Rev Bras Anestesiol.

2015;65(1):68---72

REVISTA
BRASILEIRA DE
ANESTESIOLOGIA

Ofcial Publication of the Brazilian Society of Anesthesiology

www.sba.com.br

SCIENTIFIC ARTICLE

Comparison of effects on the oxidant/antioxidant

system of sevourane, desurane and propofol
infusion during general anesthesia
Mesut Erbas a , Yavuz Demiraran b, , Hayriye Ak Yildirim c , Gulbin Sezen b ,
Abdulkadir Iskender b , Ibrahim Karagoz b , Hayati Kandis d
a

Department of Anesthesiology and Reanimation, Medical Faculty, C

anakkale Onsekiz Mart University, Canakkale, Turkey
Department of Anesthesiology and Reanimation, Medical Faculty, Duzce University, Duzce, Turkey
c
Department of Biochemistry, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul,
Turkey
d
Department of Emergency Medicine, Medical Faculty, Duzce University, Duzce, Turkey
b

Received 12 February 2014; accepted 2 May 2014

Available online 3 June 2014

KEYWORDS
Oxidant;
Antioxidant;
Propofol;
General anesthesia

Abstract
Background and objectives: Desurane and sevourane are frequently used for maintenance
of anesthesia and studies have shown that these anesthetics cause a variety of changes to the
oxidative stress and antioxidative defense mechanisms. This study aims to compare the effects
of sevourane, desurane and propofol infusion anesthesia on the oxidant and antioxidant
systems of patients undergoing laparoscopic cholecystectomy.
Methods: 45 patients between 18 and 50 years with planned laparoscopic cholecystectomy
under general anesthetic were included in the study. Patients were divided into three groups
on the way to surgery: propofol (group P n: 15), sevourane (group S n: 15) and desurane (group
D n: 15). All groups were given hypnotic 2 mg/kg propofol IV, 1 mcg/kg fentanyl IV and 0.1 mg/kg
vecuronium IV for induction. For maintenance of anesthesia group S were ventilated with 2%
sevourane, group D cases were given 6% desurane and group P were given propofol infusions
of 12 mg/kg/h for the rst 10 min, 9 mg/kg/h for the second 10 min and 6 mg/kg/h after that.
Before induction and after the operation venous blood samples were taken to evaluate the
levels of glutation peroxidase, total oxidants and antioxidants.
Results and conclusions: The 45 patients included in the study were 22 male and 23 female
patients. The demographic characteristics of the groups were similar. In the postoperative
period we observed that while sevourane and propofol increased antioxidants by a statistically
signicant level, desurane increased the total oxidants level by a signicant amount compared
to levels before the operation.
2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda.
Este um artigo Open Access sob a licena de CC BY-NC-ND

Corresponding author.
E-mail: [email protected] (Y. Demiraran).

http://dx.doi.org/10.1016/j.bjane.2014.05.004
0104-0014/ 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. Este um artigo Open Access sob a licena de CC BY-NC-ND

