The State of the Field of Pediatric Multimodality Neuromonitoring.

BACKGROUND: The use of multimodal neuromonitoring in pediatrics is in its infancy relative to adult neurocritical care. Multimodal neuromonitoring encompasses the amalgamation of information from multiple individual neuromonitoring devices to gain a more comprehensive understanding of the condition of the brain. It allows for adaptation to the changing state of the brain throughout various stages of injury with potential to individualize and optimize therapies. METHODS: Here we provide an overview of multimodal neuromonitoring in pediatric neurocritical care and its potential application in the future. RESULTS: Multimodal neuromonitoring devices are key to the process of multimodal neuromonitoring, allowing for visualization of data trends over time and ideally improving the ability of clinicians to identify patterns and find meaning in the immense volume of data now encountered in the care of critically ill patients at the bedside. Clinical use in pediatrics requires more study to determine best practices and impact on patient outcomes. Potential uses include guidance for targets of physiological parameters in the setting of acute brain injury, neuroprotection for patients at high risk for brain injury, and neuroprognostication. Implementing multimodal neuromonitoring in pediatric patients involves interprofessional collaboration with the development of a simultaneous comprehensive program to support the use of multimodal neuromonitoring while maintaining the fundamental principles of the delivery of neurocritical care at the bedside. CONCLUSIONS: The possible benefits of multimodal neuromonitoring are immense and have great potential to advance the field of pediatric neurocritical care and the health of critically ill children.

Implementation of a Pediatric Neurocritical Care Program for Children With Status Epilepticus: Adherence to Continuous Electroencephalogram Monitoring.

OBJECTIVES: To describe adherence to continuous electroencephalogram (cEEG) monitoring as part of a pediatric neurocritical care (PNCC) program for status epilepticus (SE). DESIGN: Retrospective review of pre- and postintervention cohorts. SETTING: A pediatric referral hospital. PATIENTS: Children admitted to the PICU for SE. INTERVENTIONS: We restructured the care delivery model to include a pediatric neurointensive care unit (neuro-ICU) and expanded the cEEG capacity. We created a criteria-based cEEG pathway. We provided education to all providers including the nursing staff. MEASUREMENTS AND MAIN RESULTS: The main outcomes were: 1) the percentages of children meeting American Clinical Neurophysiology Society (ACNS) criteria who underwent cEEG monitoring and 2) the time interval between PICU arrival and cEEG initiation. PICU admissions with the diagnosis of SE from May 2017 to December 2017 served as the baseline, which was compared with the same periods in 2018 to 2020 (PNCC era).There were 60 admissions in the pre-PNCC period (2017), 111 in 2018, 118 in 2019, and 108 in 2020. The percentages of admissions from each period that met ACNS criteria for cEEG monitoring were between 84% and 97%. In the pre-PNCC era, 22 of 52 (42%) admissions meeting ACNS criteria underwent cEEG monitoring. In the PNCC era, greater than or equal to 80% of the qualified admissions underwent cEEG monitoring (74/93 [80%] in 2018, 94/115 [82%] in 2019, and 87/101 [86%] in 2020). Compared with the pre-PNCC era, the neuro-ICU had a shorter interval between PICU arrival and cEEG initiation (216 min [141-1,444 min] vs 138 min [103-211 min]). CONCLUSIONS: The implementation of a PNCC program with initiatives in care delivery, allocation of resources, and education was associated with increased adherence to best care practices for the management of SE.

Fosphenytoin Population Pharmacokinetics in the Acutely Ill Pediatric Population.

