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A823
October 14, 2007 2:00 PM - 4:00 PM Room Hall D, Area K, |
| A Response Surface Model of Remifentanil and Propofol for Esophageal Instrumentation |
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Ken B. Johnson, M.D., Cris D. LaPierre, B.S., Julia L. White, R.N., Talmage D. Egan, M.D. Anesthesiology, University of Utah, Salt Lake City, Utah |
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Introduction: Using surrogates of surgical pain (electrical tetany and pressure algometry), prior work in our laboratory has demonstrated a pronounced synergistic antionocioceptive effect when propofol (P) is combined with remifentanil (R). We hypothesized that response surface methodology could be used to characterize R-P effect site concentration (Ce) pairs that would allow esophageal instrumentation (EI). Methods: Following IRB approval, using a cris-cross design, 24 volunteers received escalating target controlled infusions that targeted Ce ranges of 0-4.2 mcg/mL for P and 0-6.4 ng/mL for R. An 1.4 cm diameter blunt end bougie was used to mimic an endoscope or transesophageal echocardiography probe. An attempt was made to place the bougie in each subject at 15 different P-R Ce pairs. A response to placement was defined as raising their hand as an indication of discomfort, or > 20% increase in heart rate or blood pressure from baseline, or presence of a gag reflex. No response was defined as an absence of response with the bougie at 40 cm (mid esophageal) for 1 minute. Estimates of R and P Ces at each evaluation along with the response/no response data were used to build a response surface model using a Logit construct. Results: Model predictions of the R and P C50s were 15.6 ng/mL and 3.7 mcg/mL. The response surface model and the raw data are presented in Figure 1. Circles and square represent response and no response. Open and filled symbols indicate > and < 10% error between predicted and observed responses. The dashed, solid, and dotted lines represent the 5, 50, and 95% probabilities of no response to EI. Discussion: P and R interact synergistically in blunting the response to EI. Although synergistic, considerable P and R Ces were required to eliminate the response to EI. The response surface model predictions reveal Ce levels that are consistent with considerable sedation for P and respiratory depression for R.[figure1] Anesthesiology 2007; 107: A823 |
Figure 1
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