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AnesthesiaNCT06986109

Effect of Subanaesthetic Dose of Ketamine on Depth of Anaesthesia Consistency

A study testing Ketamine and Propofol in people with Anesthesia, run by Sir Ganga Ram Hospital at 1 site in India.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

General Anaesthesia (GA) is a medical state of controlled unconsciousness that inhibits two dimensions of consciousness: the content and the level of consciousness. This state is achieved using various anaesthetic agents, with propofol being one of the most commonly used intravenous anaesthetics. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Anesthesia
What is being tested?
Ketamine and Propofol
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
106 participants
Where
1 siteIndia
Study dates
26 May 2025to 21 Apr 2026
Phase
Interventional
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ASA physical status I and II.
  • Patients scheduled for elective laparoscopic surgery with estimated duration greater than 60-minutes.

Who cannot join

  • Known uncontrolled cardiovascular disease (e.g., hypertension, systolic and diastolic dysfunction)
  • Liver function abnormality (liver enzymes >2 times the normal range)
  • Kidney function abnormality (serum creatinine >1.4 mg/dl)
  • Known psychiatric or neurological disorder
  • Known uncontrolled endocrine disorder (diabetes mellitus, hypothyroidism)
  • Known allergy or hypersensitivity to the study drug
Show all 10Show fewer
  • Recent intake of sedative medication or anti-psychotic medication
  • Substance abuse
  • Anticipated need for postoperative ventilation
  • Refusal to informed consent

Trial locations and contacts

1 site in 1 country.

India1 site
  • Sir Ganga Ram Hospital

    New Delhi, National Capital Territory of Delhi, 110060

Other trials in India

About this study

Official title: Effect of Subanaesthetic Dose of Ketamine on Depth of Anaesthesia Consistency During Propofol Total Intravenous Anaesthesia Administered by Closed-loop Anaesthesia Delivery System in Adults Undergoing Elective Laparoscopic Surgery: a Randomised Controlled Study

General Anaesthesia (GA) is a medical state of controlled unconsciousness that inhibits two dimensions of consciousness: the content and the level of consciousness. This state is achieved using various anaesthetic agents, with propofol being one of the most commonly used intravenous anaesthetics. Propofol is a gamma amino butyric acid (GABAA) receptor agonist, which affects both the content and level of anaesthesia.

In some cases, anaesthesiologists may choose to use an adjuvant drug, ketamine, in subanaesthetic doses during inhalation GA and propofol total intravenous anaesthesia (TIVA). Ketamine is an N-methyl D-aspartate (NMDA) receptor antagonist and is primarily employed for its analgesic properties. Unlike propofol, ketamine selectively affects only the content of consciousness.

Read more

The combination of propofol and ketamine appears to have dual effects on the dimensions of consciousness, with propofol affecting both content and level, and ketamine affecting only the content. This combination is likely to complement and improve the consistency of intraoperative anaesthesia depth.

However, studies have shown that the administration of ketamine with propofol TIVA, delivered through an automated anaesthesia delivery system using electroencephalogram (EEG) feedback signals from NeuroSENSE processed electroencephalogram (pEEG) monitor, has not demonstrated any significant benefit over the use of propofol alone.

Till now, the only study on propofol-ketamine co-administration used an uncommon NeuroSENSE pEEG monitoring system. Closed loop anaesthesia delivery system (CLADS) is a more precise, efficient, and robust mechanism to facilitate automated administration of propofol TIVA which employs the standard bispectral index (BIS) pEEG monitoring to control propofol TIVA delivery. Further evidence is desirable on depth of anaesthesia consistency when ketamine is co-administered with propofol TIVA, using CLADS This randomised controlled study will compare the effect of subanaesthetic dose of ketamine versus placebo (normal saline) on anaesthesia depth consistency in patients undergoing elective laparoscopic surgery under automated propofol TIVA using CLADS. All patients undergoing elective laparoscopic surgery will be screened, and those found eligible will be enrolled. Enrolled patients will receive CLADS-controlled propofol TIVA as standard. In intervention are, patients will additionally receive subanaesthetic dose of ketamine (0.25-mg/kg bolus followed by maintenance infusion 0.25-mg/kg/h) (ketamine group); in control arm, patients will receive normal saline as placebo in addition to propofol TIVA (placebo group).

