AnalgesiaKeta-ANINCT06344858
Characterization of the Temporal Profile of the Anti-nociceptive Effect of Ketamine Bolus Measured With ANI
An observational study of Analgesia and Ketamine, run by Pontificia Universidad Catolica de Chile at 1 site in Chile.
Trial summary
Ketamine, an intravenous anesthetic, and analgesic agent has experienced a resurgence in its clinical application, particularly in subanesthetic doses. The aim of this observational study is to characterize the changes in the Nociception Analgesia Index (ANI) associated with the administration of an intravenous… Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Analgesia, Ketamine, Pharmacokinetic
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- How many people
- 20 participants
- Where
- 1 siteChile
- Study dates
- 30 Apr 2024to 1 Aug 2024
- How long will I take part?
- 1 Day
- Phase
- Observational
- 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 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients undergoing elective surgery with general anaesthesia.
Who may be able to join
- Elective surgery with general anaesthesia
- Without premedication
- ASA I, II or III
Who cannot join
- Body weight greater than 120% of ideal weight
- Ingestion of sedatives of short or long action in the 48 hours before surgery
- People with a history of adverse effects to the drug under study
Trial locations and contacts
1 site in 1 country.
Chile1 site
Pontificia Universidad Catolica de Chile
Santiago, Santiago Metropolitan, 450881
About this study
Official title: Characterization of the Temporal Profile of the Anti- Nociceptive Effect of an Intravenous Ketamine Bolus Using the Nociception Analgesia Index (ANI)
Ketamine, an intravenous anesthetic, and analgesic agent has experienced a resurgence in its clinical application, particularly in subanesthetic doses. The aim of this observational study is to characterize the changes in the Nociception Analgesia Index (ANI) associated with the administration of an intravenous ketamine bolus using a Pharmacokinetic-Pharmacodynamic (PKPD) modeling approach. The pharmacokinetic parameters of the Domino model will be used to predict ketamine plasma concentrations after the bolus dose. An Emax model and a link model assuming a first order rate constant (ke0) will be used to fit the data. Modeling analysis will use the program NONMEM. It is expected to recruit a total of 20 patients between 40 and 80 years, ASA I, II or III, programmed for elective surgery with general anesthesia. ANI values will be recorded every 6 seconds for 5 minutes from the bolus dose.
Read the detailed description
Ketamine was introduced into clinical practice in 1965 and has been widely used as an intravenous anesthetic and analgesic. In recent years there has been a resurgence in its use mainly using low intravenous doses as a multimodal analgesia strategy and attenuation of postoperative hyperalgesia. Its use in low doses as an analgesic has also grown in other areas such as in emergency medicine and in patients with chronic pain and neuropathic pain. While optimal analgesic doses are not well defined in general the recommended regimens range from 0.15 to 0.3 mg/kg bolus and infusions from 0.1 to 0.3 mg/kg/h.
Target-controlled infusion (TCI) is an intravenous anesthesia delivery technique that incorporates pharmacokinetic models in pump infusion algorithms to allow obtaining objective-stable concentrations of the drug in the plasma or effect site. The TCI mode effect site presents advantages over plasma-to-plasma TCI since plasma concentrations do not have a good correlation with the drug's effect in nonequilibrium scenarios. This modality is based on that TCI systems can be instructed to exceed the desired plasma concentration to accelerate the rate at which the drug's effect is achieved. For the pharmacokinetic model to perform this the parameter set has to have the ke0 which is the equilibrium constant between the plasma and the effect site. This parameter provides the necessary information of the time profile of the drug's effect to the model. These models are known as on-site effect models or PKPD models. The potential benefit of TCI to site effect is the most accurate titration of the desired effect. Moreover, these models allow us to better understand the temporal profile of the drug effect.
TCI has been used for ketamine administration in various settings, including critical care. The operating room, and studies in neuroscience. In routine practice, ketamine TCI is performed using the model described by Domino with plasma target concentrations lower than 1.2 ng/ml to obtain its anti-nociceptive effect. Currently ketamine TCI can only be used in plasma mode since ke0 for its analgesic effect has not been determined.
