Ketofol for Preventing Postoperative Delirium in Elderly Patients

July 30, 2023 updated by: Shereen Elsayed Abd Ellatif, Zagazig University

Ketofol vs Dexmedetomidine for Preventing Post-operative Delirium in Elderly Patients Undergoing Intestinal Obstruction Surgeries. A Randomized Controlled Study

  • Delirium is a cognitive disturbance characterized by acute and fluctuating impairment in attention and awareness. Although its incidence in the general surgical population is 2-3%, it has been reported to occur in up to 10-80% of high-risk patient groups. In addition, the occurrence of postoperative delirium is associated with considerably raised morbidity and mortality and increased healthcare resource expenditure.
  • In the general patient population, no prophylactic pharmacologic treatment has shown widespread effectiveness in preventing delirium. Several studies have failed to find a magic pharmacologic bullet for preventing delirium-ketamine, haloperidol, propofol, antipsychotic and benzodiazepine drugs have recently tested without a clear result of its effectiveness.
  • Dexmedetomidine is an attractive pharmacologic option because of its biological plausibility in modifying several known contributors to delirium.
  • Up to investigators' knowledge, there is no study done to compare the effect of infusion of dexmedetomidine and ketofol mixture as prophylactic agents for high-risk patients as elderly patients who undergoing high-risk surgery such as intestinal obstruction surgery against postoperative delirium occurrence.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Small bowel obstruction (SBO) is one of the most frequent causes of general emergency surgery in elderly patients, approximately 10-12% of adult patients above 65 years presenting with acute abdominal pain at the emergency department (ED) is diagnosed as SBO. Small bowel obstruction is complicated with dehydration, malnutrition, electrolyte and acid-base disturbance, as well as insertion of many catheters as nasogastric tube, triple-lumen tube, and foley's catheter, besides multiple drugs intake due to the associated comorbidities; all of these factors increase the risk of developing POD ].

Delirium is defined as acute onset of fluctuating disturbance of consciousness with reduced ability to focus, alteration of attention, perceptual abnormalities, circadian disruption, a decline in cognitive function (orientation, memory speech, thinking), and psychomotor disturbances. POD commonly occurs between postoperative days 2-5, and it may be hypoactive, hyperactive, or mixed, based on psychomotor clinical features. The incidence rate of postoperative delirium(POD) varies between 9% and 87% in elderly patients, depending on the patients' population and degree of operative stress.

Postoperative delirium develops in the elderly due to multiple risk factors that can be separated into patient-related and operation-related risk factors. Established patient-specific risk factors include pre-existing dementia (appears to be the strongest predictor for the occurrence of POD), older age, functional impairment, greater co-morbidities, and psychopathological symptoms. Operation-specific risk factors for POD are based on the degree of operative stress, any type of iatrogenic event including medication adverse effects (Common drugs that may precipitate delirium in the elderly include antihistamines, anticholinergics, chemotherapeutic agents, dopamine agonists, benzodiazepines, opioid analgesics, steroids, and psychostimulants), physical restraint, urinary catheterization, hospital-acquired infection, dehydration and malnutrition, and admission to the intensive care unit (ICU). The risk factors for developing POD are additive therefore, recognizing those with multiple risk factors should trigger environmental and supportive measures implementation that have been proven to prevent the onset and shorten the duration of POD because POD is associated with poor outcomes such as functional decline, longer hospitalization, greater costs, a greater need for rehabilitation and home healthcare services after discharge and higher mortality.

Ketofol which is a mixture of ketamine and propofol gains increasing interest as an agent for procedural sedation and analgesia for producing a more stable hemodynamic and respiratory profile as Ketamine and propofol appear to counter each other's adverse effects; sympathomimetic effects of ketamine and dose-dependent hypotension and respiratory depression of propofol. Ketofol has been used in different mixed ratios (1:1-1:10) and has proven effective in reducing postoperative agitation in children in several studies as well.