Read the detailed description

General Anaesthesia (GA) is a state of controlled unconsciousness that negatively affects a person's subjective experience or interaction with the external environment. GA inhibits two dimensions of consciousness: the content and the level of consciousness. The content of consciousness relates to a person's awareness or subjective experience, while the level of consciousness reflects the degree of wakefulness or arousal. Intravenous anaesthetics, such as propofol, which affect both the content and level of anaesthesia, are used for total intravenous anaesthesia (TIVA). Recently, there has been renewed interest in exploring the addition of anaesthetic adjuvants (ketamine, dexmedetomidine, lignocaine) that affect either the content or level of consciousness, or both, to propofol TIVA.

Propofol is a commonly used anaesthetic for administering TIVA. It acts on gamma-aminobutyric acid (GABAA) receptors in the brain, resulting in hyperpolarisation and inhibition of electrical activity in the neuronal circuits involving the cortex and the thalamus. It simultaneously activates the sleep-generating ventrolateral preoptic nuclei (VLPO) of the hypothalamus. The resultant effect is the depression of both the content and level of consciousness. Propofol causes a transition in electroencephalogram (EEG) waves from high-frequency, low-amplitude beta waves (13-25 Hz) and gamma oscillations (26-80 Hz) of the awake state to high-amplitude, slow delta waves (1-4 Hz) and alpha oscillations (9-12 Hz)

Ketamine is a dissociative anesthetic often used in subanesthetic doses alongside both inhalation general anesthesia (GA) and propofol total intravenous anesthesia (TIVA) due to its numerous benefits, including postoperative pain relief, reduced postoperative nausea and vomiting (PONV), and decreased shivering. It works by antagonizing the N-methyl D-aspartate (NMDA) receptor on the GABAergic inhibitory interneurons in the brain, leading to the disinhibition of excitatory or arousal-promoting neurons in the cortex. Additionally, it inhibits the VLPO nuclei of the hypothalamus. As the dose of ketamine increases, NMDA receptors on excitatory glutaminergic neurons are blocked, resulting in unconsciousness. Unlike propofol, ketamine's EEG signature is characterized by high-frequency, low-amplitude beta (13-25Hz) and gamma oscillations (25-32Hz). This unique mechanism of action, which selectively affects the content of consciousness, leads to a cataleptic state marked by dysphoria, hallucinations, and delirium.

The coadministration of propofol and ketamine has shown an additive effect on hypnosis. Additionally, evidence suggests that ketamine, like propofol, disrupts corticocortical neural activity affecting feedback neural circuits from the frontal to parietal cortex while preserving feedforward neural activity. The EEG signature of ketamine co-administered with propofol resembles that of propofol but with an augmented peak frequency of alpha wave oscillation. The propofol-ketamine combination, which appears to have both dual and solitary effects on dimensions of consciousness, is likely to improve intraoperative anesthesia depth consistency. Administering ketamine with propofol through an automated anesthesia delivery system using EEG feedback signals from the NeuroSENSE processed electroencephalogram (pEEG) monitor (NeuroWave Systems, Ohio, USA) (depth of hypnosis (DoH) index: WAVCNS index, value: '0' to '100') has demonstrated that a subanesthetic dose of ketamine maintains equivalent anesthesia depth consistency similar to when propofol is administered alone. Therefore, adding subanesthetic doses of ketamine to propofol TIVA neither compromises the automated system performance nor affects anesthesia depth consistency. Further evidence is desirable regarding propofol-ketamine TIVA administered by objective automated systems incorporating a feedback-loop mechanism using the bispectral index (BIS) (Medtronics, Minneapolis, USA) pEEG monitor (DoH index: BIS score, value: '0' to '100'), whose working algorithm differs from that of the WAVCNS index. One such automated system using the BIS pEEG monitor is the closed-loop anesthesia delivery system (CLADS). The use of CLADS in patients undergoing cardiac and non-cardiac surgery has demonstrated robust anesthesia depth consistency with propofol TIVA.

