Delirium Prevention With Ketamine in Ear, Nose, and Throat (ENT) Patients

A Randomized Placebo-controlled Pilot Study of Single-dose Intraoperative Ketamine for the Prevention of Delirium in Otolaryngeal Cancer Surgery Patients

The goal of this prospective randomized double blinded placebo controlled study is to investigate if a single dose of ketamine in addition to standard anesthesia will reduce the risk of delirium in otolaryngeal cancer patients postoperatively. Ketamine's effect on post-operative pain and opioid use will be measured as well. Electroencephalogram (EEG) will be utilized during the surgical procedure to evaluate its potential as a possible predictive device for delirium.

Study Overview

• Status: Terminated
• Conditions: Otolaryngeal Cancer
• Intervention / Treatment: Drug: Ketamine; Device: Electroencephalogram (EEG); Drug: Placebo

Detailed Description

This is a single center prospective randomized double blinded placebo controlled study.

The primary aim of the study is to optimize the intraoperative treatment protocol for head and neck cancer patients to reduce the incidence of delirium and associated postoperative cognitive dysfunction. Secondary aims are to determine the dose response relationship for intraoperative ketamine and delirium reduction, determine if a single dose of ketamine will reduce post-operative pain and opioid requirements, determine if raw electroencephalogram (EEG) data can predict postoperative delirium during general anesthesia, and to evaluate length of intensive care unit (ICU) and length of hospital stay.

Participants will be randomized to one of three groups after administration of general anesthesia; one dose of .5 mg/kg intravenous (IV) Ketamine, 1.0 mg/kg of IV Ketamine, or IV placebo.

An EEG will be used during the surgical procedure to gather raw data for off line analysis among patients developing post-operative delirium.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Current diagnosis of otolaryngeal cancer and undergoing surgery with general anesthesia
• Competent to provide informed consent

Exclusion Criteria:

• Emergency surgery
• Monitored Anesthesia Care (i.e., regional anesthesia alone without plans for general anesthesia)
• Surgery involving the eye, eyebrow, forehead, or frontal scalp near the sensor placement
• Poor health literacy
• Allergy, or have experienced any drug reaction to ketamine
• Pregnant or lactating
• Currently in active alcohol withdrawal
• Taking buprenorphine for chronic pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine 0.5 mg/kg; Participants undergoing surgery for otolaryngeal cancer will be randomized to receive one dose of IV ketamine at 0.5 mg/kg.	Drug: Ketamine; Ketamine will be administered intravenously after administration of general anesthesia and prior to the first surgical incision.; Device: Electroencephalogram (EEG); A processed EEG device will be used during the surgical procedure to gather raw EEG data for off line analysis among patients developing post-operative delirium.
Experimental: Ketamine 1.0 mg/kg; Participants undergoing surgery for otolaryngeal cancer will be randomized to receive one dose of IV ketamine at 1.0 mg/kg.	Drug: Ketamine; Ketamine will be administered intravenously after administration of general anesthesia and prior to the first surgical incision.; Device: Electroencephalogram (EEG); A processed EEG device will be used during the surgical procedure to gather raw EEG data for off line analysis among patients developing post-operative delirium.
Placebo Comparator: Placebo; Participants undergoing surgery for otolaryngeal cancer will be randomized to receive one dose of IV saline/placebo.	Device: Electroencephalogram (EEG); A processed EEG device will be used during the surgical procedure to gather raw EEG data for off line analysis among patients developing post-operative delirium.; Drug: Placebo; Placebo will be administered intravenously after administration of general anesthesia and prior to the first surgical incision.; Other Names: Saline Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Confusion Assessment Method fo Intensive Care Unit (CAM-ICU) Delirium Score	The CAM-ICU assesses four features: 1) acute change or fluctuation in mental status from baseline, 2) inattention, 3) altered level of consciousness, and 4) disorganized thinking. The measure reports whether a participant meets criteria for delirium by summing the number of features answered as "present". Feature 1 plus 2 and either 3 or 4 present = delirium positive. Results are expressed as number of participants with or without delirium at each time frame.	Baseline (Up to 30 minutes after PACU arrival), Post Operative (PACU discharge up to 6 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Behavioral Pain Scale (Non-Intubated) Score	The Behavioral Pain Scale. Scores range from 3 (no pain) to 12 (maximum pain).	Post Operation (Up to 6 Hours), Post Operation Day 0
Change in Pain Level Assessed by the Visual Analog Scale (VAS) Score	Scores range from 0 (no pain) to 10 (worst pain).	Baseline, Post Surgery (PACU), Post surgery (POD 0), Post surgery (POD 1), Post surgery (POD 2), Post surgery (POD 3), Post surgery (follow up visit - Up to 6 weeks)
Change in Mini Cog Score	The Mini-Cog is a 3-minute instrument that can increase detection of cognitive impairment. A score ranging from 0-2 indicates positive screen for dementia. A score ranging from 3-5 indicates negative screen for dementia.	Baseline, Post Surgery (Up to 6 Weeks)
Change in Mini-Mental Status Examination (MMSE) Score	The MMSE is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. Any score greater than or equal to 24 points (out of 30) indicates a normal cognition. Below this (0-24), scores can indicate cognitive impairment.	Baseline, Post Surgery (Up to 6 Weeks)
Change in Cognitive Failure Questionnaire (CFQ) Score	The CFQ is a 25-item self-report measure of failures in attention, perception, memory, and action. Participants are asked to indicate on a 5-point scale how often they have experienced each failure in the past months, from 0 (never) to 5 (very often). Scores range from 0 to 100 a higher score indicating more failures in attention.	Baseline, Post Surgery (Up to 6 Weeks)
Post Operative Narcotics Use	The total amount of narcotics used measured in morphine milligram equivalents (MME).	Post Intervention (Intraoperative), Post Intervention (POD 0), Post Intervention (POD 1),Post Intervention (POD 2),Post Intervention (POD 3), Post Intervention (Follow up visit-up to 6 weeks post intervention)
Associations of Intraoperative EEG Patterns With PACU Delirium	The investigators compared the relative beta power derived from the normalized power spectral density (PSD) in patients with and without PACU delirium (positive and negative delirium). Only a total of 38 EEGs with sufficient quality were analyzed. Results are expressed in percentage of cumulative power. A higher beta power correlates with worse outcome. Averages and standard deviations are shown.	Intraoperative EEG and delirium during PACU stay

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Vanessa Moll, PhD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2017
• Primary Completion (Actual): February 24, 2020
• Study Completion (Actual): April 24, 2020

Study Registration Dates

• First Submitted: January 31, 2017
• First Submitted That Met QC Criteria: January 31, 2017
• First Posted (Estimate): February 1, 2017

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: July 7, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Anesthesiology
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: IRB00086609

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