Hydrocortisone–Ascorbic Acid–Thiamine Use Associated with Lower Mortality in Pediatric Septic Shock (original) (raw)
Related papers
Journal of Advances in Medicine and Medical Research
Background: Millions of individuals worldwide suffer from septic shock and sepsis each year, with fatalities reaching one in four and often higher. This work was conducted to evaluate the impact of Ascorbic acid, hydrocortisone, and thiamine treatment on the 28th day mortality rate and the outcomes (changes in SOFA score, incidence of organ dysfunction, alterations in serum procalcitonin level, changes in serum lactate level and total dose of vasopressor therapy. Methods: This prospective randomised controlled double-blinded work was performed on 80 individuals ranging in age from 18 to 65 years old and presented with sepsis who were diagnosed based on the SSC 2016 and The SSC Bundle 2018 Update. The participants were divided into two groups at random. Group I (placebo): The conventional approach was used to treat those who were in this group. The participants were given 50 ml of normal saline intravenously within 30 minutes, 5 ml intravenously within 6 hours, and 10 ml intravenousl...
Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, 2021
Background: Recent studies suggest that hydrocortisone, Vitamin C, and thiamine alone or in combination may improve the clinical outcomes of patients with septic shock. The aim of this study is the effects of this combination therapy on clinical outcome and sepsis biomarkers in patients with septic shock. Materials and Methods: Fifty-eight consecutive patients suffering septic shock were randomly assigned into two groups receiving the combination therapy of hydrocortisone (50 mg/6 h, intravenously), Vitamin C (1.5 g/6 h in 100 ml normal saline or DW5%, intravenously), and thiamine (200 mg/12 h in 50 ml normal saline or DW5%, intravenously) or placebo for up to 4 days. Results: The decline in procalcitonin, lactate, and leukocyte count 72 h after the initiation of treatment was significantly greater in the intervention as compared to the control group. The intervention group has a significantly lower sequential organ failure assessment score 72 h after treatment (P < 0.001). The m...
Chest, 2016
The global burden of sepsis is estimated as 15 to 19 million cases annually with a mortality rate approaching 60% in low income countries. In this retrospective before-after clinical study, we compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone and thiamine during a 7-month period (treatment group) compared to a control group treated in our ICU during the preceding 7 months. The primary outcome was hospital survival. A propensity score was generated to adjust the primary outcome. There were 47 patients in both treatment and control groups with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared to 40.4% (19 of 47) in the control group (p < 0.001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI 0.04-0.48, p=002). The SOFA score decreased in all pati...
Hydrocortisone, ascorbic acid and thiamine for sepsis: Is the jury out?
World Journal of Diabetes, 2020
Sepsis and septic shock remain a major cause of morbidity and mortality among patients admitted in the intensive care unit. Diabetes is a major risk factor for the development of sepsis. The global mortality of sepsis remains high, despite significant interventions and guidelines. It has been known for decades that patients with sepsis have reduced levels of antioxidants, most notably vitamin C. Furthermore, experimental data has demonstrated multiple beneficial effects of vitamin C in sepsis. In addition, corticosteroids and thiamine may have synergistic biological effects together with vitamin C. Preliminary data suggests that therapy with hydrocortisone, ascorbic acid and thiamine improves the outcome of patients with sepsis with the potential to save millions of lives. However, this intervention has met with much resistance and has not been widely adopted. Ultimately, we await the final jury verdict on this simple, safe and cheap intervention.
JAMA, 2020
It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock. OBJECTIVE To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS Multicenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019. INTERVENTIONS Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days. MAIN OUTCOMES AND MEASURES The primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality. RESULTS Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was-0.6 hours (95% CI,-8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported. CONCLUSIONS AND RELEVANCE In patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone.
Adding vitamin C to hydrocortisone lacks benefit in septic shock: a historical cohort study
Canadian Journal of Anesthesia/Journal canadien d'anesthésie
Purpose Sepsis has high incidence and mortality rates, particularly in the intensive care unit (ICU). Corticosteroids may improve outcomes, and vitamin C may add benefit. We aimed to assess whether vitamin C and corticosteroids improved outcomes compared with corticosteroids alone. Methods This historical cohort study (
American Journal of Medical Science and Innovation
Systematic Inflammatory Response Syndrome and Sepsis are inflammatory responses to many health manifestations. Sepsis mortality is high despite global treatment standards, with metabolic resuscitation being a novel approach for managing Sepsis. The purpose of this systematic review is to assess the effectiveness of the critical care combination comprising hydrocortisone, Vitamin C, and thiamine in potentially mitigating Sepsis, reducing mortality associated with septic shock, and alleviating organ failure. In order to execute this scoping review, recent research based on the effect of vitamin C, hydrocortisone, and thiamine therapy in Sepsis and Septic Shock was identified. Data was gathered from Google Scholar, PubMed, NCBI, Hindawi, Scirp, Journal of Immunology, and Critical Care Medicine. Studies selected from different years ranging between 2017 to 2023 using keywords ‘Severe Sepsis,’ ‘Septic Shock,’ ‘Effect of Vitamin C on Sepsis, ‘Effect of Thiamine on Sepsis Treatment,’ ‘Hydr...
