Sepsis: Evidence-based pathogenesis and treatment

Abstract

Sepsis can develop during the body’s response to a critical illness leading to multiple organ failure, irreversible shock, and death. Sepsis has been vexing health care providers for centuries due to its insidious onset, generalized metabolic dysfunction, and lack of specific therapy. A common factor underlying sepsis is the characteristic hypermetabolic response as the body ramps up every physiological system in its fight against the underlying critical illness. A hypermetabolic response requires supraphysiological amounts of energy, which is mostly supplied via oxidative phosphorylation generated ATP. A by-product of oxidative phosphorylation is hydrogen peroxide (H 2 O 2 ), a toxic, membrane-permeable oxidizing agent that is produced in far greater amounts during a hypermetabolic state. Continued production of mitochondrial H 2 O 2 can overwhelm cellular reductive (antioxidant) capacity leading to a build-up within cells and eventual diffusion into the bloodstream. H 2 O 2 is a metabolic poison that can inhibit enzyme systems leading to organ failure, microangiopathic dysfunction, and irreversible septic shock. The toxic effects of H 2 O 2 mirror the clinical and laboratory abnormalities observed in sepsis, and toxic levels of blood H 2 O 2 have been reported in patients with septic shock. This review provides evidence to support a causal role for H 2 O 2 in the pathogenesis of sepsis, and an evidence-based therapeutic intervention to reduce H 2 O 2 levels in the body and restore redox homeostasis, which is necessary for normal organ function and vascular responsiveness.

Exploring the Muscle Metabolomics in the Mouse Model of Sepsis-Induced Acquired Weakness

“…ICU-AW in critical patients has been associated with sepsis, acute respiratory distress syndrome, and multiple organ dysfunction syndrome as prevalent complications [ 13 ]. Sepsis can cause crucial organ dysfunction of the heart, kidney, or liver, which might directly threaten the patients' survival [ 28 ]. However, the mid-long-term recovery of the patients was obstructed by the continuous failure of vital organs, usually along with the nonvital organs, such as the skeletal muscle [ 29 ].…”

“…Second, the essence of sepsis is considered to be the abnormal metabolism of cellular energy [ 28 ]. During sepsis, mitochondria, the main site of systemic oxygen consumption, may play a role in consuming excessive oxygen and creating “cytopathic hypoxia” [ 44 ].…”

“…In the case of Evidence-Based Complementary and Alternative Medicine sepsis-induced acquired weakness, leucine, cysteine, tyrosine, and serine may be considered more sensitive biomarkers. Second, the essence of sepsis is considered to be the abnormal metabolism of cellular energy [28]. During sepsis, mitochondria, the main site of systemic oxygen consumption, may play a role in consuming excessive oxygen and creating "cytopathic hypoxia" [44].…”

Several Alkaloids in Chinese Herbal Medicine Exert Protection in Acute Kidney Injury: Focus on Mechanism and Target Analysis

“…Sepsis is a systemic inflammatory response syndrome caused by the invasion of bacteria and other pathogenic microorganisms into the body [35]. It further shows multiple organ dysfunction, including renal organ dysfunction [36].…”

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“…The treatment of sepsis mainly includes etiological treatment, supportive treatment, and immuneconditioning treatment. Medications mainly focus on anti-infection treatment, prevention of deep venous thrombosis, and vasoactive drug treatment [2,8,9]. At present, there is no specific therapeutic drug.…”