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

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

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

Study Overview

• Status: Unknown
• Conditions: Major Abdominal Surgery
• Intervention / Treatment: Drug: Propofol; Drug: Ketamine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Propofol group (P); The maintenance of anesthesia , patient will receive sevoflurane 1%-2.5% with intravenous infusion of propofol 17 mcg /kg/min and 0.5 mg/kg fentanyl will be given if the heart rate or mean blood pressure increased by 30 % or more from the basal readings	Drug: Propofol; propofol 17 mcg /kg/min; Other Names: diprivan
Active Comparator: Ketamine group ((K); The maintenance of anesthesia , patient will receive sevoflurane 1%-2.5% with intravenous infusion of ketamine 5 mcg /kg/min and 0.5 mg/kg fentanyl will be given if the heart rate or mean blood pressure increased by 30 % or more from the basal readings	Drug: Ketamine; ketamine 5 mcg/kg/min will be used as intravenous anesthetic infusion; Other Names: ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Serum level of interleukin IL-1β (IL-1β)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Mansoura University Hospital
• Investigators: Principal Investigator: Reem Abdelraouf, lecturer, Mansoura University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 10, 2019
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): August 15, 2019

Study Registration Dates

• First Submitted: December 30, 2018
• First Submitted That Met QC Criteria: January 3, 2019
• First Posted (Actual): January 4, 2019

Study Record Updates

• Last Update Posted (Actual): January 7, 2019
• Last Update Submitted That Met QC Criteria: January 3, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Hypnotics and Sedatives; Ketamine; Propofol
• Other Study ID Numbers: R/18.09.287

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No