<p><strong>OBJECTIVES: </strong>Avascular necrosis (AVN) is a rare, but serious, complication after sepsis in adults. We sought to determine if sepsis is associated with postillness diagnosis of AVN, as well as potential-associated risk factors for AVN in children with sepsis.</p>

<p><strong>DESIGN: </strong>Retrospective observational study.</p>

<p><strong>SETTING: </strong>Single academic children's hospital.</p>

<p><strong>PATIENTS: </strong>Patients less than 18 years treated for sepsis or suspected bacterial infection from 2011 to 2017. Patients who developed AVN within 3 years after sepsis were compared with patients who developed AVN after suspected bacterial infection and with patients with sepsis who did not develop AVN.</p>

<p><strong>INTERVENTION: </strong>None.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>AVN was determined using International Classification of Diseases, 9th Edition/10th Edition codes and confirmed by chart review. The prevalence of AVN after sepsis was 0.73% (21/2,883) and after suspected bacterial infection was 0.43% (53/12,276; risk difference, 0.30; 95% CI, 0.0-0.63; p = 0.05). Compared with 43 sepsis controls without AVN, AVN in the 21 sepsis cases was associated with being older, having sickle cell disease and malignancy, higher body mass index, unknown source of infection, and low platelet count in the first 7 days of sepsis. Half of sepsis patients were treated with corticosteroids, and higher median cumulative dose of steroids was associated with AVN (23.2 vs 5.4 mg/kg; p &lt; 0.01). Older age at infection (odds ratio [OR], 1.3; 95% CI, 1.1-1.4), malignancy (OR, 8.8; 95% CI, 2.6-32.9), unknown site of infection (OR, 12.7; 95% CI, 3.3-48.6), and minimal platelet count less than 100,000/µL in first 7 days of sepsis (OR, 5.0; 95% CI, 1.6-15.4) were identified as potential risk factors for AVN after sepsis following adjustment for multiple comparisons.</p>

<p><strong>CONCLUSIONS: </strong>Although rare, sepsis was associated with a higher risk of subsequent AVN than suspected bacterial infection in children. Older age, malignancy, unknown site of infection, and minimum platelet count were potential risk factors for AVN after sepsis.</p>

<p><strong>OBJECTIVE: </strong>To determine how hypotension in the first 48 h of sepsis management impacts acute kidney injury (AKI) development and persistence.</p>

<p><strong>STUDY DESIGN: </strong>Retrospective study of patients &gt; 1 month to &lt; 20 years old with sepsis in a pediatric ICU between November 2012 and January 2015 (n = 217). All systolic blood pressure (SBP) data documented within 48 h after sepsis recognition were collected and converted to percentiles for age, sex, and height. Time below SBP percentiles and below pediatric advanced life support (PALS) targets was calculated by summing elapsed time under SBP thresholds during the first 48 h. The primary outcome was new or persistent AKI, defined as stage 2 or 3 AKI present between sepsis day 3-7 using Kidney Disease: Improving Global Outcomes creatinine definitions. Secondary outcomes included AKI-free days (days alive and free of AKI) and time to kidney recovery.</p>

<p><strong>RESULTS: </strong>Fifty of 217 sepsis patients (23%) had new or persistent AKI. Patients with AKI spent a median of 35 min under the first SBP percentile, versus 4 min in those without AKI. After adjustment for potential confounders, the odds of AKI increased by 9% with each doubling of minutes spent under this threshold (p = 0.03). Time under the first SBP percentile was also associated with fewer AKI-free days (p = 0.02). Time spent under PALS targets was not associated with AKI.</p>

<p><strong>CONCLUSIONS: </strong>The duration of severe systolic hypotension in the first 48 h of pediatric sepsis management is associated with AKI incidence and duration when defined by age, sex, and height norms, but not by PALS definitions. Graphical abstract.</p>

