OBJECTIVES: Animal studies have shown that the elevation of plasma glutamate levels increase cerebral edema formation whenever the blood-brain barrier is disturbed. Therefore, changes in plasma glutamate levels as influenced by the administration of a glutamate-containing amino acid solution were investigated in neurosurgical patients. DESIGN: Prospective, descriptive study. SETTING: Eight-bed neurosurgical intensive care unit in a university hospital. PATIENTS: Twenty-three neurosurgical patients requiring parenteral nutrition. INTERVENTIONS: Parenteral nutrition was begun 24 hrs after craniotomy. Patients receiving a glutamate-containing amino acid solution (3.75 g/L glutamate) were compared with patients infused with a glutamate-free solution. MEASUREMENTS AND MAIN RESULTS: Arterial plasma and urine amino acids were analyzed using high-performance liquid chromatography. Administration of a glutamate-containing solution doubled plasma glutamate levels in neurosurgical patients (from 53.3 +/- 9.8 microM [preinfusion] to 98.5 +/- 18.7 microM [after 4 hrs of infusion]; p < 0.001), whereas no elevation was seen when infusing a glutamate-free solution (from 52.3 +/- 7.3 [1 hr of infusion] to 53.6 +/- 6.4 microM [4 hrs of infusion]). Upon terminating the glutamate-containing infusion, arterial plasma glutamate levels decreased immediately (from 120 +/- 13.2 microM to 81.2 +/- 19.5 microM). Glutamate as infused in excess appears to exceed a renal threshold and is eliminated renally. CONCLUSIONS: As shown in animal models, administration of a glutamate-containing amino acid solution significantly increased plasma glutamate levels. Because such an increase in plasma glutamate levels could aggravate cerebral edema formation, glutamate-containing amino acid solutions cannot be recommended for patients with a disturbed blood-brain barrier.