Effects on oxidant/antioxidant system of sevourane, desurane, propofol

PALAVRAS-CHAVE
Oxidante;
Antioxidante;
Propofol;
Anestesia geral

69

Comparac
o dos efeitos da perfuso de sevourano, desurano e propofol sobre o
sistema oxidante/antioxidante durante anestesia geral
Resumo
Justicativa e objetivos: Desurano e sevourano so usados com frequncia para a
manutenc
o da anestesia, e estudos mostraram que esses anestsicos causam alterac
es variadas nos mecanismos de defesa antioxidante contra o estresse oxidativo. Este estudo teve
como objetivo comparar os efeitos de anestesias com perfuso de sevourano, desurano e
propofol sobre os sistemas oxidante/antioxidante de pacientes submetidos colecistectomia
laparoscpica.
Mtodos: Foram includos no estudo 45 pacientes entre 18 e 50 anos, agendados para colecistectomia laparoscpica sob anestesia geral foram includos no estudo. Os pacientes foram
divididos em trs grupos para receberem propofol (Grupo P, n: 15), sevourano (Grupo S, n:
15) e desurano (Grupo D, n: 15). Todos os grupos receberam 2 mg/kg de propofol IV, 1 mcg/kg
de fentanil IV e 0,1 mg/kg de vecurnio IV para induc
o. Para manutenc
o da anestesia, o
Grupo S recebeu ventilac
o com sevourano a 2%, o Grupo D recebeu desurano a 6% e o Grupo
P recebeu propofol em perfuses de 12 mg/kg/h nos primeiros 10 min, 9 mg/kg/h nos 10 min
seguintes e 6 mg/kg/h subsequentemente. Antes da induc
o e depois da cirurgia, amostras
de sangue venoso foram colhidas para avaliar os nveis de glutationa peroxidase e o total de
oxidantes e antioxidantes.
Resultados e concluses: Dos 45 pacientes includos no estudo, 22 eram do sexo masculino e
23 do sexo feminino. As caractersticas demogrcas dos grupos eram semelhantes. No perodo
ps-operatrio, observamos que enquanto sevourano e propofol aumentaram os antioxidantes
a um nvel de signicncia estatstica, desurano aumentou o nvel total de oxidantes em
quantidade signicativa, em comparac
o com os nveis pr-operac
o.
2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda.
Este um artigo Open Access sob a licena de CC BY-NC-ND

Introduction
Free oxygen radicals, on the one hand while they oxidize biological molecules such as the bodys building blocks
of protein, lipid and DNS, on the other hand they can
work against this oxidation as part of the bodys natural
antioxidant defense system. This situation is balanced under
normal physiological conditions. However in a situation of
meeting any stress, as a result of increasing antioxidant consumption or free radical creation, many oxidative stresses
increase.1,2 Many antioxidant molecules are found in the
blood to prevent or inhibit the harmful effects of free oxygen radicals. Measurement of total antioxidant and oxidant
levels in plasma can be used to determine the oxidative
stress reaction of the organism.3,4 Desurane and sevourane are frequently used for maintenance of anesthesia and
studies have shown that these anesthetics cause a variety
of changes to the oxidative stress and antioxidative defense
mechanisms.5 The chemical structure of propofol is similar
to some free radical consumers such as endogenous vitamin
E and butylated hydroxene toluene.6---8
In this study we aimed to compare the effects of sevourane, desurane and propofol infusion anesthesia on the
oxidant and antioxidant systems of patients undergoing
laparoscopic cholecystectomy.

Methods
After permission was given by 2009/12 no. decision of Duzce
University Medical Faculty Clinical Study Ethics Committee

and informed patient consent was obtained, 45 patients

ASA I---II between 18 and 50 years with planned laparoscopic
cholecystectomy under general anesthetic were included in
the study. Patients were divided into three groups on the
way to surgery: TIVA (group P n: 15), sevourane (group S n:
15) and desurane (group D n: 15). Patients with endocrine
dysfunction, blood transfusion in the previous 2 weeks, signs
of infection and inammation, history of preoperative medication use, anemia, and hemorrhage requiring transfusion
during the operation were excluded from the study. After
fasting for 8 h all patients in the study were given 1 mg
midazolam IV for premedication 30 min before the operation. Patients were taken to the operating room. Routine
monitoring with electrocardiogram (ECG), peripheral oxygen saturation (SPO2 ), and non-invasive blood pressure were
done. Later before the operation venous blood was taken to
evaluate total oxidant status, total antioxidant status and
glutation peroxidase levels.
All groups were given hypnotic 2 mg/kg propofol IV,
1 mcg/kg fentanyl IV and 0.1 mg/kg vecuronium IV for induction. During anesthesia induction cases were oxygenized
with 100% O2 at 6 L/min ow rate. After 3 min of controlled
ventilation, using an appropriate intubation tube for age and
weight, orotracheal intubation was completed. For maintenance of anesthesia, group S were ventilated with 2%
sevourane, 50% air and 50% O2 mix at 6 L/min ow. Group
D cases were given 6% desurane, 50% air and 50% O2 mix
at 6 L/min ow. Group P were given propofol infusions of
12 mg/kg/h for the rst 10 min, 9 mg/kg/h for the second
10 min and 6 mg/kg/h after that. Patients were ventilated
with 50% air and 50% O2 mix at 6 L/min ow. In all groups

70
after tidal volume was determined to be 6---8 mg/kg and respiration rate was 12, ventilation was begun with an Avance
S/5 anesthesia device. Ten minutes before the expected end
of surgery propofol infusion was ended. When the last skin
suture was being made inhalation agents were shut off. Manual ventilation with 100% O2 was undertaken. In this period
all parametric readings were taken. After spontaneous respiration began, neuromuscular antagonization was completed
with 0.01 mg/kg atropine and 0.03 mg/kg neostigmine. After
extubation the patient was taken to recovery. Later venous
blood was taken to evaluate total oxidant status, total
antioxidant status and glutation peroxidase levels after the
operation.

