Anesthetic technique has expanded and improved with the advent of newer drugs, methods to deliver them, and drug displays that present real-time anesthetic drug interactions. This chapter will briefly explore the following:
Use of pharmacodynamic interaction models to compare common anesthetic techniques
How substantially different dosing regimens yield near-equivalent effects
The pronounced opioid effect from common remifentanil dosing regimens
How target-controlled infusion (TCI) and total intravenous anesthesia (TIVA) compare in terms of anesthetic effects
TOTAL INTRAVENOUS ANESTHESIA VERSUS COMBINED TECHNIQUE
Anesthesiologists have long used both TIVA and potent inhaled agents combined with opioids. Both techniques are effective. TIVA is better suited for patients with a known or suspected history of postoperative nausea and vomiting; procedures such as microlaryngoscopy and rigid bronchoscopy, where delivery of potent inhaled agents is not possible; and females of childbearing age. Potent inhaled agents are better suited for patients with known or suspected ischemic cardiovascular disease. Major advantages are that there is less postoperative nausea and vomiting; improved cognitive function, at least during the first few hours after surgery1; and smooth emergence; patients simply appear happier as well. Potential disadvantages of TIVA are that it is more expensive; more complicated; and associated with a perception of more risk of awareness, although studies suggest a low risk of awareness.2 Use of inhalation agents is popular because they are easier to use and less expensive, allow for the monitoring of end-tidal concentrations, and are associated with a perceived lower risk of awareness.
With regard to the ability of either technique to provide an adequate level of anesthesia, consider the simulations presented in Figure 29–1. They present predictions of unresponsiveness for a TIVA technique using infusion rates (ie, mcg/kg/min), an intravenous technique using TCIs, and a potent inhaled agent in combination with an opioid technique. The 3 techniques used common dosing regimens that led to a predicted high probability of unresponsiveness.
Total intravenous anesthesia (TIVA) versus target-controlled infusion (TCI) versus combined techniques: simulation of the probability of unresponsiveness for 3 anesthetic dosing regimens: TIVA, TCI, and a combined potent inhaled agent (sevoflurane) and opioid technique. Unresponsiveness was defined as an Observer’s Assessment of Alertness and Sedation greater than 2. All simulations assumed a 50-year-old, 165-cm, 70-kg female undergoing a 90-minute procedure associated with minimal postoperative pain. All 3 techniques provide a high probability of unresponsiveness. The TIVA technique consisted of induction with fentanyl 1.5 mcg/kg and propofol 2 mg/kg followed by maintenance with propofol 100 mcg/kg/min and remifentanil 0.2 mcg/kg/min. A fentanyl bolus (1.5 mcg/kg) was administered as a transition opioid 15 minutes before the end of the procedure. The TCI technique consisted of a target propofol effect-site concentration of 3 mcg/mL and a target remifentanil effect-site concentration of 6 ng/mL. The combined potent inhaled agent–opioid technique consisted of induction as described for the TIVA followed by 2% sevoflurane in oxygen and remifentanil 0.2 mcg/kg/min. For both the TCI and sevoflurane techniques, a fentanyl bolus was administered as a transition opioid 15 minutes before the end of the procedure. Simulations were based on published pharmacokinetic and pharmacodynamic models.3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and 17
DIFFERENT DOSE, SAME EFFECT
Clinical pharmacologists have characterized anesthetic drug interactions for a variety of effects. This research has confirmed that various combinations of anesthetic drugs can have near-equivalent effects and that anesthetics with different mechanisms may enhance the effects of one another such that less overall anesthetic is required. Variations of the anesthetic techniques presented in Figure 29–1 illustrate this point (Table 29–1 and Figure 29–2). Low-dose opioid–high-dose sedative combinations versus high-dose opioid–low-dose sedative combinations have similar overall effects in terms of loss of responsiveness. This phenomenon persists across different types of sedatives (ie, propofol versus sevoflurane).
Different dose, same effect. Topographic representation of remifentanil–propofol (left) and remifentanil–sevoflurane (right) pharmacodynamic interaction models for loss of responsiveness. The gray shaded areas represent portions of the response surface associated with a 5% to 50% (light gray), 50% to 95% (gray), and greater than 95% (dark gray) probability of effect. Superimposed over the interaction model surface are approximate maximal concentration pairs for selected propofol and remifentanil infusion rates for various total intravenous dosing regimens (TIVA, blue circles), selected target propofol and remifentanil effect-site concentrations for various target-controlled infusion dosing regimens (TCI, pink circles), and selected sevoflurane (Sevo) vaporizer settings and remifentanil infusion rates for various potent inhaled agent–opioid dosing regimens (yellow circles). The numbers in the circles refer to dosing details presented in Table 29–1. Fentanyl concentrations are presented as remifentanil equivalents.18 All simulations assumed a 50-year-old, 165-cm, 70-kg female undergoing a 90-minute procedure associated with minimal postoperative pain. Simulations were based on published pharmacokinetic and pharmacodynamic models.3, 4, and 5,11, 12, 13, 14, 15, and 16 Many different dosing regimens yield a similar effect if dosed along isoeffect lines. Ce, effect-site concentration.