<p><strong>OBJECTIVES: </strong>A method to identify pediatric sepsis episodes that is not affected by changing diagnosis and claims-based coding practices does not exist. We derived and validated a surveillance algorithm to identify pediatric sepsis using routine clinical data and applied the algorithm to study longitudinal trends in sepsis epidemiology.</p>

<p><strong>DESIGN: </strong>Retrospective observational study.</p>

<p><strong>SETTING: </strong>Single academic children's hospital.</p>

<p><strong>PATIENTS: </strong>All emergency and hospital encounters from January 2011 to January 2019, excluding neonatal ICU and cardiac center.</p>

<p><strong>EXPOSURE: </strong>Sepsis episodes identified by a surveillance algorithm using clinical data to identify infection and concurrent organ dysfunction.</p>

<p><strong>INTERVENTIONS: </strong>None.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>A surveillance algorithm was derived and validated in separate cohorts with suspected sepsis after clinician-adjudication of final sepsis diagnosis. We then applied the surveillance algorithm to determine longitudinal trends in incidence and mortality of pediatric sepsis over 8 years. Among 93,987 hospital encounters and 1,065 episodes of suspected sepsis in the derivation period, the surveillance algorithm yielded sensitivity 78% (95% CI, 72-84%), specificity 76% (95% CI, 74-79%), positive predictive value 41% (95% CI, 36-46%), and negative predictive value 94% (95% CI, 92-96%). In the validation period, the surveillance algorithm yielded sensitivity 84% (95% CI, 77-92%), specificity of 65% (95% CI, 59-70%), positive predictive value 43% (95% CI, 35-50%), and negative predictive value 93% (95% CI, 90-97%). Notably, most "false-positives" were deemed clinically relevant sepsis cases after manual review. The hospital-wide incidence of sepsis was 0.69% (95% CI, 0.67-0.71%), and the inpatient incidence was 2.8% (95% CI, 2.7-2.9%). Risk-adjusted sepsis incidence, without bias from changing diagnosis or coding practices, increased over time (adjusted incidence rate ratio per year 1.07; 95% CI, 1.06-1.08; p &lt; 0.001). Mortality was 6.7% and did not change over time (adjusted odds ratio per year 0.98; 95% CI, 0.93-1.03; p = 0.38).</p>

<p><strong>CONCLUSIONS: </strong>An algorithm using routine clinical data provided an objective, efficient, and reliable method for pediatric sepsis surveillance. An increased sepsis incidence and stable mortality, free from influence of changes in diagnosis or billing practices, were evident.</p>

<p><strong>OBJECTIVE: </strong>Delayed antimicrobial therapy in sepsis is associated with increased hospital mortality, but the impact of antimicrobial timing on long-term outcomes is unknown. We tested the hypothesis that hourly delays to antimicrobial therapy are associated with 1-year mortality in pediatric severe sepsis.</p>

<p><strong>DESIGN: </strong>Retrospective observational study.</p>

<p><strong>SETTING: </strong>Quaternary academic pediatric intensive care unit (PICU) from February 1, 2012 to June 30, 2013.</p>

<p><strong>PATIENTS: </strong>One hundred sixty patients aged ≤21 years treated for severe sepsis.</p>

<p><strong>INTERVENTIONS: </strong>None.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>We tested the association of hourly delays from sepsis recognition to antimicrobial administration with 1-year mortality using multivariable Cox and logistic regression. Overall 1-year mortality was 24% (39 patients), of whom 46% died after index PICU discharge. Median time from sepsis recognition to antimicrobial therapy was 137 min (IQR 65-287). After adjusting for severity of illness and comorbid conditions, hourly delays up to 3 h were not associated with 1-year mortality. However, increased 1-year mortality was evident in patients who received antimicrobials ≤1 h (aOR 3.8, 95% CI 1.2, 11.7) or &gt;3 h (aOR 3.5, 95% CI 1.3, 9.8) compared with patients who received antimicrobials within 1 to 3 h from sepsis recognition. For the subset of patients who survived index PICU admission, antimicrobial therapy ≤1 h was also associated with increased 1-year mortality (aOR 5.5, 95% CI 1.1, 27.4), while antimicrobial therapy &gt;3 h was not associated with 1-year mortality (aOR 2.2, 95% CI 0.5, 11.0).</p>

