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Neurotoxic Effect of Sevoflurane-Based AnaesthesiaNCT03726580

Evaluation of Neurotoxic Effect of Sevoflurane-Based AnaesthesiaGuided by Short-Term Olfactory Identification

An observational study of Neurotoxic Effect of Sevoflurane-Based Anaesthesia, run by Tanta University at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Nowadays there is increasing doubts about the safety of anesthesia . Anesthesiologists have to console the worried patients, who are anxious about the potential risks of anesthetic-induced brain damage, by suggesting that any detrimental effects would be "mild".Anesthetics are responsible for postoperative taste and… Read more about this study

Who is it for?
Ages 60 to 75 yearsHealthy volunteers can take part
What is being tested?
Sevoflurane
Type of treatment
Injection or infusion
How many people
600 participants
Where
1 siteEgypt
Study dates
1 Mar 2017to 1 Oct 2018
How long will I take part?
6 Months
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Six hundred patients of both sex with inclusion following criteria: American Society of Anaesthesiologists I and II physical status aged from 60 to 75years scheduled for elective surgery with the anticipated duration of 100-120 min (surgical procedures included hernia repair, varicose vein surgery, incisional hernia repair, minor gynecological procedures, lower limb orthopedic procedures, and minor urological procedures)

Who may be able to join

  • American Society of Anaesthesiologists I and II physical status
  • aged from 60 to 75years
  • scheduled for elective surgery with the anticipated duration of 100-120 min.
  • surgical procedures included hernia repair,
  • varicose vein surgery,
  • incisional hernia repair,
Show all 9Show fewer
  • minor gynecological procedures,
  • lower limb orthopedic procedures,
  • minor urological procedures

Who cannot join

  • Patients with recent airway infection,
  • allergic rhinitis,
  • nasal polyps,
  • history of alcoholism,
  • smoking,
  • mental retardation,
Show all 9Show fewer
  • psychiatric illness,
  • neurosurgical or oto-rhino-laryngeal surgery
  • patients with a history of olfactory deficits and cognitive impairment

Trial locations and contacts

1 site in 1 country.

Egypt1 site
  • Ahmed Said Elgebaly

    Tanta

Other trials in Egypt

About this study

Official title: Evaluation of Neurotoxic Effect of Sevoflurane-Based Anaesthesia Guided by Significant Short-Term Olfactory Identification Impairment in Old Age

Nowadays there is increasing doubts about the safety of anesthesia . Anesthesiologists have to console the worried patients, who are anxious about the potential risks of anesthetic-induced brain damage, by suggesting that any detrimental effects would be "mild".Anesthetics are responsible for postoperative taste and odor defects and cognitive dysfunction.

Read the detailed description

Aims: The aim of this study is to assess the effect of isoflurane, sevoflurane, propofol and regional anesthesia on the olfactory threshold, olfactory identification and endocrine regulation of associative memory in the postoperative period in old age group.

Methods: 600 patients (> 60years ) fulfilling the criteria of the American society of anesthesiologists and II status were selected for this prospective single-blinded randomized controlled study. Patients were randomized into one of four groups to receive regional anesthesia (control group), general anesthesia with sevoflurane, general anesthesia with isoflurane and total intravenous anesthesia with propofol.

Mini-Mental State Examination (MMSE), olfactory threshold, and olfactory identification were tested at 12 hours preoperatively (T0), at 3 hours postoperatively (T1) and at the time of discharge or postoperative 3 days (T2). In addition, serum melatonin levels were estimated at T0 and T1.

N-butyl alcohol was used to test the olfactory threshold and the Pocket Smell Test TM series (PSTs) was used to test olfactory identification. Data were analyzed using the one-way analysis of variance, Kruskal-Wallis or Mann-Whitney tests.

Being tested
Sevoflurane
Keywords
General anesthesia., neurotoxicity,, olfaction,, olfactory identification., sevoflurane.
Medical subject headings
Neurotoxicity Syndromes, Anosmia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SevofluraneDrug

    Also called Isoflurane, Propofol

    Assess the effect of isoflurane, sevoflurane, propofol and regional anesthesia on the olfactory threshold, olfactory identification and endocrine regulation of associative memory in the postoperative period in old age group.

