Etiology and clinical course of severe and extreme thrombocytosis in children: a retrospective single-center study.

The aim of this study was to describe the etiology and clinical course in children with severe thrombocytosis (ST, platelet counts > 900 × 109/L) and extreme thrombocytosis (ET, platelet counts > 1000 × 109/L) in a tertiary pediatric hospital. Patients aged 0-18 years with platelet counts over 900 × 109/L who were admitted to our hospital were analyzed. Thrombocytosis was defined as a platelet count exceeding 450 × 109/L. Thrombosis was diagnosed based on computed tomography scans or ultrasound findings. Potential factors associated with the development of extreme thrombocytosis were identified using logistic regression models. Only one (0.8%) out of the 120 patients identified with ST (n = 61) and ET (n = 59) had primary thrombocytosis. The most common underlying condition was congenital heart disease (26.7%), followed by Kawasaki disease (16.7%). With the exception of the hemoglobin level, no major differences were found for the baseline characteristics between the ST and ET groups. A lower hemoglobin level (< 10.0 g/dL) at the onset of thrombocytosis was identified as a predictor for ET development (adjusted odds ratio 2.73, 95% confidence interval 1.18-6.28). Overall, 56 of 120 (46.7%) patients received aspirin therapy. Venous thrombosis occurred in one (0.8%) patient. CONCLUSIONS: We found a low proportion of primary thrombocytosis and a low incidence of thrombosis in children with ST and ET. Our results suggest that pediatric ST and ET may share common characteristics and may have features that are distinct from those in adults. WHAT IS KNOWN: • Secondary thrombocytosis is a frequent finding in children. • Adult extreme thrombocytosis has been found to be associated with primary thrombocytosis. WHAT IS NEW: • There were no major differences in the baseline characteristics between children with severe and extreme thrombocytosis. • The incidence of thrombosis was markedly low in both severe and extreme thrombocytosis groups.

Elevated cerebrospinal fluid neuronal injury biomarkers within 24 hours of onset in infection-triggered acute encephalopathy compared to complex febrile seizures.

OBJECTIVE: This study aimed to measure and compare cerebrospinal fluid neuronal injury biomarkers in the acute phase of complex febrile seizure (CFS) and infection-triggered acute encephalopathy (AE). Furthermore, we determined the pathogenesis of AE with biphasic seizures and late reduced diffusion (AESD). METHODS: Pediatric patients with febrile status epilepticus who visited Hyogo Prefectural Kobe Children's Hospital from November 1, 2016, to December 31, 2022, and whose cerebrospinal fluid samples were collected within 24 h of neurological symptom onset were included. Patients were classified as having CFS or infection-triggered AE according to their definitions. Patients with AE were further categorized into AESD or unclassified AE. Cerebrospinal fluid biomarkers (neuron-specific enolase, growth differentiation factor 15 [GDF-15], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein, and tau protein were measured and compared among the groups. RESULTS: Total of 63 patients (45 with CFS and 18 with AE) were included. Among the AE patients, nine were classified as having AESD and nine as having unclassified AE. S100B levels were significantly higher in patients with AESD than in patients with CFS (485 pg/ml vs. 175.3 pg/ml) and were even higher in patients with AESD and neurological sequelae (702.4 pg/ml). GDF-15 levels were significantly elevated in patients with AE compared to patients with CFS (85.8 pg/ml vs. 23.6 pg/ml). CONCLUSIONS: The elevation of S100B suggests that activated astrocytes may be closely associated with the early pathology of AESD. Elevated GDF-15 levels in infection-triggered AE suggest the activation of defense mechanisms caused by stronger neurological injury.

Lung-Protective Ventilation for Pediatric Acute Respiratory Distress Syndrome: A Nonrandomized Controlled Trial.

OBJECTIVES: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS. DESIGN: Multicenter prospective before-and-after comparison design study. SETTING: Twenty-one PICUs. PATIENTS: Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation. INTERVENTIONS: The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to F io2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets. MEASUREMENTS AND MAIN RESULTS: There were 285 of 693 (41·1%) and 408 of 693 (58·9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0·001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/F io2 combinations were associated with reduced mortality. CONCLUSIONS: Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence.