<p><strong>CONCLUSIONS: </strong>Hourly delays to antimicrobial therapy, up to 3 h, were not associated with 1-year mortality in pediatric severe sepsis in this study. The finding that antimicrobial therapy ≤1 h from sepsis recognition was associated with increased 1-year mortality should be regarded as hypothesis-generating for future studies.</p>

<p><strong>OBJECTIVES: </strong>To determine whether treatment with a protocolized sepsis guideline in the emergency department was associated with a lower burden of organ dysfunction by hospital day 2 compared to nonprotocolized usual care in pediatric patients with severe sepsis.</p>

<p><strong>DESIGN: </strong>Retrospective cohort study.</p>

<p><strong>SETTING: </strong>Tertiary care children's hospital from January 1, 2012, to March 31, 2014.</p>

<p><strong>SUBJECTS: </strong>Patients older than 56 days old and younger than 18 years old with international consensus defined severe sepsis and who required PICU admission within 24 hours of emergency department arrival were included.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>The exposure was the use of a protocolized emergency department sepsis guideline. The primary outcome was complete resolution of organ dysfunction by hospital day 2. One hundred eighty nine subjects were identified during the study period. Of these, 121 (64%) were treated with the protocolized emergency department guideline and 68 were not. There were no significant differences between the groups in age, sex, race, number of comorbid conditions, emergency department triage level, or organ dysfunction on arrival to the emergency department. Patients treated with protocolized emergency department care were more likely to be free of organ dysfunction on hospital day 2 after controlling for sex, comorbid condition, indwelling central venous catheter, Pediatric Index of Mortality-2 score, and timing of antibiotics and IV fluids (adjusted odds ratio, 4.2; 95% CI, 1.7-10.4).</p>

<p><strong>CONCLUSIONS: </strong>Use of a protocolized emergency department sepsis guideline was independently associated with resolution of organ dysfunction by hospital day 2 compared to nonprotocolized usual care. These data indicate that morbidity outcomes in children can be improved with the use of protocolized care.</p>

<p><strong>OBJECTIVES: </strong>The objective was to compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric emergency department (ED).</p>

<p><strong>METHODS: </strong>This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared.</p>

<p><strong>RESULTS: </strong>Of 19,524 eligible patient visits, 88 patients developed consensus-confirmed severe sepsis or septic shock. Physician judgment identified 159 and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% confidence interval [CI] = 72.1% to 73.4%) and specificity of 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity of 92.1% (95% CI = 91.7% to 92.4%) and specificity of 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment versus algorithmic alert were 40.3% versus 2.5% and 99.88% versus 99.96%, respectively.</p>

<p><strong>CONCLUSIONS: </strong>The electronic algorithmic alert was more sensitive but less specific than physician judgment for recognition of pediatric severe sepsis and septic shock. These findings can help to guide institutions in selecting pediatric sepsis recognition methods based on institutional needs and priorities.</p>

<p><strong>OBJECTIVES: </strong>Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock.</p>

<p><strong>DESIGN: </strong>Retrospective observational study.</p>

<p><strong>SETTING: </strong>PICU at an academic medical center.</p>

<p><strong>PATIENTS: </strong>One hundred thirty patients treated for severe sepsis or septic shock.</p>

<p><strong>INTERVENTIONS: </strong>None.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure-free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74-277 min) and to first appropriate antimicrobial was 177 minutes (90-550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27-12.06) and 3.59 (95% CI, 1.09-11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45-16.2) and 4.92 (95% CI, 1.30-18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure-free days (16 [interquartile range, 1-23] vs 20 [interquartile range, 6-26]; p = 0.04).</p>

<p><strong>CONCLUSIONS: </strong>Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.</p>