Study groups in NCT03726580
Study groupRoleWhat they receive
control groupregional anesthesia
general anesthesia(S)general anesthesia with sevoflurane
Receives: Drug: Sevoflurane
general anesthesia(I)general anesthesia with isoflurane
total intravenous anesthesiatotal intravenous anesthesia with propofol.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The changes in Mini-Mental State Examination (MMSE)

    Cognitive function evaluated by MMSE scores. The Mini-Mental State Examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used in medicine and allied health to screen for dementia.

    Measured: basically at 12 hours preoperatively (T0), then 3 hours postoperatively (T1) and at the time of discharge or postoperative 3 days (T2)

  2. The changes in olfactory threshold

    Was measured using serial dilutions (10 dilutions) of 4% n-butyl alcohol in deionized water. The test consists of 10 steps. In each step, the odorant and a blank were presented to the participant. The test progressed from weaker-to-stronger concentrations of odorant. Two bottles were presented to each participant, an odorant bottle and an identical bottle filled with distilled water. The participant sniffed each one for approximately 9 s and then chose which one smelled stronger. If the participant was incorrect at one concentration, the next higher concentration was presented. When the correct choice was made, the same concentration of odorant was presented to the participant until four consecutive correct responses were given. The threshold was defined as the butyl alcohol concentration correctly chosen over water in four consecutive trials, and the corresponding number of the concentration was taken as the threshold value.

    Measured: basically at 12 hours preoperatively (T0), then 3 hours postoperatively (T1) and at the time of discharge or postoperative 3 days (T2)

  3. The changes in olfactory identification

    Was assessed using the Pocket Smell TestTM series (PSTs). The test uses four booklets containing labels impregnated with odorous substances. The test is in multiple-choice format, with four written response alternatives for each odor. The odors are released when the labels are scratched. The examiner scraped each target patch and instructed participants to smell the patch and then select the name of the released odor from among four alternatives. Olfactory identification tested using the (PSTs) assessed both the recent memory and the remote memory of the patient as it contained odors which were a mixture of both the familiar and unfamiliar ones to the study population. Here, it is not utilized to identify patients with anosmia or hyposmia. Instead, the (PSTs) is used as a linear, unbiased unidimensional Rasch measure of human smell recognition abilities.

    Measured: basically at 12 hours preoperatively (T0), then 3 hours postoperatively (T1) and at the time of discharge or postoperative3 days (T2)

Secondary outcomes (1)
  1. The changes in olfactory melatonin levels

    Melatonin levels were measured in plasma by the enzyme-linked immunosorbent assay (ELISA) (IBL, Hamburg, Germany).

    Measured: serum melatonin levels were estimated basically at 12 hours preoperatively (T0), then 3 hours postoperatively (T1) and at the time of discharge or postoperative3 days (T2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2018
  2. Study start1 Mar 2017
  3. Primary completion1 Sep 2018
  4. Study completion1 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
600 participants (actual)
Target duration
6 Months
IDs, dates and publications
ClinicalTrials.gov ID
NCT03726580
Sponsor's protocol ID
TantaF
Status last verified
Oct 2018
First submitted
29 Oct 2018
Last updated
1 Nov 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Friedrich H, Caversaccio M, Landis BN. Olfactory disorders after general anesthesia. J Clin Anesth. 2013 Feb;25(1):73. doi: 10.1016/j.jclinane.2012.07.002. Epub 2012 Dec 12. No abstract available.

    PubMed 23246491
  • Shen X, Liu Y, Xu S, Zhao Q, Guo X, Shen R, Wang F. Early life exposure to sevoflurane impairs adulthood spatial memory in the rat. Neurotoxicology. 2013 Dec;39:45-56. doi: 10.1016/j.neuro.2013.08.007. Epub 2013 Aug 27.

    PubMed 23994303
  • Saravanan B, Kundra P, Mishra SK, Surianarayanan G, Parida PK. Effect of anaesthetic agents on olfactory threshold and identification - A single blinded randomised controlled study. Indian J Anaesth. 2018 Aug;62(8):592-598. doi: 10.4103/ija.IJA_245_18.

    PubMed 30166653
  • Obayashi K, Saeki K, Iwamoto J, Tone N, Tanaka K, Kataoka H, Morikawa M, Kurumatani N. Physiological Levels of Melatonin Relate to Cognitive Function and Depressive Symptoms: The HEIJO-KYO Cohort. J Clin Endocrinol Metab. 2015 Aug;100(8):3090-6. doi: 10.1210/jc.2015-1859. Epub 2015 Jun 8.

