Effect of Fresh Gas Flow on Isoflurane Concentrations during Low-flow Anaesthesia

The Journal of International Medical Research 2005; 33: 513 519 Effect of Fresh Gas Flow on Isoflurane Concentrations during Low-flow Anaesthesia J-Y PARK 1, J-H KIM 2, W-Y KIM 2, M-S CHANG 2, J-Y KIM 1, H-W SHIN 1 1 Department of Anaesthesiology, Korea University Anam Hospital, Seoul, Korea; 2 Department of Anaesthesiology, Korea University Ansan Hospital, Ansan, Korea The effect of fresh gas flow (FGF) on isoflurane concentrations at given vaporizer settings during low-flow anaesthesia was investigated. Ninety patients (American Society of Anaesthesiologists physical status I or II) were randomly allocated to three groups (FGF 1 l/min, FGF 2 l/min and FGF 4 l/min). Anaesthesia was maintained for 10 min with vaporizer setting isoflurane 2 vol% and FGF 4 l/min for full-tissue anaesthetic uptake in a semi-closed circle system. Low-flow anaesthesia was maintained for 20 min with end-tidal isoflurane 1.5 vol% and FGF 2 l/min. FGF was then changed to FGF 1 l/min, FGF 2 l/min or FGF 4 l/min. Measurements during the 20-min period showed that inspired and end-tidal isoflurane concentrations decreased in the FGF 1-l/min group but increased in the FGF 4-l/min group compared with baseline values. No haemodynamic changes were observed. Monitoring of anaesthetic concentrations and appropriate control of vaporizer settings are necessary during low-flow anaesthesia. KEY WORDS: ISOFLURANE; LOW-FLOW ANAESTHESIA; END-TIDAL CONCENTRATION; HAEMODYNAMIC CHANGES; FRESH GAS FLOW; VAPORIZER SETTING; BREATHING SYSTEMS Introduction Most anaesthesiologists use semi-closed systems during general anaesthesia and 3 4 l/min of fresh gas flow (FGF), 1 but such an approach may cause anaesthetic overuse, operating room contamination and atmospheric pollution. Low-flow anaesthesia has the advantage of reducing anaesthetic consumption, atmospheric pollution and costs, and is better at maintaining anaesthetic gas temperature and humidity. 2 Low-flow anaesthesia is not without problems, which include the risk of hypoventilation due to leaks, the large volume of the system, the discrepancy between the delivered fraction and the inspired fraction of inhaled gas, and the accumulation of toxic compounds such as carbon monoxide and compound A. 3,4 Changes in FGF during low-flow anaesthesia may have serious consequences, therefore anaesthesiologists must have considerable knowledge of rebreathing principles before they use low-flow anaesthesia with semiclosed circle systems. A previous study 2 examined decreases in anaesthetic gas concentrations according to reduced FGF during low-flow anaesthesia using a computer simulation program. The present 513

paper is the first clinical study to examine the effect of FGF on isoflurane concentrations and on haemodynamic and respiratory changes at a given vaporizer setting during low-flow anaesthesia. Patients and methods PATIENTS Institutional Review Board approval was obtained for this study and all patients provided informed consent. Ninety female patients (age range 23 50 years) scheduled for elective gynaecological abdominal surgery, classified as American Society of Anaesthesiologists physical status I or II, were enrolled in the study. Patients with a history of hypertension, diabetes mellitus, cardiovascular or cerebrovascular disease and anaesthetic exposure within 1 year were excluded. Patients were randomly assigned to one of three groups, each containing 30 subjects, namely, FGF 1 l/min, FGF 2 l/min and FGF 4 l/min. Patients and observers were not informed of group assignments. PROCEDURES All patients were premedicated with 0.2 mg glycopyrrolate, via intramuscular injection, 1 h before anaesthesia. Standard