Thiamine administration in septic shock: a post hoc analysis of two randomized trials.

BACKGROUND: This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock. METHODS: Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L). RESULTS: Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08-3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01-6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79-37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54-30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019). CONCLUSION: In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.

Characteristics and Outcomes of Culture-Positive and Culture-Negative Pediatric Sepsis.

OBJECTIVES: To compare the outcomes of pediatric severe sepsis and septic shock among patients with culture-positive and culture-negative sepsis and to determine if there are differentiating markers of disease severity between these 2 populations during their initial presentation and emergency department (ED) stay. STUDY DESIGN: Retrospective cohort study of patients ≤21 years of age who presented to the ED of a single children's hospital with severe sepsis or septic shock from June 1, 2017 to June 5, 2019. RESULTS: There were 235 patients who met criteria for severe sepsis or septic shock. Of these, 139 (59.1%) had culture-negative sepsis and 96 (40.9%) had culture-positive sepsis. In the adjusted multivariable model, children with culture-negative sepsis had more intensive care unit (ICU)-free days than those with culture-positive sepsis (27.3 vs 24.1; adjusted median differences [aMD] -2.6 [-4.4, -0.8]). There were no differences in mortality or hospital-free days. On initial presentation, there were no differences in fever, hypothermia, tachycardia, tachypnea, or hypotension between the 2 groups. There were no differences in proportion of patients receiving the following interventions: intravenous (IV) antibiotics, IV fluids, vasoactive medications, CPR, intubation, or time from arrival to provision of these interventions. CONCLUSIONS: Culture-negative sepsis constitutes a substantial proportion of pediatric severe sepsis and septic shock. In this study, patients with culture-negative and culture-positive sepsis presented similarly on arrival to the ED and received similar treatments while there. Patients with culture-negative sepsis had more ICU-free days than those with culture-positive sepsis, although differences in hospital length of stay (LOS) and mortality were not observed.

The Modified Clinical Progression Scale for Pediatric Patients: Evaluation as a Severity Metric and Outcome Measure in Severe Acute Viral Respiratory Illness.

OBJECTIVES: To develop, evaluate, and explore the use of a pediatric ordinal score as a potential clinical trial outcome metric in children hospitalized with acute hypoxic respiratory failure caused by viral respiratory infections. DESIGN: We modified the World Health Organization Clinical Progression Scale for pediatric patients (CPS-Ped) and assigned CPS-Ped at admission, days 2-4, 7, and 14. We identified predictors of clinical improvement (day 14 CPS-Ped ≤ 2 or a three-point decrease) using competing risks regression and compared clinical improvement to hospital length of stay (LOS) and ventilator-free days. We estimated sample sizes (80% power) to detect a 15% clinical improvement. SETTING: North American pediatric hospitals. PATIENTS: Three cohorts of pediatric patients with acute hypoxic respiratory failure receiving intensive care: two influenza (pediatric intensive care influenza [PICFLU], n = 263, 31 sites; PICFLU vaccine effectiveness [PICFLU-VE], n = 143, 17 sites) and one COVID-19 ( n = 237, 47 sites). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Invasive mechanical ventilation rates were 71.4%, 32.9%, and 37.1% for PICFLU, PICFLU-VE, and COVID-19 with less than 5% mortality for all three cohorts. Maximum CPS-Ped (0 = home at respiratory baseline to 8 = death) was positively associated with hospital LOS ( p < 0.001, all cohorts). Across the three cohorts, many patients' CPS-Ped worsened after admission (39%, 18%, and 49%), with some patients progressing to invasive mechanical ventilation or death (19%, 11%, and 17%). Despite this, greater than 76% of patients across cohorts clinically improved by day 14. Estimated sample sizes per group using CPS-Ped to detect a percentage increase in clinical improvement were feasible (influenza 15%, n = 142; 10%, n = 225; COVID-19, 15% n = 208) compared with mortality ( n > 21,000, all), and ventilator-free days (influenza 15%, n = 167). CONCLUSIONS: The CPS-Ped can be used to describe the time course of illness and threshold for clinical improvement in hospitalized children and adolescents with acute respiratory failure from viral infections. This outcome measure could feasibly be used in clinical trials to evaluate in-hospital recovery.