J. Engel

Changes in blood lymphocyte populations after multiple trauma: Association with posttraumatic complications

OBJECTIVE To study the frequency of several lymphocyte subsets, circulating cytokines, and prostaglandin plasma values at their time course over a period of 14 days in severely injured trauma patients in relation to the development of sepsis and multiple organ failure (MOF). DESIGN Prospective study. SETTING An operative intensive care unit (ICU) of a university hospital. PATIENTS Sixty-eight consecutive severely injured trauma patients. INTERVENTIONS Patients were separated into patients without sepsis and MOF (group 1, n = 51), and patients who developed sepsis and MOF (group 2, n = 17) during their stay in the ICU. Therapy was adjusted to the standards of modern intensive care management by physicians who were not involved in the study. MEASUREMENTS AND MAIN RESULTS In arterial blood samples, the profile of lymphocyte subset frequencies was performed by flow cytometry and, together with interleukin (IL)-1, IL-10, tumor necrosis factor (TNF)-alpha soluble TNF-alpha receptor 1 (sTNF-alpha r1 [p55]), and prostaglandin E2 (PGE2alpha)-alpha, serially measured after arrival in the ICU (baseline value) and during the next 14 days. Mean plasma IL-1 (29.3 +/- 5.8 [SD] pg/mL), TNF-alpha (138.5 +/- 22.4 pg/mL), and soluble TNF-alpha r1 (6.1 +/- 0.3 ng/mL) values were significantly higher in group 2 patients before clinical evidence of sepsis and MOF. With the onset of severe infections in group 2 patients, IL-1, TNF-alpha, and sTNF-alpha r1 values decreased, while immunosuppressive IL-10 (191.7 +/- 29.1 pg/mL) and PGE2alpha (87.7 +/- 20.4 pg/mL) values further increased and remained elevated during the time course. Analysis of lymphocyte subsets revealed a fall in total lymphocyte levels, in CD4+ T lymphocytes, and natural killer (NK) cells, but no change in CD8+ T lymphocyte subset. Despite a marked change in the T helper (CD4+) to T suppressor (CD8+) ratio (from 1:1.72 to 1:1.10), patients without MOF (group 1) had no significant difference in any of the markers tested compared with baseline values. In addition to the inverse CD4+/CD8+ T cell ratio (from 1:1.75 to 1:0.91) and increased activated T cells, each of these markers was significantly elevated and peaked before the onset of MOF in group 2 patients. CONCLUSIONS A severely depressed cellular immune response associated with increased suppressive mediators might be closely related to the development of severe sepsis and MOF in trauma patients. Therefore, an in-depth understanding of the deficits in host defense following multiple trauma will provide the basis for therapeutic interventions.

Plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism and prognosis of severely injured patients

A single base pair insertion/deletion (4G/SG) promoter polymorphism in the plasminogen-activator-inhibitor-1 (PAI-1) gene is thought to play a part in prognosis after severe trauma. We investigated the relation between outcome of severe trauma, PAI-1 concentrations, and PAP-1 genotype in 61 patients who had been severely injured. 11 (58%) of 19 patients with genotype 4G/4G did not survive, whereas only eight (28%) of 29 patients with heterozygous genotype 4G/SG, and two (15%) of 13 patients with genotype 5G/5G died. The PAI-1 4G allele is associated with high concentrations of PAI-1 in plasma and a poor survival rate after severe trauma.

Regional Hemostatic Status and Blood Requirements After Total Knee Arthroplasty With and Without Tranexamic Acid or Aprotinin

Antifibrinolytics seem to reduce postoperative blood loss after total knee arthroplasty. Few studies have shown the impact of these drugs on the mechanisms of coagulation. The purpose of this study was to examine coagulation/fibrinolysis variables as well as blood loss after total knee arthroplasty with and without antifibrinolytics in the operated limb on a regional level. Thirty-six patients were randomized into one of three groups to receive aprotinin, tranexamic acid, or no medication. We took blood samples of the femoral vein before deflating the tourniquet and after 5, 10, 30, 60, 120 min and on the first postoperative day. The implantation of a knee prosthesis in artificial ischemia caused a significant activation of coagulation and fibrinolysis in the regional circulation. Tranexamic acid and aprotinin did not cause a significant modulation of fibrinolysis variables or a significant reduction of postoperative bleeding and transfusion requirements. One of the differences in comparison to other studies was the decreased total blood loss. The use of bone cement as well as surgical hemostasis before wound closure may be regarded as reasons for this. Therefore, primarily these methods should be used because there is no increased risk of adverse drug effects.

