The Influence of Postoperative Analgesia on Systemic Inflammatory Response and POCD After Femoral Fractures Surgery

Study Overview
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Brief Summary
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The purpose of this study is to determine whether epidural levobupivacaine applied for the purpose of post-operative analgesia compared to systemic analgesia with morphine leads to better pain control, stronger suppression of the inflammatory response and the production of inflammatory mediators, faster recovery of patients and consequently less incidence of postoperative cognitive dysfunction (POCD) in elderly patients after surgical treatment of femoral fractures.

Detailed Description
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The research will be carried out at the Department of Surgery at Clinical Hospital Centre(CHC) Osijek after approval by the Ethics Committee of CHC Osijek and will be organized as a prospective randomized trial. Respecting the including and excluding criteria for participation in the study, the research will include 70 patients aged 65 years and over who are undergoing surgery for proximal femur fractures and will be operated with the same operating technique (osteosynthesis with nail). All participants will receive the same type of anesthesia and one of two forms of post-operative analgesia, so it will be divided into two groups (35 patients) depending on which form of post-operative analgesia receive. Randomization will be performed by drawing an envelope in which the specified one or other form of post-operative analgesia will be written. The study will be stopped in case of serious complications life-threatening (excessive sedation, respiratory insufficiency, hemodynamic instability and profound hypotension, heart rhythm disorders), which could possibly be related to the administration of drugs used for postoperative analgesia.

Official Title
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The Influence of Postoperative Analgesia on Systemic Inflammatory Response and Postoperative Cognitive Disfunction in Elderly Patients After Surgical Repair of Femoral Fractures

Conditions
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Postoperative Cognitive Dysfunction

Intervention / Treatment
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* Drug: morphine
* Drug: levobupivacaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients age 65 and over fracture of the proximal femur preoperative assessment American Society of Anesthesiologists(ASA) score I - ASA III a written consent of the patient to participate in research Exclusion Criteria: patient non-compliance ASA status IV and IV above patients younger than 65 years dementia, Parkinson's disease, cerebrovascular accident history; simultaneous head injuries,the use of opioids and benzodiazepines longer than a month before the surgery; alcoholism; serious liver disease (class C according to Child-Pugh's classification); severe kidney disease that require dialysis result of MMSE test (Mini-Mental State Examination) under 17 the existence of any contraindications for the implementation of regional anesthesia and one or other form of post-operative analgesia.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: morphine<br>The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery | Drug: morphine<br> <br> |
| Active Comparator: levobupivacaine<br>Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses). | Drug: levobupivacaine<br> <br> * Other names: Chirocaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukin-6 Concentration in Peripheral Blood. | Measurement will be done before and 24 and 72 hours after the surgery. | Before, 24 and 72 hours after the surgery | 
| Changes in Cognitive Function | Assessment of cognitive function will be done using the Mini-mental state examination (MMSE) rating scales before and 24,48,72,96 and 120 hours after the surgery at the same time every morning. Mini-Mental State Examination Scale: minimum score is 0 and maximum score is 30; the severity of cognitive impairment: no cognitive impairment=25-30; mild cognitive impairment=19-24; moderate cognitive impairment=10-18; and severe cognitive impairment<9. Higher scores mean a better and lower scores mean a worse outcome. | Before, 24,48,72,96 and 120 hours after the surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in C-reactive Protein (CRP) Levels | Measurement will be done before and 24,72 and 120 hours after the surgery. | Before, 24,72 and 120 hours after the surgery | 
| Changes in Fibrinogen Concentrations in Peripheral Blood | Measurement will be done before and 24,72 and 120 hours after the surgery. | Before, 24,72 and 120 hours after the surgery | 
| Changes in Pain Intensity | Assessment will be done using Numeric Rating Scale (NRS). During the first 72 hours after the surgery assessment will be done every 3 hours, after that assessment will be done 3 times daily. Median of 8 time points measurements during the first 24, 48 and 72 hours after the surgery will be reported. After that, median of 3 time points will be reported from the 4. to 6. postoperative day and on the day of discharge. Minimum score 0 and maximum score 10 ( 0-No Pain; 1-3 Mild Pain; 4-6 Moderate Pain; 7-10 Severe Pain ). Higher scores mean a worse and lower scores mean a better outcome. | During the first 72 hours after the surgery assessment will be done every 3 hours, after that assessment will be done 3 times daily until discharge | 
| Postoperative Hospital Stay | Duration of postoperative hospital stay in days | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative analgesia, postoperative cognitive disfunction