Safety of Extended Propofol Infusions in Critically Ill Pediatric Patients.

Introduction Propofol is a phenol agent with sedative and anesthetic properties that has been in use for decades, but with controversy in critically ill pediatric patients, given the concern for developing propofol-related infusion syndrome (PRIS). Our aim was to assess the risk of propofol infusions in the pediatric intensive care unit (PICU) at doses and durations greater than the described safety data and its associated covariables. Methods Retrospective cohort analysis of 173 patients receiving propofol in the PICU. Patients were categorized as receiving greater or less than 48-hour infusions. Demographic data and daily clinical variables were recorded for up to seven days post-infusion initiation or until infusion was stopped. Results In this descriptive analysis, patients' demographics were similar, but admission diagnosis was not. Both groups received high mean doses of propofol (>67 mcg/kg/min), with no cases of PRIS observed. The illness severity scores and the need for vasoactive infusion support varied between the cohorts, with higher illness scores and a higher percentage of subjects requiring vasoactive agents in the >48-hour cohort. Finally, there were no major differences in lactate levels or biochemical characteristics between the two groups. Conclusions This study provides pilot data in relation to the feasibility of propofol infusion in critically ill pediatric patients and underscores the need for a larger multicenter study to draw clinical recommendations.

Prognostic and Diagnostic Utility of Serum Biomarkers in Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) remains a major cause of morbidity and death among the pediatric population. Timely diagnosis, however, remains a complex task because of the lack of standardized methods that permit its accurate identification. The aim of this study was to determine whether serum levels of brain injury biomarkers can be used as a diagnostic and prognostic tool in this pathology. This prospective, observational study collected and analyzed the serum concentration of neuronal injury biomarkers at enrollment, 24h and 48h post-injury, in 34 children ages 0-18 with pTBI and 19 healthy controls (HC). Biomarkers included glial fibrillary acidic protein (GFAP), neurofilament protein L (NfL), ubiquitin-C-terminal hydrolase (UCH-L1), S-100B, tau and tau phosphorylated at threonine 181 (p-tau181). Subjects were stratified by admission Glasgow Coma Scale score into two categories: a combined mild/moderate (GCS 9-15) and severe (GCS 3-8). Glasgow Outcome Scale-Extended (GOS-E) Peds was dichotomized into favorable (≤4) and unfavorable (≥5) and outcomes. Data were analyzed utilizing Prism 9 and R statistical software. The findings were as follows: 15 patients were stratified as severe TBI and 19 as mild/moderate per GCS. All biomarkers measured at enrollment were elevated compared with HC. Serum levels for all biomarkers were significantly higher in the severe TBI group compared with HC at 0, 24, and 48h. The GFAP, tau S100B, and p-tau181 had the ability to differentiate TBI severity in the mild/moderate group when measured at 0h post-injury. Tau serum levels were increased in the mild/moderate group at 24h. In addition, NfL and p-tau181 showed increased serum levels at 48h in the aforementioned GCS category. Individual biomarker performance on predicting unfavorable outcomes was measured at 0, 24, and 48h across different GOS-E Peds time points, which was significant for p-tau181 at 0h at all time points, UCH-L1 at 0h at 6-9 months and 12 months, GFAP at 48h at 12 months, NfL at 0h at 12 months, tau at 0h at 12 months and S100B at 0h at 12 months. We concluded that TBI leads to increased serum neuronal injury biomarkers during the first 0-48h post-injury. A biomarker panel measuring these proteins could aid in the early diagnosis of mild to moderate pTBI and may predict neurological outcomes across the injury spectrum.

Ventilator Weaning and Terminal Extubation: Withdrawal of Life-Sustaining Therapy in Children. Secondary Analysis of the Death One Hour After Terminal Extubation Study.

OBJECTIVE: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not. DESIGN: Secondary analysis of multicenter retrospective cohort study. SETTING: Ten PICUs in the United States between 2009 and 2021. PATIENTS: Nine hundred thirteen patients 0-21 years old who died after WLST. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality). CONCLUSIONS: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation.

Cerebral venous sinus thrombosis and skull base osteomyelitis as manifestations of cat-scratch disease in a pediatric patient: A case report and literature review.

Cat-scratch disease (CSD) is caused by Bartonella henselae and usually presents with regional lymphadenopathy. Skull base osteomyelitis and cerebral venous sinus thrombosis are rarely reported, particularly in immunocompetent children. CSD should be considered in the differential diagnosis of any patient with persistent headaches in the setting of cat exposure.

Analgesia and Sedation at Terminal Extubation: A Secondary Analysis From Death One Hour After Terminal Extubation Study Data.

