Propofol and Dexmedetomidin vs Midazolam Intraoperative Sedation and POCD

NCT05398757 | Withdrawn

• 1 other identifier: OsijekPOCD
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Postoperative Cognitive Dysfunction; Postoperative Pain, Acute; Pertrochanteric Fracture

Keywords

Postoperative Cognitive Dysfunction; Postoperative pain; Pertrochanteric Fracture; IL-6; Dexmedetomidin; Propofol; Midazolam; Sedation

Outcome Measures

Primary Outcomes (7)

• 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.

  5 days

• 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.

  5 days

• 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.

  5 days

• 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.

  5 days

• 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.

  5 days

• 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.

  5 days

• 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.

  5 days

Secondary Outcomes (1)

• Postoperative pain

  24 hours

Study Arms (3)

Midazolam

OTHER

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

Behavioral: Mini mental state exame (MMSE); Behavioral: Digit Symbol Substitution Test (DSST); Diagnostic Test: Numeric rating Scale (NRS); Diagnostic Test: Postoperative inflammation; Drug: Midazolam

Propofol

ACTIVE COMPARATOR

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

Behavioral: Mini mental state exame (MMSE); Behavioral: Digit Symbol Substitution Test (DSST); Diagnostic Test: Numeric rating Scale (NRS); Diagnostic Test: Postoperative inflammation; Drug: Propofol

Dexmedetomidin

ACTIVE COMPARATOR

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

Behavioral: Mini mental state exame (MMSE); Behavioral: Digit Symbol Substitution Test (DSST); Diagnostic Test: Numeric rating Scale (NRS); Diagnostic Test: Postoperative inflammation; Drug: Dexmedetomidin

Interventions

Mini mental state exame (MMSE) BEHAVIORAL

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

Dexmedetomidin; Midazolam; Propofol

Digit Symbol Substitution Test (DSST) BEHAVIORAL

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

Dexmedetomidin; Midazolam; Propofol

Numeric rating Scale (NRS) DIAGNOSTIC_TEST

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

Dexmedetomidin; Midazolam; Propofol

Postoperative inflammation DIAGNOSTIC_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.

Dexmedetomidin; Midazolam; Propofol

Midazolam DRUG

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

Also known as: Control - group M

Midazolam

Propofol DRUG

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

Also known as: Group P

Propofol

Dexmedetomidin DRUG

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

Also known as: Group D

Dexmedetomidin

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Pertrochanteric fracture surgery
• Informed consent signed

You may not qualify if:

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

Sponsors & Collaborators

• Osijek University Hospital: lead
• Josip Juraj Strossmayer University of Osijek: collaborator

Study Sites (1)

University Hospital Osijek

Osijek, 31000, Croatia

Location

Related Publications (12)

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

  PMID: 21716111 BACKGROUND

• 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.

  PMID: 31828240 BACKGROUND

• 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.

  PMID: 31976614 BACKGROUND

• 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.

  PMID: 11207462 BACKGROUND

• 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.

  PMID: 1512391 BACKGROUND

• 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.

  PMID: 33281900 BACKGROUND

• 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.

  PMID: 31668347 BACKGROUND

• 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.

  PMID: 33039659 BACKGROUND

• 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.

  PMID: 18070783 BACKGROUND

• 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.

  PMID: 22144928 BACKGROUND

• 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.

  PMID: 15965071 BACKGROUND

• 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.

  PMID: 31007601 BACKGROUND

MeSH Terms

Conditions

Postoperative Cognitive Complications; Pain, Postoperative

Interventions

Midazolam; Propofol; Dexmedetomidine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Nenad Neskovic, PhD

  University Hospital Osijek

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2022
• First Posted: June 1, 2022
• Study Start: July 1, 2022
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

CR (1)