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Low-flow anaesthesia with desflurane: kinetics during clinical procedures

Johansson, A.; Lundberg, D.; Luttropp, H. H.

European Journal of Anaesthesiology: August 2001 - Volume 18 - Issue 8 - p 499-504
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Background and objective Low-flow anaesthesia is economical and less polluting. The purpose of this study was to determine the inspired and end-tidal desflurane concentrations during anaesthesia with a vaporizer setting maintained at 5%, during low-flow anaesthesia after 120 min with fresh gas inflows of 1.0 and 2.0 L min−1.

Methods The study was both prospective and randomized, including 56 patients (28 patients in each group) scheduled for elective surgery of an expected anaesthesia time of at least 120 min. Inspired and end-tidal concentrations of desflurane were measured during low-flow anaesthesia with fresh gas inflows of 1.0 and 2.0 L min−1. The vaporizer setting was fixed at 5% desflurane.

Results The inspired and end-tidal concentrations of desflurane in the 1.0 L min−1 group after 120 min were 4.54% vs. 4.37% (P < 0.001). In the 2.0 L min−1 group, the inspired and end-tidal concentrations of desflurane were 4.76% vs. 4.58% (P < 0.001). The estimated end-tidal/inspired ratios at 120 min of anaesthesia were 0.96 in both groups. At a fresh gas flow of 1.0 L min−1, the end-tidal concentration was 0.87 of the vaporizer setting. Increasing the fresh gas flow to 2.0 L min−1 increased the end-tidal value by 0.05.

Conclusion There is a significant difference between the inspired and end-tidal concentrations of desflurane when fresh gas inflows were 1.0 and 2.0 L min−1, but not for the ratio of inspired/end-tidal.

Department of Anaesthesiology and Intensive Care, University Hospital of Lund, S-221 85, Sweden

Accepted January, 2001.

Correspondence to: H. H. Luttropp Department of Anaesthesiology and Intensive Care, University Hospital of Lund, S-221 85, Sweden

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Introduction

The advantages of rebreathing gases can only be realized if low-flow system technology is adopted. The mechanical control of ventilation with low-flow anaesthesia is usually achieved by a bag-in-bottle arrangement. Berntman and his colleagues described clinical experiences with low-flow anaesthesia using a corrugated hose instead of a bag-in-bottle system [1]. This old, safe and simple method of low-flow technique was used in this study. The pharmacological kinetics of desflurane lends to the use of low-flow systems. Desflurane is the least soluble inhalation anaesthetic agent with a blood–gas partition coefficient of 0.42 and it has gained increased popularity as a result of its great precision and terms of alveolar concentration achieved with relation to vaporizer setting and economical savings [2–7].

The principal disadvantages of low-flow techniques are that inspired and end-tidal concentrations of the anaesthetic agent are not directly predictable from the vaporizer setting [8,9]. However, increasing health and ecological awareness will prompt anaesthetists to minimize gas and vapour emissions and increased knowledge of volatile anaesthetic behaviour facilitates the use of low-flows [10]. Gowrie-Mohan and his colleagues estimated inspired desflurane concentrations relative to the vaporizer setting during low-flow anaesthesia with fresh gas flows of 1.0 and 2.0 L min−1 without using a initial wash-in period [9]. We estimated the inspired and end-tidal values with a fixed vaporizer setting under maintaining clinical procedures after an initial period of denitrogenation.

The purpose of this study was to determine the inspired and end-tidal desflurane concentrations with a vaporizer setting of 5%, during low-flow anaesthesia after 120 min with fresh gas flows of 1.0 and 2.0 L min−1.

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Methods

The Ethics Committee approved the study at the University of Lund, Sweden, and written informed consent was obtained from all patients. We studied 56 patients, ASA physical status I and II scheduled for elective general or urology surgery with desflurane for anaesthesia and an anticipated anaesthesia time of 2-h duration or greater. Patients with a history, laboratory, or physical examination evidence of hepatic, renal, or significant cardiovascular disease were excluded from the study. The patients were randomly assigned to one of two treatments (28 patients in each group), and received a fresh gas flow (FGF) of 1.0 and 2.0 L min−1 (60% nitrous oxide in oxygen). Patients in group 1, received fresh gas flows of 1 L min−1. In group 2, the patients received fresh gas flows of 2 L min−1.