The analgesic monitor PhysioDolorisTM (MDoloris Medical Systems SAS, Lille, France) was developed to quantitatively evaluate the effects of nociceptive stimuli on analgesic/nociceptive balance (the balance between the sympathetic/parasympathetic nervous system) in the anesthetized patient. ANI monitoring provides information on physiological coding and processing of nociceptive stimuli by analyzing the high-frequency component of heart rate variation in relation to respiratory rate. During anesthesia, the nociception index values reflect whether analgesia is adequate and whether analgesia allows the maintenance of nociception-antinociception balance, in which parasympathetic activity predominates over sympathetic. This monitoring provides a promising and objective evaluation of nociception.
The aim of this observational study was to describe changes in the ANI value associated with the administration of an intravenous ketamine bolus in a group of patients scheduled for elective surgery under general anesthesia.
The hypothesis is that the anti-nociceptive effect of the drug can be characterized by changes in ANI associated with the administration of a ketamine bolus. Effect-site TCI will be possible by incorporating this information into the available ketamine pharmacokinetic models.
- Conditions
- Analgesia, Ketamine, Pharmacokinetic
- Being tested
- Ketamine
- Keywords
- Ketamine, Analgesia, Target controlled infusion
- Medical subject headings
- Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Analgesia using ketamine
One bolus of ketammine
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | In the preoperative room a vein of the forearm with preriferic access #18 will be established for the administration of general intravenous anesthesia and intraoperative fluids.
In the operating room, after routine monitoring (Heart Rate, Non-Invasive Blood Pressure, Oxygen Saturometry), the sensor of the Nociception Analgesia Index (ANI) monitor will be installed from the right chest to the left 5th intercostal space.
Wait XX time for calibration and capture of the electrocardiographic signal. The ANI value shall initially be measured and shall be considered as the reference value.
Inject 0.1 mg/kg of ketamine (1 mg/ml) once, then inject 5 ml of physiological saline at the same rate.
The time from ketamine administration until the ANI index rose above 50 (minimum appropriate nociception value) shall be recorded every 6 seconds. Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure ANI values after ketamine bolus dose administration.
The observed effect of ketamine is measured with the ANI monitor index in each patient (outcome is ANI values [ANI Units])
Measured: Every 6 seconds for 5 minutes after ketamine bolus
To determine the time maximum predicted concentrations in each patient
The time from the start of ketamine administration until the maximum predicted ketamine plasma concentrations value will be determined in each patient (mg/L).
Measured: Every 6 seconds for 5 minutes after ketamine bolus
To determine the time to maximum effect of a bolus dose of ketamine
The time from the start of ketamine administration until the maximum ANI index value will be determined in each patient (ANI Values/minutes)
Measured: Every 6 seconds for 5 minutes after ketamine bolus
To predict ketamine plasma concentrations values after ketamine bolus
The expected maximum plasma concentrations mg/L. Wil be estimated using the pharmacokinetic parameters of Domino knowing the administered dose (0.1 mg/Kg).
Measured: Every 6 seconds for 5 minutes after ketamine bolus
To calculate the difference between the time of maximum ANI effect
With the time (minutes) maximum predicted concentrations and the ketamine plasma concentrations (mg/mL)
Measured: At the minute of maximum effect
Secondary outcomes (1)
Patient weight
The patient's weight will be measured prior to the administration of the ketamine bolus, which will be described in kg.
Measured: Once before the procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2024
- Study start30 Apr 2024
- Primary completion1 Aug 2024
- Study completion1 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AnalgesiaStudies of the same condition, open and under way.
- More trials run by Pontificia Universidad Catolica de ChileThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Pontificia Universidad Catolica de Chile
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Luis I Cortinez, MD, Principal investigator, Pontificia Universidad Catolica de Chile
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06344858
- Sponsor's protocol ID
- 124/2021
- Acronym
- Keta-ANI
- Status last verified
- Aug 2024
- First submitted
- 5 Feb 2024
- Last updated
- 22 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Navarrete V, Ibacache M, Contreras V, Cortinez I. Characterization of the temporal profile of the antinociceptive effects of an intravenous bolus of ketamine using the analgesia nociception index in no-anesthetized adult patients. J Clin Monit Comput. 2025 Apr;39(2):349-354. doi: 10.1007/s10877-024-01240-4. Epub 2024 Nov 15.
