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Greet Van Den Berghe - One of the best experts on this subject based on the ideXlab platform.

  • anterior pituitary function in Critical Illness
    Endocrine connections, 2019
    Co-Authors: Arno Teblick, Lies Langouche, Greet Van Den Berghe
    Abstract:

    Critical Illness is hallmarked by major changes in all hypothalamic-pituitary-peripheral hormonal axes. Extensive animal and human studies have identified a biphasic pattern in circulating pituitary and peripheral hormone levels throughout Critical Illness by analogy with the fasting state. In the acute phase of Critical Illness, following a deleterious event, rapid neuroendocrine changes try to direct the human body toward a catabolic state to ensure provision of elementary energy sources, whereas costly anabolic processes are postponed. Thanks to new technologies and improvements in Critical care, the majority of patients survive the acute insult and recover within a week. However, an important part of patients admitted to the ICU fail to recover sufficiently, and a prolonged phase of Critical Illness sets in. This prolonged phase of Critical Illness is characterized by a uniform suppression of the hypothalamic-pituitary-peripheral hormonal axes. Whereas the alterations in hormonal levels during the first hours and days after the onset of Critical Illness are evolutionary selected and are likely beneficial for survival, endocrine changes in prolonged Critically ill patients could be harmful and may hamper recovery. Most studies investigating the substitution of peripheral hormones or strategies to overcome resistance to anabolic stimuli failed to show benefit for morbidity and mortality. Research on treatment with selected and combined hypothalamic hormones has shown promising results. Well-controlled RCTs to corroborate these findings are needed.

  • the role of autophagy in Critical Illness induced liver damage
    Scientific Reports, 2017
    Co-Authors: Steven Thiessen, Greet Van Den Berghe, Inge Derese, Sarah Derde, Thomas Dufour, Lies Pauwels, Youri Bekhuis, Isabel Pintelon, Wim Martinet, Ilse Vanhorebeek
    Abstract:

    Mitochondrial dysfunction and endoplasmic reticulum (ER) stress, which activates the unfolded protein response (UPR), mediate Critical Illness-induced organ failure, often affecting the liver. Autophagy is known to alleviate both and suppressed or insufficiently activated autophagy in prolonged Illness has shown to associate with organ failure. Whether insufficient autophagy contributes to organ failure during Critical Illness by affecting these underlying mechanisms is incompletely understood. In this study, we investigated whether the inability to acutely activate hepatic autophagy during Critical Illness aggravates liver damage by increasing hepatic mitochondrial dysfunction and affecting the UPR. In a mouse model of Critical Illness, induced by surgery and sepsis, we investigated the impact of inactivating hepatic autophagy on markers of hepatic mitochondrial function, the UPR and liver damage in acute (1 day) and prolonged (3 days) Critical Illness. Hepatic autophagy inactivation during Critical Illness acutely worsened mitochondrial dysfunction and time-dependently modulated the hepatic UPR. Furthermore, autophagy inactivation aggravated markers of liver damage on both time points. In conclusion, the inability to acutely activate autophagy in liver during Critical Illness worsened hepatic mitochondrial damage and dysfunction, partially prohibited acute UPR activation and aggravated liver damage, indicating that autophagy is crucial in alleviating Critical Illness-induced organ failure.

  • hypothalamic pituitary hormones during Critical Illness a dynamic neuroendocrine response
    Handbook of Clinical Neurology, 2014
    Co-Authors: Lies Langouche, Greet Van Den Berghe
    Abstract:

    Independent of the underlying condition, Critical Illness is characterized by a uniform dysregulation of the hypothalamic-pituitary-peripheral axes. In most axes a clear biphasic pattern can be distinguished. The acute phase of Critical Illness is characterized by low peripheral effector hormone levels such as T3, IGF-1 and testosterone, despite an actively secreting pituitary. The adrenal axis with high cortisol levels in the presence of low ACTH levels is a noteworthy exception. In the prolonged phase of Critical Illness, low peripheral effector hormone levels coincide with a uniform suppression of the neuroendocrine axes, predominantly of hypothalamic origin. The severity of the alterations in the different neuroendocrine axes is associated with a high risk of morbidity and mortality, but it remains unknown whether the observed changes are cause or consequence of adverse outcome. Several studies have identified therapeutic potential of hypothalamic releasing factors, but clinical outcome remains to be investigated with sufficiently powered randomized controlled trials.

  • alterations in adipose tissue during Critical Illness an adaptive and protective response
    American Journal of Respiratory and Critical Care Medicine, 2010
    Co-Authors: Lies Langouche, Sarah Vander Perre, Steven Thiessen, Jan Gunst, Greet Hermans, Andre Dhoore, Blerina Kola, Marta Korbonits, Greet Van Den Berghe
    Abstract:

    Rationale: Critical Illness is characterized by lean tissue wasting, whereas adipose tissue is preserved. Overweight and obese Critically ill patients may have a lower risk of death than lean patients, suggestive of a protective role for adipose tissue during Illness.Objectives: To investigate whether adipose tissue could protectively respond to Critical Illness by storing potentially toxic metabolites, such as excess circulating glucose and triglycerides.Methods: We studied adipose tissue morphology and metabolic activity markers in postmortem biopsies of 61 Critically ill patients and 20 matched control subjects. Adipose morphology was also studied in in vivo biopsies of 27 patients and in a rabbit model of Critical Illness (n = 22).Measurements and Main Results: Adipose tissue from Critically ill patients revealed a higher number and a smaller size of adipocytes and increased preadipocyte marker levels as compared with control subjects. Virtually all adipose biopsies from Critically ill patients displa...

  • clinical review Critical Illness polyneuropathy and myopathy
    Critical Care, 2008
    Co-Authors: Greet Hermans, Bernard De Jonghe, Frans Bruyninckx, Greet Van Den Berghe
    Abstract:

    Critical Illness polyneuropathy (CIP) and myopathy (CIM) are major complications of severe Critical Illness and its management. CIP/CIM prolongs weaning from mechanical ventilation and physical rehabilitation since both limb and respiratory muscles can be affected. Among many risk factors implicated, sepsis, systemic inflammatory response syndrome, and multiple organ failure appear to play a crucial role in CIP/CIM. This review focuses on epidemiology, diagnostic challenges, the current understanding of pathophysiology, risk factors, important clinical consequences, and potential interventions to reduce the incidence of CIP/CIM. CIP/CIM is associated with increased hospital and intensive care unit (ICU) stays and increased mortality rates. Recently, it was shown in a single centre that intensive insulin therapy significantly reduced the electrophysiological incidence of CIP/CIM and the need for prolonged mechanical ventilation in patients in a medical or surgical ICU for at least 1 week. The electrophysiological diagnosis was limited by the fact that muscle membrane inexcitability was not detected. These results have yet to be confirmed in a larger patient population. One of the main risks of this therapy is hypoglycemia. Also, conflicting evidence concerning the neuromuscular effects of corticosteroids exists. A systematic review of the available literature on the optimal approach for preventing CIP/CIM seems warranted.

Charles F. Bolton - One of the best experts on this subject based on the ideXlab platform.

  • Critical Illness polyneuropathy and myopathy a major cause of muscle weakness and paralysis
    Lancet Neurology, 2011
    Co-Authors: Nicola Latronico, Charles F. Bolton
    Abstract:

