Editor’s Choice Articles for August

My three Editor's Choice articles in the August 2024 issue focus on innovations applicable to clinical practice. First, in children supported with mechanical ventilation and receiving vasoactive infusions, the relevance of acute echocardiography findings to the strategy for fluid management (1,2). Second, in PICU admissions with suspected genetic diagnoses, the experience of using rapid whole-genome sequencing (WGS) for diagnosis and the consequence on patient care (3,4). Third, in patients receiving treatment in the PICU for severe traumatic brain injury (TBI), the choice of anticonvulsant medication for prophylaxis against early status epilepticus (5,6). In the educational sections, PCCM Connections explores acute brain dysfunction (ABD) in sepsis and septic shock (7,8). And, finally, PCCM International highlights noninvasive respiratory support for moderate to severe acute bronchiolitis and the new publication of a randomized clinical trial (RCT) from India (9,10). CAN EARLY ECHOCARDIOGRAPHY HELP CLINICIANS ADDRESS PHYSIOLOGIC CHANGES OCCURRING WITH SEPSIS? Ip PYF, Periasamy U, Staffa SJ, et al: Management Changes After Echocardiography are Associated With Improved Outcomes in Critically Ill Children (1). My first Editor's Choice article resumes a theme of PCCM's clinical research that is of international interest: that is, can early point of care ultrasound (POCUS) assessment of the heart be used to promote physiologically appropriate management of pediatric sepsis? Previously, for example, from the United States, a single-center retrospective cohort (2014−2016) study of 71 patients with suspected septic shock found a "focused cardiac ultrasound…frequently changed a clinician's characterization of hemodynamics" (11). From Malawi, a single-center prospective observational (2017−2018) study of 54 patients with severe febrile illness found that cardiac dysfunction was present in one in four cases (12,13). And, from Vietnam, a single-center retrospective cohort (2013−2021) study of 67 patients with profound dengue shock syndrome found that use of POCUS was associated with lower odds of death, a higher volume of administered resuscitation fluid, and improvements in clinical scores (14). Researchers from a single center in the United States report a retrospective cohort (2011−2020) study of 249 patients needing supportive mechanical ventilation and vasoactive infusions (1). The authors provide an interesting hypothesis-generating analysis about the presence or absence of depressed cardiac function, the continued use of vasoconstrictors versus switching to inotropes, fluid management strategy, and outcomes. Add the accompanying editorial to your reading (2); it is written by an established POCUS practitioner and researcher from India and covers a series of questions about the feasibility, timing, and findings of POCUS in septic children. Finally, review the work of the PALISI (Pediatric Acute Lung Injury and Sepsis Investigators) Pediatric Research Collaborative on Critical Ultrasound subgroup on enhancing education with competency-based POCUS training in the PICU (15,16). WHAT IS THE DIAGNOSTIC AND CLINICAL UTILITY OF RAPID WGS IN CRITICALLY ILL CHILDREN? Rodriguez KM, Vaught J, Salz L, et al: Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016−2023 (3). My second Editor's Choice article is a multisite cohort (2016−2023) study of 133 children who underwent clinical, phenotype-driven rapid GWS in the PICU or cardiovascular ICU (3). The new report is an extension of the authors' previous work (2016−2018) (17), now with more sites and patients. There is an accompanying editorial (4). Also, do seek out other 2022−2024 reports in the journals about PICU genomic diagnostics covering the implications of costs (18), ethical challenges (19), and genetic counselling (20). ARE WE ANY CLOSER TO KNOWING WHAT ANTICONVULANT PROPHYLAXIS TO USE IN SEVERE TBI PATIENTS? Ahmed N, Russo L, Kuo YH: Levetiracetam or Phenytoin as Prophylaxis for Status Epilepticus: Secondary Analysis of the "Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial" (ADAPT) Dataset, 2014−2017 (5). My third Editor's Choice article is another look at anticonvulsant medications and the decision to select levetiracetam versus phenytoin. PCCM has previously published a meta-analysis on the use of these anticonvulsant medications as second-line emergency treatment for status epilepticus (21). Now, we can read about a secondary analysis of these medications as prophylaxis for status epilepticus in severe TBI (5). Here, the ADAPT dataset was used, which was a prospective, international, multicenter, comparative effectiveness study recruiting 1,000 severe TBI cases (2014−2017) (22). The current authors have used the U.S. Federal Interagency TBI Research (FITBIR) informatics repository system (https://fitbir.nih.gov) to gain access to the ADAPT trial data of 516 patients receiving status epileptics prophylaxis: 372 levetiracetam versus 144 phenytoin. Do read the full report (5), and for more context and an opinion about how we move forward review the accompanying editorial (6) and the 2019 severe TBI management guidelines (23). "PCCM CONNECTIONS" FOR READERS The PCCM Connections educational topic this month is ABD during sepsis and septic shock. Start with the 2022 consensus criteria for acute neurologic dysfunction in critically ill children developed by the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) collaborative (24). Also, consider the Sepsis Prevalence, Outcomes and Therapies (SPROUT) study investigators report on outcomes associated with the late onset of ABD relative to recognition of pediatric sepsis (25,26). Like the PODIUM criteria, SPROUT used the Glasgow Coma Scale score and pupil examination findings. Next, review two parallel lines of investigation. First, the multicenter approach to identifying a reproducible and clinically relevant sepsis phenotype with persistent hypoxemia, encephalopathy, and shock (27,28), which is now embedded within the 2024 International Consensus criteria for pediatric sepsis and septic shock (29,30). Second, the single-center approach–which extends the SPROUT findings–focused on validating a computational phenotype to identify sepsis-related ABD (31). Now, in the August issue of PCCM these authors compare the diagnostic potential of four definitions of ABD–including their own computational phenotype (31)–in a reference single-center dataset (7,8). "PCCM INTERNATIONAL" FOR READERS More educational material with an international perspective can be found in the PCCM Trials section. The highlighted work is from India and is a single-center RCT in 118 children: the authors have tested two forms of noninvasive respiratory support for moderate to severe acute bronchiolitis (9). This research question is of worldwide interest and PCCM has published many studies on respiratory support in bronchiolitis with either high-flow nasal cannula (HFNC) or continuous positive airways pressure (CPAP). For example, from the United States and Australia reports about costs of HFNC care in bronchiolitis (32,33); two U.S. perspectives describing standardized respiratory therapist-driven HFNC protocols (34,35); and, from Spain, a systematic review and network meta-analysis of high-flow oxygen and other noninvasive respiratory support therapies in bronchiolitis (36). Compare the time course of these data with the similar interventions in the single-center RCT from India (9). The accompanying editorial (10) is written by two clinical trialists from the United Kingdom and it provides readers with more thoughts about the next steps for international research networks (15,37,38). Finally, take time to re-read two commentaries from 2022 about the paired RCTs on HFNC or CPAP as first-line support for assistance in breathing in children (39,40).