The patients were premedicated with midazolam 7.5 mg rectally 30 min prior to arriving at the operating room. Anaesthesia was induced by administration of 100% oxygen for 3–4 min followed by 2 μg kg−1 fentanyl, 1.5–2.0 mg kg−1 propofol and muscle relaxation was produced with 1.0–1.5 mg kg−1 succinylcholine. Ventilation of the lungs was manually assisted with 100% oxygen via a circle breathing system (Anmedic, Sweden) until tracheal intubation and connection to mechanical ventilation was performed with a Servo 900C ventilator (Siemens-Elema™, Sweden). The ventilator delivers the tidal volumes with oxygen into a large deadspace that consists of a corrugated hose with 2.2-L internal volume (Figure 1). Fresh gas flow (60% nitrous oxide in oxygen) was supplied to the circle system with 4.5 L min−1 (1.5 L min−1 oxygen and 3.0 L min−1 nitrous oxide) during the first 5 min and then adjusted to 1.0, 2.0 or 3.0 L min−1 with a desflurane (Suprane®, Pharmacia-Upjohn) vaporizer setting of 5%. Tidal volume was set to maintain normocapnia (34–35 mmHg). The ventilator rate was 15 bpm, the inspiratory and pause time was 33% and 10% respectively.

Figure 1.

Figure 1.

During the procedure, routine monitoring included electrocardiogram (lead II), heart rate, non-invasive mean arterial pressure (MAP) and haemoglobin oxygen saturation (SpO2) (Merlin™, Hewlett Packard). The inspired oxygen and end-tidal concentrations of desflurane, N2O, CO2 were monitored (AGM M1026A, Hewlett Packard) and analysed by infra-red light absorption technique at 1-min intervals during the first 15 min of anaesthesia and thereafter at 5-min intervals through the study. Analysed gases were sampled using a side-stream port at the heat and moisture exchanger (Humid-Vent, Gibeck) and analysed gas was returned to a port fitted into the CO2 absorber. The gas analyser used air as a reference gas, with a calibration frequency of immediately, 5 min, 15 min, 1 h and 3 h after set up. Anaesthetic gases were delivered using a desflurane anaesthetic vaporizer (TEC-6) and an AGA (Sweden) anaesthesia machine. The used TEC-6 vaporizer was calibrated at 760 mmHg and at nominal 21°C before the study by an independent medical technician. The accuracy in output from the used vaporizer, with fresh gas flows of 1.0 or 2.0 L min−1, was ±0.5% of the vaporizer setting using oxygen as a carrier gas. Prior to each anaesthetic administration, fresh soda lime (Absorber, Anmedic) was used. Additional doses of fentanyl 1 μg kg−1 were administered if MAP increased more than 20% of baseline and a similar decrease in arterial pressure was treated with ephedrine 5–10 mg intravenously (i.v.). Neuromuscular block was achieved with 0.5 mg kg−1 atracurium i.v. Incremental doses of 0.1–0.2 mg kg−1 atracurium were given when two twitches returned – detected by a train-of-four stimulus (Microstim, GlaxoWellcome). Residual muscle paralysis was antagonized using i.v. glycopyrrolate and neostigmine. At the termination of the procedure, oxygen flow rate was increased to 6 L min−1 and spontaneous ventilation allowed to return. Following eye opening to command the trachea was extubated.

All data are reported as mean values with variability expressed as SD. The inspired and end-tidal concentrations of desflurane were analysed with one-sample t-test. Demographic data were compared using the χ2-test. Wilcoxon’s two-sample test was used to test the difference between 1.0 and 2.0 L min−1 for inspired (In), end-tidal (ET) desflurane and the ratio ET/In. P < 0.05 was considered significant.

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Results

The demographic data were comparable in the two groups (Table 1). With a vaporizer setting of 5%, the desflurane inspired (In) and end-tidal (ET) concentrations in the 1.0 L min−1 group after 120 min were 4.54% vs. 4.37% (P < 0.001) (Table 2). In the 2.0 L min−1 group, the In-and ET-concentrations of desflurane were 4.76% vs. 4.58% (P < 0.001) (Table 2). The estimated difference inspired/end-tidal values, at 120 min of anaesthesia, were 0.17% in the 1.0 L min−1 group vs. 0.18% in the 2.0 L min−1 group [not significant (NS)]. These data demonstrate a similar ratio end-tidal/inspired concentration of 0.96 in both groups. The ratio end-tidal concentration/vaporizer setting was 0.87 in the 1.0 L min−1 group vs. 0.92 in the 2.0 L min−1 group. At a significance level of 5%, there was a significant difference between 1.0 and 2.0 L min−1 for In and ET of desflurane (Figure 2), but not for the ratio In/ET. There was no system-related mishap during the study.