The investigators hypothesize that administration of subanaesthetic dose of ketamine will improve the intraoperative anaesthesia depth consistency as compared to placebo in adults undergoing elective laparoscopic surgery under automated propofol TIVA using CLADS.

The proposed randomised-controlled study aims to compare the effect of addition of subanaesthetic dose of ketamine versus placebo on anaesthesia depth consistency in patients undergoing elective laparoscopic surgery under automated propofol TIVA using CLADS.

Conditions
Anesthesia
Being tested
Ketamine, Propofol, Placebo
Keywords
ketamine, propofol, Bi-spectral index, closed-loop anaesthesia delivery system

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KetamineDrug

    Ketamine (concentration 5mg/ml) will be administered at 0.05-ml/kg over 5-minutes followed by continuous intraoperative ketamine infusion of 0.05-ml/kg /h.

  • PropofolDrug

    Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the conventional closed loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.

  • PlaceboDrug

    Normal saline bolus 0.05-ml/kg will be administered over 5-minutes and it will be followed by continuous intraoperative normal saline infusion at 0.05-ml/kg /h.

Study groups in NCT06986109
Study groupRoleWhat they receive
Ketamine GroupActive comparator100 mg of ketamine will be diluted in 20 ml of normal saline to make a ketamine concentration of 5mg/ml. Patients will receive a pre-induction bolus of ketamine solution at 0.05-ml/kg administered over 5-minutes and followed by maintenance infusion rate of 0.05-ml/kg /h throughout the duration of surgery. Anaesthesia induction and maintenance will be carried with propofol delivered and controlled by closed-loop anaesthesia delivery system (CLADS) a BIS-based feedback-loop automated anaesthesia delivery system. A target BIS value of '50' will be considered adequate for both induction and maintenance of anaesthesia.
Receives: Drug: Ketamine; Drug: Propofol
Placebo GroupActive comparator20-ml of normal saline will be taken and an equivalent volume will be used with a pre-induction bolus of 0.05-ml/kg administered over 5-minutes and followed by maintenance infusion rate of 0.05-ml/kg /h throughout the duration of surgery.Anaesthesia induction and maintenance will be carried with propofol delivered and controlled by closed-loop anaesthesia delivery system (CLADS) a BIS-based feedback-loop automated anaesthesia delivery system. A target BIS value of '50' will be considered adequate for both induction and maintenance of anaesthesia.
Receives: Drug: Propofol; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Anaesthesia depth consistency

    It will be determined by the percentage of the anaesthesia time during which the BIS remained +/- 10 of the target BIS of 50

    Measured: During the surgical procedure, an average of 360 minutes

Secondary outcomes (13)
  1. Performance characteristic of propofol delivery system determined by calculating the median performance error (MDPE)

    It will be determined using the Varvel criteria parameter :median performance error (MDPE). This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. It's just an abstract number. Higher the value means worse performance of propofol delivery system. It is not a scale.

    Measured: During the surgical procedure, an average of 360 minutes

  2. Performance characteristic of propofol delivery system determined by calculating the median absolute performance error (MDAPE)

    It will be determined using the Varvel criteria parameter: median absolute performance error (MDAPE).This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. Its just an abstract number.Higher the value means worse performance of propofol delivery system. It is not a scale.

    Measured: During the surgical procedure, an average of 360 minutes

  3. Performance characteristic of propofol delivery system determined by calculating the wobble

    It will be determined using the Varvel criteria parameter: wobble. This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. Its just a abstract number.Higher the value means worse performance of propofol delivery system. It is not a scale.

    Measured: During the surgical procedure, an average of 360 minutes

  4. Performance characteristic of propofol delivery system determined by calculating the global score

    It will be determined using the Varvel criteria parameter: global score. It is calculated using the formula Median absolute performance error + wobble / percentage of the anesthesia time during which the BIS remained +/- 10 of the target BIS of 50. This parameter have no unit of measurement. Its just a abstract number.Higher the value means worse performance of propofol delivery system. It is not a scale.