Discriminative power on mortality of a modified Sequential Organ Failure Assessment score for complete automatic computation in an operative intensive care unit.

Objective To evaluate the discriminative power on mortality of a modified Sequential Organ Failure Assessment (SOFA) score and derived measures (maximum SOFA, total maximum SOFA, and delta SOFA) for complete automatic computation in an operative intensive care unit (ICU). Design Retrospective study. Setting Operative ICU of the Department of Anesthesiology and Intensive Care Medicine. Patients Patients admitted to the ICU from April 1, 1999, to March 31, 2000 (n = 524). Data from patients under the age of 18 yrs and patients who stayed <24 hrs were excluded. In the case of patient readmittance, only data from the patient’s last stay was included in the study. Interventions None. Measurements and Main Results The main outcome measure was survival status at ICU discharge. Based on Structured Query Language (SQL) scripts, a modified SOFA score for all patients who stayed in the ICU in 1 yr was calculated for each day in the ICU. Only routine data were used, which were supplied by the patient data management system. Score evaluation was modified in registering unavailable data as being not pathologic and in using a surrogate of the Glasgow Coma Scale. During the first 24 hrs, 459 survivors had an average SOFA score of 4.5 ± 2.1, whereas the 65 deceased patients averaged 7.6 ± 2.9 points. The area under the receiver operating characteristic (ROC) curve was 0.799 and significantly >0.5 (p < .01). A confidence interval (CI) of 95% covers the area (0.739–0.858). The maximum SOFA presented an area under the ROC of 0.922 (CI: 0.879–0.966), the total maximum SOFA of 0.921 (CI: 0.882–0.960), and the delta SOFA of 0.828 (CI: 0.763–0.893). Conclusion Despite a number of differences between completely automated data sampling of SOFA score values and manual evaluation, the technique used in this study seems to be suitable for prognosis of the mortality rate during a patient’s stay at an operative ICU.

Influence of colloid fluids on polymorphonuclear granulocyte function in vivo.

Background: Granulocytes have a role in the immediate immune response. In a previous investigation we could demonstrate in vitro a moderate increase of the complement receptors CR1 (CD35) and CR3 (CD11b/CD18) on the surface of polymorphonuclear neutrophils (PMN) after incubation of whole blood with colloids. To elucidate the clinical significance, we investigated if these changes were also present in vivo.

Quantitative determination of free intracellular α-keto acids in neutrophils

For the first time, a procedure is described for the quantitative analysis of free α-keto acid content in human neutrophils (PMNs) relative to single cell number by reversed-phase fluorescence high-performance liquid chromatography. The procedure is minimally invasive and is unsurpassed in the quality of PMN separation, ease of sample preparation as well as sample stability. This method can satisfy the rigorous demands for an ultra-sensitive, comprehensive and rapid intracellular α-keto acid analysis in particularly for the surveillance of severe diseases as well as cellular or organ dysfunction.

Glutamine administration in patients undergoing cardiac surgery and the influence on blood glutathione levels

Background: Cardiac surgery with an extracorporeal circulation cardiopulmonary bypass (CPB) is characterized by an oxidative stress response. Glutathione (GSH) belongs to the major antioxidative defense. In metabolic stress, glutamine (GLN) may be the rate‐limiting factor of GSH synthesis. Decreased GLN plasma levels were observed after various critical states. We evaluated, in patients undergoing open heart surgery with CPB, the effects of a peri‐operative GLN supplementation on GSH in whole blood and assessed their influence on the Sequential Organ Failure Assessment score and the intensive care unit length of stay.

