Clinical trial NCT03793075: Ketamine Versus Propofol Effect on the Immune-mediatory Response for Abdominal Surgery
Official title: Immune-mediatory Response of Intravenous Ketamine Versus Propofol for Major Abdominal Surgeries: a Prospective Randomized Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Major Abdominal Surgery
Lead sponsor: Mansoura University Hospital
Sponsor class: OTHER
First posted: 2019-01-04
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participating subject will be divided equally and randomly into two groups.The first group is propofol group while the second is the ketamine group
Primary purpose: SUPPORTIVE_CARE

Brief summary: Host systemic responses to vigorous stimuli as trauma, surgical tissue injury, anesthesia and post-operative pain, leads to release a variety of pro-inflammatory cytokines including interleukin-1 (IL-1) and interleukin-6 (IL-6) mainly from monocytes and macrophages Thus, the rise of IL-6 is regarded as an early marker of tissue damage and its rise proportional to the degree of tissue damage .

It has been demonstrated that systemic responses to stress may be modified by the anesthetic technique used . Total intravenous anesthesia (TIVA) especially propofol based greatly suppresses the stress response induced by surgery when compared to inhalation by lowering cortisol levels.

Ketamine has the ability to modulate (modify) inflammation . Even the sub-anesthetic doses of ketamine in animal models were even provided to have an effect on the inflammatory response system in the central nervous system

Detailed description: The release a variety of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) mainly from monocytes and macrophages due to surgical trauma or anesthesia .

IL-6 is constantly found in the peripheral blood and rapidly within few minutes unlike other pro inflammatory mediators. Thus, the rise of IL-6 is regarded as an early marker of tissue damage and IL-6 levels are proportional to the degree of tissue damage . The two major actions of IL-6 are having a key role in regulating stress responses by activating the hypothalamic-pituitary- adrenal (HPA) axis and synthesizing fibrinogen (which is necessary for the acute-phase response) serving as a growth factor for activated B-cells .

While appropriate inflammatory reactions are advantageous and essential for wound healing and host defense against microorganisms, excessive immune responses can be detrimental. The released mediators prompt systemic endocrine, immunological and metabolic responses result in increased pain sensitivity, altered metabolism, hyperthermia and greater secretion of liver acute phase proteins and stress hormones, so yields unstable patient's hemodynamic status

Propofol was documented to have an advantage in terms of inflammatory and immunomodulatory effects through significant effect on TNF-α, IL-6 and IL-10 release .

Ketamine has the ability to modulate (modify) inflammation and this is why it is recommended in patients with sepsis undergoing surgery . This may be possibly related with the variations in TNF-α and nuclear factor-κB expression . Even the sub-anesthetic doses of ketamine in animal models were even provided to have an effect on the inflammatory response system in the central nervous system which is involved in its therapeutic effect on depression (Yang-2 et al., 2013).

This study will be conducted to compare between the intravenous infusion of ketamine against the intravenous infusion of propofol during general anesthesia in patients undergoing major abdominal surgeries.

Eligibility criteria: Inclusion Criteria:

* Elective major abdominal surgeries with median incision with right or left extension.
* ASA -physical status I -II
* aged from 18 till 70 years

Exclusion Criteria:

* body mass index more than 35 kg/m2,
* Patients having severe cardiovascular, respiratory, hepatic, renal, Endocrinol disorders, malignant
* Patients having chronic inflammatory diseases
* Patients received suppressant drugs in the 6 weeks before surgery.
* Any known allergy or any contraindications to anesthetic drugs;
* patient refusal,
* The usage of anti- emetic drug 24 hours before operation

Primary outcomes:
measure: Serum level of interleukin 6 (IL-6)
timeFrame: The time frame extend from 10 minutes before the induction of anesthesia till the first 24 hours postoperative
measure: Serum level of interleukin IL-1β (IL-1β)
timeFrame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
Secondary outcomes:
measure: Absolute neutrophil count
timeFrame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
measure: Total leukocyte count
timeFrame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
measure: Neutrophil-lymphocyte ratio (N/L ratio)
timeFrame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
measure: Serum Cortisol level
timeFrame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
measure: C-reactive protein serum level
timeFrame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
Other outcomes:
Locations:
Study officials:
affiliation: Mansoura University
name: Reem Abdelraouf, lecturer
role: PRINCIPAL_INVESTIGATOR
References: