Improving Recognition of Pediatric Severe Sepsis in the Emergency Department: Contributions of a Vital Sign-Based Electronic Alert and Bedside Clinician Identification.

2017

2017 May 27

1097-6760

STUDY OBJECTIVE: Recognition of pediatric sepsis is a key clinical challenge. We evaluate the performance of a sepsis recognition process including an electronic sepsis alert and bedside assessment in a pediatric emergency department (ED).

METHODS: This was a cohort study with quality improvement intervention in a pediatric ED. Exposure was a positive electronic sepsis alert, defined as elevated pulse rate or hypotension, concern for infection, and at least one of the following: abnormal capillary refill, abnormal mental status, or high-risk condition. A positive electronic sepsis alert prompted team assessment or huddle to determine need for sepsis protocol. Clinicians could initiate team assessment or huddle according to clinical concern without positive electronic sepsis alert. Severe sepsis outcome defined as activation of the sepsis protocol in the ED or development of severe sepsis requiring ICU admission within 24 hours.

RESULTS: There were 182,509 ED visits during the study period, with 86,037 before electronic sepsis alert implementation and 96,472 afterward, and 1,112 (1.2%) positive electronic sepsis alerts. Overall, 326 patients (0.3%) were treated for severe sepsis within 24 hours. Test characteristics of the electronic sepsis alert alone to detect severe sepsis were sensitivity 86.2% (95% confidence interval [CI] 82.0% to 89.5%), specificity 99.1% (95% CI 99.0% to 99.2%), positive predictive value 25.4% (95% CI 22.8% to 28.0%), and negative predictive value 100% (95% CI 99.9% to 100%). Inclusion of the clinician screen identified 43 additional electronic sepsis alert-negative children, with severe sepsis sensitivity 99.4% (95% CI 97.8% to 99.8%) and specificity 99.1% (95% CI 99.1% to 99.2%). Electronic sepsis alert implementation increased ED sepsis detection from 83% to 96%.

CONCLUSION: Electronic sepsis alert for severe sepsis demonstrated good sensitivity and high specificity. Addition of clinician identification of electronic sepsis alert-negative patients further improved sensitivity. Implementation of the electronic sepsis alert was associated with improved recognition of severe sepsis.

10.1016/j.annemergmed.2017.03.019

Ann Emerg Med

28583403

Prevalence of and Associations With Avascular Necrosis After Pediatric Sepsis: A Single-Center Retrospective Study.

2022

2022 Jan 06

1529-7535

<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>

10.1097/PCC.0000000000002880

Pediatr Crit Care Med

34991135

Temperature Trajectory Sub-Phenotypes and The Immuno-Inflammatory Response In Pediatric Sepsis.

2021

2021 Dec 27

1540-0514

<p><strong>OBJECTIVE: </strong>Heterogeneity has hampered sepsis trials, and sub-phenotyping may assist with enrichment strategies. However, biomarker-based strategies are difficult to operationalize. Four sub-phenotypes defined by distinct temperature trajectories in the first 72 hours have been reported in adult sepsis. Given the distinct epidemiology of pediatric sepsis, the existence and relevance of temperature trajectory-defined sub-phenotypes in children is unknown. We aimed to classify septic children into de novo sub-phenotypes derived from temperature trajectories in the first 72 hours, and compare cytokine, immune function, and immunometabolic markers across subgroups.</p>

<p><strong>METHODS: </strong>This was a secondary analysis of a prospective cohort of 191 critically ill septic children recruited from a single academic pediatric intensive care unit. We performed group-based trajectory modeling using temperatures over the first 72 hours of sepsis to identify latent profiles. We then used mixed effects regression to determine if temperature trajectory-defined sub-phenotypes were associated with cytokine levels, immune function, and mitochondrial respiration.</p>

<p><strong>RESULTS: </strong>We identified four temperature trajectory-defined sub-phenotypes: hypothermic, normothermic, hyperthermic fast-resolvers, and hyperthermic slow-resolvers. Hypothermic patients were less often previously healthy and exhibited lower levels of pro- and anti-inflammatory cytokines and chemokines. Hospital mortality did not differ between hypothermic children (17%) and other sub-phenotypes (3 to 11%; p = 0.26).</p>

<p><strong>CONCLUSIONS: </strong>Critically ill septic children can be categorized into temperature trajectory-defined sub-phenotypes that parallel adult sepsis. Hypothermic children exhibit a blunted cytokine and chemokine profile. Group-based trajectory modeling has utility for identifying subtypes of clinical syndromes by incorporating readily available longitudinal data, rather than relying on inputs from a single timepoint.</p>

10.1097/SHK.0000000000001906

Shock

35066512

Sepsis in Complex Patients in the Emergency Department: Time to Recognition and Therapy in Pediatric Patients With High-Risk Conditions.

2020

2020 Jan 09

1535-1815

<p><strong>OBJECTIVES: </strong>To compare timeliness of sepsis recognition and initial treatment in patients with and without high-risk comorbid conditions.</p>

<p><strong>METHODS: </strong>This was a retrospective cohort study of patients presenting to a pediatric emergency department (ED) who triggered a vital sign-based electronic sepsis alert resulting in bedside "huddle" assessment per institutional practice. A positive sepsis alert was defined as age-specific tachycardia or hypotension, concern for infection, and at least 1 of the following: abnormal capillary refill, abnormal mental status, or a high-risk condition. High-risk conditions were derived from the American Academy of Pediatrics sepsis alert tool. Patients with a positive alert underwent bedside huddle resulting in a decision regarding initiation of sepsis protocol. Placement on the protocol and time to initiation of protocol and individual therapies were compared for patients with and without high-risk conditions.</p>

<p><strong>RESULTS: </strong>During the 1-year study period, there were 1107 sepsis huddle alerts out of 96,427 ED visits. Of these, 713 (65%) had identified high-risk conditions, and 394 (35%) did not. Among patients with sepsis huddles, there was no difference in sepsis protocol initiation for patients with high-risk conditions compared with those without (24.8% vs 22.0%, P = 0.305). Between patients with high-risk conditions and those without, there were no differences in median time from triage to sepsis protocol activation, triage to initial intravenous antibiotic, triage to initial intravenous fluid therapy, or ED length of stay.</p>

<p><strong>CONCLUSIONS: </strong>Timeliness of care initiation was no different in high-risk patients with sepsis when using an electronic sepsis alert and protocolized sepsis care.</p>

10.1097/PEC.0000000000002038

Pediatr Emerg Care

31929394

Gene Expression Profiles in Children With Suspected Sepsis.

2020

2020 Jan 23

1097-6760

<p><strong>STUDY OBJECTIVE: </strong>Sepsis recognition is a clinical challenge in children. We aim to determine whether peripheral blood gene expression profiles are associated with pathogen type and sepsis severity in children with suspected sepsis.</p>

<p><strong>METHODS: </strong>This was a prospective pilot observational study in a tertiary pediatric emergency department with a convenience sample of children enrolled. Participants were older than 56 days and younger than 18 years, had suspected sepsis, and had not received broad-spectrum antibiotics in the previous 4 hours. Primary outcome was source pathogen, defined as confirmed bacterial source from sterile body fluid or confirmed viral source. Secondary outcome was sepsis severity, defined as maximum therapy required for shock reversal in the first 3 hospital days. We drew peripheral blood for ribonucleic acid isolation at the sepsis protocol activation, obtained gene expression measures with the GeneChip Human Gene 2.0 ST Array, and conducted differential expression analysis.</p>

<p><strong>RESULTS: </strong>We collected ribonucleic acid samples from a convenience sample of 122 children with suspected sepsis and 12 healthy controls. We compared the 66 children (54%) with confirmed bacterial or viral infection and found 558 differentially expressed genes, many related to interferon signaling or viral immunity. We did not find statistically significant gene expression differences in patients according to sepsis severity.</p>

<p><strong>CONCLUSION: </strong>The study demonstrates feasibility of evaluating gene expression profiling data in children evaluated for sepsis in the pediatric emergency department setting. Our results suggest that gene expression profiling may facilitate identification of source pathogen in children with suspected sepsis, which could ultimately lead to improved tailoring of sepsis treatment and antimicrobial stewardship.</p>

10.1016/j.annemergmed.2019.09.020

Ann Emerg Med

31983492

Racial Differences in Sepsis Recognition in the Emergency Department.

2019

2019 Sep 13

1098-4275

<p><strong>OBJECTIVES: </strong>We assessed racial differences in sepsis recognition in a pediatric emergency department (ED) with an established electronic sepsis alert system.</p>

<p><strong>METHODS: </strong>Quality-improvement data from June 1, 2016 to May 31, 2017 was used in this retrospective cohort study. All ED visits were included for non-Hispanic black (NHB) and non-Hispanic white (NHW) patients. The sepsis pathway was activated through the alert, 2 stages and a huddle, or outside of the alert using clinician judgment alone. We evaluated racial differences in the frequency of alerts and sepsis pathway activation within and outside of the alert. Multivariable regression adjusted for high-risk condition, sex, age, and insurance.</p>

<p><strong>RESULTS: </strong>There were 97 338 ED visits: 56 863 (58.4%) and 23 008 (23.6%) from NHBs and NHWs, respectively. NHWs were more likely than NHBs to have a positive second alert (adjusted odds ratio [aOR] 2.4; 95% confidence interval [CI] 2.1-2.8). NHWs were more likely than NHBs to have the sepsis pathway activated (aOR 1.4; 95% CI 1.02-2.1). Of those treated within the alert, there was no difference in pathway activation (aOR 0.93; 95% CI 0.62-1.4). Of those recognized by clinicians when the alert did not fire, NHWs were more likely than NHBs to be treated (aOR 3.4; 95% CI 1.8-6.4).</p>

<p><strong>CONCLUSIONS: </strong>NHWs were more likely than NHBs to be treated for sepsis, although this difference was specifically identified in the subset of patients treated for sepsis outside of the alert. This suggests that an electronic alert reduces racial differences compared with clinician judgment alone.</p>

10.1542/peds.2019-0348

Pediatrics

31519793

Empiric Antibiotic Use and Susceptibility in Infants With Bacterial Infections: A Multicenter Retrospective Cohort Study.

2017

2017 Jul 20

2154-1663

<p><strong>OBJECTIVES: </strong>To assess hospital differences in empirical antibiotic use, bacterial epidemiology, and antimicrobial susceptibility for common antibiotic regimens among young infants with urinary tract infection (UTI), bacteremia, or bacterial meningitis.</p>

<p><strong>METHODS: </strong>We reviewed medical records from infants &lt;90 days old presenting to 8 US children's hospitals with UTI, bacteremia, or meningitis. We used the Pediatric Health Information System database to identify cases and empirical antibiotic use and medical record review to determine infection, pathogen, and antimicrobial susceptibility patterns. We compared hospital-level differences in antimicrobial use, pathogen, infection site, and antimicrobial susceptibility.</p>

<p><strong>RESULTS: </strong>We identified 470 infants with bacterial infections: 362 (77%) with UTI alone and 108 (23%) with meningitis or bacteremia. Infection type did not differ across hospitals (P = .85). Empirical antibiotic use varied across hospitals (P &lt; .01), although antimicrobial susceptibility patterns for common empirical regimens were similar. A third-generation cephalosporin would have empirically treated 90% of all ages, 89% in 7- to 28-day-olds, and 91% in 29- to 89-day-olds. The addition of ampicillin would have improved coverage in only 4 cases of bacteremia and meningitis. Ampicillin plus gentamicin would have treated 95%, 89%, and 97% in these age groups, respectively.</p>

<p><strong>CONCLUSIONS: </strong>Empirical antibiotic use differed across regionally diverse US children's hospitals in infants &lt;90 days old with UTI, bacteremia, or meningitis. Antimicrobial susceptibility to common antibiotic regimens was similar across hospitals, and adding ampicillin to a third-generation cephalosporin minimally improves coverage. Our findings support incorporating empirical antibiotic recommendations into national guidelines for infants with suspected bacterial infection.</p>

10.1542/hpeds.2016-0162

Hosp Pediatr

28729240

Protocolized Treatment Is Associated With Decreased Organ Dysfunction in Pediatric Severe Sepsis.

2016

2016 Jul 22

1529-7535

<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>

10.1097/PCC.0000000000000858

Pediatr Crit Care Med

27455114

Pediatric severe sepsis in U.S. children's hospitals.

2014

798-805

11/2014

1529-7535

<p><strong>OBJECTIVES: </strong>To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies.</p>

<p><strong>DESIGN: </strong>Observational cohort study from 2004 to 2012.</p>

<p><strong>SETTING: </strong>Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database.</p>

<p><strong>PATIENTS: </strong>Children 18 years old or younger.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition, Clinical Modification-based coding strategies: 1) combinations of International Classification of Diseases, 9th edition, Clinical Modification codes for infection plus organ dysfunction (combination code cohort); 2) International Classification of Diseases, 9th edition, Clinical Modification codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and ICU length of stay, and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified 176,124 hospitalizations (3.1% of all hospitalizations), whereas the sepsis code cohort identified 25,236 hospitalizations (0.45%), a seven-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p &lt; 0.001 for trend in each cohort). Length of stay (hospital and ICU) and costs decreased in both cohorts over the study period (p &lt; 0.001). Overall, hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2% [95% CI, 20.7-21.8] vs 8.2% [95% CI, 8.0-8.3]). Over the 9-year study period, there was an absolute reduction in mortality of 10.9% (p &lt; 0.001) in the sepsis code cohort and 3.8% (p &lt; 0.001) in the combination code cohort.</p>

<p><strong>CONCLUSIONS: </strong>Prevalence of pediatric severe sepsis increased in the studied U.S. children's hospitals over the past 9 years, whereas resource utilization and mortality decreased. Epidemiologic estimates of pediatric severe sepsis varied up to seven-fold depending on the strategy used for case ascertainment.</p>

10.1097/PCC.0000000000000225

Pediatr Crit Care Med

25162514

Comparison of Two Sepsis Recognition Methods in a Pediatric Emergency Department.

2015

1298-306

11/2015

1553-2712

<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>

10.1111/acem.12814

Acad Emerg Med

26474032