Ketamine Analgesic Effect by Continuous Intravenous Infusion in Refractory Cancer Pain: Considerations about the Clinical Research in Palliative Care

Background: The literature has described the use of ketamine as an adjuvant treatment for opioid-refractory cancer pain. None of these studies have used the drug in a palliative care patient population. Aims: The primary objective of the study was to assess the efficacy of continuous intravenous infusion of ketamine in patients suffering from cancer pain refractory to opiates who had been admitted to palliative care units. Secondary objectives were to assess patients' satisfaction with and tolerance of ketamine. Methods: A randomized, double-blind, placebo-controlled study was designed, and the study setting included seven French adult palliative care units. Inclusion criteria were age 18 years, and cancer pain refractory to standard opiates. Evaluations were conducted at randomization (baseline), at ketamine or placebo introduction time (T0), and at 2 hours (T1), 24 hours (T2), and 48 hours (T3) after T0. The primary evaluation criterion was pain efficacy assessed using a patient self-rated Numeric Pain Intensity Scale (NPIS) at T1. The main secondary evaluation criteria were daily morphine dose, symptom evaluation (Edmonton Symptom Assessment Scale [ESAS]), and patient satisfaction (Pain Treatment Satisfaction Scale [PTSS]). Results: Twenty patients were analyzed (11 received ketamine and 9 received placebo). Self-reported pain did not differ between the two groups, as the symptoms continued to evolve during the study period. The tolerance for ketamine was satisfactory. Conclusion: The present study did not confirm the efficacy of the ketamine-morphine combination in refractory cancer pain. The results suggest that specific populations could be "good responders" for this therapeutic approach. Further studies should be performed that take into account the difficulties of conducting clinical research in the palliative care context.