Advance treatment of sepsis and septic shock to improve outcome. vitamin C, thiamine and hydrocortisone combination is studied well and prooven to beneficial

1. Role of Vitamin C and Thiamine
in sepsis & septic shock
DR ANKIT GAJJAR
MD, IDCCM, IFCCM, EDIC

2. • Septic shock – Organ dysfunction & profound
circulatory/metabolic abnormalities
• Despite current standards of care, 40%
mortality
• So, additional interventions needs to be
researched and developed

3. • Vitamin C & Thiamine are soluble vitamins
• Deficiency results in shock, cardiac failure &
CNS disorder
• In septic shock, depletion of Vitamin C and
Thiamine lead to worsening of shock
• Both are inexpensive, easily available, safe and
rare adverse effects
Marik PE. Hydrocortisone, Ascorbic Acid and Thiamine (HAT Therapy) for the
treatment of sepsis. Focus on ascorbic acid. Nutrients. 2018;10(11):1762–15.

4. Vitamin C
• Various studies has demonstrated, mild to
severe deficiency of Vitamin C in septic
patients
• Low level of Vitamin C associated with
worsening shock, AKI, MODS & increased
mortality
• This deficiency could be due to, decrease
absorption, increase urinary loss & increase
oxidation

5. Key Roles of Vitamin C
Key Role Mechanism
Free
radical
scavenger
Scavenges extracellular, intracellular and mitochondrial
ROS; limits oxidation of mitochondrial proteins, enzymes,
lipoproteins, cell membrane, etc
Anti-inflammatory Inhibits activation of NFκB, decreases HMGB1, inhibits
histamine,
prevents NETosis, inactivates HIF-1α
Microcirculation Increases eNOS, decreases iNOS, preserves tight junctions
Immune function Supports lymphocyte proliferation, increases neutrophil
bacteriocidal action, improves chemotaxis, stimulates
interferon production, decreases T regulatory cells (Tregs)
Anti-thrombotic Decreases platelet activation and tissue factor expression,
increases thrombomodulin
Synthesis of
catecholamin
es
Acts cofactor in synthesis of epinephrine,
dopamine and vasopressin.
Increases adrenergic sensitivity
Wound Healing Hydroxylation of procollagen, increased expression of
collagen mRNA

6. Thiamine
• Thiamine deficiency occurs in 50-70% of septic
pts
• Thiamine deficiency lead to,
1) Decrease ATP production
2) Neuronal cell death
3) Increase production of ROS

7. Key role of Thiamine
• Thiamine is a cofactor in glucose metabolism, ATP
generation and NADPH generation
• Important role in brain function & inter neuronal
communication
• Anti-inflammatory effects
• Deficiency of Thiamine lead to increase in
oxidative stress and organ failure including brain
dysfunction
• Thiamine administration in septic shock improve
cellular metabolism and ATP generation

8. • Combination of Vitamin C and thiamine,
Reduces risk of renal oxalate crystallization by
preventing conversion of vitamin C into
oxalate

10. Dosage – 50 mg/kg/day & 200 mg/kg/day for 4 days

11. limitations
• Only 24 pts
• Studied on inflammatory markers
• No mortality monitoring

13. • Study group – July - December 2017 (n-229)
• Control group – Oct 2015 - Jun 2017(n-915)

14. • Dosage for 1 day
• Vitamin C – 3 gm BD
• Thiamine – 200 mg BD
• Additional dosage physician driven

17. limitations
• No blinding
• Study group and control group – number
mismatch
• Only for 1 day, additional dose physician
driven
• Most common infection intra abdominal
(39%)

20. • Retrospective, 94 pts
• Vit C 1.5 gm QID
• Thiamine 200 mg QID
• Hydrocortisone 200 mg/day

22. • Randomized, placebo control, double blind,
multicentre trial in ER of South Korea

23. • INCLUSION CRITERIA
19-89 yrs age
Directly visit assign hospital
Diagnosed with septic shock
DOSAGE
Vitamin C - 50 mg/kg BD for 48 hrs
continue infusion for 1 hr
Thiamine – 200 mg BD, mix along with Vita C
Change in SOFA score

24. UPCOMING STUDIES

25. CONCLUSION
• Vitamin C and Thiamine have important
biological effect in sepsis & septic shock pts
• It is safe, inexpensive & easily available
• No documented adverse effects
• Dosage
• Vitamin C - 50 – 100 mg/kg/day BD/QID
• Thiamine 200 mg BD