Novel Echocardiogram Analysis of Cardiac Dysfunction is Associated with Mortality in Pediatric Sepsis.

OBJECTIVES: The objective of our study was to semi-automatically generate echocardiogram indices in pediatric sepsis using novel algorithms and determine which indices were associated with mortality. We hypothesized that strain and diastolic indices would be most associated with mortality. DESIGN: Retrospective cohort study of children with sepsis from 2017-2022. Survivors and non-survivors were compared for echocardiogram indices. Multivariate Cox proportional hazard models were constructed for our primary outcome of in-hospital mortality. Linear regression was performed for secondary outcomes, which included multiple composite 28-day outcomes. RESULTS: Of the 54 patients in the study 9 (17%) died. Multiple echocardiogram indices of both right (RV) and left ventricles (LV) were associated with in-hospital mortality [RV GLS adjusted hazard ratio (aHR): 1.16 (1.03-1.29), p-value 0.011; RV global longitudinal early diastolic strain rate (GLSre) aHR:0.24 (0.07 to 0.75), p-value 0.014; LV GLSre aHR: 0.33 (0.11-0.97), p-value 0.044]. Impairment in GLS was associated with fewer ventilator-free days [RV GLS ß-coefficient: -0.47 (-0.84 to -0.10), p-value 0.013; LV GLS ß-coefficient -0.62 (-1.07 to -0.17), p-value 0.008], organ-support free days [RV GLS ß-coefficient: -0.49 (-0.87 to -0.11), p-value 0.013; LV GLS ß-coefficient: -0.64 (-1.10 to -0.17), p-value 0.008], and days free from ICU [RV GLS ß-coefficient: -0.42 (-0.79 to -0.05), p-value 0.026; LV GLS ß-coefficient:-0.58 (-1.03 to -0.13), p-value 0.012]. Systolic indices were not associated with mortality in this cohort. CONCLUSIONS: Our study demonstrates the feasibility of obtaining echocardiogram indices in a semi-automatic method using our algorithms. We showed that abnormal strain is associated with worse outcomes in a cohort of children with sepsis.

In Vivo Analysis of Tissue S-Nitrosothiols in Pediatric Sepsis.

S-nitrosothiols are endogenous, bioactive molecules. S-nitrosothiols are implicated in many diseases, including sepsis. It is currently cumbersome to measure S-nitrosothiols clinically. We have previously developed an instrument to measure tissue S-nitrosothiols non-invasively using ultraviolet light. We have performed a prospective case control study of controls and children with sepsis admitted to the PICU. We hypothesized that tissue S-nitrosothiols would be higher in septic patients than controls. Controls were patients with no cardiopulmonary instability. Cases were patients with septic shock. We measured S-nitrosothiols, both at diagnosis and after resolution of shock. A total of 44 patients were enrolled: 21 controls and 23 with sepsis. At baseline, the controls were younger [median age 5 years (IQR 0, 9) versus 11 years (IQR: 6, 16), p-value = 0.012], had fewer comorbidities [7 (33.3%) vs. 20 (87.0%), p-value < 0.001], and had lower PELOD scores [0 (IQR: 0, 0) vs. 12 (IQR: 11, 21), p-value < 0.001]. S-nitrosothiol levels were higher in sepsis cohort (1.1 ppb vs. 0.8 ppb, p = 0.004). Five patients with sepsis had longitudinal measures and had a downtrend after resolution of shock (1.3 ppb vs. 0.9 ppb, p = 0.04). We dichotomized patients based on S-nitrosothiol levels and found an association with worse clinical outcomes, but further work will be needed to validate these findings.

Objectified kidney ultrasound echogenicity and size metrics as potential predictors for kidney function in children.

