# Optimizing the use of ketamine to reduce chronic postsurgical pain

> **NIH NIH UH3** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $474,022

## Abstract

PROJECT SUMMARY
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, Einst...

## Key facts

- **NIH application ID:** 11092570
- **Project number:** 3UH3CA261067-05S1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Lisa Doan
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $474,022
- **Award type:** 3
- **Project period:** 2021-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11092570

## Citation

> US National Institutes of Health, RePORTER application 11092570, Optimizing the use of ketamine to reduce chronic postsurgical pain (3UH3CA261067-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11092570. Licensed CC0.

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