monitors (non-invasive arterial blood pressure, heart rate [HR], and pulse oximetry [Agilent V26C, M1204A, Boeblingen, Germany]) were applied in a preoperative area. Prior to the study, fresh soda lime was used and oxygen was flushed 3 times per min for 5 min to ensure denitrogenation. After preoxygenation with O 2 8 l/min, each patient received thiopental sodium 5 mg/kg intravenously and rocuronium bromide 0.9 mg/kg intravenously for tracheal intubation. Anaesthesia was maintained with isoflurane 2 vol% and FGF 4 l/min (N 2 O: O 2 = 1:1) using a semi-closed circle system (Cato edition, Dräger, Luebeck, Germany) to allow full tissue anaesthetic uptake. The FGF was then reduced from 4 l/min to 2 l/min for low-flow anaesthesia and vaporizer settings were adjusted to maintain end-tidal isoflurane at 1.5 vol%. After 20 min of maintaining low-flow anaesthesia at an endtidal isoflurane 1.5 vol%, FGF was changed in one of the following ways: decreased to FGF 1 l/min (FGF 1-l/min group), maintained at FGF 2 l/min (FGF 2-l/min group), or increased to FGF 4 l/min (FGF 4-l/min group) (N 2 O:O 2 = 1:1). We set the point that FGF was changed to FGF 1 l/min, FGF 2 l/min or FGF 4 l/min as baseline. Ventilation was controlled at a tidal volume of 8 10 ml/kg and the ventilatory rate was adjusted to maintain an end-tidal CO 2 (EtCO 2 ) around 30 mmhg. The inspired fraction of oxygen (FiO 2 ) and the concentrations of isoflurane and EtCO 2 were monitored (Cato edition) and analysed with sidestream by an infrared absorption technique. Analysed gases were sampled at the heat and moisture exchanger then returned to a port fitted in the CO 2 absorber. Dosages of fentanyl 1 µg/kg intravenously were administered only if mean arterial pressure (MAP) reached > 20% above initial value; decreases in MAP of a similar level were treated with ephedrine 4 8 mg intravenously. Mean arterial pressure, HR and inspired and end-tidal concentrations of isoflurane, FiO 2 and EtCO 2 were measured at 1-min intervals for 10 min and then at 12, 15 and 20 min after an FGF change. STATISTICAL ANALYSIS All data are expressed as mean ± SD. Differences within groups were tested by repeated measures of analysis of variance (ANOVA) and post hoc comparisons were performed using Dunnett s test. The differences between groups were verified by 514

one-way ANOVA. P-values < 0.05 were considered statistically significant. Results No significant differences were found among the three groups with respect to age, weight or height (Table 1). The vaporizer settings required to maintain end-tidal isoflurane at 1.5 vol% did not differ significantly among the groups (Table 1). INSPIRED ISOFLURANE CONCENTRATION Inspired isoflurane concentration decreased at 1 min in the FGF 1-l/min group following the FGF change compared with both the baseline value and the value of the FGF 2-l/min group (P < 0.05, Fig. 1). This concentration increased after FGF change, however, at 1 min in the FGF 4-l/min group compared with both the baseline value and the value of the FGF 2-l/min group (P < 0.05, Fig. 1). No change was observed in the FGF 2-l/min group. Inspired isoflurane concentration decreased from 1.95 vol% to 1.61 vol% in the FGF 1-l/min group (P < 0.05, Fig. 1). A nonsignificant change from 1.93 vol% to 1.92 vol% was observed in the FGF 2-l/min group, and a significant increase from 1.94 vol% to 2.33 vol% was observed in the FGF 4-l/min group (P < 0.05, Fig. 1). END-TIDAL ISOFLURANE CONCENTRATIONS End-tidal isoflurane concentrations decreased at the 1-min mark in the FGF 1-l/min group compared with the baseline value, following the FGF change (P < 0.05, Fig. 2) and they were also lower at the 3-min mark in this group compared with the value of the FGF 