Indian Journal of Critical Care Medicine, 2020
Background: Sepsis remains a leading cause of death worldwide despite advances in management strategies. Preclinical and observational studies have found mortality benefit with high-dose vitamin C in sepsis. Our study aims to prospectively evaluate the effect of intravenous hydrocortisone, vitamin C [ascorbic acid (AA)], and thiamine (HAT) administration in reducing inpatient all-cause mortality among patients with septic shock. Materials and methods: Our single-center, prospective, open-label, randomized controlled trial recruited patients with admitting diagnosis of septic shock and assigned eligible patients (1:1) into either intervention (HAT) or control group (routine). The HAT group received intravenous combination of vitamin C (1.5 g every 6 hours), thiamine (200 mg every 12 hours), and hydrocortisone (50 mg every 6 hours) within 6 hours of onset of septic shock admission. The treatment was continued for at least 4 days, in addition to the routine standard of care provided to the control group. Thiamine and hydrocortisone use in control arm was not restricted. Vitamin C levels were estimated at baseline and at the end of the 4 days of treatment for both groups. The primary outcome evaluated was mortality during inpatient stay. Results: Among 90 patients enrolled, 88 patients completed the study protocol. The baseline characteristics between the HAT (n = 45) and the routine (n = 43) groups were comparable. The all-cause mortality in the HAT cohort was 57% (26/45) compared to 53% (23/43) in the routine care group (p = 0.4, OR 1.19, 95% CI 0.51-2.76). The time to reversal of septic shock was significantly lower in the HAT (34.58 ± 22.63 hours) in comparison to the routine care (45.42 ± 24.4 hours) (p = 0.03, mean difference −10.84, 95% CI −20.8 to −0.87). No significant difference was observed between the HAT and the routine care with respect to changes in sequential organ failure assessment (SOFA) scores at 72 hours (2.23 ± 2.4 vs 1.38 ± 3.1), the use of mechanical ventilation (48% vs 46%), and mean Vasoactive Inotropic Score (7.77 ± 12.12 vs 8.86 ± 12.5). Conclusion: Intravenous administration of vitamin C, thiamine, and hydrocortisone did not significantly improve the inpatient all-cause mortality among patients with septic shock. Clinical significance: HAT protocol does not reduce hospital mortality but decreases time to shock reversal in septic shock.
Outcome of Septic Shock Patients treated with Vitamin C and Thiamine: A Prospective Cohort Study
Journal of Acute Care, 2022
Background: Although there has been great progress in the field of medicine, mortality associated with the age-old problem of sepsis still remains high. One of the newer modalities to treat sepsis is the hydrocortisone, ascorbic acid (AA), and thiamine (HAT) therapy, using HAT, which is proposed to reduce organ failure and mortality by restoring dysregulated host immune response and mitochondrial function as well as neutralizing reactive oxygen species (ROS). Studies evaluating the treatment of severe sepsis, burns, and trauma with vitamin C administration have shown inconsistent results. Several studies have also shown the detrimental effect of a positive fluid balance on patients with sepsis, including an increased risk of mortality. This study aims to evaluate the effect of vitamin C with thiamine on improving the outcome of septic shock. Materials and methods: This prospective cohort study was conducted at a tertiary care intensive care unit (ICU) and enrolled adult septic shock patients admitted over a 6-month period between April and September 2018. They formed an intervention group that received intravenous (IV) vitamin C 1.5 gm every 6 hours and thiamine 200 mg every 12 hours in addition to antibiotics. This was compared with a retrospective cohort of patients admitted between July to December 2017, which received only antibiotics. Both vitamin C and thiamine were initiated within 6 hours of admission and given for a period of 4 days. Hydrocortisone, as an infusion of 200 mg over 24 hours, was used in all patients on vasopressor support. The primary outcome evaluated was ICU mortality and secondary outcomes, ICU length of stay (LOS), hospital LOS, mechanical ventilation-free days (MVFDs), vasopressor-free days (VFDs), and cumulative fluid balance after 4 days. Results: A total of 30 patients fulfilled the inclusion criteria and formed the intervention group. This was compared with a retrospective group which was equally matched in their baseline characteristics and acute physiology and chronic health evaluation (APACHE) II scores (20 vs 21), as well as antibiotics, are given. ICU mortality was 19% in the intervention group and 34.1% in the retrospective group (p = 0.115). ICU LOS was higher in the intervention group (5 vs 4 days, p = 0.014). There was no difference in the other secondary outcome parameters, namely, hospital LOS (10 vs 8 days, p = 0.141), MVFDs (5 vs 6, p = 0.493), VFDs (4 vs 6, p = 0.415), and cumulative fluid balance (+583 mL vs +450 mL, p = 0.209). Conclusion: Intravenous (IV) administration of vitamin C and thiamine may not be beneficial in improving the outcome in patients with septic shock.
Critical Care
The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.