HypotensionPhase 4NCT05166330
Two Ratios of Propofol-ketamine Admixture for Rapid-sequence Induction Anesthesia for Emergency Laparotomy
A Phase 4 study testing Ketofol equal ratio and Ketofol 1:3 ratio in people with Hypotension and Induction of Anesthesia, run by Kasr El Aini Hospital at 1 site in Egypt.
Trial summary
Hypotension during anesthesia is associated with serious organ failure and death. The most critical period for intraoperative hypotension is the postinduction period during which, one-third of intraoperative hypotension occurs. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypotension, Induction of Anesthesia
- What is being tested?
- Ketofol equal ratio and Ketofol 1:3 ratio
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteEgypt
- Study dates
- Dec 2021to Mar 2022
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult patients (18-65 years),
- American society of anesthesiologist I-III,
- scheduled for emergency laparotomy under general anesthesia
Who cannot join
- history of difficult intubation,
- abnormal airway examination,
- cardiac morbidities (impaired contractility with ejection fraction < 50%, heart block, arrhythmias, tight valvular lesions),
- patients on angiotensin converting enzyme inhibitors and angiotensin receptor blockers medications,
- patients with uncontrolled hypertension,
- patient with allergy of any of the study drugs
Show all 10Show fewer
- Patients on vasopressor infusion,
- patients with high shock index (heart rate / systolic blood pressure >1),
- body mass index > 35 kg/m2, increased intracranial tension
- pregnant women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Different Ratios of Propofol-ketamine Admixture in Rapid-sequence Induction of Anesthesia for Emergency Laparotomy: a Randomized Controlled Trial
Hypotension during anesthesia is associated with serious organ failure and death. The most critical period for intraoperative hypotension is the postinduction period during which, one-third of intraoperative hypotension occurs. Post-induction hypotension has many contributing factors; however, it is closely related to anesthetic drugs. Therefore, manipulation of induction agents makes post-induction hypotension likely preventable. Emergency laparotomy is a critical category of surgery whose patients are usually hemodynamically compromised and prone to post-induction hypotension; furthermore, these patients are usually at high risk of aspiration of gastric contents and require rapid-sequence induction of anesthesia and optimum intubating conditions. Thus, induction of anesthesia for emergency laparotomy requires meticulous balance between achievement of adequate hypnosis and maintenance of stable blood pressure.
Propofol is the commonest hypnotic agent worldwide. However, it is usually associated with hypotension especially in compromised patients. Ketamine produces dissociative anesthesia and sympathetic stimulation which provides more stable hemodynamic profile; however, ketamine is not widely used as a routine hypnotic because it produces psychomimetic effects such as delirium and emergence agitation. Nevertheless, ketamine still has a role in induction of anesthesia in patients with shock and during procedural sedation. Ketamine is also used as analgesic adjuvant during general anesthesia.
Propofol/ketamine admixture (ketofol) was introduced in anesthetic practice aiming to compensate the side effects of the two drugs and to provide, consequently, the desired balance between adequate hypnosis and hemodynamic stability. Ketofol is currently used with a diversity in the ratio between the two drugs which ranges between 1:1 and 1:10 between ketamine and propofol. Despite its frequent use in sedation and complete anesthesia, most of the available literature for comparisons of different ketofol mixtures was restricted to procedural sedation whose results are not applicable in induction of anesthesia due to the different desirable level of hypnosis and recovery. Therefore, the best combination of the two components of ketofol for induction of anesthesia is unknown
Read the detailed description
Preoperatively, a trained anesthetist will assess the patients regarding the fasting hours, medical history, medications, laboratory investigation, as well as the patient's airway.
In the operating room, routine monitors (electrocardiogram, pulse oximetry, and non-invasive blood pressure monitor) will be applied; intravenous line will be secured, and routine pre-medications (dexamethasone 4 mg as 0.5 mg/ml slow I.V injection) will be administrated. Baseline preoperative blood pressure will be recorded in the supine position as average of 3 readings with difference less than 10% in the systolic blood pressure.
After 3-minutes preoxygenation, patients in the two groups will receive 1 mg/kg lidocaine (in a separate syringe) plus 0.15-0.2 mL/kg from the prepared mixture. This regimen will provide a dose of 1 mg/kg propofol + 1 mg/kg ketamine in the ketofol-1:1 group and 1.5 mg/kg propofol + 0.5 mg/kg ketamine in the ketofol-1:3 group.
Clinical loss of consciousness (defined as no response to auditory command and the disappearance of a patient's eyelash reflex). After loss of consciousness, succinylcholine 1 mg/kg will be administered over 5 seconds, and tracheal intubation will be done through direct laryngoscopy after 60 seconds.
The intubation conditions will be graded by the same anesthetist who performed intubation as excellent, good, or poor for :ease of laryngoscopy, Vocal cord position, Reaction to insertion of the tracheal tube and cuff inflation (Diaphragmatic movement/coughing) Excellent, all criteria excellent; good, all criteria either excellent or good; poor, presence of a single criterion graded as poor.
When the trachea is intubated, mechanical ventilation will be applied to obtain SpO2 > 95% and end-tidal CO2 between 30-40 mmHg and anesthesia will be maintained by isoflurane. Atracurium will be administered after patient recovery from succinylcholine at a dose of 0.5 mg/Kg. Atracurium increments of 10 mg will be administered every 20 min for maintenance of muscle relaxation.
Any episode of hypotension (defined as mean arterial pressure [MAP] <70 mmHg) will be managed by 5 mcg norepinephrine (which will be repeated if hypotension persists for 2 minutes).
If hypertension or tachycardia occurred (defined as MAP or heart rate >120% of baseline), it will be managed by IV 0.5 mg/kg propofol.
After skin incision, hemodynamic and anesthetic management will be according to the attending anesthetist discretion.
- Conditions
- Hypotension, Induction of Anesthesia
- Being tested
- Ketofol equal ratio, Ketofol 1:3 ratio
- Medical subject headings
- Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketofol equal ratioDrug
5mg/ml10 mL propofol (100 mg) will be mixed with 2 mL ketamine (100 mg) and then diluted to a total volume of 20 mL to have a final concentration of 5 mg/mL propofol and 5 mg/mL ketamine
Ketofol 1:3 ratioDrug
15 mL propofol (150 mg) will be mixed with 1 mL ketamine (50 mg) and then diluted to a total volume of 20 mL to have a final concentration of 7.5 mg/mL propofol and 2.5 mg/mL ketamine).
| Study group | Role | What they receive |
|---|---|---|
| ketofol 1:1 | Active comparator | 0.15-0.2 mL/kg from of 5 mg/mL propofol and 5 mg/mL ketamine mixture Receives: Drug: Ketofol equal ratio |
| ketofol 1:3 | Active comparator | 0.15-0.2 mL/kg from of 7.5 mg/mL propofol and 2.5 mg/mL ketamine mixture Receives: Drug: Ketofol 1:3 ratio |
What is being measured
The primary outcome is the main question the study is designed to answer.
norepinephrine dose
microgram
Measured: 1 minute after induction of anesthesia until 15-minutes after induction
Secondary outcomes (5)
postinduction hypotension
mean arterial pressure <70 mmHg
Measured: 1 minute after induction of anesthesia until 15-minutes after induction
severe postinduction hypotension
mean arterial pressure <60 mmHg
Measured: 1 minute after induction of anesthesia until 15-minutes after induction
postinduction hypertension
mean arterial pressure >120% baseline
Measured: 1 minute after induction of anesthesia until 15-minutes after induction
intubation condition
*Excellent, all criteria excellent; good, all criteria either excellent or good; poor, presence of a single criterion graded as poor
- Ease of laryngoscopy Excellent: Easy: jaw relaxed, no resistance to blade insertion Good : Fair: jaw not fully relaxed, slight resistance to blade insertion Poor: Difficult: poor jaw relaxation, active resistance of the patient to laryngoscopy
- Vocal cord position Excellent: Abducted Good : Intermediate/moving Poor: Closed
- Reaction to insertion of the tracheal tube and cuff inflation (Diaphragmatic movement/coughing) Excellent: None Good: Diaphragm/slight: One to two weak contractions or movement for less than 5 s. Poor: Sustained/ Vigorous: More than two contractions and/or movement for longer than 5 s.
