Dataset Information

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Health-Related Quality of Life in Sepsis.

ABSTRACT: Patients who experience sepsis often have long-term effects that may impact health-related quality of life. This study aimed to investigate whether the combination of ascorbic acid, corticosteroids, and thiamine compared with placebo improves health-related quality of life in patients with septic shock.

Design

Secondary analysis of the Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis randomized controlled trial (NCT03389555).

Setting

Thirteen tertiary-care hospitals in the United States.

Patients

Patients who were enrolled in Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis, survived to 90 days post enrollment and were able to be contacted by telephone.

Interventions

Patients were randomly assigned to parenteral ascorbic acid (1,500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days or placebo.

Measurements and main results

One hundred seventeen patients (59%) survived to 90 days and were administered the Short Form 36 questionnaire; of these, 72 (62%) completed the Short Form 36 (38 [53%] in the intervention group, 34 [47%] in placebo). Sixty-six (92%) completed all survey questions (36 [95%] in the intervention group, 30 [88%] in placebo). There was no significant difference in overall Short Form 36 score between intervention and placebo group (median score: 39.4 [interquartile range, 31.2-45.4] vs 43.2 [37.0-46.7], respectively, p = 0.18). We found no statistically significant difference between the two groups in any of the other health-related quality of life domains used.

Conclusions

We found no difference in the health-related quality of life in patients with septic shock treated with a combination of ascorbic acid, corticosteroids, and thiamine compared to placebo.

SUBMITTER: Grossestreuer AV

PROVIDER: S-EPMC7685963 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Health-Related Quality of Life in Sepsis.

Grossestreuer Anne V AV Moskowitz Ari A Andersen Lars W LW Holmberg Mathias J MJ Konacki Varun V Berg Katherine M KM Chase Maureen M Cocchi Michael N MN Donnino Michael W MW

Critical care explorations 20201123 12

Patients who experience sepsis often have long-term effects that may impact health-related quality of life. This study aimed to investigate whether the combination of ascorbic acid, corticosteroids, and thiamine compared with placebo improves health-related quality of life in patients with septic shock.<h4>Design</h4>Secondary analysis of the Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis randomized controlled trial (NCT03389555).<h4>Setting</h4>Thirteen tertiary-care hospitals in the Un ...[more]

PMID: 33251516

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Project description:ImportanceThe combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock.ObjectiveTo determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock.Design, setting, and participantsRandomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019.InterventionsPatients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102).Main outcomes and measuresThe primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses.ResultsAmong 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively).Conclusions and relevanceIn patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock.Trial registrationClinicalTrials.gov Identifier: NCT03389555.

Project description:AbstractBackground: Acute kidney injury (AKI) occurs frequently in septic patients and correlates with increased mortality. Because clinical studies investigating hydrocortisone, ascorbic acid, and thiamine (HAT) have demonstrated discordant results, studies were performed using mortality stratification for therapy to identify candidates for therapy and determine mechanisms of organ injury. Methods: Sepsis was induced using the cecal ligation and puncture (CLP) model of sepsis with fluid and antibiotic support. Heart rate (HR) measurements obtained 6 hours after CLP stratified mice into live predicted (P-Live) or die predicted (P-Die). Stratified mice were then randomized for treatment with HAT or vehicle given 7 hours after CLP. Physiologic measurements were taken again at 24 hours, and mice were killed to collect blood and organs. Results: The following five groups were created: (1) P-Live vehicle, (2) P-Live HAT, (3) P-Die vehicle, (4) P-Die HAT, and (5) naive mice. Comparisons were made to test the hypotheses that (1) P-Die vehicle mice will have significant deterioration compared with P-Live mice targeting the kidney and (2) HAT will correct these deleterious changes in P-Die mice. Compared with P-Live, P-Die mice had a significant decline in all measured physiologic parameters (HR, cardiac output, breath rate, and temperature), which were corrected with HAT therapy (P < 0.05 for all parameters). The P-Die mice had declines in the ascorbic acid within the blood, peritoneal lavage, and kidney homogenate compared with P-Live mice indicating consumption, and the decline was corrected with HAT. Elevated IL-6, KC, Macrophage Inflammatory Protein-2, and IL-1RA were found in P-Die mice and decreased with HAT. Markers of endothelial cell injury (glypican 1 and glypican 4) were elevated in the P-Die mice, and these values were decreased with HAT therapy. Low oxygen levels with subsequent oxidative stress (OS) in the kidney were visualized in histologic sections using hypoxyprobe and also with carbonyl proteins and 8-iso-prostaglandin F2α in kidney homogenates. The P-Die mice had significant elevations of renal OSs, which was ameliorated with HAT. Kidney injury was evident in the P-Die mice compared with P-Live mice with elevations in blood urea nitrogen and cystatin C, which were significantly reduced with HAT. There was no evidence of global hypoxia or organ injury because hepatic parameters remained normal. Conclusions: Our data show that in CLP-induced sepsis, P-Die mice have increased inflammation, OS, and kidney injury. Hydrocortisone, ascorbic acid, and thiamine therapy decreased renal OS and injury in the P-Die group when given after the onset of sepsis-induced physiologic changes.