OBJECTIVE: The purpose of this study is to describe the pharmacokinetics of phenytoin in pediatric patients receiving fosphenytoin. DESIGN: Retrospective, population pharmacokinetic analysis. SETTING: Emergency department or PICU of a large tertiary care children's hospital. PATIENTS: Patients less than 19 years old who received fosphenytoin in the PICU or emergency center for treatment of seizures from January 2011 to June 2017 were included. INTERVENTIONS: Population pharmacokinetic analysis was performed with NONMEM v7.3 (Icon Plc, Dublin, Ireland). Simulation was performed to determine optimal loading dose and maintenance dosing regimens. MEASUREMENTS AND MAIN RESULTS: A total of 536 patients (55.4% male; median age, 3.4 yr [interquartile range, 0.92-8.5 yr]) met study criteria. Fosphenytoin was administered at median 15.1 mg/kg/dose (interquartile range, 6.3-20.7 mg/kg/dose). Mean serum concentrations of 17.5 ± 7.8 mg/L were at a median 4.2 hours (interquartile range, 2.5-7.8 hr) after a dose. A pharmacokinetic model with two compartments, allometrically scaled fat-free mass on all parameters, and serum creatinine and concomitant phenobarbital use on clearance had the best fit. Simulation demonstrated that a 20 mg/kg loading dose followed by 6 mg/kg/dose every 8 hours had the greatest percentage of concentrations in the 10-20 mg/L range, with reduced doses to achieve therapeutic in patients with reduced kidney function. CONCLUSIONS: A loading dose of 20 mg/kg followed by 6 mg/kg/dose every 8 hours based on fat-free mass is a reasonable empiric strategy for attainment and maintenance of therapeutic trough concentrations. Concomitant phenobarbital use may increase clearance of phenytoin and fosphenytoin dose reductions should occur in patients with reduced kidney function.

Outcomes in Children Treated with Pentobarbital Infusion for Refractory and Super-Refractory Status Epilepticus.

BACKGROUND: Functional neurologic outcome for children with refractory and super-refractory status epilepticus has not been well defined. METHODS: Retrospective chart review including children age 0-17 years who received pentobarbital infusion from 2003 to 2016 for status epilepticus. Outcomes were defined in terms of mortality, need for new medical technology assistance at hospital discharge and functional neurologic outcome determined by pediatric cerebral performance category score (PCPC). Potential patient characteristics associated with functional neurologic outcome including age, sex, ethnicity, etiology of the status epilepticus, and duration of pentobarbital infusion were evaluated. RESULTS: Forty children met inclusion criteria. In-hospital mortality was 30% (12/40). Of survivors, 21% (6/28) returned to baseline PCPC while half (14/28) declined in function ≥ 2 PCPC categories at hospital discharge. 25% (7/28) of survivors required tracheostomy and 27% (7/26) required new gastrostomy. Seizures persisted at discharge for most patients with new onset status epilepticus while the majority of patients with known epilepsy returned to baseline seizure frequency. Etiology (p = 0.015), PCPC at admission (p = 0.0006), new tracheostomy (p = 0.012), and new gastrostomy tube (p = 0.012) were associated with increase in PCPC score ≥ 2 categories in univariable analysis. Duration of pentobarbital infusion (p = 0.005) and length of hospital stay (p = 0.056) were longer in patients who demonstrated significant decline in neurologic function. None of these variables maintained statistical significance when multiple logistic regression model adjusting for PCPC score at admission was applied. At long-term follow-up, 36% (8/22) of children demonstrated improvement in PCPC compared to discharge and 23% (5/22) showed deterioration including three additional deaths. CONCLUSIONS: Mortality in this population was high. The majority of children experienced some degree of disability at discharge. Despite prolonged pentobarbital infusion, there were cases of survival with good neurologic outcome.

Neurocritical care and neuromonitoring considerations in acute pediatric spinal cord injury.

Management of pediatric spinal cord injury (SCI) is an essential skill for all pediatric neurocritical care physicians. In this review, we focus on the evaluation and management of pediatric SCI, highlight a novel framework for the monitoring of such patients in the intensive care unit (ICU), and introduce advancements in critical care techniques in monitoring and management. The initial evaluation and characterization of SCI is crucial for improving outcomes as well as prognostication. While physical examination and imaging are the main stays of the work-up, we propose the use of somatosensory evoked potentials (SSEPs) and transcranial magnetic stimulation (TMS) for challenging clinical scenarios. SSEPs allow for functional evaluation of the dorsal columns consisting of tracts associated with hand function, ambulation, and bladder function. Meanwhile, TMS has the potential for informing prognostication as well as response to rehabilitation. Spine stabilization, and in some cases surgical decompression, along with respiratory and hemodynamic management are essential. Emerging research suggests that targeted spinal cerebral perfusion pressure may provide potential benefits. This review aims to increase the pediatric neurocritical care physician's comfort with SCI while providing a novel algorithm for monitoring spinal cord function in the ICU.

