Jessica T Lee1,2,3, Christine R Sanderson4, Wei Xuan5,6, Meera Agar1,6,7. 1. 1 Improving Palliative, Aged and Chronic Care Through Clinical Research and Translation, University of Technology Sydney, Ultimo, Australia. 2. 2 Concord Centre for Palliative Care, Concord Repatriation General Hospital, Sydney, Australia. 3. 3 Concord Clinical School, University of Sydney, Sydney, Australia. 4. 4 Department of Palliative Care, Calvary Healthcare, Sydney, Australia. 5. 5 Ingham Institute of Applied Medical Research, Sydney, Australia. 6. 6 Sydney South West Clinical School, University of New South Wales, Sydney, Australia. 7. 7 Discipline of Palliative and Supportive Services, Flinders University, Adelaide, Australia.
Abstract
BACKGROUND: Internationally, use of lidocaine infusions to treat cancer pain varies by center. Existing systematic reviews do not adequately inform use of lidocaine in cancer pain. OBJECTIVE: To assess the effects of systemic sodium channel blockers on cancer pain in adults, review the dose protocols for administration, and assess toxicity. DESIGN: Databases CENTRAL, MEDLINE, Embase, LILACS, CareSearch, and OpenGrey were searched from inception to 2016. Conference abstracts and reference lists were handsearched, and the lead investigators of included trials and Australian manufacturers were contacted. Included studies were randomized controlled trials evaluating one or more of lidocaine via intravenous or subcutaneous route, or mexiletine, flecainide, or tocainide via oral route; delivered at a site distant to the pain locus. The methodological quality of studies was assessed using the "risk of bias" domain-based evaluation by Jadad. Protocol is available on PROSPERO:CRD42016047092. RESULTS: One positive (n = 50) and three negative (n = 10 each) crossover trials evaluated lidocaine versus placebo, and one trial (n = 16) compared lidocaine with dexmedetomidine. Meta-analysis of pooled data in 60 patients demonstrated a significant benefit of lidocaine infusion of 4-5 mg/kg over 30-80 minutes compared with placebo for >50% reduction in cancer pain. Secondary outcomes did not show a significant difference. DISCUSSION: Based on the current available evidence, lidocaine infusion could be considered in refractory cancer pain where agents with level 1 evidence are ineffective. Further research is necessary to understand the protocol and population in which lidocaine may improve cancer pain and capitalize on the promising opportunities identified.
BACKGROUND: Internationally, use of lidocaine infusions to treat cancer pain varies by center. Existing systematic reviews do not adequately inform use of lidocaine in cancer pain. OBJECTIVE: To assess the effects of systemic sodium channel blockers on cancer pain in adults, review the dose protocols for administration, and assess toxicity. DESIGN: Databases CENTRAL, MEDLINE, Embase, LILACS, CareSearch, and OpenGrey were searched from inception to 2016. Conference abstracts and reference lists were handsearched, and the lead investigators of included trials and Australian manufacturers were contacted. Included studies were randomized controlled trials evaluating one or more of lidocaine via intravenous or subcutaneous route, or mexiletine, flecainide, or tocainide via oral route; delivered at a site distant to the pain locus. The methodological quality of studies was assessed using the "risk of bias" domain-based evaluation by Jadad. Protocol is available on PROSPERO:CRD42016047092. RESULTS: One positive (n = 50) and three negative (n = 10 each) crossover trials evaluated lidocaine versus placebo, and one trial (n = 16) compared lidocaine with dexmedetomidine. Meta-analysis of pooled data in 60 patients demonstrated a significant benefit of lidocaine infusion of 4-5 mg/kg over 30-80 minutes compared with placebo for >50% reduction in cancer pain. Secondary outcomes did not show a significant difference. DISCUSSION: Based on the current available evidence, lidocaine infusion could be considered in refractory cancer pain where agents with level 1 evidence are ineffective. Further research is necessary to understand the protocol and population in which lidocaine may improve cancer pain and capitalize on the promising opportunities identified.