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Postoperative Cognitive DysfunctionProDex-POCDNCT05398757

Propofol and Dexmedetomidin vs Midazolam Intraoperative Sedation and POCD

A study testing Mini mental state exame (MMSE), Digit Symbol Substitution Test (DSST) and Numeric rating Scale (NRS) in people with Postoperative Cognitive Dysfunction and Postoperative Pain, Acute, run by Osijek University Hospital at 1 site in Croatia.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This study will examine the effect of intraoperative sedation with midazolam, propofol and dexemdetomidine on the occurrence of postoperative cognitive impairment in patients undergoing surgical treatment of pertrochanteric fracture of the femur. Read more about this study

Who is it for?
Ages 65 years and older
What is being tested?
Mini mental state exame (MMSE), Digit Symbol Substitution Test (DSST) and Numeric rating Scale (NRS)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteCroatia
Study dates
1 Jul 2022to 1 Mar 2024
Phase
Interventional
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 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • Pertrochanteric fracture surgery
  • Informed consent signed

Who cannot join

  • MMSE before surgery < 17
  • Allergy on midazolam, propofol or dexemdetomidine
  • Contraindication for neuroaxial anesthesia

Trial locations and contacts

1 site in 1 country.

Croatia1 site
  • University Hospital Osijek

    Osijek, 31000

Other trials in Croatia

About this study

Official title: The Effect of Intraoperative Administration of Dexmedetomidine, Propofol and Midazolam on Postoperative Levels of Inflammatory Markers and Development of Postoperative Cognitive Dysfunction After Pertrochanteric Fracture Surgery.

This study will examine the effect of intraoperative sedation with midazolam, propofol and dexemdetomidine on the occurrence of postoperative cognitive impairment in patients undergoing surgical treatment of pertrochanteric fracture of the femur.

Read the detailed description

Patients undergoing surgical treatment of pertrochanteric femoral fracture by intramedullary fixation will be included in the study. Patients will be older than 65 years and will belong to class I to III anesthesia risk according to the ASA classification. All patients included in the study will sign informed consent. Patients with dementia, mental illness, psychoorganically altered patients, and patients with a contraindication to dexmedetomidine, propofol, midazolam or with a contraindication to spinal anesthesia will be excluded from the study. All patients included in the study will have their blood taken for laboratory analysis of red blood cells, leukocytes, CRP, PCT, ChE and IL-6. Analyzes will be performed before the procedure, on the 1st, 3rd and 5th postoperative day. All patients will be tested for Mini mental state exame (MMSE) score before surgery to rule out pre-existing cognitive impairment, and those patients who have an MMSE value <17 prior to surgery will be excluded from the study. In premedication, patients will be randomized using three envelopes selected by the blind researcher for the contents of each envelope. According to envelope patients will be divided into three groups: dexmedetomidine group (DS), propofol group (PS) and midazolam group (MS). Neuroaxial spinal block with intrathecal administration of 12.5 - 15 mg 0.5% levobupivacaine in the intervertebral space L3 / L4 or L4 / L5 will be the technique of anesthesia. After spinal block, patients in the DS group will receive a continuous infusion of dexmedetomidine at a dose of 0.5 mcg / kg / h, patients in the PS group will receive a continuous infusion of propofol at a dose of 25-75 mcg / kg / min, while patients in the MS group will receive 0.05-0.07 mg / kg bolus i.v. midazolam. The total dose administered and the duration of surgery will be recorded. The volume of intraoperatively administered crystalloids or blood products will be recorded in all patients included in the study. In the postoperative period, pain will be measured with a numerical rating scale (NRS) 4, 8, 12 and 24 hours after surgery. All patients will receive the usual postoperative analgesia with metamizole and tramadol according to the protocol of the Department. On the 1st, 3rd and 5th postoperative days in the morning between 8.00 and 10.00, all patients will be tested for MMSE and Digit Symbol Substitution Test (DSST) score. A researcher who will evaluate MMSE and DSST values in the postoperative period will be blind to the drug that patients received intraoperatively.

Being tested
Mini mental state exame (MMSE), Digit Symbol Substitution Test (DSST), Numeric rating Scale (NRS), Postoperative inflammation, Midazolam
Keywords
Postoperative Cognitive Dysfunction, Postoperative pain, Pertrochanteric Fracture, IL-6, Dexmedetomidin, Propofol, Midazolam, Sedation
Medical subject headings
Postoperative Cognitive Complications, Pain, Postoperative

What participants receive

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

  • Mini mental state exame (MMSE)Behavioural

    Before the operation, and on the 1st, 3rd and 5th day after the operation, the Mini mental state exam (MMSE) score will be measured

  • Digit Symbol Substitution Test (DSST)Behavioural

    Before the operation, and on the 1st, 3rd and 5th day after the operation, the Digit Symbol Substitution Test (DSST) score will be measured

  • Numeric rating Scale (NRS)Diagnostic test

    4h, 8h, 12h and 24h after surgery, pain in all patients will be assessed by the NRS scale.

