Ketamine mouthwash versus placebo in the treatment of severe oral mucositis pain in children with cancer: A randomized double‐blind placebo‐controlled trial

Abstract

Background and aims Oral mucositis (OM) is a common and distressing toxicity in children on chemotherapy. There are a limited number of safe and effective therapeutic options available for OM. Ketamine oral rinse has shown promising results in a few studies in adults. This randomized, double‐blind placebo‐controlled trial aimed to test the efficacy of ketamine mouthwash in reducing chemotherapy‐induced severe OM pain in children. Methods Children aged 8‐18 years with severe OM were randomized to a single dose of ketamine mouthwash (4 mg/mL solution; dose 1 mg/kg) or a placebo. A sample size of 44 patients was determined. Pain score (6‐point faces scale) was noted at baseline and 15, 30, 45, 60, 120, 180, and 240 min. The outcome variables were a reduction in pain score, need for rescue medications, and adverse events. Results The baseline characteristics were comparable in the two groups. The mean OM pain at 60 min decreased by 1.64 points (CI 1.13‐2.14) in the ketamine group and 1.32 points (CI 0.76‐1.87) in the placebo group (P = 0.425), with a group difference of 0.32 points. Rescue pain medication (at 60 min) was required in 13.6% in the ketamine group and 18.2% in the placebo group (P = 1.000). No significant adverse events were observed. Conclusions Among children on cancer chemotherapy with severe OM, ketamine mouthwash at a dose of 1 mg/kg did not significantly reduce OM pain. It did not decrease the need for rescue pain medications. Further research is warranted to test higher doses of ketamine for a clinically significant effect.

Efficacy of ketamine mouthwash in the management of oral and pharyngeal toxicity associated with head and neck chemoradiotherapy: protocol for a phase II, Simon’s two-stage trial

“…Only a single dose of ketamine was administered, and its effects were monitored for several hours. Although differences were observed in the ketamine and placebo groups, they did not meet significance thresholds 26…”

“…Although differences were observed in the ketamine and placebo groups, they did not meet significance thresholds. 26 The two foregoing RCTs of ketamine mouthwash are limited by sample size, by only capturing analgesia outcomes in the former case and by single dose administration with transient follow-up in the latter case. Nevertheless, they testify to the potential therapeutic value of ketamine mouthwash for patients with cancer and to a safety profile favourable enough for considering its use in children.…”

“…Although differences were observed in the ketamine and placebo groups, they did not meet significance thresholds. 26 …”

A review of the clinical applications of ketamine in pediatric oncology

“…Preliminary evidence for ketamine mouthwash for oral mucositis pain had suggested a beneficial role in adults 91–93 . However, a recent RCT by Prakash et al (from author's center) evaluating the role of ketamine mouthwash for oral mucositis pain relief in children (n = 44; 8‐18 years) with cancer found ketamine to be ineffective at a dose of 1 mg/kg 94 …”

“…The emergence of reactions can be minimized by concomitantly using a benzodiazepine with ketamine 104 . All the aforementioned adverse effects are rare with topical preparations 92–94 …”