The Association Between Telomere Length and Propofol Dose in Anesthesia-induction

NCT ID: NCT03429309

Last Updated: 2018-02-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2018-02-28

Brief Summary

Telomeres are protein-bound DNA repeat structures at the end of eukaryotic chromosomes that are made up of a simple repetitive sequence (in humans, TTAGGG) and regulate cellular replicative capacity and cellular proliferation, protect chromosomes from fusing together during mitosis and maintain genomic stability, and prevent the loss of genetic data. Telomeres are specialized repetitive DNA sequences, typically ranging from 5,000 to 15,000 bp in humans, which are the critical chromosome capping DNA sequences. The loss of telomere repeats diminishes telomeric functional capacity.Telomere length(TL) is important in determining telomere function.This is known as the end replication problem and results in a gradual decline in TL over time. Consequently,leukocyte TL shortens in a predictable way with age by roughly 20-40 base pairs per year. Cellular senescence and subsequent cell death often occur when the mean telomere length reaches a critical value.Shortened telomeres and lower telomerase are linked to age-related risk factors and disease.Peripheral blood leukocyte express telomerase at low levels, which can be measured over a short duration (hours) to demonstrate immediate, short-term changes. Shorter mean leukocyte telomere length has been shown to be associated with risk of several age-related diseases.The dosage of propofol gradually reduced with the aging process. However,it is not known whether the telomere length and variation of telomerase in PBL relate to the dosage of propofol and time of consciousness disappearance in anesthesia induction. In this exploratory study, the investigators examined that the changes of peripheral blood leukocyte telomere length was associated with the dosage of propofol and time of consciousness disappearance in anesthesia induction.

Given the importance of telomeres in nuclear and cellular function, the central role of telomere length in determining telomere function,the investigator study that the changes of telomere length in peripheral blood leukocyte of patients are associated with the dosage of propofol in anesthesia induction.

Detailed Description

A hundred patients with the American Society of Anesthesiologists (ASA) physical status I-II, aged from 18 to 80 years, gave an informed-written consent to participate.Testing took place in the morning after an overnight fast. Patients were scheduled for elective surgical procedures. After arrival to the operating theater, the peripheral venous line for fluid and drug administration was inserted. The electrocardiogram, heart rate, a noninvasive blood pressure, a pulse oximeter and bispectral (BIS) Index were monitored continuously. 100% oxygen was given for 3 min by face mask. Anesthesia was induced by intravenous infusion of propofol via the syringe pump at a rate of 30 mg/kg/h. Recordings began before propofol induction started. After the start of the propofol infusion and BIS Index at 80, patients were asked loudly "open eyes" and examined eyelash reflex at 15-s intervals until loss of consciousness (unresponsiveness to the verbal command, no spontaneous movements and loss of eyelash reflex); and recordings of the heart rate, a noninvasive blood pressure and BIS Index were obtained during awake baseline and unconsciousness induced by propofol. Propofol dosage and consciousness disappearance time were recorded after propofol-induced loss of consciousness. The commands were spoken in a loud voice by the investigator and were repeated up to three times, if the subject failed to respond. A subject who obeyed command was considered conscious. The BIS index is useful, and a reliable and sensitive indicator for assessing the level of consciousness during sedation and hypnosis with propofol so that the investigators recorded BIS index to evaluate level of consciousness. To minimize artifacts, patients were instructed not to open their eyes, talk, or move during the heart rate, a noninvasive blood pressure and BIS Index recordings before the propofol infusion and the sedation level was assessed until the patient's unconsciousness.

Conditions

General Anesthesia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Anesthesia-induction with propofol

Group Type: OTHER

Propofol

Intervention Type: DRUG

Anesthesia was induced by intravenous infusion of propofol via the syringe pump at a rate of 30 mg/kg/h.

Interventions

Propofol

Anesthesia was induced by intravenous infusion of propofol via the syringe pump at a rate of 30 mg/kg/h.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients were scheduled for elective surgical procedures

Exclusion Criteria

• patients with known cardiac, pulmonary, renal disease, hearing disorders or neurological diseases, diabetes, and patients taking drugs affecting to the central nervous system or consuming more than 20 g alcohol daily, a body mass index>30

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangzhou General Hospital of Guangzhou Military Command

OTHER

Sponsor Role: lead

Responsible Party

Weifeng Tu

Chief physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Guangzhou General Hospital of Guangzhou Military Command

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Weifeng Tu, PhD

Role: CONTACT

wftuyx02@163.com

+8613922116606

Facility Contacts

Weifeng Tu, PhD

Role: primary

wftuyx02@163.com

+8613922116606

References

Blackburn EH, Greider CW, Szostak JW. Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. Nat Med. 2006 Oct;12(10):1133-8. doi: 10.1038/nm1006-1133. No abstract available.

