OBJECTIVES:To review the longevity of extended dwell catheters (EDCs) vs. peripheral IV catheters (PIVs) in pediatric critical care and explore factors associated with catheter duration. DESIGN:Retrospective cohort study between September 2023 and August 2024. SETTING:A single mixed cardiac and general PICU in an academic health care center in Ottawa, Canada. PATIENTS:A total of 400 vascular access catheters were included, comprising 329 PIVs and 71 EDCs in 238 unique patients. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Median (interquartile range [IQR]) unadjusted catheter dwell times were 4.6 days (IQR, 2.8-7.9 d) for EDCs and 2.3 days (IQR, 1.2-4.1 d) for PIVs. In an adjusted mixed-effects multivariable regression model, EDCs as opposed to PIVs were associated with 62% greater longevity (1.62 [95% CI, 1.10-2.37]). Factors associated with increased longevity included use of upper limb location (1.49 [95% CI, 1.07-2.07]) and sedation combined with acute invasive mechanical ventilation (2.12 [95% CI, 1.47-3.05]). A sensitivity analysis of only failed devices failed to identify an associated increase or decrease in longevity for EDCs (1.38 [95% CI, 0.80-2.37]), but close inspection of the estimate and upper limit of the 95% CI shows that we are unable to exclude the possibility of more than doubling of longevity. We also failed to demonstrate an association between the proportion of catheters still functional at the time of removal and catheter type: PIV, 26% (95% CI, 21-31%) vs. EDC, 30% (95% CI, 20-42%). CONCLUSIONS:In our center, 2023-2024, use of EDCs as opposed to PIVs in PICU cases was associated with longer duration of use, suggesting preferred use of EDCs in patients requiring medium-term IV access, but not meeting criteria for central access. Further prospective studies are necessary to evaluate broader use of EDCs and optimum insertion practices.
OBJECTIVE:To determine whether intracranial pressure (ICP) monitoring is associated with decreased mortality among pediatric severe traumatic brain injury (TBI) patients. DESIGN:Retrospective cohort study of the Virtual Pediatric Systems database. PATIENTS:Patients younger than 18 years with diagnosis codes for TBI and Glasgow Coma Scale (GCS) of less than or equal to 8 between 2010 and 2024 from centers submitting ICP monitor data. MEASUREMENTS:ICP monitoring practices were described using summary statistics. To estimate time-dependent association between ICP monitor placement and 30-day mortality, time-varying Cox proportional hazards modeling was performed. In a second complementary analysis to minimize immortal time bias, landmarked unadjusted Kaplan-Meier analyses and adjusted Cox proportional hazards models of ICP monitor placement by 1, 12, and 24 hours were performed. MAIN RESULTS:There were 6636 admissions included across 94 PICUs between January 1, 2010, and December 31, 2024; 2016 of 6636 (30.7%) had ICP monitors. Patients with ICP monitors were older (8 yr [3-14] vs. 6 yr [2-13], p < 0.001), had lower GCS (3 [3-6] vs. 6 [3-7], p < 0.001), and a higher Pediatric Risk of Mortality 3 score (12.0 [8.0-21.0] vs. 9.0 [5.0-21.0], p < 0.001). ICP monitor placement was associated with lower time-specific mortality hazard until 4.4 d (95% CI, 3.7-5.2) in unadjusted and 10.5 d (95% CI, 7.2-30.0) in adjusted time-varying Cox modeling, resulting in lower 30-day cumulative mortality in the adjusted model only (29.2% [95% CI, 28.0-30.6%]) in the unmonitored group vs. (25.1% [95% CI, 23.4-26.5%]) in the monitored group. In landmark analysis and adjustment for severity, ICP monitor placement was associated with a significantly lower 30-day-mortality hazard ratio (HR) at the 1-hour (adjusted HR 0.81 [0.69, 0.94]), 12-hr (0.83 [0.73, 0.95]), and 24-hr landmarks (0.80 [0.69, 0.92]). CONCLUSIONS:ICP monitoring was associated with reduced mortality for 10 days after admission, followed by increased mortality between days 11 and 30. The stronger effect of reduced early mortality resulted in lower 30-day cumulative mortality.
