title: Co-induction of anaesthesia: the rationale.
abstract: Combination therapy with two or more different drugs, with the intention of reaching the same therapeutic goal, was heavily criticized for a long time. However, it is accepted today, especially when advantages over monotherapy can be shown. For the induction of anaesthesia or for long-term sedation in the intensive care unit, combination therapy may offer an improved effect profile, a more balanced ratio of desired versus adverse effects, an improved time-course of effect, simpler treatment requirements or lower costs. Midazolam and propofol have been investigated as potential partners for those two indications. The mechanism of action, pharmacokinetic properties, pharmacological effect, the way in which they interact at the receptor site, the differences in pharmaceutical formulations, the side-effect profiles and economic considerations were compared. Animal experiments and clinical pharmacology studies have shown that midazolam and propofol have synergy with other centrally active drugs. It could be expected that the relationship between desired effects and adverse effects could be improved by skilful use of the synergism between midazolam and propofol. Co-induction of anaesthesia and co-administration in long-term sedation can offer improvements in therapeutic situations compared with monotherapy. These improvements are in terms of a more suitable effect profile, a more favourable ratio of desirable effects to side-effects, optimization of the time-course of effects and reduced costs.
authors.affiliation: Department of Clinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Amrein
authors.forename: W
authors.initials: W
authors.lastname: Hetzel
authors.forename: S R
authors.initials: SR
authors.lastname: Allen
mesh_terms: D000758:Anesthesia / Q000379:methods*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D004338:Drug Combinations; D006801:Humans; D008874:Midazolam / Q000008:administration & dosage / Q000493:pharmacokinetics; D015742:Propofol / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D018686:Anesthetics, Intravenous; D004338:Drug Combinations; D008874:Midazolam; D015742:Propofol