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, Yasushi Tsujimoto, Andrew A Udy, Fumitaka Yanase, Paul J Young

Journal: Intensive care medicine 2022;48(1):16-24

PMID: 34750650

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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.

Address: Intensive Care Unit, Jikei University Hospital, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan. [email protected].; Australian 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. [email protected].; Department of Health Promotion and Human Behaviour, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan. [email protected].; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Australian 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.; Intensive Care Unit, Austin Hospital, Heidelberg, VIC, Australia.; The University of Melbourne, Parkville, VIC, Australia.; Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.; Department of Health Promotion and Human Behaviour, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Australian 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.; Department of Emergency Medicine, Inselspital University Hospital Bern, Bern, Switzerland.; Division of Anesthesiology, Department of Acute Medicine, Geneva University Hospitals, Geneva, Switzerland.; Department of Health Promotion and Human Behaviour, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, Japan.; Scientific Research Works Peer Support Group (SRWS-PSG), Osaka, Japan.; Australian 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.; Department of Intensive Care, The Alfred, Melbourne, VIC, Australia.; Australian 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.; Intensive Care Unit, Austin Hospital, Heidelberg, VIC, Australia.; Australian 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.; The University of Melbourne, Parkville, VIC, Australia.; Intensive Care Unit, Wellington Regional Hospital, Wellington, New Zealand.; Medical Research Institute of New Zealand, Wellington, New Zealand.

DOI: 10.1007/s00134-021-06558-0

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MeSH Terms: Adult, Ascorbic Acid, Glucocorticoids, Humans, Sepsis, Shock, Septic, Thiamine