Ketamine Versus Propofol Effect on the Immune-mediatory Response for Abdominal Surgery

Major Abdominal Surgery Clinical Trial

Official title:

Immune-mediatory Response of Intravenous Ketamine Versus Propofol for Major Abdominal Surgeries: a Prospective Randomized Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03793075
• Other study ID #: R/18.09.287
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 10, 2019
• Est. completion date: August 15, 2019

Study information

• Verified date: January 2019
• Source: Mansoura University Hospital
• Contact: Reem Abdelraouf, lecturer
• Phone: 01006151100
• Email: reemraouf64[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 36
• Est. completion date: August 15, 2019
• Est. primary completion date: June 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Major Abdominal Surgery

Intervention

Drug:
• Ketamine
ketamine 5 mcg/kg/min will be used as intravenous anesthetic infusion
• Propofol
propofol 17 mcg /kg/min

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Mansoura University Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum level of interleukin 6 (IL-6)	picogram/milliliter using ELISA techniques .Five measurement points : before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.	The time frame extend from 10 minutes before the induction of anesthesia till the first 24 hours postoperative
Primary	Serum level of interleukin IL-1ß (IL-1ß)	picogram/milliliter using ELSA techniques .Five measurement points : before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.	The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
Secondary	Absolute neutrophil count	Number multiplied by 1000/micro liter,measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.	The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
Secondary	Total leukocyte count	Number multiplied by 1000/micro liter ,measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.	The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
Secondary	Neutrophil-lymphocyte ratio (N/L ratio)	measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.	The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
Secondary	Serum Cortisol level	micro-gram /deciliter by immunoassays techniques.measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.	The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
Secondary	C-reactive protein serum level	milgram/liter using ELISA technique. measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.	The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative