Effect of Remifentanil on Postoperative Cognition Function in Patients Undergoing Major Abdominal Surgery

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of two different analgesic methods (Fentanyl vs Remifentanil) during major abdominal surgery on postoperative cognitive status of patients.

Detailed Description
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The purpose of this study is to investigate the effects of two different analgesic methods (Fentanyl vs Remifentanil) during major abdominal surgery on postoperative cognitive status of patients. In particular, whether there is a correlation between type of anesthesia and the appearance of postoperative cognitive disorder (POCD), including type of anesthesia and levels of pro and anti inflammatory cytokines and investigate whether there is an association between presence or absence of POCD and cytokines levels

Official Title
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Effect of Remifentanil on Postoperative Cognitive Function in Patients Undergoing Major Abdominal Surgery

Conditions
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Patients Undergoing Major Abdominal Surgery, Postoperative Confusion

Intervention / Treatment
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* Drug: Remifentanil
* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 60 years Patients undergoing major abdominal surgery, in General Anesthesia ASA class status I-III Exclusion Criteria: History of allergy to drugs used in the study Mini-Mental State Examination (MMSE) value < 26 Expected duration of anesthesia less than 1 hour and more than 4 hours Presence of a cognitive disorder severity of overt such as to prevent collaboration of the patient Presence of severe electrolyte disturbances or not controlled bool glucose levels History of pain or cerebral vascular disease on the basis of significant carotid or cerebral artery stenosis, to be verified by scanning eco-color doppler Habitual use of tranquillizers or other drugs affecting the central nervous system Difficulties in the management of the airways, such as to make the necessary changes in anesthesia technique Severe hypotension or hypertension or other vascular disorders, particularly thrombotic events or bleeding during surgery or in the perioperative period Bleeding that requires blood transfusion Medication needs higher or lower than that indicated in the protocol to ensure the depth of hypnosis, indicated by values of BIS targets Refusal by the patient

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remifentanyl<br>In group A induction of anesthesia will be performed with Propofol (2mg/kg), Cisatracurium (0.15mg/kg)and continous infusion of Remifentanil (0.15mcg/kg/min).Anesthesia will be maintained by Sevoflurane with oxygen (Fi=40%)and air, with a MAC value to maintain BIS between 40 and 60. Intraoperative analgesia will be obtained with Remifentanil 0.15-0.25mcg/kg/min. Additional boluses of Cisatracurium (0.02mcg/kg)will be administered as needed during surgery. At the beginning of closure of the peritoneum bolus of morphine (0.1mg/kg)and acetaminophen 1g will be administered. Propofol and remifentanil infusions will be interrupted at the end of wound closure. | Drug: Remifentanil<br>* In group A induction of anesthesia will be performed with Propofol (2mg/kg), Cisatracurium (0.15mg/kg)and continous infusion of Remifentanil (0.15mcg/kg/min).Anesthesia will be maintained by Sevoflurane with oxygen (Fi=40%)and air, with a MAC value to maintain BIS between 40 and 60. Intraoperative analgesia will be obtained with Remifentanil 0.15-0.25mcg/kg/min. Additional boluses of Cisatracurium (0.02mcg/kg)will be administered as needed during surgery. At the beginning of closure of the peritoneum bolus of morphine (0.1mg/kg)and acetaminophen 1g will be administered. Propofol and remifentanil infusions will be interrupted at the end of wound closure.<br>|
| Active Comparator: Fentanyl<br>In group B anesthesia will be induced by Propofol (2mg/kg), Fentanyl (2mcg/kg)and Cisatracurium (0.15mg/kg). Anesthesia will be maintained by Sevoflurane, oxygen (Fi=40%) and air and boluses of Fentanyl (50mcg). additional boluses of Cisatracurium (0.02mg/kg)will be administered as needed during surgery. At the beginning of closure of the peritoneum acetaminophen 1g will be administered. | Drug: Fentanyl<br>* In group B anesthesia will be induced by Propofol (2mg/kg), Fentanyl (2mcg/kg)and Cisatracurium (0.15mg/kg). Anesthesia will be maintained by Sevoflurane, oxygen (Fi=40%) and air and boluses of Fentanyl (50mcg). additional boluses of Cisatracurium (0.02mg/kg)will be administered as needed during surgery. At the beginning of closure of the peritoneum acetaminophen 1g will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rey verbal memory test of words before and after major abdominal surgery | In test of Rey to the subject is presented for 5 times the same list of 15 bisyllabic words or trisillabic common use of which he must recall as many as possible within 1 minute; after about 15 minutes the patient, meanwhile distracted by the test , must again try to remember the greatest number possible without a further reading. The maximum possible score of the first phase of the test is an expression of the ability of short term memory of the subject, the result of the test is repeated at a distance of 15 minutes is indicative of its storage capacity, to intermediate term. | participants will be followed the day before and after surgery and for the duration of hospital stay, an expected average of 5 days | 
| Stroop Test before and after surgery | In the Stroop Test patient is instructed to read a random sequence of adjectives green, red, blue written in black font, then he refers the colour of a succession of circumferences filled of the three colors above in random order; finally, another random succession of three words green, red, blue written in three characters of the same colors, but not associated with corresponding adjective. Number of errors that the subject does in reading is an indication of its ability to attention | participants will be followed the day before and after surgery and for the duration of hospital stay, an expected average of 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative determination of serum pro and anti inflammatory cytokines before and after surgery | Blood samples will be made for the quantitative determination of serum cytokines IL-1β, IL-6, IL-8, TNF-α, IL-10 and IL-12. Determinations will be given by Multiplex Elisa method. | participants will be followed the day before and after surgery and for the duration of hospital stay, an expected average of 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major abdominal surgery, analgesic method, Fentanyl, Remifentanyl, Postoperative cognitive disorder, Pro and anti inflammatory cytokines