Effect of Intravenous S-ketamine on Opioid Consumption

Effect of Intravenous S-ketamine on Opioid Consumption and Postoperative Pain in Patients Undergoing Breast Cancer Surgery：a Multicenter, Randomised, Control Trial

Female patients with an American Society of Anesthesia (ASA) physical status I-II, scheduled for elective breast cancer surgery will be included in the study. Subjects will be randomly assigned to one of three groups: the placebo group, the low-dose S-ketamine group, and the high-dose S-ketamine group. The primary outcome is the consumption of sufentanil during the surgery.

Study Overview

• Status: Completed
• Conditions: Breast Cancer Surgery
• Intervention / Treatment: Drug: Placebo; Drug: S-ketamine (low dose); Drug: S-ketamine (high dose)

Detailed Description

All patients will be scheduled to a propofol-remifentanil general anesthesia and receive non-steroid anti-inflammatory drug before incision. Bolus sufentanil will be administered according to the blood pressure, heart rate and bispectral index perioperatively. Patients unable to understand the study procedure or unable to give informed consent, with concurrent analgesic or sedative medication, with history of chronic pain, psychiatric disorders, or alcohol or drug abuse, with an allergy to the study medication, who are pregnant or breast feeding, with a BMI >30 and <18 kg/m2, with severe cardiac, pulmonary, hepatic or renal dysfunction, with intracranial hypertension will be excluded.

Subjects will be randomly assigned to one of three groups: the placebo group, the low-dose S-ketamine group, and the high-dose S-ketamine group. The study medication will be administered in a bolus injected over 30 s after induction, followed by continuous infusion, which started after the initial bolus. The placebo group will receive a bolus of 0.9% saline, followed by continuous infusion of 0.9% saline. The low-dose ketamine group will be administered a bolus of 0.5 mg/kg S-ketamine in saline, followed by 2μg/kg/min S-ketamine in saline, whereas the high-dose ketamine group will be administered a bolus of 0.5 mg/kg S-ketamine in saline, followed by continuous infusion of 4μg/kg/min S-ketamine in saline. The syringes and infusions will be identical for all of the groups and will run at the same rate in all subjects to enable blinding of the investigators. Study medication will be terminated 30 min prior to the end of the surgery. After surgery and in the postanesthesia care unit, patients will be asked about their pain level on a numeric rating scale (NRS), and about the presence of intraoperative awareness, nausea, vomiting, and hallucinations. Rescue analgesia of sufentanil will be provided when NRS ≥ 4 or patients require. Pain level will also be assessed at 0.5, 2, 4, 6, 12 and 24 hour postoperatively as well as 3 and 6 month after the surgery. Depression scale will be evaluated before the surgery and in the 7th postoperative day.

• Study Type: Interventional
• Enrollment (Actual): 345
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hefei, China, 230601
    • Second Affiliated hospital of Anhui Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female patients with an American Society of Anesthesia (ASA) physical status I-II
2. Scheduled for elective breast cancer surgery

Exclusion Criteria:

1. Patients unable to understand the study procedure or unable to give informed consent
2. with concurrent analgesic or sedative medication,
3. with history of chronic pain
4. with history of psychiatric disorders
5. with history of alcohol or drug abuse
6. with an allergy to the study medication
7. who are pregnant or breast feeding
8. with a BMI >30 and <18 kg/m^2
9. with severe cardiac, pulmonary, hepatic or renal dysfunction
10. with intracranial hypertension

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Patients in the placebo group will receive a bolus of 0.9% saline, followed by continuous infusion of 0.9% saline until 30 min prior to the end of the surgery.	Drug: Placebo; Patients in the placebo group will receive a bolus of 0.9% saline, followed by continuous infusion of 0.9% saline until 30 min prior to the end of the surgery.; Other Names: CON
Experimental: Low-dose ketamine group; Patients in the low-dose ketamine group will receive a bolus of 0.5 mg/kg S-ketamine in saline, followed by continuous infusion of 2 μg/kg/min S-ketamine in saline until 30 min prior to the end of the surgery.	Drug: S-ketamine (low dose); Patients in the low-dose ketamine group will receive a bolus of 0.5 mg/kg S-ketamine in saline, followed by continuous infusion of 2 μg/kg/min S-ketamine in saline until 30 min prior to the end of the surgery.; Other Names: LKET
Experimental: High-dose ketamine group; Patients in the low-dose ketamine group will receive a bolus of 0.5 mg/kg S-ketamine in saline, followed by continuous infusion of 4 μg/kg/min S-ketamine in saline until 30 min prior to the end of the surgery.	Drug: S-ketamine (high dose); Patients in the high-dose ketamine group will receive a bolus of 0.5 mg/kg S-ketamine in saline, followed by continuous infusion of 4 μg/kg/min S-ketamine in saline until 30 min prior to the end of the surgery.; Other Names: HKET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
consumption of sufentanil	the consumption of sufentanil during the surgery.	during the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative pain assessment	Patients will be asked about their pain level at rest and moving on a numeric rating scale evaluated on a 11-point (0 = no pain, 10 = worst pain imaginable).	at 0.5, 2, 4, 6, 12 and 24 hours respectively after surgery; Month 3 and Month 6 after surgery
consumption of analgesics	cumulative analgesic consumption after surgery	in the first 24 hour after surgery
Richmond Agitation-Sedation Scale (RASS)	Richmond Agitation-Sedation Scale is a 10-point scale. The values and definitions for each level of agitation and sedation are displayed as follows: +4, Combative, overtly combative or violent; immediate danger to staff; +3, Very agitation, pulls on or removes tube(s) or catheter(s) or has aggressive behavior toward staff; +2, Agitated, frequent nonpurposeful movement or patient-ventilator dyssynchrony; +1, Restless, anxious or apprehensive but movements not aggressive or vigorous; 0, Alert and calm; -1, Drowsy, not fully alert, but has sustained (more than 10 seconds) awakening, with eye contact, to voice; -2, Light sedation, briefly (less than 10 seconds) awakens with eye contact to voice; -3, Moderate sedation, any movement (but no eye contact) to voice; -4, Deep sedation, no response to voice, but any movement to physical stimulation; -5, Unarousable, no response to voice or physical stimulation	30 minutes after surgery
sleep quality scale	Quality of sleep in the night of surgery day using a 4-point scale (1 = "slept well," 2 = "disturbed sleep," 3 = "nightmares," and 4 = "sleepless") will be recorded.	sleep quality scale will be assessed in the morning (8:00 am）of first postoperative day
consumption of propofol	the consumption of propofol during the surgery.	during the surgery
consumption of remifentanil	the consumption of remifentanil during the surgery.	during the surgery
length of anesthesia	from beginning to the end of anesthesia	at the end of anesthesia
length of surgery	from beginning to the end of surgery	at the end of surgery
recovery time	awakening time from surgery	at the time when patients waking up
consumption of vasoactive agents	the consumption of any vasoactive agent (such as phenylephrine, urapidil, ephedrine)	during the surgery
blood pressure	noninvasive blood pressure	before anesthesia, prior to incision, 5, 10, 30, 60 and 120 minutes after incision, at the end of surgery and 30 minutes after surgery
heart rate	Heart rate of the patients	before anesthesia, prior to incision, 5, 10, 30, 60 and 120 minutes after incision, at the end of surgery and 30 minutes after surgery
bispectral index	Bispectral index during the surgery	before anesthesia, prior to incision, 5, 10, 30, 60 and 120 minutes after incision, at the end of surgery and 30 minutes after surgery
adverse effects	The presence of intraoperative awareness, nausea, vomiting, and hallucinations after surgery	through 24 hours after the surgery
ambulation time	interval time of patients' transit from bed rest to ambulation after surgery	7 days after surgery
hospitalization postoperatively	days of hospital staying after surgery	two weeks after surgery
Edinburgh postnatal depression scale	Depression scale generated from Edinburgh postnatal depression scale will be assessed. The minimum value is 0, and the maximum value is 30. The higher score means the higher possibility of depression.	before surgery, at the 7th day and 3 months after surgery

Collaborators and Investigators

• Sponsor: The Second Hospital of Anhui Medical University
• Investigators: Study Chair: Ye Zhang, M.D., Ph. D., The Second Hospital of Anhui Medical University

Publications and helpful links

General Publications

• Brinck ECV, Maisniemi K, Kankare J, Tielinen L, Tarkkila P, Kontinen VK. Analgesic Effect of Intraoperative Intravenous S-Ketamine in Opioid-Naive Patients After Major Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Anesth Analg. 2021 Jan;132(1):69-79. doi: 10.1213/ANE.0000000000004729.
• Hamp T, Baron-Stefaniak J, Krammel M, Reiter B, Langauer A, Stimpfl T, Plochl W. Effect of intravenous S-ketamine on the MAC of sevoflurane: a randomised, placebo-controlled, double-blinded clinical trial. Br J Anaesth. 2018 Dec;121(6):1242-1248. doi: 10.1016/j.bja.2018.08.023. Epub 2018 Oct 15.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2021
• Primary Completion (Actual): July 7, 2024
• Study Completion (Actual): July 7, 2024

Study Registration Dates

• First Submitted: August 22, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: August 3, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: S-ketamine; opioid consumption; breast cancer surgery
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; 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; Psychotropic Drugs; Antidepressive Agents; Ketamine; Esketamine
• Other Study ID Numbers: YX2021-070(F1)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication are to be shared with other researchers.
• IPD Sharing Time Frame: The IPD will become available when summary data are published.
• IPD Sharing Access Criteria: Yun Wu and Ye Zhang will review requests and criteria to share IPD. Requests are to be sent by email to wuyunanyi@163.com or zhangye_hassan@sina.com.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

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