OBJECTIVE:Sepsis is a leading cause of mortality in low- and middle-income countries. This study identifies computable pediatric sepsis phenotypes (PedSep A, B, C, and D) previously derived in a U.S. cohort in a new independent Argentine cohort to assess plausibility for its use in personalized clinical trials in Pan-American children. DESIGN:This retrospective cohort study uses data from the Argentinian ESSPED2 (Estudio Sepsis y Shock Séptico Pediátrico 2) Registry and the Phenotyping Pediatric Sepsis-Induced Multiple Organ Failure U.S. study. SETTING:The Argentine cohort was recruited from 51 PICUs between September 15 and December 15, 2021. The U.S. cohort involved nine PICUs between 2015 and 2017. PATIENTS:The Argentine cohort included 99 sepsis patients aged 1 month to 18 years, and the U.S. cohort included 404 sepsis patients, aged 44 weeks of gestation to 18 years. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Membership in the PedSep A, B, C, or D phenotype was identified using a computable tool (https://pedsepsis.pitt.edu) requiring 25 bedside variables at 24 hours. Phenotype prevalence and mortality were compared between Argentine and U.S. cohorts. Heterogeneity of treatment responses and power analyses were performed in the combined cohort. Mortality rates were 20 of 99 (20.2%) in Argentina and 45 of 404 (11.14%) in the United States (p = 0.025). Mortality was highest in PedSep D computable phenotype, with 9 of 28 (32.14%) in Argentina and 19 of 56 (33.93%) in the United States (p = 1.0). Heterogeneity of treatment response to anti-inflammatory therapies was observed in PedSep D compared with PedSep A, B, and C children (p < 0.05). Sample size calculations support the requirement for 55 PedSep D patients per arm to demonstrate reduction in mortality with dexamethasone or methylprednisolone with gammaglobulin compared with placebo. CONCLUSIONS:The PedSep computable tool can identify PedSep D children for enrollment in combined Argentina-U.S. randomized controlled trials evaluating effectiveness of anti-inflammatory treatment in hyperinflammatory sepsis.
OBJECTIVES:To determine the prevalence and risk factors of adverse events (AE) in pediatric patients undergoing procedural sedation outside of the operating room (PSOOR) for dental procedures. DESIGN:A retrospective analysis of prospectively collected data using the Pediatric Sedation Research Consortium database, which collects multicenter, quality-controlled data on pediatric sedations. SETTING:Twenty-five participating hospitals across the United States, with data collected from July 1, 2020, to June 30, 2024. PATIENTS:Three thousand five hundred forty-eight pediatric patients undergoing PSOOR for dental procedures. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:The primary outcome was the occurrence of one or more AEs, which were classified as either severe (including both critical and high-risk events) or low-risk based on severity. Thirty-one percent of dental sedations had an AE occur and 5% had a severe AE occur. The most prevalent severe events in dental sedations included complete airway obstruction (2.8%), hypoxia requiring major intervention (1.6%), and laryngospasm (0.8%). Multiple modeling approaches revealed that medication regimen, provider type, neurologic comorbidity, snoring, and obesity were associated with severe AEs after adjusting for confounding variables. CONCLUSIONS:While PSOOR is generally safe, children undergoing sedation for dental procedures experience high rates of AEs, most commonly airway-related complications. Patient-, provider-, and institution-level factors may increase the risk of AEs. These findings underscore the need for enhanced preprocedural risk assessment and provider training to ensure safety in pediatric dental sedation practices.
