scholarly journals 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

2019 ◽  
Vol 8 (1) ◽  
pp. 102 ◽  
Author(s):  
Tae Gun Shin ◽  
Youn-Jung Kim ◽  
Seung Mok Ryoo ◽  
Sung Yeon Hwang ◽  
Ik Joon Jo ◽  
...  

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.

2020 ◽  
Vol 9 (1) ◽  
pp. 193 ◽  
Author(s):  
Jong Eun Park ◽  
Tae Gun Shin ◽  
Ik Joon Jo ◽  
Kyeongman Jeon ◽  
Gee Young Suh ◽  
...  

Sepsis is a common cause of delirium in the intensive care unit (ICU). Recently, vitamin C and thiamine administration has been gaining interest as a potential adjunct therapy for sepsis. We investigated the impact of early vitamin C and thiamine administration on ICU delirium-free days among critically ill patients in septic shock. We performed a single-center, retrospective study of patients who visited the emergency department (ED) from January 2017 to July 2018. We categorized patients into a treatment (received vitamin C and thiamine) and control group. We compared delirium-free days within 14 days after ICU admission using propensity score matching. Of 435 patients with septic shock, we assigned 89 propensity score-matched pairs to the treatment and control groups. The median delirium-free days did not differ between treatment (11, interquartile range [IQR] 5–14 days) and control (12, IQR 6–14 days) groups (p = 0.894). Secondary outcomes were not different between the two groups, including delirium incidence and 28-day mortality. These findings were consistent after subgroup analysis for patients who met the sepsis-3 definition of septic shock. Vitamin C and thiamine administration showed no association with ICU delirium-free days among patients in septic shock.


Author(s):  
Jennifer A. frontera ◽  
Joseph O. Rahimian ◽  
Shadi Yaghi ◽  
Mengling Liu ◽  
Ariane Lewis ◽  
...  

Abstract Background: Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates.Methods: A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore. A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status.Results: Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60-0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity score-matched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44-0.91, P=0.015). There were no significant interactions for Zn+ionophore with other COVID-19 specific medications.Conclusions: Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sander Rozemeijer ◽  
Harm-Jan de Grooth ◽  
Paul W. G. Elbers ◽  
Armand R. J. Girbes ◽  
Corstiaan A. den Uil ◽  
...  

Abstract Background High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. Methods This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. Discussion Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. Trial registration ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL


Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Mikio Nakajima ◽  
Morita Kojiro ◽  
Shotaro Aso ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
...  

Abstract Background Vitamin C is a well-documented antioxidant that reduces oxidative stress and fluid infusion in high doses; however, the association between high-dose vitamin C and reduced mortality remains unclear. This study evaluates the effect of high-dose vitamin C in severe burn patients under two varying thresholds. Methods We enrolled adult patients with severe burns (burn index ≥ 15) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2016. Propensity score matching was performed between patients who received high-dose vitamin C within 1 day of admission (vitamin C group) and those who did not (control group). High-dose vitamin C was defined as a dosage in excess of 10 g or 24 g within 2 days of admission. The primary outcome was in-hospital mortality. Results Eligible patients (n = 2713) were categorized into the vitamin C group (n = 157) or control group (n = 2556). After 1:4 propensity score matching, we compared 157 and 628 patients who were administered high-dose vitamin C (> 10-g threshold) and controls, respectively. Under this particular threshold, high-dose vitamin C therapy was associated with reduced in-hospital mortality (risk ratio, 0.79; 95% confidence interval, 0.66–0.95; p = 0.006). In contrast, in-hospital mortality did not differ between the control and high-dose vitamin C group under the > 24-g threshold (risk ratio, 0.83; 95% confidence interval, 0.68–1.02; p = 0.068). Conclusions High-dose vitamin C therapy was associated with reduced mortality in patients with severe burns when used under a minimum threshold of 10 g within the first 2 days of admission. While “high-dose” vitamin C therapy lacks a universal definition, the present study reveals that different “high-dose” regimens may yield improved outcomes.


2019 ◽  
Vol 53 (9) ◽  
pp. 877-885 ◽  
Author(s):  
Bryan E. Menich ◽  
Todd A. Miano ◽  
Gourang P. Patel ◽  
Drayton A. Hammond

Background: The optimal adjuvant vasopressor to norepinephrine in septic shock remains controversial. Objective: To compare durations of shock-free survival between adjuvant vasopressin and epinephrine. Methods: A retrospective, single-center, matched cohort study of adults with septic shock refractory to norepinephrine was conducted. Patients receiving norepinephrine not at target mean arterial pressure (MAP; 65 mm Hg) were initiated on vasopressin or epinephrine to raise MAP to target. Vasopressin-exposed patients were matched to epinephrine-exposed patients using propensity scores. Mortality outcomes were examined using multivariable Poisson regression with robust variance estimation. Results: Of 166 patients, 96 (entire cohort) were included in the propensity score–matched cohort. Shock-free survival durations in the first 7 days were similar between epinephrine- and vasopressin-exposed patients in the matched cohort (median = 13.2 hours, interquartile range [IQR] = 0-121.0, vs median = 41.3 hours, IQR = 0-125.9; P = 0.51). Seven- and 28-day mortality rates were similar in the matched cohort (7-day: 47.9% vs 39.6%, P = 0.35; 28-day: 56.3% vs 58.3%, P = 0.84). Mortality rates were similar between epinephrine- and vasopressin-exposed patients in propensity score–matched regression models with and without adjustments at 7 (relative risk [RR] = 1.28, 95% CI = 0.92-1.79; RR = 1.21, 95% CI = 0.81-1.81) and 28 days (RR = 1.04, 95% CI = 0.81-1.34; RR = 0.96, 95% CI = 0.69-1.34). Conclusion and Relevance: Shock-free survival durations were similar in matched epinephrine- and vasopressin-exposed groups. Adjuvant epinephrine or vasopressin alongside norepinephrine to raise MAP to target requires further investigation.


2017 ◽  
Vol 53 (4) ◽  
pp. 2324-2345 ◽  
Author(s):  
Mauro Laudicella ◽  
Stephen Martin ◽  
Paolo Li Donni ◽  
Peter C. Smith

2020 ◽  
Author(s):  
Ting Yang ◽  
Yongchun Shen ◽  
John G. Park ◽  
Phillip J Schulte ◽  
Andrew C Hanson ◽  
...  

Abstract BackgroundAcute respiratory failure associated with sepsis contributes to higher in-hospital mortality. Intubation and invasive mechanical ventilation is a common rescue procedure. However, the 2016 International Guidelines for Management of Sepsis and Septic Shock does not provide any recommendation on indication nor timing of intubation. Timely intubation may improve outcome. The decision to intubate those patients is often hampered by the fear of further hemodynamic deterioration following intubation. MethodsThis study aimed at evaluating the impact of timely intubation on outcome in sepsis associated respiratory failure. We conducted an ancillary analysis of a prospective registry od adult ICU patients with septic shock admitted to the medical ICU in a tertiary medical center, between April 30th, 2014 and December 31st, 2017. All cases of sepsis with lactate >4 mmol/L, mean arterial pressure <65 mmHg, or vasopressor use after 30 mL/kg fluid boluses and suspected or confirmed infection. Patients who remained hospitalized at 24 hours following sepsis onset were separated into intubated and non-intubated groups. The primary outcome was hospital mortality. Univariate and multivariable analyses were used, adjusted for admission characteristics and stabilization of shock within 6 hours. In a secondary analysis, time-dependent propensity score matching was used to match intubated and non-intubated patients.ResultsWe identified 345 (33%) patients intubated within 24 hours and 707 (67%) not intubated. Intubated patients were younger, transferred more often from an outside facility, had higher severity of illness scores, more lung infection, achieved blood pressure goals more often but less often lactate normalization within 6 hours. The crude in-hospital mortality was higher, 89 (26%) vs. 82 (12%), p<0.001, as were ICU mortality, and ICU and hospital length of stay. After adjustment, intubation showed no effect on hospital mortality but fewer hospital-free days through day 28. After 1:1 propensity score matching, there was no difference in hospital mortality, but fewer hospital-free days in the intubated group. ConclusionsIntubation within 24 hours of sepsis onset was safe and not associated with hospital mortality, but was associated with less 28-day hospital-free days. Intubation should not be discouraged in appropriate patients with septic shock.


2020 ◽  
Author(s):  
Jongmin Lee ◽  
Seo Hyun Kim ◽  
Kyung Hoon Kim ◽  
Na Ri Jeong ◽  
Seok Chan Kim ◽  
...  

Abstract Background: Presepsin is a subtype of soluble CD14 that is increased in the blood of septic patients. We investigated the role of dynamic changes in serum presepsin levels in critically ill, immunocompromised patients with sepsis.Methods: This is a prospective cohort study that included 119 adult patients who were admitted to the intensive care unit (ICU) between March 2019 and June 2020. Sepsis and septic shock were defined as Sepsis-3. Patients were classified into one of the following diagnostic groups: no sepsis, sepsis, and septic shock. Presepsin level was measured on day 1 and day 3 after ICU admission. The primary outcome was in-hospital mortality.Results: Of the 119 patients, sepsis was diagnosed in 40 patients (33.6%) and septic shock was diagnosed in 60 (50.4%) patients. The Simplified Acute Physiology Score (SAPS) 3 and Sequential Organ Failure Assessment score on day 1 were 75.5 ± 14.9 and 9.0 (6.5–11.5), respectively, and the overall hospital mortality was 44.5%. In 61 immunocompromised patients, presepsin levels on day 1 were higher in patients with sepsis than those in patients without sepsis (1203.0 [773.0–2484.0] vs. 753.0 [603.5–1092.0] ng/ml; P = 0.004). The area under the curve (AUC) of presepsin for diagnosing sepsis in immunocompromised patients was 0.87, which was comparable with that of procalcitonin (AUC, 0.892). Presepsin levels on day 3 were higher in patients who died in the hospital than in those who survived (1965.0 [1149.0–3423.0] vs. 933.0 [638.0–1571.0]; P = 0.001). In immunocompromised patients who died in the hospital, presepsin levels on day 3 were significantly higher than those on day 1 (P = 0.018). In the multivariate analysis, ΔPresepsin+ (ΔPresepsin concentrations [day3 – day1] > 0) alone was independently correlated with in-hospital mortality in immunocompromised patients (odds ratio, 6.22; 95% confidence interval, 1.33–29.06; P = 0.020).Conclusion: These findings suggest that dynamic changes in presepsin levels between day 1 and day 3 are associated with in-hospital mortality in patients with sepsis, especially in immunocompromised patients.


2021 ◽  
Author(s):  
Yi Bian ◽  
Yue Le ◽  
Ping Zhang ◽  
Zhigang He ◽  
Ye Wang ◽  
...  

Abstract Background: Accumulating evidence has revealed that coagulopathy and widespread thrombosis in the lung are common in patients with Coronavirus Disease 2019 (COVID-19). This raises questions about the efficacy and safety of systemic anticoagulation (AC) in COVID-19 patients. Method: This single-center, retrospective, cohort study unselectively reviewed 2272 patients with COVID-19 admitted to the Tongji Hospital between Jan 25 and Mar 23, 2020. Propensity score-matching between patients adjusted for potential covariates was carried out with the patients divided into two groups depending on whether or not they had received AC treatment (AC group, ³7 days of treatment; non-AC group, no treatment). This yielded 164 patients in each group. Result: In-hospital mortality of the AC group was significantly lower than that of the non-AC group (14.0% vs. 28.7%, P =0.001). Treatment with AC was associated with a significantly lower probability of in-hospital death (adjusted HR=0.273, 95% CI, 0.154 to 0.484, P<0.001). The incidence of major bleeding and thrombocytopenia in the two groups was not significantly different. Subgroup analysis showed the following factors were associated with a significantly lower in-hospital mortality in patients who had received AC treatment; severe cases (13.2% vs. 24.6%, P=0.018), critical cases (20.0% vs 82.4%, P=0.003), patients with a D-dimer level ≥0.5 μg/mL (14.8% vs. 33.8, P<0.001), and moderate (16.7% vs. 60.0%, P=0.003) or severe acute respiratory distress syndrome (ARDS) cases at admission (33.3% vs. 86.7%, P=0.004). During the hospital stay, critical cases (38.3% vs. 76.7%, P<0.001) and severe ARDS cases (36.5% vs. 76.3%, P<0.001) who received AC treatment had significantly lower in-hospital mortality. Conclusions: AC treatment decreases the risk of in-hospital mortality, especially in critically ill patients, with no additional significant, major bleeding events or thrombocytopenia being observed.Trials registration - ChiCTR2000039855


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