PubMed 39546215
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of the Temporal Profile of the Anti- Nociceptive Effect of an Intravenous Ketamine Bolus Using the Nociception Analgesia Index (ANI)
- ClinicalTrials.gov ID
- NCT06344858
- Acronym / sponsor ID
- Keta-ANI / 124/2021
- Conditions
- Analgesia, Ketamine, Pharmacokinetic
- Keywords
- Ketamine, Analgesia, Target controlled infusion
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Pontificia Universidad Catolica de ChileUniversity, hospital or other
- Study start
- 30 Apr 2024 (actual)
- Primary completion
- 1 Aug 2024 (actual)
- Study completion
- 1 Aug 2024 (actual)
- First posted
- 3 Apr 2024 (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, an intravenous anesthetic, and analgesic agent has experienced a resurgence in its clinical application, particularly in subanesthetic doses. The aim of this observational study is to characterize the changes in the Nociception Analgesia Index (ANI) associated with the administration of an intravenous ketamine bolus using a Pharmacokinetic-Pharmacodynamic (PKPD) modeling approach. The pharmacokinetic parameters of the Domino model will be used to predict ketamine plasma concentrations after the bolus dose. An Emax model and a link model assuming a first order rate constant (ke0) will be used to fit the data. Modeling analysis will use the program NONMEM. It is expected to recruit a total of 20 patients between 40 and 80 years, ASA I, II or III, programmed for elective surgery with general anesthesia. ANI values will be recorded every 6 seconds for 5 minutes from the bolus dose.
Detailed description
Ketamine was introduced into clinical practice in 1965 and has been widely used as an intravenous anesthetic and analgesic. In recent years there has been a resurgence in its use mainly using low intravenous doses as a multimodal analgesia strategy and attenuation of postoperative hyperalgesia. Its use in low doses as an analgesic has also grown in other areas such as in emergency medicine and in patients with chronic pain and neuropathic pain. While optimal analgesic doses are not well defined in general the recommended regimens range from 0.15 to 0.3 mg/kg bolus and infusions from 0.1 to 0.3 mg/kg/h.
Target-controlled infusion (TCI) is an intravenous anesthesia delivery technique that incorporates pharmacokinetic models in pump infusion algorithms to allow obtaining objective-stable concentrations of the drug in the plasma or effect site. The TCI mode effect site presents advantages over plasma-to-plasma TCI since plasma concentrations do not have a good correlation with the drug's effect in nonequilibrium scenarios. This modality is based on that TCI systems can be instructed to exceed the desired plasma concentration to accelerate the rate at which the drug's effect is achieved. For the pharmacokinetic model to perform this the parameter set has to have the ke0 which is the equilibrium constant between the plasma and the effect site. This parameter provides the necessary information of the time profile of the drug's effect to the model. These models are known as on-site effect models or PKPD models. The potential benefit of TCI to site effect is the most accurate titration of the desired effect. Moreover, these models allow us to better understand the temporal profile of the drug effect.
TCI has been used for ketamine administration in various settings, including critical care. The operating room, and studies in neuroscience. In routine practice, ketamine TCI is performed using the model described by Domino with plasma target concentrations lower than 1.2 ng/ml to obtain its anti-nociceptive effect. Currently ketamine TCI can only be used in plasma mode since ke0 for its analgesic effect has not been determined.
The analgesic monitor PhysioDolorisTM (MDoloris Medical Systems SAS, Lille, France) was developed to quantitatively evaluate the effects of nociceptive stimuli on analgesic/nociceptive balance (the balance between the sympathetic/parasympathetic nervous system) in the anesthetized patient. ANI monitoring provides information on physiological coding and processing of nociceptive stimuli by analyzing the high-frequency component of heart rate variation in relation to respiratory rate. During anesthesia, the nociception index values reflect whether analgesia is adequate and whether analgesia allows the maintenance of nociception-antinociception balance, in which parasympathetic activity predominates over sympathetic. This monitoring provides a promising and objective evaluation of nociception.
