Clinical trial NCT03290495: Ketamine Effect on Isoflurane Anesthesia
Official title: Electroencephalographic Effects of Ketamine During Isoflurane Maintenance and Recovery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Post-anesthesia Recovery
Keywords: ketamine
isoflurane
electroencephalography
maintenance
recovery
anesthesia
Lead sponsor: Minia University
Sponsor class: OTHER
First posted: 2017-09-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: recovery time
timeFrame: Time Frame: 1 hour
Secondary outcomes:
measure: gamma wave activity
timeFrame: Time Frame: 2 hour
measure: processed EEG parameters
timeFrame: Time Frame: 2 hour
Other outcomes:
Locations:
city: Al Minyā
country: Egypt
facility: Minia University Hospital (main hospital)-kornish elnil st.
state: Minya
Study officials:
affiliation: Minia faculty of Medicine. Minia university. Egypt
name: Mamdouh H Hassan, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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. doi: 10.1097/00000539-199608000-00019.
citation: 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. doi: 10.1136/bmj.311.7013.1145.
citation: Florey CD. Sample size for beginners. BMJ. 1993 May 1;306(6886):1181-4. doi: 10.1136/bmj.306.6886.1181.