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

Overview

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.

Full Title of Study: “Evaluation of Neurotoxic Effect of Sevoflurane-Based Anaesthesia Guided by Significant Short-Term Olfactory Identification Impairment in Old Age”

Study Type

  • Study Type: Observational [Patient Registry]
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: September 1, 2018

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.

Interventions

  • Drug: Sevoflurane
    • 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.

Arms, Groups and Cohorts

  • control group
    • regional anesthesia
  • general anesthesia(S)
    • general anesthesia with sevoflurane
  • general anesthesia(I)
    • general anesthesia with isoflurane
  • total intravenous anesthesia
    • total intravenous anesthesia with propofol.

Clinical Trial Outcome Measures

Primary Measures

  • 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)
    • 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.
  • The changes in olfactory threshold
    • Time Frame: basically at 12 hours preoperatively (T0), then 3 hours postoperatively (T1) and at the time of discharge or postoperative 3 days (T2)
    • 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.
  • The changes in olfactory identification
    • Time Frame: basically at 12 hours preoperatively (T0), then 3 hours postoperatively (T1) and at the time of discharge or postoperative3 days (T2)
    • 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.

Secondary Measures

  • The changes in olfactory melatonin levels
    • Time Frame: 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)
    • Melatonin levels were measured in plasma by the enzyme-linked immunosorbent assay (ELISA) (IBL, Hamburg, Germany).

Participating in This Clinical Trial

Inclusion 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, – minor urological procedures Exclusion Criteria:

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

Gender Eligibility: All

Minimum Age: 60 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Tanta University
  • Collaborator
    • Amer Galal Younis,MD
  • Provider of Information About this Clinical Study
    • Principal Investigator: Ahmed Said Elgebaly,MD, director – Tanta University
  • Overall Official(s)
    • ahmed S Elgebaly, MD, Study Director, Tanta University

Citations Reporting on Results

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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.

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.

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.

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.

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.

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.

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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.

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.

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.

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.

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.

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.

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