Comparison of paediatric basic life support guidelines endorsed by member councils of Resuscitation Council of Asia.

Background: Paediatric cardiac arrest outcomes, especially for infants, remain poor. Due to different training, resource differences, and historical reasons, paediatric cardiac arrest algorithms for various Asia countries vary. While there has been a common basic life support algorithm for adults by the Resuscitation Council of Asia (RCA), there is no common RCA algorithm for paediatric life support.We aimed to review published paediatric life support guidelines from different Asian resuscitation councils. Methods: Pubmed and Google Scholar search were performed for published paediatric basic and advanced life support guidelines from January 2015 to June 2023. Paediatric representatives from the Resuscitation Council of Asia were sought and contacted to provide input from September 2022 till June 2023. Results: While most of the components of published paediatric life support algorithms of Asian countries are similar, there are notable variations in terms of age criteria for recommended use of adult basic life support algorithms in the paediatric population less than 18 years old, recommended paediatric chest compression depth targets, ventilation rates post-advanced airway intra-arrest, and first defibrillation dose for shockable rhythms in paediatric cardiac arrest. Conclusion: This was an overview and mapping of published Asian paediatric resuscitation algorithms. It highlights similarities across paediatric life support guidelines in Asian countries. There were some differences in components of paediatric life support which highlight important knowledge gaps in paediatric resuscitation science. The minor differences in the paediatric life support guidelines endorsed by the member councils may provide a framework for prioritising resuscitation research and highlight knowledge gaps in paediatric resuscitation.

Annual patterns in the outcomes and post-arrest care for pediatric out-of-hospital cardiac arrest: A nationwide multicenter prospective registry in Japan.

AIM: Out-of-hospital cardiac arrest (OHCA) has a poor prognosis in children; however, the annual patterns of prognosis and treatment have not been fully investigated. METHODS: From the Japanese Association for Acute Medicine OHCA registry, a multicenter prospective observational registry in Japan, we identified pediatric patients (zero to 17 years old) between June 2014 and December 2019. The primary outcome was one-month survival. We investigated the annual patterns in patient characteristics, treatment, and one-month prognosis. RESULTS: During the study period, 1188 patients were eligible for analysis. For all years, the zero-year-old group accounted for a large percentage of the total population (between 30% and 40%). There were significant increases in the rates of bystander-initiated cardiopulmonary resuscitation (CPR; from 50.6% to 62.3%, p = 0.003), dispatcher instructions (from 44.7% to 65.7%, p = 0.001), and adrenaline administration (from 2.4% to 6.9%, p = 0.014) over time, whereas the rate of advanced airway management decreased significantly (from 17.7% to 8.8%, p = 0.003). The odds ratios for one-month survival adjusted for potential resuscitation factors also did not change significantly (from 7.1% to 10.3%, adjusted odds ratio for one-year increment = 0.98, confidence interval: 0.86-1.11). CONCLUSION: Despite an increase in the rate of bystander-initiated CPR and pre-hospital adrenaline administration, there was no significant change in one-month survival.

Treatment optimization by monitoring vancomycin concentration in the serum and cerebrospinal fluid in a child with cystoperitoneal shunt-related infection caused by methicillin-resistant Staphylococcus aureus: a case report and literature review.

BACKGROUND: Cerebral ventricular shunt infections caused by methicillin-resistant Staphylococcus aureus (MRSA), especially strains with elevated minimum inhibitory concentration (MIC) values, have a poor prognosis. Monitoring serum vancomycin (VCM) levels with therapeutic drug monitoring and maintaining high VCM concentrations in the cerebrospinal fluid (CSF) are critical to treatment success. However, there have been a few reports about the CSF penetration and the pharmacokinetics of VCM in children. CASE PRESENTATION: Here, we report the case of a pediatric patient with cysto-peritoneal shunt-related meningitis caused by MRSA with an MIC of 2 µg/mL. The adequate VCM concentration was maintained by monitoring the VCM concentration in the CSF via the external ventricular drain, and frequent blood taking was avoided. VCM showed a good CSF penetration in our patient, and she was discharged without complications. DISCUSSION: Therapeutic drug monitoring of VCM concentration in the CSF may result in successful treatment even if MRSA shows a higher MIC. Therapeutic drug monitoring of VCM concentration in the CSF may also reduce the side effects.

