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The Centers for Disease Control and Prevention recommends tracking risk-adjusted antimicrobial prescribing. Prior studies have used prescribing variation to drive quality improvement initiatives without adjusting for severity of illness. The present study aimed to determine the relationship between antimicrobial prescribing and risk-adjusted ICU mortality in the Pediatric Health Information Systems (PHIS) database, assessed by IBM-Watson risk of mortality. A nested analysis sought to assess an alternative risk model incorporating laboratory data from federated electronic health records. METHODS: Retrospective cohort study of pediatric ICU patients in PHIS between 1/1/2010 and 12/31/2019, excluding patients admitted to a neonatal ICU, and a nested study of PHIS+ from 1/1/2010 to 12/31/2012. Hospital antimicrobial prescription volumes were assessed for association with risk-adjusted mortality. RESULTS: The cohort included 953,821 ICU encounters (23,851 [2.7%] nonsurvivors). There was 4-fold center-level variability in antimicrobial use. ICU antimicrobial use was not correlated with risk-adjusted mortality assessed using IBM-Watson. A risk model incorporating laboratory data available in PHIS+ significantly outperformed IBM-Watson (c-statistic 0.940 [95% confidence interval 0.933-0.947] versus 0.891 [0.881-0.901]; P < 0.001, area under the precision recall curve 0.561 versus 0.297). Risk-adjusted mortality was inversely associated with antimicrobial prescribing in this smaller cohort using both the PHIS+ and Watson models (P = 0.05 and P < 0.01, respectively). CONCLUSIONS: Antimicrobial prescribing among pediatric ICUs in the PHIS database is variable and not associated with risk-adjusted mortality as assessed by IBM-Watson. Expanding existing administrative databases to include laboratory data can achieve more meaningful insights when assessing multicenter antibiotic prescribing practices.
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OBJECTIVES: Neurologic complications, consisting of the acute development of a neurologic disorder, that is, not present at admission but develops during the course of illness, can be difficult to detect in the PICU due to sedation, neuromuscular blockade, and young age. We evaluated the direct relationships of serum biomarkers and clinical variables to the development of neurologic complications. Analysis was performed using mixed graphical models, a machine learning approach that allows inference of cause-effect associations from continuous and discrete data. DESIGN: Secondary analysis of a previous prospective observational study. SETTING: PICU, single quaternary-care center. PATIENTS: Individuals admitted to the PICU, younger than18 years old, with intravascular access via an indwelling catheter. INTERVENTIONS: None. MEASUREMENTS: About 101 patients were included in this analysis. Serum (days 1-7) was analyzed for glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, and alpha-II spectrin breakdown product 150 utilizing enzyme-linked immunosorbent assays. Serum levels of neuron-specific enolase, myelin basic protein, and S100 calcium binding protein B used in these models were reported previously. Demographic data, use of selected clinical therapies, lengths of stay, and ancillary neurologic testing (head CT, brain MRI, and electroencephalogram) results were recorded. The Mixed Graphical Model-Fast-Causal Inference-Maximum algorithm was applied to the dataset. MAIN RESULTS: About 13 of 101 patients developed a neurologic complication during their critical illness. The mixed graphical model identified peak levels of the neuronal biomarker neuron-specific enolase and ubiquitin C-terminal hydrolase-L1, and the astrocyte biomarker glial fibrillary acidic protein to be the direct causal determinants for the development of a neurologic complication; in contrast, clinical variables including age, sex, length of stay, and primary neurologic diagnosis were not direct causal determinants. CONCLUSIONS: Graphical models that include biomarkers in addition to clinical data are promising methods to evaluate direct relationships in the development of neurologic complications in critically ill children. Future work is required to validate and refine these models further, to determine if they can be used to predict which patients are at risk for/or with early neurologic complications.
