To Study the Effect of Sevoflurane and Propofol V Sevoflurane and Dexmedetomidine on Postoperative Cognitive Dysfunction (POCD)

To Study the Effect of Sevoflurane and Propofol Versus Sevoflurane and Dexmedetomidine on Postoperative Cognitive Dysfunction

Postoperative Cognitive Dysfunction (POCD), is a subtle decline in cognitive function characterized by impairment of memory and reduced ability to concentrate in elderly patients exposed to general anaesthesia. This prospective study aims to compare incidence and severity of POCD in two groups of patients. Group P receiving Intravenous Propofol and Inhalational anesthetic Sevoflurane. Group D receiving Intravenous Dexmedetomidine and Inhalational anesthetic Sevoflurane, Neuropsychological Test will be performed 24 hours before surgery and on postoperative day 3 and day 7.

Study Overview

• Status: Completed
• Conditions: Postoperative Cognitive Dysfunction
• Intervention / Treatment: Drug: Maintainance of anesthesia with Intravenous Propofol infusion; Drug: Maintainance of anesthesia with Intravenous Dexmedetomidine

Detailed Description

The adult patients posted for major surgery under general anesthesia will be included in the study, patients will be allotted randomly to either Group P (Propofol) or Group D (Dexmedetomidine). In the Operation Room (OR) monitoring Electrocardiography (ECG), Pulse Oximetry (SPO2), Noninvasive Blood Pressure (NIBP), End tidal Carbon di oxide (ETCO2) and Bispectral Index (BIS) Covidien, will be attached to all patients. In both groups Anesthesia will be induced with Fentanyl 1mcg /kg-1, Morphine 0.1mg/kg-1, Propofol 1-1.5mg /kg1- and neuromuscular blocking agent Atracurium 0.5 mg/kg-1. Oral Cuffed Endotracheal Tube (ETT) will be placed in the trachea. Anaesthesia will be maintained controlled ventilation , intermittent fentanyl boluses 20 mcg and in Group P with medicated Air/Oxygen (O2) with Fractional Inspired Oxygen (FiO2 50%), Sevoflurane and Propofol Infusion to maintain BIS between 40-60. In Group D anesthesia will be maintained with Medicated Air/Oxygen (FiO2 50%), Sevoflurane and Dexmedetomidine infusion to maintain BIS between 40-60. Intraoperatively monitoring of vitals, BIS numerical value, Minimum Alveolar Concentration (MAC) Value for Sevoflurane, Expired concentration of Sevoflurane and rate of infusion of Propofol/Dexmedetomidine will be noted every 30 minutes. Intraoperative decrease in Mean Arterial Pressure (MAP) < 60 mmHg, Heart rate (HR) < 50, SPO2 < 90 % will also be noted. At the end of surgery total dosage of Propofol/Dexmedetomidine and total amount of Sevoflurane consumed will be calculated. At the end of surgery neuromuscular blockade will be reversed. Total Duration of anesthesia will be noted. On emergence from anesthesia any episode of acute delirium will be recorded. Time from end of anesthesia to eye opening will be noted in both the groups. Neuropsychological Test consisting of Letter Digit Substitution Test, Trail Making Test Part A, Part B, Stroop Colour Word Test, Visual Verbal Learning Test will be performed 24 hours prior to surgery in the preanesthesia clinic and on postoperative day 3 and day 7.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi, India, 110085
    • Rajiv Gandhi Cancer Institute and Research Centre
  • Delhi, India, 110078
    • Dr Anita Kulkarni

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient subjected to general anaesthesia for elective noncardiac surgical procedure with duration above 2 hours and postoperative stay for 3 days. Patient should be available for follow up on 7 th postoperative day.

Exclusion Criteria:

• Patients having severe psychosis on antidepressant medications, cerebral disease, pre-existing cognitive dysfunction with Mini Mental State Examination (MMSE) Score less than 23, history of drug abuse, significant visual and hearing impairment ,language difficulties and illiteracy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Propofol/Sevoflurane (Group P); Standard technique of induction of anaesthesia . Maintenance of anesthesia with intravenous (IV) Propofol Infusion at rate 100-150 mcg/kilogram/hour and Inhalational Anesthetic Sevoflurane during the surgery. Intervention is to titrate dosage of Propofol and Sevoflurane to maintain Bispectral Index between 40-60. Total dosage of IV Propofol and Sevoflurane uptake will be calculated at the end of surgery.	Drug: Maintainance of anesthesia with Intravenous Propofol infusion; The dosage of Intravenous Propofol will be titrated to maintain BIS Values between 40 -60.
ACTIVE_COMPARATOR: Dexmedetomidine/Sevoflurane (Group D); Standard technique of induction of anaesthesia . Maintenance of anesthesia with intravenous Dexmedetomidine Infusion at rate 1- 4 mcg/kilogram/hour and Inhalational Anesthetic Sevoflurane during the surgery. Intervention is to titrate dosage of Dexmedetomidine and Sevoflurane to maintain Bispectral Index between 40 - 60. Total dosage of IV Dexmedetomidine and Sevoflurane uptake will be calculated at the end of surgery.	Drug: Maintainance of anesthesia with Intravenous Dexmedetomidine; The dosage of Intravenous Dexmedetomidine will be titrated to maintain BIS Values between 40 -60.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Cognitive Dysfunction (POCD) after major noncardiac surgery under general anesthesia in Propofol and Dexmedetomidine Group	Postoperative Changes in Neuropsychological Tests Score compared with baseline preoperative Neuropsychological Test scores in both the groups.	day 3 to day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery time from the stopping of anesthetics agents to eye opening in both Propofol and Dexmedetomidine Group	Time in seconds required for patients to respond to verbal commands on stopping the anesthetic agents in both groups.	30 seconds to 30 minutes.

Collaborators and Investigators

• Sponsor: Rajiv Gandhi Cancer Institute & Research Center, India
• Investigators: Principal Investigator: Anita Kulkarni, M.D., Rajiv Gandhi Cancer Institue & Research Centre , Delhi, INDIA

Publications and helpful links

General Publications

• Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. Br J Anaesth. 2009 Dec;103 Suppl 1(Suppl 1):i41-46. doi: 10.1093/bja/aep291.
• Akeju O, Pavone KJ, Westover MB, Vazquez R, Prerau MJ, Harrell PG, Hartnack KE, Rhee J, Sampson AL, Habeeb K, Gao L, Pierce ET, Walsh JL, Brown EN, Purdon PL. A comparison of propofol- and dexmedetomidine-induced electroencephalogram dynamics using spectral and coherence analysis. Anesthesiology. 2014 Nov;121(5):978-89. doi: 10.1097/ALN.0000000000000419. Erratum In: Anesthesiology. 2015 Apr;122(4):958. Lei, Gao [corrected to Gao, Lei].
• Kotekar N, Kuruvilla CS, Murthy V. Post-operative cognitive dysfunction in the elderly: A prospective clinical study. Indian J Anaesth. 2014 May;58(3):263-8. doi: 10.4103/0019-5049.135034.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2017
• Primary Completion (ACTUAL): February 10, 2018
• Study Completion (ACTUAL): March 28, 2018

Study Registration Dates

• First Submitted: March 7, 2017
• First Submitted That Met QC Criteria: May 5, 2017
• First Posted (ACTUAL): May 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 4, 2019
• Last Update Submitted That Met QC Criteria: January 31, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Elderly; POCD
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Postoperative Complications; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Postoperative Cognitive Complications; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Anesthetics; Propofol; Dexmedetomidine
• Other Study ID Numbers: RGCI&RC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No