  • Postoperative inflammationDiagnostic test

    All patients included in the study will have their blood taken for laboratory analysis of red blood cells, leukocytes, CRP, PCT, ChE and IL-6. Analyzes will be performed before the procedure, on the 1st, 3rd and 5th postoperative day.

  • MidazolamDrug

    Also called Control - group M

    For sedation during surgery, patients in midazolam group will receive i.v. midazolam in dose 0.05 - 0.07 mg/kg after spinal anesthesia.

  • PropofolDrug

    Also called Group P

    For sedation during surgery, patients in propofol group will receive i.v. propofol in dose 25-27 mcg/kg/min.

  • DexmedetomidinDrug

    Also called Group D

    For sedation during surgery, patients in dexmedetomidin gropu will receive i.v. dexmedetomidin in dose 0.5 mcg/kg/h

Study groups in NCT05398757
Study groupRoleWhat they receive
MidazolamOtherFor sedation during surgery, patients will receive i.v. midazolam in dose 0.05 - 0.07 mg/kg.
Receives: Behavioral: Mini mental state exame (MMSE); Behavioral: Digit Symbol Substitution Test (DSST); Diagnostic Test: Numeric rating Scale (NRS); Diagnostic Test: Postoperative inflammation; Drug: Midazolam
PropofolActive comparatorFor sedation during surgery, patients will receive i.v. propofol in dose 25-27 mcg/kg/min.
Receives: Behavioral: Mini mental state exame (MMSE); Behavioral: Digit Symbol Substitution Test (DSST); Diagnostic Test: Numeric rating Scale (NRS); Diagnostic Test: Postoperative inflammation; Drug: Propofol
DexmedetomidinActive comparatorFor sedation during surgery, patients will receive i.v. dexmedetomidin in dose 0.5 mcg/kg/h
Receives: Behavioral: Mini mental state exame (MMSE); Behavioral: Digit Symbol Substitution Test (DSST); Diagnostic Test: Numeric rating Scale (NRS); Diagnostic Test: Postoperative inflammation; Drug: Dexmedetomidin

What is being measured

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

  1. Occurrence of postoperative cognitive dysfunction (POCD) measured by MMSE

    The incidence of POCD with respect to intraoperative sedation in the postoperative period will be measured by MMSE test on the first, third and fifth postoperative day. An absolute z-score greater than 1.96 in postoperative testing or a decrease in the postoperative MMSE value by more than 20% relative to the preoperative value will be considered the occurrence of POCD in the postoperative period.

    Measured: 5 days

  2. Occurrence of postoperative cognitive dysfunction (POCD) measured by DSST

    The incidence of POCD with respect to intraoperative sedation in the postoperative period will be measured by DSST on the first, third and fifth postoperative day. An absolute z-score greater than 1.96 in postoperative testing or a decrease in the postoperative DSST value by more than 20% relative to the preoperative value will be considered the occurrence of POCD in the postoperative period.

    Measured: 5 days

  3. Postoperative inflammation measured by serum CRP levels

    Postoperative inflammation with respect to intraoperative sedation will be assessed by serum levels of CRP at postoperative day 1, 3 and 5. CRP > 50 mg/L and rising dynamic of CRP in postoperative serial measurements will be considered as systemic inflammation state.

    Measured: 5 days

  4. Postoperative inflammation measured by white blood cells count

    Postoperative inflammation with respect to intraoperative sedation will be assessed by serum levels of white blood cells. Leukocytes > 12.000/mm3 or < 4.000/mm3 in postoperative serial measurements will be considered as systemic inflammation state.

    Measured: 5 days

  5. Postoperative inflammation measured by serum IL-6 levels

    Postoperative inflammation with respect to intraoperative sedation will be assessed by serum levels IL-6 at postoperative day 1, 3 and 5. Continuous increase of IL-6 in postoperative serial measurements will be considered as systemic inflammation state.

    Measured: 5 days

  6. Postoperative inflammation measured by serum cholinesterase activity

    Postoperative inflammation with respect to intraoperative sedation will be assessed by serum cholinesterase activity at postoperative day 1, 3 and 5. Cholinesterase activity < 4000 U/L in postoperative serial measurements will be considered as systemic inflammation state.

    Measured: 5 days

  7. Postoperative inflammation measured by serum PCT levels

    Postoperative inflammation with respect to intraoperative sedation will be assessed by serum levels of PCT at postoperative day 1, 3 and 5. PCT > 0.5 ng/ml and continuous increase in postoperative serial measurements will be considered as systemic inflammation state.

    Measured: 5 days

Secondary outcomes (1)
  1. Postoperative pain

    Postoperative pain with respect to intraoperative sedation will be examined by Numeric rating scale (NRS) 4, 8, 12 and 24 hours after surgery. NRS is a scale from 0 to 10, where 0 means no pain and 10 means the strongest pain. NRS above or equal to 4 will be considered inadequate postoperative analgesia.

