Inhaled Volatiles for Status Asthmaticus, Epilepsy, and Difficult Sedation in Adult ICU and PICU: A Systematic Review.

OBJECTIVES: Inhaled volatile anesthetics support management of status asthmaticus (SA), status epilepticus (SE), and difficult sedation (DS). This study aimed to evaluate the effectiveness, safety, and feasibility of using inhaled anesthetics for SA, SE, and DS in adult ICU and PICU patients. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. STUDY SELECTION: Primary literature search that reported the use of inhaled anesthetics in ventilated patients with SA, SE, and DS from 1970 to 2021. DATA EXTRACTION: Study data points were extracted by two authors independently. Quality assessment was performed using the Joanna Briggs Institute appraisal tool for case studies/series, Newcastle criteria for cohort/case-control studies, and risk-of-bias framework for clinical trials. DATA SYNTHESIS: Primary outcome was volatile efficacy in improving predefined clinical or physiologic endpoints. Secondary outcomes were adverse events and delivery logistics. From 4281 screened studies, the number of included studies/patients across diagnoses and patient groups were: SA (adult: 38/121, pediatric: 28/142), SE (adult: 18/37, pediatric: 5/10), and DS (adult: 21/355, pediatric: 10/90). Quality of evidence was low, consisting mainly of case reports and series. Clinical and physiologic improvement was seen within 1-2 hours of initiating volatiles, with variable efficacy across diagnoses and patient groups: SA (adult: 89-95%, pediatric: 80-97%), SE (adults: 54-100%, pediatric: 60-100%), and DS (adults: 60-90%, pediatric: 62-90%). Most common adverse events were cardiovascular, that is, hypotension and arrhythmias. Inhaled sedatives were commonly delivered using anesthesia machines for SA/SE and miniature vaporizers for DS. Few (10%) of studies reported required non-ICU personnel, and only 16% had ICU volatile delivery protocol. CONCLUSIONS: Volatile anesthetics may provide effective treatment in patients with SA, SE, and DS scenarios but the quality of evidence is low. Higher-quality powered prospective studies of the efficacy and safety of using volatile anesthetics to manage SA, SE, and DS patients are required. Education regarding inhaled anesthetics and the protocolization of their use is needed.

Cerebral Oximetry During Pediatric In-Hospital Cardiac Arrest: A Multicenter Study of Survival and Neurologic Outcome.

OBJECTIVES: To determine if near-infrared spectroscopy measuring cerebral regional oxygen saturation (crS o2 ) during cardiopulmonary resuscitation is associated with return of spontaneous circulation (ROSC) and survival to hospital discharge (SHD) in children. DESIGN: Multicenter, observational study. SETTING: Three hospitals in the pediatric Resuscitation Quality (pediRES-Q) collaborative from 2015 to 2022. PATIENTS: Children younger than 18 years, gestational age 37 weeks old or older with in-hospital cardiac arrest (IHCA) receiving cardiopulmonary resuscitation greater than or equal to 1 minute and intra-arrest crS o2 monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was ROSC greater than or equal to 20 minutes without extracorporeal membrane oxygenation. Secondary outcomes included SHD and favorable neurologic outcome (FNO) (Pediatric Cerebral Performance Category 1-2 or no change from prearrest). Among 3212 IHCA events (index and nonindex), 123 met inclusion criteria in 93 patients. Median age was 0.3 years (0.1-1.4 yr) and 31% (38/123) of the cardiopulmonary resuscitation events occurred in patients with cyanotic heart disease. Median cardiopulmonary resuscitation duration was 8 minutes (3-28 min) and ROSC was achieved in 65% (80/123). For index events, SHD was achieved in 59% (54/91) and FNO in 41% (37/91). We determined the association of median intra-arrest crS o2 and percent of crS o2 values above a priori thresholds during the: 1) entire cardiopulmonary resuscitation event, 2) first 5 minutes, and 3) last 5 minutes with ROSC, SHD, and FNO. Higher crS o2 for the entire cardiopulmonary resuscitation event, first 5 minutes, and last 5 minutes were associated with higher likelihood of ROSC, SHD, and FNO. In multivariable analysis of the infant group (age < 1 yr), higher crS o2 was associated with ROSC (odds ratio [OR], 1.06; 95% CI, 1.03-1.10), SHD (OR, 1.04; 95% CI, 1.01-1.07), and FNO (OR, 1.05; 95% CI, 1.02-1.08) after adjusting for presence of cyanotic heart disease. CONCLUSIONS: Higher crS o2 during pediatric IHCA was associated with increased rate of ROSC, SHD, and FNO. Intra-arrest crS o2 may have a role as a real-time, noninvasive predictor of ROSC.

Pediatric Death After Withdrawal of Life-Sustaining Therapies: A Scoping Review.

OBJECTIVES: Evaluate literature on the dying process in children after withdrawal of life sustaining measures (WLSM) in the PICU. We focused on the physiology of dying, prediction of time to death, impact of time to death, and uncertainty of the dying process on families, healthcare workers, and organ donation. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, and Web of Science. STUDY SELECTION: We included studies that discussed the dying process after WLSM in the PICU, with no date or study type restrictions. We excluded studies focused exclusively on adult or neonatal populations, children outside the PICU, or on organ donation or adult/pediatric studies where pediatric data could not be isolated. DATA EXTRACTION: Inductive qualitative content analysis was performed. DATA SYNTHESIS: Six thousand two hundred twenty-five studies were screened and 24 included. Results were grouped into four categories: dying process, perspectives of healthcare professionals and family, WLSM and organ donation, and recommendations for future research. Few tools exist to predict time to death after WLSM in children. Most deaths after WLSM occur within 1 hour and during this process, healthcare providers must offer support to families regarding logistics, medications, and expectations. Providers describe the unpredictability of the dying process as emotionally challenging and stressful for family members and staff; however, no reports of families discussing the impact of time to death prediction were found. The unpredictability of death after WLSM makes families less likely to pursue donation. Future research priorities include developing death prediction tools of tools, provider and parental decision-making, and interventions to improve end-of-life care. CONCLUSIONS: The dying process in children is poorly understood and understudied. This knowledge gap leaves families in a vulnerable position and the clinical team without the necessary tools to support patients, families, or themselves. Improving time to death prediction after WLSM may improve care provision and enable identification of potential organ donors.

A Comparison of Ketamine and Midazolam as First-Line Anesthetic Infusions for Pediatric Status Epilepticus.

BACKGROUND: Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to compare the efficacy and adverse effects of midazolam and ketamine infusions as first-line anesthetics for pediatric RSE. METHODS: Retrospective single-center study of consecutive study participants treated with ketamine or midazolam as the first-line anesthetic infusions for RSE at a quaternary care children's hospital from December 1, 2017, until September 15, 2021. RESULTS: We identified 117 study participants (28 neonates), including 79 (68%) who received midazolam and 38 (32%) who received ketamine as the first-line anesthetic infusions. Seizures terminated more often in study participants administered ketamine (61%, 23/38) than midazolam (28%, 22/79; odds ratio [OR] 3.97, 95% confidence interval [CI] 1.76-8.98; P < 0.01). Adverse effects occurred more often in study participants administered midazolam (24%, 20/79) than ketamine (3%, 1/38; OR 12.54, 95% CI 1.61-97.43; P = 0.016). Study participants administered ketamine were younger, ketamine was used more often for children with acute symptomatic seizures, and midazolam was used more often for children with epilepsy. Multivariable logistic regression of seizure termination by first-line anesthetic infusion (ketamine or midazolam) including age at SE onset, SE etiology category, and individual seizure duration at anesthetic infusion initiation indicated seizures were more likely to terminate following ketamine than midazolam (OR 4.00, 95% CI 1.69-9.49; P = 0.002) and adverse effects were more likely following midazolam than ketamine (OR 13.41, 95% CI 1.61-111.04; P = 0.016). Survival to discharge was higher among study participants who received midazolam (82%, 65/79) than ketamine (55%, 21/38; P = 0.002), although treating clinicians did not attribute any deaths to ketamine or midazolam. CONCLUSIONS: Among children and neonates with RSE, ketamine was more often followed by seizure termination and less often associated with adverse effects than midazolam when administered as the first-line anesthetic infusion. Further prospective data are needed to compare first-line anesthetics for RSE.

