The Australasian Resuscitation In Sepsis Evaluation : fluids or vasopressors in emergency department sepsis (ARISE FLUIDS), a multi-centre observational study describing current practice in Australia and New Zealand

Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30-day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6- and 24-h post-enrolment, time to antimicrobial administration, intensive care admission, organ support and in-hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre-enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in-hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy

Prenatal alcohol exposure and traumatic childhood experiences : a systematic review

Prenatal alcohol exposure (PAE) and traumatic childhood experiences (trauma) such as abuse or neglect can each cause central nervous system neurobiological changes or structural damage which can manifest as cognitive and behavioural dysfunction. In cases where both exposures have occurred, the risk of neurodevelopmental impairment may be greater, but this interaction has not been well studied. Here we present a systematic review that identified five primary research studies which investigated either the impact of trauma in children with PAE, or of PAE in children with trauma. Due to the heterogeneity of studies, narrative analysis was applied. Children in these cohorts with both exposures were more likely to show deficits in language, attention, memory and intelligence, and exhibit more severe behavioural problems than children with one exposure in absence of the other. However, the current literature is scarce and methodologically flawed. Further studies are required that: assess dual exposure in other neurodevelopmental domains; feature developmentally impaired yet non-exposed controls; and account for the wide spectrum of effects and different diagnostic criteria associated with PAE

Use of a Computerized C-Reactive Protein (CRP) Based Sepsis Evaluation in Very Low Birth Weight (VLBW) Infants: A Five-Year Experience

<div><p>Background</p><p>Serial C-reactive protein (CRP) values may be useful for decision-making regarding duration of antibiotics in neonates. However, established standard of practice for its use in preterm very low birth weight (<1500 g, VLBW) infants are lacking.</p><p>Objective</p><p>Evaluate compliance with a CRP-guided computerized decision support (CDS) algorithm and compare characteristics and outcomes of compliant versus non-compliant cases. Measure correlation between CRPs and white blood count (WBC) indices.</p><p>Methods</p><p>We examined 3 populations: 1) all preterm VLBW infants born at Vanderbilt 2006–2011 – we assessed provider compliance with CDS algorithm and measured relevant outcomes; 2) all patients with positive blood culture results admitted to the Vanderbilt NICU 2006–2012 – we tested the correlation between CRP and WBC results within 7 days of blood culture phlebotomy; 3) 1,000 randomly selected patients out of the 7,062 patients admitted to the NICU 2006–2012 – we correlated time-associated CRP values and absolute neutrophil counts.</p><p>Results</p><p>Of 636 VLBW infants in cohort 1), 569 (89%) received empiric antibiotics for suspected early-onset sepsis. In 409 infants (72%) the CDS algorithm was followed; antibiotics were discontinued ≤48 hours in 311 (55%) with normal serial CRPs and continued in 98 (17%) with positive CRPs, resulting in significant reduction in antibiotic exposure (p<0.001) without increase in complications or subsequent infections. One hundred sixty (28%) were considered non-compliant because antibiotics were continued beyond 48 hours despite negative serial CRPs and blood cultures. Serial CRPs remained negative in 38 (12%) of 308 blood culture-positive infants from cohort 2, but only 4 patients had clinically probable sepsis with single organisms and no immunodeficiency besides extreme prematurity. Leukopenia of any cell type was not linked with CRPs in cohorts 2 and 3.</p><p>Conclusions</p><p>CDS/CRP-guided antibiotic use is safe and effective in culture-negative VLBW infants. CRP results are not affected by low WBC indices.</p></div

Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Preterm Infants With Late-Onset Infection