    Measured: 24 hours

Timeline

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

  1. First posted1 Jun 2022
  2. Study start1 Jul 2022
  3. Primary completion1 Mar 2024 (estimated)
  4. Study completion1 Mar 2024 (estimated)

Why it stopped: Too long recruitment period due to small number of patients

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05398757
Sponsor's protocol ID
OsijekPOCD
Acronym
ProDex-POCD
Status last verified
Sep 2024
First submitted
19 Apr 2022
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Monk TG, Price CC. Postoperative cognitive disorders. Curr Opin Crit Care. 2011 Aug;17(4):376-81. doi: 10.1097/MCC.0b013e328348bece.

    PubMed 21716111
  • Urits I, Orhurhu V, Jones M, Hoyt D, Seats A, Viswanath O. Current Perspectives on Postoperative Cognitive Dysfunction in the Ageing Population. Turk J Anaesthesiol Reanim. 2019 Dec;47(6):439-447. doi: 10.5152/TJAR.2019.75299. Epub 2019 Sep 2.

    PubMed 31828240
  • Xiao QX, Liu Q, Deng R, Gao ZW, Zhang Y. Postoperative cognitive dysfunction in elderly patients undergoing hip arthroplasty. Psychogeriatrics. 2020 Jul;20(4):501-509. doi: 10.1111/psyg.12516. Epub 2020 Jan 24.

    PubMed 31976614
  • Rasmussen LS, Larsen K, Houx P, Skovgaard LT, Hanning CD, Moller JT; ISPOCD group. The International Study of Postoperative Cognitive Dysfunction. The assessment of postoperative cognitive function. Acta Anaesthesiol Scand. 2001 Mar;45(3):275-89. doi: 10.1034/j.1399-6576.2001.045003275.x.

    PubMed 11207462
  • Tombaugh TN, McIntyre NJ. The mini-mental state examination: a comprehensive review. J Am Geriatr Soc. 1992 Sep;40(9):922-35. doi: 10.1111/j.1532-5415.1992.tb01992.x.

    PubMed 1512391
  • van Sinderen K, Schwarte LA, Schober P. Diagnostic Criteria of Postoperative Cognitive Dysfunction: A Focused Systematic Review. Anesthesiol Res Pract. 2020 Nov 16;2020:7384394. doi: 10.1155/2020/7384394. eCollection 2020.

    PubMed 33281900
  • Wang K, Wu M, Xu J, Wu C, Zhang B, Wang G, Ma D. Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis. Br J Anaesth. 2019 Dec;123(6):777-794. doi: 10.1016/j.bja.2019.07.027. Epub 2019 Oct 24.

    PubMed 31668347
  • Mei B, Li J, Zuo Z. Dexmedetomidine attenuates sepsis-associated inflammation and encephalopathy via central alpha2A adrenoceptor. Brain Behav Immun. 2021 Jan;91:296-314. doi: 10.1016/j.bbi.2020.10.008. Epub 2020 Oct 8.

    PubMed 33039659
  • Hohener D, Blumenthal S, Borgeat A. Sedation and regional anaesthesia in the adult patient. Br J Anaesth. 2008 Jan;100(1):8-16. doi: 10.1093/bja/aem342.

    PubMed 18070783
  • Tobias JD, Leder M. Procedural sedation: A review of sedative agents, monitoring, and management of complications. Saudi J Anaesth. 2011 Oct;5(4):395-410. doi: 10.4103/1658-354X.87270.

    PubMed 22144928
  • Chen RM, Chen TG, Chen TL, Lin LL, Chang CC, Chang HC, Wu CH. Anti-inflammatory and antioxidative effects of propofol on lipopolysaccharide-activated macrophages. Ann N Y Acad Sci. 2005 May;1042:262-71. doi: 10.1196/annals.1338.030.

    PubMed 15965071
  • Kochiyama T, Li X, Nakayama H, Kage M, Yamane Y, Takamori K, Iwabuchi K, Inada E. Effect of Propofol on the Production of Inflammatory Cytokines by Human Polarized Macrophages. Mediators Inflamm. 2019 Mar 17;2019:1919538. doi: 10.1155/2019/1919538. eCollection 2019.

    PubMed 31007601

Questions about this trial

What is this clinical trial studying?

A study testing Mini mental state exame (MMSE), Digit Symbol Substitution Test (DSST) and Numeric rating Scale (NRS) in people with Postoperative Cognitive Dysfunction and Postoperative Pain, Acute, run by Osijek University Hospital at 1 site in Croatia.

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 2 inclusion and 3 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: withdrawn, as of the sponsor's last update on 19 Sep 2024. 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 Croatia. 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 was withdrawn before enrolling participants, so there are no results.

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?

Occurrence of postoperative cognitive dysfunction (POCD) measured by MMSE (time frame: 5 days). The study lists 7 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 NCT05398757, which also lists 12 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 19 Sep 2024.

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