OBJECTIVES: To describe the doses of opioids and benzodiazepines administered around the time of terminal extubation (TE) to children who died within 1 hour of TE and to identify their association with the time to death (TTD). DESIGN: Secondary analysis of data collected for the Death One Hour After Terminal Extubation study. SETTING: Nine U.S. hospitals. PATIENTS: Six hundred eighty patients between 0 and 21 years who died within 1 hour after TE (2010-2021). MEASUREMENTS AND MAIN RESULTS: Medications included total doses of opioids and benzodiazepines 24 hours before and 1 hour after TE. Correlations between drug doses and TTD in minutes were calculated, and multivariable linear regression performed to determine their association with TTD after adjusting for age, sex, last recorded oxygen saturation/F io2 ratio and Glasgow Coma Scale score, inotrope requirement in the last 24 hours, and use of muscle relaxants within 1 hour of TE. Median age of the study population was 2.1 years (interquartile range [IQR], 0.4-11.0 yr). The median TTD was 15 minutes (IQR, 8-23 min). Forty percent patients (278/680) received either opioids or benzodiazepines within 1 hour after TE, with the largest proportion receiving opioids only (23%, 159/680). Among patients who received medications, the median IV morphine equivalent within 1 hour after TE was 0.75 mg/kg/hr (IQR, 0.3-1.8 mg/kg/hr) ( n = 263), and median lorazepam equivalent was 0.22 mg/kg/hr (IQR, 0.11-0.44 mg/kg/hr) ( n = 118). The median morphine equivalent and lorazepam equivalent rates after TE were 7.5-fold and 22-fold greater than the median pre-extubation rates, respectively. No significant direct correlation was observed between either opioid or benzodiazepine doses before or after TE and TTD. After adjusting for confounding variables, regression analysis also failed to show any association between drug dose and TTD. CONCLUSIONS: Children after TE are often prescribed opioids and benzodiazepines. For patients dying within 1 hour of TE, TTD is not associated with the dose of medication administered as part of comfort care.

Multicentric validation of a prognostic tool for predicting brain death following out-of-hospital cardiac arrest in children.

AIM: Out-of-hospital cardiac arrest (OHCA) in pediatric patients is associated with high rates of mortality and neurologic injury, with no definitive evidence-based method to predict outcomes available. A prognostic scoring tool for adults, The Brain Death After Cardiac Arrest (BDCA) score, was recently developed and validated. We aimed to validate this score in pediatric patients. METHODS: Retrospective cohort study of pediatric patients admitted to 5 PICUs after OHCA between 2011 and 2021. We extracted BDCA score elements for those who survived at least 24 hours but died as a result of their OHCA. We assessed score discrimination for the definitive outcome of brain death. Subgroup analysis was performed for infants < 12mo versus children ≥ 12mo, those who likely had brain death but had withdrawal of life sustaining therapy (WLST) prior to declaration, and by etiology and duration of arrest. RESULTS: 389 subjects were identified across 5 institutions, with 282 meeting inclusion criteria. 169 (59.9%) were formally declared brain dead; 58 (20.6%) had findings consistent with brain death but had withdrawal of life sustaining therapies prior to completion of formal declaration. Area under the receiver operating characteristic curve for the age ≥ 12mo cohort was 0.82 [95% CI 0.75, 0.90], which mirrored the adult subject AUCs of 0.82 [0.77, 0.86] and 0.81 [0.76, 0.86] in the development and validation cohorts. Scores demonstrated worse discrimination in the infant cohort (AUC = 0.61). CONCLUSIONS: The BDCA score shows promise in children ≥ 12mo following OHCA and may be considered in conjunction with existing multimodal prognostication approaches.

Imaging Findings in Neonatal and Pediatric Posterior Reversible Encephalopathy Syndrome (PRES) Differ From Adults.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is classically a reversible clinical radiographic syndrome associated with predominantly posterior leukoencephalopathy on neuroimaging. Magnetic resonance imaging (MRI) in adults demonstrates almost universally reversible parietal-occipital disease. We aimed to demonstrate in a cohort of children that "atypical" distribution is expected, acutely and on follow-up. METHODS: A retrospective review of children diagnosed with PRES from 2010 to 2018 at our children's hospital was performed. All had MRI at diagnoses, with over half having follow-up MRIs. Images were reviewed by a neuroradiology-trained pediatric radiologist for confirmation of findings consistent with PRES/identification of involved regions. RESULTS: Nineteen patients (aged zero to 18 years, 53% female) were included. Notably, two were infants. Nearly all had seizures; all had altered mental status and hypertension. Fifteen (84%) had MRI described as "atypical." Distribution of MRI findings was anatomically widespread, including nine with frontal findings. Twelve (63%) had follow-up imaging, of which approximately half remained abnormal. CONCLUSIONS: Pediatric PRES MRI findings were more often atypical at time of diagnosis. Vasogenic edema related to the acute phases of PRES typically resolved; however, follow-up imaging identified new volume loss in the areas affected. Two of our subjects were younger than 13 months, younger than typically described. Our series demonstrates that imaging distribution in children with PRES does not mirror the classical posterior, reversible distribution described in adults and continues the recent trend of identifying PRES in infants.

Changes in Critical Bronchiolitis After COVID-19 Lockdown.

