EFFECTS OF ISOFLURANE ON POSTOPERATIVE OLFACTORY

Acta Medica Mediterranea, 2014, 30: 453
EFFECTS OF ISOFLURANE ON POSTOPERATIVE OLFACTORY MEMORY
MURAT BILGI1, ABDULLAH DEMIRHAN1, AKCAN AKKAYA1, UMIT YASAR TEKELIOGLU1, KEMALETTIN ERDEM2 TAYFUN APUHAN3,
ADEM KURT4, HASAN KOCOGLU5
1
Assistant Professor, Department of Anaesthesiology and Reanimation, Abant Izzet Baysal University Medical School, Bolu - 2Assistant
Professor, Department of cardiovascular surgery, Abant Izzet Baysal University Medical School, Bolu - 3Assistant Professor, Department
of Head & Neck Surgery, Abant Izzet Baysal University Medical School, Bolu - 4Department of Anesthesiology and Reanimation, Abant
Izzet Baysal University Medical School, Bolu - 5Professor, Department of Anesthesiology and Reanimation, Abant Izzet Baysal
University Medical School, Bolu, Turkey
ABSTRACT
Purpose: In this study, we planned to investigate the effects of isoflurane 1.2%, on olfactory memory.
Methods: This is a prospective clinical study conducted over 40 patients aged 18-50 who had elective surgery and American
Society of Anesthesiologists (ASA) physical status I-II. The Brief Smell Identification Test (BSIT) was used for interpreting patients’
olfactory memories before and after the surgical procedure. Patients received standard general anesthesia protocol and routine monitoring. For induction, 1.5 mg/kg of fentanyl, 2 mg/kg of propofol, and 0.5 mg/kg of rocuronium bromide were administered.
Anesthesia was maintained with the inhalational of anesthetic isoflurane (1.2%). The scores are recorded 30 minute before the
surgery and when the Aldrate Recovery Score reached 10 in the postoperative period. Preoperative and postoperative results were
compared and p-values <0.05 were considered statistically significant.
Results: The patients’ mean age were 38.4±13.8. Preoperative total correct answer rate to odorous substances was 91.4%, and
postoperative rate was 90.8%. Percentage of the odor substance identification by the patients revealed no statistically significant difference when pre and post-operative rates have been compared. (P>0.05)
Conclusion: In conclusion, it is the first time we demonstrate general anesthesia with isoflurane 1.2 % has no significant effect
on the olfactory memory. Further studies with larger samples will be required to confirm our findings.
Key words: isoflurane 1.2%, olfactory memory
Received January 18, 2014; Accepted January 24, 2014
Introduction
Halogenated volatile anesthetic agents are usually well tolerated by patients without systemic disease. However, these agents may cause rare complications, including amnesia, taste and odor disorders
and olfactory memory impairment. Olfactory memory is important in recognition of foods, the relationship between mother and baby, the perception of
harmful odors, and remembering our experiment of
the past. Additionally, olfactory impairments may be
a prognostic sign of various diseases including such
as Parkinson's disease, Alzheimer’s disease, Multiple
sclerosis,Huntington's disease(1-3).
Odor impulses in the brain reach the olfactory
cortex by traveling along the course of the bulbus
olfactorius, tractus olfactorius, and stria olfactorius
(medialis, lateralis, intermedia). The structures
involved in olfactory memory are the piriform cortex, amygdalae, and the entorhinal cortex(4-6). In our
review of the literature, we could not find any imaging studies that reported general anesthesia to be the
cause of olfactory dysfunction by affecting these
anatomical structures.
Effects on the olfactory system of anesthetic
agents and anesthetic techniques (general anesthesia,
regional anesthesia,neuraxial anesthesia) have not
been researched in literature excessively.
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Murat Bilgi, Abdullah Demirhan et Al
Demirhan at.al have reported that olfactory
memory is not affected after spinal anesthesia(7).
Kostopanagiotou G at al. have reported that, olfactory memory is affected after sevoflurane anesthesia(6).
Volatile anesthetic agents have been blamed for
olfactory dysfunction, but these claims could not be
proven in clinical trials. However, two cases of anosmia have been reported in the literature following
general anesthesia(8, 9).
Isoflurane is a volatile anesthetic with a pungent odor. Isoflurane has many favourable effects,
including analgesia and muscle relaxation. But it has
some side effects, such as respiratory depression and
amnesia(10). There is an experimental study examining the effects of isoflurane on olfactory memory, but
clinical trials are not available yet.
