Post-anesthesia RecoveryPhase 4NCT03290495
Ketamine Effect on Isoflurane Anesthesia
A Phase 4 study testing ketamine and saline in people with Post-anesthesia Recovery, run by Minia University at 1 site in Egypt.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Post-anesthesia Recovery
- What is being tested?
- ketamine and saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteEgypt
- Study dates
- 30 Sep 2017to 25 Nov 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Egypt1 site
Minia University Hospital (main hospital)-kornish elnil st.
Minya, Minya Governorate, 61511
About this study
Official title: Electroencephalographic Effects of Ketamine During Isoflurane Maintenance and Recovery
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.
Read the 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.
- Conditions
- Post-anesthesia Recovery
- Being tested
- ketamine, saline
- Keywords
- ketamine, isoflurane, electroencephalography, maintenance, recovery, anesthesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ketamineDrug
Also called Calypsol
ketamine hydrochloride 250microgram/ ml for iv injection after 30 minutes of stable isoflurane anesthesia
salineDrug
Also called normal saline, Atsuka
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.
| Study group | Role | What they receive |
|---|---|---|
| isonly | Active comparator | This arm will receive spinal anesthesia. then this arm will receive saline during isoflurane anesthesia. this arm will serve as a control group. Receives: Drug: saline |
| isoket | Active comparator | 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. Receives: Drug: ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Time Frame: 1 hour
Secondary outcomes (2)
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.
Measured: Time Frame: 2 hour
processed EEG parameters
this include but not limited to BIS value, spectral edge frequency 95. these value will be online received from BIS monitor.
Measured: Time Frame: 2 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2017
- Study start30 Sep 2017
- Primary completion15 Nov 2017
- Study completion25 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Post-anesthesia RecoveryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Minia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hassan, Mamdouh Hassan Mohamed, Minia University
- Investigators
- Mamdouh H Hassan, MD, Principal investigator, Minia faculty of Medicine. Minia university. Egypt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03290495
- Sponsor's protocol ID
- isoflurane ketamine gamma
- Status last verified
- Nov 2017
- First submitted
- 8 Sep 2017
- Last updated
- 28 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 28392760Mashour 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.
PubMed 24076246Philip 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.
PubMed 8694311Campbell 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.
PubMed 7580713Florey CD. Sample size for beginners. BMJ. 1993 May 1;306(6886):1181-4. doi: 10.1136/bmj.306.6886.1181.
PubMed 8499826
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electroencephalographic Effects of Ketamine During Isoflurane Maintenance and Recovery
- ClinicalTrials.gov ID
- NCT03290495
- Acronym / sponsor ID
- isoflurane ketamine gamma
- Conditions
- Post-anesthesia Recovery
- Keywords
- ketamine, isoflurane, electroencephalography, maintenance, recovery, anesthesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Minia UniversityUniversity, hospital or other
- Study start
- 30 Sep 2017 (actual)
- Primary completion
- 15 Nov 2017 (actual)
- Study completion
- 25 Nov 2017 (actual)
- First posted
- 25 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| isonly | Active comparator | Drug: salineThis arm will receive spinal anesthesia. then this arm will receive saline during isoflurane anesthesia. this arm will serve as a control group. |
| isoket | Active comparator | Drug: ketaminethis 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ketamineAlso: Calypsolketamine hydrochloride 250microgram/ ml for iv injection after 30 minutes of stable isoflurane anesthesia | Drug | isoket |
| salineAlso: normal saline, Atsukaa 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. | Drug | isonly |
Primary outcome
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.
2 secondary outcomes
gamma wave activity
Time frame: Time Frame: 2 hour
processed EEG parameters
Time frame: Time Frame: 2 hour
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2017.
- Background: PubMed 28392760Li 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.
- Background: PubMed 24076246Mashour 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.
- Background: PubMed 8694311Philip 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.
- Background: PubMed 7580713Campbell 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.
- Background: PubMed 8499826Florey CD. Sample size for beginners. BMJ. 1993 May 1;306(6886):1181-4. doi: 10.1136/bmj.306.6886.1181.
- Individual participant dataSharing planned: Undecided
Related trials for Post-anesthesia Recovery
RecruitingObservational study
Anesthetic Technique and Quality of Recovery After Cesarean Delivery
Ceserean Section, Obstetric Quality of Recovery
Enrolling by invitation
Long-term Follow-up of Bio-signals and Quality of Recovery Following Implementation of ERAS Based on the Mobile Application
Gynecologic Surgery, General Anesthesia
Recruiting
Effect of Opioid-sparing Anesthesia on Quality of Recovery After Emergency Laparotomy
Emergency Abdominal Surgery, Opioid Sparing Anaesthesia
Not yet recruiting
Effect of Opioid-free Anesthesia on Sleep Quality, Cognitive Function and Recovery Quality After General Anesthesia in Elderly Patients
Opioid-Free Anesthesia, POCD
Not yet recruiting
A Randomized Comparison of the Efficacy of the IPACK Block Versus the Popliteal Plexus Block for Posterior Knee Analgesia, in Patients Undergoing a Total Knee Arthroplasty and Receiving a Continuous Distal Femoral Triangle Block
Osteoarthritis, Knee, Postoperative Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mamdouh H Hassan, MD principal investigator
Minia faculty of Medicine. Minia university. Egypt
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ketamine and saline in people with Post-anesthesia Recovery, run by Minia University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
recovery time (time frame: Time Frame: 1 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03290495, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2017.