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

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ClinicalTrials.gov Identifier: NCT03793075
Recruitment Status : Not yet recruiting
First Posted : January 4, 2019
Last Update Posted : January 4, 2019
Sponsor:
Information provided by (Responsible Party):
Abdelraouf Elsharkawy, Mansoura University Hospital

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


Condition or disease Intervention/treatment Phase
Major Abdominal Surgery Drug: Ketamine Drug: Propofol Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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
Masking: Double (Participant, Care Provider)
Masking Description: Double -blinded ( masking of both participant and care provider)
Primary Purpose: Supportive Care
Official Title: Immune-mediatory Response of Intravenous Ketamine Versus Propofol for Major Abdominal Surgeries: a Prospective Randomized Study
Estimated Study Start Date : January 10, 2019
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : August 15, 2019

Resource links provided by the National Library of Medicine


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 Name: 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 Name: ketalar




Primary Outcome Measures :
  1. Serum level of interleukin 6 (IL-6) [ Time Frame: The time frame extend from 10 minutes before the induction of anesthesia till the first 24 hours postoperative ]
    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.

  2. Serum level of interleukin IL-1β (IL-1β) [ Time Frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative ]
    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.


Secondary Outcome Measures :
  1. Absolute neutrophil count [ Time Frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative ]
    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.

  2. Total leukocyte count [ Time Frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative ]
    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.

  3. Neutrophil-lymphocyte ratio (N/L ratio) [ Time Frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative ]
    measured before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.

  4. Serum Cortisol level [ Time Frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative ]
    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.

  5. C-reactive protein serum level [ Time Frame: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative ]
    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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03793075


Contacts
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Contact: Reem Abdelraouf, lecturer 01006151100 reemraouf64@gmail.com

Sponsors and Collaborators
Mansoura University Hospital
Investigators
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Principal Investigator: Reem Abdelraouf, lecturer Mansoura University

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Responsible Party: Abdelraouf Elsharkawy, Lecturer of anesthesia and surgical intensive care, Mansoura University Hospital
ClinicalTrials.gov Identifier: NCT03793075     History of Changes
Other Study ID Numbers: R/18.09.287
First Posted: January 4, 2019    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: January 2019

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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

Additional relevant MeSH terms:
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Propofol
Ketamine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Dissociative
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action