Concerns with the revised Japanese recommendation for administering vitamin C to septic patients

In the revision of the recommendation for administering vitamin C for sepsis patients, Egi and Ogura write “the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020… suggested administering vitamin C to septic patients”. They carried out a new literature search and identified 12 new RCTs, performing a revised meta-analysis of 23 RCTs in all and reversing the 2020 recommendation. However, 13 of the 23 listed trials administered combinations of antioxidants and other drugs, such as hydrocortisone and thiamine. If the scientific question is about the specific effect of vitamin C on sepsis, then the included trials should only examine vitamin C. For example, a recent observational study indicated significantly different effects from vitamin C alone and from vitamin C together with hydrocortisone...