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Ambition: A Minuet in Power. Lewd Story. Brons Quest. The Mating Season. Further, when spontaneous breathing is desired, lower than optimal effect site opioid concentrations e. Whereas, in contrast, in the cardiovascular-compromised patient, the hemodynamic function may become less depressed in the presence of higher than optimal effect site alfentanil and correspondingly lower than optimal effect site propofol concentrations.

In spontaneously breathing and cardiovascularly compromised patients, suboptimal propofol-opioid concentrations are indicated intraoperatively at the expense of a prolonged recovery. Translation of EC 50 and EC 95 values to infusion rates. Again, these infusion schemes should be used as guidelines, and adjustments should be made to the individual needs of the patient and in anticipation of factors such as age, sex, and stimulus intensity related to the type of surgery.

Table 4. Validation of the simulations. The data displayed in this manuscript are the result of computer simulations. Ideally, these data should be confirmed in clinical studies in the near future. At least five patients are needed to evaluate each data point in the diagrams of Figure 2 , Figure 3 , Figure 4 , Figure 5.

Consequently, 3, patients are needed to validate each diagram. Approximately 51, patients are then needed to validate the entire study. Hence, only fragments of the data shown here will actually be checked in a scientific manner, whereas for most data, only the simulations will be available.

Propofol interacts in a similar manner with all opioids. Is this assumption justified? According to Shafer et al. The potency ratio of the four opioids for all these pharmacologic endpoints is the same, which suggests that the opioids in the presence and absence of other agents behave pharmacodynamically in a similar manner and only differ from a pharmacokinetic point of view. Similarly, it also is clear that the opioids interact in a similar manner with various inhalational anesthetic agents.

In summary, the interaction between the opioids and other agents is similar for combinations of opioids with nitrous oxide, [ 6 ] with volatile anesthetic agents, [ 16—19 ] and with propofol. Based on the previously described studies, the assumption is justified that all opioids interact in a similar manner with propofol for various endpoints, just as they do combined with nitrous oxide and with volatile anesthetic agents.

Relation between EC 50 and EC 95 values. Again, this can be explained on the basis of the pharmacokinetics of propofol relative to that of the opioids. At intraoperative effect site EC 95 concentrations, return of consciousness is less postponed by relatively high propofol concentrations than by high alfentanil, fentanyl, or sufentanil concentrations because the decay in the propofol concentrations is steeper compared with these three opioids.

In contrast, combined with remifentanil, return of consciousness is less postponed by high remifentanil concentrations because remifentanil concentrations decrease more rapidly than those of propofol. The time to return of consciousness after propofol-opioid anesthesia depends predominantly on the selected opioid and only marginally on the duration of infusion. Optimal effect site propofol concentrations that allow the most rapid return of consciousness are lower when propofol is combined with remifentanil than when combined with either alfentanil, fentanyl, or sufentanil.

The target concentrations or the infusion rates of propofol and of the opioid with which propofol is combined should be adjusted in relation to the selected opioid and the duration of the infusion to allow an optimal rapid return of consciousness. Pharmacokinetic and pharmacodynamic models were implemented in a spreadsheet Quattro Pro, Borland International Inc. Simulations were performed in two stages. In the first stage, a central compartment target drug concentration was maintained constant for any desired length of time 15, 60, , or min.

In stage 2, after termination of the simulated infusion, the decreasing effect compartment concentrations of propofol and one of the opioids fentanyl, alfentanil, sufentanil, or remifentanil were determined simultaneously. In a stepwise manner, the simulation program is described as follows. The concentrations in the various compartments of the three-compartment model and the effect compartment at time t were calculated using Equation 1, Equation 2, Equation 3, Equation 4.

With the use of recently published pharmacokinetic parameter sets [ 9—13 ] and effect site equilibration constants [ 11,14,15 ] and with Equation 1, Equation 2, Equation 3, Equation 4, the central compartment concentrations C 1 of propofol and the opioids alfentanil, fentanyl, sufentanil, and remifentanil could be maintained constant for any desired duration of infusion, and after termination of the simulated infusion, the decay in the effect compartment concentration of these agents could subsequently be studied.

For propofol and alfentanil, multiple concentration combinations increasing with a step size in the propofol concentration of 0. After termination of the target-controlled infusion of propofol and alfentanil, effect site concentrations of propofol and alfentanil decreased according to Equation 7:Equation 7where t is the time elapsed after termination of infusion and A 1 , B 1 , D 1 , alpha, beta, and gamma were derived according to Hull.

With the optimizer function, t was iterated until C e ,prop t Equation 7 equaled the EC 50 of propofol for return of consciousness given by Equation 6. This was possible under the assumption, as based on the recent literature, [ 1—3,5,6,15—19 ] that the opioids alfentanil, fentanyl, sufentanil, and remifentanil all interact in a similar synergistic manner with propofol for the suppression of responses to surgical stimuli and for the return of consciousness postoperatively.

With the use of the corresponding pharmacokinetic parameter sets [ 9,11—13 ] and Equation 1, Equation 2, Equation 3, Equation 4, and Equation 7, the optimal effect site propofol-fentanyl, propofol-sufentanil, and propofol-remifentanil concentrations were defined for infusion durations of 15, 60, , and min.

In the end, we thus defined the optimal intraoperative effect site EC 50 -EC 95 therapeutic window for the combinations of propofol-alfentanil, propofol-fentanyl, propofol-sufentanil, and propofol-remifentanil for infusions lasting 15, 60, , and min.

The original publication on which the simulations are based only describes the intraoperative propofol-alfentanil EC 50 values for suppression of responses to surgical stimuli. The data were best fitted using the model exploring the possibility of a nonadditive interaction. Figure 6. New intravenous anesthetic agents. Refresher course , in the 46th annual refresher course lectures and clinical updata program. American Society of Anesthesiologists. Sign In or Create an Account. Advanced Search.

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