piperidines and sodium-metabisulfite

Propofol (Diprivan(TM); AstraZeneca, Wilmington, DE) is a commonly used drug for the induction of general anesthesia in the ambulatory setting. With the availability of a new bisulfite-containing generic formulation of propofol, questions have arisen regarding its cost effectiveness and safety compared with Diprivan(TM). Two hundred healthy outpatients were randomly assigned, according to a double-blinded protocol, to receive either Diprivan(TM) or bisulfite-containing propofol 1.5 mg/kg IV as part of a standardized induction sequence. Maintenance of anesthesia consisted of either desflurane (4%-8% end-tidal) or sevoflurane (1%-2% end-tidal) in combination with a remifentanil infusion (0.125 microg x kg(-1) x min(-1) IV). Patient assessments included pain on injection, induction time, hemodynamic and bispectral electroencephalographic changes during induction, emergence time, and incidence of postoperative nausea and vomiting. The two propofol groups were comparable demographically, and the induction times and bispectral index values during the induction were also similar. However, the bisulfite-containing formulation was associated with less severe pain on injection (5% vs 11%), with fewer patients recalling pain on injection after surgery (38% vs. 51%, P<0.05). None of the patients manifested allergic-type reactions after the induction of anesthesia. The acquisition cost (average wholesale price in US dollars) of a 20-mL ampoule of Diprivan(TM) was $15 compared with $13 for the bisulfite-containing propofol formulation. Therefore, we concluded that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan(TM) for the induction of outpatient anesthesia.. Bisulfite-containing propofol and Diprivan(TM) (AstraZeneca, Wilmington, DE) were similar with respect to their induction characteristics; however, the generic formulation was associated with a smaller incidence of injection pain. Assuming that the drug costs are similar, these data suggest that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan(TM).

Topics: Ambulatory Care; Anesthesia Recovery Period; Anesthetics, Inhalation; Anesthetics, Intravenous; Cost-Benefit Analysis; Desflurane; Double-Blind Method; Drugs, Generic; Electroencephalography; Female; Hemodynamics; Humans; Isoflurane; Male; Methyl Ethers; Middle Aged; Pain Measurement; Patient Satisfaction; Pharmaceutic Aids; Piperidines; Postoperative Nausea and Vomiting; Propofol; Prospective Studies; Remifentanil; Safety; Sevoflurane; Sulfites; Therapeutic Equivalency

We have investigated the effects of CP-96,345 and SR-48968, new nonpeptide (neurokinin) NK1 and NK2 receptor antagonists, respectively, against bronchoconstriction and airway microvascular leakage induced by inhaled sodium metabisulfite (MBS) in anesthetized guinea pigs. Lung resistance (RL) was measured for 6 min after challenge, followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. MBS (80 mM, 30 breaths) caused a significant increase in RL and leakage of dye at all airway levels. CP-96,345 (2 mg/kg, intravenous) but not SR-48968 (1.5 mg/kg, intravenous) significantly inhibited the leakage of dye at all airway levels except for trachea. Each antagonist inhibited significantly the maximal increase in RL. The combination had a significant additive effect against the bronchoconstriction, when compared with SR-48968 alone, and significantly inhibited the leakage of dye at the same airway levels as CP-96,345. We conclude that bronchoconstriction induced by inhaled MBS is, at least partly, mediated by activation of both NK1 and NK2 receptors, and the airway microvascular leakage by NK1 receptor stimulation alone.

Topics: Administration, Inhalation; Animals; Benzamides; Biphenyl Compounds; Bronchoconstriction; Capillary Permeability; Female; Guinea Pigs; Pharmaceutic Aids; Piperidines; Receptors, Tachykinin; Sulfites