Christoph Puchstein

Total parenteral nutrition with glutamine dipeptide after major abdominal surgery - A randomized, double-blind, controlled study

OBJECTIVE To assess the efficacy of glutamine (Gln) dipeptide-enriched total parenteral nutrition (TPN) on selected metabolic, immunologic, and clinical variables in surgical patients. SUMMARY BACKGROUND DATA Depletion of Gln stores might lead to severe clinical complications. Recent studies indicate that the parenteral provision of Gln or Gln-containing dipeptides improves nitrogen balance, maintains the intracellular Gln pool, preserves intestinal permeability and absorption, and shortens hospital stay. METHODS Twenty-eight patients (age range, 42-86 years, mean 68 years) undergoing elective abdominal surgery were allocated, after randomization, to two groups to receive isonitrogenous (0.24 g nitrogen kg(-1) day(-1)) and isoenergetic (29 kcal/122 kJ kg(-1) day(-1)) TPN over 5 days. Controls received 1.5 g of amino acids kg(-1) day(-1), and the test group received 1.2 g of amino acids and 0.3 g of L-alanyl-L-glutamine (Ala-Gln) kg(-1) day(-1). Venous heparinized blood samples were obtained before surgery and on days 1, 3, and 6 after surgery for routine clinical chemistry and for the measurement of plasma free amino acids. Lymphocytes were counted and the generation of cysteinyl-leukotrienes from polymorphonuclear neutrophil granulocytes was analyzed before surgery and on days 1 and 6 after surgery. Nitrogen balances were calculated postoperatively on days 2, 3, 4, and 5. RESULTS No side effects or complaints were noted. Patients receiving Gln dipeptide revealed improved nitrogen balances (cumulative balance over 5 days: -7.9 +/- 3.6 vs. -23.0 +/- 2.6 g nitrogen), improved lymphocyte recovery on day 6 (2.41 +/- 0.27 vs. 1.52 +/- 0.17 lymphocytes/nL) and improved generation of cysteinyl-leukotrienes from polymorphonuclear neutrophil granulocytes (25.7 +/- 4.89 vs. 5.03 +/- 3.11 ng/mL). Postoperative hospital stay was 6.2 days shorter in the dipeptide-supplemented group. CONCLUSION We confirm the beneficial effects of Gln dipeptide-supplemented TPN on nitrogen economy, maintenance of plasma Gln concentration, lymphocyte recovery, cysteinyl-leukotriene generation, and shortened hospital stay in surgical patients.

Cysteinyl-leukotriene generation as a biomarker for survival in the critically ill.

ObjectiveTo evaluate the capacity of cysteinyl-leukotriene generation in the progression of critical illness compared with that in healthy volunteers and to clarify interrelationships between the rate of leukotriene generation, severity of the disease, and clinical outcome. DesignProspective, observational study. SettingSurgical intensive care unit (ICU) in a German university hospital. PatientsWe studied 14 ICU patients (nine men, five women; aged 42–82 yrs) suffering from systemic inflammatory response syndrome, sepsis, or sepsis syndrome, with a calculated sepsis severity score of 17.7 ± 4.2 and a Simplified Acute Physiology score of 17.6 ± 3.0. In addition, five healthy volunteers (three men, two women; aged 34–38 yrs) were included in the study. InterventionsNone. Measurements and Main ResultsBlood samples were obtained every second day from septic patients until discharge from the ICU or death. Leukotriene C4 (LTC4) synthesizing capacity was assessed in isolated and stimulated leukocytes (Ca-ionophore) by using combined reversed-phase, high-pressure liquid chromatography and radioimmunoassay methods. Initially, all patients synthesized less LTC4 than the healthy subjects. In patients who did not survive, the low LTC4 generation persisted throughout the observation period, whereas in surviving patients, its formation was normalized during convalescence. In surviving patients, LTC4 concentrations correlated with sepsis severity score. ConclusionsLTC4 generation is impaired in sepsis and may serve as a biomarker for survival in the critical ill.

Decrease in Leukotriene Synthesis from Leukocytes Isolated in Septic Patients

Many experimental and clinical investigations support the hypothesis that the leukotrienes are likely contributors to the nonhydrostatic edema associated with organ damage in sepsis [1–8]. In this study the capacity of leukocytes to synthesize leukotrienes was measured. The production of leukotriene C4 (LTC4) from leukocytes isolated in septic patients was compared to the values obtained in healthy volunteers.