Pathways involved in alanyl-glutamine-induced changes in neutrophil amino- and α-keto acid homeostasis or immunocompetence

Summary.We examined the effects of DON [glutamine-analogue and inhibitor of glutamine-requiring enzymes], alanyl-glutamine (regarding its role in neutrophil immunonutrition) and alanyl-glutamine combined with L-NAME, SNAP, DON, β-alanine and DFMO on neutrophil amino and α-keto acid concentrations or important neutrophil immune functions in order to establish whether an inhibitor of •NO-synthase [L-NAME], an •NO donor [SNAP], an analogue of taurine and a taurine transport antagonist [β-alanine], an inhibitor of ornithine-decarboxylase [DFMO] as well as DON could influence any of the alanyl-glutamine-induced effects. In summary, irrespective of which pharmacological, metabolism-inhibiting or receptor-mediated mechanisms were involved, our results showed that impairment of granulocytic glutamine uptake, modulation of intracellular glutamine metabolisation and/or de novo synthesis as well as a blockade of important glutamine-dependent metabolic processes may led to significant modifications of physiological and immunological functions of the affected cells.

Relationship of taurine and other amino acids in plasma and in neutrophils of septic trauma patients

Summary.Recently, an interdependency of plasma taurine and other amino acids as well as metabolic and clinical variables implicating therapeutic options was reported. This result may be an indication that plasma taurine levels are directly related to intracellular levels. Therefore, the aim of this study was to analyse the possible relationship between taurine levels in plasma and in neutrophils, the relationship to other amino acids, and variables quantifying metabolic impairment and severity of sepsis in multiple trauma patients developing sepsis. After multiple trauma taurine decreased significantly in plasma in thirty-two patients as well as within the neutrophil and does not recover in sepsis. Lower individual levels in the neutrophil did not follow lower individual levels in plasma and no correlation of taurine in plasma and in the neutrophils could be observed. In sepsis, only plasma showed an interdependency of taurine, aspartate, and glutamate. No association between taurine plasma or intracellular levels and SOFA score as indicator for severity of sepsis or metabolic variables was observed. After multiple trauma and in sepsis, taurine uptake in cells (which is regulated in different ways), and intracellular taurine (which serves e.g. as an osmolyte) can be influenced. Therefore a prediction of the neutrophil taurine pool seems not fully possible from taurine plasma levels. Intracellular taurine has some unique properties explaining the missing interdependency despite some similarities in osmoregulation and metabolic interactions to other amino acids. The association of taurine, aspartate, and glutamate in plasma cannot be simply transferred to the neutrophils intracellular level. The clinical meaning of the plasma correlation remains unclear. A dependency of plasma and neutrophil taurine to severity of sepsis and to metabolic variables seems not possible because of the multifactorial pathophysiology of sepsis.

Alterations in neutrophil (PMN) free intracellular alpha-keto acid profiles and immune functions induced by L-alanyl-L-glutamine, arginine or taurine.

Summary.The objective of this study was to determine the dose as well as duration of exposure-dependent effects of L-alanyl-L-glutamine, arginine or taurine on polymorphonuclear neutrophil (PMN) free α-keto acid profiles and, in a parallel study, on PMN immune functions. Exogenous L-alanyl-L-glutamine significantly increased PMN α-ketoglutarate, pyruvate PMN superoxide anion (O2−) generation, hydrogen peroxide (H2O2) formation and released myeloperoxidase (MPO) activity. Arginine also led to significant increases in α-ketoglutarate, pyruvate, MPO release and H2O2 generation. Formation of O2− on the other hand was decreased by arginine. Incubation with taurine resulted in lower intracellular pyruvate and α-ketobutyrate levels, decreased O2− and H2O2 formation and a concomitant significantly increased MPO activity. We therefore believe that considerable changes in PMN free-α-keto-acid profiles, induced for example by L-alanyl-L-glutamine, arginine or taurine, may be one of the determinants in cell nutrition that considerably modulates the immunological competence of PMN.