Degradation products of sevoflurane during low-flow

British Journal of Anaesthesia 1995; 74: 56-59
Degradation products of sevoflurane during low-flow anaesthesia
H . BlTO AND K . IKEDA
Summary
Key w o r d s
Anaesthetics volatile, sevoflurane. Equipment, breathing systems.
Sevoflurane is known to react with soda lime to
produce degradation products [1,2]. The concentrations of degradation products in the breathing
system during low-flow anaesthesia have been investigated [3], but there have been no quantitative
studies of degradation products during low-flow
anaesthesia in laparoscopic cholecystectomy. As
carbon dioxide elimination by the patient is higher in
laparoscopic cholecystectomy because carbon dioxide is infused into the peritoneal cavity [4], the
temperature of the carbon dioxide absorbent increases. When the temperature of the carbon dioxide
absorbent is high, the production of degradation
products is known to be increased [5, 6]. Therefore,
it is assumed that more degradation products are
formed during laparoscopic cholecystectomy than
other surgical procedures. Low-flow sevoflurane
anaesthesia was performed in patients undergoing
either laparoscopic cholecystectomy or tympano-
Patients and methods
This study was approved by the local Ethics
Committee and informed consent was obtained from
all patients.
We studied 16 patients undergoing laparoscopic
cholecystectomy (group LSC, n = 8) or tympanoplasty (group TP, n = 8), and who were judged to be
ASA I or II.
Premedication comprised hydroxyzine 50 mg and
atropine sulphate 0.5 mg administered i.m. 45 min
before induction of anaesthesia. Anaesthesia was
induced with thiopentone 4—5 mg kg"1 and vecuronium 0.12-0.15 mg kg"1. After tracheal intubation,
the totalflowrate for maintenance of anaesthesia was
set at 1 litre min"1. The ratio of the oxygen and
nitrous oxide flow rates was controlled so that the
oxygen concentration in the inspiratory limb exceeded 30%. The sevoflurane concentration was regulated so that systolic arterial pressure was maintained
within ± 20 % of the baseline value. Ventilation was
controlled mechanically with a tidal volume of 10-12
ml kg"1, and ventilatory frequency was regulated to
maintain end-tidal carbon dioxide concentration at
4.0-5.3 kPa. The carbon dioxide insufflation pressure for laparoscopy was 8-10 mm Hg.
Soda lime (Sodasorb, W. R. Grace & Co., Lexington, MA, USA) was used as the carbon dioxide
absorbent, and it was replaced with fresh absorbent
before the start of each anaesthetic. The anaesthesia
Table 1 Patient characteristics(mean (SEM or range)). LSC =
Laparoscopic cholecystectomy, TP = tympanoplasty
Group LSC
Group TP
Age
(yr)
Height
(cm)
Body weight
(kg)
51.1 (22-73)
53.5 (24-69)
158.9(3.0)
159.6(4.4)
57.5 (3.1)
61.3 (5.1)
HIROMICHI BITO, MD, KAZUYUKI IKEDA, MD, Department of
Anesthesiology and Intensive Care, Hamamatsu University
School of Medicine, 3600 Handa-cho, Hamamatsu 431 -31, Japan.
Accepted for publication: August 1, 1994.
Correspondence to H.B.
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Low-flow (1 litre mirr 1 ) sevoflurane anaesthesia
was used in 16 patients undergoing laparoscopic
cholecystectomy (group LSC, n = 8) or tympanoplasty (group TP, n = 8), and concentrations of
sevoflurane degradation products were measured.
Degradation products in the circuit were measured
hourly, and end-tidal carbon dioxide concentration,
inspired and end-tidal sevoflurane concentrations,
and carbon dioxide elimination were monitored.
The only degradation product detected was
CF2=C(CF3)-O-CH2F (compound A). The mean
maximum concentrations of compound A were
21.6 (SEM 1.6) ppm and 1 9.6 (0.8) ppm in the LSC
and TP groups, respectively (ns). The maximum
temperatures of soda lime were 46.4 (0.5) °C and
44.8 (0.5) °C, respectively (P < 0.05). Hourly endtidal sevoflurane concentrations and concentrations
of sevoflurane degradation products were the same
for both groups. Carbon dioxide elimination was
the same for both groups 1 h after the start of
anaesthesia, but was higher in group LSC after 2 h
(P <0.05). Intraperitoneal carbon dioxide insufflation associated with laparoscopic cholecystectomy had no effect on the concentration of
sevoflurane degradation products. (Br. J. Anaesth.