BACKGROUND: Kidney echogenicity is typically determined subjectively but may have a quantifiable relationship to kidney function. Similarly, kidney length has been shown to correlate with kidney function. This study sought to quantify echogenicity using readily available software. Secondarily, we aimed to evaluate the correlation between quantified echogenicity and kidney length to the estimated glomerular filtration rate (eGFR) in children with acute kidney injury (AKI) and chronic kidney disease (CKD). METHODS: In a single-center retrospective observational study, echogenicity index (EI) was determined using a ratio of right kidney to liver mean pixel density. The kidney length ratio (KLR) was determined by the actual to predicted lengths of both kidneys. Both variables were correlated to eGFR using correlation analyses and predictive capacity was determined with receiver operating characteristic curve (ROC) analysis. RESULTS: Of 94 subjects, 46% (43/94) had AKI, 28% (26/95) had CKD and 26% (25/95) were controls. The higher the EI the lower the eGFR (r = - 0.46, p < 0.0001). EI between 1.0 and 1.1 predicted an eGFR < 90 ml/min/1.73m2 with an AUC of 0.71-0.78 while an EI between 1.1 and 1.2 predicted an eGFR < 60 ml/min/1.73m2 with AUC of 0.75-0.80. Overall, the larger the KLR the lower the eGFR (r = - 0.25, p 0.018). CONCLUSION: We have developed an accessible methodology to quantify kidney echogenicity. Overall, there was an inverse correlation between EI and eGFR in pediatric CKD and AKI. However, these correlations did not persist within subgroups which could be due to small sample size and heterogeneity of etiologies. Overall, KLR had a weaker correlation to eGFR, compared to EI. Despite these correlations, both EI and KLR had "fair" to "good" performance as a biomarker for an eGFR < 60 ml/min/1.73m2.

Risk Factors Associated With Development of Multiple-Organ Dysfunction Syndrome After Pediatric Drowning.

OBJECTIVE: This study aimed to describe a single-center experience of pediatric drowning and to investigate risk factors associated with the development of pediatric multiple-organ dysfunction syndrome (MODS) after drowning events. METHODS: A single-center retrospective case-control study was performed at a tertiary children's hospital examining patients aged 1 month to 25 years who were admitted to the pediatric intensive care unit after a drowning event. The study period was June 2016 to June 2021. Patients who developed MODS at day 1 of intensive care admission were compared with those who did not. RESULTS: A total of 48 patients with a median age of 2.3 years were included. Twenty-nine (60%) had MODS at 24 hours. Those with MODS at 24 hours were more likely to require cardiopulmonary resuscitation (CPR), required longer duration of CPR, and had longer submersion times; otherwise, there were no differences in baseline characteristics. Those who developed MODS at 24 hours had longer lengths of stays, longer lengths of mechanical ventilation, and higher mortality. Multiple admission parameters were evaluated based on MODS-free survival at 24 hours. On univariable analysis, patients without MODS-free survival at 24 hours had higher rates of CPR, higher blood glucose on admission, higher illness severity scores, higher lactates, and lower Glasgow Coma Scale scores. A multivariable model was constructed using risk factors at presentation that were significant on univariable analysis; blood glucose greater than 200 mg/dL was associated with decreased odds of MODS-free survival at 24 hours after controlling for CPR administration of greater than 5 minutes and body temperature. CONCLUSIONS: Development of MODS in pediatric drowning is associated with worse patient outcomes. Hyperglycemia was identified as a potentially modifiable risk factor for the development of MODS at 24 hours and could serve as a useful prognostic parameter in this unique patient population.

Outcomes of a respiratory therapist driven high flow nasal cannula management protocol for pediatric critical asthma patients.

INTRODUCTION: This study aimed to determine if a respiratory therapist (RT)-driven high flow nasal cannula (HFNC) protocol could decrease duration of HFNC use, pediatric intensive care unit (PICU) and hospital length of stay (LOS), and duration of continuous albuterol use in pediatric patients with critical asthma. METHODS: This was a quality improvement project performed at a quaternary academic PICU. Patients admitted to the PICU between 2 and 18 years of age with a diagnosis of asthma requiring continuous albuterol and HFNC were included. Implementation of an RT-driven HFNC protocol [Plan-Do-Study-Act (PDSA) 1] occurred in October 2017. Additional interventions included weaning continuous albuterol and HFNC simultaneously (PDSA 2; March 2019), adjusting HFNC wean rate (PDSA 3; July 2020), and a HFNC holiday (PDSA 4; October 2021). HFNC duration was the primary outcome. Secondary outcomes included LOS data and continuous albuterol duration. Noninvasive ventilation (NIV), invasive mechanical ventilation (IMV), and 7-day PICU and hospital readmission rates were used as balancing measures. RESULTS: A total of 410 patients were included. Patient demographics and adjunct therapy use did not differ among the groups. After PDSA 2, mean HFNC duration decreased (26.8-18.1 h). Mean PICU LOS decreased (41-31.8 h). Mean hospital LOS also decreased (86.5-68 h). These outcomes remained stable during PDSA 3 and 4. Continuous albuterol duration and NIV use were unchanged, while IMV use decreased. CONCLUSIONS: An RT-driven HFNC protocol led to decreased length of HFNC and PICU and hospital LOS for pediatric patients with critical asthma without an increase in adverse events.

