Endometriosis and Pain Treatment by Intraoperative Administration of Low-dose Ketamine

April 28, 2025 updated by: Insel Gruppe AG, University Hospital Bern

Endometriosis and Pain Treatment by Intraoperative Administration of Low-dose Ketamine A Single-Centre, Prospective, Randomized, Controlled Trial

RCT comparing intraoperative administration of low-dose ketamine during laparoscopic endometriosis operation and the postoperative pain outcome

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Endometriosis affects 10% of women of childbearing age and 25% - 50% of infertile women worldwide. Although most patients with endometriosis are completely asymptomatic, there are still a significant proportion of patients whose quality of life is impaired by the disease, resulting in chronic pelvic pain.

Hysterectomy is the most common surgical procedure performed in nonpregnant women when conservative strategies are ineffective. However, there is a poor correlation between objective findings of significant endometriosis and pain severity. Women with endometriosis are at a four-fold greater risk of long-term opioid use than those without endometriosis. Approximately 30% of women who undergo surgery for endometriosis report persistent pain after the surgical removal of the lesion(s). In addition to surgical trauma, other predisposing factors can influence the recovery or progression of chronic diseases, which should be considered when selecting perioperative treatment. Furthermore, studies have shown that in many surgical procedures, incision size and degree of tissue trauma are poorly related to postoperative pain intensity, depending on the pain treatment. After surgery, postoperative pain may be severe overall but usually resolves within the first day of surgery with a Numeric Rating Scale (NRS) pain score ≤ 4. Pain from laparoscopic endometriosis operation includes incisional pain, which may also be severe initially but subsides within the first half of the day; visceral pain that takes longer to resolve (up to a day); and shoulder pain (e.g., shoulder tip pain) that is milder. However, approximately 80% of women develop this condition after gynecologic laparoscopy procedures, which usually disappears within 24 hours and may last for several days. The typical duration of opioid rescue medication use is approximately four days. They should not cause discomfort or limit postoperative recovery.

Although the cause of endometriosis is not yet fully understood, chronic inflammation(s) and increased menstrual bleeding often leads to iron deficiency and even anemia. Iron deficiency anemia is the most common form of anemia, accounting for 50%. In 2019, the prevalence of girls and women of childbearing age (15 - 49 years) with anemia worldwide averaged 30%. For Switzerland, iron deficiency anemia is reported at 11.2 % and is well below the global average. Since iron and its deficiency play an important role in the pathogenesis of endometriosis and possibly also maintain it, it does not surprise that endometriosis patients have an increased risk of iron deficiency or anemia.These patients with a latent or manifest iron deficiency also complain of pain. Up to now, there are only indications that iron could play a role in the proinflammatory pain transmission pathways in endometriosis and could probably maintain and trigger chronic pain. As with nonsurgical chronic pain, psychological and social factors have an important impact that may persist for months or years after surgery. Suboptimal treatment of acute pain has many negative consequences including increased morbidity, impaired physical function and quality of life, slower recovery, prolonged opioid use during and after hospitalization, and increased care costs. Furthermore, in a significant proportion of patients, early postoperative pain appears to trigger pain that may persist for several months. Specifically, younger age, non-white race, lower education, history of sleep disorders, current smoking and alcohol use, high preoperative fibromyalgia screening scores, and high anxiety levels were associated with higher pain severity and excessive pain and may be underlying determinants. Also previous opioid consumption contributes to persistent postoperative pain. As pain is both a sensory and an emotional experience, psychological factors such as mood, disability, and pain coping (e.g., pain self-efficacy and pain catastrophizing) play an important role in this setting. Therefore, patients, particularly those with a predisposition or known tendency for depression, anxiety, or catastrophic symptoms, are at a high risk of developing chronic postsurgical pain. However, in some patients, acute postoperative pain persists beyond the tissue-healing period and develops into a chronic pain state. Approximately 10% of the patients undergoing surgery and 30% of those with endometriosis experience chronic pain. Patients, who have already taken preoperative painkillers or have significantly excessive postoperative analgesic consumption are at a risk of developing chronic pain. Nevertheless, opioids are often overused, particularly during the post discharge period. Even today, acute pain management in the setting of trauma, exacerbation of chronic painful conditions, and postsurgical pain, particularly in patients who are opioid-tolerant remains a challenge in the perioperative setting. In this context, ketamine can be used, generally at subanesthetic doses. However, some patients reported severe debilitating side effects of ketamine administration that did not tolerate higher ketamine doses, an adequate balance of analgesia, and adverse effects in continuous low-dose ketamine in the range of 0.1 - 0.5 mg·kg-1·h-1 was described as sufficient.

