By using AAI monitoring, we demonstrated that, relative to patients receiving inspiratory 5% or 3% sevoflurane, those receiving inspiratory 6% sevoflurane had a shorter time to loss of consciousness with comparable AAI values and a shorter time required to reach the target AAI values under mechanical ventilation but higher end-tidal concentrations at the same end-point AAI values. The estimated jugular bulb concentrations were similar between the 6% and 5% groups at the same AAI levels. These findings indicate that alveolar concentration may overestimate anaesthesia depth because of a notable gap between end-tidal and brain concentrations during rapid wash-in of a higher concentration of sevoflurane.
The minimum alveolar concentration (MAC) required to prevent movement in response to surgical incision in 50% of patients has been used as an indicator of anaesthesia depth of inhalational anaesthetics for decades.(16) This value is derived from a steady end-tidal concentration representing the arterial and brain concentrations of the anaesthesia. Lu et al.(7) demonstrated that the ratio of arterial/end-tidal concentration of sevoflurane remained at 0.63 after 30 min of mechanical ventilation with inspiratory 3.5% sevoflurane. They also revealed that a higher inspiratory concentration of isoflurane could accelerate its brain uptake.(8) Equilibrium between arterial and jugular bulb concentrations was achieved after 40 min for inspiratory 2% isoflurane and 50 min for 1% isoflurane.(8) The arterial and jugular bulb concentrations in the 2% isoflurane group were approximately double those of the 1% isoflurane group.(8) In the current study, a similar pharmacokinetic phenomenon was observed in estimated jugular bulb concentrations at 30 min (2.8% vs. 1.4%) between the 6% and 3% sevoflurane groups. As expected, the time to loss of consciousness and the time required to achieving the target AAI values were shorter in the 6% sevoflurane group. Theoretically, the clinical MAC values calculated using end-tidal concentrations should be similar at the same target AAI levels regardless of whether inspiratory 5% or 6% sevoflurane is used. However, the actual end-tidal concentrations were higher in the 6% group at the same AAI values: ≤20, ≤ 10, and at the start of burst suppression. The estimated jugular bulb concentrations were similar at the same end points of AAI values between the 6% and 5% sevoflurane groups, which is consistent with our previous observations regarding the pharmacokinetics of sevoflurane uptake.(7) This finding indicates a lag in the time required to achieve transition of anaesthesia across the alveolar membrane and blood–brain barrier,(17) which is determined by various blood/gas and brain/blood partition coefficients of inhalational anaesthetics.(18) The MAC value might be overestimated as a result of higher end-tidal concentration during wash-in with a higher inspiratory concentration of anaesthetics, which may result in de facto inadequate anaesthesia depth under surgical stimulation.
A composite AEP index incorporating EEG has been used as an indicator for anaesthesia depth according to dose(2) and in relation to age,(3) which is a more discriminant predictor of different clinical states of general anaesthesia.(19) However, some studies have failed to observe a graded response with steady-state end-tidal concentrations of sevoflurane, neither decreasing from 2–1.5% and 1% in adults(20) nor increasing from 1.5–2% and 2.5% in infants and children.(21) The so-called steady-state is based on the constant administration of an end-tidal concentration of sevoflurane for 11 min(20) and was calculated using the Gas Man Anesthesia Simulator programme for equilibration of partial pressures between the brain and the lungs.(22) Our previous pharmacokinetic study, which employed blood sampling for sevoflurane concentration analysis, demonstrated that the time required to achieve equilibration between arterial and jugular bulb concentrations (no further brain uptake) was 38.5 min following mechanical ventilation with inspiratory 3.5% sevoflurane, and a near constant end-tidal concentration was achieved after 30 min of ventilation.(7) Therefore, the early change in end-tidal concentrations during wash-in or wash-out may not accurately reflect the true brain uptake and anaesthesia depth. The application of EEG processing could facilitate the adjustment of anaesthesia depth during the wash-in or wash-out periods.
The AAI values in the 3% sevoflurane group did not decrease to less than 10 during 60 min of ventilation despite the ultimate end-tidal concentration being 2.7%. Young male patients were recruited for this study to reduce the impact of interindividual comorbidities and age- or sex-related variability on MAC values.(23) One MAC of sevoflurane is 1.8% at the age of 40 years, with an approximate decrease of 6% every decade.(23) Women appear to have the same MAC as men.(24) However, AAI values were reported to be severely attenuated or reach a value of 0 under a 2% steady-state end-tidal concentration of sevoflurane in women aged 20–60 years.(25)
Two limitations of the current study should be addressed. First, all 30 patients were young male patients aged 20–25 years. The small sample size and the inclusion of only young men in this observational study may have limited the clinical application of the findings; future research could include a more diverse sample. Second, AAI values only indicated the sedation levels before surgery in our patients and not the clinical anaesthesia depth during surgery. Possible confounding factors that could interfere with EEG processing were excluded, such as surgical stimulation, noisy environment, hypoglycaemia, cerebral ischaemia, and neurological disorders,(1) and intravenous benzodiazepine and propofol.
In conclusion, we demonstrated that patients receiving a higher sevoflurane concentration had a shorter time to loss of consciousness with comparable AAI values and had higher end-tidal concentrations of sevoflurane at the same end-point AAI levels. Their estimated jugular bulb concentrations were also similar at the same AAI levels. Anaesthesia depth, calculated according to alveolar concentration, may be overestimated during the rapid wash-in of inhalation anaesthesia. This discrepancy between alveolar and brain concentrations at the same AAI values of anaesthesia should be considered by practitioners.