Study on Metabolic Resuscitation in Sepsis and Septic Shock

Multiple studies have shown the value of steroids in sepsis and septic shock in terms of hastening the shock reversal. However, a recent study suggests that metabolic resuscitation with vitamin C, glucocorticoids, vitamin B1, or combinations of these drugs was not proven to decrease longer-term mortality. The study findings were published in the journal Intensive Care Medicine on November 09, 2021.

Recently, there has been considerable interest in "metabolic resuscitation" as adjunctive therapy for sepsis and septic shock. Such metabolic resuscitation has generally involved a combination of vitamin C, glucocorticoids, and vitamin B1 or one of its components. Dr. Tomoko Fujii and his team conducted a study 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.

They conducted a random-effects network meta-analysis and, where applicable, a random-effects component network meta-analysis. They searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and WHO-ICTRP for 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
• Placebo/usual care

They included a total of forty-three RCTs with 10,257 patients. They used the Confidence in Network Meta-Analysis framework to assess the degree of treatment effect certainty.

The major outcome assessed was longer-term mortality (90-days to 1-year). They also assessed the severity of organ dysfunction over 72 h, time to cessation of vasopressor therapy, and length of stay in the intensive care unit (ICU).

Key Findings of the Study

• Upon analysis, the researchers found 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).
• They also found no evidence that vitamin C or B1 affect organ dysfunction or ICU length of stay.
• However, they noted that glucocorticoid to other treatments shortened the duration of vasopressor therapy (incremental mean difference, − 29.8 h) and ICU stay (incremental mean difference, − 1.3 days).

The authors concluded, "Metabolic resuscitation with vitamin C, glucocorticoids, vitamin B1, or combinations of these drugs was not significantly associated with a decrease in longer-term mortality."

For further information:

DOI: https://doi.org/10.1007/s00134-021-06558-0