A Quality Improvement Initiative to Reduce Unnecessary Screening Chest Radiographs in a Pediatric ICU.

BACKGROUND: The Critical Care Societies Collaborative included not ordering diagnostic tests at regular intervals as one of their Choosing Wisely initiatives. A reduction in unnecessary chest radiographs (CXRs) can help reduce exposure to radiation and eliminate health care waste. We aimed to reduce daily screening CXRs in a pediatric ICU (PICU) by 20% from baseline within 4 months of implementation of CXR criteria. METHODS: All intubated patients in the PICU were included in this quality improvement project. Patients with tracheostomies were excluded. We developed criteria delineating which patients were most likely to benefit from a daily screening CXR, and these criteria were discussed for each patient on rounds. Patients on extracorporeal membrane oxygenation, on high-frequency oscillatory ventilation, or on high support on conventional mechanical ventilation were included as needing a daily screening CXR. We tracked the percentage of intubated subjects receiving a screening CXR as an outcome measure. Unplanned extubations and the number of non-screening CXRs per intubated subject were followed as balancing measures. RESULTS: The percentage of intubated subjects receiving a daily screening CXR was reduced from 79% to 31%. There was no increase in frequency of unplanned extubations or number of non-screening CXRs. With an estimated subject charge of roughly $270 and hospital cost of $54 per CXR, this project led to an estimated $300,000 in patient charge savings and $60,000 in hospital cost savings. CONCLUSIONS: Adopting criteria to delineate which patients are most likely to benefit from screening CXRs can lead to a reduction in the percentage of intubated patients receiving screening CXRs without appearing to increase harm.

Noninvasive Ventilation Exposure Prior to Intubation in Pediatric Hematopoietic Cell Transplant Recipients.

BACKGROUND: Noninvasive ventilation (NIV) has become more studied in immunocompromised patients. However, it has not been studied in hematopoietic cell transplantation (HCT) recipients, who have higher mortality and higher pulmonary complication rates than other immunocompromised patients. This population may be prone to negative effects from this treatment modality. The aim of this study was to determine whether NIV use is associated with worse outcomes in this vulnerable patient population. METHODS: A secondary analysis of a retrospective multi-center database was performed. Twelve pediatric ICUs across the United States enrolled HCT subjects from 2009-2014 that were admitted to the pediatric ICU (PICU) with the diagnosis of acute respiratory failure. Subjects exposed to NIV prior to intubation were compared against those not exposed to NIV. Our primary outcome was all-cause mortality at 90 d; secondary outcomes included ventilator-free days (VFD) at 28 d and development of pediatric ARDS. Multivariable logistic and linear regression models were constructed using variables significant on univariable analysis. RESULTS: Two-hundred eleven subjects were included. Of these, 82 (39%) received NIV prior to intubation. Those that received NIV prior to intubation were older (13 vs 6 y, P < .001) and more commonly diagnosed with respiratory distress (90% vs 74%, P = .004). On multivariable analysis, NIV use prior to intubation was associated with a higher PICU mortality (hazard ratio 1.51 [95% CI 1.18-2.28], P = .02) and fewer VFD at 28 d (ß -3.50 [95% CI -6.09 to 0.91], P = .008). Those with NIV exposure prior to intubation also had higher rates of development of pediatric ARDS (95% vs 78%, P = .001). CONCLUSIONS: In this cohort of children post-HCT, NIV use prior to intubation was associated with worse outcomes. The benefits and risks of NIV in this patient population should be carefully evaluated prior to its use, and careful patient selection is crucial for its optimal utilization.