Safe administration of sotrovimab to a COVID-19 patient with acute phase type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) and poor glycemic control are risk factors for severe coronavirus disease 2019 (COVID-19). Sotrovimab can treat mild-to-moderate COVID-19 in patients at a high risk of progression to severe COVID-19. However, its safety and efficacy in T1DM patients remain to be elucidated. We report the case of a 12-yr-old patient who was treated with sotrovimab for COVID-19 immediately after treatment for diabetic ketoacidosis (DKA) due to new-onset T1DM. He presented with nausea and sore throat and was diagnosed with severe DKA and COVID-19. A productive cough and sputum developed after admission. On the 3rd day of admission, the DKA resolved, and sotrovimab was administered to prevent exacerbation of COVID-19. Although the blood glucose levels increased after the administration of sotrobimab, there was no recurrence of DKA. Hyperglycemia may be a sotrovimab-related adverse event in T1DM patients. Nevertheless, the benefits of sotrovimab treatment may far outweigh the potential risks. Thus, sotrovimab was considered safe for patients with T1DM immediately after treatment of severe DKA.

Early metabolic derangements and unfavorable outcomes in pediatric traumatic brain injury: a retrospective multi-center cohort study.

Background: To study the association in moderate and severe pediatric traumatic brain injury (TBI) between hyperglycemia, hyperlactatemia, acidosis and unfavorable outcome, as assessed by Pediatric Cerebral Performance Category (PCPC) on discharge from the pediatric intensive care unit (PICU). Methods: Children <16 years old with TBI and Glasgow Coma Scale (GCS) ≤13 in an Asian multi-center PICU TBI cohort from January 2014 to October 2017 were included in this study. We defined unfavorable outcome as PCPC ≥3-moderate disability, severe disability, vegetative state, and death. We performed logistic regression to investigate the association between metabolic changes with unfavorable outcome. We divided hyperglycemia (glucose >11.1 mmol/L) during PICU admission into early-onset (within 24 h), late-onset (beyond 48 h) and persistent (throughout first 72 h). Results: Among the 305 children analyzed, 136 (44.6%) had unfavorable outcome. Children with unfavorable outcome were more likely to have early hyperglycemia (75/136, 55.1% vs. 33/169, 19.5%; P<0.001), high lactate levels >2.0 mmol/L (74/136, 54.4% vs. 56/169, 32.5%; P<0.001) and initial acidosis (85/136, 62.5% vs. 78/169, 56.1%; P=0.003) compared to those with favorable outcome. After adjusting for gender, GCS ≤8 and presence of polytrauma, early hyperglycemia [adjusted odds ratio (aOR) =3.68, 95% CI: 2.12-6.39, P<0.001] and late hyperglycemia (aOR =13.30, 95% CI: 1.64-107.8, P=0.015] were independently associated with unfavorable outcome. All children with persistent hyperglycemia died. Conclusions: We described unfavorable outcome in pediatric TBI especially with persistent hyperglycemia. Future trials should investigate the causal relationship between glycemic trends, early intervention and outcome in this cohort.

Clinical and laboratory characteristics of complex febrile seizures in the acute phase: a case-series study in Japan.

