Effects of perioperative nutrition on insulin action in postoperative metabolism

Detta är en avhandling från Stockholm : Karolinska Institutet, Center for Surgical Sciences CFSS

Sammanfattning: Surgical operations are a fundamental part of contemporary treatment of disease. For example, 43 % of in-patients in Sweden undergo a surgical operation. Surgery is not yet without significant risks. Infectious complication rates following abdominal surgery, for instance, remain at 9-25 %. It has recently been recognised that hyperglycaemia is a significant risk factor for postoperative infectious complications. Hyperglycaemia in the postoperative patient occurs on the basis of postoperative insulin resistance, a transient state of reduced sensitivity to the anabolic effects of insulin. This state, similar to type 2 diabetes mellitus, is not traditionally treated in routine perioperative care. Development of methods to attenuate postoperative insulin resistance may improve outcome of surgical care. One such method is preoperative oral carbohydrate treatment. In surgical patients, insulin resistance is best quantified by measuring insulin sensitivity before and after surgery using the hyperinsulinaemic-euglycaemic clamp method. However, reproducibility of the clamp method has not been conclusively demonstrated. Therefore, seven healthy volunteers underwent three two-h hyperinsulinaemic (60 µmol·l 1)-euglycaemic (4.5 mmol·l 1) clamps on days 0, 2 and 14, respectively. The mean intra-individual coefficient of variation of measured whole-body insulin sensitivity between the first and second clamp was 7.0 (2.8) % (mean (SEM)) and, between the first and third clamp, 8.0 (2.4) %. The clamp method was therefore considered reproducible. To study the effects of preoperative oral carbohydrate treatment on postoperative insulin resistance in the absence of postoperative confounding factors such as hypocaloric nutrition and bed rest, 15 patients were studied before and immediately after total hip replacement. They were double-blindly treated with either a preoperative carbohydrate-rich beverage (12.5 %, 800+400 ml, n=8) or placebo (n=7). Glucose kinetics (6, 6 D2 D glucose), substrate utilisation (indirect calorimetry) and insulin sensitivity (clamp) were measured. Whole-body insulin sensitivity decreased in both groups, but significantly less in carbohydrate-treated patients ( 18 (6) vs 43 (9) %, P<0.05 vs placebo, ANOVA). The attenuation of immediate postoperative insulin resistance was attributable to an attenuated reduction in whole-body glucose disposal and accelerated glucose oxidation rates. Effects of preoperative oral carbohydrate treatment later in the postoperative course were also examined. Fourteen patients undergoing total hip replacement were double-blindly treated with either oral carbohydrates (n=8) or placebo (n=6). Insulin resistance was measured on the third day after surgery, and whole-body nitrogen balance was measured. Whole-body insulin sensitivity decreased similarly in carbohydrate-treated vs placebo-treated patients ( 36 (10) % vs 49 (7) %, P=0.33). In placebo-treated patients, the decrease in whole-body insulin sensitivity was associated with a significant increase in endogenous glucose release, suggesting a shift of the site of postoperative insulin resistance from the periphery to the liver three days after surgery. Preoperative oral carbohydrate treatment significantly attenuated this postoperative increase in endogenous glucose release as well as mean whole-body nitrogen losses (136 (4) vs 161 (10) mg·kg 1·day 1, P<0.05 vs placebo). Recently, so-called enhanced-recovery after surgery protocols have been introduced, integrating a number of perioperative interventions individually shown to improve outcome. To investigate the metabolic stress responses in enhanced-recovery protocols, insulin resistance and whole-body nitrogen balance were measured in 18 patients four days after major colorectal surgery. An enhanced-recovery protocol was implemented incorporating preoperative carbohydrate treatment, postoperative multimodal pain control based on epidural analgesia and early postoperative mobilisation. Moreover, to assess the role of immediate postoperative complete enteral nutrition in enhanced-recovery protocols, patients were double-blindly treated with either an energy-dense residue-free enteral nutritional solution (1.5 kcal·ml 1, 49 energy-% carbohydrates, 35 energy-% fat, 9.6 mg N·ml 1, n=9) or a hypocaloric placebo solution (glucose 50 mg·ml 1, n=9) given immediately postoperatively for four days. Postoperative metabolic responses were strikingly limited in both treatment groups. Urinary nitrogen losses were low (10.7 (1.0) and 10.5 (0.7) g·day 1, in fed and placebo-treated patients, respectively) and insulin resistance was insignificant ( 20 (7) and 27 (11) %). Complete enteral feeding was given without hyperglycaemia (mean plasma glucose concentration 6.8 (0.4) during feed vs 6.0 (0.4) mmol·l 1, ns vs placebo) and resulted in a neutral whole-body nitrogen balance (0.1 (0.8) vs 12.6 (0.6) g N·day-1, P<0.001 vs placebo). In conclusion, preoperative oral carbohydrate treatment attenuates postoperative insulin resistance and whole-body nitrogen losses within three days after surgery. An enhanced-recovery protocol including preoperative oral carbohydrate treatment minimises metabolic stress responses after major colorectal surgery, and allows for immediate postoperative complete enteral nutrition without significant hyperglycaemia and with a neutral nitrogen balance.

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