2-l/min group, following the FGF changes (P < 0.05, Fig. 2). Again, there were no significant changes in the FGF 2-l/min group. End-tidal isoflurane concentrations increased at the 1-min mark in the FGF 4-l/min group compared with the baseline value, following the FGF change (P < 0.05, Fig. 2) and they were also higher at the 3-min mark in this group compared with the value of the FGF 2-l/min group, after the FGF change (P < 0.05, Fig. 2). End-tidal concentrations of isoflurane decreased from 1.50 vol% to 1.32 vol% in the FGF 1-l/min group (P < 0.05, Fig. 2), and a non-significant change from 1.50 vol% to 1.53 vol% was observed in the FGF 2-l/min group. There was a significant increase from 1.50 vol% to 1.88 vol% in the FGF 4-l/min group (P < 0.05, Fig. 2). TABLE 1: Demographics of the 90 women undergoing elective gynaecological surgery recruited to this trial measuring the effect of fresh gas flow on isoflurane concentrations during low-flow anaesthesia. There were no significant differences between the groups FGF 1 l/min FGF 2 l/min FGF 4 l/min (n = 30) (n = 30) (n = 30) Age (y) 42.1 ± 5.8 41.6 ± 9.5 37.6 ± 4.0 Body weight (kg) 58.8 ± 6.0 63.8 ± 8.2 68.9 ± 7.2 Height (cm) 158.8 ± 3.9 157.9 ± 4.4 161.5 ± 7.2 Vaporizer set (vol%) 2.4 ± 0.1 2.5 ± 0.1 2.4 ± 0.2 All values are mean ± SD. FGF, fresh gas flow; FGF 1 l/min, N 2 O 0.5 l/min + O 2 0.5 l/min; FGF 2 l/min, N 2 O 1 l/min + O 2 1 l/min; FGF 4 l/min, N 2 O 2 l/min + O 2 2 l/min. 515

FGF 1 l/min FGF 2 l/min FGF 4 l/min N 2 O 0.5 l/min + O 2 0.5 l/min N 2 O 1 l/min + O 2 1 l/min N 2 O 2 l/min + O 2 2 l/min 2.4 2.2 Isoflurane inspired concentration (vol%) 2.0 1.8 1.6 1.4 1.2 1.0 baseline 1 2 3 4 5 6 7 8 9 10 12 15 20 Time (min) FIGURE 1: The effect of different levels of fresh gas flow (FGF) on inspired isoflurane concentrations at isoflurane vaporizer setting 2 vol% during low-flow anaesthesia. Inspired isoflurane concentration was lower in the FGF 1-l/min group compared with the baseline value and the value of the FGF 2-l/min group, but it was higher in the FGF 4-l/min group compared with the baseline value and the value of the FGF 2-l/min group. P < 0.05 versus baseline values; + P < 0.05 versus FGF 2-l/min group;, standard deviation HAEMODYNAMIC CHANGES No significant change was observed in FiO 2 in the FGF 1-l/min group or the FGF 2-l/min group, but FiO 2 increased in the FGF 4-l/min group after FGF change compared with the baseline value and the value of the 2-l/min group (P < 0.05, Fig. 3). No significant differences were observed in EtCO 2, MAP or HR among any of the groups. Discussion Generally, low-flow anaesthesia is used to reduce anaesthetic consumption by reducing FGF after achieving adequate tissue uptake during the induction phase of inhalational anaesthesia. While anaesthesia is being maintained, FGF may be changed at a constant vaporizer setting. A sudden increase in FGF introduces the possibility of unintentional inhalation anaesthetic overdose. 3 5 For this reason, anaesthesiologists must have sufficient knowledge of rebreathing during low-flow anaesthesia using semi-closed circle systems. Virtue 6 recommended the use of FGFs of 0.5 l/min and 1 l/min for minimal flow anaesthesia and low-flow anaesthesia, respectively, but Eger 7 stated that low-flow anaesthesia requires an FGF of less than half the min volume, usually < 3 l/min, and that high-flow anaesthesia requires > 5 l/min. In this study, we used an FGF of 2 l/min for low-flow anaesthesia. If FGF is altered during low-flow 516