BACKGROUND: Patients with complex febrile seizures (CFS) often display abnormal laboratory results, unexpectedly prolonged seizures, and/or altered consciousness after admission. However, no standardized values have been established for the clinical and laboratory characteristics of CFS in the acute phase, making the management of CFS challenging. This study aimed to determine the clinical and laboratory characteristics of children with CFS during the acute phase. In particular, the duration of impaired consciousness and the detailed distribution of blood test values were focused. METHODS: We retrospectively reviewed medical records of a consecutive pediatric cohort aged 6-60 months who were diagnosed with CFS and admitted to Kobe Children's Hospital between October 2002 and March 2017. During the study period, 486 seizure episodes with confirmed CFS were initially reviewed, with 317 seizure episodes included in the analysis. Detailed clinical and laboratory characteristics were summarized. RESULTS: Among 317 seizure episodes (296 children with CFS), 302 required two or fewer anticonvulsants to be terminated. In 296 episodes showing convulsive seizures, median seizure duration was 30.5 min. The median time from onset to consciousness recovery was 175 min. Impaired consciousness lasting > 6, 8, and 12 h was observed in 13.9%, 7.6%, and 1.9% patients with CFS, respectively. Additionally, the distribution of aspartate aminotransferase, lactate dehydrogenase, creatinine, and glucose were clarified with 3, 10, 50, 90, and 97 percentile values. CONCLUSION: This study detailed the clinical and laboratory findings of acute-phase CFS using the data of the largest 15-year consecutive cohort of children with CFS. These results provide important information for appropriate acute management of CFS.

Time course of serum cytokine level changes within 72 h after onset in children with acute encephalopathy and febrile seizures.

BACKGROUND: Cytokine levels have been measured in acute encephalopathy (AE) to determine its pathology or as a diagnostic biomarker to distinguish it from febrile seizures (FS); however, the dynamics of cytokine level changes have not yet been fully captured in these two neurological manifestations. Thus, we aimed to explore the time course of serum cytokine level changes within 72 h after onset in AE and FS. METHODS: We retrospectively measured cytokine level in residual serum samples at multiple timepoints in seven children whose final diagnoses were AE or FS. RESULTS: The levels of 13 cytokines appeared to increase immediately after onset and peaked within 12-24 h after onset: interleukin (IL)-1ß, IL-4 IL-5, IL-6, IL-8, IL-10, IL-17, eotaxin, fibroblast growth factor, granulocyte colony-stimulating factor, interferon gamma, interferon-inducible protein-10, and macrophage chemoattractant protein-1. There were no dynamic changes in the levels of three cytokines (IL-1 receptor agonist, macrophage inflammatory protein-1α, and platelet-derived growth factor-bb) 72 h after onset. Levels of some cytokines decreased to around control levels within 48 h after onset: IL-1ß, IL-4, IL-5, IL-17, fibroblast growth factor, and interferon gamma. The levels of most cytokines appeared to be higher in AE, especially in hemorrhagic shock encephalopathy syndrome, than in FS. CONCLUSIONS: Cytokine levels in both AE and FS change dynamically, such as the levels of several cytokines increased within a few hours after onset and decreased at 12-24 h after onset. Therefore, it will be desirable to make clinical decisions regarding the administration of anti-inflammatory therapy in 24 h after onset in AE.

Machine learning predicts blood lactate levels in children after cardiac surgery in paediatric ICU.

BACKGROUND: Although serum lactate levels are widely accepted markers of haemodynamic instability, an alternative method to evaluate haemodynamic stability/instability continuously and non-invasively may assist in improving the standard of patient care. We hypothesise that blood lactate in paediatric ICU patients can be predicted using machine learning applied to arterial waveforms and perioperative characteristics. METHODS: Forty-eight post-operative children, median age 4 months (2.9-11.8 interquartile range), mean baseline heart rate of 131 beats per minute (range 33-197), mean lactate level at admission of 22.3 mg/dL (range 6.3-71.1), were included. Morphological arterial waveform characteristics were acquired and analysed. Predicting lactate levels was accomplished using regression-based supervised learning algorithms, evaluated with hold-out cross-validation, including, basing prediction on the currently acquired physiological measurements along with those acquired at admission, as well as adding the most recent lactate measurement and the time since that measurement as prediction parameters. Algorithms were assessed with mean absolute error, the average of the absolute differences between actual and predicted lactate concentrations. Low values represent superior model performance. RESULTS: The best performing algorithm was the tuned random forest, which yielded a mean absolute error of 3.38 mg/dL when predicting blood lactate with updated ground truth from the most recent blood draw. CONCLUSIONS: The random forest is capable of predicting serum lactate levels by analysing perioperative variables, including the arterial pressure waveform. Thus, machine learning can predict patient blood lactate levels, a proxy for haemodynamic instability, non-invasively, continuously and with accuracy that may demonstrate clinical utility.