In this study, we investigated the effects of
isoflurane 1.2 % on olfactory memory.
answers given by the participants were recorded.
Patients were then taken to the operating room and
received standard general anesthesia protocol and
routine monitoring (echocardiogram, SpO2, and noninvasive arterial pressure). For induction, 1.5 mg/kg
of fentanyl, 2 mg/kg of propofol, and 0.5 mg/kg of
rocuronium bromide were administered. Tracheal
intubation was performed after obtaining sufficient
muscle relaxation. The respiration rate was adjusted
so that the mechanical ventilator settings of patients
after intubation were as follows: 6-8 ml/kg tidal volume, FiO2: 0.5, end-tidal CO2 respiration rate: 35-45
mmHg. Anesthesia was maintained with the inhalational of anesthetic isoflurane (1.2%). Patients were
taken to the postoperative recovery room after
surgery. When the Aldrate Recovery Score reached
10, the BSIT test was repeated to test the olfactory
memory of the patients.
Materials and methods
Statistical Analysis
Data analysis was performed using the
Statistical Package for the Social Sciences (SPSS
15.0) program. Descriptive variables, such as age,
height, weight, heart rate (HR), mean arterial pressure (MAP), and duration of surgery, were shown in
the form of mean ± standard deviation, and a pairedsamples T test was used for their analysis. Goodman
and Kruskal tau tests were used for the analysis of
BSIT scores. The results were considered statistically
significant for p-values <0.05.
After receiving institutional ethical committee
approval (Clinical Ethical Committee of Abant Izzet
Baysal University, Bolu, Turkey, Ethical Committee
No: 2012/264), our study included 40 American
Society of Anaesthesiologists (ASA) I-II patients
aged 18-50 who were scheduled for expected surgery
duration of 40 - 120 minutes. Exclusion criteria for
this study were patients with upper and lower respiratory tract disease, inflammatory disease in the nose
and sinuses, allergic rhinitis, nasal polyps, alcohol
and drug addiction, mental retardation, Alzheimer's
disease, and psychiatric diseases. In addition, any
patient who had undergone nose surgery or had been
exposed to head trauma was also excluded from the
study. To evaluate the patients' olfactory memories,
The Brief Smell Identification Test (BSIT) was used
30 min before surgery. Written consent of all the
patients included into the study was obtained after
providing adequate information. Participants were
asked to read the instructions on the front side of the
booklet so they would know how the test would be
performed.
This test uses a 12-page booklet. There is one
label on every page of this booklet, and four answer
choices of smelling substance names are listed as a,
b, c, and d. The label was scratched with the aid of a
fine-tipped pen, and the patient sniffed the resulting
odor. If the odor perceived by the patient was not
listed on the page, participants were instructed to
select the closest choice instead. These processes
were repeated for all 12 pages in the booklet, and the
Results
Forty patients were included in the study. The
demographic data of the patients are shown in the
table (Table 1). (P>0.05). The patients’ average preoperative and intraoperative heart rates were 84.1 ±
18.8 and 78.3 ± 16.0, respectively (p>0.05) while the
mean preoperative and intraoperative arterial pressures were 94.5 ± 20.5 and 84.4 ± 16.4, respectively
(p>0.05).
In the evaluation of olfactory memory, BSIT
scores measured before surgery were considered as a
baseline, and compared with the BSIT scores measured when the postoperative Aldrete evaluation
duration became 10. When we compared the percentage of identification of odors by the patients,
there was no statistically significant difference
between the pre and the postoperative periods.
(P>0.05) (Table 2). Preoperatively, the rate of correct
answers of patients to the BSIT test was found as
91.4%, this rate was 90.8% after the operation.
Effects of isoflurane on postoperative olfactory memory
455
Patients experienced difficulty in recognizing
the smell of Leather. In preoperative period, the ratio
was 77.5% and post-operatively 77.5%.
Number of patients (n)
40
Age
38.4±13.8
Height
167.1±8.1
Weight
77.2±13.1
Gender (Male/ Female)
24/26
Duration of surgery (min)
66.1±27.5
Type of surgery
Head and neck surgery (except the
mouth and nose surgery)
20 (50%)
Abdominal surgery
5(12.5%)
urological surgery
15(37.5%)
Table 1: The demographic characteristics of patients and
the mean values (Mean±SD,n).
