Pharmacokinetics of antibiotic prophylaxis in major orthopedic surgery and blood-saving techniques.

The pharmacokinetics of cefuroxime, cefotiam, cefamandole, and ampicillin/sulbactam were randomly measured in 40 patients undergoing major orthopedic surgery associated with high blood and volume turnover and intraoperative blood salvage. Serum and bone concentrations and the pharmacokinetics occurring in the context of these procedures were measured. No changes in elimination half-life relative to a normal population occurred with cefuroxime, cefotiam, and ampicillin. Serum and tissue concentrations were slightly lower with cefamandole and sulbactam, but reapplication of the initial dose was required with all antibiotics 4 hours after the first application.

Effects of diazepam on neutrophil (PMN) free amino acid profiles and immune functions in vitro. Metabolical and immunological consequences of L-alanyl-L-glutamine supplementation.

The objective of this study was to determine the effects of diazepam, L-alanyl-L-glutamine (ala-gln) or diazepam combined with ala-gln on polymorphonuclear leukocyte (PMN) free amino acid profiles. In a parallel study the effects on PMN immune functions were also documented for the first time. The incubation of whole blood with diazepam led to significant changes in PMN free glutamine, aspartate, glutamate, ornithine, arginine, citrulline, taurine and methionine as well as branched chain and neutral amino acid concentrations. Ala-gln caused significant increases in PMN glutamine and alanine and asparagine, aspartate, glutamate, ornithine, arginine, serine and glycine profiles. Regarding PMN immune functions, diazepam significantly decreased superoxide anion (O(2)(-)) and hydrogen peroxide production (H(2)O(2)) and myeloperoxidase activity (MPO) while ala-gln significantly increased PMN immune functions. Ala-gln supplemented to diazepam largely reversed the changes in PMN amino acid profiles and PMN immune functions brought about by diazepam. Overall, diazepam or ala-gln lead to significant changes in PMN free amino acids. Important PMN immune functions also seem to be affected. In regards to the results, there is significant relevance to the pharmacological regimens which enhance the supply of diazepam or ala-gln in whole blood suggesting that considerable changes in PMN "labile free amino acid pool" occur. These regimens often follow beneficial nutritional therapy or maleficent pharmacological stress and may be one of the determinants in cell nutrition which influence PMN function. It is partially through its effect on PMN labile free amino acid pool that ala-gln supplemented to diazepam may maintain PMN immune functions in vitro.

Cerebral blood flow velocity during isovolemic hemodilution and subsequent autologous blood retransfusion.

PURPOSE: To quantify the influence of hematocrit on cerebral blood flow velocity (CBFV) in healthy volunteers undergoing acute isovolemic hemodilution (HD) with hydroxyethyl starch 10% (HES) and subsequent autologous whole blood retransfusion (RT). METHODS: In 11 volunteers 20 ml x kg(-1) blood was withdrawn over 30 min and simultaneously replaced with HES 10%. Thirty min later, RT was started at a constant rate over 30 min. Recorded parameters included: CBFV pulsatility-index (PI) and resistance-index (RI) of the middle cerebral artery (MCA). Blood pressure (BP), heart rate (HR), hemoglobin (Hb), hematocrit (Hc) peripheral O2-saturation (SpO2), P(ET)CO2, arterial oxygen content (CaO2) and cerebral arterial O2-transport (C(E)-DO2= CaO2 x Vm-MCA) were monitored. RESULTS: An average of 1570 total blood was withdrawn which resulted in a decrease in Hb from 14.5 mg x dl(-1) to 10.3 mg x dl(-1); Hc (and CaO2) decreased from 41.8% (19.8 ml x dl(-1)) to 29.6% (14.2 ml x dl(-1); P < 0.01). Vm-MCA increased from 61.2 cm x sec(-1) to 77.3 cm x sec(-1) (P < 0.01). Following RT, Vm-MCA decreased again, but remained higher than baseline (P < 0.01). PI decreased by 13% following RT (P < 0.05). There were no changes in RI, HR, BP SpO2 and P(ET)CO2. Regression lines could be fitted between Hc and Vm-MCA, Vm-MCA and CaO2, and between Hc and C(E)DO2. CONCLUSIONS: Transcranial Doppler changes in blood flow velocities correlated with the simultaneously recorded systemic Hc and CaO2 values. We found a 2% increase in CBFV for each 1% decrease in Hc and CaO2.