Feasibility of Achieving Nutritional Adequacy in Critically Ill Children with Critical Neurological Illnesses (CNIs)?-A Quaternary Hospital Experience.

The literature on the nutritional needs and outcomes of critically ill children is scarce, especially on those with critical neurological illnesses (CNIs). Current evidence shows a lower mortality in patients who achieve two-thirds of their nutritional needs during the first week of pediatric intensive care unit (PICU) admission. We hypothesized that achieving 60% of the recommended dietary intake during the first week of a PICU stay is not feasible in patients with CNI. We designed an observational retrospective cohort study where we included all index admissions to the PICU in our institution of children (1 month to 18 years) with CNI from January 2018 to June 2021. We collected patient demographics, anthropometric measures, and caloric and protein intake (enteral and parenteral) information during the first week of PICU admission. Goal adequacy for calories and protein was defined as [(intake/recommended) × 100] ≥ 60%. A total of 1112 patients were included in the nutrition assessment, 12% of whom were underweight (weight for age z score < -2). Of this group, 180 met the criteria for nutrition support evaluation. On the third day of admission, 50% of the patients < 2 years achieved caloric and protein goal adequacy, compared to 25% of patients > 2 years, with p-values of 0.0003 and 0.0004, respectively. Among the underweight patients, 60% achieved both caloric and protein goal adequacy by day 3 vs. 30% of non-underweight patients with p-values of 0.0006 and 0.002, respectively. The results show that achieving 60% of the recommended dietary intake by days 5 and 7 of admission was feasible in more than half of the patients in this cohort. Additionally, children who were evaluated by a clinical dietician during the first 48 h of PICU admission reached higher nutrition adequacy.

A Survey of Pediatric Neurocritical Care Fellowship Training in North America.

BACKGROUND: Pediatric neurocritical care (PNCC) has emerged as a field to care for children at the intersection of critical illness and neurological dysfunction. PNCC fellowship programs evolved over the past decade to train physicians to fill this clinical need. We aimed to characterize PNCC fellowship training infrastructure and curriculum in the United States and Canada. METHODS: Web-based survey of PNCC fellowship program leaders during November 2019 to January 2020. RESULTS: There were 14 self-identified PNCC fellowship programs. The programs were supported by Child Neurology and/or Pediatric Critical Care Medicine divisions at tertiary/quaternary care institutions. Most programs accepted trainees who were board-eligible or board-certified in child neurology or pediatric critical care medicine. Clinical training consisted mostly of rotations providing PNCC consultation (n = 13) or as a provider on the pediatric intensive care unit-based neurointensive care team (n = 2). PNCC-specific didactics were delivered at most institutions (n = 13). All institutions provided training in electroencephalography use in the intensive care unit and declaration of death by neurological criteria (n = 14). Scholarly activity was supported by most programs, including protected time for research (n = 10). CONCLUSIONS: We characterized PNCC fellowship training in the United States and Canada, which in this continuously evolving field, lays the foundation for exploring standardization of training going forward.

Creating a Robust Community of Practice as a Foundation for the Successful Development of a Pediatric Neurocritical Care Program.

