1-1-12 one-step wash-in scheme for desflurane low flow anesthesia: performance without nitrous oxide

Introduction

Low flow anesthesia (fresh gas flow [FGF] ≤1 L/min) is gaining in popularity because of its advantages (vis-à-vis economy, less pollution, and conservation of heat and humidity)¹ in addition to the availability of modern anesthetic machines and anesthetic gas monitors. Desflurane, with its properties of low blood and fat solubility and no limitation of FGF even with older CO₂ absorbers, is most suitable for low flow anesthesia.² Low flow anesthesia needs an initial wash-in phase to build up the required concentration of desflurane in the circle circuit (F_ID) and alveoli (F_AD).³ Most reported wash-in schemes need a very high FGF or vaporizer concentration of desflurane, yet achieve only some of the targeted F_AD.^2,4,5 There is one scheme that can achieve every F_AD, but it is a complex logistic regression equation needing a computer to perform the calculation,⁶ so is inconvenient for everyday use. Recently, the authors reported a simple, single step 1-1-12 wash-in scheme using an FGF of N₂O:O₂ 1:1 L/min and desflurane 12%, that can rapidly yield every F_AD from 1% to 6% within 4 minutes without tachycardia.⁷ Although N₂O is widely used because of its desirable effects (eg, analgesia and additive effect to the minimum alveolar concentration [MAC] of desflurane), there are still some situations where N₂O should not be used,^8–11 which effectively limits the generalizability of this scheme. The objective of the present study was to evaluate the 1-1-12 wash-in scheme in situations where N₂O is currently excluded.

Materials and methods

This study was approved by the institutional review board of Khon Kaen University (HE561247) and was registered at www.clinicaltrials.gov (NCT01348984). All patients gave their written informed consent before enrollment.

This was a descriptive trial. The sample size comprising 106 patients was determined in the same way as in our previous related study.⁷ We included patients with an American Society of Anesthesiologists physical status of I or II, aged 16–64 years, and scheduled for elective surgery under general anesthesia with endotracheal intubation and controlled ventilation. Patients with pulmonary or cardiac disease, a body mass index >30 kg/m², or a contraindication to use of succinylcholine were excluded.

All patients were managed by standard intraoperative monitoring and care in the same way as in our previous study.⁷ They were monitored with electrocardiography, pulse oximetry, noninvasive blood pressure measurement, capnography, and anesthetic gas analyzing equipment. The anesthetic machine, integrated with an anesthetic gas analyzer, used in this study was a Primus (Dräger AG, Lübeck, Germany). We used a standard circle circuit with a soda lime absorber. Each patient’s heart rate and blood pressure were recorded before induction as a baseline measurement. The patients were then premedicated with intravenous fentanyl 1 μg/kg and induced with propofol 2 mg/kg. Intubation was facilitated with succinylcholine 1.5 mg/kg. Ventilation was controlled using an FGF of air:O₂ 1:1 L/min and desflurane 12%. The initial ventilator setting was at a tidal volume 7 mL/kg and a respiratory rate of 12 per minute adjusted to keep the P_ACO₂ around 30–35 mmHg. The time to achieve an F_AD at 1%, 2%, 3%, 4%, 5%, 6%, and 7% was recorded as the primary outcome. F_ID, heart rate, and blood pressure at each F_AD were also recorded. After an F_AD of 7% was achieved, FGF was reduced to 0.5–1 L/min and desflurane adjusted according to the judgment of the anesthesiologist.

Statistical analysis

The statistical analysis was performed using Statistical Package for the Social Sciences for Windows version 16.0 software (SPSS Inc, Chicago, IL, USA). Continuous demographic data are presented as the mean ± standard deviation and the categorical data as the number of patients (percentage). The primary outcome is presented as the mean ± standard deviation and 95% confidence interval. The unpaired Student’s t-test was used to compare the time and F_ID to achieve each F_AD in this study, consistent with our previous study.⁷ Heart rate and blood pressure values at different time points were compared using repeated measures analysis of variance. P<0.05 was considered to be statistically significant.

