it is now known that BD is not the loss of integrated functioning of the organism as a whole. […] The BD Hypothesis is that without the brain serving to integrate and unify the dynamic metabolic processes, the organism is no longer a unified whole that acts together to maintain homeostasis and resist entropy and disintegration. […] In the state of BD, there is only a mere collection of parts, and not an organism. This is why the state of BD meets the concept/definition of death – that there is no longer an organism as a whole. […] The problem is that it is now known that BD is not the loss of integrated functioning of the organism as a whole. […] These cases demonstrated many signs of homeostasis including the following: homeostasis of a countless variety of mutually interacting chemicals, macromolecules and physiological parameters, through the functions especially of liver, kidneys, cardiovascular and endocrine systems, elimination, detoxification and recycling of cellular wastes throughout the body, energy balance, maintenance of body temperature, wound healing, fighting of infections (including development of a febrile response), cardiovascular and hormonal stress responses to unanesthetized incision for organ retrieval, successful gestation of a fetus, sexual maturation (i.e., puberty), proportional growth, resuscitatability and stabilizability following cardiac arrest, and ability to bounce back from episodes of hypotension, aspiration, sepsis and other serious systemic setbacks, spontaneous improvement in general health i.e., the gradual stabilizing of cardiovascular status so that initially required pressor drugs can be successfully withdrawn, the gradual return of gastrointestinal motility so that initially required parenteral fluids and nutrition can be successfully switched to the enteral route ability to maintain fluid and electrolyte balance with no or rare monitoring or adjustments in fluid and hormonal therapy.

• #13 Immunomodulatory effects of thalidomide in an experimental brain death liver donor model | Scientific Reports

  https://www.nature.com/articles/s41598-021-98538-z

  Brain death is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify graft immunogenicity. […] Brain death (BD) is characterized by blood-brain barrier dysfunction, resulting in intense cellular and molecular activation that quickly evokes an immune response with both cellular and humoral components, both systemically and intragraftly, thereby increasing graft immunogenicity. Therefore, BD itself has been recognized as an important risk factor for graft failure. […] Several investigations have postulated that immunomodulatory factors produced during BD may be mediated by increased levels of cytokines, such as interleukin TNF-, IL-1, and IL-6. […] In this context, nuclear factor kappa B (NF-B) has a remarkable role in coordinating the expression of a variety of genes, especially those that participate in inflammation and alloimmunity.

• #14

  https://journals.lww.com/neur/fulltext/2018/66020/brain_death_revisited.5.aspx

  Severe damage to neuronal tissue leads to edema and increase in intracranial pressure (ICP). Elevated ICP reduces cerebral perfusion pressure and cerebral blood flow. A vicious cycle is established in which decreasing cerebral perfusion and increasing ICP reinforce one another until blood no longer enters the cranial cavity and transtentorial herniation and coning at the foramen magnum occurs. This herniation crushes the brain-stem leading to permanent dysfunction. […] Total loss of neurophysiological functions of the brain for more than 8 minutes confirms total and irreversible loss of brain function. […] Complete cardiovascular and autonomic uncoupling has been shown after brain stem death. […] Diffuse metabolic cellular injury due to lack of hypothalamic control, producing generalized metabolic and hypoxic lesions in all tissues also occurs.

• #15 Diagnosis of brain death – UpToDate

  https://www.uptodate.com/contents/diagnosis-of-brain-death

  Death of the brain therefore qualifies as death, as the brain is essential for integrating critical functions of the body. […] Brain death signifies the complete, irreversible cessation of brain function, including the capacity for the brainstem to regulate respiratory and vegetative activities. […] In most adult series, trauma and subarachnoid hemorrhage are the most common events leading to brain death.

• #16 Exploring Brain Death at a Tertiary Pediatric Intensive Care Unit in Turkey; Incidence, Etiology and Organ Donation – Journal of Pediatric Emergency and Intensive Care Medicine

  https://caybdergi.com/articles/doi/cayd.79663

  Severe traumatic brain injury (TBI) is associated with brain death. […] The overall incidence of pediatric brain death, especially in severe TBI is not known in Turkey. […] Brain death is a common mode of death after severe TBI, more frequent than non-trauma cases admitted to our PICU. […] Brain death, defined as irreversible cessation of all functions of the brain, including brain stem, is valid for medicolegal determination of death. […] The prevalence of pediatric brain death, specifically due to severe TBI, is not known in Turkey. […] Our study revealed that brain death was more common in severe TBI patients admitted to PICU compared to other critically ill children without a history of trauma (0.8% vs. 0.3%). […] We conclude that patients with severe TBI are the most likely candidates for brain death declaration and donation of suitable organs for children in need.

• #17 Diagnosis of brain death – UpToDate

  https://www.uptodate.com/contents/diagnosis-of-brain-death/print

  Death of the brain therefore qualifies as death, as the brain is essential for integrating critical functions of the body. […] Brain death signifies the complete, irreversible cessation of brain function, including the capacity for the brainstem to regulate respiratory and vegetative activities. […] In most adult series, trauma and subarachnoid hemorrhage are the most common events leading to brain death. Others include intracerebral hemorrhage, hypoxic-ischemic encephalopathy, and ischemic stroke. Any condition causing permanent widespread brain injury can lead to brain death.

• #18

  https://www.nhs.uk/conditions/brain-death/

  Brain death (also known as brain stem death) is when a person on an artificial life support machine no longer has any brain functions. This means they will not regain consciousness or be able to breathe without support. […] A person who is brain dead is legally confirmed as dead. They have no chance of recovery because their body is unable to survive without artificial life support. […] Brain death can happen when the blood or oxygen supply to the brain is stopped. […] Brain death can also be caused by a severe head injury, a brain haemorrhage, infections, such as encephalitis, or a brain tumour. […] After brain death, it is not possible for someone to remain conscious. […] The difference between brain death and a vegetative state (a disorder of consciousness), which can happen after extensive brain damage, is that it’s possible to recover from a vegetative state, but brain death is permanent.

• #19 Facts about brain death and how it’s determined – Gift of Life Michigan

  https://giftoflifemichigan.org/blog/facts-about-brain-death-and-how-its-determined

  Brain death is death. […] According to the American Academy of Neurology, brain death is the irreversible and complete loss of brain and brain stem function. […] Brain death typically occurs after a major injury or illness where the blood supply to the brain is blocked, or the brain begins to swell within the skull. […] Brain death is determined by strict medical and legal criteria. […] Many things may cause severe, permanent brain damage that leads to brain death. […] The brain needs blood and oxygen to function, so any serious injury or illness that keeps blood and oxygen from the brain may cause brain death. […] In brain death, patients dont react to noise, lights or touch as they would before a brain injury. […] If the patient has a catastrophic brain injury, they cant breathe on their own and rely on ventilators.

• #20 Brain death: a clinical overview | Journal of Intensive Care | Full Text

  https://jintensivecare.biomedcentral.com/articles/10.1186/s40560-022-00609-4

  The second concept refers to brainstem death which is the accepted construct in the United Kingdom (U.K.) and a few other countries, asserting that destruction of the brainstem alone is equivalent to the death of a human, given that the brainstem partially houses the centers for consciousness, as well as essential cardiac and respiratory centers. […] A third but less traditional concept of brain death is the higher brain formulation, which postulates that only destruction of the higher brain, including the cortex and bilateral hemispheres, is necessary to diagnose BD/DNC, given these areas are critical to cognition. […] The clinical determination of BD/DNC is detailed and can be daunting even to experienced critical care providers and neurologists. Correct diagnosis is of utmost importance, and the minimum clinical criteria and examination involves many steps.

• #21 Brain Death – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538159/

  For TBIs or other intracranial injuries, increasing ICP leads to a decrease in CPP and prevents adequate oxygenation of neuronal tissues. This situation will result in further injury, edema, and, eventually, the process initially described above. […] The physiology of brain death is similar regardless of the etiology.

• #22

  https://journals.lww.com/neur/fulltext/2018/66020/brain_death_revisited.5.aspx

  Even with maximal support, cardio-respiratory deterioration leading to somatic death will occur within days, although persistence of the cardio-respiratory drive for prolonged periods, even over 100 days, has been reported. […] The medullary reticular formation (RF) contains the vital centers controlling heartbeat, breathing and circulation. The pontine RF contains centers for coordination of acoustic, vestibular, respiratory and cardiovascular processes. The midbrain RF contains centers for visuospatial orientation and eating behavior. […] As brain-stem is structurally and functionally very compact, even small lesions can destroy vital cardiac and respiratory centers, disconnect the cerebral cortex from the brain-stem, and damage sensory fibers from higher centers of consciousness, perception and cognition. Damage to the RF may lead to loss of cognition, persistent unconsciousness and coma. The brain stem, which includes the midbrain, pons and medulla, contains the nuclei of the last ten cranial nerves and ascending and descending tracts. The reticular activating system provides the anatomical and physiological basis for wakeful consciousness.

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