scholarly journals Right Dose Right Now: bedside data-driven personalized antibiotic dosing in severe sepsis and septic shock — rationale and design of a multicenter randomized controlled superiority trial

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Luca F. Roggeveen ◽  
Lucas M. Fleuren ◽  
Tingjie Guo ◽  
Patrick Thoral ◽  
Harm Jan de Grooth ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Data Driven ◽  
Control Group ◽  
Target Attainment ◽  
Clinical Endpoints ◽  
Randomized Controlled ◽  
Superiority Trial ◽  
Sepsis And Septic Shock ◽  
Antibiotic Dosing

Abstract Background Antibiotic exposure is often inadequate in critically ill patients with severe sepsis or septic shock and this is associated with worse outcomes. Despite markedly altered and rapidly changing pharmacokinetics in these patients, guidelines and clinicians continue to rely on standard dosing schemes. To address this challenge, we developed AutoKinetics, a clinical decision support system for antibiotic dosing. By feeding large amounts of electronic health record patient data into pharmacokinetic models, patient-specific predicted future plasma concentrations are displayed graphically. In addition, a tailored dosing advice is provided at the bedside in real time. To evaluate the effect of AutoKinetics on pharmacometric and clinical endpoints, we are conducting the Right Dose Right Now multicenter, randomized controlled, two-arm, parallel-group, non-blinded, superiority trial. Methods All adult intensive care patients with a suspected or proven infection and having either lactatemia or receiving vasopressor support are eligible for inclusion. Randomization to the AutoKinetics or control group is initiated at the bedside when prescribing at least one of four commonly administered antibiotics: ceftriaxone, ciprofloxacin, meropenem and vancomycin. Dosing advice is available for patients in the AutoKinetics group, whereas patients in the control group receive standard dosing. The primary outcome of the study is pharmacometric target attainment during the first 24 h. Power analysis revealed the need for inclusion of 42 patients per group per antibiotic. Thus, a total of 336 patients will be included, 168 in each group. Secondary pharmacometric endpoints include time to target attainment and fraction of target attainment during an entire antibiotic course. Secondary clinical endpoints include mortality, clinical cure and days free from organ support. Several other exploratory and subgroup analyses are planned. Discussion This is the first randomized controlled trial to assess the effectiveness and safety of bedside data-driven automated antibiotic dosing advice. This is important as adequate antibiotic exposure may be crucial to treat severe sepsis and septic shock. In addition, the trial could prove to be a significant contribution to clinical pharmacometrics and serve as a stepping stone for the use of big data and artificial intelligence in the field. Trial registration Netherlands Trial Register (NTR), NL6501/NTR6689. Registered on 25 August 2017. European Clinical Trials Database (EudraCT), 2017-002478-37. Registered on 6 November 2017.

scholarly journals Is Presepsin a Reliable Marker of Sepsis Diagnosis in Pediatric Intensive Care Unit?

2020 ◽  
Vol 8 (B) ◽  
pp. 66-70
Author(s):  
Hebat-Allah Algebaly ◽  
Hala M. Fouad ◽  
Maha M. Elkholy ◽  
Sally K. Ibrahim ◽  
Nermin M. Riad
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Intensive Care ◽  
Consensus Conference ◽  
University Teaching ◽  
Control Group ◽  
Healthy Children ◽  
International Consensus ◽  
Critical Patients ◽  
Sepsis And Septic Shock