BACKGROUND: There has been a growing impetus for developing pediatric neurocritical care (PNCC) programs to improve care delivery for children with critical neurological conditions. We sought to develop a unique PNCC program using the concept of Community of Practice (CoP). METHODS: This is a process improvement project in an academic Children's Hospital. Using CoP framework (domain, community, practice), we created a domain of PNCC with a stated vision and formal organizational structure, a core community of intensivists and neurologists interested in PNCC, and a standardized practice approach by establishing core competencies for PNCC and implementing practice guidelines. RESULTS: We evaluated the program through the Four-Frame Model of Organizational Theory and Behavior (structural, human resource, political, symbolic) and by the Neurocritical Care Society's (NCS's) standards for a Level I Neurocritical Care Unit (Neuro-ICU). Structural frame included opening a pediatric Neuro-ICU, identifying PNCC leaders across specialties, and developing a multidisciplinary care delivery model. Human resource frame included forming physician and nurse groups with a primary role in PNCC and ongoing education through workshops, lecture series, and certification. Politically, program implementation was tailored to each department gaining institution-wide support for program initiatives. Symbolically, the PNCC program highlighted the vision to advance knowledge and best practices. Our program met 232 of 252 (92%) proposed NCS standards. CONCLUSIONS: The CoP as the foundation for program development has enabled us to achieve the majority of standards proposed by NCS for a Level I Neuro-ICU. The generalizability of these frameworks may facilitate the development of a PNCC program for other institutions.

Pharmacologic and Acute Management of Spinal Cord Injury in Adults and Children.

Purpose of Review: This review provides guidance for acute spinal cord injury (SCI) management through an analytical assessment of the most recent evidence on therapies available for treating SCI, including newer therapies under investigation. We present an approach to the SCI patient starting at presentation to acute rehabilitation and prognostication, with additional emphasis on the pediatric population when evidence is available. Recent Findings: Further studies since the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) demonstrated a potential functional outcome benefit with ultra-early surgical intervention ≤ 8 h post-SCI. Subsequent analysis of the National Acute Spinal Cord Injury Study (NASCIS) II and NASCIS III trials have demonstrated potentially serious complications from intravenous methylprednisolone with limited benefit. Newer therapies actively being studied have demonstrated limited or no benefit in preclinical and clinical trials with insufficient evidence to support use in acute SCI treatment. Summary: Care for SCI patients requires a multi-disciplinary team. Immediate evaluation and management are focused on preventing additional injury and restoring perfusion to the affected cord. Rapid assessment and intervention involve focused neurological examination, targeted imaging, and surgical intervention when indicated. There are currently no evidence-based recommendations for pathomechanistically targeted therapies.

A Survey of Neuromonitoring Practices in North American Pediatric Intensive Care Units.

BACKGROUND: Neuromonitoring is the use of continuous measures of brain physiology to detect clinically important events in real-time. Neuromonitoring devices can be invasive or non-invasive and are typically used on patients with acute brain injury or at high risk for brain injury. The goal of this study was to characterize neuromonitoring infrastructure and practices in North American pediatric intensive care units (PICUs). METHODS: An electronic, web-based survey was distributed to 70 North American institutions participating in the Pediatric Neurocritical Care Research Group. Questions related to the clinical use of neuromonitoring devices, integrative multimodality neuromonitoring capabilities, and neuromonitoring infrastructure were included. Survey results were presented using descriptive statistics. RESULTS: The survey was completed by faculty at 74% (52 of 70) of institutions. All 52 institutions measure intracranial pressure and have electroencephalography capability, whereas 87% (45 of 52) use near-infrared spectroscopy and 40% (21/52) use transcranial Doppler. Individual patient monitoring decisions were driven by institutional protocols and collaboration between critical care, neurology, and neurosurgery attendings. Reported device utilization varied by brain injury etiology. Only 15% (eight of 52) of institutions utilized a multimodality neuromonitoring platform to integrate and synchronize data from multiple devices. A database of neuromonitoring patients was maintained at 35% (18 of 52) of institutions. Funding for neuromonitoring programs was variable with contributions from hospitals (19%, 10 of 52), private donations (12%, six of 52), and research funds (12%, six of 52), although 73% (40 of 52) have no dedicated funds. CONCLUSIONS: Neuromonitoring indications, devices, and infrastructure vary by institution in North American pediatric critical care units. Noninvasive modalities were utilized more liberally, although not uniformly, than invasive monitoring. Further studies are needed to standardize the acquisition, interpretation, and reporting of clinical neuromonitoring data, and to determine whether neuromonitoring systems impact neurological outcomes.

A Virtual Community of Practice: An International Educational Series in Pediatric Neurocritical Care.