    Critical Illness polyneuropathy (CIP) and myopathy (CIM) are complications of Critical Illness that present with muscle weakness and failure to wean from the ventilator. In addition to prolonging mechanical ventilation and hospitalisation, CIP and CIM increase hospital mortality in patients who are Critically ill and cause chronic disability in survivors of Critical Illness. Structural changes associated with CIP and CIM include axonal nerve degeneration, muscle myosin loss, and muscle necrosis. Functional changes can cause electrical inexcitability of nerves and muscles with reversible muscle weakness. Microvascular changes and cytopathic hypoxia might disrupt energy supply and use. An acquired sodium channelopathy causing reduced muscle membrane and nerve excitability is a possible unifying mechanism underlying CIP and CIM. The diagnosis of CIP, CIM, or combined CIP and CIM relies on clinical, electrophysiological, and muscle biopsy investigations. Control of hyperglycaemia might reduce the severity of these complications of Critical Illness, and early rehabilitation in the intensive care unit might improve the functional recovery and independence of patients.

  • The discovery of Critical Illness polyneuropathy.
    European Journal of Anaesthesiology, 2008
    Co-Authors: Charles F. Bolton
    Abstract:

    In 1892 Osler described 'rapid loss of flesh' in prolonged sepsis. Thereafter, for years, limb weakness was attributed to cachectic myopathy, and difficulty weaning from mechanical ventilation was attributed to diaphragmatic fatigue. In 1961 Mertens described 'coma-polyneuropathies', and in 1971 Henderson and colleagues described polyneuropathy in patients with burns. In 1984 Bolton and colleagues, in a series of reports, defined the clinical, electrophysiological and morphological features of septic encephalopathy and Critical Illness polyneuropathy. Evidence suggested that polyneuropathy was due to the 'toxic' effects of sepsis. Polyneuropathy was a common cause of difficulty in weaning when lung and cardiac cause had been excluded. Since 1984, cases of Critical Illness polyneuropathy have been reported from several countries. Moreover, a number of investigators reported instances of Critical Illness myopathy. Comprehensive studies by Latronico and colleagues indicated that polyneuropathy and myopathy often occurred together in the same patient. With successful treatment of sepsis, improvement often occurred in encephalopathy, polyneuropathy and myopathy, except in very severe cases.

  • neuromuscular manifestations of Critical Illness
    Muscle & Nerve, 2005
    Co-Authors: Charles F. Bolton
    Abstract:

    Critical Illness, more precisely defined as the systemic inflammatory response syndrome (SIRS), occurs in 20%-50% of patients who have been on mechanical ventilation for more than 1 week in an intensive care unit. Critical Illness polyneuropathy (CIP) and myopathy (CIM), singly or in combination, occur commonly in these patients and present as limb weakness and difficulty in weaning from the ventilator. Critical Illness myopathy can be subdivided into thick-filament (myosin) loss, cachectic myopathy, acute rhabdomyolysis, and acute necrotizing myopathy of intensive care. SIRS is the predominant underlying factor in CIP and is likely a factor in CIM even though the effects of neuromuscular blocking agents and steroids predominate in CIM. Identification and characterization of the polyneuropathy and myopathy depend upon neurological examination, electrophysiological studies, measurement of serum creatine kinase, and, if features suggest a myopathy, muscle biopsy. The information is valuable in deciding treatment and prognosis.

  • Critical Illness polyneuropathy
    Current Treatment Options in Neurology, 2000
    Co-Authors: Charles F. Bolton, G. Bryan Young
    Abstract:

    Critical Illness polyneuropathy (CIP) is common among patients in intensive care units (ICUs) [1, Class III]. However, it is rarely diagnosed in patients in most ICUs, because of the lack of knowledge, difficulties in clinical assessment, and failure to perform electrophysiologic studies. Nonetheless, CIP is a significant cause of difficulty in weaning patients from the ventilator and of long-term morbidity in survivors. Although no specific treatment is available, diagnosis is important for the institution of various nonspecific treatments and for prognosis. Moreover, research is important in arriving at a better understanding of the pathophysiologic mechanisms and, hence, possible avenues of specific treatment. Thus, this chapter emphasizes the nature of Critical Illness and the possible pathophysiology, the clinical and electrophysiologic features, and the differential diagnosis of CIP. Nonspecific and potential specific treatments are also discussed.

