Two Ratios of Propofol-ketamine Admixture for Rapid-sequence Induction Anesthesia for Emergency Laparotomy

December 8, 2021 updated by: Maha Mostafa Ahmad, MD, Kasr El Aini Hospital

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
74

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Egypt
      • Cairo, Egypt, 11562
        • Kasr Alaini hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • adult patients (18-65 years),
  • American society of anesthesiologist I-III,
  • scheduled for emergency laparotomy under general anesthesia

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: ketofol 1:1
0.15-0.2 mL/kg from of 5 mg/mL propofol and 5 mg/mL ketamine mixture
Drug: Ketofol equal ratio
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
Active Comparator: ketofol 1:3
0.15-0.2 mL/kg from of 7.5 mg/mL propofol and 2.5 mg/mL ketamine mixture
Drug: Ketofol 1:3 ratio
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).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
norepinephrine dose
Time Frame: 1 minute after induction of anesthesia until 15-minutes after induction
microgram
1 minute after induction of anesthesia until 15-minutes after induction

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
postinduction hypotension
Time Frame: 1 minute after induction of anesthesia until 15-minutes after induction
mean arterial pressure <70 mmHg
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
mean arterial pressure <60 mmHg
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
mean arterial pressure >120% baseline
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

*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.
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
mg
0 second after induction of anesthesia to 180 seconds after induction

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
mean arterial pressure
Time Frame: 1-minte before the induction, immediately after induction, immediately after intubation, then every 2-minutes for 15-minutes after induction
mmHg
1-minte before the induction, immediately after induction, immediately after intubation, then every 2-minutes for 15-minutes after induction
heart rate
Time Frame: 1-minte before the induction, immediately after induction, immediately after intubation, then every 2-minutes for 15-minutes after induction
beat per minute
1-minte before the induction, immediately after induction, immediately after intubation, then every 2-minutes for 15-minutes after induction

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kasr El Aini Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 24, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 21, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 21, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MS-450-2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

will be provided upon reasonable request

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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