PCCM Journal

February 2024 of Pediatric Critical Care Medicine (PCCM) is yet another important issue of the Journal. First, read the Foreword about “fair use of augmented intelligence and artificial intelligence in the preparation and review of submissions” to all three Society of Critical Care Medicine (SCCM) journals (i.e., Critical Care Medicine, PCCM, and Critical Care Explorations) (¹). For PCCM authors, readers, and reviewers, this position statement adds to PCCM’s 2023 recommendations for engaging with citation to references in the Chatbot Generative Pre-Trained Transformer era (²).

After the Foreword, by way of celebrating this year’s SCCM annual conference, look at the three Late Breaker (i.e., not previously published ahead of print) items that serve as my Editor’s Choices (^3–5). Taken together with the PCCM Connections section this month, all this material builds toward definitive answers to clinical questions; ultimately preparing for randomized controlled trials (RCT) or the equivalent form of clinical information.

Choong K, Fraser DD, Al-Farsi A, et al; Canadian Critical Care Trials Group: Early Rehabilitation in Critically Ill Children: A Two-Center Implementation Study (³).

My first editor’s choice article is our first late breaker report for the SCCM meeting. Here, the authors from two centers in Canada (during 2018 to 2020) performed an implementation study of “bundled care” consisting of analgesia-first sedation, delirium monitoring and prevention, and early mobilization (³). In over 1,000 patients, representing over 4,000 patient days, the authors looked for relationships between the use of bundled care and the incidence of delirium, ventilator-free days, length-of-stay, and mortality. The accompanying editorial provides important insight and gives background to the use of an alternative to RCTs when evaluating effectiveness of a bundle of care; that is, what is now called a “hybrid implementation study” with type 2 design (⁶).

The potential impacts of this work and editorial are, primarily, the addition of new information to the 2022 SCCM clinical practice guideline on “Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients with Consideration of the ICU Environment and Early Mobility” (⁷). The report also provides much needed detail about the ABCDEF (i.e., Assessing pain, Both spontaneous awakening and breathing trials, Choice of sedation, Delirium monitoring/management, Early exercise/mobility, and Family engagement/empowerment) approach in pediatric critical care (^8,9). Last, the report should be seen as exemplary in its dealings with the complexities of Implementation Science, as recently outlined by the subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network focused on Excellence in Pediatric Implementation Science (ECLIPSE) (^10,11).

Mills KI, Albert BD, Bechard LJ, et al: Stress Ulcer Prophylaxis Versus Placebo–A Blinded Randomized Controlled Pilot Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants With Congenital Heart Disease (SUPPRESS-CHD) (²).

My second editor’s choice and late breaker article is a report of a prospective pilot RCT in the cardiac intensive care unit (CICU) population carried out 2019-2022 (²). In the COVID-19 era, the authors were able to screen over 1,400 CICU admissions and recruited 58 patients to their pilot RCT about stress ulcer prophylaxis (i.e., histamine-2 receptor antagonist versus placebo) during CICU management in infants with congenital heart disease. The study adds to the catalogue of PCCM Trials content that I summarized in my end of 2023 review (¹²). Importantly, it follows an investigative approach using pragmatic trials to answer clinical questions in the CICU; for more information about pragmatic trials do review PCCM’s content on such studies (^13,14). The next question is whether the authors can use their pilot-RCT experience to deliver a definitive RCT. The answer would be so useful to our practice, by either informing the decision to stop giving unnecessary treatment or encouraging the decision to continue with routine stress ulcer prophylaxis.

Harley A, George S, Phillips N, et al; Resuscitation in Paediatric Sepsis Randomized Controlled Pilot Platform Study in the Emergency Department (RESPOND ED) Study Group: Resuscitation With Early Adrenaline Infusion for Children With Septic Shock–A Randomized Pilot Trial (³).

My third editor’s choice is another RCT feasibility study, which in this instance looks at a fluid-vasopressor algorithm in pediatric septic shock care (³). The question being asked is whether a protocol comparing early epinephrine infusion (i.e., started after a 20 mL/kg fluid bolus) versus standard care (i.e., 40−60 mL/kg fluid bolus followed by inotrope infusion) is safe and feasible in children with septic shock? Again, another pragmatic approach to answering a clinical question (see above and references 13, 14). Here, the investigators recruited 40 patients presenting to four pediatric emergency departments in Australia and concluded that a fluid-sparing algorithm, with early vasopressors, in septic shock is feasible and there is a rationale for performing a definitive RCT in children.

