The results of this study indicate that the reduction of the MACBAR of sevoflurane is dose-dependent. A ceiling effect of the decrease of MACBAR of sevoflurane was found when sufentanil plasma target concentration increased to > 0.5 ng ml− 1 (Table 2). The ceiling effect of sufentanil was similar to the result measured by Brunner and colleagues[] at the same plasma target concentration when they evaluated the reduction of isoflurane’s MAC by sufentanil responding to skin incision. As all know, sufentanil is a µ receptor agonist, which can be saturated when its plasma target concentration beyond a certain level[]. Therefore, we speculate that a similar ceiling effect will occur under a similar plasma target concentration of sunfentanil no matter what kinds of surgery and stimulus are selected. However, the plasma target concentration of sunfentanil (0.18 ng ml− 1) for occurring ceiling effect in Shun-Huang and colleague’s study[] is significantly lower than that of our experiment result. It may be reasonably explained by the concomitant administration of 60% nitrous oxide[−]. Studies shows nitrous oxide can combine with the µ receptor and decrease the binding sites of sufentanil in humans[,,,,].
In this study, the MACBAR of sevoflurane (5.33%) under laparoscopic pneumoperitoneum stimulation is higher than that measured by Katoh and his colleagues (4.15%) under skin incision[]. It indicates that the laparoscopic pneumoperitoneum stimulus is stronger than the skin incision stimulus, so that a higher concentration of sevoflurane is needed to inhibit the stress reaction in laparoscopic surgery, which is consistent with the results of our previous study[]. However, the MACBAR of sevoflurane measured in this study is also significantly higher than the value (4.6%) reported in our previous study in gynecologic patients[9]Although the same CO2 pneumoperitoneum stimulus was used, the MACBAR of sevoflurane could be affected by many factors, such as the location of perforation for establishing pneumoperitoneum, the patient’s age and sex[,]the methods of measurement[25–26] and the criterion of judgment for a positive or negative response, et al[27–28]. Dixon thought that the MACBAR values could be estimated as the mean of four independent crossovers of responses[]. Paul and his colleagues thought that the reliability of the Dixon method increased with the number of pairs and six pairs was enough[]. An increase of 15% or more from the baseline value of MAP or HR was taken as the criterion of a positive response in many studies[,]. However, in clinic, the fluctuation of MAP or HR within the range of 20% is also acceptable and reasonable. Therefore, in our current study, an increase of 20% or more from pre-pneumoperitoneum stimulation values of MAP or HR was taken as the standard to judge a positive response.
Our results indicated the delta epinephrine or norepinephrine concentration did not differ among all the 5 groups (Table 3). It implied that when the sympathetic adrenergic response was inhibited in half patients to pneumoperitoneum stimulation in each group, the change of epinephrine or norepinephrine concentration would be similar, no matter the target controlled sufentanil concentration and the end tidal sevoflurane concentration. Our results also showed patients’ HR could be depressed to some degree with the increase of sufentanil plasma target concentration (Table 3). However, the decrease in HR did not result in the decrease of patients’ MAP, especially when high concentration of sufentanil was administrated. It implies the safety range of sufentanil is large, which is consistent with the results of Fechner and his colleagues[]. Nevertheless, our study showed the use of sufentanil at a large dose results in the delay of anaesthesia recovery (table1). Therefore, the administration of sufentanil in large dose for short surgeries such as laparoscopic cholecystectomy is not recommended.
One limitation of the study is that we did not measure arterial blood gas during the pneumoperitoneum period. Although the end-expiratory CO2 partial pressure was maintained in normal range by adjusting the tidal volume and respiratory rate, it was still necessary to measure the actual CO2 partial pressure to exclude the influence of hypercarbia on sympathetic adrenergic response. Another limitation is that we did not measure the actual plasma sufentanil concentration. Although the Bovill pharmacokinetic model for target-controlled infusion has been shown to be safe in Asian people, it is still necessary to measure the actual plasma sufentanil concentration to exclude individual error.
In conclusion, target-controlled infusion of sufentanil can significantly reduce the MACBAR of sevoflurane responding to laparoscopic pneumoperitoneum stimulation. Moreover, when the plasma target concentration of sufentanil is higher than 0.5 ng ml− 1, a capping effect of decrease will occur. In addition, when the sympathetic adrenergic response is inhibited at a same extent, the changes of epinephrine and norepinephrine concentrations are not affected by the sufentanil target concentration.