Comparison of CRP Levels, Neutrophil Count, and Clinical Outcomes of Low Dose Ketamine Between at Anesthesia Induction and at the End of Surgery in Patients Undergo Elective Laparotomy

Study Overview
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Brief Summary
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The effects of anesthesia and surgery can lead to stress responses that result in hormonal and metabolic changes in the body. The immune system and the nervous system communicate both ways, and it was found that nociception and proinflammatory cytokines play a joint regulatory role, i.e., increased production of proinflammatory cytokines can worsen the pain. Major surgery can trigger the release of cytokines such as IL-1, IL-6, and TNF-α.

Detailed Description
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The effects of anesthesia and surgery can lead to stress responses that result in hormonal and metabolic changes in the body. The immune system and the nervous system communicate both ways, and it was found that nociception and proinflammatory cytokines play a joint regulatory role, i.e., increased production of proinflammatory cytokines can worsen the pain. Major surgery can trigger the release of cytokines such as IL-1, IL-6, and TNF-α. The acute analgesic effect of ketamine is generally believed to be mediated through the blockade of the phencyclidine binding site of the N-methyl-d-aspartate (NMDA) receptor of nociceptive neurons. Ketamine can reduce the inflammatory response marked by a decrease in CRP levels to surgical trauma and can prevent secondary damage to tissues/organs that were not initially affected by surgery by reducing inflammation. This also reduces postoperative pain and analgesics.

Official Title
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Comparison of CRP Levels, Neutrophil Count, and Clinical Outcomes of Low Dose Ketamine Between at Anesthesia Induction and at the End of Surgery in Patients Undergo Elective Laparotomy

Conditions
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General Anesthesia, Laparotomy, Inflammation

Intervention / Treatment
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* Drug: Ketamine 0.3 mg/kg at end-of-surgery
* Drug: Ketamine 0.3 mg/kg at anesthesia induction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing elective laparotomy with general anesthesia at Sanglah Hospital from July to September 2020. Patients aged 18-65 years. Patient physical status American American Society of Anesthesiologist (ASA) 1 and 2. Exclusion Criteria: Contraindication to ketamine. Allergy to morphine Presence of cardiorespiratory chronic diseases. Presence of autoimmune diseases. History of the central nervous system or psychiatric disorders. BMI <18.5 kg/m2 or ≥30 kg/m2. A history of chronic pain killer medications (such as opioid or non-steroidal anti- inflammatory drugs) Drop Out Criteria Patients with class 3 bleeding during the surgery Patients with more than 5-hours duration of surgery Patients need mechanical ventilation after the surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a double-blind, randomized control trial. It provides a controlled care comparison between low-dose ketamine given at anesthesia induction and at the end-of-surgery.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: End-of-surgery<br>Low-dose ketamine (0.3 mg/kg) in 3 ml normal saline solution given at the end of surgery | Drug: Ketamine 0.3 mg/kg at end-of-surgery<br>* Ketamine 0.3 mg/kg at end-of-surgery (intravenously)<br>* Other names: Group E;Drug: Ketamine 0.3 mg/kg at anesthesia induction<br>* Ketamine 0.3 mg/kg at anesthesia induction (intravenously)<br>* Other names: Group I;|
| Placebo Comparator: Induction<br>Low-dose ketamine (0.3 mg/kg) in 3 ml normal saline solution given at induction | Drug: Ketamine 0.3 mg/kg at end-of-surgery<br>* Ketamine 0.3 mg/kg at end-of-surgery (intravenously)<br>* Other names: Group E;Drug: Ketamine 0.3 mg/kg at anesthesia induction<br>* Ketamine 0.3 mg/kg at anesthesia induction (intravenously)<br>* Other names: Group I;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum CRP level | Serum C-reactive protein level | 1-hour before surgery | 
| Serum CRP level | Serum C-reactive protein level | 24-hours after surgery | 
| serum neutrophil-count | serum neutrophil-count (from a complete blood count test) | 1-hour before surgery | 
| serum neutrophil-count | serum neutrophil-count (from a complete blood count test) | 24-hours after surgery | 
| VAS (visual analog score) | minimum=0; maximum=10; higher score corresponds to more severe pain | first 24 hours after the surgery | 
| morphine consumption (mg) | total morphine consumption in 24 hours after the surgery | first 24 hours after the surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stress response, infammation, general anesthesia