Biochemical analysis
Blood samples taken in anticoagulant free vacuum gel tubes
were centrifuged at 2000 g for 15 min. The serum was portioned into clean tubes. For glutation studies the serum
separated in the tube was deproteinized. For the deproteinization procedure 5 g metaphosphoric acid was dissolved
in 50 mL distilled water and 200 L samples were mixed with
200 L metaphosphoric acid solution and vortexed. They
were rested at room temperature for 5 min and were centrifuged at 2000 g for 4 min. The supernatant was carefully
separated to a different tube. This supernatant to measure glutation and the serum portions designated to measure
other parameters were stored at 80 C until measurements
could be made. Glutation was measured based on enzymatic
measurements using Cayman (Cayman Inc., Ann Arbor, MI,
USA) commercial kits, which use 5-thio-2-nitrobenzoic acid
(TNB) to react with the DTNB (5,5 -dithio-bis-2-nitrobenzoic
acid) of the sulfhydryl group in GSH glutation reductase
forming a yellow color. On the day of measurement, samples
were thawed and mixed, then prepared 4 M triethanolamine
solution of 10 L was added to 200 L samples and vortexed.
After samples were diluted at 1:2 (v/v) ratio with MES buffer,
standards were prepared according to the prospectus. They
were added to 50 m wells, and the plate was covered with
the lid from within the kit. At this stage, according to the
prospectus an assay cocktail of MES buffer (11.25 mL), GSH
co-factor mixture (0.45 mL), GSH enzyme mixture (2.1 mL),
distilled water (2.3 mL), and GSH DTNB (0.45 mL) was prepared and 150 L freshly-prepared assay cocktail was added
to all wells, the plate was covered and incubated on an
orbital mixer in the dark for 25 min. In the 25th minute measurement was taken using a Bio-Rad 680 Microplate reader
at 414 nm. Total antioxidant measurements used a Cayman
(Cayman Inc., Ann Arbor, MI, USA) commercial kit based on
oxidation inhibition of ABTS + by the metmyoglobin in ABTS
(2,2 -azino-di-[3-ethylbenzthiazoline sulphonate]). On the
day of measurement samples were thawed and mixed, then
for antioxidant measurements the samples were diluted with
assay buffer at 1:19 (v/v) and standards were prepared
according to the prospectus. After 10 L trolox standard or
10 L sample was added to all wells 10 L metmyoglobin
and 150 L chromogen solution were added and to begin
the reaction immediately 40 L 441 M antioxidant assay
hydrogen peroxide was added. The plate was covered and
incubated on a mixer at room temperature for 5 min. Measurement was made using a Bio-Rad 680 Microplate reader

M. Erbas et al.
at 405 nm. Total oxidant capacity measurements used a Rel
Assay kit (Rel Assay Diagnostics, Mega Tp San and Tic Ltd
Sti, Turkey) developed by Erel.9 This method is based on
oxidants in the sample turning a ferrous iron chelator into
ferric ions, which in an acid environment form a color complex with chromogen and this complex is then measured
spectrophotometrically. Stabilized stock standard solution
(SSSS) was diluted 40,000 times by deionized water then
150 L or the sample was mixed with 1000 L reactive I.
First absorbance was measured using a spectrophotometer at 530 nm wavelength. Fifty L prochromogen solution
was added, mixed and incubated at room temperature for
10 min. Second absorbance was measured at 530 nm.
For calculations the following formulae were used:


TOS =

Absorbance sample
Absorbance standard


standard value

Absorbance sample = 2nd absorbance sample 1st

absorbance sample,
Absorbance standard = 2nd absorbance standard 1st
absorbance standard,
Standard value: 20 mol H2 O2 equiv./L.

