Hydrocortisone, ascorbic acid, and thiamine (HAT) for sepsis and septic shock: a meta-analysis with sequential trial analysis

Abstract

Background Sepsis is a primary global health threat and costs a lot, requiring effective and affordable treatments. We performed this meta-analysis to explore the treatment of hydrocortisone, ascorbic acid, and thiamine (HAT) in sepsis and septic shock. Methods We searched Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to August 14, 2021. We included randomized controlled trials (RCTs) that evaluated the HAT treatments in sepsis and septic shock. The primary outcome was the change in SOFA score over the 72 h. The second outcomes were the hospital, and 28-/30-day mortality, the duration of vasopressors, PCT clearance, hospital length of stay (LOS), and ICU LOS. We performed a subgroup analysis and a trial sequential analysis (TSA). The Der Simonian–Laird random-effects models were used to report the pooled risk ratios (RR) or mean difference (MD) with confidence intervals (CI). Results Nine RCTs, enrolling 1427 patients of sepsis and septic shock treated with HAT (717) or only standard care (710), were included. There was a significant difference between the two groups in the change in SOFA score over the first 72 h (MD 0.65, 95% CI 0.30 to 1.00), the duration of vasopressors (MD − 18.16, 95% CI − 25.65 to − 10.68) and the PCT clearance (MD 14.54, 95% CI 0.64 to 28.43). In addition, there was no significant difference in the hospital mortality (RR 1.07, 95% CI 0.85 to 1.34), the 28-/30-day mortality (RR 0.96, 95% CI 0.80 to 1.15), the hospital LOS (MD 0.78, 95% CI − 0.30 to 1.86), and ICU LOS (MD 0.12, 95% CI − 0.53 to 0.78). Conclusions The HAT combination improves the SOFA score in the first 72 h and reduces the duration of vasopressors in patients with sepsis. Given the minor mean difference of the change in SOFA score, the mortality benefit has not been observed. Trial registration PROSPERO, CRD42020203166.

Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial

“…In spite of theoretical plausibility of hydrocortisone, vitamin C, and thiamine combination therapy, our study’s results do not provide any significant survival benefit in septic shock patients, which is consistent with the results of previous RCTs [ 5 , 6 , 9 , 19 ] and meta-analyses [ 20 , 21 ]. It is worth pointing out that Marik et al [ 4 ] and Chang et al [ 22 ] highlighted that the early use of the combination therapy appeared to be associated with patients’ survival improvement.…”

The effect of intravenous vitamin C on clinical outcomes in patients with sepsis or septic shock: A meta-analysis of randomized controlled trials

“…In recent years, multiple randomized controlled trials (RCTs) evaluating the effect of intravenous (IV) vitamin C with or without hydrocortisone and thiamine have been completed. Several recently published meta-analyses (14)(15)(16)(17)(18)(19)(20) assessed the combination of hydrocortisone, ascorbic acid, and thiamine (HAT) treatment in septic patients. The results indicated that the HAT treatment improved the Sequential Organ Failure Assessment (SOFA) score and reduced the duration of vasopressor, but was not associated with lower short-term mortality.…”

Neonatal Paenibacilliosis:Paenibacillus thiaminolyticusas a Novel Cause of Neonatal Sepsis with High Risk of Sequelae in Uganda

“…24 Recent studies have failed to show a mortality benefit of the combination of thiamine, vitamin C with and without hydrocortisone in mortality outcomes for adults with sepsis. [64][65][66] However, in a retrospective analysis, thiamine supplementation improved survival for adults with hospital-acquired pneumonia. 67 Thiamine supplementation may yet have a role for certain types of infection, in cases when sepsis is caused by a thiamine-consuming organism or when pre-existing thiamine deficiency exists.…”