1995; 74: 56-59)
plasty, and the concentrations of degradation products in the two groups were compared. The
temperature of the carbon dioxide absorbent and
carbon dioxide elimination by the patient, which is
affected by the temperature of the carbon dioxide
absorbent, were also measured and compared.
57
Sevoflurane in laparoscopic cholecystectomy
Table 2 Maximum concentration of compound A, maximum temperature of soda lime, MAC-h and anaesthesia
time (mean (SEM)). LSC = Laparoscopic cholecystectomy, TP = tympanoplasty. *P < 0 05 vs group TP
Group LSC
Group TP
Max. concn
compound A
(ppm)
Max. temp,
soda lime
21.6(1.6)
19.6 (0.8)
46.4 (0.5)*
44.8 (0.5)
Anaesthesia
time (h)
3.17(0.22)
3.87(0.16)
3.08(0.19)*
3.84(0.19)
30 -i
1
2
Anaesthesia time (h)
3
Figure 1 Comparison of concentrations of compound A in
laparoscopic cholecystectomy ( # ) vs tympanoplasty (O) (mean,
SEM). n = 8 in each group.
0
1
2
Anaesthesia time (h)
Figure 2 Comparison of end-tidal sevoflurane concentrations
in laparoscopic cholecystectomy ( 0 ) vs tympanoplasty (O)
(mean, SEM). n = 8 in each group.
Results
There were no differences in age, height or body
weight between the two groups (table 1). Of the
degradation products of sevoflurane, only
CF2=C(CF3)-O-CH2F (compound A) was detected. The maximum concentration of compound A in
the circuit was 21.6 (1.6) (12.2-27.0) ppm in group
LSC and 19.6 (0.8) (16.1-22.6) ppm in group TP;
there was no significant difference between the two
groups (table 2). The maximum soda lime temperature was 46.4 (0.5) °C in group LSC and 44.8
(0.5) °C in group TP (P < 0.05) (table 2). There
were no significant differences in MAC-h between
the two groups (table 2).
When the concentrations of compound A in the
circuit at each measurement time were compared
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equipment used was the Modulas II anaesthesia
system (Ohmeda, Madison, WI, USA).
Two temperature probes (temperature probe
model 9182, Hioki Electric Co., Nagano, Japan)
were inserted at points above and below the centre of
the upper compartment of the canister to measure
the temperature of the soda lime, and the measured
values were recorded at 15-min intervals.
End-tidal carbon dioxide concentration and inspired and end-tidal sevoflurane concentrations
during anaesthesia were monitored using mass
spectrometry (Medical Gas Analyzer 1100, Perkin
Elmer, Pomona, CA, USA). Minute carbon dioxide
elimination by the patient was calculated as minute
expired volume multiplied by mean expired carbon
dioxide concentration. Minute expired volume was
measured using a linearized electronic Wright respirometer (BOC Medishield Essex, UK). Mean
expired carbon dioxide concentration was obtained
using a bypassed mini-mixing chamber and then
measured by mass spectrometry [7]. Hourly mean
values were calculated from the values measured
every 1 min. Sevoflurane MAC-h exposure was
calculated from the percent anaesthetic concentration and the duration of exposure. A MAC value
of 2.05% was used for sevoflurane [8].
Sample gas for measurement of degradation
products was collected from the inspiratory limb of
the anaesthesia circuit. The concentrations of the
degradation products were measured every 1 h by a
gas chromatograph (model GC-9A, Shimadzu,
Kyoto, Japan) equipped with a gas sampler (model
MGS-5, Shimadzu, Kyoto, Japan).
A column temperature of 100 °C and an injection
inlet temperature of 140 °C were used, with nitrogen
as the carrier gas at a flow rate of 50 ml min"1. The
detector was a hydrogen flame ionization detector
(FID). The column was a glass column, 5 m in
length and 3 mm in internal diameter, filled with
20% DOP Chromosorb WAW (Technolab S.C.