    Measured: During the surgical procedure, an average of 360 minutes

  5. Propofol induction dose (mg/kg)

    Dose of propofol required for induction of anaesthesia

    Measured: From start of propofol injection till target BIS value of '50' is achieved, an average of 5 minutes after beginning of anesthesia

  6. Propofol maintenance dose (mg/kg/h)

    Dose of propofol required for maintenance of anaesthesia

    Measured: From achieving target BIS value of '50' till skin closure, during the surgical procedure an average of 360 minutes

  7. Intraoperative haemodynamic instability

    Episodes (frequency) of occurrence of hypotension, hypertension, bradycardia and tachycardia will be noted. Hypotension will be defined as decrease in systolic blood pressure below 90 mmHg or >20% fall from pre-induction baseline. Hypertension will be defined as increase in systolic blood pressure above 140 mmHg or > 20% change from the baseline. A heart rate <50 bpm will be defined as 'bradycardia'. 'Tachycardia' will be defined as heart rate >100-bpm.

    Measured: From beginning of anaesthesia till 10 hours intraoperatively

  8. Early recovery from anaesthesia (measured in minutes)

    Time taken by the patient to open his/her eyes after discontinuation of anaesthesia will be noted

    Measured: From end of anaesthesia till 20-minutes postoperatively

  9. Early recovery from anaesthesia (measured in minutes)

    Time taken for tracheal extubation after discontinuation of anaesthesia will be noted

    Measured: From end of anaesthesia till 20-minutes postoperatively

  10. Postoperative pain assesment

    Will be assessed using the 11-point numeric rating scale (NRS) ('0': no pain to '10': worst possible pain).

    Measured: From the end of anaesthesia till 24-hours, postoperatively

  11. Postoperative nausea and vomiting

    Will be assessed using the 3-point PONV score ('0' = No emetic symptoms; '1' = nausea; '2' = vomiting)

    Measured: From the end of anaesthesia till 24-hours, postoperatively

  12. Postoperative sedation

    Modified observer's assessment of alertness/sedation scale (MOAA/S) will be used to assess postoperative sedation levels.26 The scale assesses the level of sedation with score range 0 to 5; score-0 means deeply sedated and score-5 means wide awake

    Measured: From the end of anaesthesia till 24-hours, postoperatively

  13. Intraoperative awareness

    Will be assessed using modified brice interview

    Measured: From the end of anaesthesia till 48-hours, postoperatively

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2025
  2. Study start26 May 2025
  3. Primary completion21 Apr 2026
  4. Study completion21 Apr 2026

Resources

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 N/A
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Model description
One hundred and six participants (53/group) aged 18-65 years, ASA physical status I-II, of either sex, and undergoing elective laparosocpic surgery will be randomly divided into one of the two groups: Group I: Ketamine Group Prior to anaesthesia induction, a bolus dose of ketamine solution 0.05-ml/kg (concentration 5mg/ml) will be administered followed by continuous intraoperative ketamine infusion of 0.05-ml/kg /h along with automated propofol TIVA delivered using CLADS. Group II: Placebo Group Prior to anaesthesia induction, an equivalent volume bolus (0.05-ml/kg) of 0.9% normal saline will be administered and it will be followed by continuous intraoperative 0.9% normal saline infusion at 0.05-ml/kg /h along with automated propofol TIVA delivered using CLADS.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
106 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06986109
Sponsor's protocol ID
EC/03/25/2670
Status last verified
Jun 2026
First submitted
7 May 2025
Last updated
24 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A study testing Ketamine and Propofol in people with Anesthesia, run by Sir Ganga Ram Hospital at 1 site in India.

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 2 inclusion and 10 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 24 Jun 2026. 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 India. 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.

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?

Anaesthesia depth consistency (time frame: During the surgical procedure, an average of 360 minutes). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 24 Jun 2026.

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