Importance: Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown. Objective: To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm (72 hours of life) infection including bacteremia, fungemia, or surgical peritonitis. Main Outcomes and Measures: The primary outcome was late-onset infection episode mortality. The nSOFA scores from survivors and nonsurvivors with confirmed late-onset infection were compared at 9 time points (T) preceding and following event onset. Results: In the 653 infants who met inclusion criteria, median gestational age was 25.5 weeks (interquartile range, 24-27 weeks) and median birth weight was 780 g (interquartile range, 638-960 g). A total of 366 infants (56%) were male. Late-onset infection episode mortality occurred in 97 infants (15%). Area under the receiver operating characteristic curves for mortality in the total cohort ranged across study centers from 0.71 to 0.95 (T0 hours), 0.77 to 0.96 (T6 hours), and 0.78 to 0.96 (T12 hours), with utility noted at all centers and in aggregate. Using the maximum nSOFA score at T0 or T6, the area under the receiver operating characteristic curve for mortality was 0.88 (95% CI, 0.84-0.91). Analyses stratified by sex or Gram-stain identification of pathogen class or restricted to infants born at less than 25 weeks' completed gestation did not reduce the association of the nSOFA score with infection-related mortality. Conclusions and Relevance: The nSOFA score was associated with late-onset infection mortality in preterm infants at the time of evaluation both in aggregate and in each center. These findings suggest that the nSOFA may serve as the foundation for a consensus definition of sepsis in this population

Patient demographics by CRP-protocol compliance status.¹

1<p>Compliance with the CRP-protocol in the setting of negative blood cultures was defined as (1) antibiotics were discontinued ≤48 hours after 2 consecutive negative CRP results, or continued if at least one positive CRP was present [“CRP-protocol compliant” (Comp)], and (2) antibiotics were continued >48 hours despite negative serial CRP results [“CRP-protocol non-compliant” (Non-Comp)].</p>2<p>Pair-wise comparison between Comp and Non-Comp group.</p>3<p>Median (lower quartile; upper quartile).</p>4<p>Wilcoxon test.</p>5<p>Pearson test.</p>6<p>C =  Caucasian, AA  =  African American, H =  Hispanic, O =  Other, U =  Unknown.</p>7<p>Absolute neutrophil count at time of initial sepsis evaluation.</p>8<p><2,500/µL.</p>9<p>Absolute neutrophil count at 48 hours.</p

Number of cases (N) with confirmed positive blood cultures and low WBC indices with positive (>10 mg/L) CRP values versus negative (<10 mg/L) serial CRP results.¹

1<p> =  Only cases with a full set of reported WBC and differential were analyzed.</p>2<p> =  CONS  =  coagulase-negative <i>Staphylococcus</i>.</p>3<p> =  Total serial CRP pos. N = 43; total serial CRP neg. N = 17.</p>4<p> =  Total serial CRP pos. N = 54; total serial CRP neg. N = 16.</p

Organisms isolated from positive blood cultures in patients with confirmed infections (N = 38) and CRP persistently <10 mg/L.

<p>Organisms isolated from positive blood cultures in patients with confirmed infections (N = 38) and CRP persistently <10 mg/L.</p

Outcomes (%) by CRP-protocol compliance status.¹

1<p>Compliance with the CRP-protocol in the setting of negative blood cultures was defined as (1) antibiotics were discontinued ≤48 hours after 2 consecutive negative CRP results or continued after at least one positive CRP value [“CRP-protocol compliant” (Comp)], and (2) antibiotics were continued >48 hours despite negative serial CRP results [“CRP-protocol non-compliant” (Non-Comp)].</p>2<p>Pearson test.</p>3<p>Defined as supplemental oxygen requirement ≥36 weeks postconceptional age.</p>4<p>CONS  =  Coagulase-negative <i>Staphylococcus</i>.</p

Screenshot decision support to stop antibiotics.

<p>The CRP protocol's recommendation on antibiotic use was based on repeat CRP and WBC results drawn 48 hours following initial evaluation. In cases with two consecutively negative CRP results (CRP <10 mg/L), this discontinuation screen appeared, allowing the provider to choose to stop antibiotics. If the provider chose to continue antibiotics despite negative CRP results, they were prompted to provide reasoning for doing so. No complete white blood count (CBC) data is depicted in this screenshot, because a “test” patient had to be generated to produce this figure.</p