The results of our current study show that sevoflurane and propofol do not have different actions on the onset of the effects of rocuronium or on intubation conditions. However, sevoflurane significantly prolongs the duration of action of rocuronium compared with propofol. In addition, 0.9 mg/kg rocuronium was necessary to achieve adequate conditions for intubation under both propofol- and sevoflurane-remifentanil anesthesia in an Asian population.
Previously, Dahaba et al. [2] reported that there is a significant difference in rocuronium potency and duration of action among Austrian, Chinese, and American patients. According to their report, the ED95 of rocuronium in Chinese patients is 0.48 ± 1.6 mg/kg, which is significantly higher than the dose in American patients (0.36 ± 1.5 mg/kg). We show in our current investigation that clinically acceptable intubation conditions were achieved for 82 % (TIVA group) and 85 % (SEVO group) of patients after 0.6 mg/kg of rocuronium. However, for 0.9 mg/kg of rocuronium, 97 % (TIVA group) and 90 % (SEVO group) of patients showed acceptable intubation conditions (P < 0.001) and there was no difference between the types of anesthetic. Hence, we confirmed that the administration of 0.9 mg/kg of rocuronium can provide better intubation conditions under both propofol-remifentanil and sevoflurane-remifentanil anesthesia.
Several reports have shown that inhalational agents potentiate the neuromuscular effects of rocuronium. The mechanism by which inhalational anesthetics potentiate the effects of muscle relaxants is unknown. The proposed mechanisms include a central effect on alpha-motor neurons and interneuronal synapses [8], inhibition of postsynaptic nicotinic acetylcholine receptors [9], or augmentation of the antagonist’s affinity at the receptor site [10]. In addition, more than one mechanism is simultaneously involved and different inhalational anesthetics may not act exactly in the same way [11].
Such potentiation is not evident during induction and only becomes significant as the anesthesia duration becomes more prolonged [6]. In a study to quantify the relationship between the dose–response curve of vecuronium and the duration of exposure to an end-tidal concentration of sevoflurane, Suzuki et al. [5] showed that the duration of sevoflurane anesthesia influenced the dose–response of vecuronium and that 30 min inhalation of 1.7 % end-tidal concentration was sufficient to achieve a stable potentiating effect. In another report, 30 to 80 min was required to achieve maximal neuromuscular effects under 1 MAC halothane and isoflurane [12].
No report to date has shown that propofol could clinically potentiate neuromuscular blocking effects, but propofol has been reported to potentiate the effects of vecuronium, pancuronium, and suxamethonium in vitro [13]. Interestingly, intravenous anesthetics may have a direct effect on skeletal muscle [14]. Opioids are commonly used for anesthesia and are often administered with muscle relaxants. Opioids theoretically could affect neuromuscular blocking agents by reducing acetylcholine release [15]. However, we used remifentanil similarly in both our SEVO and TIVA groups and, therefore, the effects of remifentanil can be assumed the same in both groups.
We find from our current analyses that the type of anesthetic did not influence the time to maximum block. At the same dose of rocuronium, the mean time was similar between the TIVA and SEVO groups, but a higher dose of rocuronium shortened the time to maximum block. Furthermore, we found that there were no significant differences in the intubation conditions between the TIVA and SEVO groups at the same dose of rocuronium and that an increased rate of acceptable intubation conditions occurred with larger doses of rocuronium in both groups. These findings are in agreement with those reported by Lowry et al. [16], which showed that the onset time of mivacurium did not differ between sevoflurane and propofol. Ahmed et al. [17] also reported that an increase in sevoflurane exposure time did not shorten the time to maximum block. However, Yamaguchi et al. [18] reported that 8 % sevoflurane induction accelerates the onset of the vecuronium neuromuscular blockade. They found that the maximum block in the 8 % sevoflurane group was shorter than that in the propofol/fentanyl group and the N2O/2 % sevoflurane group (139 ± 35 s, 193 ± 35 s, and 188 ± 47 s, respectively). This finding is contrary to our present results. In their study, Yamaguchi et al. [18] administered vecuronium intravenously at 3 min after the start of anesthetic induction with sevoflurane, and the end-tidal concentration of sevoflurane reached between 6 and 7 % in the sevoflurane 8 % group. Tracheal intubation was performed approximately 2 min after administration of vecuronium. In our present study, we performed tracheal intubation and assessed the intubation conditions at 3 min after administration of rocuronium. Thus, the concentration of sevoflurane could be much less than that used by Yamaguchi et al. [18].
Cannon et al. [19] reported that patients receiving inhalational anesthetics require significantly lower vecuronium infusion rates to achieve a 90 % blockade than those receiving fentanyl, which represents a change in the pharmacodynamics of vecuronium-induced neuromuscular blockade rather than a change in the pharmacokinetics. The authors studied the effects of enflurane, isoflurane, and fentanyl, each in combination with 60 % nitrous oxide, on the vecuronium infusion rate necessary to maintain a constant 90 % depression of control muscle twitch tension. Yamaguchi et al. [18] also reported that the clinical duration from maximal block to 25 % recovery of the TOF ratio in two sevoflurane groups (2 and 8 %) was longer than that in a propofol/remifentanil group (47 ± 15, 48 ± 14, and 36 ± 10 min, respectively). Lowry et al. [16] studied the potency and time course of action of rocuronium in patients anesthetized with 66 % nitrous oxide in oxygen and 1.5 MAC sevoflurane, isoflurane, or propofol infusion. These authors reported that the mean ED50 and ED95 doses during sevoflurane anesthesia were significantly lower than those during propofol anesthesia. The recovery index and the times to recovery of Tl to 90 % and TOF ratio to 0.8 in the sevoflurane group were all significantly longer than in the propofol group. This accords well with our current results, where our SEVO groups showed a significantly longer recovery index than our TIVA groups at each dose of rocuronium. Furthermore, our SEVO groups showed a significantly longer recovery time to T90 than the TIVA groups. We therefore confirmed that the type of anesthetic could influence the recovery from neuromuscular block.
This study may have several limitations. First, our study results should be applied only to an Asian population. Second, we compared two anesthetic protocols with sevoflurane-remifentanil and propofol-remifentanil. Remifentanil infusion with sevoflurane in SEVO group rather than sevoflurane alone can be a confounding factor for interpretation of the intubation condition and the depth of anesthesia. Nevertheless, the reason we adopted this study design is that the protocol of this study was based on the daily practice protocol used in the clinical practice in Korea and Japan, and the results of of our study can be a real help to them. Third, we did not present BIS, hemodynamic variable, end-tidal sevoflurane concentration at the time of tracheal intubation. We considered the anesthetic depth by values measured at 1 min after intubation. There was no significant difference in diastolic blood pressure, heart rate and BIS except systolic blood pressure between groups. Therefore, we estimated that the same depth of anesthesia was provided to each group. However, some readers may not agree on that point. Lastly, sample sizes are approximate because calculation was based on our clinical assumptions not from previous references.
