PART - 2 CONTINUED

Theresa A. Byrne, MS, RD, Thomas B. Morrissey, MD, Christopher Gatzen, FRCS (E), Kathleen Benfell, R.Ph, Thomas V Nattakom, MD, Marc R. Scheltinga, MD, Ph.D., Meryl S. Leboff, MD, Thomas R. Ziegler, MD, and Douglas W. Wilmore, MD.

From the Departments of Surgery, Medicine, and Pharmacy and the Laboratories for Surgical Metabolism and Nutrition, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

Objective: The authors investigated the effects of exogenous growth hormone (GH) on protein accretion and the compsition of weight gain in a group of stable, nutritionally compromised postoperative patients receiving standard hypercaloric nutritional therapy.

Summary Background Data: A significant loss of body protein impairs normal physiologic functions and is associated with increased postoperative complications and prolonged hospitalization. Previous studies have demonstrated that standard methods of nutritional support enhance the deposition of fat and extracellular water but are ineffective in repleting body protein.

Methods: Fourteen patients requiring long-term nutritional support for severe gastrointestinal dysfunction received standard nutritional therapy (STD) providing approximately 50 kcal/kg/day and 2 g of protein/kg/day during an initial 7-day equilibrium period. The patients then continued on STD (n=4) or, in addition, received GH 0.14 mg/kg/day (n=10). On day 7 of the equilibrium period and again after 3 weeks of treatment, the components of body weight were determined; these included body fat, mineral content, lean (nonfat and nonmineral-containing tissue) mass, total body water, extracellular water (ECW), and body protein. Daily and cumulative nutrient balance and substrate oxidation studies determined the distribution, efficiency, and utilization of calories for protein, fat, and carbohydrate deposition.

Results: The GH-treated patients gained minimal body fat but had significantly more lean mass (4.311± 0.6 kg vs 1.988± 0.2 kg, p< 0.03) and more protein (l.417± 0.3 kg vs. 0.086± 0.1 kg, p< 0.03) than did the STD-treated patients. The increase in lean mass was not associated with an inappropriate expansion of ECW. In contrast, patients receiving STD therapy tended to deposit a greater proportion of body weight as ECW and significantly more fat than did GH-treated patients (1.004± 0.3 kg vs 0.129± 0.2 kg, p< 0.05). GH administration altered substrate oxidation (respiratory quotient = 0.94± 0.02 GH vs. 1.18± 0.05 STD, p < 0.0002) and the use of available energy, resulting in a 66% increase in the efficiency of protein deposition (13.37± 0.8 g/1000 kcal vs. 8.04g± 3.06 g/1000 kcal, p< 0.04).

SURGICAL PATIENTS WITH LOST MEAN MASS

Departments of Surgery and Medicine/Endocrinology, State University of New York, Stony Brook, New York 11794; and Metabolism Unit, Shriners Burns Institute, and the Department of Surgery.

University of Texas Medical Branch, Galveston, Texas 77550

Abstract

The aim of the present investigation was to determine whether there is a net uptake of inulin-like growth factor I (IGF-I) or IGF-binding proteins (IGFBPs) by the leg after burn injury and to elucidate the regulatory role of insulin exerted on this system under in vivo conditions in burn patients. Studies were performed on nine patients after burn injury (-60% body surface area). Each patient was studied twice during a continuous infusion of a carbohydrate-rich enteral diet. Blood was collected simultaneously from the femoral artery and vein for the measurement of various elements of the IGF system after 7 days of enteral diet alone (basal period) and after 7 days of the enteral die4t plus the infusion of insulin (insulin period). Data from these patients were compared to values in age-matched fed healthy volunteers. During the basal period, burn patients demonstrated a significant reduction in the venous concentration of IGF-I and an increase in both IGFBP-1 and -2 compared to control values. Insulin produced a significant 15% increase in the IGF-I concentration in burn patients, but decreased the circulating levels of IGFBP-12 by 50%. The IGF-I and IGFBP-1 concentrations at the end of the insulin period were still significantly different from those in control subjects.

Burn patients also exhibited a marked reduction in intact IGFBP-3 and the acid-labile subunit under basal conditions, and these alterations were not reversed by insulin. Under basal conditions, all burn patients had a positive arterio-venous (A-V) difference for IGF-I across the leg. The A-V difference was increased 50% in response to insulin. The net uptake of IGF-I by the leg was m g/min under basal conditions, and as leg blood flow also tended to increase in response to insulin, IGF-I uptake was elevated more than 3 fold during the insulin period. No A-V difference across the leg was detected for IGFBP-1, -2, or -3 in burn patients. In conclusion, burn injury in humans produces dramatic and sustained alterations in various components of the IGF system that persist despite adequate nutritional support. Our data indicate the presence of a net uptake of IGF-I by the leg in burn patients that may serve to counteract the catabolic state. 

Jukka Takala, MD, Ph.D., Esko Ruokonen, MD, PhD, Nigel R. Webster, MD, Michael S. Nielsen, MD, Durk F. Zandstra, MD, Guy Vundelinckx, MD, and Charles J. Hinds, MD.

Background: The administration of growth hormone can attenuate the catabolic response to injury, surgery, and sepsis. However, the effect of high doses of growth hormone on the length of stay in intensive care and in the hospital, the duration of mechanical ventilation, and the outcome in critically ill adults who are hospitalized for long periods is not known.

Methods: We carried out two prospective, multicenter, double-blind, randomized, placebo-controlled trials in parallel involving 247 Finnish patients and 285 patients in other European countries who had been in an intensive care unit for 5 to 7 days and who were expected to require intensive care for at least 10 days. The patients had had cardiac surgery, abdominal surgery, multiple trauma, or acute respiratory failure. The patients received either growth hormone (mean [± SD) daily dose, 0.10± 0.02 mg per kilogram of body weight) or placebo until discharge from intensive care or for a maximum of 21 days.

Results: The in-hospital mortality rate was higher in the patients who received growth hormone than in those who did not (P± < 0.001 for both studies). In the Finnish study, the mortality rate was 39 percent in the growth hormone group, as compared with 20 percent in the placebo group. The respective rates in the multinational study were 44 percent and 18 percent. The relative risk of death for patients receiving growth hormone was 1.9 (95 percent confidence interval, 1.3 to 2.9) in the Finnish study and 2.4 (95 percent confidence interval, 1.6 to 3.5) in the multinational study. Among the survivors, the length of stay in intensive care and in the hospital and the duration of mechanical ventilation were prolonged in the growth hormone group.