Pediatric neurocritical care (PNCC) is a rapidly growing field. Challenges posed by the COVID-19 pandemic on trainee exposure to educational opportunities involving direct patient care led to the creative solutions for virtual education supported by guiding organizations such as the Pediatric Neurocritical Care Research Group (PNCRG). Our objective is to describe the creation of an international, peer-reviewed, online PNCC educational series targeting medical trainees and faculty. More than 1600 members of departments such as pediatrics, pediatric critical care, and child neurology hailing from 75 countries across six continents have participated in this series over a 10-month period. We created an online educational channel in PNCC with over 2500 views to date and over 130 followers. This framework could serve as a roadmap for other institutions and specialties seeking to address the ongoing problems of textbook obsolescence relating to the rapid acceleration in knowledge acquisition, as well as those seeking to create new educational content that offers opportunities for an interactive, global audience. Through the creation of a virtual community of practice, we have created an international forum for pediatric healthcare providers to share and learn specialized expertise and best practices to advance global pediatric health.

Continuing Care For Critically Ill Children Beyond Hospital Discharge: Current State of Follow-up.

OBJECTIVES: Survivors of the PICU face long-term morbidities across health domains. In this study, we detail active PICU follow-up programs (PFUPs) and identify perceptions and barriers about development and maintenance of PFUPs. METHODS: A web link to an adaptive survey was distributed through organizational listservs. Descriptive statistics characterized the sample and details of existing PFUPs. Likert responses regarding benefits and barriers were summarized. RESULTS: One hundred eleven respondents represented 60 institutions located in the United States (n = 55), Canada (n = 3), Australia (n = 1), and the United Kingdom (n = 1). Details for 17 active programs were provided. Five programs included broad PICU populations, while the majority were neurocritical care (53%) focused. Despite strong agreement on the need to assess and treat morbidity across multiple health domains, 29% were physician only programs, and considerable variation existed in services provided by programs across settings. More than 80% of all respondents agreed PFUPs provide direct benefits and are essential to advancing knowledge on long-term PICU outcomes. Respondents identified "lack of support" as the most important barrier, particularly funding for providers and staff, and lack of clinical space, though successful programs overcome this challenge using a variety of funding resources. CONCLUSIONS: Few systematic multidisciplinary PFUPs exist despite strong agreement about importance of this care and direct benefit to patients and families. We recommend stakeholders use our description of successful programs as a framework to develop multidisciplinary models to elevate continuity across inpatient and outpatient settings, improve patient care, and foster collaboration to advance knowledge.

Neurocritical Care and Brain Monitoring.

The goal of neurocritical care (NCC) is to improve the outcome of patients with neurologic insults. NCC includes the management of the primary brain injury and prevention of secondary brain injury; this is achieved with standardized clinical care for specific disorders along with neuromonitoring. Neuromonitoring uses multiple modalities, with certain modalities better suited to certain disorders. The term "multimodality monitoring" refers to using multiple modalities at the same time. This article reviews pediatric NCC, the various physiologic parameters used, especially continuous electroencephalographic monitoring.

Evidence-Based Protocols in Child Neurology.

Medical care has become more complex as the scientific method has expanded medical knowledge. Medicine is also now practiced across different medical systems of varying complexity, and creating standard treatment guidelines is one way of establishing uniform treatment across these systems. The creation of guidelines ensures the delivery of quality medical care and improved patient outcomes. Evidence-based medicine is the application of scientific research to produce these treatment guidelines. This article shall focus on the current treatment guidelines used for inpatient pediatric neurology.

Practice Recommendations for Transcranial Doppler Ultrasonography in Critically Ill Children in the Pediatric Intensive Care Unit: A Multidisciplinary Expert Consensus Statement.

Transcranial Doppler ultrasonography (TCD) is being used in many pediatric intensive care units (PICUs) to aid in the diagnosis and monitoring of children with known or suspected pathophysiological changes to cerebral hemodynamics. Standardized approaches to scanning protocols, interpretation, and documentation of TCD examinations in this setting are lacking. A panel of multidisciplinary clinicians with expertise in the use of TCD in the PICU undertook a three-round modified Delphi process to reach unanimous agreement on 34 statements and then create practice recommendations for TCD use in the PICU. Use of these recommendations will help to ensure that high quality TCD images are captured, interpreted, and reported using standard nomenclature. Furthermore, use will aid in ensuring reproducible and meaningful study results between TCD practitioners and across PICUs.

