An Intravenous Ketamine Test as a Predictive Response Tool in Opioid-Exposed Patients with Persistent Pain

• Published in: Journal of pain and symptom management 2009-04, Vol.37 (4), p.698-708
• Main Authors: Cohen, Steven P., MD, Wang, Shuxing, MD, PhD, Chen, Lucy, MD, Kurihara, Connie, RN, McKnight, Geselle, CRNA, Marcuson, Matthew, MD, Mao, Jianren, MD, PhD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Analgesics, Opioid - adverse effects; Analgesics, Opioid - therapeutic use; Anesthesia & Perioperative Care; Anesthetics, Dissociative - adverse effects; Biological and medical sciences; Chronic Disease; Chronic pain; Dextromethorphan; Drug resistant; Female; Humans; Infusion devices; infusion test; Injections, Intravenous; Ketamine; Ketamine - adverse effects; Male; Medical sciences; Middle Aged; N-methyl- d-aspartate; opioid; Opioids; Pain - drug therapy; Pain Medicine; Pharmacology. Drug treatments; predictive value; Predictive Value of Tests; Relief; tolerance; Young Adult
• ISSN: 0885-3924; 1873-6513
• DOI: 10.1016/j.jpainsymman.2008.03.018

Abstract Chronic pain patients who are treated with opioid therapy represent a significant challenge to medical professionals. When pain recurs in the face of a previously effective opioid regimen, treatment options include dose escalation, opioid rotation, drug holidays, and the addition of adjuvants. Some experts advocate the use of N -methyl- d -aspartate receptor (NMDA-R) antagonists to combat tolerance. Recently, the use of an intravenous (i.v.) ketamine infusion to predict the response to a dextromethorphan (DX) treatment trial has been described. In this study, 56 opioid-exposed patients with recurrent pain were treated with a low-dose (0.1 mg/kg) i.v. ketamine test followed by a DX treatment course. Using previously designated cutoff values for a positive response to ketamine (67% or more pain relief) and DX (50% or more pain relief), the sensitivity, specificity, positive predictive value, and negative predictive value for an i.v. ketamine infusion to predict subsequent response to DX treatment were 72%, 68%, 52%, and 85%, respectively. The observed agreement between analgesic responses was 78%, indicating a highly significant correlation ( r = 0.54, P = 0.0001). Subgroup classification revealed no significant differences in the response to either ketamine or DX treatment based on pain classification (i.e., nociceptive, neuropathic, or mixed) or placebo response. In contrast, a weaker correlation between ketamine and DX response was found in subjects requiring high-dose rather than low-dose opioid therapy. A significant correlation also was noted between the development of side effects for the two NMDA-R antagonists. Based on these results, we conclude that an i.v. ketamine test may be a valuable tool in predicting subsequent response to DX treatment in opioid-exposed patients. with persistent pain.