The Efficacy of vitamin C, thiamine, and corticosteroid therapy in adult sepsis patients: a systematic review and meta-analysis

Somagutta, Manoj Reddy; Pormento, Maria Kezia Lourdes; Khan, Muhammad Adnan; Hamdan, Alaa; Hange, Namrata; Kc, Manish; Pagad, Sukrut; Jain, Molly S; Lingarajah, Sivasthikka; Sharma, Vishal; Kaur, Jaspreet; Emuze, Bernard; Batti, Erkan; Iloeje, Obumneme Jude

doi:10.4266/acc.2021.00108

Cited by 14 publications

(11 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two meta-analyses regarding the effects of HAT therapy were published recently. Both Zayed et al [ 30 ] and Somagutta et al [ 31 ] concluded that HAT therapy significantly improved the SOFA score but appeared not to have significant benefits in the mortality, which was consistent with the results of this meta-analysis with a larger sample size. However, in our meta-analysis, instead of focusing on mortality, we set the change in SOFA score as the primary outcome.…”

Section: Discussionsupporting

confidence: 85%

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

Shen

et al. 2021

j intensive care

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 85%

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

Shen

et al. 2021

j intensive care

View full text Add to dashboard Cite

show abstract

“…Two recent meta-analyses found that both HAT therapy and the combined therapy of thiamine and Vitamin C significantly reduce the duration of vasopressor use and are associated with a reduced SOFA score on day 3. There was however insufficient data to analyse the delta SOFA scores in more detail [20,21].…”

Section: Background and Rationalementioning

confidence: 99%

Early administration of Vitamin C in patients with sepsis or septic shock in emergency departments: A multicenter, double blinded, randomized controlled trial: The C-EASIE trial protocol

et al. 2021

View full text Add to dashboard Cite

Background Sepsis is a potentially life-threatening condition characterized by a deregulated body’s response to infection causing injury to its own tissues and organs. Sepsis is the primary cause of death from infection. If not recognized and treated timely, it can evolve within minutes/hours to septic shock. Sepsis is associated with an acute deficiency of Vitamin C. Despite the proof-of-concept of the benefit of administering Vitamin C in patients with sepsis or septic shock, Vitamin C administration is not yet current practice. Objective To investigate the potential benefit of early administration of high doses of Vitamin C in addition to standard of care in patients with sepsis or septic shock. Methods This phase 3b multi-center trial is conducted in 8 hospitals throughout Belgium. In total 300 patients will be randomly assigned to one of two groups in a 1:1 allocation ratio. The intervention group will receive 1.5 g Vitamin C 4 times a day during 4 days, started within 6 hours after admission. The primary outcome is the average post-baseline patient SOFA score. Conclusion This trial will determine whether the early administration of Vitamin C in patients with sepsis or septic shock can lead to a more rapid solution of shock and less deterioration from sepsis to septic shock, hereby reducing morbidity and mortality as well as the length of hospital stay in this patient population. Trial registration The C-EASIE trial has been registered on the ClinicalTrials.gov website on 10 February 2021 with registration number NCT04747795. Trial Sponsor UZ Leuven (sponsor’s reference S63213)

show abstract

“…Recent years have witnessed the expanding use of high-dose vitamin C in the management of critically ill patients with sepsis, acute respiratory distress syndrome (ARDS), cancer, and even severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. 1 – 4 Vitamin C or ascorbic acid has been explored in the treatment of sepsis and septic shock because of its antioxidant properties, scavenging free radicals, and postulated bacteriostatic effect. 1 Besides, working as an enzyme cofactor for many important biological reactions, vitamin C has other proposed mechanism of actions including the prevention of mitochondrial dysfunction and septic cardiomyopathy, regulating macrophage function, and preservation of macro- or microvascular function.…”

Section: Introductionmentioning

confidence: 99%

“… 1 – 4 Vitamin C or ascorbic acid has been explored in the treatment of sepsis and septic shock because of its antioxidant properties, scavenging free radicals, and postulated bacteriostatic effect. 1 Besides, working as an enzyme cofactor for many important biological reactions, vitamin C has other proposed mechanism of actions including the prevention of mitochondrial dysfunction and septic cardiomyopathy, regulating macrophage function, and preservation of macro- or microvascular function. 1 , 5 Moreover, because of its potential anti-inflammatory and immune-enhancing properties, its therapeutic role has expanded well beyond the treatment of scurvy and promoted even in healthy individuals as “immune-booster”.…”

Section: Introductionmentioning

confidence: 99%

“… 1 Besides, working as an enzyme cofactor for many important biological reactions, vitamin C has other proposed mechanism of actions including the prevention of mitochondrial dysfunction and septic cardiomyopathy, regulating macrophage function, and preservation of macro- or microvascular function. 1 , 5 Moreover, because of its potential anti-inflammatory and immune-enhancing properties, its therapeutic role has expanded well beyond the treatment of scurvy and promoted even in healthy individuals as “immune-booster”. 5 Vitamin C is a water-soluble vitamin and is generally considered safe to use even in higher doses.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin C-induced Hemolysis: Meta-summary and Review of Literature

Juneja¹,

Nasa²,

Jain³

2022

Indian Journal of Critical Care Medicine

View full text Add to dashboard Cite

Vitamin C is increasingly being used, and even high doses are considered safe. However, complications including hemolysis have been reported. We performed a systematic search from PubMed, Science Direct, and Google Scholar databases from January 1975 till July 31, 2021. Search terms used were “Vitamin C” OR “ascorbic acid” AND “haemolysis” OR “haemolytic anaemia.” Data regarding patient's demographics, outcomes and dose, duration, and form of vitamin C were extracted. Fourteen case reports matched the selected criteria, with age ranging from 3 weeks to 75 years with 78.6% being males. About 71.4% were diagnosed to have glucose-6-phosphate dehydrogenase (G6PD) deficiency but previous hemolysis was reported in only two patients, and 57.1% were prescribed vitamin C for nutritional supplementation. The dose ranged from 1 to 200 g/day with 57.1% receiving intravenous formulations. Half of these patients developed other complications including acute kidney injury (AKI), disseminated intravascular coagulation, oxalosis, and methemoglobinemia. About 78.6% developed complications within 3 days of starting vitamin C and only one death was reported. Vitamin C is generally a safe drug but it should be prescribed with caution and only when benefits outweigh the risks. Physicians should be aware of potential complications like severe hemolysis and AKI, especially when using high doses and in G6PD deficiency. How to cite this article Juneja D, Jain R, Nasa P. Vitamin C-induced Hemolysis: Meta-summary and Review of Literature. Indian J Crit Care Med 2022;26(2):224–227.

show abstract

The Efficacy of vitamin C, thiamine, and corticosteroid therapy in adult sepsis patients: a systematic review and meta-analysis

Cited by 14 publications

References 57 publications

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

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

Early administration of Vitamin C in patients with sepsis or septic shock in emergency departments: A multicenter, double blinded, randomized controlled trial: The C-EASIE trial protocol

Vitamin C-induced Hemolysis: Meta-summary and Review of Literature

Contact Info

Product

Resources

About