Bo Thiesson - One of the best experts on this subject based on the ideXlab platform.

  • Explainable artificial intelligence model to predict acute Critical Illness from electronic health records.
    Nature communications, 2020
    Co-Authors: Simon Meyer Lauritsen, Mads Kristensen, Mathias Vassard Olsen, Morten Skaarup Larsen, Katrine Meyer Lauritsen, Marianne Johansson Jørgensen, Jeppe Lange, Bo Thiesson
    Abstract:

    Acute Critical Illness is often preceded by deterioration of routinely measured clinical parameters, e.g., blood pressure and heart rate. Early clinical prediction is typically based on manually calculated screening metrics that simply weigh these parameters, such as early warning scores (EWS). The predictive performance of EWSs yields a tradeoff between sensitivity and specificity that can lead to negative outcomes for the patient. Previous work on electronic health records (EHR) trained artificial intelligence (AI) systems offers promising results with high levels of predictive performance in relation to the early, real-time prediction of acute Critical Illness. However, without insight into the complex decisions by such system, clinical translation is hindered. Here, we present an explainable AI early warning score (xAI-EWS) system for early detection of acute Critical Illness. xAI-EWS potentiates clinical translation by accompanying a prediction with information on the EHR data explaining it. Acute Critical Illness is often preceded by deterioration of routinely measured clinical parameters, e.g., blood pressure and heart rate. Here, the authors develop an explainable artificial intelligence early warning score system for its early detection.

  • Explainable artificial intelligence model to predict acute Critical Illness from electronic health records
    arXiv: Artificial Intelligence, 2019
    Co-Authors: Simon Meyer Lauritsen, Mads Kristensen, Mathias Vassard Olsen, Morten Skaarup Larsen, Katrine Meyer Lauritsen, Marianne Johansson Jørgensen, Jeppe Lange, Bo Thiesson
    Abstract:

    We developed an explainable artificial intelligence (AI) early warning score (xAI-EWS) system for early detection of acute Critical Illness. While maintaining a high predictive performance, our system explains to the clinician on which relevant electronic health records (EHRs) data the prediction is grounded. Acute Critical Illness is often preceded by deterioration of routinely measured clinical parameters, e.g., blood pressure and heart rate. Early clinical prediction is typically based on manually calculated screening metrics that simply weigh these parameters, such as Early Warning Scores (EWS). The predictive performance of EWSs yields a tradeoff between sensitivity and specificity that can lead to negative outcomes for the patient. Previous work on EHR-trained AI systems offers promising results with high levels of predictive performance in relation to the early, real-time prediction of acute Critical Illness. However, without insight into the complex decisions by such system, clinical translation is hindered. In this letter, we present our xAI-EWS system, which potentiates clinical translation by accompanying a prediction with information on the EHR data explaining it.

Ernst Hund - One of the best experts on this subject based on the ideXlab platform.

  • neurological complications of sepsis Critical Illness polyneuropathy and myopathy
    Journal of The Peripheral Nervous System, 2002
    Co-Authors: Ernst Hund
    Abstract:

    Sepsis may cause not only failure of parenchymal organs but can also cause damage to peripheral nerves and skeletal muscles. It is now recognized that sepsis-mediated disorders of the peripheral nerves and the muscle, called Critical Illness polyneuropathy (CIP) and Critical Illness myopathy, are responsible for weakness and muscle atrophy occurring de novo in intensively treated patients. CIP represents an acute axonal neuropathy that develops during treatment of severely ill patients and remits spontaneously, once the Critical condition is under control. The course is monophasic and self-limiting. Among the Critical Illness myopathies, three main types have been identified: a non-necrotizing “cachectic” myopathy (Critical Illness myopathy in the strict sense), a myopathy with selective loss of myosin filaments (“thick filament myopathy”) and an acute necrotizing myopathy of intensive care. Clinical manifestations of both Critical Illness myopathies and CIP include delayed weaning from the respirator, muscle weakness, and prolonging of the mobilization phase. The pathogenesis of these neuromuscular complications of sepsis is not understood in detail but most authors assume that the inflammatory factors that mediate systemic inflammatory response and multiple organ failure are closely involved. In thick filament myopathy and acute necrotizing myopathy, administration of steroids and neuromuscular blocking agents may act as triggers. Specific therapies have not been discovered. Stabilization of the underlying Critical condition and elimination of sepsis appear to be of major importance. Steroids and muscle relaxants should be avoided or administered at the lowest dose possible.

