Antibiotics modulate the stimulated cytokine response to endotoxin in a human ex vivo, in vitro model.

BACKGROUND: Sepsis may lead to the suppression of stimulated cytokine release after Gram-negative stimuli, correlating with a fatal outcome. Treatment of sepsis includes adequate therapy with antibiotics. The aim of this study was to investigate the role of antibiotics in the modulation of the lipopolysaccharide (LPS)-stimulated cytokine response of human monocytes. METHODS: In this ex vivo, in vitro study, whole blood samples were taken from 10 healthy volunteers, stimulated with LPS in the presence or absence of various antibiotics (penicillin, amoxicillin, cefuroxime, ceftazidime, cefotaxime, piperacillin/tazobactam, imipenem/cilastatin, gentamicin, netilmicin, ciprofloxacin, vancomycin) and cultured for 24 h. Thereafter, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). Furthermore, CD14 and HLA-DR expression on monocytes was assessed using flow cytometry. RESULTS: All cephalosporins decreased LPS-stimulated IL-10 release. Cefuroxime and cefotaxime also decreased the expression density of the LPS recognition molecule CD14 on monocytes. An increase in LPS-stimulated IL-10 release was observed with vancomycin. A suppression of LPS-stimulated TNF-alpha and IL-10 release was observed in the presence of ciprofloxacin. CONCLUSION: These results indicate a modulation of the expression density of CD14 on monocytes, together with a shift from a balanced to an inflammatory cytokine release pattern, by cefuroxime and cefotaxime. Vancomycin changes the response to an anti-inflammatory release pattern. After ciprofloxacin, a profound unresponsiveness of immune-competent cells to LPS stimulation is observed. Because of the critical role of a balanced innate immune response, these data may be of importance for the selection of antibiotics in septic patients.

[Desflurane and isoflurane in minimal-flow anesthesia. Consumption and costs with forced fresh gas reduction]. / Desfluran und Isofluran bei Niedrigflussnarkosen. Verbrauch und Kosten bei forcierter Frischgasreduktion.

BACKGROUND: In the present investigation we compared the consumption of desflurane (DES) and isoflurane (ISO) using a standardized minimal-flow protocol with a forced reduction of the fresh gas flow (FGF). METHODS: 54 adult women were examined. After induction of anaesthesia a forced reduction of the FGF was started: 5 min 0.5 l/min O(2) + 1 l/min N(2)O, 10 min 0.5 l/min O(2) + 0.5 l/min N(2)O; finally 0.3 l/min O(2) + 0.2 l/min N(2)O up to the end of surgery. The consumption of DES/ISO was determined with a precision balance. RESULTS: In the DES group the uptake was around 0.3 vol-%, i.e. less than 8% of the target 2/3 MAC value was taken up. For ISO the uptake was around 0.25 vol-%, i.e. the uptake was approximately 30% of the target 2/3-MAC value. The DES consumption was after 60 min 17.0+/-1.1 g, 120 min--27.3+/-1.8 g and 180 min--36.5+/-1.7 g. ISO consumption was significantly lower: 7.6+/-0.8 g, 12.4+/-1.7 g and 15.5+/-1.6 g. The use of DES yielded higher costs, i.e. 2.28 EUR for 60 min, 3.63 EUR for 120 min and 4.97 EUR for 180 min. The consumption of the inhaled anaesthetics can be calculated as: DES (g)=4.84+0.184 x duration (min) (R(2)=0.981), ISO (g)=2.049+0.0826 x duration (R(2)=0.979). The costs are: DES (EUR)=0.85+0.0323 x duration (min); ISO (EUR)=0.19+0.0077 x duration (min). CONCLUSION: With a forced reduction of the FGF the DES consumption is still higher.

[Myocardial preconditioning with volatile anesthetics. General anesthesia as protective intervention?]. / Myokardiale Präkonditionierung durch volatile Anästhetika. Narkose als protektive Intervention?

Reduction of the perioperative cardiovascular risk with pharmacological interventions plays a prominent role in routine anesthesia practice. For example, perioperative beta-blockade is well established in anesthesiological treatment of patients. There is a growing body of evidence supporting the cardioprotective effects of volatile anesthetics known as anesthetic-induced preconditioning. There are numerous and complex data from animal studies. The mechanisms of anesthetic-induced preconditioning have been extensively studied but have still not been clearly identified. Initial clinical data show the cardioprotective effects of volatile agents by looking at parameters of myocardial function and laboratory values and therefore, the question of the relevance of these data for routine clinical practice has been raised. This review gives a summary of the currently available data focusing on the mechanisms of anesthesiological preconditioning and clinical studies.

[Influence of gender on propofol consumption and recovery times]. / Einfluss des Geschlechts auf Propofolverbrauch und Aufwachzeiten bei standardisierter Anästhesietiefe.

