The Effect of Low Dose Ketamine on Narcotic Consumption in Patients Undergoing Laparoscopic Cholecystectomy

This double-blinded randomized control trial aims to analyze the effect of low dose Ketamine on narcotic consumption, in patients undergoing Laparoscopic cholecystectomy.

Study Overview

• Status: Completed
• Conditions: Cholelithiasis
• Intervention / Treatment: Drug: Ketamine Hydrochloride

Detailed Description

Pain management is an essential component of every surgical procedure due to its effect on early mobilization. Adequate pain relief leads to rapid recovery and improved surgical outcome. It also decreases the chances of deep vein thrombosis, neuropathic pain and cardio-respiratory complications resulting in decreased cost and length of stay in the hospital. Poorly managed pain is not only inhuman but also detrimental for the patient's overall condition.

Several narcotic and non-narcotic modalities have been used to achieve for adequate post-operative analgesia. Among these, opioid narcotics are widely used due to their potent analgesic effect. Unfortunately opioids have a number of unwanted side-effects including respiratory depression, chest rigidity, drowsiness, nausea and vomiting. These unwanted side-effects had been shown to be decreased by the use of low-dose ketamine used immediately before wound closure in a number of surgeries. It has been reported that single dose of 0.15-1 mg/kg ketamine along with opioids was effective in decreasing the post-operative narcotic consumption. Availability of narcotics is also an issue worldwide particularly in low income countries. Alternate drugs and methods have been tried to minimize opioid use. Low dose ketamine seems to be an effective adjunct in reducing opioid requirement during perioperative period. Subcutaneous and spray of low dose ketamine has also been tried successfully for tonsillectomy pain. The role of low dose ketamine in patients undergoing laparoscopic cholecystectomy is not clear and is yet to be studied in our population. To analyze this effect a randomized controlled trial was performed to study the effect of low-dose ketamine on the narcotic consumption in PACU after laparoscopic cholecystectomy.

Materials and Methods:

The Double Blind Randomized Controlled trial was carried out at the Department of Anaesthesia, Aga Khan University Hospital, after approval from the ethical review committee. Sample size was calculated to be 86 (43 in each arm receiving either ketamine or saline) using 80% power at 5% level of significance assuming a 30% difference in the mean narcotic consumption in the ketamine group as compared to the control group using NCSS~Pass (version, 11.04).

ASA I and II patients undergoing laparoscopic cholecystectomy between 25 to 60 years of age were randomly selected and informed consent was taken. Patients having psychological problems, seizures or any CNS disease, history of substance abuse, allergy to ketamine and pethidine, pregnancy, cardiovascular, hepatic or renal disease were excluded from the study.

Intraoperative analgesia was standardized in all patients by giving 3μgm/kg fentanyl at induction. Syringes containing 10 ml ketamine or normal saline were prepared and documented. Patients were randomly allocated by sealed envelopes into two groups. Group S was given placebo (saline) while group K was given ketamine 0.5mg/kg intravenously just after the wound closure.

Patient and the observer were blinded to the groups. Pain scores were documented in a proforma by using VAS as soon as patients were shifted to recovery room and repeated at 15 and 30 minutes interval. Pethidine 10 mg was administered intravenously as rescue analgesia whenever pain score was ≥ 4. Total pethidine consumption in initial 30 minutes of recovery stay was calculated and documented.

All patients were given supplemental oxygen in recovery room to prevent hypoxia. Tachycardia (heart rate ≥120bpm) and hypertension (SBP >140 mmHg) were managed by beta blockers.

All analyses were conducted using the Statistical Package for Social Science version 19 (SPSS Inc, Chicago, IL). Continuous data are presented as mean and standard deviation after normality testing by Kolmogorov-Smirnov and histogram and analyzed by independent sample t-test. Categorical data are presented as frequency and percentage and analyzed by Chi-square test or fisher exact test. Effect of the intervention on amount of pethidine consumption was assessed by general liner model and regression coefficient were reported. To assess whether the effect of the intervention differed over time, an interaction between time and intervention was tested. Effect of the intervention on pain (measured 5 times during the first postoperative day) was assessed using a generalized estimating equation with continuous time, exchangeable working correlation matrix structure. Main effects were time and intervention. Interaction between time and intervention was also tested. p≤0.05 was considered as significant.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• all ASA 1 and 2 patients undergoing Laparoscopic Cholecystectomy electively.

Exclusion Criteria:

• Hepatic and renal disease and ASA 3 and 4 patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine group (Group K); Group K was given ketamine @ 0.5mg/kg (prepared by dilution in 0.9% normal saline in 10 ml syringe) at the time of wound closure.	Drug: Ketamine Hydrochloride; Ketamine was given prior to wound closure.; Other Names: ketasol
Other: Saline group (Group S); Group S was given saline in 10 ml syringe	Drug: Ketamine Hydrochloride; Ketamine was given prior to wound closure.; Other Names: ketasol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain score using Visual Analogue scale, ranging from 0 (minimum) and 10 (maximum), 3 and below showing no pain and scores above 3 showing moderate to severe pain.	Change in pain score using Visual Analogue Scale	Baseline on arrival in the post anaesthesia care unit and then every fifteen minutes unto one hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
narcotic consumption in the post operative anaesthesia care unit	requirement of narcotic in the post anaesthesia care unit	postoperatively, after arrival in the post anaesthesia care unit at every fifteen minutes unto one hour

Collaborators and Investigators

• Sponsor: Aga Khan University

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2013
• Primary Completion (Actual): November 30, 2013
• Study Completion (Actual): November 30, 2013

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: July 1, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathological Conditions, Anatomical; Gallbladder Diseases; Biliary Tract Diseases; Calculi; Gallstones; Cholelithiasis; Cholecystolithiasis; 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: 2387-Ane-ERC-12

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
• product manufactured in and exported from the U.S.: No