Dexmedetomidine, a highly selective alpha-2 adrenoreceptor (α2) agonist, has been widely used in surgical patients and has positive sedation, anti-anxiety, and analgesic effects. The mechanism of action of dexmedetomidine is unique compared with traditionally administered sedative agents due to its lack of activity at the gamma-aminobutyric acid (GABA) receptor and missing anticholinergic activity.1that may contribute to pathophysiological explanations of the development of delirium 'neurotransmitter hypothesis' and include dysfunction of cholinergic transmission.

The investigators hypothesized that administration of ketofol following induction of general anesthesia, would reduce the incidence of emergence delirium and postoperative delirium, and has a comparable effect to dexmedetomidine on investigators' groups of high-risk elderly patients undergoing urgent exploration of intestinal obstruction.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • 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 Locations

  • Egypt
    • Alsharqia
      • Zagazig, Alsharqia, Egypt, 4115
        • Faculty of medicine, Zagazig university

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

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient acceptance.
  • Age ≥ 60 years old.
  • American society of anesthesia (ASA) (II-III).
  • Gender: males &females
  • BMI < 35kg/m2.
  • able to communicate verbally.
  • Scheduled for exploration surgery for intestinal obstruction under general anesthesia of at least 60 min duration

Exclusion Criteria:

  • Patient refusal.
  • Patients with delirium prior to surgery.
  • Patients with drug misuse history or taking anti-psychotic drugs.
  • Previous hospitalization within 3 months.
  • Legal blindness, severe deafness.
  • History of Acute cerebrovascular conditions; stroke or transient ischemic attack.
  • Patients who could not be prepared with proper fluid resuscitation, electrolyte and acid-base correction prior to surgery.
  • Patients who could be discharged from the intensive care unit (ICU) within two days.
  • Patients with a known history of allergy to study drugs

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control group
21 ml of normal saline 0.9% will be I.V continuously infused fifteen minutes after induction of anesthesia up to two hours postoperatively.
Other: normal saline
normal saline 0.9% in a syringe pump
Active Comparator: ketofol group
21 ml of a mixture of (ketamine and propofol) will be I.V continuously infused fifteen minutes after induction of anesthesia up to two hours postoperatively
Drug: ketofol
prepared in a ratio of (1:4) respectively), where 1ml of ketamine will be added to 20 ml of propofol in a syringe pump
Other Names:
  • a mixture of propofol and ketamine
Active Comparator: dexmedetomidine group
21 ml of a mixture of (dexmedetomidine diluted with normal saline 0.9%) will be I.V continuously infused fifteen minutes after induction of anesthesia up to two hours postoperatively
Drug: dexmedetomidine
2 ml (200 µg) of dexmedetomidine added to 0.9% normal saline in a syringe pump
Other Names:
  • precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
incidence of post operative delirium
Time Frame: up to first three postoperative days
Patients will be assessed for postoperative delirium using Confusion Assessment Method (CAM), or the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)
up to first three postoperative days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
changes of pain assessment
Time Frame: 30 minutes, 1 hour, 2, 4, 18, 12, 24 hours postoperatively
Visual analogue scale
30 minutes, 1 hour, 2, 4, 18, 12, 24 hours postoperatively
changes of hemodynamics
Time Frame: immediately prior to surgery, intraoperative (after starting infusion of study drug, then every 10 minute till end of surgery), later on they will be measured every 15 min postoperatively up to two hours postoperatively
by non invasive blood pressure
immediately prior to surgery, intraoperative (after starting infusion of study drug, then every 10 minute till end of surgery), later on they will be measured every 15 min postoperatively up to two hours postoperatively

Collaborators and Investigators

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

Sponsor

Zagazig University

Investigators

  • Principal Investigator: Shereen E Abd Ellatif, MD, faculty of human medicine,zagazig university

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

March 25, 2021

Primary Completion (Actual)

November 1, 2022

Study Completion (Actual)

February 1, 2023

Study Registration Dates

First Submitted

March 22, 2021

First Submitted That Met QC Criteria

March 24, 2021

First Posted (Actual)

March 25, 2021

Study Record Updates

Last Update Posted (Actual)

August 1, 2023

Last Update Submitted That Met QC Criteria

July 30, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6704/10-3-2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

planned after the completion of the study and publication

IPD Sharing Time Frame

planned after the completion of the study and publication

IPD Sharing Access Criteria

contact with principal investigator

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

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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