Corp., Osaka, Japan), 80/100 mesh. The sample
volume was 1 ml. The gas chromatograph was
calibrated by preparing standard calibration gas
from stock solutions of compounds A and B supplied
by Maruishi Pharmaceutical Co., Ltd. (Osaka,
Japan).
All results are expressed as mean (SEM). Maximum
and hourly degradation product concentrations, the
temperature of the soda lime, end-tidal sevoflurane
concentration and carbon dioxide elimination were
measured in each patient, and groups LSC and TP
were compared using repeated measures ANOVA
where appropriate and Student's t tests. P values less
than 0.05 were considered statistically significant.
MAC-h
58
British Journal of Anaesthesia
200 i
c
E
I
•o
2 150
to
c
o
o
100
1
2
Anaesthesia time (h)
Figure 3 Comparison of hourly mean carbon dioxide (CO2)
eliminated by the patient during laparoscopic cholecystectomy
( # ) vs tympanoplasty (O) (mean, SEM). *P < 0.05 vs
tympanoplasty. n = 8 in each group.
Discussion
During laparoscopic cholecystectomy, some of the
insufflated carbon dioxide is absorbed and the
amount of carbon dioxide eliminated by the patient
increases [4]. Thus with low-flow anaesthetic techniques the temperature of the soda lime increases to
higher levels during laparoscopic cholecystectomy
than during surgical procedures not requiring a
pneumoperitoneum. In the present study, carbon
dioxide elimination by the patient was higher in
laparoscopic cholecystectomy than in tympanoplasty, and the temperature of the soda lime was
higher in the former group. It is known that the
production of degradation products increases when
the temperature of soda lime is high [5, 6] and it is
reasonable to assume therefore, that the concentration of degradation products may be higher during
laparoscopic cholecystectomy than during tympanoplasty. However, we found no significant differences
in the concentrations of degradation products between the two groups in the present study. The
reason for this may be that the difference in the
mean soda lime temperature between the two groups
was only 1.6 °C and thus was not sufficient to cause
a significant difference in the concentrations of
degradation products.
Factors other than the temperature of the soda
lime which affect the concentrations of degradation
products include sevoflurane concentration in the
system [2], type of carbon dioxide absorbent used [3,
9], freshness of the carbon dioxide absorbent [3, 10]
and total flow rate [11]. In the present study there
were no differences in sevoflurane concentration in
the circuit or the total flow rate between the two
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between the two groups, no significant differences
were observed at any of the measurement times (fig.
1). End-tidal sevoflurane concentration during the
measurement of degradation products also showed
no difference between groups (fig. 2). Mean carbon
dioxide elimination per hour did not differ significantly between the two groups 1 h after the start of
anaesthesia, but values in group LSC were significantly higher than those in group TP after 2 h (P <
0.05) (fig. 3).
groups, and fresh soda lime was used for each
patient. Therefore, factors affecting degradation
product concentrations, other than the type of
surgical procedure, were the same for both groups.
The fact that, contrary to expectations, the concentrations of degradation products were the same in the
two groups indicates that no factor other than the
temperature of the soda lime was involved.
In this study, pneumoperitoneum associated with
laparoscopic cholecystectomy had no effect on the
concentrations of degradation products, but when
carbon dioxide uptake is abnormally high for some
reason, such as extraperitoneal carbon dioxide insufflation during pelviscopy [4], carbon dioxide elimination by patients appears to be higher than that
observed in the present study. For this reason, it is
possible that the temperature of the soda lime is
increased further, resulting in increased concentrations of degradation products.
The LQo value of compound A in rats has been
reported to be 1050-1090 ppm for 1-h inhalation and
340-^190 ppm for 3-h inhalation [12]. The concentrations of compound A observed in the present
study were comparable with those reported in
previous studies [11, 13], and were low compared
with the LC50 in rats. In low-flow [3] or closed
system [14] sevoflurane anaesthesia, it has been
reported that no abnormalities in renal and liver
function tests occurred. However, it is necessary to
further clarify the safety of low-flow sevoflurane
anaesthesia under various conditions, including lowflow anaesthesia in patients undergoing laparoscopic
cholecystectomy.
Sevoflurane in laparoscopic cholecystectomy
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59
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