Acute Crit Care.  2021 Aug;36(3):185-200. 10.4266/acc.2021.00108.

The Efficacy of vitamin C, thiamine, and corticosteroid therapy in adult sepsis patients: a systematic review and meta-analysis

Affiliations
  • 1Department of Clinical and Translational Research, Larkin Community Hospital, South Miami, FL, USA
  • 2Department of Medicine, Saint James School of Medicine, Park Ridge, IL, USA
  • 3Department of Medicine, Windsor University School of Medicine, Cayon (St. Kitts and Nevis), USA
  • 4Department of Medicine, Medical University of Silesia, Katowice, Poland
  • 5Department of Medicine, Washington University of Health and Science, San Pedro, Belize
  • 6Department of Medicine, University of Health Sciences, Antigua, Antigua and Barbuda

Abstract

Background
Previous studies have suggested favorable outcomes of hydrocortisone, ascorbic acid (vitamin C), and thiamine (HAT) therapy in patients with sepsis. However, similar results have not been duplicated in sequential studies. This meta-analysis aimed to reevaluate the value of HAT treatment in patients with sepsis.
Methods
Electronic databases were searched up until October 2020 for any studies that compared the effect of HAT versus non-HAT use in patients with sepsis.
Results
Data from 15 studies (eight randomized controlled trials [RCTs] and seven cohort studies) involving 67,349 patients were included. The results from the RCTs show no significant benefit of triple therapy on hospital mortality (risk ratio [RR], 0.99; P=0.92; I2=0%); intensive care unit (ICU) mortality (RR, 0.77; P=0.20; I2=58%); ICU length of stay (weighted mean difference [WMD], 0.11; P=0.86; I2=37%) or hospital length of stay (WMD: 0.57; P=0.49; I2=17%), and renal replacement therapy (RR, 0.64; P=0.44; I2=39%). The delta Sequential Organ Failure Assessment (SOFA) score favored treatment after a sensitivity analysis (WMD, –0.72; P=0.01; I2=32%). However, a significant effect was noted for the duration of vasopressor use (WMD, –25.49; P<0.001; I2=46%). The results from cohort studies have also shown no significant benefit of HAT therapy on hospital mortality, ICU mortality, ICU length of stay, length of hospital stay, the delta SOFA score, the use of renal replacement therapy, or vasopressor duration.
Conclusions
HAT therapy significantly reduced the duration of vasopressor use and improved the SOFA score but appeared not to have significant benefits in other outcomes for patients with sepsis. Further RCTs can help understand its benefit exclusively.

Keyword

ascorbic acid; HAT therapy; septic shock; steroids; thiamine; vitamin C

Figure

  • Figure 1. Preferred reporting items for systematic reviews and meta-analyses flow diagram.

  • Figure 2. Forest plot showing results of triple therapy from randomized controlled trials (RCTs) and cohorts studies on the hospital mortality. HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine; CI: confidence interval; df: degrees of freedom.

  • Figure 3. Forest plot showing results of triple therapy from randomized controlled trials (RCTs) and cohort studies on the intensive care unit. HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine; CI: confidence interval; df: degrees of freedom.

  • Figure 4. Forest plot showing results of triple therapy from randomized controlled trials (RCTs) and cohorts studies on the intensive care unit length of stay. HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine; SD: standard deviation; IV: weighted mean difference; CI: confidence interval; df: degrees of freedom.

  • Figure 5. Forest plot showing results of triple therapy from randomized controlled trials (RCTs) and cohorts studies on delta Sequential Organ Failure Assessment (SOFA) score. HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine; SD: standard deviation; IV: weighted mean difference; CI: confidence interval; df: degrees of freedom.

  • Figure 6. Forest plot showing results of triple therapy from randomized controlled trials (RCTs) and cohort studies on delta Sequential Organ Failure Assessment (SOFA) score without the studies of Karimpour et al. [43] and Marik et al. [39]. HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine; SD: standard deviation; IV: weighted mean difference; CI: confidence interval; df: degrees of freedom.

  • Figure 7. Forest plot showing results of triple therapy from randomized controlled trials (RCTs) and cohort studies on hospital length of stay. HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine; SD: standard deviation; IV: weighted mean difference; CI: confidence interval; df: degrees of freedom.

  • Figure 8. Forest plot showing results of triple therapy from randomized controlled trials (RCTs) and cohort studies on renal replacement therapy. HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine; CI: confidence interval; df: degrees of freedom.

  • Figure 9. Forest plot showing results of triple therapy from randomized controlled trials (RCTs) and cohort studies on duration of vasopressors. HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine; SD: standard deviation; IV: weighted mean difference; CI: confidence interval; df: degrees of freedom.


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