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Muscle wasting is a problem in many diseases but during the more severe diseases (like critical illness and cancer cachexia) this loss negatively affects morbidity and mortality. In the more severe diseases this loss is mostly driven by an increased protein breakdown rather than an decreased protein synthesis in skeletal muscle. Protein breakdown is regulated by several proteolytic systems with the lysosomal-autophagy and the ubiquitin-proteasome systems as the major ones. In a recent study we show that muscle wasting in patinets with severe cancer cachexia is driven by an increased activation of the lysosomal-autophagy system rather then the proteasome system. This finding is different from most animal models for cancer cachexia in which the proteasome system has been found to be activated. The increased activation of the lysosomal-autophagy system was assessed by lysosomal enzyme activities and confirmed by protein levels of severeal key regulators of the system. The article can be found here.
One of the most characterist feature of critically ill patients treated in the ICU is the loss of lean body mass, also refered to as catabolism. This loss of body protein is progressive and eventually affects outcome and succes of recovery. The idea is that appropriate feeding of protein at the right time and with the right amount can prevent or at least reduce this loss of body protein. Recommendations for protein feeding for this type of patients is sub-optimal and more research is needed to improve the recommendations. Our approach is that we study the effect of different feeding regimes on a direct measure of the patient's protein turnover (synthesis, breakdown and balance) using stable isotope tracers. Recently we have published the first results of this new line of research. In this study we investigated the effect of hypo-caloric feeding of patients with head trauma treated in the ICU on their protein turnover. The study shows that feeding patinets a hypo-caloric diet (with less protein as well) results in a more negative protein balance (patients loose more body protein) compared with normo-caloric feeding (based on individual indirect calorimetry measurements) in a cross over design. The results have recently been published in a open-access journal, Critical Care, and can be found here.
As mentioned below continuous glucose monitoring is critically needed in the ICU for performing better studies and for better clinical glucose control. In 2 earlier papers (see bleow) we have been validating an intravenous micordialysis technique in combination with an on-line analyser and monitor for continuous glucose monitoring. Now in our latest paper we have used a central vein cathater with a microdialysis membrane in combination with an on-line analysed and minotor for glucose and lactate. Both plasma glucose and lactate are shown continuously witha 5 minutes dalay. The study performed in 10 surgical patients over 20 hours shown very promissing results justifying further validation of this approach. Paper is open access and can be found here.
Continuous glucose monitoring is something that is urgently needed in the ICU to enable better studies and improved clinical care in relation to intensive insulin treatment to prevent hyperglycemia. Soon our second paper in a series of papers testing and validating intravenous microdialysis for continuous glucose monitoring in critically ill patients. In a first paper published in 2010 we show that this an intravenous catheter with a microdialysis membrane works nicely over several days but that the agreement with plasma references values is not good. We also showed that many critically ill patients actually have very limited peripheral veins allowing for this to facilitate continuous glucose monitoring. In a second paper we show that increasing the membrane length and decreasing the perfusion flow rate actually significantly imporve the agreement to plasma reference values. See paper here.
Recent results show that if one keeps glucose at lower levels during major surgery that the patients are less insulin resistant following surgery. In this study glucose was kept under 8 mM during surgery using insulin. Since post-surgical insulin resistance is clearly related to compålications this finding may have effects on the outcome for the patient. For details, see the paper.
In a recent paper published in Clinical Science we describe how low glutamine levels at admittance to the ICU predicts a worsen outcome independent from APACHE II score. In this paper we also describe that a low percentage of blood glutathione rather then a high percentage is related to a worsen outcome in ICU patients. For details, see the paper.
In another recent paper in Clinical Science we show that the loss of muscle mass in ICU patients with multiple organ failure is due to a dramatic increase in protein breakdown rates and NO change in protein synthesis rates. We also show that this increased breakdown is due to increased activities of both the proteasome and the lysosomes. You find the paper here.
We have recently compared 3 different machines for measuring energy expenditure with indirect calorimetry in ICU patients that are mechanically ventilated. This project was done by a medical student (Martin Sundström). Results shown rather large differences between the machines. We have written a preliminary report on this that we make available on an individual base to those interested. The on-line version of the paper is available now.