Emergence from anesthesia is complex period where, as with induction, several competing interests influence an anesthesiologist’s course of action. Timely emergence from anesthesia, adequate ventilatory function, and pain control once emerged from anesthesia; prevention of postoperative nausea and vomiting; and proper management of other comorbidities are some of these interests. This chapter will briefly review the selected issues regarding emergence from anesthesia, including:
Is there any advantage of target-controlled infusion (TCI) over total intravenous anesthesia (TIVA) when using conventional infusion rates in terms of a timely emergence from anesthesia?
Are end-tidal potent inhaled agent levels under non–steady-state conditions, such as emergence, useful in predicting wake-up times?
What is a rational approach to opioid administration for safe postoperative analgesia?
What technique can be used to estimate intraoperative and postoperative opioid requirements in patients who chronically consume opioids?
TARGET-CONTROLLED INFUSION VERSUS TOTAL INTRAVENOUS ANESTHESIA
No definitive outcomes study has explored whether administering a total intravenous anesthetic via TCI or with conventional continuous infusion rates impacts emergence. One might hypothesize that if administering a lengthy anesthetic, TCI would provide a more economical anesthetic and avoid unnecessary drug delivery that would perhaps delay emergence. Figure 30–1 presents a simulation of 2 intravenous techniques: one using TCI and the other set infusion rates for 2, 4, 6, and 8 hours. Both approaches used a high-dose remifentanil and low dose propofol technique. In fact the TCI target effect-site concentrations were selected to be near the effect-site concentrations that resulted from propofol infusions of 100 mcg/kg/min and remifentanil 0.2 mcg/kg/min. In general, with increasing duration of the anesthetic, the simulation predicted the time to emergence would become longer. Time to emergence was defined as the time required for the model of loss of responsiveness to predict that only 1 out of 20 people would be unresponsive (5%). Either technique (TCI or TIVA) was within 1 or 2 minutes of the other. For shorter infusions (2 and 4 hours), the TIVA technique was 1 minute ahead of the TCI for emergence. For the long infusion (8 hours), that relationship was reversed; time for emergence from TCI occurred a few minutes before that for TIVA. A potential explanation for the negligible differences between TIVA and TCI is that a high-dose opioid technique was used reducing the amount of propofol used.
Emergence for anesthesia: is there a difference between total intravenous anesthesia (TIVA) and target-controlled infusion (TCI)? Here are simulations of the predicted probability of unresponsiveness once an anesthetic has been terminated for TCI and TIVA using propofol and remifentanil. TIVA consisted of propofol 100 mcg/kg/min and remifentanil 0.2 mcg/kg/min. TCI consisted of propofol and remifentanil target effect-site concentrations of 3 mcg/mL and 6 ng/mL, respectively. Each technique was administered for 2, 4, 6, and 8 hours. The end of emergence (gray horizontal line) was defined as a 5% probability of unresponsiveness (ie, 19 out of 20 people would be awake). The time from turning off all infusions until reaching a 5% probability of unresponsiveness is presented in parentheses. All simulations assumed a 50-year-old, 165-cm, 70-kg female. Simulations were based on published pharmacokinetic and pharmacodynamic models.1, 2, 3, 4, and 5 The main point of these simulations is that for infusions up to 8 hours, technique (TIVA versus TCI) has minimal impact on the predicted time to emergence.
END-TIDAL INHALED AGENT CONCENTRATIONS
Gas monitors provide measurements of end-tidal inhaled agent concentrations that anesthesiologists may use to predict when patients will emerge from anesthesia. A key phenomenon illustrated in Figure 30–2 is that effect-site concentrations lag behind end-tidal concentrations under non–steady-state conditions (ie, emergence). In this example, sevoflurane has been maintained at 2% for 4 hours. Once administration is terminated, end-tidal concentrations quickly drop to below 0.5% in less than 5 minutes. In fact, effect-site concentrations do not catch up to end-tidal concentrations for up to 15 minutes. These times are somewhat arbitrary, given than anesthesiologists often manipulate ventilatory function to remove as much inhaled agent as quickly as possible, but the relationship stays the same. Thus, making prediction of emergence based on end-tidal concentrations is likely to be misleading.