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.

Effect of inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults: a systematic review and meta-analysis.

BACKGROUND: Sedation of critically ill patients with inhaled anaesthetics may reduce lung inflammation, time to extubation, and ICU length of stay compared with intravenous (i.v.) sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes in this population is unclear. In this systematic review, we aimed to summarise the effect of inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults. METHODS: We searched MEDLINE, EMBASE, and PsycINFO for case series, retrospective, and prospective studies in critically ill adults sedated with inhaled anaesthetics. Outcomes included delirium, psychomotor and neurological recovery, long-term cognitive dysfunction, ICU memories, anxiety, depression, post-traumatic stress disorder (PTSD), and instruments used for assessment. RESULTS: Thirteen studies were included in distinct populations of post-cardiac arrest survivors (n=4), postoperative noncardiac patients (n=3), postoperative cardiac patients (n=2), and mixed medical-surgical patients (n=4). Eight studies reported delirium incidence, two neurological recovery, and two ICU memories. One study reported on psychomotor recovery, long-term cognitive dysfunction, anxiety, depression, and PTSD. A meta-analysis of five trials found no difference in delirium incidence between inhaled and i.v. sedatives (relative risk 0.95 [95% confidence interval: 0.59-1.54]). Compared with i.v. sedatives, inhaled anaesthetics were associated with fewer hallucinations and faster psychomotor recovery but no differences in other outcomes. There was heterogeneity in the instruments used and timing of these assessments. CONCLUSIONS: Based on the limited evidence available, there is no difference in cognitive and psychiatric outcomes between adults exposed to volatile sedation or intravenous sedation in the ICU. Future studies should incorporate outcome assessment with validated tools during and after hospital stay. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021236455.

Defining Pediatric Chronic Critical Illness: A Scoping Review.

OBJECTIVES: Children with chronic critical illness (CCI) are hypothesized to be a high-risk patient population with persistent multiple organ dysfunction and functional morbidities resulting in recurrent or prolonged critical care; however, it is unclear how CCI should be defined. The aim of this scoping review was to evaluate the existing literature for case definitions of pediatric CCI and case definitions of prolonged PICU admission and to explore the methodologies used to derive these definitions. DATA SOURCES: Four electronic databases (Ovid Medline, Embase, CINAHL, and Web of Science) from inception to March 3, 2021. STUDY SELECTION: We included studies that provided a specific case definition for CCI or prolonged PICU admission. Crowdsourcing was used to screen citations independently and in duplicate. A machine-learning algorithm was developed and validated using 6,284 citations assessed in duplicate by trained crowd reviewers. A hybrid of crowdsourcing and machine-learning methods was used to complete the remaining citation screening. DATA EXTRACTION: We extracted details of case definitions, study demographics, participant characteristics, and outcomes assessed. DATA SYNTHESIS: Sixty-seven studies were included. Twelve studies (18%) provided a definition for CCI that included concepts of PICU length of stay (n = 12), medical complexity or chronic conditions (n = 9), recurrent admissions (n = 9), technology dependence (n = 5), and uncertain prognosis (n = 1). Definitions were commonly referenced from another source (n = 6) or opinion-based (n = 5). The remaining 55 studies (82%) provided a definition for prolonged PICU admission, most frequently greater than or equal to 14 (n = 11) or greater than or equal to 28 days (n = 10). Most of these definitions were derived by investigator opinion (n = 24) or statistical method (n = 18). CONCLUSIONS: Pediatric CCI has been variably defined with regard to the concepts of patient complexity and chronicity of critical illness. A consensus definition is needed to advance this emerging and important area of pediatric critical care research.