Measured: 60 seconds after induction of anesthesia to 180 seconds after induction
total propofol dose
mg
Measured: 0 second after induction of anesthesia to 180 seconds after induction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2021
- Study startDec 2021 (estimated)
- Primary completionMar 2022 (estimated)
- Study completionMar 2022 (estimated)
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 HypotensionStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kasr El Aini Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maha Mostafa Ahmad, MD, Kasr El Aini Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05166330
- Sponsor's protocol ID
- MS-450-2021
- Status last verified
- Dec 2021
- First submitted
- 24 Nov 2021
- Last updated
- 21 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: will be provided upon reasonable request
Publications
Elsherbiny M, Hasanin A, Kasem S, Abouzeid M, Mostafa M, Fouad A, Abdelwahab Y. Comparison of different ratios of propofol-ketamine admixture in rapid-sequence induction of anesthesia for emergency laparotomy: a randomized controlled trial. BMC Anesthesiol. 2023 Oct 3;23(1):329. doi: 10.1186/s12871-023-02292-w.
PubMed 37789329
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Different Ratios of Propofol-ketamine Admixture in Rapid-sequence Induction of Anesthesia for Emergency Laparotomy: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05166330
- Acronym / sponsor ID
- MS-450-2021
- Conditions
- Hypotension, Induction of Anesthesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 74 participants (estimated)
- Lead sponsor
- Kasr El Aini HospitalUniversity, hospital or other
- Study start
- Dec 2021 (estimated)
- Primary completion
- Mar 2022 (estimated)
- Study completion
- Mar 2022 (estimated)
- First posted
- 21 Dec 2021 (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.
Hypotension during anesthesia is associated with serious organ failure and death. The most critical period for intraoperative hypotension is the postinduction period during which, one-third of intraoperative hypotension occurs. Post-induction hypotension has many contributing factors; however, it is closely related to anesthetic drugs. Therefore, manipulation of induction agents makes post-induction hypotension likely preventable. Emergency laparotomy is a critical category of surgery whose patients are usually hemodynamically compromised and prone to post-induction hypotension; furthermore, these patients are usually at high risk of aspiration of gastric contents and require rapid-sequence induction of anesthesia and optimum intubating conditions. Thus, induction of anesthesia for emergency laparotomy requires meticulous balance between achievement of adequate hypnosis and maintenance of stable blood pressure.
Propofol is the commonest hypnotic agent worldwide. However, it is usually associated with hypotension especially in compromised patients. Ketamine produces dissociative anesthesia and sympathetic stimulation which provides more stable hemodynamic profile; however, ketamine is not widely used as a routine hypnotic because it produces psychomimetic effects such as delirium and emergence agitation. Nevertheless, ketamine still has a role in induction of anesthesia in patients with shock and during procedural sedation. Ketamine is also used as analgesic adjuvant during general anesthesia.
Propofol/ketamine admixture (ketofol) was introduced in anesthetic practice aiming to compensate the side effects of the two drugs and to provide, consequently, the desired balance between adequate hypnosis and hemodynamic stability. Ketofol is currently used with a diversity in the ratio between the two drugs which ranges between 1:1 and 1:10 between ketamine and propofol. Despite its frequent use in sedation and complete anesthesia, most of the available literature for comparisons of different ketofol mixtures was restricted to procedural sedation whose results are not applicable in induction of anesthesia due to the different desirable level of hypnosis and recovery. Therefore, the best combination of the two components of ketofol for induction of anesthesia is unknown
Detailed description
Preoperatively, a trained anesthetist will assess the patients regarding the fasting hours, medical history, medications, laboratory investigation, as well as the patient's airway.
In the operating room, routine monitors (electrocardiogram, pulse oximetry, and non-invasive blood pressure monitor) will be applied; intravenous line will be secured, and routine pre-medications (dexamethasone 4 mg as 0.5 mg/ml slow I.V injection) will be administrated. Baseline preoperative blood pressure will be recorded in the supine position as average of 3 readings with difference less than 10% in the systolic blood pressure.
After 3-minutes preoxygenation, patients in the two groups will receive 1 mg/kg lidocaine (in a separate syringe) plus 0.15-0.2 mL/kg from the prepared mixture. This regimen will provide a dose of 1 mg/kg propofol + 1 mg/kg ketamine in the ketofol-1:1 group and 1.5 mg/kg propofol + 0.5 mg/kg ketamine in the ketofol-1:3 group.
Clinical loss of consciousness (defined as no response to auditory command and the disappearance of a patient's eyelash reflex). After loss of consciousness, succinylcholine 1 mg/kg will be administered over 5 seconds, and tracheal intubation will be done through direct laryngoscopy after 60 seconds.