Statistical analysis
Data were analyzed using the SPSS v 11.5 (SPSS, Inc.,
Chicago, IL, USA) computer program. Distribution of numerical data within the groups was evaluated using the
Shapiro---Wilk test. Data with normal distribution are given
as mean standard deviation (SD); categorical variables are
given as frequencies. To determine any differences in average numerical data between the groups the one-way ANOVA
was used. To nd groups responsible for signicant differences multivariate analysis used the Scheffe test. Before and
after measurements were analyzed with the paired samples
t test as they had normal distribution. Categorical variables were compared between the groups with the chi-square
test. A p value <0.05 was accepted as statistically signicant.

Results
Our study comprised a total of 45 patients: 15 were given
sevourane, 15 were given desurane and 15 were given
propofol infusion. Of the 45 patients 22 were male and 23
were female patients. There was no statistical difference
between the patients in the groups in terms of average age,
weight, and anesthesia duration (Table 1) (p > 0.05). Hemo-

Table 1

Demographic characteristics of patients.

Age (years)
Heavy (kg)
Sex (M/F)
Anesthesia time (min)
M, male; F, female.

Group S

Group D

Group P

35 8
69 9.3
9/6
106 13

36 8
68 8.8
7/8
113 18

34 8
0.84
67 8.6 0.92
6/9
107 10 0.43

Effects on oxidant/antioxidant system of sevourane, desurane, propofol

71

84
82
80
78
76
74
72
70
68

Group S
Group D
Group P

op

e-

Pr

1.

in

5.

in

.
15

in

.
30

in

.
60

in

t-o

s
Po

Figure 1

Table 2

POSTOP

in

t-o

s
Po

5.

in

-o

st

Po

.
15

in

Hemodynamic data from the groups.

TAS, TOS and GSH-PX levels of patients.

PREOP

1.

TAS (mmol/L)
Group S
Group D
Group P

0.6 0.1
0.8 0.2
0.6 0.1

0.8 0.2
0.7 0.2
0.7 0.1

0.02a
0.24
0.04a

TOS (mol/L)
Group S
Group D
Group P

7.1 4.5
9.1 4.6
8.4 6.3

10.5 6.4
12.6 4.1
6.4 4.2

0.07
0.03b
0.10

GSH-PX (mmol/L)
Group S
0.7 0
Group D
0.7 0.1
Group P
0.8 0.1

0.7 0.1
0.7 0.1
0.7 0.1

0.42
0.89
0.79

a There is statistically signicant difference in TAS between

the preoperative and postoperative period in groups S and P.
b There is statistically signicant difference in TOS between
the preoperative and postoperative period in group D.

dynamic monitoring of patients was completed during the

operation. During this monitoring the patients preoperative, intraoperative and postoperative mean blood pressure
(MBP) was recorded (Fig. 1). The MBP values of patients
in groups S, D and P were similar. It was observed that
sevourane and propofol signicantly increases the total
antioxidant capacity. Furthermore we found that desurane
signicantly increases the total oxidant capacity.
The TAS, TOS and glutation peroxidase levels of patients
before and after the operation are shown in Table 2.

Discussion
In this study we reached the conclusion that sevourane
and propofol have antioxidant properties while desurane
increased oxidative stress.
The aim of general anesthetic applications is to create
anesthesia effectively while reducing to minimal levels the
conditions that may harm the organism. Anesthetic material appropriate for this aim should be pure and stable
chemically, have quick onset and slow end to effect, and
not create any unwanted effects on vital functions during
and after administration.10 In fact anesthetic materials and