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Estado Terminal , Doenças do Sistema Nervoso , Adolescente , Biomarcadores , Criança , Proteína Glial Fibrilar Ácida , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , Estudos ProspectivosRESUMO
OBJECTIVES: Targets for treatment of raised intracranial pressure or decreased cerebral perfusion pressure in pediatric neurocritical care are not well defined. Current pediatric guidelines, based on traumatic brain injury, suggest an intracranial pressure target of less than 20 mm Hg and cerebral perfusion pressure minimum of 40-50 mm Hg, with possible age dependence of cerebral perfusion pressure. We sought to define intracranial pressure and cerebral perfusion pressure thresholds associated with inhospital mortality across a large single-center pediatric neurocritical care cohort. DESIGN: Retrospective chart review. SETTING: PICU, single quaternary-care center. PATIENTS: Individuals receiving intracranial pressure monitoring from January 2012 to December 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure and cerebral perfusion pressure measurements from 262 neurocritical care patients (87 traumatic brain injury and 175 nontraumatic brain injury; 63% male; 8.3 ± 5.8 yr; mortality 11.1%). Mean intracranial pressure and cerebral perfusion pressure had area under the receiver operating characteristic curves of 0.75 and 0.64, respectively, for association of inhospital mortality. Cerebral perfusion pressure cut points increased with age (< 2 yr = 47, 2 to < 8 yr = 58 mm Hg, ≥ 8 yr = 73 mm Hg). In the traumatic brain injury subset, mean intracranial pressure and cerebral perfusion pressure had area under the receiver operating characteristic curves of 0.70 and 0.78, respectively, for association of inhospital mortality. Traumatic brain injury cerebral perfusion pressure cut points increased with age (< 2 yr = 45, 2 to < 8 yr = 57, ≥ 8 yr = 68 mm Hg). Mean intracranial pressure greater than 15 mm Hg, male sex, and traumatic brain injury status were independently associated with inhospital mortality (odds ratio, 14.23 [5.55-36.46], 2.77 [1.04-7.39], and 2.57 [1.03-6.38], respectively; all p < 0.05). Mean cerebral perfusion pressure less than 67 mm Hg and traumatic brain injury status were independently associated with inhospital mortality (odds ratio, 5.16 [2.05-12.98] and 3.71 [1.55-8.91], respectively; both p < 0.01). In the nontraumatic brain injury subset, mean intracranial pressure had an area under the receiver operating characteristic curve 0.77 with an intracranial pressure cut point of 15 mm Hg, whereas mean cerebral perfusion pressure was not predictive of inhospital mortality. CONCLUSIONS: We identified mean intracranial pressure thresholds, utilizing receiver operating characteristic and regression analyses, associated with inhospital mortality that is below current guidelines-based treatment targets in both traumatic brain injury and nontraumatic brain injury patients, and age-dependent cerebral perfusion pressure thresholds associated with inhospital mortality that were above current guidelines-based targets in traumatic brain injury patients. Further study is warranted to identify data-driven intracranial pressure and cerebral perfusion pressure targets in children undergoing intracranial pressure monitoring, whether for traumatic brain injury or other indications.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/terapia , Circulação Cerebrovascular , Criança , Feminino , Mortalidade Hospitalar , Humanos , Pressão Intracraniana , Masculino , Estudos RetrospectivosRESUMO
A relationship between Pao2 and mortality has previously been observed in single-center studies. We performed a retrospective cohort study of the Pediatric Health Information System plus database including patients less than or equal to 21 years old admitted to a medical or cardiac ICU who received invasive ventilation within 72 hours of admission. We trained and validated a multivariable logistic regression mortality prediction model with very good discrimination (C-statistic, 0.86; 95% CI, 0.79-0.92; area under the precision-recall curve, 0.39) and acceptable calibration (standardized mortality ratio, 0.96; 95% CI, 0.75-1.23; calibration belt p = 0.07). Maximum Pao2 measurements demonstrated a parabolic ("U-shaped") relationship with PICU mortality (Box-Tidwell p < 0.01). Maximum Pao2 was a statistically significant predictor of risk-adjusted mortality (standardized odds ratio, 1.27; 95% CI, 1.23-1.32; p < 0.001). This analysis is the first multicenter pediatric study to identify a relationship between the extremes in Pao2 values and PICU mortality. Clinicians should remain judicious in the use of oxygen when caring for children.