The intubation conditions will be graded by the same anesthetist who performed intubation as excellent, good, or poor for :ease of laryngoscopy, Vocal cord position, Reaction to insertion of the tracheal tube and cuff inflation (Diaphragmatic movement/coughing) Excellent, all criteria excellent; good, all criteria either excellent or good; poor, presence of a single criterion graded as poor.
When the trachea is intubated, mechanical ventilation will be applied to obtain SpO2 > 95% and end-tidal CO2 between 30-40 mmHg and anesthesia will be maintained by isoflurane. Atracurium will be administered after patient recovery from succinylcholine at a dose of 0.5 mg/Kg. Atracurium increments of 10 mg will be administered every 20 min for maintenance of muscle relaxation.
Any episode of hypotension (defined as mean arterial pressure [MAP] <70 mmHg) will be managed by 5 mcg norepinephrine (which will be repeated if hypotension persists for 2 minutes).
If hypertension or tachycardia occurred (defined as MAP or heart rate >120% of baseline), it will be managed by IV 0.5 mg/kg propofol.
After skin incision, hemodynamic and anesthetic management will be according to the attending anesthetist discretion.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ketofol 1:1 | Active comparator | Drug: Ketofol equal ratio0.15-0.2 mL/kg from of 5 mg/mL propofol and 5 mg/mL ketamine mixture |
| ketofol 1:3 | Active comparator | Drug: Ketofol 1:3 ratio0.15-0.2 mL/kg from of 7.5 mg/mL propofol and 2.5 mg/mL ketamine mixture |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- adult patients (18-65 years),
- American society of anesthesiologist I-III,
- scheduled for emergency laparotomy under general anesthesia
Key exclusion criteria (10 listed)
- history of difficult intubation,
- abnormal airway examination,
- cardiac morbidities (impaired contractility with ejection fraction < 50%, heart block, arrhythmias, tight valvular lesions),
- patients on angiotensin converting enzyme inhibitors and angiotensin receptor blockers medications,
- patients with uncontrolled hypertension,
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 |
|---|---|---|
| Ketofol equal ratio5mg/ml10 mL propofol (100 mg) will be mixed with 2 mL ketamine (100 mg) and then diluted to a total volume of 20 mL to have a final concentration of 5 mg/mL propofol and 5 mg/mL ketamine | Drug | ketofol 1:1 |
| Ketofol 1:3 ratio15 mL propofol (150 mg) will be mixed with 1 mL ketamine (50 mg) and then diluted to a total volume of 20 mL to have a final concentration of 7.5 mg/mL propofol and 2.5 mg/mL ketamine). | Drug | ketofol 1:3 |
Primary outcome
norepinephrine dose
Time frame: 1 minute after induction of anesthesia until 15-minutes after induction
microgram
5 secondary outcomes
postinduction hypotension
Time frame: 1 minute after induction of anesthesia until 15-minutes after induction
severe postinduction hypotension
Time frame: 1 minute after induction of anesthesia until 15-minutes after induction
postinduction hypertension
Time frame: 1 minute after induction of anesthesia until 15-minutes after induction
intubation condition
Time frame: 60 seconds after induction of anesthesia to 180 seconds after induction
total propofol dose
Time frame: 0 second after induction of anesthesia to 180 seconds after induction
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2021.
- Derived from this study: PubMed 37789329Elsherbiny M, Hasanin A, Kasem S, Abouzeid M, Mostafa M, Fouad A, Abdelwahab Y. Comparison of different ratios of propofol-ketamine admixture in rapid-sequence induction of anesthesia for emergency laparotomy: a randomized controlled trial. BMC Anesthesiol. 2023 Oct 3;23(1):329. doi: 10.1186/s12871-023-02292-w.
- Individual participant dataSharing planned: No. will be provided upon reasonable request
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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.
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 Ketofol equal ratio and Ketofol 1:3 ratio in people with Hypotension and Induction of Anesthesia, run by Kasr El Aini Hospital 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 3 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: status not confirmed, as of the sponsor's last update on 21 Dec 2021. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact ahmed hasanin, M.D (01095076954 ext. +2, ahmedmohamedhasanin@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
norepinephrine dose (time frame: 1 minute after induction of anesthesia until 15-minutes after induction). 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 NCT05166330, 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 21 Dec 2021.