BACKGROUND: Sepsis is a major challenge in emergency departments and intensive care units (ICUs). Sepsis also mimics or interacts with many other disorders causing high mortality and morbidity. There is no accurate biomarker or test to diagnose or predict sepsis. The treatment of sepsis is often based on the clinician’s experience. AIM: We conducted this study to analyze the serum level of presepsin in pediatric critical patients with SIRS, sepsis, severe sepsis, and septic shock. METHODS: The study included 58 children, 32 septic pediatric patients admitted to the Pediatric ICU (PICU) of Cairo University Teaching Hospital and 26 healthy children who served as a control group. The aim was to estimate the diagnostic accuracy of presepsin in predicting sepsis in PICU. We classified the patients into systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock according to the international consensus conference criteria. RESULTS: In our study, we detected a positive correlation between C-reactive protein and presepsin levels at day 1 and day 3 of admission and a negative correlation between hemoglobin and presepsin levels at day 1. However, we found no difference in the serum presepsin between the children who had sepsis and the healthy ones (at day 1 [p = 0.430) and at day 3 [p = 0.845]). We also found that serum levels of presepsin were not significantly increased with the increasing severity of sepsis despite the higher median values with increasing sepsis severity. CONCLUSIONS: It was noted that presepsin levels increased in anemic critical patients, whereas presepsin had no role in differentiating the septic critical patients from healthy children. However, its level increased with increasing severity of sepsis grade.

Evaluation of red cell distribution width (RDW) as a septic marker in comparison with clinical scores and C-reactive protein

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Ali Ahmed Naga ◽  
Mohammed Ismaeil Abdel Fattah ◽  
Walid Hamed Nofal ◽  
Mohammed Abd-elsalam AlMenshawe
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Controlled Study ◽  
Control Group ◽  
Study Group ◽  
Distribution Width ◽  
Clinical Scores ◽  
Group I ◽  
Significant Difference ◽  
Sepsis And Septic Shock

Abstract Background Challenges of diagnosing and treating sepsis only seem more difficult as incidence increases, patients become older and sicker, and pathogenic organisms evolve. New understanding of inflammatory mediators and pathways, immunity, and genetic variability in this disease state suggests that the current definitions of SIRS, sepsis, severe sepsis, and septic shock are oversimplified. Objective The aim of our study is to evaluate the level of RDW, CRP and clinical scores "SOFA and APACHI" as markers in patients with sepsis and their levels on the outcome and resolution of sepsis in ICU. Methodology We conducted a prospective observational controlled study on 90 adult persons of both sex, 45 of them are adult patients and served as the study group (Group I), and the other 45 are healthy adult volunteers and served as the control group (Group II). The study group represented patients admitted to the ICU of Intensive Care Unit at Damanhour Medical National Institute who fulfilled the diagnostic criteria for sepsis, severe sepsis and septic shock on arrival to ICU according to the SCCM/ ESICM/ ACCP/ ATS/SIS International Sepsis Definitions Conference. Results. In the present study we found that CRP measured on admission was not a predictor of mortality, while that measured at day 5 and day 10 predicted mortality, where there was no statistically significant difference in CRP levels between survivors and non-survivors at the day of admission while there were statistically significant differences between survivors and non survivors according to CRP levels at day 5 (p = 0.001*) and at day 10 (p = 0.001*). It was found also that there were statistically significant differences between survivors and non-survivors according to RDW at day 1(p = 0.011*) and at day 5(p = 0.009*), at day 10 was found there was no statistically significant difference between survivors and non-survivors (p = 0.338). Conclusion RDW is a new promising cheap and readily available biomarker that can be able to diagnose patients with sepsis with accuracy comparable to CRP. Also, RDW at admission is able to predict mortality.

scholarly journals Effects of Safflower Yellow on the Treatment of Severe Sepsis and Septic Shock: A Randomized Controlled Clinical Trial

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-jin Li ◽  
Ru-rong Wang ◽  
Yan Kang ◽  
Jin Liu ◽  
Yun-xia Zuo ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Survival Curve ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Study Group ◽  
Kaplan Meier ◽  
New Strategy ◽  
Lactate Levels ◽  
Sepsis And Septic Shock