OBJECTIVE:To evaluate the association between obesity and ICU length of stay (LOS) in children with critical asthma and assess whether socioeconomic factors modify this relationship. DESIGN:A multicenter retrospective cohort study using the Virtual PICU Systems (VPS) database of children 2-19 years old admitted to ICUs with asthma between 2010 and 2020. Patients were classified by body mass index (BMI) percentile. Children with chronic medical conditions and those missing relevant data were excluded. Multivariable Cox and logistic regression models were performed and adjusted for confounders. SETTING:All PICUs in the VPS database. PATIENTS:A total of 16,412 children from 53 centers with available data to assign BMI, race, and insurance type were included. INTERVENTIONS:None. MEASUREMENTS:The primary outcome was hazard of ICU discharge among survivors, with ICU LOS as the time-to-event variable. Secondary outcomes included the use of invasive or noninvasive mechanical ventilation (NIV) within the first hour of ICU admission and after the first hour. MAIN RESULTS:Obesity was associated with a lower hazard of ICU discharge among survivors (hazard ratio [HR] 0.87 [95% CI, 0.83-0.91]), consistent with longer ICU LOS. Obesity was associated with higher odds of MV in the first hour (odds ratio [OR] 1.24 [95% CI, 1.12-1.39]) and after the first hour (OR 1.63 [95% CI, 1.39-1.92]). These associations remained after adjustment for age, sex, race, insurance type, pneumonia diagnosis, transfer status, and overall severity of illness (Pediatric Risk of Mortality III). Among Black children, obesity was not associated with longer ICU LOS (HR 0.95 [95% CI, 0.89-1.03], p = 0.22). Otherwise, race and insurance type did not significantly modify these associations. CONCLUSIONS:Obesity is independently associated with longer ICU stays and increased respiratory support in children with critical asthma. These findings are predominantly consistent across racial and socioeconomic groups.
OBJECTIVES:To determine the association between abnormal pupillary reactivity using automated infrared pupillometry and unfavorable outcome after pediatric cardiac arrest (CA). DESIGN:Single-center, retrospective, cohort study, 2018-2023. SETTING:Large tertiary PICU in the United States. PATIENTS:We identified 127 patients 18 years old or younger with 8464 pupillary assessments, greater than or equal to 2 measured within 72 hours after return of circulation (ROC). INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Abnormal pupillary reactivity was defined as greater than or equal to 2 neurological pupil index (NPi) values less than 3 in either eye. Unfavorable outcome was hospital discharge Pediatric Cerebral Performance Category of 4-6 and increase greater than or equal to 1 from pre-CA status. We explored the diagnostic performance of abnormal NPi for categorizing unfavorable outcome in the first 72 hours post-ROC, and at the time periods of 0-12, 12-24, 24-48, and 48-72 hours. We used a mixed-effects linear regression model to evaluate whether NPi values were associated with favorable vs. unfavorable outcome, after adjusting for clinical variables. Group-based trajectory modeling (GBTM) characterized NPi trajectories over time. Abnormal pupillary reactivity had a sensitivity of 66%, specificity 79%, positive predictive value of 82%, negative predictive value of 63%, and area under the receiver operating characteristic curve of 0.73 (95% CI, 0.65-0.80) for unfavorable outcome. Specificity did not differ between time periods. In the mixed-effects model, unfavorable outcome was associated with lower NPi values that decreased over time (interaction of time from ROC and outcome β = -0.02; p < 0.001). Through GBTM we identified a subgroup of patients with favorable outcome whose NPi was initially abnormal but subsequently improved over time. CONCLUSIONS:In our 2018-2023 experience, the presence of at least two NPi values less than 3 post-CA was associated with unfavorable outcome, with an acceptable level of diagnostic characterization. Of note, some patients with initially lower NPi values improved over time and had favorable outcome.
