Effects of Dexmedetomidine Versus Ketamine on Inflammatory Response and Hemodynamic in Patients

NCT ID: NCT06490731

Last Updated: 2025-05-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2026-01-01

Brief Summary

Inflammatory response and hemodynamic response in patients with intraabdominal sepsis and Effects of Dexmedetomidine versus ketamine on it .

Detailed Description

Severe sepsis is a major healthcare problem with a reported incidence of 1-2% in all hospitalizations. It is a major cause of death in intensive care units worldwide and is the second leading cause of death in noncoronary intensive care unit patients. Mortality remains high at 30-50% despite a better understanding of sepsis pathophysiology and improved advanced care in the past decade . It is defined as a life-threatening organ dysfunction with a Sequential Organ Failure Assessment (SOFA) score > 2 and a mortality of over 10% in hospitals . These patients suffer from circulatory disorders including decreased intravascular volume, peripheral vasodilatation, and myocardial dysfunction, increased metabolism, which may result in hypoxia due to the imbalance between systemic oxygen delivery and oxygen demand .

The pathophysiology of septic shock is well known. However, septic shock therapy is still limited, and the mortality of patients with septic shock remains high. The innate immune system is the first line of defense mechanism against pathogens . The activation of the immunocompetent cells, including macrophages, monocytes, natural killer cells, dendritic cells, and endothelial cells mediate the innate immune response to respond to pathogens or their components . Activated immune cells also secrete pro-inflammatory mediators such as cytokines interleukin (IL-1, IL-6, IL-8), tumor necrosis factor-α (TNF-α), prostaglandins, and histamine . These mediators act on vascular endothelial cells and cause vasodilation, increased vascular permeability, and recruitment of neutrophils to the tissue .

The coagulation cascade is activated locally by upregulating endothelial tissue factors and decreased thrombomodulin and its antithrombotic products .

Ketamine is one of the most rational anaesthetic and sedative agents for patients with sepsis because of its ability to maintain hemodynamics Ketamine also suppresses pro-inflammatory cytokines, apoptosis, and increases intracellular calcium . In the hyperinflammatory phase, ketamine can also reduce anti-inflammatory cytokines such as IL-10 in the hypoinflammatory phase. Ketamine was thought to reduce the risk of secondary infection in the hypoinflammatory phase. However, there has yet to be further research on this hypothesis . Therefore, ketamine is expected to be developed as a candidate for immunotherapy in sepsis.

Dexmedetomidine (alpha2 receptor agonist) has anti-inflammatory and anti-bacterial effects, which are superior to those of gamma-aminobutyric acid agonists, such as benzodiazepines and propofol . Furthermore, it also reduces neuronal apoptosis high doses of central alpha-2-agonists like dexmedetomidine increase vasopressor responsiveness Moreover, even in non-septic patients, alpha-2-agonists are associated with lower vasopressor requirements, increased arterial blood pressure, and enhanced baroreceptor response .

Conditions

Haemodynamic Rebound

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: TRIPLE

Study Groups

Patients will receive dexmedetomidine

Patients will receive dexmedetomidine (Precedex®; 200 µg/2 ml; at one µg/kg loading dose over 10 minutes followed by a 0.5 µg/kg/hr. maintenance dose for 48 hours Dexmedetomidine will be diluted in normal saline at a 4 µg/ ml concentration

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

Patients will receive dexmedetomidine

Patients will receive ketamine

Patients will receive ketamine at one mg/kg IV loading dose over 10 minutes, then a continuous infusion starting at 300 µg /kg/hr over 48 hours

Group Type: ACTIVE_COMPARATOR

Ketamine

Intervention Type: DRUG

patients Will receive ketamine

Interventions

Dexmedetomidine

Patients will receive dexmedetomidine

Intervention Type: DRUG

Ketamine

patients Will receive ketamine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• • Adult patients admitted to ICU after ileus surgery (perforated viscus, infarcted bowel, strangulated hernia, anastomotic leakage, diverticulitis, and intestinal obstruction), and who will be expected to require postoperative sedation and ventilation.

• Abdominal sepsis was determined as organ dysfunction with a substantial change in overall SOFA score (2) ≥ 2 points because of intra-abdominal sepsis.

Exclusion Criteria

• • Known allergy to ketamine, dexmedetomidine,

• Confirmed pregnancy,
• Heart failure (class 3 or 4 of the New York Heart Association),
• Renal failure (RIFLE classification),
• Liver failure (manifested by serum total protein concentration <3 g/dl and total bilirubin >5 mg/dl)
• Known or suspected brain death.
• Patients who receive neuromuscular blockers during the first 48 hours of ICU admission will also be excluded.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New Valley University

OTHER

Sponsor Role: lead

Responsible Party

Ahmed Ismail Abdelsabour

lecture of anesthesia and ICU

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ahmed Ismail Abdel Sabour, MD

Role: PRINCIPAL_INVESTIGATOR

NewValley University

Locations

asyut University

Asyut, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Ahmed Ismail ABDEL sabour, MD

Role: CONTACT

ahmed_ismail87@med.nvu.edu.eg

01097845491 ext. 2

ayman Mohamed Fawzy, Msc

Role: CONTACT

fawzyayman629@med.nvu.edu.eg

01028697487 ext. 2

Facility Contacts

Alaa attia, professur

Role: primary

01099923117

Other Identifiers

New valley anesthesia 4

Identifier Type: -

Identifier Source: org_study_id