Intraoperative Ketamine on Chronic Pain After Mastectomy

Summary

Preventive analgesia is when an administered analgesic drug provides reduction in pain beyond its duration of action. This can be used to reduce acute postoperative pain and prevent occurrence of chronic post-surgical pain.

According to the International Association for the Study of Pain (IASP), chronic pain can be defined as pain that persisted beyond the time of normal tissue healing (usually 3 months) and that was not related to other causes. Mastectomy is associated with a high incidence of chronic post-surgical pain. Breast cancer is the most common malignancy affecting females around the world. Many undergo mastectomy as part of curative treatment. However, a significant proportion of patients experience chronic post-surgical pain. This results in significant negative impact on physical, psychological and social wellbeing.

Ketamine is an intravenous anaesthetic drug with analgesic effects. It can be used to treat both acute and chronic pain. A recent meta-analysis of different surgeries showed that patients receiving ketamine had a modest but statistically significant reduction in incidence of chronic post-surgical pain. In a small sample single dose pilot study, patients given low dose intravenous ketamine intraoperatively had a statistically non-significant reduction in incidence of pain around the surgical scar at three months after radical mastectomy. Randomized control trials with larger sample sizes are needed to determine the effectiveness and optimal dosing regime of ketamine for reduction of chronic post-mastectomy pain. It is therefore hypothesized that intravenous ketamine given intraoperatively will reduce the incidence and severity of chronic pain after modified radical mastectomy. A double blind randomized controlled trial comparing placebo group with two different doses of ketamine is proposed.

The mechanism of action of ketamine in reducing pain is complex and multiple. How ketamine can prevent and reduce chronic pain is unknown. Ketamine has been shown to reduce immediate gene expression at site of mechanical injury. Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Ankyrin 1 (TRPA1) are receptors shown to mediate acute and chronic pain. Ketamine, shown to affect gene expression, may alter the expression of TRPV1 and TRPA1 via epigenetic mechanisms.

Conditions

• Chronic Pain

Interventions

DRUG

Saline

10ml bolus injection of saline followed by intravenous infusion of saline during the operation

DRUG

Ketamine 0.5mg/kg

0.5mg/kg intravenous ketamine injection followed by 0.25mg/kg/hr intravenous ketamine infusion during the operation

DRUG

Ketamine 0.75mg/kg

0.75mg/kg intravenous ketamine injection followed by 0.5mg/kg/hr intravenous ketamine infusion during the operation

Sponsors & Collaborators

• The University of Hong Kong

  lead OTHER

Principal Investigators

• Stanley SC Wong, MBBS · The University of Hong Kong

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-08-18

Primary Completion

2024-06-30

Completion

2024-06-30

Countries

• Hong Kong

Study Locations