OBJECTIVES:Biomarkers with adequate precision to rule-in/rule-out sepsis in children represent an unmet need. SeptiCyte RAPID is a point-of-care, U.S. Food and Drug Administration-cleared, host gene expression biomarker test for the determination of sepsis probability (reported in 1 hr as a SeptiScore) using a small-volume peripheral blood sample. We have previously reported on SeptiCyte RAPID performance in adults. Here we report a retrospective, noninterventional clinical validation study of SeptiCyte RAPID, as a sepsis diagnostic adjunct in children. DESIGN, SETTING, AND PATIENTS:Critically ill children (n = 284), 1 month to 18 years old, admitted to PICUs, with or without suspected or documented infection, but all of whom met criteria for systemic inflammatory response syndrome (SIRS) and were enrolled at multiple clinical sites in the United States and Australia in four separate studies. INTERVENTIONS:None; SeptiCyte RAPID results were not used to guide patient treatment. MEASUREMENTS AND MAIN RESULTS:A combination of clinical adjudication and an independent panel of three physicians (Retrospective Physician Diagnosis [RPD]), blinded to SeptiCyte RAPID results, were used to retrospectively categorize patients into sepsis vs. noninfectious SIRS categories. Diagnostic performance of SeptiCyte RAPID for differentiating sepsis and noninfectious SIRS compared with RPD was measured using area under the curve (AUC), likelihood ratio, and a monotonic increase in probability of sepsis and increasing SeptiScores. Binomial logistic regression analysis was used to integrate clinical parameters in a model based on SeptiCyte RAPID. Higher SeptiScores correlated with higher probability of sepsis. SeptiCyte RAPID AUC for identifying sepsis in children ranged from 0.80 to 0.83. A model additionally integrating lactate, platelet number, mean arterial pressure, Paco2, mechanical ventilation, weight, age, and leukocyte count increased SeptiCyte RAPID performance (AUC, 0.86; 95% CI, 0.85-0.87). CONCLUSIONS:SeptiCyte RAPID demonstrated similar performance characteristics in children to that previously reported for adults. Additional real world effectiveness studies are warranted to determine real-time clinical utility, patient benefits, and health economic impact.
OBJECTIVES:Minimally invasive cardiac output (CO) monitoring technologies lack validation in the adolescent population. We aimed to test the accuracy and precision of the FloTrac arterial pressure cardiac output (APCO) and ClearSight photoplethysmography cardiac output (PPGCO; Edwards Lifesciences, Irvine, CA) technologies in adolescents undergoing elective cardiac catheterization. DESIGN:Prospective, single-arm, nonrandomized, observational study. SETTING:Cardiac catheterization laboratory at three freestanding pediatric hospitals in the United States. PATIENTS:Adolescent patients 12-18 years of age undergoing surveillance cardiac catheterization after heart transplantation. INTERVENTIONS:Swan-Ganz pulmonary artery catheterization with the intermittent thermodilution CO (iCO) technique was used as the gold standard for CO measurements. APCO was measured using an existing femoral arterial sheath, and PPGCO was measured utilizing a volumetric cuff placed on the finger of the upper extremities. Two sets of simultaneous iCO, APCO, and PPGCO measurements were compared. Bias and level of concordance were assessed using Bland-Altman analysis. MEASUREMENTS AND MAIN RESULTS:Out of the 89 subjects enrolled, 73 underwent measurements and provided a total of 60 sets of measurements for each device. The median age was 16 years (interquartile range [IQR], 14-17 yr) with a median body surface area of 1.6 m2 (IQR, 1.5-1.8 m2). The median averaged intermittent cardiac index was 2.7 L/min/m2 (IQR, 2.3-3.1 L/min/m2). FloTrac APCO mean bias was 0.32 L/min/m2 (IQR, 0.20-0.44 L/min/m2) with a precision of 0.70 L/min/m2 (IQR, 0.58-0.82 L/min/m2). ClearSight PPGCO mean bias was 0.28 L/min/m2 (95% CI, 0.16-0.41 L/min/m2) with a precision of 0.71 L/min/m2 (95% CI, 0.59-0.84 L/min/m2). No serious adverse events were reported related to the devices. CONCLUSIONS:The minimally and noninvasive CO measurements with FloTrac and ClearSight APCO show acceptable bias and precision under standardized elective clinical conditions in an adolescent pediatric population, making them useful tools in the routine clinical management of critically ill children.