Table 1

Table 1

Table 2

Table 2

Figure 2.

Figure 2.

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Discussion

Anaesthesiologists have a moral and ethical commitment to minimize the cost of the drugs they use [11]. To minimize the cost of volatile agents, a low-flow technique can be used, and further advantages of low-flow anaesthesia include reduction of environmental pollution and preservation of the heat and humidity in the breathing system [12–16].

The purpose of this study was to determine the inspired and end-tidal desflurane concentrations under ordinary clinical procedures. The delivery of volatile agents into a low-flow system must normally be dramatically modified when using high solubility agent’s [17]. As the fresh gas flow rates decreases, the anaesthetic agent concentration delivered from the vaporizer has to be increased in order to provide an adequate amount of vapour. This study demonstrated a discrepancy between inspired and end-tidal desflurane concentrations compared with the vaporizer setting. After 120 min of low-flow anaesthesia, the inspired and end-tidal concentrations of the desflurane in the 1.0 L min−1 group was 4.54% vs. 4.37%. This demonstrates an end-tidal concentration of 0.87 of the vaporizer setting. In the 2.0 L min−1 group, the desflurane inspired and end-tidal concentrations were 4.76% vs. 4.58%, and correspond to an end-tidal concentration of 0.92 of the vaporizer setting. In addition, increasing the FGF to 2.0 L min−1 has only a limited increase (0.05) of the inspired and end-tidal values, compared with the 1.0 L min−1 group.

Ventilation with dry gases leads to considerable loss of water and heat that is lost directly from the respiratory tract as a result of the vaporization of water [18]. We have previously found that, after 120 min of anaesthesia, the mean inspiratory absolute humidity without use of a heat and moisture exchanger (HME) was increased by b≅4 mg H2O L−1 if 1.0 L min−1 fresh gas flow was used compared with 3.0 L min−1 fresh gas flow (unpublished observations) [19]. These data demonstrated that the absolute humidity of the inspiratory gases was significantly higher with a low-than with a high-flow. This may be because the continuous flow of fresh gas in the present low-flow system, at high inflow rates, washes out water throughout the hoses and lung ventilator. It is possible that different values of absolute humidity, at different fresh gas flows, have influenced the measurements of the present end-tidal desflurane values. However, in our previous study when using HMEs, the mean inspiratory absolute humidity was similar in the both groups (32 mg H2O L−1) [19]. In the present study, we used 1.0 and 2.0 L min−1 fresh gas flows in combination with a heat and moisture exchanger. We believe that this minimized the influence of differences in absolute humidity values on the determined end-tidal desflurane concentrations.

The low-flow technique used in this study is an alternative to the bag-in-bottle arrangement [1]. We used a lung ventilator connected to the anaesthesia circle via a large deadspace that prevents ventilator gas from entering the circle. This is a described and safe method that combines the facilities of a powerful ventilator with the advantages of a circle system with a carbon dioxide absorber. However, a mixing of ventilator driving gas through the tube deadspace with anaesthetic fresh gas inflow in the circle system is well known and depends on four variables: tidal volume, internal deadspace of the connecting tube, anaesthetic fresh gas flow and ventilator rate [20]. Mixing of the ventilator gas with anaesthetic fresh gas inflow occurs when tidal volumes is increased to exceed the connecting deadspace volumes at 30 and 15 bpm, respectively, provided that the fresh gas flow is 2 L min−1 [1]. Mixing becomes inevitable when the anaesthetic gas flow is decreased and the tidal volume increased. Similar mixing could be expected during high-frequency ventilation, due to an increase in inspiratory flow rate that will push the wave front of the ventilator gas further into the connecting deadspace at the end of the previous expiration. Berntman and his colleagues found that no mixing occurred in the present circle system by changing tidal volumes from 380 to 1170 mL when deadspace volume was 1650 or 2200 mL [1]. In the present study, we used a deadspace volume of 2200 mL with a ventilation frequency of 15 min−1 in order to increase the margins.