Results

In total, 106 patients participated in and completed the study. The demographic data for these patients are presented in Table 1.

Table 1 Demographic data for the 106 patients Notes: Data for age, weight, and height are presented as the mean ± standard deviation. Sex and ASA classification are presented as number of patients (%). Abbreviation: ASA, American Society of Anesthesiologists.

The trajectories of time taken to reach each F_AD by each patient during wash-in are presented in Figure 1. The times taken to achieve F_AD from 1% to 7% and the 95% confidence intervals are presented in Table 2. Mean times in seconds were converted into approximate time in minutes for practical use. An F_AD of 1%, 2%, 3%, 4%, 5%, 6%, and 7% can thus be expected at 0.6, 1, 1.5, 2, 3, 4, and 6 minutes, respectively.

Figure 1 Trajectories of time to achieve each FAD during wash-in. Abbreviation: FAD, alveolar concentration of desflurane.

Table 2 FID and time at different end points of FAD Note: Data are presented as the mean ± standard deviation. Abbreviations: FID, inspired concentration of desflurane; CI, confidence interval; FAD, alveolar concentration of desflurane.

The rising pattern of F_AD and F_ID is similar to that observed in our previous study,⁷ except for some statistically but not clinically significant differences at 5%, 6% and 4%, 5%, 6%, respectively (Figures 2 and 3).

Figure 2 Rising patterns of FAD during wash-in when N2O was included versus excluded. Notes: Data for FAD in cases where N2O was included were retrieved from a study by Sathitkarmnanee et al.7 *P=0.026, **P<0.001. Abbreviations: FAD, alveolar concentration of desflurane; N2O, nitrous oxide; O2, oxygen.

Figure 3 Rising pattern of FID during wash-in when N2O was included versus excluded. Notes: Data for FID in cases where N2O was included were from a previous study by Sathitkarmnanee et al.7 *P=0.005, **P<0.001. Abbreviations: FAD, alveolar concentration of desflurane; FID, inspired concentration of desflurane; N2O, nitrous oxide; O2, oxygen.

The rise in heart rate during wash-in was statistically but not clinically significant (Figure 4). Blood pressure decreased slightly; this was statistically significant but not clinically so (Figure 5). These patterns are similar to those in our earlier study.⁷

Figure 4 Heart rate at different FAD during wash-in when N2O was excluded. Notes: Data are presented as the mean ± standard deviation. P<0.001. Abbreviation: FAD, alveolar concentration of desflurane.

Figure 5 Blood pressure at different FAD during wash-in when N2O was excluded. Notes: Data are presented as the mean ± standard deviation. P<0.001. Abbreviation: FAD, alveolar concentration of desflurane.

Discussion

The pattern of the trajectories of time taken to achieve each F_AD in Figure 1 reveals that this scheme has acceptable intrasubject and intersubject variability. Although there are statistically significant differences in the increasing pattern of time and F_ID at some points of F_AD, these are in the order of a few seconds and not clinically significant. The times taken to achieve F_AD from 1% to 6% in this study (without N₂O as the carrying gas) is the same as that reported in our previous study, which used N₂O as a part of FGF.⁷ The results of the present study show that the performance of the 1-1-12 wash-in scheme is not affected by the use of N₂O. The second gas effect of N₂O¹² does not influence the uptake of desflurane because both N₂O and desflurane have nearly the same very low blood-gas solubility (0.47 versus 0.42). We extended the end point of F_AD in this study to 7%, which took 6 minutes to achieve, because without N₂O, which has an additive effect on the MAC of desflurane,¹³ a higher F_AD may be required to control the depth of anesthesia. The time required to increase F_AD from 6% to 7% was 2 minutes, which is double the time required to increase each 1% from 4% to 6%. This may be due to the narrower gradient between F_ID and F_AD at the high end of F_AD.

Our scheme requires less FGF, but can achieve each F_AD from 1% to 7% within 6 minutes, which is more rapid and simpler than most reported wash-in schemes. Baum et al used an FGF of 4.4 L/min and found that F_AD reached 90%–95% of the fresh gas concentration within 10–15 minutes.² Mapleson reported a spreadsheet model comprising two components: a circle circuit and a 70 kg anesthetized “standard man”, using an FGF equal to the total ventilation with 3 MAC of desflurane that could achieve an F_AD of one MAC in 1 minute.⁴ Hendrickx et al used an FGF of O₂:N₂O 2:4 L/min with desflurane 6.5% and found that an F_AD of 4.5% could be achieved in 15 minutes.⁵

The aforementioned schemes used higher FGFs yet achieved only some specific F_ADs. Hendrickx et al thus proposed an empirical model that could be used to predict FGF-desflurane combinations that achieved a target F_AD within the first 5 minutes.⁶ Their model, however, is a complex logistic regression equation requiring a computer to calculate, making it impractical for daily use. In comparison, our scheme is simpler and more practical, and yields a rapid wash-in with an expected F_AD from 1% to 7% at 0.6, 1, 1.5, 2, 3, 4, and 6 minutes, respectively. This range of F_AD covers the concentration for both balanced and pure inhalation anesthesia. This scheme can be applied with or without N₂O.

While Nyktari et al¹⁴ reported that a rapid increase in F_ID to 1.5 MAC without the support of premedication caused a significant increase in airway resistance, we did not find such a problem. The explanation is that, with a lower FGF, an F_ID of 1.5 MAC was gradually achieved in 7 minutes and fentanyl was used as a premedication.

In the current study, there was a statistically significant but not clinically increase in heart rate and decrease in blood pressure. This result is similar to our previous study using N₂O as a carrying gas⁷ and also consistent with the report by Warltier and Pagel,¹⁵ but different from the study by Ebert and Muzi,¹⁶ who reported hypertension and tachycardia in healthy volunteers receiving titration of desflurane from 1 to 1.5 MAC following thiopental induction. The explanation is that fentanyl, used as a premedication, attenuates sympathetic stimulation.¹⁷ Moreover, the rapid increase in F_ID in our scheme (to the level exceeding the MAC of desflurane before the therapeutic level of the induction agent is on the wane) maintains the patient in the surgical stage throughout the study without sympathetic overactivity.

The 1-1-12 wash-in scheme has many advantages: simplicity (just one step for setting); coverage (every targeted F_AD from 1% to 6% [7% where N₂O is omitted]); rapidity (achieving the targets within 0.6 to 4 minutes [6 minutes for 7%]); flexibility (applicable to situations both with or without N₂O); safety (wash-in without sympathetic overactivity); and economy (just 2 L/min of FGF and 12% desflurane). After achieving the required F_AD, the FGF can be reduced to a low flow anesthesia range of 0.5–1 L/min and the target F_AD can be simply maintained by setting the desflurane above the F_AD by 1%–2%.^3,18

Given that we excluded patients with a body mass index >30 kg/m², this scheme may not be generalized to such conditions, so further study is required.

Conclusion

The 1-1-12 wash-in scheme using a simple, single step FGF of N₂O or air:O₂ 1:1 L/min and desflurane 12% for low flow anesthesia in patients requiring general anesthesia with endotracheal intubation and controlled ventilation has the same performance with or without N₂O. Each concentration of F_AD from 1% to 7% can be expected at 0.6, 1, 1.5, 2, 3, 4, and 6 minutes, respectively. The 1-1-12 wash-in scheme covers the F_AD required for both balanced and pure inhalation anesthesia. There were nonclinically significant increases in heart rate and decreases in blood pressure during this wash-in period.

Acknowledgments

This study was funded by the Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. We thank Bryan Roderick Hamman and Janice Loewen-Hamman for assistance with English language presentation of the manuscript via Publication Clinic KKU, Thailand.

Disclosure

The authors report no conflicts of interest in this work.

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References

1.		Odin I, Feiss P. Low flow and economics of inhalational anaesthesia. Best Pract Res Clin Anaesthesiol. 2005;19(3):399–413.
2.		Baum J, Berghoff M, Stanke HG, Petermeyer M, Kalff G. Low-flow anesthesia with desflurane. Anaesthesist. 1997;46(4):287–293.
3.		Baum JA. Low-flow anesthesia: theory, practice, technical preconditions, advantages, and foreign gas accumulation. J Anesth. 1999;13(3):166–174.
4.		Mapleson WW. The theoretical ideal fresh-gas flow sequence at the start of low-flow anaesthesia. Anaesthesia. 1998;53(3):264–272.
5.		Hendrickx JF, Dewulf BB, De Mey N, et al. Development and performance of a two-step desflurane-O(2)/N(2)O fresh gas flow sequence. J Clin Anesth. 2008;20(7):501–507.
6.		Hendrickx JF, Lemmens H, De Cooman S, et al. Mathematical method to build an empirical model for inhaled anesthetic agent wash-in. BMC Anesthesiol. 2011;11:13.
7.		Sathitkarnmanee T, Tribuddharat S, Suttinarakorn C, et al. 1-1-12 one-step wash-in scheme for desflurane-nitrous oxide low-flow anesthesia: rapid and predictable induction. Biomed Res Int. 2014;2014:867504.
8.		Becker DE, Rosenberg M. Nitrous oxide and the inhalation anesthetics. Anesth Prog. 2008;55(4):124–130.
9.		Imberger G, Orr A, Thorlund K, Wetterslev, Myles JP, Moller AM. Does anaesthesia with nitrous oxide affect mortality or cardiovascular morbidity? A systematic review with meta-analysis and trial sequential analysis. Br J Anaesth. 2014;112(3):410–426.
10.		Leslie K, Myles PS, M. Chan T, et al. Nitrous oxide and long-term morbidity and mortality in the ENIGMA trial. Anesth Analg. 2011;112(2):387–393.
11.		Myles PS, Leslie K, M. Chan T, et al. Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial. Anesthesiology. 2007;107(2):221–231.
12.		Epstein RM, Rackow H, Salanitre E, Wolf GL. Influence of the concentration effect on the uptake of anesthetic mixtures: the second gas effect. Anesthesiology. 1964;25(3):364–371.
13.		Albertin A, Casati A, Bergonzi PC, Moizo E, Lombardo F, Torri G. The effect of adding nitrous oxide on MAC of sevoflurane combined with two target-controlled concentrations of remifentanil in women. Eur J Anaesthesiol. 2005;22(6):431–437.
14.		Nyktari VA, Papaioannou A, Volakakis N, Lappa A, Margaritsanaki P, Askitopoulou H. Respiratory resistance during anaesthesia with isoflurane, sevoflurane, and desflurane: a randomized clinical trial. Br J Anaesth. 2011;107(3):454–461.
15.		Warltier DC, Pagel PS. Cardiovascular and respiratory actions of desflurane: is desflurane different from isoflurane? Anesth Analg. 1992;75 (4 Suppl):S17–S29.
16.		Ebert TJ, Muzi M. Sympathetic hyperactivity during desflurane anesthesia in healthy volunteers. A comparison with isoflurane. Anesthesiology. 1993;79(3):444–453.
17.		Katoh T, Kobayashi S, Suzuki A, Iwamota T, Bito H, Ikeda K. The effect of fentanyl on sevoflurane requirements for somatic and sympathetic responses to surgical incision. Anesthesiology. 1999;90(2):398–405.
18.		Johansson A, Lundberg D, Luttropp HH. Low-flow anaesthesia with desflurane: kinetics during clinical procedures. Eur J Anaesthesiol. 2001;18(8):499–504.