  • Critical Illness polyneuropathy
    Current Opinion in Neurology, 2001
    Co-Authors: Ernst Hund
    Abstract:

    Critical Illness polyneuropathy is a self-limited acute axonal neuropathy that develops during treatment of severely ill patients and remits spontaneously once the Critical condition is under control. Clinical manifestations include muscle weakness and atrophy, delayed weaning from the respirator, and prolongation of the mobilization phase. The pathogenesis is not understood in detail but most authors assume that the inflammatory cascade that mediates the systemic inflammatory response and multiple organ failure play a pivotal role. This review summarizes current knowledge of this common neuropathic complication during intensive care treatment.

Wolfgang Zink - One of the best experts on this subject based on the ideXlab platform.

  • intensive care unit acquired weakness in the Critically ill Critical Illness polyneuropathy and Critical Illness myopathy
    Anaesthesist, 2011
    Co-Authors: K Judemann, Dirk Lunz, Y A Zausig, B M Graf, Wolfgang Zink
    Abstract:

    Intensive care unit-acquired weakness (ICUAW) is a severe complication in Critically ill patients which has been increasingly recognized over the last two decades. By definition ICUAW is caused by distinct neuromuscular disorders, namely Critical Illness polyneuropathy (CIP) and Critical Illness myopathy (CIM). Both CIP and CIM can affect limb and respiratory muscles and thus complicate weaning from a ventilator, increase the length of stay in the intensive care unit and delay mobilization and physical rehabilitation. It is controversially discussed whether CIP and CIM are distinct entities or whether they just represent different organ manifestations with common pathomechanisms. These basic pathomechanisms, however, are complex and still not completely understood but metabolic, inflammatory and bioenergetic alterations seem to play a crucial role. In this respect several risk factors have recently been revealed: in addition to the administration of glucocorticoids and non-depolarizing muscle relaxants, sepsis and multi-organ failure per se as well as elevated levels of blood glucose and muscular immobilization have been shown to have a profound impact on the occurrence of CIP and CIM. For the diagnosis, careful physical and neurological examinations, electrophysiological testing and in rare cases nerve and muscle biopsies are recommended. Nevertheless, it appears to be difficult to clearly distinguish between CIM and CIP in a clinical setting. At present no specific therapy for these neuromuscular disorders has been established but recent data suggest that in addition to avoidance of risk factors early active mobilization of Critically ill patients may be beneficial.

  • Critical Illness polyneuropathy and myopathy in the intensive care unit
    Nature Reviews Neurology, 2009
    Co-Authors: Wolfgang Zink, Rainer Kollmar, Stefan Schwab
    Abstract:

    Critical Illness polyneuropathy (CIP) and Critical Illness myopathy (CIM) are major complications that occur in severely ill patients who require intensive care treatment. CIP and CIM affect the limb and respiratory muscles, and, as a consequence, they characteristically complicate weaning from the ventilator, increase the length of stay on the intensive care unit, and prolong physical rehabilitation. The basic pathophysiology of both disorders is complex and involves metabolic, inflammatory and bioenergetic alterations. It is unclear at present whether CIP and CIM are distinct entities, or whether they just represent different 'organ' manifestations of a common pathophysiological mechanism. This article provides an overview of the clinical and diagnostic features of CIP and CIM and discusses current pathophysiological and therapeutic concepts relating to these neuromuscular disorders.