Application of adult prehospital resuscitation rules to pediatric out of hospital cardiac arrest.

BACKGROUND: Prehospital termination of resuscitation (TOR) rules can be recommended for adults with out-of-hospital cardiac arrests (OHCAs). This study aimed to investigate whether adult basic life support (BLS) and advanced life support (ALS) TOR rules can predict neurologically unfavorable one-month outcome for pediatric OHCA patients. METHODS: From a nationwide population-based observational cohort study, we extracted data of consecutive pediatric OHCA patients (0-17 years old) from January 1, 2005, to December 31, 2011. The BLS TOR rule has three criteria, whereas the ALS TOR rule includes two additional criteria. We selected pediatric OHCA patients that met all criteria for each TOR rule and calculated the specificity and positive predictive value (PPV) of each TOR rule for identifying pediatric OHCA patients who did not have neurologically favorable one-month outcome. RESULTS: Of the 12,740 pediatric OHCA patients eligible for the evaluation of the BLS TOR rule, 10,803 patients met the BLS TOR rule, with a specificity of 0.785 and a PPV of 0.987 for predicting a lack of neurologically favorable one-month survival. Of the 2,091 for the ALS TOR rule, 381 patients met the ALS TOR rule, with a specificity of 0.986 and a PPV of 0.997 for predicting neurologically unfavorable one-month outcome. CONCLUSIONS: The adult BLS and ALS TOR rules had a high PPV for predicting pediatric OHCA patients without a neurologically favorable survival at one month after onset.

Changes Adopted in Asian Pediatric Hospitals during the COVID-19 Pandemic: A Report from the Pediatric Acute and Critical Care COVID-19 Registry of Asia.

There is wide variation in the overall clinical impact of novel coronavirus disease 2019 (COVID-19) across countries worldwide. Changes adopted pertaining to the management of pediatric patients, in particular, the provision of respiratory support during the COVID-19 pandemic is poorly described in Asia. We performed a multicenter survey of 20 Asian pediatric hospitals to determine workflow changes adopted during the pandemic. Data from centers of high-income (HIC), upper middle income (UMIC), and lower middle income (LMIC) countries were compared. All 20 sites over nine countries (HIC: Japan [4] and Singapore [2]; UMIC: China [3], Malaysia [3] and Thailand [2]; and LMIC: India [1], Indonesia [2], Pakistan [1], and Philippines [2]) responded to this survey. This survey demonstrated substantial outbreak adaptability. The major differences between the three income categories were that HICs were (1) more able/willing to minimize use of noninvasive ventilation or high-flow nasal cannula therapy in favor of early intubation, and (2) had greater availability of negative-pressure rooms and powered air-purifying respirators. Further research into the best practices for respiratory support are warranted. In particular, innovation on cost-effective measures in infection control and respiratory support in the LMIC setting should be considered in preparation for future waves of COVID-19 infection.

Outcomes of Pediatric Patients in Secondary Transport to Tertiary Hospital: A Retrospective Observational Study.

