Author:

Abstract:

Endocrine disturbances during critical illness lead to a feeding-resistant wasting-syndrome, characterised by negative protein balance, promoting delayed recovery and poor outcome. Parenteral nutrition failed to counteract the hypercatabolic state, possibly due to aggravation of the hyperglycemic response to critical illness. In our rabbit model of prolonged critical illness we investigated the impact of varying intravenous glucose load, while maintaining normoglycemia, on mortality, organ damage, and markers of catabolism/anabolism. Critically ill rabbits were randomised into a fasting group, a standard low caloric parenteral nutrition group, and two groups receiving either an intermediate or high additional amount of intravenous glucose within the physiological range, all maintained normoglycemic with insulin. These normoglycemic groups were compared with a hyperglycemic group (similar high glucose load as the last normoglycemic group) and with healthy rabbits. Protein and lipid load was equal for all fed groups. Varying intravenous glucose load did not affect mortality or organ damage, provided normoglycemia was maintained. Fasted critically ill rabbits lost weight, which was attenuated by increasing intravenous glucose load. As compared with healthy rabbits, mRNA expression of cathepsin L, calpain 1 and of several components of the ubiquitin-proteasome-pathway (Murf-1, atrogin, E2 14kDa, HC2) was elevated in skeletal muscle of fasted critically ill rabbits. Intravenous feeding was able to counteract this response. Excessive glucose load and/or hyperglycemia however may reduce the protective effect of feeding. Genes investigated in diaphragm and myocardium revealed roughly a similar response. Except in the normoglycemic group with intermediate glucose load, circulating IGF-1 and thyroid hormone levels decreased in all groups, most pronounced in hyperglycemic rabbits. In conclusion, provided normoglycemia is maintained, increasing intravenous glucose within the physiological range is safe for organ function and survival of critically ill rabbits. Concomitantly it reduces the catabolic responses as compared with fasting. Whether this will have a beneficial effect on muscle function and counteraction of muscle breakdown remains unknown.