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Ketamine Effect on Isoflurane Anesthesia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03290495
Recruitment Status : Completed
First Posted : September 25, 2017
Last Update Posted : November 28, 2017
Sponsor:
Information provided by (Responsible Party):
Hassan, Mamdouh Hassan Mohamed, Minia University

Tracking Information
First Submitted Date  ICMJE September 8, 2017
First Posted Date  ICMJE September 25, 2017
Last Update Posted Date November 28, 2017
Actual Study Start Date  ICMJE September 30, 2017
Actual Primary Completion Date November 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2017)
recovery time [ Time Frame: Time Frame: 1 hour ]
recovery time in this study is defined as time between stop of isoflurane inhalation and recovery of consciousness . this will be assessed by calling the patient first name loudly until the patient verbally respond.time will be recorded in seconds.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2017)
  • gamma wave activity [ Time Frame: Time Frame: 2 hour ]
    EEG will recorded after test drug administration and during recovery. recorded data will be offline analysed for EEG wave activity. the results will be compared between the two study groups.
  • processed EEG parameters [ Time Frame: Time Frame: 2 hour ]
    this include but not limited to BIS value, spectral edge frequency 95. these value will be online received from BIS monitor.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine Effect on Isoflurane Anesthesia
Official Title  ICMJE Electroencephalographic Effects of Ketamine During Isoflurane Maintenance and Recovery
Brief Summary

Ketamine effect on isoflurane anesthesia This study is designed to study the effect of ketamine on isoflurane anesthesia. As both drugs are hypnotic and are used to cause sleep during surgery and other painful procedures, it was long believed that the actions of two drugs add to each other. For example if a man received both drugs, this man will become awake from anesthesia much later than if this man was given either of them alone.

However recent studies showed that this is not the case and ketamine can cause fast recovery from hypnotic effects of isoflurane. This was confirmed in animals.

The aim of current study is to investigate if this effect applies for humans, using a state of art brain monitoring device in wide use nowadays called BIS or bispectral index. This device can also shed some light on how ketamine can cause, if any, fast recovery from isoflurane anesthesia. Simply, by studying electrical wave coming from brain to head skin.

Detailed Description

In an animal study, the authors found that intraperitoneal injection of a sub-anesthetic dose of ketamine amidst isoflurane anesthesia in rats induced early recovery. A finding the authors explained, to be due to increased NMDA mediated increase of acetyl choline secretion in the prefrontal area of rats' brains. This rise, in the authors opinion, antagonized the GABA mediated isoflurane anesthesia resulting in hastened recovery. Meanwhile, the authors found association between hastened recovery and increased Electroencephalographic gamma (EEG γ) wave fronto-parietal projection. This is compatible with cognitive unbinding explanation of unconsciousness during anesthesia.

In current proposed study, the investigator will examine tow hypothesis:

Recovery time:

If the recovery hastening effect of sub anesthetic ketamine on recovery from isoflurane anesthesia is also present in human patients. The assumption will be that ketamine either prolong or has no effect on recovery time from isoflurane anesthesia. The claim well be that ketamine will decrease the recovery time.

Put in statistical terms:

H0: recovery with ketamine ≥ recovery without ketamine. H1: recovery with ketamine ˂ recovery without ketamine. 2. EEG (γ) wave activity: As the investigator will record EEG activity during the procedure via Bispectral monitor, the investigator will analyze the records for presence of enhanced (γ) activity during recovery. the investigator aim is also to detect any significant difference in (γ) wave amplitude or other characteristics between isoflurane only and ketamine group.

The assumption will be that (γ) activity will either show no difference between the two groups or be lower than in ketamine group than isoflurane group during recovery. The claim will be increased (γ) activity with ketamine group during recovery.

Put in statistical terms:

H0: (γ) activity with ketamine ≤ isoflurane only. H1: (γ) activity with ketamine > isoflurane only. N.P: as the sampling frequency of EEG data exported from BIS Vista is 128Hz, the upper limit of the current study of (γ) activity will necessarily be 64Hz.

