ProDex-POCD: Propofol and Dexmedetomidin vs Midazolam Intraoperative Sedation and POCD

Sponsor

Osijek University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05398757

Collaborator

Josip Juraj Strossmayer University of Osijek (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

6.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Cognitive Dysfunction Postoperative Pain, Acute Pertrochanteric Fracture	Behavioral: Mini mental state exame (MMSE) Behavioral: Digit Symbol Substitution Test (DSST) Diagnostic Test: Numeric rating Scale (NRS) Diagnostic Test: Postoperative inflammation Drug: Midazolam Drug: Propofol Drug: Dexmedetomidin	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Prevention

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.

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: Midazolam For sedation during surgery, patients will receive i.v. midazolam in dose 0.05 - 0.07 mg/kg.	Behavioral: Mini mental state exame (MMSE) Before the operation, and on the 1st, 3rd and 5th day after the operation, the Mini mental state exam (MMSE) score will be measured Behavioral: Digit Symbol Substitution Test (DSST) Before the operation, and on the 1st, 3rd and 5th day after the operation, the Digit Symbol Substitution Test (DSST) score will be measured Diagnostic Test: Numeric rating Scale (NRS) 4h, 8h, 12h and 24h after surgery, pain in all patients will be assessed by the NRS scale. Diagnostic Test: Postoperative inflammation 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. Drug: Midazolam For sedation during surgery, patients in midazolam group will receive i.v. midazolam in dose 0.05 - 0.07 mg/kg after spinal anesthesia.
Active Comparator: Propofol For sedation during surgery, patients will receive i.v. propofol in dose 25-27 mcg/kg/min.	Behavioral: Mini mental state exame (MMSE) Before the operation, and on the 1st, 3rd and 5th day after the operation, the Mini mental state exam (MMSE) score will be measured Behavioral: Digit Symbol Substitution Test (DSST) Before the operation, and on the 1st, 3rd and 5th day after the operation, the Digit Symbol Substitution Test (DSST) score will be measured Diagnostic Test: Numeric rating Scale (NRS) 4h, 8h, 12h and 24h after surgery, pain in all patients will be assessed by the NRS scale. Diagnostic Test: Postoperative inflammation 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. Drug: Propofol For sedation during surgery, patients in propofol group will receive i.v. propofol in dose 25-27 mcg/kg/min.
Active Comparator: Dexmedetomidin For sedation during surgery, patients will receive i.v. dexmedetomidin in dose 0.5 mcg/kg/h	Behavioral: Mini mental state exame (MMSE) Before the operation, and on the 1st, 3rd and 5th day after the operation, the Mini mental state exam (MMSE) score will be measured Behavioral: Digit Symbol Substitution Test (DSST) Before the operation, and on the 1st, 3rd and 5th day after the operation, the Digit Symbol Substitution Test (DSST) score will be measured Diagnostic Test: Numeric rating Scale (NRS) 4h, 8h, 12h and 24h after surgery, pain in all patients will be assessed by the NRS scale. Diagnostic Test: Postoperative inflammation 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. Drug: Dexmedetomidin For sedation during surgery, patients in dexmedetomidin gropu will receive i.v. dexmedetomidin in dose 0.5 mcg/kg/h

Arm

Intervention/Treatment

Other: Midazolam

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

Behavioral: Mini mental state exame (MMSE)

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

Behavioral: Digit Symbol Substitution Test (DSST)

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

Diagnostic Test: Numeric rating Scale (NRS)

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

Diagnostic Test: Postoperative inflammation

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.

Drug: Midazolam

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

Active Comparator: Propofol

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

Behavioral: Mini mental state exame (MMSE)

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

Behavioral: Digit Symbol Substitution Test (DSST)

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

Diagnostic Test: Numeric rating Scale (NRS)

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

Diagnostic Test: Postoperative inflammation

Drug: Propofol

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

Active Comparator: Dexmedetomidin

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

Behavioral: Mini mental state exame (MMSE)

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

Behavioral: Digit Symbol Substitution Test (DSST)

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

Diagnostic Test: Numeric rating Scale (NRS)

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

Diagnostic Test: Postoperative inflammation

Drug: Dexmedetomidin

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

Outcome Measures

Primary Outcome Measures

Occurrence of postoperative cognitive dysfunction (POCD) measured by MMSE [5 days]
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.
Occurrence of postoperative cognitive dysfunction (POCD) measured by DSST [5 days]
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.
Postoperative inflammation measured by serum CRP levels [5 days]
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.
Postoperative inflammation measured by white blood cells count [5 days]
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.
Postoperative inflammation measured by serum IL-6 levels [5 days]
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.
Postoperative inflammation measured by serum cholinesterase activity [5 days]
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.
Postoperative inflammation measured by serum PCT levels [5 days]
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.

Secondary Outcome Measures

Postoperative pain [24 hours]
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.