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 (PRO-Ketamine)

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; General Anesthesia; Laparotomy
• Intervention / Treatment: Drug: Ketamine 0.3 mg/kg at end-of-surgery; Drug: Ketamine 0.3 mg/kg at anesthesia induction

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • Bali
    • Denpasar, Bali, Indonesia, 80114
      • Sanglah General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients undergoing elective laparotomy with general anesthesia at Sanglah Hospital from July to September 2020.
2. Patients aged 18-65 years.
3. Patient physical status American American Society of Anesthesiologist (ASA) 1 and 2.

Exclusion Criteria:

1. Contraindication to ketamine.
2. Allergy to morphine
3. Presence of cardiorespiratory chronic diseases.
4. Presence of autoimmune diseases.
5. History of the central nervous system or psychiatric disorders.
6. BMI <18.5 kg/m2 or ≥30 kg/m2.
7. A history of chronic pain killer medications (such as opioid or non-steroidal anti- inflammatory drugs)

Drop Out Criteria

1. Patients with class 3 bleeding during the surgery
2. Patients with more than 5-hours duration of surgery
3. Patients need mechanical ventilation after the surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: End-of-surgery; 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; Ketamine 0.3 mg/kg at end-of-surgery (intravenously); Other Names: Group E; Drug: Ketamine 0.3 mg/kg at anesthesia induction; Ketamine 0.3 mg/kg at anesthesia induction (intravenously); Other Names: Group I
PLACEBO_COMPARATOR: Induction; 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; Ketamine 0.3 mg/kg at end-of-surgery (intravenously); Other Names: Group E; Drug: Ketamine 0.3 mg/kg at anesthesia induction; Ketamine 0.3 mg/kg at anesthesia induction (intravenously); Other Names: Group I

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Udayana University
• Investigators: Principal Investigator: Christopher Ryalino, Dr, Udayana University; Study Director: Made SP Adi, Dr, Udayana University

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 27, 2020
• Primary Completion (ACTUAL): September 30, 2020
• Study Completion (ACTUAL): November 10, 2020

Study Registration Dates

• First Submitted: June 26, 2020
• First Submitted That Met QC Criteria: July 1, 2020
• First Posted (ACTUAL): July 8, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 12, 2020
• Last Update Submitted That Met QC Criteria: November 9, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: general anesthesia; stress response; infammation
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; 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; Ketamine
• Other Study ID Numbers: UNUD-CTR-FK260620-002; 1143/UN14.2.2.VII.14/LT/2020 (OTHER: Committee of Ethical Research of Udayana University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No