Objective.To evaluate the clinical effect of safflower yellow on the treatment of severe sepsis and septic shock.Methods.85 patients with severe sepsis and septic shock were randomly selected to receive either therapy according to the international guidelines for management of severe sepsis and septic shock (Surviving Sepsis Campaign 2012) (control group,n= 45) or conventional therapy plus safflower yellow (study group,n= 40). The 28-day mortality and 28-day Kaplan-Meier survival curves were compared as primary outcomes.Results.The 28-day mortality from all causes and in-hospital mortality were significantly lower in the study group (50%, 17.5%) as compared to the control group (78.58%, 54.76%) (P= 0.007, all causes,P< 0.001, in-hospital), and the 28-day Kaplan-Meier survival curve was higher in the study group than in the control group (P= 0.008, all causes,P< 0.001, in-hospital, Log Rank). 72 hours after treatment, secondary outcomes including heart rate, leukocyte counts, lactate levels, and platelet counts of patients in the study group were ameliorated significantly as compared with the control group.Conclusion.This study offers a potential new strategy employing safflower yellow to more effectively treat patients with severe sepsis and septic shock. This trial is registered with identifierChiCTR-TRC-14005196.

scholarly journals Echocardiography-Guided Hemodynamic Management of Severe Sepsis and Septic Shock in Adults: A Randomized Controlled Trial

2020 ◽  
Author(s):  
Walid S. Alhabashy ◽  
Osama M. Shalaby ◽  
Ahmed S. Elgebaly ◽  
Mohammed S. Abd El Ghafar
Keyword(s):  
Septic Shock ◽  
Randomized Controlled Trial ◽  
Severe Sepsis ◽  
Controlled Trial ◽  
Total Fluid Intake ◽  
Early Goal Directed Therapy ◽  
Randomized Controlled ◽  
Group I ◽  
Hospital Stays ◽  
Sepsis And Septic Shock

Abstract Background: Echocardiography (ECHO) is used to guide septic shock resuscitation, but without evidence for efficacy. Therefore, we compared the outcome of early goal-directed therapy (EGDT) and ECHO-guided management of hemodynamics in severe sepsis and septic shock. Materials and Methods: This is a single center, randomized controlled trial conducted on 100 adult patients with severe sepsis or septic shock. Patients were assessed and treated with either EGDT protocol (EGDT group) or ECHO-guided resuscitation protocol (ECHO group). Results: Only 87 patients (45 in group I and 42 in group II) were analyzed. There was a significant increase of mean norepinephrine and dobutamine doses and a significant decrease in total fluids in the first 24 hours, time to normalization, time to weaning of vasopressors, total MV days, MV free days and ICU and hospital stays in ECHO group. At 30 days, the mortality rate in EGDT group was 35.6% which was significantly higher compared to 14.3% in ECHO group. At 90 days, the overall mortality was significantly higher in EGDT group compared to Echo group (40.0% vs 16.7% respectively). Hazardous ratio of mortality was 1.630 (95% confidence interval (CI): 1.123 - 2.366) and 1.653 (95% CI: 1.137 - 2.404) at 30 and 90 days respectively in EGDT group compared to ECHO group. Conclusions: In severe sepsis and septic shock, ECHO-guided management of hemodynamics resulted in a decrease in mortality, lower total fluid intake, higher vasopressor and inotrope support, earlier weaning of vasopressors and less MV days, ICU and hospital stay.

1453: INFUSION OF METHYLENE BLUE IN SEVERE SEPSIS AND SEPTIC SHOCK: A RANDOMIZED CONTROLLED TRIAL

2016 ◽  
Vol 44 (12) ◽  
pp. 439-439
Author(s):  
Hoyoung Yune ◽  
Kyuseok Kim ◽  
You Hwan Jo ◽  
Joonghee Kim ◽  
Jae Hyuk Lee ◽  
...  
Keyword(s):  
Septic Shock ◽  
Methylene Blue ◽  
Randomized Controlled Trial ◽  
Severe Sepsis ◽  
Controlled Trial ◽  
Randomized Controlled ◽  
Sepsis And Septic Shock

scholarly journals Prognostic importance of tissue Doppler imaging of systolic and diastolic functions in dogs with severe sepsis and septic shock