Sample size calculation:

the mean measured variable of the current study will be the recovery time. Recovery time will be defined as the time between stop of isoflurane inhalation until recovery of verbal response to name called every 30 seconds. A 30% reduction in recovery time in ketamine group as compared with isoflurane is considered to be statically significant enough to reject the null hypothesis of recovery time. According to one study , recovery time from isoflurane only anesthesia is around 12 minutes so the sample size calculation will be as following:

Equation:

n>((ᶻ "1- α ̸2" +ᶻ"1-β" )"2" σ"2" )/δ"2" Where n = sample size required for each group, ᶻ "1-α" = the value for the standard normal distribution for (1-α̸2) percentile, ᶻ "1-β" =the standard normal distribution for 100(1-β) percentile, δ"2" = the difference to detect, σ"2" = the variance in the underling 2 population.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

An intravenous catheter was placed and normal saline (0.9%) will be infused. Spinal anesthesia will be given. The stability of spinal anesthesia will be assured before propofol injection and at the end of procedure.

Propofol will be given to facilitate isoflurane inhalation which will be varied between 0.8-1.2percent to keep (BIS) in the range 40-60. Anesthesia will be kept as so for 30 minutes. Then the test drug (either ketamine or saline) will be given slowly, to pressor response in case of ketamine. Anesthesia will be maintained for another 30 minutes then isoflurane is discontinued. Recovery from anesthesia will then be tested.. No other drugs will be routinely given. Development of complications or signs of inadequate anesthesia will cause drop of the case from study and any measures will be taken to insure patient safety and comfort.The patient will be let to recover from anesthesia then transferred to postoperative care unit.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
The patients well be randomized to one of the two groups by closed envelope technique. After opening the envelope, the study drug (ketamine 100µg/kg total body weight (Isoket group)) or normal saline ((Isonly) or control group) will be prepared, made up to 10 ml and administered by an assistant in the proper timing. The patient identification will be written on a slip and put back into an envelope and sealed. The person doing the procedure and monitoring along with the patient will be blinded to the dose and nature of solution. The equal volume test solution will be given intravenously by an assistant who was not involved in the administration of anesthesia and monitoring
Primary Purpose: Basic Science
Condition  ICMJE Post-anesthesia Recovery
Intervention  ICMJE
  • Drug: ketamine
    ketamine hydrochloride 250microgram/ ml for iv injection after 30 minutes of stable isoflurane anesthesia
    Other Name: Calypsol
  • Drug: saline
    a similar volume of normal saline 0.9% for intravenous injection instead of ketamine will be given to the control group. this because the attending anesthesiologist will be blinded to the study drugs and aim according to the study proposal.
    Other Name: normal saline, Atsuka
Study Arms  ICMJE
  • Active Comparator: isonly
    This arm will receive spinal anesthesia. then this arm will receive saline during isoflurane anesthesia. this arm will serve as a control group.
    Intervention: Drug: saline
  • Active Comparator: isoket
    this arm will receive spinal anesthesia. then will receive isoflurane inhalation. during isoflurane inhalation, this arm will receive single injection of ketamine. at end of anesthesia, effect of ketamine on recovery will be monitored.
    Intervention: Drug: ketamine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 19, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 25, 2017
Actual Primary Completion Date November 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Consent: patient must be legally fit to consent. Informed consent will be get from each patient.
  • ASA status: I or II.
  • Fully conscious at time of induction of anesthesia.
  • No history of side effects related to any drugs used in the study.
  • Planned surgery can be performed under spinal anesthesia

Exclusion Criteria:

  • Incompetence: failure to give informed consent or refusal.
  • Neurological or psychiatric disorders
  • Addiction
  • Recent intake of drugs affecting central nervous system
  • ASA state more than II
  • Morbid obesity
  • Surgery cannot solely performed under spinal anesthesia
  • Contraindication to spinal anesthesia as coagulopathy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Egypt
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03290495
Other Study ID Numbers  ICMJE isoflurane ketamine gamma
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Hassan, Mamdouh Hassan Mohamed, Minia University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Minia University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mamdouh H Hassan, MD Minia faculty of Medicine. Minia university. Egypt
PRS Account Minia University
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP