The Role of Coadministration of Lidocaine and Ketamine in Opioid-Refractory Chronic Cancer-Related Pain.

Inclusion Criteria

Age ≥18 years. Capacity to provide informed consent, ability to complete study assessments, and comply with study procedures.

Meets the IASP definition for chronic cancer-related pain. Moderate or severe pain, defined as average pain ≥4 on an 11-point (0-10) Numerical Rating Scale (NRS) in the past 24 hours.

Adequate trial of opioid medication, defined as a dose of ≥60 mg/day oral morphine equivalent or the patient's maximum tolerated dose in the past 24 hours.

For patients with a neuropathic component to pain: adequate trial of at least one adjuvant analgesic, defined as a daily dose of at least:

Amitriptyline 37.5 mg, Duloxetine 30 mg, Gabapentin 900 mg, Pregabalin 150 mg, Venlafaxine 60 mg, or equivalent, or maximum tolerated dose in the past 24 hours.

Exclusion Criteria Previous adverse reaction to ketamine, lidocaine, other amide-type local anesthetics, or midazolam.

Severe liver disease (Child-Pugh Class B or C) or SGPT/SGOT \>5× the upper limit of normal.

End-stage kidney disease.

Serious cardiac comorbidity, including:

Unstable angina, poorly controlled hypertension or tachycardia, high-risk coronary artery disease, symptomatic heart failure (NYHA Class III-IV), history of heart block, Wolff-Parkinson-White syndrome, Adams-Stokes syndrome. elevated intracranial or intraocular pressure, Pheochromocytoma or poorly controlled hyperthyroidism.

History of psychosis, schizophrenia, or substance abuse. Pregnant or breastfeeding. Porphyria. Life expectancy shorter than the duration of the study.