Isoflurane end-tidal concentration (vol%) 2.4 2.2 2.0 1.8 1.6 1.4 1.2 FGF 1 l/min FGF 2 l/min FGF 4 l/min N 2 O 0.5 l/min + O 2 0.5 l/min N 2 O 1 l/min + O 2 1 l/min N 2 O 2 l/min + O 2 2 l/min 1.0 baseline 1 2 3 4 5 6 7 8 9 10 12 15 20 Time (min) FIGURE 2: The effect of different levels of fresh gas flow (FGF) on end-tidal isoflurane concentrations. End-tidal isoflurane concentration was lower in the FGF 1-l/min group compared with the baseline value and the value of the FGF 2-l/min group, but it was higher in the FGF 4-l/min group compared with the baseline value and the value of the FGF 2-l/min group. P < 0.05 versus baseline values; + P < 0.05 versus FGF 2-l/min group;, standard deviation FiO 2 (%) 60 FGF 1 l/min N 2 O 0.5 l/min + O 2 0.5 l/min FGF 2 l/min N 2 O 1 l/min + O 2 1 l/min FGF 4 l/min N 2 O 2 l/min + O 2 2 l/min 55 50 + + + + + + + + 45 40 baseline 1 2 3 4 5 6 7 8 9 10 12 15 20 Time (min) FIGURE 3: The changes in the inspired oxygen fraction (FiO 2 ) at isoflurane vaporizer setting 2 vol% during low-flow anaesthesia. No change in FiO 2 was observed in the FGF 1-l/min or FGF 2-l/min groups but FiO 2 was higher in the FGF 4-l/min group compared with the value of the FGF 1-l/min and FGF 2-l/min groups. P < 0.05 versus baseline values; + P < 0.05 versus FGF 2 l/min;, standard deviation 517

anaesthesia, this would change the rebreathing fraction in the anaesthetic machine, which would influence anaesthetic depth. 3 5 We compared changes in isoflurane concentration at given vaporizer settings due to FGF changes during low-flow anaesthesia. In our study, inspired and end-tidal isoflurane concentrations were reduced in the FGF 1-l/min group after reducing FGF 1 l/min from 2 l/min, raising the possibility of light anaesthesia. The concentrations were increased in the FGF 4-l/min group after increasing FGF 4 l/min from 2 l/min, raising the possibility of anaesthetic overdose. The vaporizer settings required to attain and maintain a constant end-tidal concentration in a circle system with any FGF level are determined by uptake of oxygen, nitrous oxide the potent, inhaled anaesthetic H 2 O, carbon dioxide production, dead-space ventilation, system leaks and FGF. 8 In the present study, we examined the relationship between anaesthetic gas concentration and FGF, with the assumption that the other conditions were at a constant level. Mixing the ventilator gas with anaesthetic FGF through the tube dead space in the circle system is a well-known procedure that relies on the tidal volume, the internal dead space of the connecting tube, anaesthetic FGF and ventilator rate. 9 A mixing of the ventilator gas with FGF occurs when tidal volume is increased to exceed the connecting dead space volumes at 15 beats/min, provided that the FGF is 2 l/min. Mixing becomes inevitable when the anaesthetic gas flow is reduced and the tidal volume is increased. 10 We need to develop a better understanding of the rebreathing fraction during low-flow anaesthesia. In terms of anaesthetic depth according to FGF changes in a semi-closed circle system, FGF containing anaesthetic gas is delivered to the patient and subsequently, after anaesthetic uptake, some of the exhaled gas is discharged into the atmosphere; the remainder is reused after CO 2 elimination. If the FGF is reduced, the volume of excess gas discharged is reduced and the reused proportion increases. Moreover, if FGF is increased to 5 l/min, the effect of rebreathing is negligable. 