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OBJECTIVES: Neurologic complications occur in up to 40% of adult abdominal solid organ transplant recipients and are associated with increased mortality. Comparable pediatric data are sparse. This study describes the occurrence of neurologic and behavioral complications (neurobehavioral complications) in pediatric abdominal solid organ transplant recipients. We examine the association of these complications with length of stay, mortality, and tacrolimus levels. DESIGN: The electronic health record was interrogated for inpatient readmissions of pediatric abdominal solid organ transplant recipients from 2009 to 2017. A computable composite definition of neurobehavioral complication, defined using structured electronic data for neurologic and/or behavioral phenotypes, was created. SETTING: Quaternary children's hospital with an active transplant program. PATIENTS: Pediatric abdominal solid organ transplant recipients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Computable phenotypes demonstrated a specificity 98.7% and sensitivity of 63.0% for identifying neurobehavioral complications. There were 1,542 readmissions among 318 patients, with 65 (20.4%) having at least one admission with a neurobehavioral complication (total 109 admissions). Median time from transplant to admission with neurobehavioral complication was 1.2 years (interquartile range, 0.52-2.28 yr). Compared to encounters without an identified neurobehavioral complication, encounters with a neurobehavioral complication were more likely to experience ICU admission (odds ratio, 3.9; 2.41-6.64; p < 0.001), have longer ICU length of stay (median 10.3 vs 2.2 d; p < 0.001) and hospital length of stay (8.9 vs 4.3 d; p < 0.001), and demonstrate higher maximum tacrolimus level (12.3 vs 9.8 ng/mL; p = 0.001). Patients with a neurobehavioral complication admission were more likely to die (odds ratio, 5.04; 1.49-17.09; p = 0.009). In a multivariable analysis, type of transplant, ICU admission, and tacrolimus levels were independently associated with the presence of a neurobehavioral complication. CONCLUSIONS: Common electronic health record variables can be used to accurately identify neurobehavioral complications in the pediatric abdominal solid organ transplant population. Late neurobehavioral complications are associated with increased hospital resource utilization, mortality, and tacrolimus exposure. Additional studies are required to delineate the relationship between maximum tacrolimus level and neurobehavioral complications to guide therapeutic drug monitoring and dosing.
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Transplante de Órgãos , Adulto , Criança , Recursos em Saúde , Hospitalização , Humanos , Razão de Chances , Transplante de Órgãos/efeitos adversos , Estudos RetrospectivosRESUMO
OBJECTIVE: To identify whether a high PaO2 (hyperoxemia) at the time of presentation to the PICU is associated with in-hospital mortality. DESIGN: Single-center observational study. SETTING: Quaternary-care PICU. PATIENTS: Encounters admitted between January 1, 2009, and December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Encounters with a measured PaO2 were included. To account for severity of illness upon presentation, we calculated a modified Pediatric Risk of Mortality IV score excluding PaO2 for each encounter, calibrated for institutional data. Logistic regression was used to determine whether hyperoxemia (PaO2 ≥ 300 torr [39.99 kPa]) in the 12 hours surrounding PICU admission was associated with in-hospital mortality. We reperformed our analysis using a cutoff for hyperoxemia obtained by comparisons of observed versus predicted mortality when encounters were classified by highest PaO2 in 50 torr (6.67 kPa) bins. Results are reported as adjusted odds ratios with 95% CIs. Of 23,719 encounters, 4,093 had a PaO2 recorded in the period -6 to +6 hours after admission. Two hundred seventy-four of 4,093 (6.7%) had in-hospital mortality. The prevalence of hyperoxemia increased with rising modified Pediatric Risk of Mortality IV and was not associated with mortality in multivariable models (adjusted odds ratio, 1.38; 95% CI, 0.98-1.93). When using a higher cutoff of hyperoxemia derived from comparison of observed versus predicted rates of mortality of greater than or equal to 550 torr (73.32 kPa), hyperoxemia was associated with mortality (adjusted odds ratio, 2.78; 95% CI, 2.54-3.05). CONCLUSIONS: A conventional threshold for hyperoxemia at presentation to the PICU was not associated with in-hospital mortality in a model using a calibrated acuity score. Extreme states of hyperoxemia (≥ 73.32 kPa) were significantly associated with in-hospital mortality. Prospective research is required to identify if hyperoxemia before and/or after PICU admission contributes to poor outcomes.
