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OBJECTIVES: Acute brain dysfunction (ABD) in pediatric sepsis has a prevalence of 20%, but can be difficult to identify. Our previously validated ABD computational phenotype (CP ABD ) used variables obtained from the electronic health record indicative of clinician concern for acute neurologic or behavioral change. We tested whether the CP ABD has better diagnostic performance to identify confirmed ABD than other definitions using the Glasgow Coma Scale or delirium scores. DESIGN: Diagnostic testing in a curated cohort of pediatric sepsis/septic shock patients. SETTING: Quaternary freestanding children's hospital. SUBJECTS: The test dataset comprised 527 children with sepsis/septic shock managed between 2011 and 2021 with a prevalence (pretest probability) of confirmed ABD of 30% (159/527). MEASUREMENTS AND MAIN RESULTS: CP ABD was based on use of neuroimaging, electroencephalogram, and/or administration of new antipsychotic medication. We compared the performance of the CP ABD with three GCS/delirium-based definitions of ABD-Proulx et al, International Pediatric Sepsis Consensus Conference, and Pediatric Organ Dysfunction Information Update Mandate. The posttest probability of identifying ABD was highest in CP ABD (0.84) compared with other definitions. CP ABD also had the highest sensitivity (83%; 95% CI, 76-89%) and specificity (93%; 95% CI, 90-96%). The false discovery rate was lowest in CP ABD (1-in-6) as was the false omission rate (1-in-14). Finally, the prevalence threshold for the definitions varied, with the CP ABD being the definition closest to 20%. CONCLUSIONS: In our curated dataset of pediatric sepsis/septic shock, CP ABD had favorable characteristics to identify confirmed ABD compared with GCS/delirium-based definitions. The CP ABD can be used to further study the impact of ABD in studies using large electronic health datasets.
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Registros Eletrônicos de Saúde , Choque Séptico , Humanos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Pré-Escolar , Feminino , Masculino , Criança , Choque Séptico/diagnóstico , Choque Séptico/fisiopatologia , Lactente , Eletroencefalografia/métodos , Escala de Coma de Glasgow , Adolescente , Sepse/diagnóstico , Sepse/fisiopatologia , Neuroimagem , Delírio/diagnóstico , Recém-Nascido , Conjuntos de Dados como AssuntoRESUMO
OBJECTIVES: To validate a computational phenotype that identifies acute brain dysfunction (ABD) based on clinician concern for neurologic or behavioral changes in pediatric sepsis. DESIGN: Retrospective observational study. SETTING: Single academic children's hospital. PATIENTS: Four thousand two hundred eighty-nine index sepsis episodes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An existing computational phenotype of ABD was optimized to include routinely collected variables indicative of clinician concern for acute neurologic or behavioral change (completion of CT or MRI, electroencephalogram, or new antipsychotic administration). First, the computational phenotype was compared with an ABD reference standard established from chart review of 527 random sepsis episodes to determine criterion validity. Next, the computational phenotype was compared with a separate validation cohort of 3,762 index sepsis episodes to determine content and construct validity. Criterion validity for the final phenotype had sensitivity 83% (95% CI, 76-89%), specificity 93% (90-95%), positive predictive value 84% (77-89%), and negative predictive value 93% (90-96%). In the validation cohort, the computational phenotype identified ABD in 35% (95% CI 33-36%). Content validity was demonstrated as those with the ABD computational phenotype were more likely to have characteristics of neurologic dysfunction and severe illness than those without the ABD phenotype, including nonreactive pupils (15% vs 1%; p < 0.001), Glasgow Coma Scale less than 5 (44% vs 12%; p < 0.001), greater than or equal to two nonneurologic organ dysfunctions (50% vs 25%; p < 0.001), and need for intensive care (81% vs 65%; p < 0.001). Construct validity was demonstrated by higher odds for mortality (odds ratio [OR], 6.9; 95% CI, 5.3-9.1) and discharge to rehabilitation (OR, 11.4; 95% CI 7.4-17.5) in patients with, versus without, the ABD computational phenotype. CONCLUSIONS: A computational phenotype of ABD indicative of clinician concern for new neurologic or behavioral change offers a valid retrospective measure to identify episodes of sepsis that involved ABD. This computational phenotype provides a feasible and efficient way to study risk factors for and outcomes from ABD using routinely collected clinical data.
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Encefalopatias , Sepse , Humanos , Estudos Retrospectivos , Mortalidade Hospitalar , Sepse/diagnóstico , Encefalopatias/diagnóstico , Encefalopatias/etiologia , Fenótipo , Encéfalo/diagnóstico por imagemRESUMO
OBJECTIVES: Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND) outcomes. Previous studies have identified patient factors, such as prematurity and genetic syndromes, to be associated with worse ND outcomes. However, no consistent relationships have been identified among modifiable management factors, including cardiopulmonary bypass strategies, and ND outcomes after cardiac surgery in infancy. Studies in immature animals, including primates, have demonstrated neurodegeneration and apoptosis in the brain after certain levels and extended durations of anesthetic exposure. Retrospective human studies have also suggested relationships between adverse ND effects and anesthetic exposure. METHODS: Cumulative minimum alveolar concentration hours (MAC-hrs) of exposure to volatile anesthetic agents (VAA) (desflurane, halothane, isoflurane, and sevoflurane) were collected from an anesthetic database and medical record review for 96 patients with HLHS or variants. ND testing was performed between ages 4 and 5 years, including full-scale IQ, verbal IQ, performance IQ, and processing speed. Four generalized linear modes were hypothesized a priori and tested using a Gaussian (normal) distribution with an identity link. RESULTS: Cumulative VAA exposure ranged from 0 to 35.3 MAC-hrs (median 7.5 hours). Using specified covariates identified previously as significant predictors of ND outcomes, statistically significant relationships were identified between total MAC-hrs exposure and worse full-scale IQ and verbal IQ scores (P's < .05) alone and after adjusting for relevant covariates. CONCLUSIONS: Increased cumulative MAC-hrs exposure to VAA is associated with worse ND outcomes in certain domains in children with HLHS and variants.