Reference Type: BACKGROUND

PMID: 17024208 (View on PubMed)

Aubert G, Lansdorp PM. Telomeres and aging. Physiol Rev. 2008 Apr;88(2):557-79. doi: 10.1152/physrev.00026.2007.

Reference Type: BACKGROUND

PMID: 18391173 (View on PubMed)

Biegler KA, Anderson AK, Wenzel LB, Osann K, Nelson EL. Longitudinal change in telomere length and the chronic stress response in a randomized pilot biobehavioral clinical study: implications for cancer prevention. Cancer Prev Res (Phila). 2012 Oct;5(10):1173-82. doi: 10.1158/1940-6207.CAPR-12-0008. Epub 2012 Jul 24.

Reference Type: BACKGROUND

PMID: 22827974 (View on PubMed)

Starkweather AR, Alhaeeri AA, Montpetit A, Brumelle J, Filler K, Montpetit M, Mohanraj L, Lyon DE, Jackson-Cook CK. An integrative review of factors associated with telomere length and implications for biobehavioral research. Nurs Res. 2014 Jan-Feb;63(1):36-50. doi: 10.1097/NNR.0000000000000009.

Reference Type: BACKGROUND

PMID: 24335912 (View on PubMed)

Munoz P, Blanco R, Blasco MA. Role of the TRF2 telomeric protein in cancer and ageing. Cell Cycle. 2006 Apr;5(7):718-21. doi: 10.4161/cc.5.7.2636. Epub 2006 Apr 1.

Reference Type: BACKGROUND

PMID: 16582635 (View on PubMed)

Codd V, Mangino M, van der Harst P, Braund PS, Kaiser M, Beveridge AJ, Rafelt S, Moore J, Nelson C, Soranzo N, Zhai G, Valdes AM, Blackburn H, Mateo Leach I, de Boer RA, Kimura M, Aviv A; Wellcome Trust Case Control Consortium; Goodall AH, Ouwehand W, van Veldhuisen DJ, van Gilst WH, Navis G, Burton PR, Tobin MD, Hall AS, Thompson JR, Spector T, Samani NJ. Common variants near TERC are associated with mean telomere length. Nat Genet. 2010 Mar;42(3):197-9. doi: 10.1038/ng.532. Epub 2010 Feb 7.

Reference Type: BACKGROUND

PMID: 20139977 (View on PubMed)

Cesare AJ, Reddel RR. Alternative lengthening of telomeres: models, mechanisms and implications. Nat Rev Genet. 2010 May;11(5):319-30. doi: 10.1038/nrg2763. Epub 2010 Mar 30.

Reference Type: BACKGROUND

PMID: 20351727 (View on PubMed)

Capezzone M, Cantara S, Marchisotta S, Filetti S, De Santi MM, Rossi B, Ronga G, Durante C, Pacini F. Short telomeres, telomerase reverse transcriptase gene amplification, and increased telomerase activity in the blood of familial papillary thyroid cancer patients. J Clin Endocrinol Metab. 2008 Oct;93(10):3950-7. doi: 10.1210/jc.2008-0372. Epub 2008 Jul 29.

Reference Type: BACKGROUND

PMID: 18664542 (View on PubMed)

Epel ES, Lin J, Dhabhar FS, Wolkowitz OM, Puterman E, Karan L, Blackburn EH. Dynamics of telomerase activity in response to acute psychological stress. Brain Behav Immun. 2010 May;24(4):531-9. doi: 10.1016/j.bbi.2009.11.018. Epub 2009 Dec 16.

Reference Type: BACKGROUND

PMID: 20018236 (View on PubMed)

Humphreys J, Epel ES, Cooper BA, Lin J, Blackburn EH, Lee KA. Telomere shortening in formerly abused and never abused women. Biol Res Nurs. 2012 Apr;14(2):115-23. doi: 10.1177/1099800411398479. Epub 2011 Mar 8.

Reference Type: BACKGROUND

PMID: 21385798 (View on PubMed)

Other Identifiers

Telomere length and propofol

Identifier Type: -

Identifier Source: org_study_id