11 According to the results of our study, vaporizer settings must be controlled to maintain a constant anaesthetic depth after changing FGF. In addition, to maintain a constant end-tidal isoflurane concentration the vaporizer setting must be increased when FGF is decreased, but decreased when FGF is increased during low-flow anaesthesia. In the present study, FiO 2 changed from 48.7% to 47.8% at 20 min in the FGF 1-l/min group after FGF change but there was no significant difference. Baum 2 reported that FiO 2 decreased by 35% in patients receiving FGF 1 l/min due to oxygen consumption. Had FiO 2 been measured for a longer period in this study it is probable that there would have been a greater decrease in FiO 2 concentration. Monitoring FiO 2 in longduration operations with low-flow anaesthesia should therefore be considered. We anticipated that changes would occur in EtCO 2 when changes were made to the FGF administered to the groups, although no statistically significant changes were observed. This was attributed to the wide standard deviation of EtCO 2. Marked differences in isoflurane concentrations were observed in this study when FGF was changed in the FGF 2-l/min group to FGF 1 or 4 l/min. During anaesthetic maintenance, if FGF was lowered, the vaporizer setting was increased due to an increase in the rebreathing fraction containing low concentration anaesthetic. During the 518

awakening period, however, the vaporizer was off. If FGF with O 2 was increased, the time to arousal was determined by the ratio of FGF and the rebreathing fraction. As a result, if FGF was lowered, patients took longer to awaken, because anaesthetic gas removal took more time. Thus, the wakening time at anaesthetic emergence can be controlled using FGF. In conclusion, a considerable difference was found between the inspired and end-tidal concentrations of isoflurane according to FGF changes during low-flow anaesthesia. As changes to anaesthetic depth create the possibilities of light anaesthesia or overdose during anaesthesia, the monitoring of anaesthetic agents and appropriate control of inhalation vaporizers are necessary during low-flow anaesthesia. Conflicts of interest No conflicts of interest were declared in relation to this article. Received for publication 6 May 2005 Accepted subject to revision 13 May 2005 Revised accepted 10 June 2005 Copyright 2005 Cambridge Medical Publications References 1 Jang YH, Kim JW: Practical choice and knowledge of Korean anaesthesiologists for fresh gas flow. Korean J Anesthesiol 2004; 46: 78 82. 2 Baum JA (ed): low-flow Anesthesia, 2nd edn. Boston: Butterworth-Heinemann, 2001; pp38 41, pp88 107. 3 Hargasser S, Hipp R, Breinbauer B, Mielke L, Entholzner E, Rust M. A lower solubility recommends the use of desflurane more than isoflurane, halothane, and enflurane under low-flow conditions. J Clin Anesth 1995; 7: 49 53. 4 Johansson A, Lundberg D, Luttropp HH. lowflow anaesthesia with desflurane: kinetics during clinical procedures. Eur J Anaesthesiol 2001; 18: 499 504. 5 Johansson A, Lundberg D, Luttropp HH. The quotient end-tidal/inspired concentration of sevoflurane in a low-flow system. J Clin Anesth 2002; 14: 267 270. 6 Virtue RW. Minimal flow nitrous oxide anesthesia. Anesthesiology 1974; 40: 196 198. 7 Eger EI 2nd: Uptake and distribution. In: Anesthesia. 5th edn. (Miller RD, ed). Philadelphia: Churchill Livingstone, 2000; pp74 95. 8 Lowe HJ, Ernst EA (eds): The Quantitative Practice of Anesthesia Use of Closed Circuit. Baltimore: Williams and Wilkins, 1981; p146. 9 Chakrabarti MK, Stacey RG, Holdcroft A, Whitwam JG. A low-flow open circle system for anaesthesia. Part I: Laboratory evaluation at normal and high frequencies. Anaesthesia 1990; 45: 314 317. 10 Berntman L, Luttropp HH, Werner O. Mechanical ventilation during low-flow anaesthesia. Experience with an alternative to the bag-inbottle. Anaesthesia 1990; 45: 855 858. 11 Harper M, Eger EI 2nd. A comparison of the efficiency of three anesthesia circle systems. Anesth Analg 1976; 55: 724 729. Address for correspondence Dr HW Shin Assistant Professor, Department of Anaesthesiology, Korea University Anam Hospital, 126-1, 5-Ga, Anam-dong, Sungbuk-Gu, Seoul, 136-705, South Korea. E-mail: hwshin99@yahoo.com 519