Response Surface Model Predictions of Emergence and Response to Pain in the Recovery Room

Abstract

Introduction Sevoflurane - remifentanil interaction models that predict responsiveness and response to painful stimuli have been evaluated in patients undergoing elective surgery. Preliminary evaluations of model predictions were found to be consistent with observations in patients anesthetized with sevoflurane, remifentanil and fentanyl. The present study explored the feasibility of adapting the predictions of sevoflurane-remifentanil interaction models to an isoflurane-fentanyl anesthetic. We hypothesized that model predictions adapted for isoflurane and fentanyl are consistent with observed patient responses and are similar to the predictions observed in our prior work with sevoflurane-remifentanil/fentanyl anesthetics. Methods Twenty-five patients scheduled for elective surgery received a fentanyl-isoflurane anesthetic. Model predictions of unresponsiveness were recorded at emergence and predictions of a response to noxious stimulus were recorded when patients first required analgesics in the recovery room. Model predictions were compared to observations with graphical and temporal analyses. Results were also compared to our prior predictions following a sevoflurane-remifentanil/fentanyl anesthetic. Results While patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (≥ 99%). Following termination of the anesthetic, model predictions of responsiveness well described the actual fraction of patients observed to be responsive during emergence. Half of the patients awoke within 2 minutes of the 50% model predicted probability of unresponsiveness; 70% awoke within 4 minutes. Similarly, predictions of a response to a noxious stimulus were consistent with the number of patients who required fentanyl in the recovery room. Model predictions following an isoflurane-fentanyl anesthetic were similar to model predictions following a sevoflurane-remifentanil/fentanyl anesthetic. Discussion Results confirmed our study hypothesis; model predictions for unresponsiveness and no response to painful stimuli, adapted to isoflurane-fentanyl, were consistent with observations. These results were similar to our prior study comparing model predictions and patient observations following a sevoflurane-remifentanil/fentanyl anesthetic.

Pharmacokinetic and pharmacodynamic interactions in anaesthesia. A review of current knowledge and how it can be used to optimize anaesthetic drug administration

“…42 This is supported by a study revealing that 50% of the subjects undergoing fentanylisoflurane anaesthesia woke within 2 min of the time predicted by extrapolation from a sevoflurane-remifentanil model-predicted wake-up time, on the basis of equivalence. 93 More recently, a study showed accurate predictions for wake-up time from a sevoflurane-remifentanil interaction model adapted to equipotent sufentanil-desflurane doses that were used. 94…”

A Response Surface Model Exploration of Dosing Strategies in Gastrointestinal Endoscopies Using Midazolam and Opioids

“…A surface will encompass the complete set of isobolograms, concentration–effect curves, and curve shift effects. The RSMs are most often used clinically to predict wake up time, 1 , 18 , 19 tolerance to stimuli, 20 – 22 or occurrence of side effects. 1 , 23 We can help define the optimal dosing regimen by analyzing different but relevant surfaces simultaneously.…”

An introduction to predictive modelling of drug concentration in anaesthesia monitors

“…The numbers in the circles represent the number of minutes above a 95% probability of no response to laryngoscopy. To simplify presentation, fentanyl was converted to remifentanil equivalents using standardised opioid equivalency ratios . No response to laryngoscopy was defined as no movement, and no haemodynamic response in heart rate or blood pressure to direct laryngoscopy.…”

“…The time window presented starts 50 min into the anaesthetic to 20 min after the anaesthetic is turned off. Isoflurane and fentanyl simulations were performed using published pharmacokinetic and pharmacodynamic models . Definitions, simulated patients’ characteristics, assumptions and limitations are presented below Table .…”

“…The simulation assumes that a sufentanil infusion was started at the beginning of the procedure at a rate of 0.7 μg.kg −1 .h −1 , desflurane was maintained at 6.6%, and the anaesthetic duration is 3 h. The sufentanil infusion was stopped 45 min, 30 min, 15 min and 0 min before turning the desflurane off. Desflurane and sufentanil simulations were performed using published pharmacokinetic and pharmacodynamic models . Definitions, simulated patients’ characteristics, assumptions and limitations are presented below Table .…”