OBJECTIVES:To evaluate whether parental resolution of infants' congenital heart disease (CHD) diagnosis contributes to parent-infant bonding above and beyond psychological distress during hospitalization in a pediatric cardiac ICU (PCICU). The study focused on an understudied population of ultra-Orthodox Jews and Muslim-Arabs. DESIGN:A cross-sectional study. SETTING:PCICU; Hadassah University Medical Center, Israel. SUBJECTS:Fifty-eight parents (43% fathers; 72% ultra-Orthodox Jewish; 28% Muslim-Arab) of 37 infants (Mdays = 65.22; sd = 84.61) hospitalized after cardiac surgery or catheterization. INTERVENTIONS:None. MEASUREMENTS:Parents completed the Reaction to Diagnosis Questionnaire, the Postpartum Bonding Questionnaire, the Edinburgh Postnatal Depression Scale, and the posttraumatic stress disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and responded to an open-ended question about how infants' birth and medical condition affected their lives. Responses' coding included affect, crisis, growth, religious faith, and social support. Clinical data were extracted from infants' medical records. MAIN RESULTS:Resolution was associated with healthier bonding (r = -0.55; p < 0.001; higher bonding scores indicate impaired bonding). Depressive and PTSD symptoms correlated with poorer resolution (r = -0.47; p < 0.001 and r = -0.51; p < 0.001) and more impaired bonding (r = 0.44; p = 0.001 and r = 0.48; p < 0.001). Controlling for depressive and PTSD symptoms and diagnosis timing (prenatally vs. postpartum), resolution predicted healthier bonding (β = -0.35;i p = 0.032; ΔR2 = 0.08). Parents who expressed less negative affect and addressed personal growth in the open-ended question demonstrated better resolution and healthier bonding (p's < 0.029). Lack of reference to religious faith and framing the experience as a crisis were associated with more impaired bonding (p's < 0.037). CONCLUSIONS:Parental resolution of infants' CHD diagnosis may contribute to the formation of nurturing parent-infant relationships. Findings highlight the need for early psychological interventions for families facing a CHD diagnosis.
OBJECTIVE:To characterize piperacillin population pharmacokinetics (PK) in critically ill children with and without extracorporeal membrane oxygenation (ECMO) support and to optimize piperacillin dosing regimens to attain the PK target of 100% free time above minimum inhibitory concentration (fT > minimum inhibitory concentration). DESIGN:Post hoc secondary analysis of a two-center, population PK modeling and simulation study (registered at clinicaltrials.gov, NCT02539407). SETTINGS:PICUs at tertiary care centers, September 2015-November 2021. PATIENTS:Thirty-three children supported with ECMO and 50 non-ECMO control patients treated with piperacillin (± tazobactam). INTERVENTIONS:Administration of piperacillin at 300 mg/kg/d by continuous infusion or 75 mg/kg every 6 hours by intermittent infusion. MEASUREMENTS AND MAIN RESULTS:A one-compartment linear-elimination model described best the piperacillin data. Clearance was driven by body weight and estimated glomerular filtration rate (eGFR). In a typical 11-kg patient, ECMO circuit volume-to-weight ratio increased the volume of distribution by 34%. Monte Carlo simulations across eGFR strata (30-60, 60-90, 90-150, 150-200, 200-300 mL/min/1.73 m2) showed that a continuous infusion of 300 mg/kg/d allowed greater than or equal to 90% of target attainment in all groups. Patients with an eGFR greater than 200 mL/min/1.73 m2 required 400 mg/kg/d to have 90% of target attainment. CONCLUSIONS:Continuous infusion of 300 mg/kg/d piperacillin reliably achieves PK target across all renal-function ranges in children undergoing support with ECMO. Dose escalation to 400 mg/kg/d is required for augmented renal clearance (eGFR > 200 mL/min/1.73 m2).