INTRODUCTION: We investigated gender differences of drug consumption and recovery times for propofol-remifentanil anaesthesia. METHODS: Adult patients scheduled for minor orthopaedic surgery were randomised to receive a propofol-remifentanil anaesthesia controlled either by EEG monitoring (Narcotrend or BIS) or solely by clinical parameters. Anaesthesia was induced with remifentanil 0.4 microg/kg/min and a propofol target-controlled infusion (TCI) at 3.5 microg/ml. After intubation remifentanil was reduced to 0.2 microg/kg/min whereas propofol TCI was adjusted according to clinical parameters or to the following EEG target values: during maintenance to "D(0)" (Narcotrend) or "50" (BIS), 15 min before the end of surgery to "C(1)" (Narcotrend) or "60" (BIS). Recovery times were recorded and average normalised propofol consumption was calculated from induction and maintenance doses. RESULTS: A total of 60 male and 60 female patients completed the study. Gender differences were observed for recovery times (with standard practice) and for propofol consumption (with BIS monitoring). In the standard protocol group, propofol consumption was nearly identical for male and female patients whereas recovery times were significantly longer in the male group. In both EEG-guided groups propofol consumption was less for male patients while recovery times were slightly longer. In the group of female patients higher propofol TCI concentrations had to be used to reach the same BIS or Narcotrend values. CONCLUSION: With propofol-remifentanil anaesthesia, gender has impact on recovery times and propofol consumption. If the same amounts of propofol are applied, males awake later, with BIS or Narcotrend monitoring males receive less propofol for comparable EEG effects.

Modulation of the inflammatory response to cardiopulmonary bypass by dopexamine and epidural anesthesia.

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction. Microcirculation-dependent alteration of the gut mucosal barrier with subsequent translocation of endotoxins is a postulated mechanism for this inflammatory response. This study was designed to elucidate whether two different approaches to modulate splanchnic perfusion may influence systemic inflammation to CPB. METHODS: We examined 40 patients scheduled for elective coronary bypass surgery in a prospective, randomized study. One group (DPX) received dopexamine (1 micro g. kg-1. min-1) continuously after induction of anesthesia until 18 h after CPB. The control group (CON) received equal volumes of NaCl 0.9% in a time-matched fashion. In a third group (EPI) a continuous epidural infusion of bupivacaine 0.25% [(body height (cm) - 100). 10-1=ml.h-1] was administered for the whole study period. Procalcitonin (PCT), tumor necrosis factor (TNF-alpha), soluble TNF receptor, human soluble intercellular adhesion molecule-1, C-reactive protein (CRP) and leukocyte count were measured as parameters of inflammation. RESULTS: All parameters significantly increased following CPB. Increases of PCT, TNF-alpha and leukocyte count were significantly attenuated in the DPX and EPI groups at different time points. However, neither splanchnic blood flow nor oxygen delivery and consumption were different when compared with the CON-group. CONCLUSION: These results do suggest that mechanisms other than an improved splanchnic blood flow by DPX and EPI treatment have to be considered for the anti-inflammatory effects.

Effect of intravenous anesthetics on spontaneous and endotoxin-stimulated cytokine response in cultured human whole blood.

BACKGROUND: Various anesthetics have been suggested to interfere with the immune system. The ability of leukocytes to express surface receptors and mediators is fundamental to a successful host defense. Therefore, the effects of intravenous anesthetics on cytokine release by leukocytes and expression of surface molecules known to modulate this response were determined. METHODS: Concentration-dependent effects of thiopentone, etomidate, propofol, ketamine, midazolam, and fentanyl on spontaneous and endotoxin (lipopolysaccharide; 1 microg/ml)-stimulated cytokine release were studied in whole blood from volunteers (n = 6) cultured for 25 h. In addition, expression of the lipopolysaccharide-recognition molecule CD14 and the major histocompatibility complex class II molecule human leukocyte locus A system-DR (HLA-DR) on monocytes were assessed using flow cytometry. RESULTS: All anesthetics studied elicited only minor effects on spontaneous cytokine release even at pharmacologic concentrations. However, expression density of CD14 was reduced in the presence of thiopentone, etomidate, and propofol, whereas HLA-DR was unaffected. Lipopolysaccharide-stimulated tumor necrosis factor response was inhibited by thiopentone (12.8% [median]; 7.6-18.8 [25-75 percentile]) of control, and ketamine (46.4% [median]; 44.4-56.4 [25-75 percentile]), at pharmacologic concentrations, whereas it was augmented even in the presence of low concentrations of propofol (172.3% [median]; 120.5-200.7 [25-75 percentile]). Ketamine additionally decreased the concentration of interleukin (IL)-1beta (14.8% [median]; 12.0-18.0 [25-75 percentile]). Release of IL-1 receptor antagonist (IL-1ra) was inhibited by thiopentone, etomidate, and propofol, whereas the same anesthetics increased IL-10 concentration simultaneously. Midazolam and fentanyl did not alter the concentrations of any cytokine. CONCLUSIONS: These results suggest a complex modulation of the cytokine response by the studied anesthetics in cultured whole blood. Although effects on spontaneous cytokine release by leukocytes were negligible, some anesthetics affected their ability to respond to lipopolysaccharide.