# Optimizing the use of ketamine to reduce chronic postsurgical pain

> **NIH NIH UH3** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $106,127

## 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 particula rly 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
perioperative 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 perioperative 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 adult women after mastectomy or breast
conserving surgery with lymph node dissection will be randomized to receive either a standard continuous
ketamine infusion starting after induction (bolus of 0.35mg/kg followed by infusion at the rate of 0.30mg/kg/hr)
and continued for 2 hours after surgery, a 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 12 months after surgery. We will use Brief Pain Inventory (BPI) severity
score at 3 months after surgery as primary endpoints. Secondary endpoints include pain incidence, BPI, short-
form McGill’s Pain Questionnaire, opioid use, NIH PROMIS scales, Hospital Anxiety and Depression Scale,
Pain Catastrophizing Scale, and Breast Cancer Pain Questionnaire. 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 12 sites, including 7 Clinical and Translational Science A...

## Key facts

- **NIH application ID:** 10405697
- **Project number:** 3UH3CA261067-02S1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Lisa Doan
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $106,127
- **Award type:** 3
- **Project period:** 2021-09-22 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405697

## Citation

> US National Institutes of Health, RePORTER application 10405697, Optimizing the use of ketamine to reduce chronic postsurgical pain (3UH3CA261067-02S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10405697. Licensed CC0.

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