During emergence, are end-tidal agent levels useful in predicting time to wake-up? All simulations assumed a 30-year-old, 175-cm, 80-kg male undergoing a 4-hour anesthesia with sevoflurane combined with either hydromorphone or fentanyl. Simulations also assumed a minute volume of 6 L/min, normal pulmonary mechanics, and normal cardiopulmonary function. Hydromorphone or fentanyl was administered as a transition opioid near the end of the procedure. Hydromorphone, either 0.5 mg or 1 mg, was administered 1 hour before the end of the procedure. Fentanyl, either 2 or 3 mcg/kg, was administered 15 minutes before the end of the procedure. The top plot presents the predicted end-tidal and effect-site concentration (Ce) levels for sevoflurane. Of note, the effect concentration lags behind the end-tidal concentration by up to 15 minutes.
The second plot presents the predicted Ce levels during the first 30 minutes following the 4-hour anesthetic use. Of note, although the hydromorphone was administered 1 hour before the end of the procedure, the Ce levels are still rising, whereas the fentanyl concentrations are on the decline. The third plot presents the predicted probability of unresponsiveness during the first 30 minutes after the anesthetic has been turned off. The end of emergence (gray horizontal line) was defined as a 5% probability of unresponsiveness (ie, 19 out of 20 people would be awake). The time from turning off the sevoflurane until reaching a 5% probability of unresponsiveness is presented in parentheses for sevoflurane alone and sevoflurane in combination with fentanyl (a simulation for sevoflurane in combination with hydromorphone is not available). The bottom plot presents an expanded view of the third plot to visualize where each sevoflurane–fentanyl combination crosses over the 5% probability of unresponsiveness. Simulations were based on published pharmacokinetic and pharmacodynamic models.3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 The most important points from these simulations are that sevoflurane Ce levels lag behind end-tidal concentrations during non–steady-state conditions (such as emergence) and that the addition of a small amount of opioid can substantially prolong unresponsiveness.
The addition of even a small amount of opioid can substantially prolong emergence. In this simulation, an opioid was administered as a transition analgesic. Fentanyl was administered 15 minutes before the end of the procedure in either a 2- or 3-mcg/kg bolus. Hydromorphone was administered 1 hour before the end of the procedure in either a 0.5- or a 1-mg bolus. Although once the sevoflurane is discontinued, the time to emergence (again, time to reach a 5% probability of unresponsiveness) is markedly increased in the presence of fentanyl (from 24 to 40 minutes with 2 mcg/kg of fentanyl).
Figure 30–3 presents simulations of predicted effect-site concentrations following administration and effects for bolus doses of fentanyl, morphine, and hydromorphone. The aim of these simulations was to visualize the kinetic advantages and/or disadvantages of these opioids. The simulations demonstrate how effect-site concentrations of both hydromorphone and morphine persist for more than 8 hours in comparison to fentanyl, which lasts up to 1 hour. Both morphine and fentanyl provide analgesia and some probability of intolerable ventilatory depression, although these effects are short-lived for fentanyl but prolonged with morphine. Modeling parameters are not yet available to make similar predictions for hydromorphone.
Which opioid is best for postoperative analgesia? Here are simulations of morphine, fentanyl, and hydromorphone boluses administered near the end of a surgical procedure for moderate postoperative pain. Simulations present predicted effect-site concentration (Ce) levels and drug effects including analgesia and intolerable ventilatory depression (IVD) for 8 hours after administration. Analgesia was defined as a loss of response to painful tibial pressure found to be consistent with pain experienced in the postanesthesia care unit where patients requested analgesics.1,6 IVD was defined as respiratory rate less than 4 breaths/ min.14,15 A simulation of analgesia and IVD for hydromorphone is not available. All simulations assumed a 30-year-old, 183-cm, 100-kg male. Simulations were based on published pharmacokinetic and pharmacodynamic models.11,12 and 13 16,17 The main points of this figure are that the kinetic profile of morphine and hydromorphone is substantially different than fentanyl. Both morphine and hydromorphone provide effect long after the fentanyl effect has dissipated. Higher dose morphine (20 mg) may lead to ventilatory depression for several hours after administration.