Location
Utah State University
Start Date
5-10-2010 1:15 PM
Description
Intro-Differences in anesthetic technique when using propofol, remifentanil and fentanyl can result in different emergence and nociception outcomes. After surgery, a brief emergence period combined with an extended duration of analgesia is desired. We propose to use pharmacokinetic (PK)1-4 and pharmacodynamic (PD)5,6 models to find optimized ratios of propofol and remifentanil to shorten emergence time and extend the time until inadequate analgesia is experienced during patient recovery. Modeling has been used to find the optimum effect site concentrations (CeS) for rapid wake up7; however, an optimization technique which also accounts for analgesic effect is desirable.
Method-Anesthesiologists gave general anesthesia to 21 patients for laproscopic procedures using propofol, remifentanil, and fentanyl using a standard of care anesthetic technique. Baseline model predictions for CeS were calculated for remifentanil, fentanyl, and propofol. PD response surface models were used to calculate the probabilities of unconsciousness and response to noxious stimulus (30 PSI tibial pressure algometry, a surrogate of postoperative pain) during and after the anesthetic. Post-hoc optimized PK and PD model predictions were made for both sedation and analgesia by varying the ratio of propofol and remifentanil CeS, constrained to the same or higher PD model predicted probabilities, and leaving fentanyl CeS unchanged from baseline. For each patient, optimized changes to the recorded propofol and remifentanil infusions were made every 5 minutes during the general anesthetic. The theoretical improvement provided by the optimization was measured by comparing the time differences between the baseline model predications and the optimized prediction of the emergence time and time to inadequate analgesia.
Results-The baseline model predictions found an average emergence time of 8.2 +/- 5.6 minutes after end of surgery and a duration of analgesia of 9.9 +/- 13.6 minutes after patient emergence. The optimized remifentanil and propofol CeS theoretically reduced the emergence time to 3.9 +/- 1.6 (p<0.01, t-test) minutes and increased the duration of adequate analgesia to 15.4 +/- 12.5 (p<0.05, t-test) minutes.
Discussion-Optimized ratios of propofol and remifentanil resulted in a theoretically shorter emergence time and a longer period of adequate postoperative analgesia. These results require clinical verification in a new study, but the optimization algorithm shows potential for real-time clinical guidance in drug management.
Minimizing Post-Surgery Time While Providing Adequate Analgesia
Utah State University
Intro-Differences in anesthetic technique when using propofol, remifentanil and fentanyl can result in different emergence and nociception outcomes. After surgery, a brief emergence period combined with an extended duration of analgesia is desired. We propose to use pharmacokinetic (PK)1-4 and pharmacodynamic (PD)5,6 models to find optimized ratios of propofol and remifentanil to shorten emergence time and extend the time until inadequate analgesia is experienced during patient recovery. Modeling has been used to find the optimum effect site concentrations (CeS) for rapid wake up7; however, an optimization technique which also accounts for analgesic effect is desirable.
Method-Anesthesiologists gave general anesthesia to 21 patients for laproscopic procedures using propofol, remifentanil, and fentanyl using a standard of care anesthetic technique. Baseline model predictions for CeS were calculated for remifentanil, fentanyl, and propofol. PD response surface models were used to calculate the probabilities of unconsciousness and response to noxious stimulus (30 PSI tibial pressure algometry, a surrogate of postoperative pain) during and after the anesthetic. Post-hoc optimized PK and PD model predictions were made for both sedation and analgesia by varying the ratio of propofol and remifentanil CeS, constrained to the same or higher PD model predicted probabilities, and leaving fentanyl CeS unchanged from baseline. For each patient, optimized changes to the recorded propofol and remifentanil infusions were made every 5 minutes during the general anesthetic. The theoretical improvement provided by the optimization was measured by comparing the time differences between the baseline model predications and the optimized prediction of the emergence time and time to inadequate analgesia.
Results-The baseline model predictions found an average emergence time of 8.2 +/- 5.6 minutes after end of surgery and a duration of analgesia of 9.9 +/- 13.6 minutes after patient emergence. The optimized remifentanil and propofol CeS theoretically reduced the emergence time to 3.9 +/- 1.6 (p<0.01, t-test) minutes and increased the duration of adequate analgesia to 15.4 +/- 12.5 (p<0.05, t-test) minutes.
Discussion-Optimized ratios of propofol and remifentanil resulted in a theoretically shorter emergence time and a longer period of adequate postoperative analgesia. These results require clinical verification in a new study, but the optimization algorithm shows potential for real-time clinical guidance in drug management.