Sevoflurane is a popular and widely used volatile anesthetic because it does not irritate the airway, hence it can be used as an induction agent, especially in children. Moreover, its low blood and fat solubility leads to rapid onset, easy depth of anesthesia adjustment, and early recovery . Due to its high cost, however, LFA is used to reduce the amount needed . The more important reasons to implement sevoflurane LFA are benefits to environment and mucociliary function of the patient . Previously, the recommended lowest FGF to be used with sevoflurane was 1 L·min-1 for exposures up to 1 h and 2 L·min-1 for exposures > 1 h because of compound A concern . With the introduction of strong base-free CO2 absorbents (e.g., Amsorb Plus and Litholyme), the issue with compound A from sevoflurane has been resolved and sevoflurane can be safely used in LFA . LFA, however, needs a wash-in phase to rapidly build up FAS to the required target concentration. The wash-in can be achieved by (a) increasing FGF to reduce the time constant ; (b) increasing FVS to induce a concentration effect ; or (c) integrating both methods.
A few studies have addressed the wash-in technique for sevoflurane LFA. Lindqvist et al. reported a 2-step wash-in technique to achieve a FAS of 1.2%; starting with FGF 1 L·min-1 and FVS 8% for 1 min, then reducing FGF to 1, 0.7, 0.5, and 0.3 L·min-1. They found that the respective time to achieve the target FAS was 1.8, 1.5, 2.5, and 3.6 min . Horwitz et al. reported that by using a FGF of 1.0 or 0.5 L·min-1 with a FVS 6% during the wash-in, the respective time to reach 1 MAC was 6.2 ± 1.3 and 15.2 ± 2.4 min and up to 1.5 MAC at 7.5 ± 2.5 and 19 ± 4.4 min . The limitation of these two schemes is that they cover only 1 or 2 FAS targets, and hence cannot be applied for other required FAS targets.
Jakobsson et al. reported a wash-in in a test-lung model with a respective FGF of 0.3 and 4 L·min-1 and a FVS of 8%. They found that the FAS reached 1 MAC (2.1%) at 547 ± 83 and 38 ± 6 sec, respectively . Leijonhufvud et al. reported a wash-in in a test-lung using a respective FGF of 1, 2, 4, 4.8, 6, and 8 L·min-1 and a FVS 6% in a Flow-I and a Aisys anesthetic machine. They found that the respective mean time to achieve 1 MAC was 431.3, 185.6, 66, 53.6, 53.6, and 52.6 sec for the Flow-I and 262.7, 144.3, 57.7, 52.3, 57.7, and 58.3 sec for the Aisys . Finally, Shin et al. performed a wash-in study using a Primus anesthetic machine connected to a test-lung, using a FGF of 0.5, 1, and 3 L·min-1 and setting the FVS to 6%. The respective mean time to reach a FAS of 4% for each FGF was 1,165, 534, and 155 sec . The latter 3 studies were, however, all performed in test-lungs such that the uptake of sevoflurane by body tissues was not considered, so the results cannot be generalized to clinical practice.
The current study proposed a 1-1-8 wash-in scheme for sevoflurane LFA using N2O or Air—which can rapidly and predictably achieve each FAS (i.e., 1% to 3.5% as is used in daily practice within 4.5 and 5 min, respectively). The time to achieve every FAS was identical for both groups except at FAS of 3% and 3.5% where the time in group Air was a nominally longer than group N2O because of the second gas effect of N2O . When this wash-in scheme uses O2:N2O 1:1 L·min-1 as the carrier gases, 50% N2O provides 0.5 MAC in addition to the MAC of sevoflurane , hence this protocol can further reduce the use of sevoflurane. When N2O is contraindicated or Air is preferred, a higher FAS is required, and yet this wash-in scheme consistently, precisely, and promptly achieves the required target.
Comparing with a similar 1-1-12 wash-in scheme for desflurane LFA which uses desflurane 12% (2 MAC) [15,16], the current 1-1-8 sevoflurane wash-in scheme uses a higher MAC (8% or 4 MAC) of sevoflurane. The reasons are that (a) sevoflurane has greater blood and fat solubility than desflurane, leading to higher body tissue uptake, which results in a longer time to achieve an equivalent MAC; and, (b) sevoflurane has a 3 times lower MAC value, hence 4 MAC of sevoflurane was used to augment a concentration effect .
The trajectories of the times to achieve each FAS in both groups (Figure 1 and 2) suggests that the tested wash-in scheme has acceptable intra- and inter-subject variability. The parallel rising pattern of FAS and FIS (Figure 3) shows that the wash-in scheme has enough power to drive both FAS and FIS to the desired target of both groups within 4.5 and 5 min, as reflected in the rising FAS/FIS ratio pattern (Figure 4). The rising FA/FI ratio pattern reflects the onset of volatile anesthetic: the more rapid the rise the shorter the onset. The rapidly rising FAS/FIS ratio of the 1-1-8 wash-in scheme in both groups underscores the efficacy of this scheme. The higher FAS/FIS ratio of the group N2O reflects the second gas effect .
The changes in heart rate and blood pressure during the wash-in process are similar to the 1-1-12 wash-in scheme for desflurane [15-16] (i.e., slightly increasing initially then gradually decreasing as presented in Figure 5).7) The changes are statistically but not clinically significant.
The 1-1-8 wash-in scheme has many advantages: (a) simplicity – just a one-step setting; (b) coverage – includes every FAS target from 1% to 3.5% used in daily practice both in balanced anesthesia and pure inhalation anesthesia; (c) swiftness – accomplishing the desired target within 1 to 4.5 or 5 min; (d) safety – no clinically significant change in heart rate and blood pressure; (e) economy – just 2 L·min-1 of FGF; and (f) applicability – can be applied with both N2O and Air. When the target FAS is achieved, the FGF can be reduced to 1 L· min-1 and the FAS can simply be maintained by setting the FVS above the desired FAS by 50% to 60% . The current study used Litholyme as the CO2 absorbent to guarantee the safety of sevoflurane LFA.
Most hospitals in developed countries have an anesthetic gas analyzer in the operating theatre, making any wash-in scheme unnecessary during low-flow anesthesia. Many operating theatres in less developed areas, however, still lack such equipment. The tested wash-in scheme may thus be applied as guidance to perform sevoflurane LFA provided that an inspired oxygen concentration monitor is available.
Since we excluded patients with a BMI >30 kg m-2; having pulmonary or cardiac disease; or, being pregnant, this wash-in scheme may not be applied in those groups of patients. Further studies are required.