Association Between Continuous Kidney Replacement Therapy Clearance and Outcome in Pediatric Patients With Hyperammonemia Not Due to Inborn Error of Metabolism.

OBJECTIVES: To describe a single-center experience of pediatric patients with hyperammonemia not due to inborn errors of metabolism and determine the association between use of continuous kidney replacement therapy (CKRT) treatment and outcomes. DESIGN: Retrospective cohort study. SETTING: Tertiary-care children's hospital. PATIENTS: All children less than 21 years old admitted to the hospital with hyperammonemia defined as an elevated ammonia levels (>100 µmol/L) not due to inborn error of metabolism. INTERVENTIONS: None. MEASURES AND MAIN RESULTS: Of 135 children with hyperammonemia, the most common reason for admission was infection in 57 of 135 (42%), congenital heart disease in 20 of 135 (14%), and bone marrow transplantation in 10 of 135 (7%). The overall mortality was 61% (82 of 135), which increased with degree of hyperammonemia (17 of 23 [74%] in those with ammonia >250 µmol/L). After multivariable regression, hyperammonemia severity was not associated with mortality (aOR, 1.4; 95% CI, 0.92-2.1; p = 0.11). Of the 43 patients (32%) receiving CKRT, 21 were prescribed standard clearance and 22 high clearance. The most common indications for CKRT were fluid overload in 17 of 43 (42%) and acute kidney injury or uremia in 16 of 43 (37%). Mean CKRT duration was 13 days. There was no difference between standard and high clearance groups in risk of death (76% vs 86%; p = 0.39), cerebral edema on CT scan (19% vs 27%; p = 0.52), nor decrease in ammonia levels after 24 or 48 hours of CKRT ( p = 0.20, p = 0.94). Among those receiving CKRT, we failed to find an association between high clearance and decreased risk of death in multivariable analysis (aOR, 1.2; 95% CI, 0.64-2.3; p = 0.55). CONCLUSIONS: In our single-center retrospective study, we failed to find an association between clearance on CKRT and improved survival nor decreased cerebral edema on head imaging. In fact, we failed to find an association between ammonia level and mortality, after controlling for illness severity.

Photolytic Measurement of Tissue S-Nitrosothiols in Rats and Humans In Vivo.

S-nitrosothiols are labile thiol-NO adducts formed in vivo primarily by metalloproteins such as NO synthase, ceruloplasmin, and hemoglobin. Abnormal S-nitrosothiol synthesis and catabolism contribute to many diseases, ranging from asthma to septic shock. Current methods for quantifying S-nitrosothiols in vivo are suboptimal. Samples need to be removed from the body for analysis, and the S-nitrosothiols can be broken down during ex vivo processing. Here, we have developed a noninvasive device to measure mammalian tissue S-nitrosothiols in situ non-invasively using ultraviolet (UV) light, which causes NO release in proportion to the S-nitrosothiol concentration. We validated the assay in vitro; then, we applied it to measure S-nitrosothiols in vivo in rats and in humans. The method was sensitive to 0.5 µM, specific (did not detect other nitrogen oxides), and was reproducible in rats and in humans. This noninvasive approach to S-nitrosothiol measurements may be applicable for use in human diseases.

The association of postoperative dexmedetomidine with pain, opiate utilization, and hospital length of stay in children post-Chiari malformation decompression.

