Clinical trial NCT05060068: Effect of Intravenous S-ketamine on Opioid Consumption
Official title: Effect of Intravenous S-ketamine on Opioid Consumption and Postoperative Pain in Patients Undergoing Breast Cancer Surgery：a Multicenter, Randomised, Control Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer Surgery
Keywords: breast cancer surgery
S-ketamine
opioid consumption
Lead sponsor: The Second Hospital of Anhui Medical University
Sponsor class: OTHER
First posted: 2021-09-28
Enrollment: 345
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: consumption of sufentanil
timeFrame: during the surgery
Secondary outcomes:
measure: postoperative pain assessment
timeFrame: at 0.5, 2, 4, 6, 12 and 24 hours respectively after surgery; Month 3 and Month 6 after surgery
measure: consumption of analgesics
timeFrame: in the first 24 hour after surgery
measure: Richmond Agitation-Sedation Scale (RASS)
timeFrame: 30 minutes after surgery
measure: sleep quality scale
timeFrame: sleep quality scale will be assessed in the morning (8:00 am）of first postoperative day
measure: consumption of propofol
timeFrame: during the surgery
measure: consumption of remifentanil
timeFrame: during the surgery
measure: length of anesthesia
timeFrame: at the end of anesthesia
measure: length of surgery
timeFrame: at the end of surgery
measure: recovery time
timeFrame: at the time when patients waking up
measure: consumption of vasoactive agents
timeFrame: during the surgery
measure: blood pressure
timeFrame: before anesthesia, prior to incision, 5, 10, 30, 60 and 120 minutes after incision, at the end of surgery and 30 minutes after surgery
measure: heart rate
timeFrame: before anesthesia, prior to incision, 5, 10, 30, 60 and 120 minutes after incision, at the end of surgery and 30 minutes after surgery
measure: bispectral index
timeFrame: before anesthesia, prior to incision, 5, 10, 30, 60 and 120 minutes after incision, at the end of surgery and 30 minutes after surgery
measure: adverse effects
timeFrame: through 24 hours after the surgery
measure: Edinburgh postnatal depression scale
timeFrame: before surgery, at the 7th day and 3 months after surgery
measure: ambulation time
timeFrame: 7 days after surgery
measure: hospitalization postoperatively
timeFrame: two weeks after surgery
Other outcomes:
Locations:
city: Hefei
country: China
facility: Second Affiliated Hospital of Anhui Medical University
Study officials:
affiliation: The Second Hospital of Anhui Medical University
name: Ye Zhang, M.D., Ph. D.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.