Co-administration of Ketamine in Pediatric Patients with Neurologic Conditions at Risk for Intracranial Hypertension.

BACKGROUND: Ketamine has traditionally been avoided as an induction agent for tracheal intubation in patients with neurologic conditions at risk for intracranial hypertension due to conflicting data in the literature. The objective of this study was to evaluate and compare the effects of ketamine versus other medications as the primary induction agent on peri-intubation neurologic, hemodynamic and respiratory associated events in pediatric patients with neurologic conditions at risk for intracranial hypertension. METHODS: This retrospective observational study enrolled patients < 18 years of age at risk for intracranial hypertension who were admitted to a quaternary children's hospital between 2015 and 2020. Associated events included neurologic, hemodynamic and respiratory outcomes comparing primary induction agents of ketamine versus non-ketamine for tracheal intubation. RESULTS: Of 143 children, 70 received ketamine as the primary induction agent prior to tracheal intubation. Subsequently after tracheal intubation, all the patients received adjunct analgesic and sedative medications (fentanyl, midazolam, and/or propofol) at doses that were inadequate to induce general anesthesia but would keep them comfortable for further diagnostic workup. There were no significant differences between associated neurologic events in the ketamine versus non-ketamine groups (p = 0.42). This included obtaining an emergent computed tomography scan (p = 0.28), an emergent trip to the operating room within 5 h of tracheal intubation (p = 0.6), and the need for hypertonic saline administration within 15 min of induction drug administration for tracheal intubation (p = 0.51). There were two patients who had clinical and imaging evidence of herniation, which was not more adversely affected by ketamine compared with other medications (p = 0.49). Of the 143 patients, 23 had pre-intubation and post-intubation intracranial pressure values recorded; 11 received ketamine, and 3 of these patients had intracranial hypertension that resolved or improved, whereas the remaining 8 children had intracranial pressure within the normal range that was not exacerbated by ketamine. There were no significant differences in overall associated hemodynamic or respiratory events during tracheal intubation and no 24-h mortality in either group. CONCLUSIONS: The administration of ketamine as the primary induction agent prior to tracheal intubation in combination with other agents after tracheal intubation in children at risk for intracranial hypertension was not associated with an increased risk of peri-intubation associated neurologic, hemodynamic or respiratory events compared with those who received other induction agents.

Paediatric death after withdrawal of life-sustaining therapies: a scoping review protocol.

INTRODUCTION: The physiology of dying after withdrawal of life-sustaining measures (WLSM) is not well described in children. This lack of knowledge makes predicting the duration of the dying process difficult. For families, not knowing this process's duration interferes with planning of rituals related to dying, travel for distant relatives and emotional strain during the wait for death. Time-to-death also impacts end-of-life care and determines whether a child will be eligible for donation after circulatory determination of death. This scoping review will summarise the current literature about what is known about the dying process in children after WLSM in paediatric intensive care units (PICUs). METHODS AND ANALYSIS: This review will use Joanna Briggs Institute methodology for scoping reviews. Databases searched will include Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials via EBM Reviews Ovid, Ovid PsycINFO, CINAHL and Web of Science. Literature reporting on the physiology of dying process after WLSM, or tools that predict time of death in children after WLSM among children aged 0-18 years in PICUs worldwide will be considered. Literature describing the impact of prediction or timing of death after WLSM on families, healthcare workers and the organ donation process will also be included. Quantitative and qualitative studies will be evaluated. Two independent reviewers will screen references by title and abstract, and then by full text, and complete data extraction and analysis. ETHICS AND DISSEMINATION: The review uses published data and does not require ethics review. Review results will be published in a peer-reviewed scientific journal.

Ketamine for Management of Neonatal and Pediatric Refractory Status Epilepticus.

