Metabolic costs of excessive nutritional support in stressed patients have been increasingly recognized. The decreased endogenous protein synthesis efficiency (PSE) following major injury has been attributed to the predominant need of amino acid precursors for gluconeogenesis. The present study tested the hypothesis that provision of glucose alone, not to exceed the resting energy expenditure (REE), for the first 4 to 5 days after trauma would be enough to restore PSE and stimulate the injured body to accept full nutrition. Eight severely injured, adult, hypermetabolic, and highly catabolic patients admitted to the Trauma Intensive Care Unit (TICU) served as our subjects. Integrated measurements of whole body fuel-substrate kinetics were obtained for energy metabolism (indirect calorimetry), protein kinetics (primed constant infusion of 15N-glycine), and glucose kinetics (labeled glucose infusions). Two studies were conducted on each same subject, one in the early flow phase of injury (48 to 60 hours after trauma) and a second after 4 to 5 days of hypertonic glucose (4.1 +/- 0.5 mg/kg/min; 80% REE calories) infusion with electrolytes, trace elements, and minerals. Significant (P less than .05) increases in PSE (14%, 65% +/- 2% to 74% +/- 2%), plasma growth hormone and insulin levels, and respiratory quotient (RQ) (31%, 0.74 +/- 0.03 to 0.97 +/- 0.04), and decreases in endogenous glucose appearance rate (55%, 3.1 +/- 0.5 to 1.4 +/- 0.1 mg/kg/min), and negative N balance (48%, 219 +/- 26 to 114 +/- 15 mgN/kg/d) were observed. The results suggest that hypertonic glucose infusion alone may be sufficient for physiological adaptation in the immediate posttrauma days. This therapy restores normal PSE, which should protect the labile protein pool.(ABSTRACT TRUNCATED AT 250 WORDS)