Use of S+Ketamine During Target-Controlled Intravenous Anaesthesia After Abdominal Hysterectomy

The Use of S+Ketamine Versus Placebo During Target-Controlled Intravenous Anaesthesia to Reduce Morphine Consumption and Side Effects After Abdominal Hysterectomy: A Randomized Controlled Trial

The investigators want to investigate the effect of low dose S+ ketamine compared to placebo on cumulative morphine consumption at 24 hours in 90 women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion (TCI) in KK Women's and Children's Hospital. The secondary aims are to investigate the use of low dose S+ ketamine on the incidence of nausea, vomiting, pruritus (opioid side effect), sedation score and psycho mimetic assessment compared to placebo group. The investigators propose to conduct a double blinded, randomized controlled study in women undergoing open abdominal hysterectomy with remifentanil-propofol TCI. (1) Treatment Group: intravenous ketamine 0.5 mg/kg at the beginning and 0.5 mg/kg 20 minutes before extubation. (2) Control Group: intravenous normal saline (as placebo) at the beginning and 20 minutes before extubation.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Ketamine; Hysterectomy; Morphine
• Intervention / Treatment: Drug: Esketamine; Drug: Remifentanil; Drug: Propofol; Drug: Saline

Detailed Description

A number of 90 American Society of Anesthesiologists (ASA) I and II patients undergoing elective open abdominal hysterectomies will be randomly distributed in two groups of 45 patient's each and assigned to receive one of the of the following:

1. Treatment Group: intravenous S+ketamine 0.25 mg/kg (i.v. bolus) at the beginning and 0.25 mg/kg (i.v. bolus) 20 minutes before extubation along with remifentanil according to Minto model and propofol infusion according to Marsh model through target control infusion pump.
2. Control Group: intravenous normal saline (as placebo, with similar volume) at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model through target control infusion pump.

Randomization procedure is performed by the unblinded study team investigator. Patients will be randomized to either the treatment or control groups with a 1:1 allocation ratio. Sequence generation will be performed using a computerized random number generator, employing a permuted block randomization scheme. Allocation concealment will be maintained by having the random numbers pre-generated by an off-site statistician who will not be involved in subject recruitment. Implementation will be via serially numbered opaque sealed envelopes.

Throughout the study period, blinded study members will perform drug administration and data collection, while unblinded study members will be in charge for the investigational drug storage, dispensing and preparation. Any premature unblinding (e.g. accidental unblinding, unblinding due a serious adverse event) of the investigational product will be promptly documented and explained. In the case of adverse effect or severe adverse effect requiring information on the study treatment to manage a patient, the treatment code of the patient will be unblinded.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 229899
    • KK Women's and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female ASA I/II patients above age of 21 years old scheduled gynecological open surgery for benign condition (fibroids, adenomyosis), who are willing and able to give written informed consent for participation in this study.

Exclusion Criteria:

• Contraindications to the use of S+ ketamine, as listed in the product label e.g. untreated or insufficiently treated thyroid hyperfunction, unstable angina pectoris or myocardial infarction within the last 6 months, diseases of the central nervous system, increased intraocular pressure and perforating ocular injuries, surgical procedures in the upper respiratory tract;
• History of drug or alcohol abuse;
• Regular use of analgesics, or use of opioids within 12 hours of surgery;
• Chronic use of benzodiazepine or neuroleptics;
• Thyroid replacement hormone;
• History of ischaemic heart disease, hypertension, psychiatric disorder;
• BMI> 30kg/m2;
• Laparoscopic surgery converted to open surgery;
• Pregnant or breast feeding females.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Esketamine; Esketamine and remifentanil to be given alongside with propofol through target control infusion pump.	Drug: Esketamine; intravenous S+ketamine 0.25 mg/kg (i.v. bolus) at the beginning and 0.25 mg/kg (i.v. bolus) 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Marsh model; Other Names: S+ ketamine; Drug: Remifentanil; Either S+ketamine or saline at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model; Other Names: Ultiva; Drug: Propofol; Either S+ketamine or saline at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model; Other Names: Diprivan
Placebo Comparator: Control; Saline and remifentanil to be given alongside with propofol through target control infusion pump.	Drug: Remifentanil; Either S+ketamine or saline at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model; Other Names: Ultiva; Drug: Propofol; Either S+ketamine or saline at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model; Other Names: Diprivan; Drug: Saline; intravenous normal saline (as placebo, with similar volume) at the beginning and 20 minutes before extubation along with remifentanil according to Minto model and propofol according to Schnider model; Other Names: Sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative Cumulative morphine consumption at 24 hours	Post-operative Cumulative morphine consumption at 24 hours will be measured in the S-ketamine group compared to the placebo group	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of nausea	The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion.	1 day
Incidence of vomiting	The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion.	1 day
Incidence of pruritus	The use of low dose S-ketamine will reduce the incidence of nausea / vomiting, pruritus (opioid side effect) compared to placebo in women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion.	1 day

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital
• Investigators: Principal Investigator: Farida Ithnin, MBBCh, KK Women's and Children's Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: September 3, 2015
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (Actual): July 27, 2017

Study Record Updates

• Last Update Posted (Actual): July 27, 2017
• Last Update Submitted That Met QC Criteria: July 24, 2017
• Last Verified: September 1, 2016

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; Analgesics, Opioid; Narcotics; Psychotropic Drugs; Antidepressive Agents; Hypnotics and Sedatives; Ketamine; Remifentanil; Propofol; Esketamine
• Other Study ID Numbers: EC 200801014

Plan for Individual participant data (IPD)

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