OBJECTIVE: The aim of this study was to determine the association of postoperative dexmedetomidine with markers of pain in children undergoing Chiari malformation decompression. The authors hypothesized that patients receiving dexmedetomidine postoperatively would have decreased cumulative opiate use. They further hypothesized that there would be no difference in median pain scores, outcomes, or medication adverse events. METHODS: An IRB-approved retrospective cohort study of patients undergoing Chiari malformation decompression from December 1, 2015, to December 31, 2018, was performed. Patients aged 0-21 years who underwent intradural Chiari malformation decompression at a single institution were included. Data for those who used dexmedetomidine postoperatively were compared with those who did not use dexmedetomidine. The primary outcome was cumulative opiate use throughout hospitalization. Secondary outcomes included pain scores, ancillary medication use, adverse events, hospital and ICU length of stay, readmission rates, and hospital cost. RESULTS: The authors reviewed the records of 172 patients who underwent Chiari malformation decompression. Of those patients, 86 received dexmedetomidine postoperatively and 86 did not. Demographics were not different between the groups. Patients who received dexmedetomidine postoperatively received more doses of dexamethasone and were also more frequently exposed to dexmedetomidine intraoperatively (p = 0.028). Patients who received dexmedetomidine postoperatively used fewer morphine equivalents during their admission (1.02 mg/kg vs 1.43 mg/kg, p = 0.003). The patients who received dexmedetomidine postoperatively also had lower median pain scores on postoperative day 0 (0 vs 2, p < 0.001), lower median pain scores throughout the entire admission (1 vs 2, p < 0.001), and lower maximum pain scores recorded (6 vs 8, p = 0.005). Adjusting for steroid dose number and intraoperative dexmedetomidine exposure, postoperative dexmedetomidine remained associated with lower opiate dosing, lower pain scores on postoperative day 0, lower scores throughout hospital stay, and lower maximum pain scores. Patients who received dexmedetomidine had shorter hospital lengths of stay by 19 hours (p < 0.001). There were no statistically significant differences in medication adverse events or hospital costs between the two groups. CONCLUSIONS: Postoperative dexmedetomidine use was associated with decreased opiate use, lower pain scores, and shorter hospital length of stay in this cohort. Dexmedetomidine may be considered as a safe adjuvant medication that may have opiate-sparing effects for this patient population.

The Use of a Kinetic Therapy Rotational Bed in Pediatric Acute Respiratory Distress Syndrome: A Case Series.

Patients with acute respiratory distress syndrome (ARDS) commonly have dependent atelectasis and heterogeneous lung disease. Due to the heterogenous lung volumes seen, the application of positive end expiratory pressure (PEEP) can have both beneficial and deleterious effects. Alternating supine and prone positioning may be beneficial in ARDS by providing more homogenous distribution of PEEP and decreasing intrapulmonary shunt. In pediatrics, the pediatric acute lung injury and consensus conference (PALICC) recommended to consider it in severe pediatric ARDS (PARDS). Manually prone positioning patients can be burdensome in larger patients. In adults, the use of rotational beds has eased care of these patients. There is little published data about rotational bed therapy in children. Therefore, we sought to describe the use of a rotational bed in children with PARDS. We performed a retrospective case series of children who utilized a rotational bed as an adjunctive therapy for their PARDS. Patient data were collected and analyzed. Descriptive statistical analyses were performed and reported. Oxygenation indices (OI) pre- and post-prone positioning were analyzed. Twelve patients with PARDS were treated with a rotational bed with minimal adverse events. There were no complications noted. Three patients had malfunctioning of their arterial line while on the rotational bed. Oxygenation indices improved over time in 11 of the 12 patients included in the study while on the rotational bed. Rotational beds can be safely utilized in pediatric patients. In larger children with PARDS, where it may be more difficult to perform a manual prone position, use of a rotational bed can be considered a safe alternative.

Emergency department utilisation and critical readmission in patients with Fontan circulation.

BACKGROUND: We aimed to conduct a multi-centre study characterising emergency department utilisation and critical readmissions experienced by children with Fontan circulation. METHODS: We conducted a retrospective review of children who underwent the Fontan operation at three institutions (i.e., centres A, B, and C) between 2009 and 2014, with follow-up through December 2015. Multi-variable analyses were performed to determine factors associated for emergency department utilisation within 1 year of surgery, emergency department utilisation at any time following surgery, or critical readmission (defined as admission to ICU, operating room, or cardiac catheterisation). RESULTS: We reviewed 297 patients, of which 147 patients (49%) had 607 emergency department encounters. Forty-six patients (15%) required 71 critical readmissions. Multi-variable analyses revealed centre C (p = 0.02) and post-operative hospitalisation ≥ 14 days (p = 0.03) to be significantly associated with emergency department utilisation within 1 year, whereas centre B (p < 0.001), post-operative hospitalisation ≥ 14 days (p = 0.002), and African-American/Black race (p = 0.04) were significantly associated with critical readmission. CONCLUSIONS: In this multi-centre study, nearly half of patients with Fontan circulation received emergency department care, often presenting with high disease acuity requiring readmission. Emergency department utilisation and need for critical readmission were independently influenced by the centre at which surgery was performed, prolonged post-operative hospitalisation, and racial background. These data could help guide quality improvement efforts aimed at reducing morbidity in this unique patient population.

