OBJECTIVE: The objective of this study was to report the benefit of a therapeutic approach consisting of intravenous (IV) continuous anakinra (recombinant human interleukin-1 receptor antagonist) infusions in treating severely ill adult patients with secondary hemophagocytic lymphohistiocytosis or macrophage activation syndrome (MAS). METHODS: A retrospective chart review of five patients treated at Regions Hospital from 2016 to 2019 was conducted. Demographic, clinical, and laboratory characteristics and outcomes were recorded. RESULTS: Continuous IV anakinra infusions up to 2400 mg/d resulted in rapid serologic, then clinical response in 4 of 5 severely ill patients who were refractory to all other therapies, including subcutaneous anakinra. Subsequently, 3 of 5 patients have been maintained on anakinra or canakinumab, with no recurrence of MAS. CONCLUSION: Continuous infusion of IV anakinra may result in rapid serologic and subsequent clinical improvement in adult patients with MAS. This method for treating cytokine storm should be considered in the current COVID-19 pandemic in the subgroup of patients with severe disease who have a cytokine storm presentation.