2019 ◽  
Vol 67 (4) ◽  
pp. 517-528
Author(s):  
Mehmet Ege Ince ◽  
Kursad Turgut ◽  
Aybars Akar ◽  
Amir Naseri ◽  
Ismail Sen ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Diastolic Dysfunction ◽  
Sensitivity And Specificity ◽  
Mitral Annulus ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Doppler Imaging ◽  
Control Group ◽  
Sepsis And Septic Shock

The goal of this study was to determine the distribution of left ventricular (LV) systolic and diastolic dysfunctions and their prognostic value in canine parvovirus-infected dogs suffering from severe sepsis and septic shock (SS/SS). Twenty dogs with SS/SS (experimental group) and 18 healthy dogs (control group) were used in the study. Systolic and diastolic dysfunction was present in three (15%) and 14 (70%) diseased dogs, respectively, with both types of dysfunction present in two (10%) of the patients. These dogs were split into two groups: survivors (Sv, n = 14) and non-survivors (non-Sv, n = 6). The pulsed wave tissue Doppler (PW-TDI) septal mitral annulus systolic velocity (LVS'), an index of systolic dysfunction, had a high sensitivity and specificity to differentiate Sv and non-Sv animals, with values of 83.3% (95% CI: 41.6–98.4) and 83.3% (95% CI: 59.8–94.8), respectively, at an optimum cut-off point of ≥ 9.90. The PW-TDI septal early mitral annulus early-diastolic peak velocity (E'), an index of diastolic dysfunction, had the best sensitivity and specificity to differentiate Sv and non-Sv dogs, with values of 100% (95% CI: 55.2–100) and 100% (95% CI: 78.9–100), respectively, at an optimum cut-off point of ≤ 6.50. Therefore, diastolic dysfunction determined by E' is a good independent outcome predictor.

scholarly journals Clinical Outcomes of Severe Sepsis and Septic Shock Patients with Left Ventricular Dysfunction Undergoing Continuous Renal Replacement Therapy: A Multicenter Retrospective Study

2020 ◽  
Author(s):  
Guangwei Yu ◽  
Kun Cheng ◽  
Qing Liu ◽  
Zhenhao Zhu ◽  
Fenghui Lin ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Retrospective Study ◽  
Renal Replacement Therapy ◽  
Left Ventricular ◽  
Control Group ◽  
Early Group ◽  
Icu Mortality ◽  
Lv Dysfunction ◽  
Sepsis And Septic Shock

Abstract Background: Baseline left ventricular (LV) dysfunction is associated with subsequent risks of acute kidney injury (AKI) and mortality in patients with sepsis. This study investigated the therapeutic effects of continuous renal replacement therapy (CRRT) in hemodynamically unstable patients with severe sepsis and septic shock combined with LV dysfunction.Methods: In this multicenter retrospective study, severe sepsis and septic shock patients with LV dysfunction were classified into one of two groups according to the timing of CRRT: the early group (before AKI was detected) or the control group (patients with AKI). All-cause intensive care unit (ICU) mortality and ICU stay were compared between the groups. Patients were weighted by stabilized inverse probability of treatment weights (sIPTW) to overcome differences in baseline characteristics.Results: After sIPTW analysis, the ICU mortality was significantly lower in the early group than the control group (25.9% vs 59.0%, p < 0.001). Weighted multivariable analysis showed that early CRRT initiation was a protective factor for the risk of ICU mortality. Early CRRT initiation significantly improved the ICU mortality compared to the control group (OR, 0.322; 95% CI, 0.125-0.834; p = 0.020).Conclusions: Early CRRT in the absence of AKI is suggested for hemodynamically unstable patients with severe sepsis and septic shock combined with LV dysfunction since it benefits survival outcomes.Trial registration: The study was preregistered in the Chinese Clinical Trial Registry (number, ChiCTR2000033083).

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