Intra- and inter-individual variation of BIS-index and Entropy during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study

INTRODUCTION: We studied intra-individual and inter-individual variability of two online sedation monitors, BIS and Entropy, in volunteers under sedation. METHODS: Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS and Entropy (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered. RESULTS: Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy values showed greater variability than BIS(R) values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation. CONCLUSIONS: The large intra-individual and inter-individual variability of BIS and Entropy values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability. TRIAL REGISTRATION: clinicaltrials.gov Nr. NCT00641563.

Application of primary allyl amines afforded by the Baylis-Hillman adducts for heterocyclic synthesis: Generation of 5-benzyl-4(3H)-pyrimidinones and 2-benzylidene-2,3-dihydro-pyrrolizin-1-ones

The applications of the primary allyl amines afforded by the acetyl derivative of Baylis-Hillman adducts of acrylate for the synthesis of heterocycles using robust reactions are described. In the first strategy a one-pot synthesis of 5-benzyl-4(3H)-pyrimidinones have been achieved via N-formylation of the amines in the presence of neat formamide followed by ammonium formate-mediated cyclization. These pyrimidinones have been demonstrated to be excellent precursor to the 4-pyridinamine derivatives. In the second strategy the synthesis of 2-benzylidene-2,3-dihydro-pyrrolizin-1-ones have been accomplished via treatment of allyl amine with dimethoxyfuran followed by saponification and PPA-mediated intramolecular cyclization.

Intermolecular crosslinking of fatty acyl chains in phospholipids: Use of photoactivable carbene precursors

Phospholipids containing photolysable carhene precursors (beta-trifluoro-a-diazopropionoxy and m-diazirinophenoxy groups) in w-positions of sn-2 fatty acyl chains were prepared. Photolysis of their vesicles produced crosslinked products in 40-60 % yields. Crosslinking was mostly intermolecular and occurred bv carbene insertion into the C-H bonds of a second fatty acyl chain. Crosslinking products were characterized by (i) their gel permeation behavior, (ii) analysis of produets formed by base-catalyzed transesterification. (iii) degradation with phosphoiipases A2 and C, (iv) gas chromatography/mass spectrometry, and-(v) use of mixtures of phospholipids carrying thf' carhene precursors and a phospholipid containing radioactively labeled fatty acyl groups. Nitrenes generated from the aliphatic or aromatic azido groups in phospholipids were unsatisfactory for forming crosslinks by insertion in C-H bond

Sites of intermolecular crosslinking of fatty acyl chains in phospholipids carrying a photoactivable carbene precursor

Sonicated vesicles of l-fatty acyl-2-w-(2-diazo-3.3,3-trifluoropropionoxy) fatty acyl sn-glycero-3-phosphorylcholines were shown recently to form intermolecular crosslinks by insertion of the photogenerated carbene into a C-H bond of a neighboring hydrocarbon chain. We now report that photolysis of multilamellar dispersions gives a second series of products in which carbene insertion is accompanied by elimination of a molecule of hydrogen fluoride. The sites of crosslinking in the latter compounds have been studied by mass spectrometry using phospholipids with varying chain lengths of the fatty acyl groups carrying the carbene precursor. The patterns observed show that the point of maximum crosslinking is consistent with the recent conclusion that in phospholipids the sn-2 fatty acyl chain trails the sn-1 chain by 2-4 atoms.