    PubMed 26052727
  • Kalsbeek A, Cutrera RA, Van Heerikhuize JJ, Van Der Vliet J, Buijs RM. GABA release from suprachiasmatic nucleus terminals is necessary for the light-induced inhibition of nocturnal melatonin release in the rat. Neuroscience. 1999;91(2):453-61. doi: 10.1016/s0306-4522(98)00635-6.

    PubMed 10366002
  • Lehrner JP, Gluck J, Laska M. Odor identification, consistency of label use, olfactory threshold and their relationships to odor memory over the human lifespan. Chem Senses. 1999 Jun;24(3):337-46. doi: 10.1093/chemse/24.3.337.

    PubMed 10400452
  • Rawal S, Hoffman HJ, Honda M, Huedo-Medin TB, Duffy VB. The Taste and Smell Protocol in the 2011-2014 US National Health and Nutrition Examination Survey (NHANES): Test-Retest Reliability and Validity Testing. Chemosens Percept. 2015 Sep;8(3):138-148. doi: 10.1007/s12078-015-9194-7. Epub 2015 Aug 7.

    PubMed 27833669
  • Jackman AH, Doty RL. Utility of a three-item smell identification test in detecting olfactory dysfunction. Laryngoscope. 2005 Dec;115(12):2209-12. doi: 10.1097/01.mlg.0000183194.17484.bb.

    PubMed 16369168
  • Kostopanagiotou G, Kalimeris K, Kesidis K, Matsota P, Dima C, Economou M, Papageorgiou C. Sevoflurane impairs post-operative olfactory memory but preserves olfactory function. Eur J Anaesthesiol. 2011 Jan;28(1):63-8. doi: 10.1097/EJA.0b013e328340702b.

    PubMed 20962652
  • Lotsch J, Reichmann H, Hummel T. Different odor tests contribute differently to the evaluation of olfactory loss. Chem Senses. 2008 Jan;33(1):17-21. doi: 10.1093/chemse/bjm058. Epub 2007 Aug 30.

    PubMed 17761724
  • Lecker I, Yin Y, Wang DS, Orser BA. Potentiation of GABAA receptor activity by volatile anaesthetics is reduced by alpha5GABAA receptor-preferring inverse agonists. Br J Anaesth. 2013 Jun;110 Suppl 1(Suppl 1):i73-81. doi: 10.1093/bja/aet038. Epub 2013 Mar 27.

    PubMed 23535829
  • Ren Y, Zhang FJ, Xue QS, Zhao X, Yu BW. Bilateral inhibition of gamma-aminobutyric acid type A receptor function within the basolateral amygdala blocked propofol-induced amnesia and activity-regulated cytoskeletal protein expression inhibition in the hippocampus. Anesthesiology. 2008 Nov;109(5):775-81. doi: 10.1097/ALN.0b013e31818a37c4.

    PubMed 18946287
  • Salmi E, Kaisti KK, Metsahonkala L, Oikonen V, Aalto S, Nagren K, Hinkka S, Hietala J, Korpi ER, Scheinin H. Sevoflurane and propofol increase 11C-flumazenil binding to gamma-aminobutyric acidA receptors in humans. Anesth Analg. 2004 Nov;99(5):1420-1426. doi: 10.1213/01.ANE.0000135409.81842.31.

    PubMed 15502041
  • Alkire MT, Gorski LA. Relative amnesic potency of five inhalational anesthetics follows the Meyer-Overton rule. Anesthesiology. 2004 Aug;101(2):417-29. doi: 10.1097/00000542-200408000-00023.

    PubMed 15277925
  • Shen FY, Song YC, Guo F, Xu ZD, Li Q, Zhang B, Ma YQ, Zhang YQ, Lin R, Li Y, Liu ZQ. Cognitive Impairment and Endoplasmic Reticulum Stress Induced by Repeated Short-Term Sevoflurane Exposure in Early Life of Rats. Front Psychiatry. 2018 Aug 2;9:332. doi: 10.3389/fpsyt.2018.00332. eCollection 2018.

    PubMed 30116207

Questions about this trial

What is this clinical trial studying?

An observational study of Neurotoxic Effect of Sevoflurane-Based Anaesthesia, run by Tanta University at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The changes in Mini-Mental State Examination (MMSE) (time frame: basically at 12 hours preoperatively (T0), then 3 hours postoperatively (T1) and at the time of discharge or postoperative 3 days (T2)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03726580, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2018.

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