Evidence map›Paper›PMID 34750650›Full record

SynthesisIntensive care medicine2022

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.

Tomoko Fujii, Georgia Salanti, Alessandro Belletti, Rinaldo Bellomo, Anitra Carr, Toshi A Furukawa, Nora Luethi, Yan Luo, Alessandro Putzu, Chiara Sartini and 4 more

Open access · hybridAbstract readSystematic ReviewNetwork Meta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Intensive care medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 12 pooled it
11.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 12 syntheses or guidelines pooled it, 110 citations in OpenAlex.

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  3. [S3 guideline on sepsis-prevention, diagnosis, therapy, and follow-up care-update 2025].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2025
    Guideline
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 9 institutions in 5 countries.

Tomoko FujiiIntensive Care Unit, Jikei University Hospital, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan. tofujii-tky@umin.net.ORCID http://orcid.org/0000-0003-3854-4081
Georgia SalantiInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Alessandro BellettiDepartment of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Rinaldo BellomoAustralian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Anitra CarrDepartment of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
Toshi A FurukawaDepartment of Health Promotion and Human Behaviour, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Nora LuethiAustralian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Yan LuoDepartment of Health Promotion and Human Behaviour, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Alessandro PutzuDivision of Anesthesiology, Department of Acute Medicine, Geneva University Hospitals, Geneva, Switzerland.
Chiara SartiniDepartment of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Yasushi TsujimotoDepartment of Health Promotion and Human Behaviour, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Andrew A UdyAustralian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Fumitaka YanaseAustralian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Paul J YoungAustralian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Kyoto University · JPThe University of Melbourne · AUVita-Salute San Raffaele University · ITAustin Hospital · AUThe Alfred Hospital · AUUniversity Hospital of Bern · CHUniversity Hospital of Geneva · CHUniversity of Bern · CHUniversity of Otago · NZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

SepsisShock, SepticAdultAscorbic AcidGlucocorticoidsHumansThiamineAscorbic AcidGlucocorticoidsThiamineHydrocortisoneNetwork meta-analysisSepsisSystematic reviewThiamineVitamin C

Identifiers

PMID34750650
PMCPMC8724116
OpenAlexW3211482156

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.