Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group in the Pediatric Population.

BACKGROUND: The fundamental gap obstructing forward progress of evidenced-based care in pediatric and neonatal disorders of consciousness (DoC) is the lack of defining consensus-based terminology to perform comparative research. This lack of shared nomenclature in pediatric DoC stems from the inherently recursive dilemma of the inability to reliably measure consciousness in the very young. However, recent advancements in validated clinical examinations and technologically sophisticated biomarkers of brain activity linked to future abilities are unlocking this previously formidable challenge to understanding the DoC in the developing brain. METHODS: To address this need, the first of its kind international convergence of an interdisciplinary team of pediatric DoC experts was organized by the Neurocritical Care Society's Curing Coma Campaign. The multidisciplinary panel of pediatric DoC experts proposed pediatric-tailored common data elements (CDEs) covering each of the CDE working groups including behavioral phenotyping, biospecimens, electrophysiology, family and goals of care, neuroimaging, outcome and endpoints, physiology and big Data, therapies, and pediatrics. RESULTS: We report the working groups' pediatric-focused DoC CDE recommendations and disseminate CDEs to be used in studies of pediatric patients with DoC. CONCLUSIONS: The CDEs recommended support the vision of progressing collaborative and successful internationally collaborative pediatric coma research.

Brain-based arterial pulse pressure threshold for death determination: a systematic review.

PURPOSE: There is lack of consensus regarding the minimum arterial pulse pressure required for confirming permanent cessation of circulation for death determination by circulatory criteria in organ donors. We assessed direct and indirect evidence supporting whether one should use an arterial pulse pressure of 0 mm Hg vs more than 0 (5, 10, 20, 40) mm Hg to confirm permanent cessation of circulation. SOURCE: We conducted this systematic review as part of a larger project to develop a clinical practice guideline for death determination by circulatory or neurologic criteria. We systematically searched Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, and Web of Science for articles published from inception until August 2021. We included all types of peer-reviewed original research publications related to arterial pulse pressure as monitored by an indwelling arterial pressure transducer around circulatory arrest or determination of death with either direct context-specific (organ donation) or indirect (outside of organ donation context) data. PRINCIPAL FINDINGS: A total of 3,289 abstracts were identified and screened for eligibility. Fourteen studies were included; three from personal libraries. Five studies were of sufficient quality for inclusion in the evidence profile for the clinical practice guideline. One study measured cessation of cortical scalp electroencephalogram (EEG) activity after withdrawal of life-sustaining measures and showed that EEG activity fell below 2 µV when the pulse pressure reached 8 mm Hg. This indirect evidence suggests there is a possibility of persistent cerebral activity at arterial pulse pressures > 5 mm Hg. CONCLUSION: Indirect evidence suggests that clinicians may incorrectly diagnose death by circulatory criteria if they apply any arterial pulse pressure threshold of greater than 5 mm Hg. Moreover, there is insufficient evidence to determine that any pulse pressure threshold greater than 0 and less than 5 can safely determine circulatory death. STUDY REGISTRATION: PROSPERO (CRD42021275763); first submitted 28 August 2021.

RéSUMé: OBJECTIF: Il n'y a pas de consensus concernant la pression artérielle minimale requise pour confirmer l'arrêt permanent de la circulation pour la détermination du décès selon des critères circulatoires chez les donneurs d'organes. Nous avons évalué les données probantes directes et indirectes soutenant l'utilisation d'une pression pulsée artérielle de 0 mmHg vs plus de 0 (5, 10, 20, 40) mm Hg pour confirmer l'arrêt définitif de la circulation. SOURCES: Nous avons réalisé cette revue systématique dans le cadre d'un projet plus vaste visant à élaborer des lignes directrices de pratique clinique pour la détermination du décès selon des critères circulatoires ou neurologiques. Nous avons mené des recherches systématiques dans Ovid MEDLINE, Ovid Embase, le registre Cochrane des études contrôlées (CENTRAL) via la Cochrane Library et Web of Science pour trouver des articles publiés depuis leur création jusqu'en août 2021. Nous avons inclus tous les types de publications de recherches originales évaluées par des pairs liées à la pression pulsée artérielle telle que surveillée par un transducteur de pression artérielle à demeure entourant un arrêt circulatoire ou de une détermination de décès avec des données directes spécifiques au contexte (don d'organes) ou indirectes (en dehors d'un contexte du don d'organes). CONSTATATIONS PRINCIPALES: Au total, 3289 résumés ont été identifiés et examinés pour déterminer leur admissibilité. Quatorze études ont été incluses, trois provenant de bibliothèques personnelles. Cinq études étaient de qualité suffisante pour être incluses dans le profil de données probantes des Lignes directrices de pratique clinique. Une étude a mesuré l'arrêt de l'activité de l'électroencéphalogramme (EEG) au niveau du scalp cortical après l'interruption des thérapies de maintien des fonctions vitales et a montré que l'activité EEG tombait en dessous de 2 µV lorsque la pression pulsée atteignait 8 mm Hg. Ces données probantes indirectes suggèrent qu'il existe une possibilité d'activité cérébrale persistante à des pressions pulsées artérielles > 5 mm Hg. CONCLUSION: Des données probantes indirectes suggèrent que les cliniciens pourraient diagnostiquer à tort un décès selon des critères circulatoires s'ils appliquent un seuil de pression pulsée artérielle supérieur à 5 mm Hg. De plus, il n'y a pas suffisamment de données probantes pour déterminer que tout seuil de pression pulsée supérieur à 0 et inférieur à 5 peut permettre de déterminer en toute sécurité un décès cardiocirculatoire. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021275763); soumis pour la première fois le 28 août 2021.

