Changes in Intermediary Metabolism in Severe Surgical Illness

Wolfe, Robert R.; Martini, Wenjun Z.

doi:10.1007/s002689910105

Cited by 76 publications

(55 citation statements)

References 48 publications

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“…Critical illness is hallmarked by striking endocrine and metabolic disturbances, the severity of which has been associated with a high risk of morbidity and mortality (730,732,784).…”

Section: Metabolic Effects In Critical Illnessmentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

294

329

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Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca 2ϩ dysregulation is present through altered Ca 2ϩ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

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“…Critical illness is hallmarked by striking endocrine and metabolic disturbances, the severity of which has been associated with a high risk of morbidity and mortality (730,732,784).…”

Section: Metabolic Effects In Critical Illnessmentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

294

329

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“…The acid-base status can be assessed by measuring pH and lactate and by calculated values of base excess and bicarbonate. Lactate usually serves as a marker for the adequacy of tissue oxygenation but can also reflect stress induced glycolysis (Wolfe & Martini, 2000). Blood gases and acid-base status are valuable means for evaluation of the physiological effects that different capture methods and drugs have on wild animals (Suzuki et al, 2001).…”

Section: Evaluation Of Clinical and Physiological Effects Of Chemicalmentioning

confidence: 99%

Efficacy of a Portable Oxygen Concentrator with Pulsed Delivery for Treatment of Hypoxemia During Anesthesia of Wildlife

Fahlman¹,

Caulkett²,

Arnemo³

et al. 2012

Journal of Zoo and Wildlife Medicine

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Improvement of chemical capture is an important part of wildlife conservation and animal welfare to minimise distress for the animals and the risk of morbidity and mortality. The aim of this thesis was to improve wildlife immobilisation and anaesthesia by studying physiological variables and clinically evaluate different drug combinations and methods of capture in selected species. Reversible anaesthetic protocols were developed for use in free-ranging lions and four species of SouthEast Asian primates. Capture and anaesthesia of free-ranging wolverines, brown bears, black and white rhinoceros were physiologically evaluated. The effect of intranasal oxygen supplementation on arterial oxygenation was assessed in brown bears and rhinoceros. Partial reversal of the opioid effect and different body positions were evaluated in rhinoceros.Capture methods used included darting from a helicopter or the ground, and physical restraint followed by drug injection. Medetomidine-ketamine was used in wolverines and medetomidine-zolazepam-tiletamine in primates, lions and brown bears. Rhinoceros were immobilised with a combination of an opioid, azaperone and an alpha 2 -agonist. Body temperature and cardiorespiratory variables were monitored in all animals. Arterial blood samples were analysed to interpret pulmonary gas exchange and acid-base status in carnivores and rhinoceros.Low doses of medetomidine-zolazepam-tiletamine rapidly anaesthetised primates and lions, and reversal with atipamezole resulted in a smooth and calm recovery. Physiological alterations varied with different protocols and species and included changes in body temperature, respiratory and heart rates, gas exchange and acid-base balance. Hypoxaemia was recorded in all rhinoceros and most carnivore species. The major contributor to hypoxaemia was likely ventilation-perfusion mismatch including shunt. In rhinoceros, hypoventilation contributed to an impaired gas exchange and the animals remained hypoxaemic despite partial reversal. However, in black rhinoceros arterial oxygenation was higher during sternal compared to lateral recumbency. Capture-induced lactic acidaemia was recorded in carnivores and rhinoceros. Intranasal oxygen supplementation improved arterial oxygenation.In conclusion, this thesis increases the understanding of the effects of capture and anaesthesia in several wildlife species. Physiological derangements were identified, potential causative factors were investigated and methods for improvement were evaluated.

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“…yperglycemia in critically ill patients is brought about by hepatic and peripheral insulin resistance and by concomitant relative insulin deficiency due to limited compensatory ability of pancreatic ␤-cells, largely independent of the underlying disease (1). Hyperglycemia during critical illness has long been considered essential to provide fuel for vital organ systems and hence was interpreted as a beneficial adaptation.…”

mentioning

confidence: 99%

Survival Benefits of Intensive Insulin Therapy in Critical Illness

Ellger

Debaveye²,

Vanhorebeek³

et al. 2006

Diabetes

203

121

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Tight blood glucose control with insulin reduces morbidity and mortality of critically ill patients. However, the relative impact of maintaining normoglycemia and of glycemiaindependent actions of insulin remains unknown. We therefore independently manipulated blood glucose and plasma insulin levels in burn-injured, parentally fed rabbits over 7 days to obtain four study groups: two normoglycemic groups with either normal or elevated insulin levels and two hyperglycemic groups with either normal or elevated insulin levels. We studied the relative impact of glycemia and glycemia-independent effects of insulin on survival; myocardial contractility in an open chest preparation; endothelial function in isolated aortic rings; and liver, kidney, and leukocyte function in a rabbit model of critical illness. Mortality was significantly lower in the two normoglycemic groups independent of insulin levels. Maintaining normoglycemia, independent of insulin levels, prevented endothelial dysfunction as well as liver and kidney injury. To increase myocardial systolic function, elevated insulin levels and prevention of hyperglycemia were required concomitantly. Leukocyte dysfunction was present in the two hyperglycemic groups, which could in part be rescued by insulin. The results suggest that the observed benefits of intensive insulin therapy required mainly maintenance of normoglycemia; whereas glycemia-independent actions of insulin exerted only minor, organ-specific impact. Diabetes 55:1096 -1105, 2006 H yperglycemia in critically ill patients is brought about by hepatic and peripheral insulin resistance and by concomitant relative insulin deficiency due to limited compensatory ability of pancreatic ␤-cells, largely independent of the underlying disease (1). Hyperglycemia during critical illness has long been considered essential to provide fuel for vital organ systems and hence was interpreted as a beneficial adaptation. Evidence is now growing against this notion as hyperglycemia is identified as an independent risk factor for adverse outcome of numerous surgical and medical conditions (2-4), and avoiding hyperglycemia with intensive insulin therapy has been shown to improve outcome (5,6). The risks of hyperglycemia comprise increased vulnerability to infectious complications, impaired recovery of organ failure, myocardial dysfunction, and neuromuscular weakness (7-12). The cardiovascular and immune systems thus emerge as two important target systems of glycemic control in the critically ill (7,10,13).It remains unclear, however, to what extent maintaining normoglycemia and glycemia-independent actions of insulin account for the different clinical benefits of intensive insulin therapy in the critically ill. A post hoc analysis of the randomized controlled study of intensive insulin therapy in surgical intensive care patients suggested that blood glucose control best explains the clinical benefits of the intervention (14). In contrast, insulin-induced promotion of glycolysis in cardiomyocytes and a diversion of fatty acids...

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Changes in Intermediary Metabolism in Severe Surgical Illness

Cited by 76 publications

References 48 publications

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Efficacy of a Portable Oxygen Concentrator with Pulsed Delivery for Treatment of Hypoxemia During Anesthesia of Wildlife

Survival Benefits of Intensive Insulin Therapy in Critical Illness

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