Item
No
Odor
Preoperative
n(%)
Postoperative
Aldrete scores 10
n(%)
1
Mint
38(95)
9(97.5)
2
Banana
38(95)
37(92.5)
3
Clove
39(97.5)
37(92.5)
4
Leather
31(77.5)
31(77.5)
5
Strawberry
33(82.5)
34(85)
6
Pine
39(97.5)
38(95)
7
Cinnamon
35(87.5)
35(87.5)
8
Soot
39(97.5)
39(97.5)
9
Lemon
36(90)
37(92.5)
10
Soap
40(100)
39(97.5)
11
Baby powder
38(95)
39(97.5)
12
Rose
33(82.5)
31(77.5)
Total
Correct identification
439 (91.4)
436(90.8)
P value
P>0.05
Table 2: Preoperative BSIT score and postoperative
BSIT score when it reaches 10 of Aldrete score.
n(%):The number of patients’ correct answers to odorous substances (n) and the percentage of correct answers(%).
Discussion
The perception of odor impulses and olfactory
memory are important for people. A decrease in
one’s sense of odor (hyposmia), the complete
absence of a sense of odor (anosmia), or not being
able to distinguish odours (dysosmia) affects the
quality of life(11). Anosmia cases have been reported
after general anesthesia(8, 9). The authors of that study
used fentanyl, propofol, and sevoflurane to maintain
general anesthesia(8, 9).
It is known that, volatile anesthetics affect
memory and learning functions. Volatile anesthetics
have shown their effects via the gamma-aminobutyric acidergic (GABAergic), glutamatergic, and
adrenergic neurotransmitter system(12, 13). In particular,
it has been reported that, GABA ergic system is
related with learning and olfactory memory (14).
Isoflurane is an inhalation agent commonly used in
general anesthesia. Isoflurane has been blamed for
the development of neurodegeneration in human
neuroglioma cells when used at a concentration of
2%(15). It has been reported that isoflurane affected
the levels of acetylcholine in brain tissue and also
impaired learning and memory functions when used
in high doses(16, 17).
In a study conducted by Pearce RA et al. in rats,
isoflurane impaired odors discrimination by affecting
long-term memory (24 hours after anesthesia)(18). In
our study, we investigated the short-term olfactory
memory. All patients have reached the value of 10 in
Alderete Score before 24th hours postoperatively,
and we have repeated BSIT test at that time. It has
been reported that isoflurane may affect olfactory
memory in animal studies, but we could not find any
clinical studies on this issue in our literature review.
In an animal study conducted by Jugovac et al. the
electroencephalographic effect of four anesthetic
agents infused intracerebro ventricularly (pentobarbital, propofol, fentanyl, and midazolam) were examined. The study reported that fentanyl and propofol
depressed olfactory response(19).
In our study, we used propofol and fentanyl for
induction, but our study showed that these agents did
not affect olfactory memory. Demirhan et al. evaluated olfactory memory, using Turkish version of BSIT
test after spinal anesthesia and reported that it does
not affect olfactory memory(7).
In a randomized clinical trial(6), the olfactory
memories of three groups were compared after
epidural anesthesia, total intravenous anesthesia with
propofol, and anesthesia induced with sevoflurane.
Minor cases whose operation duration was expected
to last from 40 to 120 minutes were included in the
study. Olfactory memory was evaluated 30 minutes
and 3 hours after the operation, and was impaired in
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Murat Bilgi, Abdullah Demirhan et Al
the group for which sevoflurane was used both 30
minutes and 3 hours postoperatively. In their study,
the University of Pennsylvania Smell Identification
Test (UPSIT) was used(6). Another commonly used
test to evaluate olfactory function is the BSIT(20). This
test, which includes 12 different odors, is called as
“the Cross-Cultural Smell Identification Test” (CCSIT). This test is different for each culture, and it
contains local odors(20, 21).
In a previous study, the sensitivity and specificity of the BSIT was reported to be 82%(22). In our
study, we used the Turkish version of the BSIT.
Main limitations of our study are the use of
only one concentration of isoflurane (1.2%), untested
long-term olfactory memory, and relatively small
sample size.
In conclusion, we demonstrated for the first
time in the literature that general anesthesia using
isoflurane (1.2%) did not affect short-term olfactory
memory. Further studies with larger sample size will
be necessary to confirm our findings.
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11)
12)
13)
14)
15)
16)
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_________
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MURAT BILGI
Department of Anesthesiology and Reanimation
Abant Izzet Baysal University Medical School
14280 Golkoy
BOLU
(Turkey)