Abstract
Background and aims: Oral mucositis (OM) is a common and distressing toxicity in children on chemotherapy. There is a limited number of safe and effective therapeutic options available for OM. Ketamine oral rinse has shown promising results in 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). There were no significant adverse events 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.
INTRODUCTION
Oral mucositis (OM) refers to the inflammation and ulceration of the oral cavity’s mucous membranes. It is a common adverse effect of cancer treatment, including both chemotherapy and radiotherapy. Children are more prone to the development of OM following cancer chemotherapy as compared to adults. The reported incidence rates range from 50-80% in children receiving cancer chemotherapy and 90-100% during a hematopoietic stem cell transplant.1,2,3 However, OM in children has also been reported to heal faster in comparison to that in adults.4 The OM following chemotherapy often develops within a week of starting chemotherapy, and usually resolves by the end of 2nd week. The OM leads to a significant decline in the quality of patient’s life, which stems from the considerable pain at rest and a burning feeling in the oral cavity (stomatodynia) as well as on swallowing (odynophagia), difficulty in swallowing (dysphagia) and difficulty in speaking (dysarthria). This leads to inadequate oral intake causing poor nutrition and weight loss and a possible requirement of parenteral nutrition. It also predisposes to secondary infection of the oral lesion, in addition to prolonging the duration of the hospital course and increasing the cost of treatment. It may entail a dose reduction or discontinuation of a chemotherapeutic agent, which would naturally correlate with a poorer prognosis for the primary malignancy. Currently, the mainstay of therapy for OM is pain management, comprising of systemic (oral, parenteral) and topical agents. Several agents have been tried for the prevention and treatment of OM, with a handful showing a beneficial role, such as palifermin, low-level laser therapy, and doxepin oral rinse.5,6,7Other interventions with possible efficacy include oral hygiene protocols and cryotherapy. There is a paucity of evidence-based recommendations for OM pain in children with cancer.
Ketamine is a dissociative anesthetic agent with a potent NMDA receptor-channel blocking activity. It has also been shown to have some opioid-like effects and anti-inflammatory properties.8Commonly seen adverse effects of ketamine include sedation, nausea, vomiting, hallucinations, excessive salivation, and ataxia.9,10 However, these effects have been reported to be minimal with its topical use. Ketamine has been used for pain relief in many conditions, including cancer-related pain. Topical ketamine has also been found to be a safe and effective analgesic for decreasing post-tonsillectomy pain in children.11,12Ketamine oral rinse has shown promising results in a few non-randomized studies in adults with chemotherapy-related OM pain.13,14,15 This randomized, double-blind placebo-controlled trial aimed to test the efficacy of ketamine mouthwash in the reduction of chemotherapy-induced severe OM (WHO grade-III or grade-IV) pain.
MATERIALS AND METHODS