The Intravenous Ketamine Test: A Predictive Response Tool for Oral Dextromethorphan Treatment in Neuropathic Pain

IV infusion tests performed to predict subsequent response to oral analgesics are an increasingly popular method used to enhance medical care and conserve resources. Because no infusion test is completely accurate, the potential benefits of these tests must be weighed against the frustration and waste in resources encountered with false-positive results, and the failure to use a potentially beneficial treatment with false-negative results. In recent years, drugs that act antagonistically at N-methyl-d-aspartate receptors have been shown to be valuable adjuncts in the treatment of pain. To determine the predictive value of small-dose (0.1 mg/kg) IV ketamine on an oral dextromethorphan (DX) treatment regimen, we analyzed the analgesic response to these drugs in 25 patients at 2 tertiary care military treatment facilities, institutions at which DX is not readily accessible. When ≥50% response for both drugs was used as the outcome measure for success, the positive predictive value of the ketamine test was 64%, the negative predictive value 73%, and the observed agreement 68%. However, when ≥67% relief with ketamine was used as an outcome measure (as determined by a receiver operating characteristic curve), the positive predictive value was 90%, the negative predictive value 80%, and the observed agreement increased to 84%. Based on these results, we conclude that an IV ketamine test may be useful in predicting response to oral DX. More research is needed to determine the ideal candidates for such a test, and the optimal dose and cutoff value for the response to ketamine.

[1]  R. B. Abraham,et al.  Dextromethorphan for Phantom Pain Attenuation in Cancer Amputees: A Double-Blind Crossover Trial Involving Three Patients , 2002, The Clinical journal of pain.

[2]  John Ludbrook,et al.  Statistical Techniques For Comparing Measurers And Methods Of Measurement: A Critical Review , 2002, Clinical and experimental pharmacology & physiology.

[3]  J. Mao Translational pain research: bridging the gap between basic and clinical research , 2002, Pain.

[4]  M. Max,et al.  Dextromethorphan and Memantine in Painful Diabetic Neuropathy and Postherpetic Neuralgia: Efficacy and Dose-Response Trials , 2002, Anesthesiology.

[5]  C. Goodchild,et al.  Potentiation by ketamine of fentanyl antinociception. I. An experimental study in rats showing that ketamine administered by non-spinal routes targets spinal cord antinociceptive systems. , 2002, British journal of anaesthesia.

[6]  H. Kehlet,et al.  A Qualitative and Quantitative Systematic Review of Preemptive Analgesia for Postoperative Pain Relief: The Role of Timing of Analgesia , 2002, Anesthesiology.

[7]  H. Ramadan,et al.  Improved Postoperative Pain Control in Pediatric Adenotonsillectomy With Dextromethorphan , 2001, The Laryngoscope.

[8]  J. Mao,et al.  Systemic lidocaine for neuropathic pain relief , 2000, Pain.

[9]  A. Weinbroum,et al.  The role of dextromethorphan in pain control , 2000, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[10]  L. Trentin.,et al.  [The predictive lidocaine test in treatment of neuropathic pain]. , 2000, Minerva anestesiologica.

[11]  A. Sandler,et al.  Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes , 1999, Pain.

[12]  S. Ho,et al.  Preincisional dextromethorphan treatment decreases postoperative pain and opioid requirement after laparoscopic cholecystectomy. , 1999, Anesthesia and analgesia.

[13]  H. Hays,et al.  Clinical experience with oral ketamine. , 1999, Journal of pain and symptom management.

[14]  M. Durieux,et al.  Ketamine: Teaching an Old Drug New Tricks , 1998, Anesthesia and analgesia.

[15]  M. Max,et al.  High‐dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia , 1997, Neurology.

[16]  M. Rowbotham,et al.  Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study. , 1996, Journal of pain and symptom management.

[17]  D. Price,et al.  Continuous co-administration of dextromethorphan or MK-801 with morphine: attenuation of morphine dependence and naloxone-reversible attenuation of morphine tolerance , 1996, PAIN.

[18]  M. Georgieff,et al.  The Effects of Ketamine-Isomers on Neuronal Injury and Regeneration in Rat Hippocampal Neurons , 1996, Anesthesia and analgesia.

[19]  P. Eide,et al.  Continuous subcutaneous administration of the N-methyl-d-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia , 1995, Pain.

[20]  A. Jadad,et al.  Dextromethorphan for the treatment of neuropathic pain: a double-blind randomised controlled crossover trial with integral n-of-1 design , 1994, Pain.

[21]  G. Bennett,et al.  Neuropathic pain sensations are differentially sensitive to dextrorphan , 1994, Neuroreport.

[22]  G. Bennett,et al.  Dextrorphan relieves neuropathic heat-evoked hyperalgesia in the rat , 1993, Neuroscience Letters.

[23]  D. Price,et al.  Intrathecal treatment with dextrorphan or ketamine potently reduces pain-related behaviors in a rat model of peripheral mononeuropathy , 1993, Brain Research.

[24]  D. Price,et al.  Intrathecal MK-801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy , 1992, Brain Research.

[25]  T. Yaksh,et al.  Spinal pharmacology of thermal hyperesthesia induced by constriction injury of sciatic nerve. Excitatory amino acid antagonists , 1992, Pain.

[26]  A. Dickenson,et al.  The combination of NMDA antagonism and morphine produces profound antinociception in the rat dorsal horn , 1992, Brain Research.

[27]  A. Dickenson,et al.  Dextromethorphan and levorphanol on dorsal horn nociceptive neurones in the rat , 1991, Neuropharmacology.