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Estado Terminal/mortalidade , Mortalidade Hospitalar , Hiperóxia/diagnóstico , Adolescente , Gasometria , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Humanos , Hiperóxia/mortalidade , Hipóxia/diagnóstico , Hipóxia/mortalidade , Unidades de Terapia Intensiva Pediátrica , Modelos Logísticos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Oxigênio/sangue , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: Develop and test the performance of electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV and electronic version of the Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 scores. DESIGN: Retrospective, single-center cohort derived from structured electronic health record data. SETTING: Large, quaternary PICU at a freestanding, university-affiliated children's hospital. PATIENTS: All encounters with a PICU admission between January 1, 2009, and December 31, 2017, identified using electronic definitions of inpatient encounter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome was predictive validity of each score for hospital mortality, assessed as model discrimination and calibration. Discrimination was examined with the area under the receiver operating characteristics curve and the area under the precision-recall curve. Calibration was assessed with the Hosmer-Lemeshow goodness of fit test and calculation of a standardized mortality ratio. Models were recalibrated with new regression coefficients in a training subset of 75% of encounters selected randomly from all years of the cohort and the calibrated models were tested in the remaining 25% of the cohort. Content validity was assessed by examining correlation between electronic versions of the scores and prospectively calculated data (electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV) and an alternative informatics approach (Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 score). The cohort included 21,335 encounters. Correlation coefficients indicated strong agreement between different methods of score calculation. Uncalibrated area under the receiver operating characteristics curves were 0.96 (95% CI, 0.95-0.97) for electronic version of the Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 score and 0.87 (95% CI, 0.85-0.89) for electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV for inpatient mortality. The uncalibrated electronic version of the Children's Hospital of Pittsburgh Pediatric Risk of Mortality-IV standardized mortality ratio was 0.63 (0.59-0.66), demonstrating strong agreement with previous, prospective evaluation at the study center. The uncalibrated electronic version of the Children's Hospital of Pittsburgh Pediatric Logistic Organ Dysfunction-2 score standardized mortality ratio was 0.20 (0.18-0.21). All models required recalibrating (all Hosmer-Lemeshow goodness-of-fit, p < 0.001) and subsequently demonstrated acceptable goodness-of-fit when examined in a test subset (n = 5,334) of the cohort. CONCLUSIONS: Electronically derived intensive care acuity scores demonstrate very good to excellent discrimination and can be calibrated to institutional outcomes. This approach can facilitate both performance improvement and research initiatives and may offer a scalable strategy for comparison of interinstitutional PICU outcomes.
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Mortalidade Hospitalar , Escores de Disfunção Orgânica , Adolescente , Criança , Pré-Escolar , Registros Eletrônicos de Saúde/estatística & dados numéricos , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de RiscoRESUMO
OBJECTIVE: To determine the incidence and clinical consequences of postoperative hyponatremia in children. STUDY DESIGN: We performed a retrospective analysis of postoperative admissions to the pediatric intensive care unit (excluding cardiac, neurosurgical, and renal). The incidence of severe (serum sodium < 125 mmol/L or symptoms) and moderate (serum sodium < 130 mmol/L) hyponatremia in children receiving hypotonic (HT) and normotonic (NT) fluids was calculated. RESULTS: Out of a total of 145 children (568 sodium measurements; 116 HT and 29 NT), we identified 16 with hyponatremia (11%). The incidences of moderate (10.3% vs 3.4%, P = .258) and severe (2.6% vs 0%; P = .881) hyponatremia were not significantly different in the HT and NT groups. There were no neurologic sequelae or deaths related to hyponatremia. CONCLUSIONS: In our study group, hyponatremia was common, but morbidity and death were not observed. Careful monitoring of serum sodium level may be responsible for this lack of adverse outcomes. Larger, prospective studies are needed to determine whether the incidence of hyponatremia differs between the HT and NT groups.