Program Official
Principal Investigator
Jing
Wang
Awardee Organization
New York University School Of Medicine
United States
Fiscal Year
2024
Activity Code
UH3
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date
NIH RePORTER
For more information, see NIH RePORTER Project 3UH3CA261067-05S1
Optimizing the use of ketamine to reduce chronic postsurgical pain
Chronic pain contributes significantly to the current opioid epidemic. Up to 20% of postoperative patients develop chronic postsurgical pain (CPSP). CPSP is highly associated with chronic opioid use and dependence, and yet routine multimodal analgesia as a combination of acetaminophen, NSAIDs, and anti-neuropathic agents is only moderately effective in preventing CPSP. The incidence for CPSP is particularly high in patients undergoing mastectomy or breast conserving surgery with lymph node dissections (25- 60%). This specific postsurgical pain condition is known as post-mastectomy pain syndrome (PMPS), and a recent study showed that 1 in 10 patients continue to use opioids 3 months after surgery. We aim to study the effectiveness of postoperative ketamine for the prevention of PMPS, within the NIH HEAL Pain Management Effectiveness Research Network (Pain ERN). Our rationale is that ketamine can reduce key risks for CPSP including acute pain severity, anxiety and depression, and pain catastrophizing, and in doing so can prevent the development of PMPS. Mechanistically, ketamine is known to enhance endogenous cortical control of pain and mood. There is strong clinical evidence for postoperative ketamine infusion in reducing postsurgical pain, and for a single ketamine bolus (0.3-0.5mg/kg) to treat depression and anxiety associated with postsurgical pain. However, studies are urgently needed to test the efficacy of ketamine in the perioperative period for preventing CPSP, particularly PMPS, in a large cohort of patients and to assess clinical variables predictive for chronic pain severity and for treatment effects. We aim to conduct a multi-site, three-arm RCT to study the effectiveness of ketamine in reducing the incidence and severity of PMPS. 750 patients after mastectomy or breast conserving surgery with lymph node dissection will be randomized to receive either a standard continuous ketamine infusion starting after surgical incision (bolus of 0.35mg/kg followed by infusion at the rate of 0.25mg/kg/hr) and continued for 2 hours after surgery, a unique regimen of single-bolus ketamine (0.6mg/kg) administered right after surgery, or placebo (saline) control. To maintain the pragmatic nature of an effectiveness trial, all patients will receive routine postoperative multimodal analgesia. Compatible with recent NIH recommendations, we will assess pain, function and mood over 6 months after surgery. We will use Brief Pain Inventory (BPI) severity score at 3 months after surgery as primary endpoints. Secondary and exploratory endpoints include pain incidence, BPI, opioid use, and NIH PROMIS Anxiety and Depression scales as well as for neuropathic pain and physical function. We will also build precision medicine models to analyze clinical variables associated with CPSP and with success of ketamine treatment. Agreements have been reached with 15 sites, including 7 Clinical and Translational Science Awards (CTSA) hubs, NYU, Columbia, Einstein, Brigham and Women’s Hospital, UT Southwestern, UT MD Anderson, University of Pittsburgh, Memorial Sloan Kettering Cancer Center, Univ. of Alabama, Univ. of Arkansas, Mayo Clinic, Rush University, MetroHealth, and Univ. of Washington, to carry out this study successfully.
Publications
- Doan LV, Li A, Brake L, Ok D, Jee HJ, Park H, Cuevas R, Calvino S, Guth A, Schnabel F, Hiotis K, Axelrod D, Wang J. Single-Dose of Postoperative Ketamine for Postoperative Pain After Mastectomy: A Pilot Randomized Controlled Trial. Journal of pain research. 2023 Mar 14;16:881-892. doi: 10.2147/JPR.S389564. eCollection 2023. PMID: 36942305
- Wang J, Doan LV, Axelrod D, Rotrosen J, Wang B, Park HG, Edwards RR, Curatolo M, Jackman C, Perez R, NCATS Trial Innovation Network. Optimizing the use of ketamine to reduce chronic postsurgical pain in women undergoing mastectomy for oncologic indication: study protocol for the KALPAS multicenter randomized controlled trial. Trials. 2024 Jan 19;25(1):67. PMID: 38243266
- Lilaonitkul M, Cosden CW, Markley JC, Pian-Smith M, Lim G, Yeh P, Aleshi P, Boscardin C, Sullivan K, George RB. Development of obstetric anesthesia core competencies for USA residency programs through a Delphi process. Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2023 Oct;70(10):1611-1622. Epub 2023 Aug 3. PMID: 37535252
- Park YL, Clifton B, Ashraf R, Barlow R, Anderson A, Altamirano V, Miller E, Neuman M, Lim G. Patient and provider perspectives on pain and other dimensions of anesthesia experience for cesarean delivery: A qualitative study. Research square. 2024 Aug 30. PMID: 39257975