Use of Ketamine for the Treatment of Opioid Induced Hyperalgesia
Daily opioid use produces chronic stimulation of opioid receptors that increases sensitivity to pain (central sensitization) through a variety of mechanisms. The clinical implications of central opioid sensitization include: 1) opioid tolerance and 2) opioid-induced hyperalgesia (OIH), in which patients with chronic opioid exposure experience pain with less noxious stimuli. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that is used for the treatment of acute and chronic pain.1-5 For patients with chronic opioid use, ketamine is an ideal non-opioid treatment choice for the management of intractable pain.
A 48 year old female with a past medical history of metastatic melanoma was admitted for intractable pain. Patient was on transdermal fentanyl 125 mcg/hr every 72 hours and oxycodone 10 mg to 20 mg every 4 hours as needed for pain as an outpatient. Ultimately after four days of titration by her primary team , her inpatient pain regimen consisted of hydromorphone patient controlled analgesia (PCA) pump with the following settings: basal rate of 0.5mg/h, demand dose of 0.5 mg, a 12 min lockout interval, one hour limit of 3 mg, and a clinician bolus of one mg every hour as needed for a pain score greater than four. Due to a medication error after her last titration, the patient received a 5 mg/hr basal rate of hydromorphone (a ten fold dosing error) for a 24 hour period. Despite the large doses of hydromorphone, the patient continued to complain of poorly controlled pain. Addiction medicine service was consulted to assist with pain management and recommended a ketamine infusion at 0.3mg/kg/h. The patient was successfully weaned off the hydromorphone PCA over three days. Indeed, the patient was discharged to home on a lower dose of transdermal fentanyl (100 mcg/hr) than admission with an improvement in her pain scores and ability to function.
Pain management regimens for inpatients with intractable pain suffering from OIH may benefit from the use of ketamine by: 1) decreasing pain scores and increasing functionality, 2) lowering overall opioid use as an inpatient, and 3) decreasing outpatient opioid dosing.
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