[Intensive insulin therapy in critically ill patients--pro].
Explore the source record for details and available documents.
Blood Glucose↗
Biomedical subjects
Björn Ellger
Publications and source records attributed to Björn Ellger.
Survival benefits of intensive insulin therapy in critical illness: impact of maintaining normoglycemia versus glycemia-independent actions of insulin.
Tight blood glucose control with insulin reduces morbidity and mortality of critically ill patients. However, the relative impact of maintaining normoglycemia and of glycemia-independent 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.
Acetylcholine↗
Tissue deiodinase activity during prolonged critical illness: effects of exogenous thyrotropin-releasing hormone and its combination with growth hormone-releasing peptide-2.
Prolonged critical illness is characterized by reduced pulsatile TSH secretion, causing reduced thyroid hormone release and profound changes in thyroid hormone metabolism, resulting in low circulating T(3) and elevated rT(3) levels. To further unravel the underlying mechanisms, we investigated the effects of exogenous TRH and GH-releasing peptide-2 (GHRP-2) in an in vivo model of prolonged critical illness. Burn-injured, parenterally fed rabbits were randomized to receive 4-d treatment with saline, 60 microg/kg.h GHRP-2, 60 microg/kg.h TRH, or 60 microg/kg.h TRH plus 60 microg/kg.h GHRP-2 started on d 4 of the illness (n = 8/group). The activities of the deiodinase 1 (D1), D2, and D3 in snap-frozen liver, kidney, and muscle as well as their impact on circulating thyroid hormone levels were studied. Compared with healthy controls, hepatic D1 activity in the saline-treated, ill animals was significantly down-regulated (P = 0.02), and D3 activity tended to be up-regulated (P = 0.06). Infusion of TRH and TRH plus GHRP-2 restored the catalytic activity of D1 (P = 0.02) and increased T(3) levels back within physiological range (P = 0.008). D3 activity was normalized by all three interventions, but only addition of GHRP-2 to TRH prevented the rise in rT(3) seen with TRH alone (P = 0.02). Liver D1 and D3 activity were correlated (respectively, positively and negatively) with the changes in circulating T(3) (r = 0.84 and r = -0.65) and the T(3)/rT(3) ratio (r = 0.71 and r = -0.60). We conclude that D1 activity during critical illness is suppressed and related to the alterations within the thyrotropic axis, whereas D3 activity tends to be increased and under the joint control of the somatotropic and thyrotropic axes.
Animals↗
Endocrine interventions in the ICU.
Patients with critical illness, particularly those who depend on intensive care for a prolonged period of time, have a high morbidity and mortality. The acute and chronic phases of critical illness are associated with distinct endocrine alterations. Acute endocrine adaptations to the severe stress of critical illness, comprising an activated anterior pituitary function, have been selected by nature and can, as such, be considered as beneficial for surviving. These adaptations disappear or wane during the prolonged phase of critical illness. In this phase there is a reduced pulsatile secretion of different anterior pituitary hormones and the so-called "wasting syndrome" occurs. This prolonged endocrine/metabolic stress response is quite different from the acute response and may, to some extent, no longer be adaptive. Intervention within the endocrine system, however, remains highly controversial, as it is difficult to differentiate between beneficial adaptations and harmful abnormalities and to outline strategies for therapy. Insulin infusion titrated to maintain normoglycemia may be a notable exception, as this intervention has been proven to increase survival and reduce morbidity of surgical intensive care patients. Treatment of "relative adrenal failure" with hydrocortisone also appears to improve the outcome of patients with septic shock, but diagnostic and dosing issues still remain unresolved. Although extensive research has shown that infusion of hypothalamic-releasing peptides is able to restore physiological hormonal patterns within the somatotropic, thyrotropic, and gonadal axes and, thereby, to generate a controlled anabolic response, further research is needed to investigate whether such interventions actually improve the outcome of critical illness.
Journal Article↗