Research has focused on the semisynthetic opioids fentanyl, alfentanil, sufentanil, and remifentanil which are more expensive than morphine; further studies are needed as their use may be associated with a reduction in overall costs and improved outcomes. Electroencephographic analysis and computer simulation are used to characterize these drugs, although there is no relationship with the level of analgesia. These correlate well with standard clinical doses, but studies have not taken into account the altered pharmacokinetics and dynamics in the critical care setting. Multicompartmental modeling suggests that the time to peak biophase concentration following an intravenous bolus is a function of both the rate of decline of plasma concentration and the rate of equilibration of plasma concentration with the site of the drug effect. Infusion regimes require an exponentially decreasing series of infusion rates before steady state is reached. These concepts are extremely relevant to the infusion of analgesics and sedative agents; for example, a fall of 80 to 90 per cent in opioid concentration is required for adequate ventilation after an opioid-oxygen anesthetic.
Reference to Fig 2 shows that if a rapid decrease in opioid concentration at the effect site is required, alfentanil is the drug of choice for operations lasting longer than
6 to 8 h and sufentanil is preferable for operations lasting up to 6 to 8 h. Fentanyl accumulates and thus may be associated with prolonged recovery if used for more than 1 h.
Fig. 2 Context-sensitive half-lives as a function of infusion duration for each of the pharmacokinetic models simulated: F, fentanyl; A, alfentanil; S, sufentanil; R, remifentanil. Thiopental (thiopentone) (T), midazolam (M), and propofol (P) are included for comparison.
Remifentanil is an exciting new opioid which is inactivated by blood and tissue esterases. The context-sensitive half-life is 3 to 4 min; it is constant over a 15-fold variation in effect-site concentration and is independent of duration of infusion. This allows for rapid titration of effect with ideal characteristics for critical care if a rapid reversal of effect is required. All these drugs appear to provide significant advantages over morphine, but further studies are required.
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