Abstract
Excessive protein depletion and poor clinical outcome are characteristic features of the metabolic response to severe injury. Inability to achieve heightened ketosis may be, in part, responsible for the extent of protein loss. Carnitine has a significant role in the development of ketosis. Insufficiency of carnitine has been reported in critical illness; this may contribute to blunted ketosis. This hypothesis was tested by investigating the relationship between ketone bodies and carnitine status, in conditions of altered ketone body concentrations. A study of surgical patients showed marked urinary carnitine losses, associated with the extent of negative nitrogen balance. No relationship between serum or urine carnitine, and ketones were found in these moderately traumatised patients in the short term. Nutritional support was grossly inadequate. On a basis of these findings, three areas of research emerged:- 1. A comparative study of adequately with inadequately fed patients, showed losses of fat and lean body tissue occurred in both groups. This suggested that nutrients, provided during the initial acute injury phase may be poorly utilised. 2. Carnitine status and ketones were studied in more severely stressed burns patients, over an extended period. Substantial carnitine losses were observed, which were related to nitrogen balance and percent burn but not ketotic potential. Blunted ketosis, in the presence of hyperglucagonaemia, was attributed to inadequate NEFA supply. It was suggested that supplementation with carnitine and MCT may enhance ketosis following severe injury. Wasting, despite nutrient provision, was attributed to poor nutrient utilisation during an extended acute injury phase. 3. Limitations of the clinical studies were overcome by study of carnitine and ketones, and effects of carnitine supplementation, in a diabetic animal model. Supplementary carnitine is retained by tissues. Supplementation enhanced ketosis in non-diabetic, but not diabetic rats. Changes in liver carnitine bore more similarity to ketones than did serum carnitine. The thesis concludes that efficacy of carnitine supplementation in trauma needs investigating. Research into methods of reducing catabolism should continue. Meanwhile, long term nutritional support into the convalescent period may be advocated.