Fujii, TomokoTomokoFujiiSalanti, GeorgiaGeorgiaSalanti0000-0002-3830-8508Belletti, AlessandroAlessandroBellettiBellomo, RinaldoRinaldoBellomoCarr, AnitraAnitraCarrFurukawa, Toshi AToshi AFurukawaLüthi, NoraNoraLüthiLuo, YanYanLuoPutzu, AlessandroAlessandroPutzuSartini, ChiaraChiaraSartiniTsujimoto, YasushiYasushiTsujimotoUdy, Andrew AAndrew AUdyYanase, FumitakaFumitakaYanaseYoung, Paul JPaul JYoung2024-10-062024-10-062022-01https://boris-portal.unibe.ch/handle/20.500.12422/57508We 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.enHydrocortisone Network meta-analysis Sepsis Systematic review Thiamine Vitamin C600 - Technology::610 - Medicine & health300 - Social sciences, sociology & anthropology::360 - Social problems & social servicesarticle10.48350/1611823475065010.1007/s00134-021-06558-0