Study Type

Interventional

Enrollment (Estimated)

118

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients undergoing surgery for endometriosis operation requiring general anaesthesia at the Inselspital, Bern University Hospital, University of Bern, Department of gynaecology and obstetrics.
  • Age ≥ 18 years
  • American Society of Anesthesiologist (ASA) physical status 1-3
  • Patients with known or suspected endometriosis
  • Written informed consent.

Exclusion Criteria:

  • Age < 18 years
  • ASA physical status ≥4
  • Higher-grade atrioventricular block without pacemaker
  • Severe hypovolemia or bradycardia
  • Uncontrolled hyper- or hypotension
  • Liver disease
  • Known malignant hyperthermia
  • Cardiovascular instability or severe heart failure (New York Heart Association classification (NYHA) > III)
  • Myocardial infarction during the last 30 days prior to surgery
  • Increased intracranial or increased intraocular pressure
  • Limited peripheral autonomic activity, hypersensitivity to ketamine or propofol or its components
  • Pregnancy
  • Rejection or lack of consent of the patient or relatives

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group Ketamine
Standard anaesthesia with propofol and administration of ketamine.
Drug: Ketamine
Low-dose administration of ketamine during laparoscopic surgery
Drug: Propofol
Control group
Other: Group Control
Standard anaesthesia with propofol.
Drug: Propofol
Control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total opioids prescribed and consumed during hospitalization for endometriosis.
Time Frame: During hospitalisation, expected to be on average 2-5 days
The primary study outcome is the total opioids consumed during hospitalisation (converted in oral morphine equivalents)
During hospitalisation, expected to be on average 2-5 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Daily pain severity during hospitalization
Time Frame: During hospitalisation, expected to be on average 2-5 days
Pain score, measured by questionaire, scale from 0 to 10, with higher values corresponding to higher pain level
During hospitalisation, expected to be on average 2-5 days
Postoperative complications
Time Frame: During hospitalisation, expected to be on average 2-5 days
Number of patients with nausea, vomiting or dizziness
During hospitalisation, expected to be on average 2-5 days
Patient wellbeing
Time Frame: 30 days to 6 months after surgery
Measured by questionnaire
30 days to 6 months after surgery
Preoperative iron status
Time Frame: Preoperatively (expected to be on average 2-5 days prior to surgery)
Iron status will be classified as normal, latent iron deficiency, or manifest iron deficiency based on laboratory values (e.g., hemoglobin, ferritin, transferrin saturation). Evaluation of manifest or latent iron deficiency, measured by laboratory testing. The scale typically ranges from 0 to over 300 µg/L in clinical practice, but the diagnostic focus is on lower values. For adults, a ferritin concentration below 10-15 µg/L is generally considered indicative of iron deficiency. Higher values indicate better iron stores, but values above the upper reference limit may suggest iron overload or inflammation.
Preoperatively (expected to be on average 2-5 days prior to surgery)
Pain score
Time Frame: During hospitalisation, expected to be on average 2-5 days
Assessed using the Numeric Rating Scale (NRS), which ranges from 0 (no pain) to 10 (worst imaginable pain). Higher scores indicate worse pain. NRS score (0-10)
During hospitalisation, expected to be on average 2-5 days
Total postoperative analgesic consumption before discharge
Time Frame: During hospitalisation, expected to be on average 2-5 days
The total amount of analgesics consumed postoperatively, converted to intravenous morphine equivalents using standard conversion tables. Higher values indicate greater analgesic requirement. Milligrams of intravenous morphine equivalent (mg IV MEQ)
During hospitalisation, expected to be on average 2-5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Insel Gruppe AG, University Hospital Bern

Investigators

  • Study Chair: Christian Vetter, MD, Dep. of Anaesthesiology and Pain Medicine, Inselsptial Bern

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 3, 2024

Primary Completion (Estimated)

June 30, 2025

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

April 16, 2025

First Submitted That Met QC Criteria

April 28, 2025

First Posted (Actual)

April 30, 2025

Study Record Updates

Last Update Posted (Actual)

April 30, 2025

Last Update Submitted That Met QC Criteria

April 28, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-01677

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Endometriosis

Clinical Trials on Ketamine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Panama

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe