Can Vitamin C, Thiamine and Hydrocortisone Save the Lives of Septic Patients?

 

The consequence was, that the most sudden and visible good effects were perceived from the use of oranges and lemons. – James Lind

Hydrocortisone, Vitamin C and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study CHEST (2017), doi: 10.1016/j.chest.2016.11.036.

Background

The global rate of sepsis is estimated as 15 to 19 million cases annually with a mortality rate nearing 60% in developing countries. Sepsis results in multiple short and long term complications.

Thiamine deficiency has been associated with increased mortality in sepsis, and vitamin C deficiency correlates with multi-organ failure and death. It maintains endothelial boundaries and is required for catecholamine synthesis.

Trial Question

‘Does intravenous vitamin C, hydrocortisone and thiamine in addition to standard treatment, improve mortality in ICU patients with severe sepsis or septic shock, compared with standard treatment alone?’

 Methods

This was a retrospective observational single centered study. It took place in one tertiary care hospital in America between June 2015 and July 2016. It included all patients (with reasonable exceptions) with severe sepsis or septic shock and a procalcitonin level of ≥ 2ng/ml (based on 1992 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definitions). The control group was the first 7 months, and the intervention group was the next 7 months. There were a total of 47 patients in each group and the baseline characteristics were similarly matched.

All patients received standard intensive care treatment, and the intervention group received in addition the following:

– 1.5g QDS Vitamin C intravenously for 4 days or until ICU discharge

– Hydrocortisone 50mg QDS intravenously for 7 days or until ICU discharge followed by a taper over 3 days

– 200mg thiamine BD for 4 days or until ICU discharge

Outcomes

Primary outcome

  • In-hospital mortality

Secondary outcomes

  • mean duration of vasopressor therapy
  • use of Renal Replacement Therapy
  • median ICU LOS
  • 72 hours delta SOFA score (difference between subsequent scores)

Results

Primary Outcome

  • Hospital mortality: 8.5% (4 of 47) in the treatment group compared to 40.4% (19 of 47) in the control group (p < 0.001)

Secondary Outcomes

  • Mean duration of vasopressor therapy: 18.3 ± 9.8 hours with vitamin C vs 54.9 ± 28.4 hours in control (P<0.001)
  • RRT in patients with AKI: 3 patients (10%) in the treatment group vs 11 (37%) in the control group (P=0.02)
  • Median ICU LOS: 4 days in both groups
  • The 72-hour delta SOFA score was 4.8 ± 2.4 in the treatment group compared to 0.9 ± 2.7 in the control group (p<0.001)

 Strengths

  • Biologically acceptable explanations for the potential benefit of vitamin C in sepsis
  • Patient baseline characteristics well matched between the two groups
  • Vitamin C and thiamine are cheap and safe
  • Multiple supporting trials

 Weaknesses

  • Not an RCT
  • Only 47 patients
  • Single-centre, before-after (not concurrent), non-blinded design
  • There were three simultaneous interventions. Which one was responsible for the clinical improvement?
  • Control and intervention groups fell within different seasons and this could be a confounding factor
  • Sixty percent of patients in the control group were also treated with corticosteroids
  • Details are provided for the intervention group underlying reason for death (dementia, HF, and COPD) but not for control group
  • The paper states ‘None of the patients in the treatment group died from complications related to sepsis’. This statement needs clarification.

Conclusion

The results suggest that the early use of IV vitamin C, with hydrocortisone and thiamine may reduce the mortality, and reduce RRT and vasopressor use of patients with severe sepsis and septic shock.

Ultimately

Inexpensive interventions with proven benefits and low risk.

 

Summary by Dr Hannah Bykar

 


Second Opinion

Here’s what The Bottom Line thought of this study

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