Sepsis affects 30 million people worldwide, leading to 6 million deaths every year (WHO), and despite decades of research, novel initiatives are drastically needed. According to the current literature, oxidative imbalance and mitochondrial dysfunction are common features of septic patients that can cause multiorgan failure and death. Melatonin, alongside its traditionally accepted role as the master hormonal regulator of the circadian rhythm, is a promising adjunctive drug for sepsis through its anti-inflammatory, antiapoptotic and powerful antioxidant properties. Several animal models of sepsis have demonstrated that melatonin can prevent multiorgan dysfunction and improve survival through restoring mitochondrial electron transport chain (ETC) function, inhibiting nitric oxide synthesis and reducing cytokine production. The purpose of this article is to review the current evidence for the role of melatonin in sepsis, review its pharmacokinetic profile and virtual absence of side effects. While clinical data is limited, we propose the adjunctive use of melatonin is patients with severe sepsis and septic shock.

Authors: Brouwer WP, Duran S, Kuijper M, Inc C PMID: 31533846 PMCID: PMC6749645 DOI: 10.1186/s13054-019-2588-1 Abstract Background and aims: Innovative treatment modalities have not yet shown a clinical benefit in patients with septic shock. To reduce severe cytokinaemia, CytoSorb as an add-on to continuous renal replacement therapy (CRRT) showed promising results in case reports. However, [...]

Authors: Woolum JA, Abner EL, Kelly A, Thompson Bastin ML, Morris PE, Flannery AH. PMID: 30028362 DOI: 10.1097/CCM.0000000000003311 Abstract Objectives: Mounting evidence has shown that critically ill patients are commonly thiamine deficient. We sought to test the hypothesis that critically ill patients with septic shock exposed to thiamine would demonstrate improved lactate clearance and more [...]

Authors: Busund R, Koukline V, Utrobin U, Nedashkovsky E PMID: 12373468 DOI: 10.1007/s00134-002-1410-7 Abstract Objective: To determine the therapeutic efficacy and safety of plasmapheresis in the treatment of patients with severe sepsis and septic shock. Design: Prospective, randomised, clinical trial with a planned, midstudy, interim analysis. Setting: Intensive care unit in a university hospital in [...]