Introduction In response to the coronavirus disease 2019 (COVID-19) pandemic, state and local governments implemented mitigation strategies, including lockdowns, thereby averting the typical fall/winter 2020 bronchiolitis season and reducing the incidence of respiratory viruses, such as respiratory syncytial virus (RSV). Florida implemented a strict lockdown from April 1, 2020, to April 30, 2020. The removal of lockdown precautions on September 25, 2020, was followed by an atypical out-of-season surge of bronchiolitis in April 2021. Anecdotally, this surge appeared to be associated with both increased poly-viral coinfections and disease severity. Objective To determine if the bronchiolitis out-of-season surge differed from historical seasonal case patterns. Methods A single-center retrospective cohort study of admissions to the pediatric intensive care unit (PICU) with International Classification of Diseases, Tenth Revision (ICD-10) codes of bronchiolitis, from December 9, 2019, to February 29, 2020 (12 weeks, pre-lockdown group or PreLD), was compared to March 29, 2021, to June 19, 2021 (12 weeks, post-lockdown group or PostLD). Variables used for comparison were gender, ethnicity, age, viral coinfections, viruses detected, PICU length of stay, hospital length of stay, mortality, maximum respiratory support needed, mechanical ventilation days, extracorporeal life support (ECLS) days, and severity of disease measured by Pediatric Logistic Organ Dysfunction-2 (PELOD-2) and Pediatric Sequential Organ Failure Assessment (pSOFA). Categorical data were analyzed using Fisher's exact test, and a t-test was used for continuous variables. A two-sided p < 0.05 was considered significant. Results A total of 135 subjects were analyzed from the two cohorts. More patients were admitted during the PostLD phase (87 vs. 48). The PostLD group had a higher age at admission (11.2 ± 12.3 vs. 6.6 ± 7.5, p = 0.0075), but there were no differences in gender or race/ethnicity. The PostLD group also exhibited a higher proportion of RSV infections (73 vs. 16, p < 0.0001) and poly-viral infections (p < 0.0001). Higher coronavirus OC43 (9 vs. 0, p = 0.0263) and parainfluenza types 1-4 (human parainfluenza virus (HPIV)) (19 vs. 1, p = 0.0017) detections, yet fewer human metapneumovirus (HMPV) detections (0 vs. 4, p = 0.0147), were observed PostLD. No differences were found in hospital length of stay, PICU length of stay, mortality, mechanical ventilation days, ECLS days, or severity of illness scores based on PELOD-2 or pSOFA scores. Conclusion In the bronchiolitis out-of-season surge, there were an increased number of admissions to the PICU. Those patients were older, and more likely to have RSV, as well as a coinfection with coronavirus OC43 or HPIV, yet less likely to have HMPV. No difference in length of stay or disease severity was demonstrated.

Bolus gastric feeds improve nutrition delivery to mechanically ventilated pediatric medical patients: Results of the COntinuous vs BOlus multicenter trial.

BACKGROUND: Comparison of bolus gastric feeding (BGF) vs continuous gastric feeding (CGF) with respect to timing and delivery of energy and protein in mechanically ventilated (MV) pediatric patients has not been investigated. We hypothesized that bolus delivery would shorten time to goal nutrition and increase the percentage of goal feeds delivered. METHODS: Multicenter, prospective, randomized comparative effectiveness trial conducted in seven pediatric intensive care units (PICUs). Eligibility criteria included patients aged 1 month to 12 years who were intubated within 24 h of PICU admission, with expected duration of ventilation at least 48 h, and who were eligible to begin enteral nutrition within 48 h. Exclusion criteria included patients with acute or chronic gastrointestinal pathology or acute surgery. RESULTS: We enrolled 158 MV children between October 2015 and April 2018; 147 patients were included in the analysis (BGF = 72, CGF = 75). Children in the BGF group were slightly older than those in the CGF; otherwise, the two groups had similar demographic characteristics. There was no difference in the percentage of patients in each group who achieved goal feeds. Time to goal feeds was shorter in the BGF group (hazard ratio 1.5 [CI 1.02-2.33]; P = 0.0387). Median percentage of target kilocalories (median kcal 0.78 vs 0.59; P ≤ 0.0001) and median percentage of protein delivered (median protein 0.77 vs 0.59; P ≤ 0.0001) was higher for BGF patients. There was no difference in serial oxygen saturation index between groups. CONCLUSION: Our study demonstrated shorter time to achieve goal nutrition via BGF compared with CGF in MV pediatric patients. This resulted in increased delivery of target energy and nutrition. Further study is needed in other PICU populations.

Emphysematous Cystitis Following Bone Marrow Transplant.

Emphysematous cystitis is an exceedingly rare complication of urinary tract infection in children and adults. Characterized by air within the bladder wall, this life-threatening condition most often impacts diabetic women. The inciting pathogen is typically Escherichia coli or Klebsiella pneumoniae, though many other organisms have also been reported. Diagnosis is most commonly made via computed tomography scan; however, plain radiographs have also been described to be diagnostic. Medical management is the mainstay of therapy, consisting of bladder decompression and treatment of the underlying infection. Urologic surgery is required in 10% of cases. We report a 10-year-old child with a recent history of bone marrow transplantation complicated by gut-associated graft-versus-host disease who was diagnosed with emphysematous cystitis following a change in his abdominal pain.