Of note, the “fluid-sparing” algorithm is not a new concept in the Journal, since the evolution of this idea was covered at the time of publication of the post-FEAST (i.e., Fluid Expansion as Supportive Therapy) trial era data analysis from Uganda and Kenya (^15,16). The next step for this algorithm should include broadening relevance to the international setting, as was highlighted in the recent Special Article on international sepsis diagnosis and care (¹⁷). Thought will also need to be given to the practicalities of early administration of peripheral vasoactive agents, as was covered in 2022 (^18–20). So, enjoy the read, and follow closely the next iterations of this work.

The pilot RCT about early vasopressors in septic shock (³) also provides us with an opportunity to focus on additional PCCM material about potential metabolic interventions in septic shock patients.

Looking back to 2022, the Journal published a four-article Mini Symposium on the topic of vitamins in sepsis and critical illness. There was a single-center prospective study from Switzerland of patients with blood culture proven-sepsis that demonstrated the frequent finding of low and deficient vitamin C (ascorbic acid) and vitamin B1 (thiamine) levels (²¹). There was also a single-center study from the United States that showed vitamin C deficiency in a significant proportion of critically ill patients, compared with a control group (²²). Last, there was a single-center study from Turkey that examined the prevalence and time course of thiamine deficiency in PICU patients (²³). Then, to bring this information together, there was an accompanying editorial about metabolic resuscitation during sepsis using the combination of Hydrocortisone, Ascorbic acid, and Thiamine in so-called HAT-therapy (²⁴). The conclusion being “…promising, but unproven therapeutic option for pediatric sepsis-associated organ dysfunction.”

Now, in this February issue there are two new articles about vitamin C and vitamin B1 in children with suspected sepsis. First, a study from Australia showing that critically ill children evaluated for sepsis frequently have decreased levels of vitamin C, with lower levels in children with higher severity, but no similar associations were evident for thiamine (²⁵). Second, a pilot RCT testing the feasibility of HAT-therapy in 60 children requiring vasopressors for septic shock; the authors from Australia and New Zealand concluded than a RCT was feasible, and it would require a sample size of 384 patients (²⁶).

Regarding the educational connection between the 2022 Mini Symposium (21−²⁴) and the two new reports (^25,26) on metabolic interventions in septic shock, it is worth spending time reviewing the contemporary PCCM data about hydrocortisone in pediatric septic shock from the United States. There is the 2013-−2017 life after pediatric sepsis evaluation (LAPSE) study that failed to identify an association between early corticosteroid therapy in children with septic shock and clinical and 1-month health-related quality of life outcomes (^27,28). There is also the 2015−2018 sepsis biomarker model (PERSEVERE)-II risk stratification study of pediatric septic shock, which had an opposite result to the LAPSE data and showed that corticosteroid administration was associated with increased mortality in a subgroup of children with high PERSEVERE-II risk score (^29,30). Hence, at present, we do not have a definitive answer about hydrocortisone. However, there is an ongoing RCT about Stress Hydrocortisone in Pediatric Septic Shock (SHIPSS, see ClinicalTrials.gov registration NCT03401398), which has now extended its recruitment to several international sites. Given the emerging international data on vitamin C and vitamin B1 levels in critically ill children with septic shock, the question is whether the metabolic dimension has more importance than previously thought?

It’s January 2024 and the 25^th volume of Pediatric Critical Care Medicine (PCCM) begins. It is a jubilee year for the Journal and at the start I draw your attention to another three Editor’s Choice articles. First, a secondary analysis of outcomes after in-hospital cardiac arrest (IHCA) in the 2016-2021 ICU-RESUScitation dataset (¹). Second, a single-center, retrospective review of experience using a prostacyclin analogue as the sole anticoagulant in continuous renal replacement therapy (CRRT) for critically ill children with liver diseases (2010−2019) (²). Third, a systematic review and meta-analysis registered with the International Prospective Register of Systematic Reviews (PROSPERO, see https://www.crd.york.ac.uk/prospero/) about tools and measures to predict fluid responsiveness in pediatric shock states (up to May 2022) (³). Each report has an accompanying editorial (^4–6).