Spectrograms for Seizure Detection in Critically Ill Children.

SUMMARY: Electrographic seizures are common in critically ill children and a significant proportion of these seizures are nonconvulsive. There is an association between electrographic seizures and neurophysiological disturbances, worse short- and long-term neurologic outcomes, and mortality in critically ill patients. In this context, timely diagnosis and treatment of electrographic seizures in critically ill children becomes important. However, most institutions lack the resources to support round-the-clock or frequent review of continuous EEG recordings causing significant delays in seizure diagnosis. Given the current gaps in review of continuous EEG across institutions globally, use of visually simplified, time-compressed quantitative EEG trends such as spectrograms has the potential to enhance timeliness of seizure diagnosis and treatment in critically ill children.

Moyamoya Syndrome in an Infant with Aicardi-Goutières and Williams Syndromes: A Case Report.

Stroke in infancy is a rare phenomenon but can lead to significant long-term disability. We present the story of a 6-month-old Old Order Amish infant with underlying Williams syndrome, a rare neurodevelopmental disorder caused by a microdeletion, encompassing the elastin gene that produces abnormalities in elastic fibers of the lungs and vessels. This infant presented with lethargy, irritability, and a new-onset generalized tonic-clonic seizure. Brain magnetic resonance imaging (MRI) was consistent with ischemic stroke in the supratentorial regions. MR angiogram demonstrated bilateral narrowing of the internal carotid arteries with "ivy sign," suggestive of Moyamoya. Moyamoya disease/syndrome is a cerebrovascular condition that is associated with progressive stenosis of the intracranial vessels and can cause ischemic stroke in young children. Targeted mutation analysis revealed a homozygous c.1411-2A > G splice site variant in the SAMHD1 gene, consistent with a diagnosis of Aicardi-Goutières syndrome type 5 (AGS5), an autosomal recessive condition with multisystem involvement. In our unique case of infantile stroke with Moyamoya syndrome and dual diagnosis of Williams syndrome and AGS5, both diagnoses likely contributed to the cerebrovascular pathology. This case report highlights the importance of suspecting and testing for multiple genetic abnormalities in children presenting with Moyamoya-related stroke.

Community-Acquired Methicillin-Resistant Staphylococcus aureus Infections in Acutely Ill Children: A Retrospective Case-Control Study.

OBJECTIVES: To test if admission clinical and laboratory variables could reliably discriminate community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections from methicillin-sensitive Staphylococcus aureus (MSSA) infections in acutely ill children, and to describe the epidemiology, clinical features and outcomes among children with Staphylococcal infections admitted to the hospital. METHODS: The authors conducted this retrospective case-control study comparing children with CA-MRSA and MSSA infections admitted to hospital between June 2014 and June 2017. They describe the evolving epidemiology and attempt to identify clinical and laboratory variables that can differentiate MRSA cases from MSSA controls. They used multivariate logistic regression to identify independent predictors of MRSA infection and Cox-proportional hazard analysis to compare survival times. RESULTS: Seventy-three children were enrolled, of which 35 had CA-MRSA and 38 had MSSA infections. Children in MRSA group were younger [median (IQR) age in months: 36 (12, 62) vs. 56 (37, 96); p = 0.032]. MRSA and MSSA groups had similar rate of skin and soft tissue involvement (SSTI) [62.9% vs. 54.1%; p = 0.449]. Median duration of illness was lower in MRSA, 6 vs. 8.5 d (p = 0.001). TLC of 8100 or less was 82% sensitive and 94% specific for MRSA sepsis at admission [AUROC = 0.64 (0.51-0.77), p = 0.04]. Mortality (8.6% vs. 10.5% p = 1.0) and length of ICU stay (7.2 vs. 9.3 d, p = 0.24) were similar in both. None of the admission variables were predictive of MRSA culture-positivity on regression analysis. CONCLUSIONS: The hospital-based incidence of CA-MRSA infections among children appears to be increasing. None of the admission clinical or laboratory variables could reliably identify CA-MRSA infections. As there seems to be no reliable way to differentiate children with MSSA and MRSA infections, physicians may consider empiric initiation of broad-spectrum antibiotics at admission to cover both MSSA and MRSA, especially in critically ill children with suspected Staphylococcal infections.

Composite Outcomes for Clinical Trials in Critical Care: The Devil is in the Detail.

How to cite this article: Lalgudi Ganesan S, Parameswaran N. Composite Outcomes for Clinical Trials in Critical Care: The Devil is in the Detail. Indian J Crit Care Med 2020;24(10):903-904.

Seizure Detection Algorithms in Critically Ill Children: A Comparative Evaluation.

OBJECTIVES: To evaluate the performance of commercially available seizure detection algorithms in critically ill children. DESIGN: Diagnostic accuracy comparison between commercially available seizure detection algorithms referenced to electroencephalography experts using quantitative electroencephalography trends. SETTING: Multispecialty quaternary children's hospital in Canada. SUBJECTS: Critically ill children undergoing electroencephalography monitoring. INTERVENTIONS: Continuous raw electroencephalography recordings (n = 19) were analyzed by a neurophysiologist to identify seizures. Those recordings were then converted to quantitative electroencephalography displays (amplitude-integrated electroencephalography and color density spectral array) and evaluated by six independent electroencephalography experts to determine the sensitivity and specificity of the amplitude-integrated electroencephalography and color density spectral array displays for seizure identification in comparison to expert interpretation of raw electroencephalography data. Those evaluations were then compared with four commercial seizure detection algorithms: ICTA-S (Stellate Harmonie Version 7; Natus Medical, San Carlos, CA), NB (Stellate Harmonie Version 7; Natus Medical), Persyst 11 (Persyst Development, Prescott, AZ), and Persyst 13 (Persyst Development) to determine sensitivity and specificity in comparison to amplitude-integrated electroencephalography and color density spectral array. MEASUREMENTS AND MAIN RESULTS: Of the 379 seizures identified on raw electroencephalography, ICTA-S detected 36.9%, NB detected 92.3%, Persyst 11 detected 75.9%, and Persyst 13 detected 74.4%, whereas electroencephalography experts identified 76.5% of seizures using color density spectral array and 73.7% using amplitude-integrated electroencephalography. Daily false-positive rates averaged across all recordings were 4.7 with ICTA-S, 126.3 with NB, 5.1 with Persyst 11, 15.5 with Persyst 13, 1.7 with color density spectral array, and 1.5 with amplitude-integrated electroencephalography. Both Persyst 11 and Persyst 13 had sensitivity comparable to that of electroencephalography experts using amplitude-integrated electroencephalography and color density spectral array. Although Persyst 13 displayed the highest sensitivity for seizure count and seizure burden detected, Persyst 11 exhibited the best trade-off between sensitivity and false-positive rate among all seizure detection algorithms. CONCLUSIONS: Some commercially available seizure detection algorithms demonstrate performance for seizure detection that is comparable to that of electroencephalography experts using quantitative electroencephalography displays. These algorithms may have utility as early warning systems that prompt review of quantitative electroencephalography or raw electroencephalography tracings, potentially leading to more timely seizure identification in critically ill patients.

Electrographic seizure burden and outcomes following pediatric status epilepticus.

Pediatric status epilepticus carries a substantial risk for morbidity and mortality, but the relationship between seizure burden, treatment, and outcome remains incompletely understood. This review summarizes the evidence linking seizure burden and outcomes among critically ill children in the intensive care unit (ICU), a population in whom accurate quantification of seizure burden is possible using continuous electroencephalographic monitoring. Several high-quality observational studies among critically ill children have reported an association between higher seizure burden and worse outcome, even after adjusting for potential confounders such as age, etiology, and illness severity. Although these studies support the hypothesis that seizures contribute to brain injury and worsen outcome, a causal link between seizures and outcome remains to be proven. The relationship between seizures and outcome is likely complex, and dependent on factors such as etiology, preexisting neurological disability, medication exposure, and possibly individual genetic factors. Studies attempting to define this complex relationship will need to measure and account for these factors in their analyses. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Airway pressure release ventilation in children.

PURPOSE OF REVIEW: In patients with acute respiratory distress syndrome (ARDS), airway pressure release ventilation (APRV) has been purported to have several physiological benefits. This review synthesizes recent research evaluating APRV mode and provides perspectives on the utility of this mode in children with ARDS. RECENT FINDINGS: Two single-center clinical trials on APRV, one adult and one pediatric, have been published this year. These two trials have not only elicited editorials and letters that highlight some of their strengths and weaknesses but also rekindled debate on several aspects of APRV. Despite their contradicting results, both trials provide significant insights into APRV strategies that work and those that may not. This review places the newer evidence in the context of existing literature and provides a comprehensive analysis of APRV use in children. SUMMARY: There have been significant recent advancements in our understanding of the clinical utility of APRV in children with ARDS. The recent trial highlights the urgent need to evolve a consensus on definition of APRV and identify strategies that work. Pending further research, clinicians should avoid the use of a zero-PLOW Personalized-APRV strategy as a primary ventilation modality in children with moderate-severe ARDS.

Seizure Identification by Critical Care Providers Using Quantitative Electroencephalography.

OBJECTIVES: To compare the performance of critical care providers with that of electroencephalography experts in identifying seizures using quantitative electroencephalography display tools. DESIGN: Diagnostic accuracy comparison among healthcare provider groups. SETTING: Multispecialty quaternary children's hospital in Canada. SUBJECTS: ICU fellows, ICU nurses, neurophysiologists, and electroencephalography technologists. INTERVENTION: Two-hour standardized one-on-one training, followed by a supervised individual review of 27 continuous electroencephalography recordings with the task of identifying individual seizures on eight-channel amplitude-integrated electroencephalography and color density spectral array displays. MEASUREMENTS AND MAIN RESULTS: Each participant reviewed 27 continuous electroencephalograms comprising 487 hours of recording containing a total of 553 seizures. Performance for seizure identification was compared among groups using a nested model analysis with adjustment for interparticipant variability within groups and collinearity among recordings. Using amplitude-integrated electroencephalography, sensitivity for seizure identification was comparable among ICU fellows (83.8%), ICU nurses (73.1%), and neurophysiologists (81.5%) but lower among electroencephalographic technologists (66.7%) (p = 0.003). Using color density spectral array, sensitivity was comparable among ICU fellows (82.4%), ICU nurses (88.2%), neurophysiologists (83.3%), and electroencephalographic technologists (73.3%) (p = 0.09). Daily false-positive rates were also comparable among ICU fellows (2.8 for amplitude-integrated electroencephalography, 7.7 for color density spectral array), ICU nurses (4.2, 7.1), neurophysiologists (1.2, 1.5), and electroencephalographic technologists (0, 0) (p = 0.41 for amplitude-integrated electroencephalography; p = 0.13 for color density spectral array). However, performance varied greatly across individual electroencephalogram recordings. Professional background generally played a greater role in determining performance than individual skill or electroencephalogram recording characteristics. CONCLUSIONS: Following standardized training, critical care providers and electroencephalography experts displayed similar performance for identifying individual seizures using both amplitude-integrated electroencephalography and color density spectral array displays. Although these quantitative electroencephalographic trends show promise as a tool for bedside seizure screening by critical care providers, these findings require confirmation in a real-world ICU environment and in daily clinical use.

Airway Pressure Release Ventilation in Pediatric Acute Respiratory Distress Syndrome. A Randomized Controlled Trial.

RATIONALE: Although case series describe benefits of airway pressure release ventilation (APRV), this mode of ventilation has not been evaluated against the conventional low-tidal volume ventilation (LoTV) in children with acute respiratory distress syndrome (ARDS). OBJECTIVES: To compare the effect of APRV and conventional LoTV on ventilator-free days in children with ARDS. METHODS: This open-label, parallel-design randomized controlled trial was conducted in a 15-bed ICU. Children aged 1 month to 12 years satisfying the modified Berlin definition were included. We excluded children with air leaks, increased intracranial pressure, poor spontaneous breathing efforts, chronic lung disease, and beyond 24 hours of ARDS diagnosis or 72 hours of ventilation. Children were randomized using unstratified, variable-sized block technique. A priori interim analysis was planned at 50% enrollment. All enrolled children were followed up until 180 days after enrollment or death, whichever was earlier. MEASUREMENTS AND MAIN RESULTS: The trial was terminated after 50% enrollment (52 children) when analysis revealed higher mortality in the intervention arm. Ventilator-free days were statistically similar in both arms (P = 0.23). The 28-day all-cause mortality was 53.8% in APRV as compared with 26.9% among control subjects (risk ratio, 2.0; 95% confidence interval, 0.97-4.1; Fisher exact P = 0.089). The multivariate-adjusted risk ratio of death for APRV compared with LoTV was 2.02 (95% confidence interval, 0.99-4.12; P = 0.05). Higher mean airway pressures, greater spontaneous breathing, and early improvement in oxygenation were seen in the intervention arm. CONCLUSIONS: APRV, as a primary ventilation strategy in children with ARDS, was associated with a trend toward higher mortality compared with the conventional LoTV. Limitations should be considered while interpreting these results. Clinical trial registered with www.clinicaltrials.gov (NCT02167698) and Clinical Trials Registry of India (CTRI/2014/06/004677).