BACKGROUND AND OBJECTIVES: Few data are available regarding the use of anesthetic infusions for refractory status epilepticus (RSE) in children and neonates, and ketamine use is increasing despite limited data. We aimed to describe the impact of ketamine for RSE in children and neonates. METHODS: Retrospective single-center cohort study of consecutive patients admitted to the intensive care units of a quaternary care children's hospital treated with ketamine infusion for RSE. RESULTS: Sixty-nine patients were treated with a ketamine infusion for RSE. The median age at onset of RSE was 0.7 years (interquartile range 0.15-7.2), and the cohort included 13 (19%) neonates. Three patients (4%) had adverse events requiring intervention during or within 12 hours of ketamine administration, including hypertension in 2 patients and delirium in 1 patient. Ketamine infusion was followed by seizure termination in 32 patients (46%), seizure reduction in 19 patients (28%), and no change in 18 patients (26%). DISCUSSION: Ketamine administration was associated with few adverse events, and seizures often terminated or improved after ketamine administration. Further data are needed comparing first-line and subsequent anesthetic medications for treatment of pediatric and neonatal RSE. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence on the therapeutic utility of ketamine for treatment of RSE in children and neonates.

Paediatric critical COVID-19 and mortality in a multinational prospective cohort.

Background: To understand critical paediatric coronavirus disease 2019 (COVID-19) and evaluate factors associated with mortality in children from high and low-middle income countries. Methods: Prospective, observational study of critically ill children hospitalised for COVID-19 in 18 countries throughout North America, Latin America, and Europe between April 1 and December 31, 2020. Associations with mortality were evaluated using logistic regression. Findings: 557 patients (median age, 8 years; 24% <2 years) were enrolled from 55 sites (63% Latin American). Half had comorbidities. Invasive (41%) or non-invasive (20%) ventilation and vasopressors (56%) were the most common support modalities. Hospital mortality was 10% and higher in children <2 years old (15%; odds ratio 1·94, 95%CI 1·08-3·49). Most who died had pulmonary disease. When adjusted for age, sex, region, and illness severity, mortality-associated factors included cardiac (aOR 2·89; 95%CI 1·2-6·94) or pulmonary comorbidities (aOR 4·43; 95%CI 1·70-11·5), admission hypoxemia (aOR 2·44; 95%CI 1·30-4·57), and lower respiratory symptoms (aOR 2·96; 95%CI 1·57-5·59). MIS-C (aOR 0·25; 95%CI 0·1-0·61) and receiving methylprednisolone (aOR 0·5; 95%CI 0·25-0·99), IVIG (aOR 0·32; 95%CI 0·16-0·62), or anticoagulation (aOR 0·49; 95%CI 0·25-0·95) were associated with lower mortality although these associations might be limited to children >2 years old. Interpretation: We identified factors associated with COVID-19 mortality in critically ill children from both high and low-middle income countries, including higher mortality with younger age and COVID-related pulmonary disease but lower mortality in MIS-C. Further research is needed on optimal treatments for younger children and respiratory failure in paediatric COVID-19. Funding: None.

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.

Effect of sedation with inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults: a systematic review protocol.

INTRODUCTION: The COVID-19 pandemic has renewed interest in the use of inhaled anaesthetics for sedation of ventilated critically ill patients. Preliminary data show that inhaled anaesthetics reduce lung inflammation, time to extubation and intensive care unit length of stay compared with intravenous sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes is not well described in this setting. Randomised controlled trials are underway to establish if inhaled anaesthetics affect these and other patient and health system outcomes. Our aim is to summarise the known effects of inhaled sedatives on cognitive and psychiatric outcomes. METHODS AND ANALYSIS: In this systematic review, we will use MEDLINE, EMBASE, and PsycINFO to identify studies from 1970 to 2021 that assessed cognitive and psychiatric outcomes in critically ill adult patients sedated with inhaled anaesthetics. We will include case series, observational and cohort studies and randomised controlled trials. We will exclude case studies due to the heterogeneity of reporting in these studies. For randomised controlled trials comparing inhaled to intravenous sedation, we will report cognitive and psychiatric outcomes for both study arms. Studies will be selected based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Data will be extracted using a standardised data extraction tool by two independent reviewers. Studies will be assessed for bias using the Cochrane risk of bias tool for randomised controlled trials, or the Newcastle-Ottawa Scale for cohort and case-control studies. Findings will be reported according to outcome and descriptive statistics will be used to illustrate findings in a narrative fashion. ETHICS AND DISSEMINATION: The systematic review uses published data and therefore does not require ethics approval. Results will be disseminated via publication in peer-reviewed journals and presentation at conferences related to the field. PROSPERO REGISTRATION NUMBER: CRD42021236455.

Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C.

BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

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.

Use of inhalational anaesthetic agents in paediatric and adult patients for status asthmaticus, status epilepticus and difficult sedation scenarios: a protocol for a systematic review.

INTRODUCTION: Inhaled volatile anaesthetics have a long tradition of use as hypnotic agents in operating rooms and are gaining traction as sedatives in intensive care units (ICUs). However, uptake is impeded by low familiarity with volatiles, unique equipment and education needs. Inhaled anaesthetics are often reserved in ICUs as therapies for refractory and life threatening status asthmaticus, status epilepticus, high and difficult sedation need scenarios given they possess unique pharmacological properties to manage these medical conditions while providing sedation to acutely ill patients. The objective of this systematic review is to collate evidence regarding the efficacy, safety and feasibility of volatile anaesthetics in adult and paediatric ICU patients for these three emergency conditions. METHODS AND ANALYSIS: We will conduct a systematic review of the primary studies in adult and paediatric ICU patients with status asthmaticus, status epilepticus and high/difficult sedation needs. We will include observational and interventional studies published from 1970 to 2021 in English or French investigating patients who have received a volatile inhalational agent for the above indications. We will evaluate the efficacy, safety, feasibility and implementation barriers for the volatile anaesthetics for each of three specified indications. Included studies will not be limited by necessity of a comparator arm. We will also evaluate clinical characteristics, patient demographics and provider attitudes towards volatile anaesthetic administration in defined critical care scenarios. Data will be extracted and analysed across these domains. The databases MEDLINE, EMBASE, the Science Citation Index as well as the Cochrane Central Controlled Trials Register will be queried with our search strategy.Descriptive and statistical analysis will be employed where appropriate. Data extraction and quality assessment will be performed in duplicate using a standardised tool. A narrative approach and statistical analyses will be used to describe patient characteristics, volatile efficacy, safety concerns, technical administration, attitudes towards administration and other implementation barriers. ETHICS AND DISSEMINATION: No ethics board approval will be necessary for this systematic review. This research is independently funded. Results will be disseminated in a peer-reviewed journal and conference presentation. PROSPERO NUMBER: CRD42021233083.

Variability in Pediatric Brain Death Determination Protocols in the United States.

OBJECTIVE: To determine the variability in pediatric death by neurologic criteria (DNC) protocols between US pediatric institutions and compared to the 2011 DNC guidelines. METHODS: Cross-sectional study of DNC protocols obtained from pediatric institutions in the United States (US) via regional organ procurement organizations. Protocols were evaluated across five domains: general DNC procedures, prerequisites, neurologic examination, apnea testing and ancillary testing. Descriptive statistics compared protocols to each other and the 2011 guidelines. RESULTS: One hundred and thirty protocols were analyzed with 118 dated after publication of the 2011 guidelines. Of those 118 protocols, identification of a mechanism of irreversible brain injury was required in 97%, while 67% required an observation period after acute brain injury before DNC evaluation. Most protocols required guideline-based prerequisites such as exclusion of hypotension (94%), hypothermia (97%), and metabolic derangements (92%). On neurologic examination, 91% required a lack of responsiveness, 93% no response to noxious stimuli, and 99% loss of brainstem reflexes. 84% of protocols required the guideline-recommened two apnea tests. CO2 targets were consistent with guidelines in 64%. Contrary to guidelines, fifteen percent required ancillary testing for all patients and 15% permitted ancillary studies that are not validated in pediatrics. CONCLUSIONS: and Relevance: Variability exists between pediatric institutional DNC protocols in all domains of DNC determination, especially with respect to apnea and ancillary testing. Better alignment of DNC protocols with national guidelines may improve the consistency and accuracy of DNC determination.