OBJECTIVES: Emergency medical service (EMS) providers play an important role in determining which hospital to choose. To date, there is no evidence-based guideline to support their decisions, except for major trauma cases. Secondary transport is considered when a patient needs further investigation or treatment after primary transport, but this can delay treatment and put patients at unnecessary risk. The objective of this study was to investigate the outcomes of pediatric secondary transport patients to tertiary hospitals. METHODS: This was a citywide population-based observational study conducted in Kobe, Japan. We reviewed the EMS registry to identify secondary transport patients younger than 19 years and investigated their clinical characteristics. We excluded cases of unknown hospital destinations, nontransported cases, and major trauma patients who followed a different protocol for a hospital destination. The primary endpoint was the hospital outcome 12 hours after transport. Because there was no link between the EMS patient transport data and the hospital medical records, a probabilistic linkage was performed to obtain the hospital outcomes. Patients who required secondary transport were compared with patients transported directly to tertiary hospitals. RESULTS: A total of 13,720 pediatric patients were transported from the field by Kobe EMS between January 2013 and December 2015. Among them, 81 pediatric patients (0.6%) required secondary transport to tertiary hospitals within 24 hours of the primary transport, whereas a total of 3673 patients (27%) were transported directly to tertiary hospitals. Despite no apparent difference in prehospital severity, secondary transport patients were associated with higher hospitalization rates and a need for critical care compared with those who had direct transport. Seizure was the most common reason for the use of secondary transport, and 89% of the seizure patients were hospitalized after undergoing secondary transport; minor trauma was the second most common reason for the use of secondary transport, and 53% of the patients were hospitalized. CONCLUSIONS: In this study, the characteristics of the secondary transport patients and hospital outcomes revealed a heterogeneity in pediatric prehospital transport. It is recommended that the development of pediatric EMS destination guidelines cover children's diverse conditions. Further studies are required, and linkages between prehospital and hospital data will help promote a better understanding of appropriate hospital destinations.

The association between prehospital vital signs of children and their critical clinical outcomes at hospitals.

Vital signs are important for patient assessment, but little is known about interpreting those of children in prehospital settings. We conducted an observational study to investigate the association between prehospital vital signs of children and their clinical outcomes in hospitals. We plotted the data of patients with critical outcomes on published reference ranges, such as those of healthy children to evaluate the clinical relevance. Of the 18,493 children screened, 4477 transported to tertiary hospitals were included in the analysis. The outcomes 12 h after being transported to a tertiary hospital were as follows: deceased, 41; hospitalization with critical deterioration events, 65; hospitalization without critical deterioration events, 1086; returned home, 3090; and unknown, 195. The reference ranges of the heart rates (sensitivity: 57.7%, specificity: 67.5%) and respiratory rates (sensitivity: 54.5%, specificity: 67.7%) of healthy children worked best to detect the critical outcomes. Therefore, the reference ranges of healthy children were concluded to be suitable in prehospital settings; however, excessive reliance on vital signs carried potential risks due to their limited sensitivities and specificities. Future studies are warranted to investigate indicators with higher sensitivities and specificities.

Prognostic effects of treatment protocols for febrile convulsive status epilepticus in children.

BACKGROUND: Febrile status epilepticus is the most common form of status epilepticus in children. No previous reports compare the effectiveness of treatment strategies using fosphenytoin (fPHT) or phenobarbital (PB) and those using anesthetics as second-line anti-seizure medication for benzodiazepine-resistant convulsive status epilepticus (CSE). We aimed to examine the outcomes of various treatment strategies for febrile convulsive status epilepticus (FCSE) in a real-world setting while comparing the effects of different treatment protocols and their presence or absence. METHODS: This was a single-center historical cohort study that was divided into three periods. Patients who presented with febrile convulsive status epilepticus for ≥60 min even after the administration of at least one anticonvulsant were included. During period I (October 2002-December 2006), treatment was performed at the discretion of the attending physician, without a protocol. During period II (January 2007-February 2013), barbiturate coma therapy (BCT) was indicated for FCSE resistant to benzodiazepines. During period III (March 2013-April 2016), BCT was indicated for FCSE resistant to fPHT or PB. RESULTS: The rate of electroencephalogram monitoring was lower in period I than period II+III (11.5% vs. 85.7%, p<0.01). Midazolam was administered by continuous infusion more often in period I than period II+III (84.6% vs. 25.0%, p<0.01), whereas fPHT was administered less often in period I than period II+III (0% vs. 27.4%, p<0.01). The rate of poor outcome, which was determined using the Pediatric Cerebral Performance Category scale, was higher in period I than period II+III (23.1% vs. 7.1%, p=0.03). The rate of poor outcome did not differ between periods II and III (4.2% vs. 11.1%, p=0.40). CONCLUSIONS: While the presence of a treatment protocol for FCSE in children may improve outcomes, a treatment protocol using fPHT or PB may not be associated with better outcomes.