Ketamine Effect on Isoflurane Anesthesia

Post-anesthesia Recovery Clinical Trial

Official title:

Electroencephalographic Effects of Ketamine During Isoflurane Maintenance and Recovery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03290495
• Other study ID #: isoflurane ketamine gamma
• Status: Completed
• Phase: Phase 4
• First received: September 8, 2017
• Last updated: November 25, 2017
• Start date: September 30, 2017
• Est. completion date: November 25, 2017

Study information

• Verified date: November 2017
• Source: Minia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 25, 2017
• Est. primary completion date: November 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Post-anesthesia Recovery

Intervention

Drug:
• ketamine
ketamine hydrochloride 250microgram/ ml for iv injection after 30 minutes of stable isoflurane anesthesia
• 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.

Locations

Country	Name	City	State
Egypt	Minia University Hospital (main hospital)-kornish elnil st.	Al Minya	Minya

Sponsors (1)

Lead Sponsor	Collaborator
Minia University

Country where clinical trial is conducted

Egypt, 

References & Publications (5)

Campbell MJ, Julious SA, Altman DG. Estimating sample sizes for binary, ordered categorical, and continuous outcomes in two group comparisons. BMJ. 1995 Oct 28;311(7013):1145-8. Review. Erratum in: BMJ 1996 Jan 13;312(7023):96. — View Citation

Florey CD. Sample size for beginners. BMJ. 1993 May 1;306(6886):1181-4. Review. — View Citation

Li D, Hambrecht-Wiedbusch VS, Mashour GA. Accelerated Recovery of Consciousness after General Anesthesia Is Associated with Increased Functional Brain Connectivity in the High-Gamma Bandwidth. Front Syst Neurosci. 2017 Mar 24;11:16. doi: 10.3389/fnsys.2017.00016. eCollection 2017. — View Citation

Mashour GA. Cognitive unbinding: a neuroscientific paradigm of general anesthesia and related states of unconsciousness. Neurosci Biobehav Rev. 2013 Dec;37(10 Pt 2):2751-9. doi: 10.1016/j.neubiorev.2013.09.009. Epub 2013 Sep 26. Review. — View Citation

Philip BK, Kallar SK, Bogetz MS, Scheller MS, Wetchler BV. A multicenter comparison of maintenance and recovery with sevoflurane or isoflurane for adult ambulatory anesthesia. The Sevoflurane Multicenter Ambulatory Group. Anesth Analg. 1996 Aug;83(2):314-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	recovery time	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.	Time Frame: 1 hour
Secondary	gamma wave activity	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.	Time Frame: 2 hour
Secondary	processed EEG parameters	this include but not limited to BIS value, spectral edge frequency 95. these value will be online received from BIS monitor.	Time Frame: 2 hour