Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: a systematic review and a component network meta-analysis.

2021-11-09
Intensive care medicine 48(1)
- Tomoko Fujii
- Georgia Salanti
- Alessandro Belletti
- Rinaldo Bellomo
- Anitra Carr
- Toshi A Furukawa
- Nora Luethi
- Yan Luo
- Alessandro Putzu
- Chiara Sartini
- Yasushi Tsujimoto
- Andrew A Udy
- Fumitaka Yanase
- Paul J Young

PubMed: 34750650
DOI: 10.1007/s00134-021-06558-0

Study Design

Type: Systematic Review
Sample size: n = 257
Population: adults with sepsis or septic shock
Methods: random-effects network meta-analysis and component network meta-analysis of 43 RCTs (10,257 patients)

We aimed to compare the effects of vitamin C, glucocorticoids, vitamin B1, combinations of these drugs, and placebo or usual care on longer-term mortality in adults with sepsis or septic shock. MEDLINE, Embase, CENTRAL, ClinicalTrials.gov and WHO-ICTRP were searched. The final search was carried out on September 3rd, 2021. Multiple reviewers independently selected randomized controlled trials (RCTs) comparing very-high-dose vitamin C (≥ 12 g/day), high-dose vitamin C (< 12, ≥ 6 g/day), vitamin C (< 6 g/day), glucocorticoid (< 400 mg/day of hydrocortisone), vitamin B1, combinations of these drugs, and placebo/usual care. We performed random-effects network meta-analysis and, where applicable, a random-effects component network meta-analysis. We used the Confidence in Network Meta-Analysis framework to assess the degree of treatment effect certainty. The primary outcome was longer-term mortality (90-days to 1-year). Secondary outcomes were severity of organ dysfunction over 72 h, time to cessation of vasopressor therapy, and length of stay in intensive care unit (ICU). Forty-three RCTs (10,257 patients) were eligible. There were no significant differences in longer-term mortality between treatments and placebo/usual care or between treatments (10 RCTs, 7,096 patients, moderate to very-low-certainty). We did not find any evidence that vitamin C or B1 affect organ dysfunction or ICU length of stay. Adding glucocorticoid to other treatments shortened duration of vasopressor therapy (incremental mean difference, - 29.8 h [95% CI - 44.1 to - 15.5]) and ICU stay (incremental mean difference, - 1.3 days [95% CI - 2.2 to - 0.3]). Metabolic resuscitation with vitamin C, glucocorticoids, vitamin B1, or combinations of these drugs was not significantly associated with a decrease in longer-term mortality.

Research Insights

Vitamin B1→Reduced Length of Stay
We did not find any evidence that vitamin C or B1 affect organ dysfunction or ICU length of stay.
Effect
Neutral
Effect size
Small
Dose
very-high-dose (≥ 12 g/day), high-dose (< 12, ≥ 6 g/day), or low-dose (< 6 g/day)
Vitamin B1→Reduced Mortality
There were no significant differences in longer-term mortality between treatments and placebo/usual care or between treatments (10 RCTs, 7,096 patients, moderate to very-low-certainty).
Effect
Neutral
Effect size
Small
Dose
very-high-dose (≥ 12 g/day), high-dose (< 12, ≥ 6 g/day), or low-dose (< 6 g/day)
Vitamin B1→Reduced Organ Dysfunction Severity
We did not find any evidence that vitamin C or B1 affect organ dysfunction or ICU length of stay.
Effect
Neutral
Effect size
Small
Dose
very-high-dose (≥ 12 g/day), high-dose (< 12, ≥ 6 g/day), or low-dose (< 6 g/day)
Vitamin B1→Reduced Time to Vasopressor Cessation
Adding glucocorticoid to other treatments shortened duration of vasopressor therapy (incremental mean difference, - 29.8 h [95% CI - 44.1 to - 15.5]) and ICU stay (incremental mean difference, - 1.3 days [95% CI - 2.2 to - 0.3]). [The effect of vitamin B1 alone on this outcome was not significant in the network meta-analysis; all comparisons not involving glucocorticoid showed no significant benefit.]
Effect
Neutral
Effect size
Small
Dose
very-high-dose (≥ 12 g/day), high-dose (< 12, ≥ 6 g/day), or low-dose (< 6 g/day)
Vitamin C→Reduced Length of Stay
We did not find any evidence that vitamin C or B1 affect organ dysfunction or ICU length of stay.
Effect
Neutral
Effect size
Small
Dose
very-high-dose (≥ 12 g/day), high-dose (< 12, ≥ 6 g/day), or low-dose (< 6 g/day)
Vitamin C→Reduced Mortality
There were no significant differences in longer-term mortality between treatments and placebo/usual care or between treatments (10 RCTs, 7,096 patients, moderate to very-low-certainty).
Effect
Neutral
Effect size
Small
Dose
very-high-dose (≥ 12 g/day), high-dose (< 12, ≥ 6 g/day), or low-dose (< 6 g/day)
Vitamin C→Reduced Organ Dysfunction Severity
We did not find any evidence that vitamin C or B1 affect organ dysfunction or ICU length of stay.
Effect
Neutral
Effect size
Small
Dose
very-high-dose (≥ 12 g/day), high-dose (< 12, ≥ 6 g/day), or low-dose (< 6 g/day)
Vitamin C→Reduced Time to Vasopressor Cessation
Adding glucocorticoid to other treatments shortened duration of vasopressor therapy (incremental mean difference, - 29.8 h [95% CI - 44.1 to - 15.5]) and ICU stay (incremental mean difference, - 1.3 days [95% CI - 2.2 to - 0.3]). [The effect of vitamin B1 alone on this outcome was not significant in the network meta-analysis; all comparisons not involving glucocorticoid showed no significant benefit.]
Effect
Neutral
Effect size
Small
Dose
very-high-dose (≥ 12 g/day), high-dose (< 12, ≥ 6 g/day), or low-dose (< 6 g/day)