SUMMARY:

• Sepsis identification and management remain a global challenge.

• Metabolic resuscitation has become an area of focus as a therapeutic strategy to address mitochondrial function to counter sepsis-induced organ dysfunction and improve survival.

• The efficacy of a combined therapy including corticosteroids, Vitamin C, and Thiamine in sepsis patients has produced varied results.

REVIEW:

• The pathophysiology of sepsis is an intricate response between inflammatory responses, dysfunction of the immune system, alterations in neuroendocrine function, coagulation abnormalities, and mitochondrial damage.

• These disruptions all contribute to sepsis

• The mitochondrial dysfunction plays a critical role in the development of sepsis and multiorgan dysfunction syndrome.

• Metabolic resuscitation is a recent attempt to restore the energy balance at a cellular level and address mitochondrial dysfunction.

• Several micronutrients have been suggested to help mitigate the mitochondrial dysfunction. These include:

• • Vitamin C

• • Thiamine

• • Vitamin E

• • Selenium

• • Zinc

• • Coenzyme Q

• • L-carnitin

• • Cytochrome oxidase

• • Melatonin

• Interest has been generated with the triple combination of Vitamin C, Thiamine, and corticosteroids.

Corticosteroids

• The use of corticosteroids in sepsis has been controversial for decades.

• Corticosteroids may reduce the expression of pro-inflammatory markers.

• Corticosteroids may also blunt the inflammatory response.

• The debate over corticosteroids continues due to study design variations:

• • Small, uncontrolled studies

• • Different agents

• • Differing doses

• • Different time of administration

VITAMIN C

• Vitamin C offers antioxidant, anti-inflammatory and immunomodulation properties.

• Early studies of small scale and observational in nature have reported positive findings (usually in combination with corticosteroids and thiamine).

• Recent larger randomized trials of Vitamin C alone have resulted in conflicting results.

• Vitamin C monotherapy was found ineffective in impacting sepsis 28-day mortality (35.4% Vit C vs 31.6% in placebo).

• • Organ dysfunction was longer in the Vitamin C group.

• Vitamin C was also found to be ineffective when combined with hydrocortisone.

Thiamine

• Thiamine can provide a protective effect on mitochondrial activity.

• Thiamine deficiency also contributes to the development of lactic acidosis.

• Thiamine also plays a role in antioxidant pathways.

• The use of thiamine and vitamin C combinations may restore organ function in patients with sepsis and septic shock.

Triple Combination Therapy ( Vitamin C, Corticosteroids and Thiamine (HAT):

• Recent investigations have considered the impact of a combined triple therapy (hydrocortisone, ascorbic acid, and thiamine (HAT) on the progression of sepsis.

• Investigations have produced varying results.

• Studies typically report no change in hospital or ICU mortality.

• Some have found a reduction in the duration of vasopressor use, and or reduction in SOFA score, whereas others have not.

• The combination does not appear to increase the occurrence of adverse events.

CONCLUSIONS:

• Current Surviving Sepsis Campaign Guidelines recommend:

  • Consider corticosteroid use in sepsis patients with septic shock and ongoing vasopressor needs (weak level recommendation).

  • Against the use of IV Vitamin C (weak level recommendation

  • No recommendation on Metabolic Resuscitation

• There does not appear to be a value to Metabolic Resuscitation in sepsis at this time.

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Erkan Hassan is the Co-Founder & Chief Clinical Officer of Sepsis Program Optimization where he designs & oversees the implementation of solutions to optimize sepsis programs.

To discuss your organization’s Barriers of Effective Sepsis Care, contact Erkan by phone (844) 4SEPSIS (844-473-7747), email (erkan@spo.icu), or video chat.