OBJECTIVES:This study describes pediatric intermediate care unit (PIMCU) and patient-level characteristics and the association of different PIMCU models with key patient and hospitalization outcomes. DESIGN:Retrospective analysis of hospital admissions. SETTING:Registry data from six PIMCUs in the U.S. Pediatric Health Information Systems database. PATIENTS:All PIMCU hospitalizations from January 2022 to December 2023. INTERVENTIONS:None. MEASUREMENTS:Key demographic data, clinical characteristics, and outcomes were extracted. MAIN RESULTS:There were 8397 PIMCU encounters included from six units. All included PIMCUs had similar nurse staffing models and commonly cared for patients with respiratory illness. They all cared for a large percentage of patients with complex chronic conditions (CCC), ranging from 31.4% to 94.8%. Compared to high-complexity units (>75% of patients with a CCC; n = 2), mixed-complexity units (25-75% of patients with a CCC; n = 4) were more likely to source patients from the ED (45.1% vs. 20.2%) and prioritize high-acuity/low-complexity diagnoses. Mixed-complexity units had shorter hospital length of stays (median 3 vs. 8 d), lower readmission rates (11% vs. 20.8%), and lower ICU transfer rates (3.9% vs. 7.3%). CONCLUSIONS:Although all PIMCUs had similarities in nurse staffing, unit structure, and a focus on respiratory illness, we observed two PIMCU models: high-complexity and mixed-complexity units. These two unit types had distinct patient populations, reflecting different admissions practices, with high-complexity units more likely to admit ICU patients and technology-dependent patients. Units with higher CCC patient burden had significantly higher ICU transfer rates, readmission rates, and longer length of stay, associations that we hypothesize are a product of unit complexity. Further investigation is needed to understand the impact of these two PIMCU models on clinical outcomes and appropriate ICU-bed utilization. In the meantime, PIMCU patient composition could be considered when selecting unit benchmarks.
Introduction: We have explored the use of early biomarkers for the timely identification of acute kidney injury (AKI) in critically ill children. Design: Single-center cohort study. Setting: Tertiary medical-surgical PICU in Coimbra, Portugal. Patients: Pediatric patients admitted for longer than 48 hours over a 10-month period during 2024–2025. Interventions: None. Measurements and Results: Among 75 patients (55.3% male; median age 3.9 yr), 22 patients (29.3%) developed AKI (defined by Kidney Disease Improving Global Outcomes criteria) on day 1. On comparing those with or without AKI, urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels were elevated on day 1 ( p < 0.001), day 2 ( p = 0.003), and day 3 ( p = 0.013) in AKI patients. Cystatin-C (Cys-C) was only increased on day 1 ( p = 0.013). Shock ( p < 0.001) and vasoactive drug use ( p = 0.007) were more commonly present in AKI patients, who also had lower albumin ( p = 0.012), platelets ( p = 0.001), and bicarbonate level ( p = 0.032). AKI patients also had higher C-reactive protein (CRP; p = 0.018), procalcitonin ( p = 0.002), and lactate concentration ( p = 0.022). Shock and CRP were associated with greater odds (presented as odds ratio [OR] with 95% CI) of AKI, respectively as: OR, 6.10 (95% CI, 1.50–16.52); p = 0.002; and OR, 1.07 (95% CI, 1.00–1.12); p = 0.022; as well as day 1 Renal Angina Index (RAI; OR, 1.10 [95% CI, 1.03–1.17]; p = 0.005). On day 1, the discrimination performance (using the area under the receiver operating characteristic curve [AUC]) for AKI was good-to-excellent for, respectively: uNGAL, 0.847 (95% CI, 0.74–0.96); p value of less than 0.001; and blood urea nitrogen, 0.848 (95% CI, 0.75–0.95); p value of less than 0.001. Regarding uNGAL, the pretest probability of AKI was 29.3%, and the posttest probability of AKI on finding a uNGAL greater than 87 ng/mL rose to 73.1%, which leaves significant diagnostic uncertainty. Also, the day 1 RAI was an acceptable to good discriminator of the severity of AKI in those identified with AKI: AUC, 0.796 (95% CI, 0.60–0.99); p = 0.019. Conclusions: In our PICU cohort, day 1 uNGAL level greater than 87 ng/mL has good-to-excellent discriminative capacity in identifying AKI, but the diagnostic uncertainty of AKI remains.