Label-Free Time-of-Flight Secondary Ion Mass Spectrometry Imaging of Sulfur-Producing Enzymes inside Microglia Cells following Exposure to Silver Nanowires.

There are no methods sensitive enough to detect enzymes within cells, without the use of analyte labeling. Here we show that it is possible to detect protein ion signals of three different H2S-synthesizing enzymes inside microglia after pretreatment with silver nanowires (AgNW) using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Protein fragment ions, including the fragment of amino acid (C4H8N+ = 70 amu), fragments of the sulfur-producing cystathionine-containing enzymes, and the Ag+ ion signal could be detected without the use of any labels; the cells were mapped using the C4H8N+ amino acid fragment. Scanning electron microscopy imaging and energy-dispersive X-ray chemical analysis showed that the AgNWs were inside the same cells imaged by TOF-SIMS and transformed chemically into crystalline Ag2S within cells in which the sulfur-producing proteins were detected. The presence of these sulfur-producing cystathionine-containing enzymes within the cells was confirmed by Western blots and confocal microscopy images of fluorescently labeled antibodies against the sulfur-producing enzymes. Label-free TOF-SIMS is very promising for the label-free identification of H2S-contributing enzymes and their cellular localization in biological systems. The technique could in the future be used to identify which of these enzymes are most contributory.

Modification and Assessment of the Bedside Pediatric Early Warning Score in the Pediatric Allogeneic Hematopoietic Cell Transplant Population.

OBJECTIVES: To determine the validity of the Bedside Pediatric Early Warning Score system in the hematopoietic cell transplant population, and to determine if the addition of weight gain further strengthens the association with need for PICU admission. DESIGN: Retrospective cohort study of pediatric allogeneic hematopoietic cell transplant patients from 2009 to 2016. Daily Pediatric Early Warning Score and weights were collected during hospitalization. Logistic regression was used to identify associations between maximum Pediatric Early Warning Score or Pediatric Early Warning Score plus weight gain and the need for PICU intervention. The primary outcome was need for PICU intervention; secondary outcomes included mortality and intubation. SETTING: A large quaternary free-standing children's hospital. PATIENTS: One-hundred two pediatric allogeneic hematopoietic cell transplant recipients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 102 hematopoietic cell transplant patients included in the study, 29 were admitted to the PICU. The median peak Pediatric Early Warning Score was 11 (interquartile range, 8-13) in the PICU admission cohort, compared with 4 (interquartile range, 3-5) in the cohort without a PICU admission (p < 0.0001). Pediatric Early Warning Score greater than or equal to 8 had a sensitivity of 76% and a specificity of 90%. The area under the receiver operating characteristics curve was 0.83. There was a high negative predictive value at this Pediatric Early Warning Score of 90%. When Pediatric Early Warning Score greater than or equal to 8 and weight gain greater than or equal to 7% were compared together, the area under the receiver operating characteristic curve increased to 0.88. CONCLUSIONS: In this study, a Pediatric Early Warning Score greater than or equal to 8 was associated with PICU admission, having a moderately high sensitivity and high specificity. This study adds to literature supporting Pediatric Early Warning Score monitoring for hematopoietic cell transplant patients. Combining weight gain with Pediatric Early Warning Score improved the discriminative ability of the model to predict the need for critical care, suggesting that incorporation of weight gain into Pediatric Early Warning Score may be beneficial for monitoring of hematopoietic cell transplant patients.