anesthetic duration used in general anesthesia, together

with the stress of surgical trauma, are important factors that
disrupt the bodys immunological and antioxidant defense
systems.11 Laparoscopic surgery exposes the parietal peritoneum and visceral peritoneum to ischemic trauma. Studies
have shown that if intraabdominal pressure is held at
15 mmHg during laparoscopy, blood ow to the parietal peritoneum reduces by a signicant amount, while at 10 mmHg
there is no change. For this reason pneumoperitoneum
may potentially cause ischemia and increase free oxygen
radicals.12 General anesthesia disrupts the immunological
defense mechanisms and induces an inammatory reaction in alveolar macrophages. In generalized inammatory
reactions including production of leukocytes, inammation
mediators and free oxygen radicals are released. Membrane
damage caused by free radicals during general anesthesia
presents as observed lipid peroxidation products.13 Studies
have shown that a variety of medications used in anesthesia have effects on the oxidant-antioxidant system. However
the effect on the antioxidant system of the inhalation anesthetic desurane has not been fully studied. Knowledge of
the interactions of inhalation agent used on patients under
oxidative stress carries clinical importance.14 Baysal et al.15
examined the total oxidative status and antioxidative status
levels of pediatric patients undergoing laparoscopic surgery
and concluded that the surgical stress of laparoscopy with
inhalation anesthetics increased total oxidant capacity and
reduced total antioxidant capacity.
In recent years many studies on the antioxidant system
have been completed, these studies found that the antioxidant system has major effects on patient mortality and
morbidity.16 Antioxidant systems normally work as a whole,
protecting cells from the toxic effects of oxygen radicals.
This maintains the oxidant and antioxidant systems in the
organism in a balanced fashion. In situations where this balance is disrupted toward oxidation, inammatory mediators
and free oxygen radicals are produced by leukocytes. These
create lipid peroxidation in cell membranes, damaging DNA
and causing disease.17
In our study we observed in the desurane group
total oxidant capacity, an indicator of oxidative stress,
was statistically increased, while antioxidant capacity was
reduced, though not at statistically signicant levels. In the
sevourane group oxidative stress was increased compared
to values before the operation, though not signicantly,

72
while antioxidant capacity was statistically signicantly
increased. Dikmen et al.18 looked at the effect of sevourane on the enzymatic antioxidant defense system in the
livers of rats and showed that sevourane produced an
increase in lipid peroxidation before any insufciency in
the enzymatic antioxidant defense system. Allaouchiche
et al.19 compared propofol (8 mg/kg/h), desurane (10%)
and sevourane (2.5%) to determine oxidative situation
in pigs. Pigs were exposed to the anesthetic agents for
about 120 min; propofol increased glutation peroxidase levels (GSH-Px) signicantly in both bronchoalveolar lavage
(BAL) uid and in circulation. Desurane caused a signicant
decrease of GSH-Px in both BAL uid and circulation, while
in the sevourane group there were no signicant changes
identied in BAL uid and in circulation. They stated that
oxidative stress due to desurane anesthesia might be
related to extreme increases in proinammatory cytokines
in alveolar macrophages. Sivaci et al.20 used sevourane
or desurane on patients undergoing laparoscopic surgery
and observed that both agents had cytotoxic effects due to
free radical formation. Desurane changes oxidative stress
and antioxidant mechanisms negatively; they stated that
the nitrogen mixture used with desurane might increase
this effect even more. Sivaci et al. determined that desurane reduced serum GSH levels. However we did not identify
any effect on serum GSH levels due to either desurane or
propofol.
Propofol has been found to increase the uidity of the
erythrocyte membrane preventing hemolysis, similar to vitamin E, and shows antioxidant activity. Propofol protects
erythrocytes from oxidative and physical stress. Ascorbic
acid has been shown to make this effect more pronounced.
Inversely volatile anesthetics reduce erythrocyte membrane
uidity inducing hemolysis.21 In our study in the propofol infusion group oxidative stress after the operation was
reduced compared to values before operation, though not
signicantly, while at the same time antioxidant capacity was statistically increased after operation. In all three
groups statistically signicant changes in glutation peroxidase levels were not observed. In the propofol infusion group
in the postoperative period they were a little reduced, in
the sevourane group in the postoperative period they were
a little increased while in the desurane group no changes
were observed. In our study in both sevourane and propofol
infusion groups TAS values after operation were statistically
signicantly increased compared to values before surgery.

Conclusion
This study gives an idea that in general anesthesia, necessary for a variety of reasons, in cases under oxidative stress
the agent that will least damage the antioxidant system, an
important cascade in the humoral defense system, and that
will have least effect on the immune system should be chosen. Further research into the immune situation of patients
receiving general anesthetic and the relationship between
oxidant/antioxidant systems are required.

Conicts of interest
The authors declare no conicts of interest.

M. Erbas et al.

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