[The art of reasonable combining drugs in anesthesia]

As yet no single intravenous anaesthetic drug can effectively and safely provide hypnosis, analgesia and amnesia. Thus intelligent combinations of hypnotics and opioids are necessary, especially for total intravenous anaesthesia (TIVA). Inescapable interactions occur, most of which are synergistic and should be evaluated for the optimal care of the patient. This synergism varies considerably according to the different drugs, the different endpoints of anaesthesia and the differently combined dosage of both agents. Because of their complex pharmacological properties, a valuable approach to evaluating interactions consists in administering both drugs to known plasma concentrations with the help of pharmacokinetic model-driven drug delivery systems (computer assisted continuous infusion). The Cp50 concept (plasma concentration that will prevent a pre-defined response to a given stimulus in 50% of the patients) is of prime interest. Recent (and current) studies have tried to define Cp50s of various hypnotics (such as propofol) and opioids (fentanyl, alfentanil, sufentanil). The best IV delivery technique appears to be infusing an opioid drug at analgesic concentrations (1-3 ng.ml-1 for fentanyl) and the hypnotic drug at modulated (but always hypnotic, no less than 3.0 micrograms.ml-1 for propofol) concentrations according to the different surgical stimuli and the patient's responses. The opposite approach (fixed hypnotic concentration, varying analgesic concentration) would be much less satisfactory. In addition, preoperative medications should be taken into account. Thus a better knowledge of the type and degree of interactions, as in a well-administered inhalational anaesthesia supplemented by opioids, will very likely contribute to develop TIVA liability and popularity.