Ketofol for Preventing Postoperative Delirium in Elderly Patients

Delirium on Emergence Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04816162
• Other study ID #: 6704/10-3-2021
• Status: Completed
• Phase: Phase 4
• Start date: March 25, 2021
• Est. completion date: February 1, 2023

Study information

• Verified date: July 2023
• Source: Zagazig University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: February 1, 2023
• Est. primary completion date: November 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Delirium
• Delirium on Emergence
• Emergence Delirium

Intervention

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
• dexmedetomidine
2 ml (200 µg) of dexmedetomidine added to 0.9% normal saline in a syringe pump

Other:
• normal saline
normal saline 0.9% in a syringe pump

Locations

Country	Name	City	State
Egypt	Faculty of medicine, zagazig university	Zagazig	Alsharqia

Sponsors (1)

Lead Sponsor	Collaborator
Zagazig University

Country where clinical trial is conducted

Egypt, 

References & Publications (6)

Dale O, Somogyi AA, Li Y, Sullivan T, Shavit Y. Does intraoperative ketamine attenuate inflammatory reactivity following surgery? A systematic review and meta-analysis. Anesth Analg. 2012 Oct;115(4):934-43. doi: 10.1213/ANE.0b013e3182662e30. Epub 2012 Jul 23. — View Citation

Li WX, Luo RY, Chen C, Li X, Ao JS, Liu Y, Yin YQ. Effects of propofol, dexmedetomidine, and midazolam on postoperative cognitive dysfunction in elderly patients: a randomized controlled preliminary trial. Chin Med J (Engl). 2019 Feb;132(4):437-445. doi: 10.1097/CM9.0000000000000098. — View Citation

Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009 May-Jun;50(3):206-17. doi: 10.1176/appi.psy.50.3.206. — View Citation

Ozturk E, van Iersel M, Stommel MM, Schoon Y, Ten Broek RR, van Goor H. Small bowel obstruction in the elderly: a plea for comprehensive acute geriatric care. World J Emerg Surg. 2018 Oct 20;13:48. doi: 10.1186/s13017-018-0208-z. eCollection 2018. — View Citation

Smischney NJ, Hoskote SS, Gallo de Moraes A, Racedo Africano CJ, Carrera PM, Tedja R, Pannu JK, Hassebroek EC, Reddy DR, Hinds RF, Thakur L. Ketamine/propofol admixture (ketofol) at induction in the critically ill against etomidate (KEEP PACE trial): study protocol for a randomized controlled trial. Trials. 2015 Apr 21;16:177. doi: 10.1186/s13063-015-0687-0. — View Citation

Spangler R, Van Pham T, Khoujah D, Martinez JP. Abdominal emergencies in the geriatric patient. Int J Emerg Med. 2014 Oct 21;7:43. doi: 10.1186/s12245-014-0043-2. eCollection 2014. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	incidence of post operative delirium	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	changes of pain assessment	Visual analogue scale	30 minutes, 1 hour, 2, 4, 18, 12, 24 hours postoperatively
Secondary	changes of hemodynamics	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