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Early Vitamin C and Thiamine Administration to Patients with Septic Shock in Emergency Departments: Propensity Score-Based Analysis of a Before-and-After Cohort Study.

ABSTRACT: BACKGROUND:Intravenous vitamin C and thiamine administration may be a potential adjuvant therapy for septic shock. We aimed to investigate the impact of early vitamin C and thiamine administration in septic shock patients. METHODS:This retrospective before-and-after cohort study used data extracted from the Korean Shock Society's prospective septic shock registry. We compared 28-day and in-hospital mortality rates between patients treated with intravenous vitamin C (3 g/12 h or 1.5 g/6 h) and thiamine (200 mg/12 h) <6 hours after shock recognition from July through December 2017 (n = 229) and control patients from October 2015 through June 2017 (n = 915) using propensity score matching. RESULTS:The 28-day (18.3% vs. 17.5%; P = 0.76) and in-hospital (16.6% vs. 18.3%; P = 0.55) mortality rates did not differ between treatment and control groups, nor did 28-day (18.5% vs. 17.5%; P = 0.84) and in-hospital (16.7% vs. 18.4%; P = 0.54) mortality rates after matching. In the subgroup analysis, treatment was associated with lower in-hospital mortality rates in patients with albumin <3.0 mg/dL or a Sequential Organ Failure Assessment (SOFA) score >10. CONCLUSION:Early vitamin C and thiamine administration in patients with septic shock did not improve survival; however, administration could benefit conditions that are more severe, such as hypoalbuminemia or severe organ failure.

SUBMITTER: Shin TG

PROVIDER: S-EPMC6352246 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Early Vitamin C and Thiamine Administration to Patients with Septic Shock in Emergency Departments: Propensity Score-Based Analysis of a Before-and-After Cohort Study.

Shin Tae Gun TG Kim Youn-Jung YJ Ryoo Seung Mok SM Hwang Sung Yeon SY Jo Ik Joon IJ Chung Sung Phil SP Choi Sung-Hyuk SH Suh Gil Joon GJ Kim Won Young WY

Journal of clinical medicine 20190116 1

<h4>Background</h4>Intravenous vitamin C and thiamine administration may be a potential adjuvant therapy for septic shock. We aimed to investigate the impact of early vitamin C and thiamine administration in septic shock patients.<h4>Methods</h4>This retrospective before-and-after cohort study used data extracted from the Korean Shock Society's prospective septic shock registry. We compared 28-day and in-hospital mortality rates between patients treated with intravenous vitamin C (3 g/12 h or 1. ...[more]

PMID: 30654592

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Project description:BackgroundIntravenous vitamin C administration in septic shock may have a sparing effect on vasopressor requirements, and vitamin C's enzyme cofactor functions provide a mechanistic rationale. Our study aimed to determine the effect of intravenous vitamin C administration on vasopressor requirements and other outcomes in patients with septic shock.MethodsThis was a double-blind, randomised placebo-controlled trial in 40 patients with septic shock who were randomised (1:1) to receive intravenous vitamin C (at a dose of 25 mg/kg of body weight every 6 h) or placebo (intravenous 5% dextrose) for up to 96 h, or until death or discharge. The primary outcome was intravenous vasopressor requirements (dose and duration), and secondary outcomes included Sequential Organ Failure Assessment (SOFA) scores, intensive care unit (ICU) and hospital length of stay, and mortality. In addition, blood samples were collected to determine vitamin C kinetics and inflammatory marker concentrations.ResultsMedian plasma vitamin C concentrations were deficient at baseline (9.2 [4.4, 12] µmol/L) and increased to 408 (227, 560) µmol/L following 72 h of intervention. The mean duration of intravenous vasopressor infusion in the vitamin C group was 48 (95% CI 35-62) hours and in the placebo group was 54 (95% CI 41-62) hours (p = 0.52). The dose of vasopressor delivered over time was comparable between the two groups, as were SOFA scores (p > 0.05). The median ICU length of stay in the intervention group was 3.8 (2.2, 9.8) days versus 7.1 (3.1, 20) days in the placebo group (p = 0.12). The median hospital length of stay for the vitamin C group was 18 (11, 35) days versus 22 (10, 52) days for the placebo group (p = 0.65). Mortality was comparable between the two groups (p > 0.05). Of the inflammatory markers, neutrophil counts were elevated in the vitamin C group relative to placebo by 72 h (p = 0.01). C-reactive protein and myeloperoxidase concentrations were elevated at baseline, however, the two groups were comparable over time (p > 0.05).ConclusionsOur pilot study indicated that intravenous vitamin C did not provide significant decreases in the mean dose or duration of vasopressor infusion. Further research that takes into account the potential impact of intervention timing, dose and duration, and location of trial, may provide more definitive evidence.Trial registrationACTRN12617001184369 (11/8/2017).

Project description:BACKGROUND:Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. METHODS:A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. RESULTS:Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h. CONCLUSION:A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.

Project description:PurposeIt is not clear whether vasopressin versus norepinephrine changed mortality in clinical practice in the Vasopressin and Septic Shock Trial (VASST) coordinating center hospital after VASST was published. We tested the hypothesis that vasopressin changed mortality compared to norepinephrine using propensity matching of vasopressin to norepinephrine-treated patients in the VASST coordinating center hospital before (SPH1) and after (SPH2) VASST was published.MethodsVasopressin-treated patients were propensity score matched to norepinephrine-treated patients based on age, APACHE II, respiratory, renal, and hematologic dysfunction, mechanical ventilation status, medical/surgical status, infection site, and norepinephrine dose. The propensity score estimated the probability that a patient would have received vasopressin given baseline characteristics. For sensitivity analysis, we then excluded patients who had underlying severe congestive heart failure. The primary outcome was 28-day mortality.ResultsVasopressin- and norepinephrine-treated patients were similar after matching in SPH1 (pre-VASST); vasopressin-treated patients (n =?158) had a significantly higher mortality than norepinephrine-treated patients (n =?158) (60.8 vs. 46.2%, p =?0.009). In SPH2 after matching, the 28-day mortality rates were not significantly different; 31.2% and 26.9% in the vasopressin (n =?93) and norepinephrine (n =?93) groups, respectively (p =?0.518). The day 1 vasopressin dose in SPH1 vs. SPH2 was 0.036 units/min (SD 0.009) vs. 0.032 units/min (SD 0.005), p?=?0.001, significantly lower in SPH2 after VASST.ConclusionsBefore VASST, vasopressin use was associated with increased mortality compared to norepinephrine in the VASST coordinating center hospital. After VASST, there was no difference in mortality between vasopressin- and norepinephrine-treated patients. This may be the first retrospective propensity-matched cohort study of a sepsis treatment in a center that had previously coordinated a large pivotal randomized controlled trial of that treatment and could be a useful approach for other sepsis therapies.Trial registrationRegistration: ISRCTN94845869.

Dataset Information

Early Vitamin C and Thiamine Administration to Patients with Septic Shock in Emergency Departments: Propensity Score-Based Analysis of a Before-and-After Cohort Study.

Publications

Early Vitamin C and Thiamine Administration to Patients with Septic Shock in Emergency Departments: Propensity Score-Based Analysis of a Before-and-After Cohort Study.

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