Assessment of midazolam pharmacokinetics in the treatment of status epilepticus.

OBJECTIVES: Refractory status epilepticus (RSE) is often treated with midazolam boluses and continuous infusions, but there is considerable variability in dosing and efficacy. We aimed to evaluate the performance of a clinical midazolam dose escalation pathway for the treatment of pediatric RSE that was designed based on a novel midazolam pharmacokinetic model. DESIGN: Prospective pharmacokinetic study of midazolam bolus and escalation of continuous midazolam infusion. SETTING: Pediatric Intensive Care Unit in quaternary-care academic hospital. SUBJECTS: Children between two months to seventeen years of age who received clinically-indicated midazolam infusion for treatment of RSE. INTERVENTION: Blood sampled at regular intervals during treatment. Main study outcome measure was the accuracy of a pharmacokinetic model to predict serum midazolam concentrations. MEASUREMENTS AND MAIN RESULTS: We analysed data from six subjects. Three subjects had serum midazolam concentrations close to those predicted by our initial model (accuracy 88.9-170.2 %) which incorporates body weight, hepatic function, and renal function. For the other three subjects, all of whom were receiving pre-existing chronic benzodiazepine therapy prior to the RSE episode, the model grossly overestimated serum concentrations (predictive error 420.3-722.5 %). Once the model was corrected for the impact of pre-existing chronic benzodiazepine use on clearance, predicted concentrations more closely reflected those measured in subjects. CONCLUSION: We evaluated a clinical midazolam RSE treatment pathway but discovered that the model on which the pathway was based was not accurate for all patients. We therefore developed a novel pharmacokinetic midazolam model in children with RSE treated with continuous midazolam infusion. This model incorporates body weight, hepatic and renal function, and importantly, a correction factor for pre-existing chronic benzodiazepine use. Once validated, this model may guide dosing and drive the development of more effective treatment pathways for continuous midazolam in RSE.

Apnea Testing Using Continuous Positive Airway Pressure When Determining Death by Neurologic Criteria in Children: Retrospective Analysis of Potential Adverse Events.

OBJECTIVES: To determine the prevalence of adverse events during apnea testing for determination of death by neurologic criteria using continuous positive airway pressure in children. DESIGN: Single-center retrospective descriptive study. SETTING: Academic children's hospital. PATIENTS: Children evaluated for death by neurologic criteria in the PICU from 2013 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each patient evaluated for death by neurologic criteria, we abstracted the number of apnea tests performed, vital signs and arterial blood gases during apnea testing, and outcome from the medical record. Adverse events were defined as oxygen-hemoglobin desaturation (arterial oxygen saturation < 85%), hypotension, or other significant event (e.g. arrhythmia, cardiac arrest) based on documentation in the medical record. We determined which adverse events resulted in early termination of the apnea test. We used oxygenation index, ventilator variables, and presence of vasopressors to determine preapnea test cardiopulmonary dysfunction. Seventy-two patients (age 7 yr [2.7-13.2 yr]; 48% male) underwent 121 apnea tests. Nine patients (12%) had 13 potential apnea tests deferred due to concern for cardiopulmonary instability as determined by the attending physician. Patients who underwent apnea testing had an oxygenation index of 3.5 (2.5-4.8) and were receiving vasopressors at the time of 108 apnea tests (89%). Hypotension was reported during seven apnea tests (6%) and resulted in the early termination of one apnea test (<1%). No other adverse events were reported. One hundred and twenty apnea tests (99%) were consistent with death by neurologic criteria. CONCLUSIONS: Apnea testing following a protocol that uses continuous positive airway pressure for apneic oxygenation has a low rate of adverse events in children meeting prerequisite criteria and determined by a pediatric intensivist to be physiologically appropriate for testing.