Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: A double-blind placebo controlled study

Abstract

Complex regional pain syndrome (CRPS) is a severe chronic pain condition that most often develops following trauma. The pathophysiology of CRPS is not known but both clinical and experimental evidence demonstrate the important of the NMDA receptor and glial activation in its induction and maintenance. Ketamine is the most potent clinically available safe NMDA antagonist that has a well established role in the treatment of acute and chronic pain. This randomized double-blind placebo controlled trial was designed to evaluate the effectiveness of intravenous ketamine in the treatment of CRPS. Before treatment, after informed consent was obtained, each subject was randomized into a ketamine or a placebo infusion group. Study subjects were evaluated for at least 2 weeks prior to treatment and for 3 months following treatment. All subjects were infused intravenously with normal saline with or without ketamine for 4h (25ml/h) daily for 10 days. The maximum ketamine infusion rate was 0.35mg/kg/h, not to exceed 25mg/h over a 4h period. Subjects in both the ketamine and placebo groups were administered clonidine and versed. This study showed that intravenous ketamine administered in an outpatient setting resulted in statistically significant (p<0.05) reductions in many pain parameters. It also showed that subjects in our placebo group demonstrated no treatment effect in any parameter. The results of this study warrant a larger randomized placebo controlled trial using higher doses of ketamine and a longer follow-up period.

The Use of Ketamine in Neuropathic Pain

“…The Scwartzman et al [91] randomized, placebo-controlled trial studied the efficacy of ketamine IV infusions at 25 mL/h for 4 h daily for 10 days versus placebo infusions in 19 CPRS patients. At 12 weeks post-treatment, significant decreases in pain in most affected area, burning pain, pain when touched or lightly touched or brushed lightly, overall pain level, as well as decreased nighttime awakening were found in the ketamine group.…”

“…The titration of ketamine infusions has also differed with some studies titrating in set intervals while others titrating to analgesia or feelings of inebriation [54]. Reported durations of intravenous ketamine infusions have also varied from minutes to hours to infusions up to 10 days [11,91].…”

Intravenous Ketamine Alleviates Pain in a Rheumatoid Arthritis Patient With Comorbid Fibromyalgia

“…Moreover, the ketamine group also produced less TNF-α post-operation. Numerous clinical studies have shown that ketamine possesses significant analgesic properties [9][10][11]. Our own clinical experience using ketamine for treatment-refractory pain has been positive and we have previously reported long-term pain relief in a patient with fibromyalgia [12].…”

Gardner-Diamond syndrome associated with complex regional pain syndrome

“…She has been treated with both ketamine and lidocaine infusions for her CRPS. 5,6 The ketamine has shown benefit in terms of decreasing the diffuse erythema and swelling which occur intermittently over her entire body and face. Lidocaine infusions produce some relief of her pain.…”