Variation in Treatment and Outcomes of Children With Acute Disseminated Encephalomyelitis.

OBJECTIVES: To characterize variation in treatments and outcomes of pediatric patients admitted to children's hospitals with acute disseminated encephalomyelitis (ADEM). METHODS: In this retrospective cohort study, we used data from the Pediatric Health Information System. Children >30 days old who were hospitalized from 2010 to 2015 with ADEM were included. Variables analyzed were treatments and admission to an ICU. Primary outcomes were discharge disposition and readmissions for relapses (ADEM readmissions) or for continued comorbidities (non-ADEM readmissions). RESULTS: A total of 954 patients with ADEM had 1117 admissions. Treatments included steroids (80%), immunoglobulin (22%), and plasmapheresis (6.6%); 15% of admissions included none of these treatments. Treatments varied by center (P < .001). Thirty-four percent of admissions included ICU admission, which was associated with an increased number and duration of treatments (P < .01). The discharge disposition was home in 85% of admissions; home with health services, rehab facility, or other in 13.6%; and mortality in 1.4%. Twelve percent (117 of 954) of patients had >1 admission for ADEM. Treatment choice and ICU stay were not associated with ADEM readmissions. Sixteen percent (181 of 1101) of ADEM admissions had a non-ADEM readmission within 90 days. Prolonged ICU hospitalization was associated with non-ADEM readmission (adjusted odds ratio 1.9; P = .017) and decreased likelihood of discharge from the hospital to home (adjusted odds ratio 0.1; P < .001). After adjusting for ICU duration, treatment choice and duration were not associated with non-ADEM readmission or hospital disposition. CONCLUSIONS: Significant variation in ADEM treatment exists across centers. Admission to an ICU for ADEM was associated with increased immunotherapy, additional health services at discharge, and readmission for diagnoses other than ADEM.

Evaluation of the Effects of Extracorporeal Membrane Oxygenation on Antiepileptic Drug Serum Concentrations in Pediatric Patients.

OBJECTIVES: Patients supported on extracorporeal membrane oxygenation (ECMO) have an increased incidence of seizures. Phenobarbital (PB) and fosphenytoin (fos-PHT) are common antiepileptic drugs (AEDs) used to manage seizures in the pediatric population; however, it is unknown what effect ECMO has on the serum concentrations of AEDs. The purpose of this study is to evaluate the effect of ECMO on AED serum concentrations. METHODS: A retrospective, matched-cohort study was performed in patients younger than 18 years who received ECMO and were treated with intravenous (IV) PB or fos-PHT at Texas Children's Hospital between 2004 and 2014. Patients receiving IV AED therapy and ECMO were matched, based on age, sex, and weight, with patients receiving IV AED therapy without ECMO. The 24-hour cumulative AED dose, serum concentrations, number of doses per serum concentration drawn ratio, volume of distribution, therapeutic serum concentrations, and time to therapeutic serum concentration were compared between both groups. The fos-PHT and PB groups were analyzed in all patients and in neonates only. RESULTS: Fourteen patients met inclusion criteria. The fos-PHT neonatal (20.1 vs 11.3 mg/kg/day, p = 0.044), PB composite (33.9 vs 21.6 mg/kg/day, p = 0.012), and PB neonatal (40.3 vs 20 mg/kg/day, p = 0.04) had larger 24-hour cumulative doses compared with non-ECMO patients. Lower serum concentrations were observed in the PB composite ECMO group (19.1 vs 35.4 mg/L, p < 0.001) and the PB neonatal ECMO group (20.5 vs 27.8 mg/L, p = 0.01) compared with non-ECMO patients. CONCLUSION: Pediatric patients receiving PB on ECMO and neonatal patients receiving fos-PHT on ECMO required larger doses, and in pediatric patients achieved lower serum concentrations, suggesting the necessity for alternative dosing strategies in these populations.