Project description:OBJECTIVES:Mortality from pediatric sepsis has steadily declined over the past several decades; however, little is known about morbidity among survivors. We aimed to determine the prevalence of and risk factors for failure to recover to baseline health-related quality of life following community-acquired pediatric sepsis. DESIGN:Retrospective cohort study. SETTING:Seattle Children's Hospital. PATIENTS:Children aged 1 month to 21 years admitted to the inpatient wards or ICUs from 2012 to 2015 who met 2005 consensus sepsis criteria within 4 hours of hospitalization and were enrolled in the hospital's Outcomes Assessment Program with baseline, admission, and post-discharge health-related quality of life data available. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We assessed health-related quality of life with the Pediatric Quality of Life Inventory for pre-admission baseline, admission, and post-discharge (median, 31 d) status. We determined associations between patient and illness characteristics with failure to recover within 4.5 points of baseline at follow-up (the minimum clinically significant difference between two scores). Of 790 patients, 23.8% failed to recover to baseline health-related quality of life at follow-up. Factors associated with failure to recover were septic shock, older age, private insurance, complex chronic disease, immune compromise, CNS infection or bacteremia, ICU admission, and longer length of stay. On multivariable analysis controlling for time to follow-up, failure to recover was independently associated with septic shock (relative risk, 1.79; 95% CI, 1.24-2.58), older age (relative risk, 1.02/yr; 95% CI, 1.01-1.05), immune compromise (relative risk, 1.83; 95% CI, 1.40-2.40), and length of stay (relative risk, 1.03/d; 95% CI, 1.01-1.04). CONCLUSIONS:Nearly one-quarter of children surviving hospitalization for community-acquired sepsis experienced a clinically significant deterioration in health-related quality of life. We identify risk factors for poor outcomes following sepsis and highlight the need for ongoing evaluation and treatment by primary and specialty care providers for pediatric sepsis survivors after hospital discharge.

Project description:BACKGROUND:Due to the rise in incidence, the long term effect of sepsis are becoming more evident. There is increasing evidence that sepsis may result in an impaired health related quality of life. The aim of this study was to investigate whether health related quality of life is impaired in sepsis survivors and which clinical parameters are associated with the affected health related quality of life. METHODS:We analyzed 880 Short Form 36 (SF-36) questionnaires that were sent to sepsis survivors who participated in the Prehospital Antibiotics Against Sepsis (PHANTASi) trial. These questionnaires were sent by email, 28 days after discharge. Data entry and statistical analyses were performed in SPSS. The data from the general Dutch population, was obtained from the Netherlands Cancer Institute (NKI-AVL) and served as a control group. Subsequently, 567 sepsis survivors were matched to 567 controls. Non-parametric Wilcoxon signed-rank test was performed to compare these two groups. Within the group, we sought to explain the diminished health related quality of life by factor analysis. RESULTS:We found that sepsis survivors have a worse health related quality of life compared to the general Dutch population. This negative effect was more evident for the physical component than the mental component of health related quality of life. We found that health related quality of life was significantly altered by advancing age and female sex. We also found that the total length of stay (in the hospital) and (previous) comorbidity negatively affect the physical component of health related quality of life. CONCLUSION:In our study we found that health related quality of life in sepsis survivors, 28 days after discharge, is severely diminished in comparison with the general Dutch population. The physical domain is severely affected, whereas the mental domain is less influenced. The length of stay, comorbidity, advancing age and female sex all have a negative effect on the Physical Component Scale of the health related quality of life.

Dataset Information

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Health-Related Quality of Life in Sepsis.

Design

Setting

Patients

Interventions

Measurements and main results

Conclusions

Publications

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Health-Related Quality of Life in Sepsis.

Similar Datasets

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