The circuit gas analyser, commonly used today, simplifies the practice of low-flow anaesthesia. Furthermore, with the technical adjuncts available, anaesthesiologists have an opportunity to become more knowledgeable: knowledge of how anaesthetic agents behave in low-flow anaesthesia is necessary to provide a delivery of agents that establishes and maintains the expired concentration needed for the desired depth of anaesthesia. If leaks occur in the present system, the concentrations of nitrous oxide and the volatile agent will slightly decrease, while those of oxygen from the hose slightly increases in the circle circuit. There was no such system-related mishap over the 56 patients in the study.

Patients with significant cardiovascular disease were not included in the study with the aim that an unchanged cardiac output maintains the amount of agent that is offered to the total body each minute throughout anaesthesia. The tidal volume was set to maintain normocapnia. To maintain cardiac output and carbon dioxide production, additional doses of 1 μg kg−1 fentanyl were administered if MAP increased more than 20% of baseline and a similar decrease, in pressure was treated with ephedrine 5–10 mg. However, when relatively insoluble inhalation anaesthetics are used (e.g. desflurane and nitrous oxide), variation in uptake due to increases in cardiac output is of less importance. Doubling of cardiac output reduces the arterial concentration of nitrous oxide by less than 15% [21]. As desflurane is less soluble than nitrous oxide, and based on our demographic data and results, the influence of fentanyl and ephedrine administration on the results seem to be of minor importance. The determined desflurane values in this study presents a gas tight function of the ventilator and the circle system, without drastically changes in ventilation or cardiac output.

The results of the characteristics of desflurane in the present study are comparable with other desflurane low-flow studies [17,22]. During low-flow anaesthesia, an initial period of high fresh gas flow is recommended to denitrogenate the circle system and the functional residual capacity of the patient. Six minutes with a 5-L min−1 fresh gas inflow was found to be sufficient to achieve nitrogen concentrations < 3% [23]. In the used low-flow system, the nitrogen concentration was even found to decrease due to escape of excess gas via the deadspace into the ventilator exhaust [1].

An increase of nitrogen can readily be detected from the total concentrations of all used gases resulting in unexpectedly decreased nitrous oxide concentration. There were no such episodes. Consequently, there is no need to wash-out nitrogen and trace gases at intervals with high fresh gas inflows, but similar wash-out effects on volatile agents is to be expected in the used low-flow system.

We used an ordinary initial denitrogenation and wash-in period of 5 min using high-flow of 4.5 L min−1 and the vaporizer setting of 5% was not altered throughout the study. The desflurane concentrations after the denitrogenation period are in context with the observations of Baum and his colleagues, who demonstrated a reached inspired desflurane concentration of 90–95% of the vaporizer setting during the initial phase using high-flows (Figure 2) [12]. The ratio end-tidal and inspired concentrations at 120 min of anaesthesia, was 0.96 in both groups. Although between groups there is a difference in the end-tidal values, this was not seen when the end-tidal to inspired ratio was compared. This may be explained by the continuous fresh gas flow washing out a similar amount of desflurane through the hose and ventilator that is offered to the circle system.

The results from the study suggest that the inspired and end-tidal values are more dependent on the low blood–gas partition coefficient of desflurane than the fresh gas inflow, compared with other volatile agents [8,17]. In our study, desflurane could be administered with unchanged vaporizer settings in both groups. There is less uptake than for the other volatile anaesthetic agents and the vaporizer and patient exhaled concentrations are close to each other. Therefore, after the initial high-flow phase, the pharmacokinetic properties of desflurane facilitate a predictable end-tidal value during the procedure and leaks could be detected regardless of the flow rates to be used. These findings consistently demonstrated that desflurane low-flow anaesthesia could safely be used with decreased flow rates to 1.0 L min−1, for surgical procedures of any duration.

We concluded that after 120 min of desflurane anaesthesia with a vaporizer setting at 5%, that there is a significant difference between 1.0 and 2.0 L min−1 for inspired and end-tidal concentrations, but not for the ratio end-tidal/inspired. Using FGF of 1.0 L min−1, the end-tidal concentration was 0.87 of vaporizer setting. Changing the FGF to 2.0 L min−1 increased the end-tidal values 0.05.

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Keywords:

ANAESTHETICS, VOLATILE; desflurane; EQUIPMENT; breathing systems, low-flow

© 2001 European Academy of Anaesthesiology