The aim of this observational study was to describe changes in the ANI value associated with the administration of an intravenous ketamine bolus in a group of patients scheduled for elective surgery under general anesthesia.
The hypothesis is that the anti-nociceptive effect of the drug can be characterized by changes in ANI associated with the administration of a ketamine bolus. Effect-site TCI will be possible by incorporating this information into the available ketamine pharmacokinetic models.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Day
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketamine | – | Drug: KetamineIn the preoperative room a vein of the forearm with preriferic access #18 will be established for the administration of general intravenous anesthesia and intraoperative fluids. In the operating room, after routine monitoring (Heart Rate, Non-Invasive Blood Pressure, Oxygen Saturometry), the sensor of the Nociception Analgesia Index (ANI) monitor will be installed from the right chest to the left 5th intercostal space. Wait XX time for calibration and capture of the electrocardiographic signal. The ANI value shall initially be measured and shall be considered as the reference value. Inject 0.1 mg/kg of ketamine (1 mg/ml) once, then inject 5 ml of physiological saline at the same rate. The time from ketamine administration until the ANI index rose above 50 (minimum appropriate nociception value) shall be recorded every 6 seconds. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients undergoing elective surgery with general anaesthesia.
Key inclusion criteria (3 listed)
- Elective surgery with general anaesthesia
- Without premedication
- ASA I, II or III
Key exclusion criteria (3 listed)
- Body weight greater than 120% of ideal weight
- Ingestion of sedatives of short or long action in the 48 hours before surgery
- People with a history of adverse effects to the drug under study
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: Analgesia using ketamineOne bolus of ketammine | Drug | Ketamine |
Primary outcome
To measure ANI values after ketamine bolus dose administration.
Time frame: Every 6 seconds for 5 minutes after ketamine bolus
The observed effect of ketamine is measured with the ANI monitor index in each patient (outcome is ANI values [ANI Units])
To determine the time maximum predicted concentrations in each patient
Time frame: Every 6 seconds for 5 minutes after ketamine bolus
The time from the start of ketamine administration until the maximum predicted ketamine plasma concentrations value will be determined in each patient (mg/L).
To determine the time to maximum effect of a bolus dose of ketamine
Time frame: Every 6 seconds for 5 minutes after ketamine bolus
The time from the start of ketamine administration until the maximum ANI index value will be determined in each patient (ANI Values/minutes)
To predict ketamine plasma concentrations values after ketamine bolus
Time frame: Every 6 seconds for 5 minutes after ketamine bolus
The expected maximum plasma concentrations mg/L. Wil be estimated using the pharmacokinetic parameters of Domino knowing the administered dose (0.1 mg/Kg).
To calculate the difference between the time of maximum ANI effect
Time frame: At the minute of maximum effect
With the time (minutes) maximum predicted concentrations and the ketamine plasma concentrations (mg/mL)
1 secondary outcome
Patient weight
Time frame: Once before the procedure
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 22 Aug 2024.
- Derived from this study: PubMed 39546215Navarrete V, Ibacache M, Contreras V, Cortinez I. Characterization of the temporal profile of the antinociceptive effects of an intravenous bolus of ketamine using the analgesia nociception index in no-anesthetized adult patients. J Clin Monit Comput. 2025 Apr;39(2):349-354. doi: 10.1007/s10877-024-01240-4. Epub 2024 Nov 15.
- Individual participant dataSharing planned: Undecided
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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.
Luis I Cortinez, MD principal investigator
Pontificia Universidad Catolica de Chile
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Analgesia and Ketamine, run by Pontificia Universidad Catolica de Chile at 1 site in Chile.
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 3 inclusion and 3 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 22 Aug 2024. 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 Chile. 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?
To measure ANI values after ketamine bolus dose administration. (time frame: Every 6 seconds for 5 minutes after ketamine bolus). The study lists 5 primary outcomes in all. 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 NCT06344858, which also lists 1 linked publication.
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 22 Aug 2024.