TY - JOUR
T1 - Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock
T2 - a systematic review and a component network meta-analysis
AU - Fujii, Tomoko
AU - Salanti, Georgia
AU - Belletti, Alessandro
AU - Bellomo, Rinaldo
AU - Carr, Anitra
AU - Furukawa, Toshi A.
AU - Luethi, Nora
AU - Luo, Yan
AU - Putzu, Alessandro
AU - Sartini, Chiara
AU - Tsujimoto, Yasushi
AU - Udy, Andrew A.
AU - Yanase, Fumitaka
AU - Young, Paul J.
N1 - Funding Information:
This research was conducted during the tenure of Health Research Council of New Zealand Clinical Practitioner Research Fellowship held by PY and Sir Charles Hercus Health Research Fellowship held by AC. The Medical Research Institute of New Zealand is supported by independent research organization funding from the Health Research Council of New Zealand. This study was in part supported by JSPS Grant-in-Aid for Scientific Research (Grant Number 19K10509) to TAF.
Publisher Copyright:
© 2021, The Author(s).
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - Hydrocortisone
KW - Network meta-analysis
KW - Sepsis
KW - Systematic review
KW - Thiamine
KW - Vitamin C
UR - http://www.scopus.com/inward/record.url?scp=85118642510&partnerID=8YFLogxK
U2 - 10.1007/s00134-021-06558-0
DO - 10.1007/s00134-021-06558-0
M3 - Review Article
C2 - 34750650
AN - SCOPUS:85118642510
SN - 0342-4642
VL - 48
SP - 16
EP - 24
JO - Intensive Care Medicine
JF - Intensive Care Medicine
IS - 1
ER -