Ketamine Infusion Successful in Some Patients

We read with interest the observational re-port of Kapural et al (1) titled “Opioid-sparing effect of intravenous outpatient ketamine infu-sions appears short-lived in chronic-pain patients with high opioid requirements.” While we do not disagree that in some patients the pain-relieving effect of intravenous ketamine can be short-lived, we do disagree with the authors’ conclusion that this is not a feasible option for pain relief in this chronic pain population. The statement imply-ing that the infusion was not successful is unfor-tunately misleading and misses the more obvious and important clinical and scientific questions of why some patients responded and others did not. Despite the lack of internal validity in their study design, there was still improved analgesia in some patients for up to 6 months, similar to our experi-ence with low and moderate dose infusion of ket-amine in the CRPS population (2,3).We would like to briefly discuss some of the critical aspects relating to this study:The study is a retrospective analysis, of a non-homogenous population with multiple diagnoses, and lacks a true matched control population. The studies quoted, specifically those of Koffler et al (4), Goldberg et al (2), and Sigtermans et al (5) all deal with a single group of patients, those with a diagnosis of CRPS. The authors regrettably fail to mention the placebo controlled trial of Schwartz-man et al (6) that reported significant decreases in multiple pain measures after a 10-day ketamine infusion in patients with CRPS who had failed all other therapies. Also significant in Kapural et al’s study (1) was the fact that 6 months post treat-ment, almost 50% (5/11) of the subjects main-tained their opioid use at less than 50% of their baseline. In our opinion this seems to represent a clinically significant improvement.The notion of expense outweighing benefit can-not be supported by the study of Kapural et al (1). The low dose outpatient infusion is performed simi-larly to blood transfusions and is covered by insur-ance in most cases. The moderate dose 5-day infusion in the inpatient setting is performed with telemetry monitoring and is often covered by insurance in our practice. The high dose therapy is not performed in the United States and does require ICU admission and intensive monitoring. This is a recommended treatment to reduce opioid load in the chronic pain patient, but is reserved only for the most refractory cases of CRPS.Finally, we have recently reported the results from an initial study of the plasma concentrations of ketamine and norketamine, and other major ket-amine metabolites in CRPS patients (7). The data indicate that the ketamine metabolites, other than norketamine, were the predominant circulating me-tabolites and suggest that these compounds play a role in ketamine-related pain relief. Thus, it is likely that metabolic differences based upon pharmacoge-netic factors play a role in the determination of re-sponder and non-responder populations. Once these factors are identified, it will be possible to preselect candidates for treatment with ketamine and to indi-vidualize their treatment.We therefore continue to support a role for ketamine and/or its metabolites in the treatment of chronic pain in the patients with CRPS.MIchael E. Goldberg, MDProfessor and ChiefDepartment of AnesthesiologyCooper University HospitalUMDNJNewark, NJE-mail: goldberg-Mike@cooperhealth.edu