Effect of Sevoflurane, Propofol, and Remifentanil on Hemodynamic Response to Pneumoperitoneum and Laparoscopic Surgery: A Randomized Controlled Trial

BACKGROUND: Although the interaction of sevoflurane, propofol, and opioids has been investigated regarding motor response to laryngoscopy, their hemodynamic impact during surgical stimulation remains unexplored. We therefore assessed the effect of sevoflurane, propofol, and remifentanil on the hemodynamic response to pneumoperitoneum and laparoscopic surgery. METHODS: The American Society of Anesthesiologists (ASA) physical status I or II patients scheduled for elective laparoscopic surgery were randomly assigned to one of six groups with different combinations of sevoflurane-remifentanil, propofol-remifentanil, or sevoflurane-propofol-remifentanil, respectively. The Ce50 BARPP (pneumoperitoneum) for sevoflurane and propofol in combination with remifentanil was determined with the up-and-down method, and the interaction of the three drugs on mean arterial pressure (MAP) response was described with a linear-additive model. During surgery remifentanil was titrated to keep the MAP <100 mm Hg at fixed concentrations of sevoflurane (1 vol%), propofol (3 µg mL-1), or sevoflurane (0.5 vol%) plus propofol (1.5 µg mL-1). The relationship between remifentanil and MAP during surgery was described with a linear mixed-effects model. RESULTS: Data of 155 patients were analyzed. At remifentanil 5 ng mL-1 the Ce50 BARPP (95% CI) of sevoflurane was 1.56 (1.18-1.95) vol%, and of propofol 4.82 (4.29-5.36) µg mL-1. At remifentanil 3 ng/ml plus either propofol 1.8 µg mL-1 or sevoflurane 0.6 vol%, the values were 2.2 (2.0-2.4) vol% and 5.9 (5.7-6.0) µg mL-1. The drug interaction model revealed a propofol scaling factor (scaleSP) of 0.31 (0.19-0.44), representing the potency of propofol relative to sevoflurane, and a remifentanil constant kremi of 2.03 (0.82-3.24), representing the hypnotic-sparing effect of remifentanil. The median (interquartile range) of remifentanil during surgery was 6.4 (5.8-7.7), 4.9 (3.6-6.7), and 5.0 (3.7-6.0) ng mL-1 in groups SR, PR, and SPR, respectively. The MAP did not correlate with the remifentanil concentrations, demonstrating evidence for the drug titration paradox. CONCLUSIONS: The relative potency of sevoflurane to propofol in reducing the MAP response to pneumoperitoneum is similar to that for tolerance of laryngoscopy but differs from that for hypnotic endpoints. The effect of remifentanil on reducing the MAP response is similar whether it is combined with sevoflurane or propofol. Because titration to a dynamic clinical end point decouples the traditional relationship between drug input and clinical outcome, titration data cannot be used to validate pharmacodynamic models.