Ketofol for Preventing Postoperative Delirium in Elderly Patients

Sponsor

Zagazig University (Other)

Overall Status

Completed

CT.gov ID

NCT04816162

Collaborator

(none)

120

Enrollment

Location

Arms

14.7

Actual Duration (Months)

8.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Delirium on Emergence	Drug: ketofol Drug: dexmedetomidine Other: normal saline	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A computer-generated table will be used to divide patients equally into three study groups In group C (control group):21 ml of normal saline 0.9% will be I.V infused at a rate of 0.3-0.4 mg/kg/h to the patient. In group K: ketofol (a mixture of ketamine and propofol will be prepared in a ratio of (1:4) respectively), will be I.V infused at a rate of 0.3-0.4 mg/kg/h to the patient. In group D: adding dexmedetomidine 2 ml (200 µg) to 19 ml of 0.9% normal saline to start I.V infusion to the patientA computer-generated table will be used to divide patients equally into three study groups In group C (control group):21 ml of normal saline 0.9% will be I.V infused at a rate of 0.3-0.4 mg/kg/h to the patient. In group K: ketofol (a mixture of ketamine and propofol will be prepared in a ratio of (1:4) respectively), will be I.V infused at a rate of 0.3-0.4 mg/kg/h to the patient. In group D: adding dexmedetomidine 2 ml (200 µg) to 19 ml of 0.9% normal saline to start I.V infusion to the patient

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

double-blinded(participants and outcome assessors)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Mar 12, 2021

Actual Primary Completion Date :

Feb 1, 2022

Actual Study Completion Date :

Jun 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

incidence of post operative delirium [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)

Secondary Outcome Measures

changes of pain assessment [30 minutes, 1 hour, 2, 4, 18, 12, 24 hours postoperatively]
Visual analogue scale
changes of hemodynamics [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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