Opioid-sparing by low-dose ketamine for endometriosis surgery. A single-center, prospective, randomized, trial

ABSTRACT Endometriosis affects 10% of women of childbearing age and 25–50% of infertile women worldwide. Although most patients with endometriosis are completely asymptomatic, there is still a significant proportion of patients, whose quality of life is impaired by the disease, resulting in chronic pelvic pain. However, there is a poor correlation between objective findings of significant endometriosis and pain severity. Opioids typically form part of a postoperative analgesic regimen. However, opioid tolerance, adverse effects, contraindications, or a combination of these factors may limit their use. As part of the multimodal regime, ketamine may play a critical role for patients undergoing surgery when postoperative pain is expected to be severe. It is most commonly used for acute pain management in settings involving trauma, the exacerbation of chronic painful conditions, and postsurgical pain, particularly in opioid-tolerant patients, generally at subanesthetic doses. Notably, in therapy-refractory pharmacological situations, surgical treatment of endometriosis with intraoperative low-dose ketamine could be helpful and may constitute an effective strategy for limiting disease recurrence. However, it is important to evaluate the significance of ketamine in endometriosis surgery for preventing chronic pain syndrome, which in turn would result in an improvement in the quality of life of patients with endometriosis. Clinical trial registration: www.clinicaltrials.gov identifier is NCT06951802. Plain Language Summary Endometriosis is a condition that affects about 10% of women who can have children and up to half of women who have trouble getting pregnant. Many women with endometriosis do not have symptoms, but a good number suffer from chronic pelvic pain that really lowers their quality of life. Interestingly, how bad the pain feels do not always match what doctors see during examinations. After surgery, opioids are commonly used to manage pain. However, opioids are not always the best choice because some people develop tolerance, have side effects, or cannot take them due to other health issues. That is where the medicament “ketamine” can be useful as part of a combined pain relief plan, especially for patients expected to have severe pain after surgery. Ketamine is often given in low doses to help with acute pain, particularly in patients who have become tolerant to opioids. In cases where regular drugs do not work well, ketamine given during surgery for endometriosis might help not only with pain relief but also help prevent in reducing long-term pain syndromes, improving the overall quality of life for these patients. So, while ketamine is not a magic fix, it might be an important part of managing severe pain in endometriosis surgery and helping women feel better in the long run. Article highlights Endometriosis affects approximately 10–15% of women of reproductive age and is associated with chronic pelvic pain and infertility. Many patients experience persistent postoperative pain despite surgical excision of endometriotic lesions. This prospective, randomized controlled trial investigates whether adding low-dose ketamine (0.1 mg·kg−1 ·h−1) to propofol anesthesia reduces postoperative opioid consumption compared with propofol alone. Secondary outcomes include daily opioid use, pain intensity (NRS), postoperative side effects (e.g., nausea, dizziness), a long-term pain, and opioid use up to 6 months post-surgery. The impact of preoperative iron deficiency (manifest or latent) on analgesic requirements and pain outcomes is also evaluated. The study enrolls 118 adult women with endometriosis undergoing laparoscopic surgery at Bern University Hospital. Patients are randomized to receive either standard TIVA with propofol plus ketamine or propofol alone, in combination with standard adjunct anesthetics. The primary endpoint is total in-hospital opioid consumption (morphine equivalents). Ethical approval was obtained from the Bern Cantonal Ethics Committee; all procedures adhere to the Helsinki Declaration, SPIRIT, and CONSORT guidelines. Ketamine’s NMDA receptor antagonism and local anesthetic effects are expected to improve analgesia and reduce opioid-related risks. The trial aims to inform multimodal pain management strategies in endometriosis surgery and improve long-term outcomes and quality of life. Author contributions CV: Conceptualization, Methodology, Project administration, Writing – original draft, Writing – review and editing. Disclosure statement The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. Reviewer disclosures Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Ethical declaration The study was approved by cantonal Ethics Committee with number 2024–01677. Informed written consent to take part in the research will be obtained prior to the commencement of the study. Data availability statement Data not available due to ethical restrictions.