Effect of Intravenous S-ketamine on Opioid Consumption

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer Surgery

Intervention / Treatment
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* Drug: S-ketamine (low dose)
* Drug: Placebo
* Drug: S-ketamine (high dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients with an American Society of Anesthesia (ASA) physical status I-II Scheduled for elective breast cancer surgery Exclusion Criteria: Patients unable to understand the study procedure or unable to give informed consent with concurrent analgesic or sedative medication, with history of chronic pain with history of psychiatric disorders with history of alcohol or drug abuse with an allergy to the study medication who are pregnant or breast feeding with a BMI >30 and <18 kg/m^2 with severe cardiac, pulmonary, hepatic or renal dysfunction with intracranial hypertension
Sexes Eligible for Study
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Female

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group<br>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<br>* 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.<br>* Other names: CON;|
| Experimental: Low-dose ketamine group<br>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)<br>* 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.<br>* Other names: LKET;|
| Experimental: High-dose ketamine group<br>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)<br>* 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.<br>* Other names: HKET;|

What is the study measuring?
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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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer surgery, S-ketamine, opioid consumption