Federman M, Sutton RM, Reeder RW, et al: Survival With Favorable Neurological Outcome and Quality of Cardiopulmonary Resuscitation Following In-Hospital Cardiac Arrest In Children With Cardiac Disease Compared With Noncardiac Disease (¹).

This month’s reading could begin with a secondary analysis of the 2016−2021 ICU-RESUScitation dataset (¹). This report is PCCM’s third item in a series from a cluster randomized controlled trial about IHCA care (^1,7,8). The authors have selected 1,100 patients and assessed the odds of favorable neurologic outcome in three groups: medical cardiac, surgical cardiac, and non-cardiac cases. The authors also examined cardiopulmonary resuscitation (CPR) quality and physiology, including features of chest compression, end-tidal partial pressure of cardon dioxide, and blood pressure. The accompanying editorial is from the newest member of PCCM’s Associate Editor team, Dr. Ravi Thiagarajan (⁴). There are useful insights into the recent history of CPR outcomes after IHCA, as well as a call to designing studies of CPR quality metrics.

Deep A, Alexander EC, Khatri A, et al: Epoprostenol (Prostacyclin Analogue) as a Sole Anticoagulant in Continuous Renal Replacement Therapy for Critically Ill Children With Liver Disease: Single Center Retrospective Study, 2010−2019 (²).

Prothrombotic risk and coagulopathy is a problem in critically ill patients with liver disease requiring CRRT. Therefore, my second Editor’s Choice is a timely evaluation. The report comes from a hepatology-focused PICU in the United Kingdom, which has a 10-year experience of using Epoprostenol (a prostacyclin analogue) as its sole CRRT anticoagulant (²). The authors describe their practice in 96 patients undergoing 353 filter episodes of CRRT, lasting over 18,500 hours. The accompanying editorial gives a helpful overview of anticoagulation strategies during various forms of extracorporeal support (⁵); it also comments on the practicalities of the Epoprostenol protocol (which can be found in the supplemental file of the U.K. report).

Walker SB, Winters JM, Schauer JM, et al: Performance of Tools and Measures to Predict Fluid Responsiveness In Pediatric Shock and Critical Illness: A Systematic Review and Meta-Analysis (³).

My third highlighted article is a PROSPERO-registered systematic review of the literature (³); the a priori registration underlines the rigor of this type of report for PCCM (⁹). In this review the authors identified 62 articles (up to May 2022) containing analyses of 54 unique fluid responsiveness predictive tools primarily in ventilated children in the operating room or PICU (³). Our editorialist discusses these tools, with a useful account about point of care ultrasound (POCUS) (⁶). Please read this information on POCUS in the context of other PCCM commentaries about regulating POCUS training and practice in the PICU (^10–12). Finally, it is also worth rereading PCCM’s two concise clinical physiology articles about the cardiovascular system in severe sepsis (¹³) and cardiogenic shock (¹⁴), and the helpful pressure-volume illustrations from the cardiovascular simulator when using fluid boluses for resuscitation.

This year we continue with the educational “connections” reading for our subscribers and trainees. This month’s focus is on links with the topic of IHCA, which was highlighted as an Editor’s Choice (^1,4). There are three reports (and their editorials) to review from large datasets that provide insight into other aspects of treatment during IHCA resuscitation. Take time to refresh your memory with these therapies. What about calcium administration during CPR for IHCA in children with heart disease, as reported in the American Heart Association’s “Get With The Guidelines Resuscitation” (GWTG-R) registry (^15,16)? What about sodium bicarbonate administration in pediatric cases of IHCA, as described in the ICU-RESUScitation project (^4,17)? And last, what about inappropriate shock delivery during pediatric IHCA, as identified by the international pediatric cardiac arrest quality improvement collaborative in the Pediatric Resuscitation Quality (pediRES-Q) study (¹⁸)?

December 2023 and we’re closing this year with another strong issue of Pediatric Critical Care Medicine (PCCM). There are four Editor’s Choice articles: two about severe acute viral respiratory illness and one focused on parents of critically ill children. The fourth Editor’s Choice article covers malnutrition and nutritional support in the PICU and serves as a stimulus to the further reading mentioned in the PCCM Connections section. Finally, there is a PCCM Narrative this month.

Leland SB, Staffa SJ, Newhams MM, et al; Pediatric Acute Lung and Sepsis Investigator’s Network Pediatric Intensive Care Influenza Study Group (PALISI PICFLU) Investigators and Overcoming COVID-19 Investigators: The Modified Clinical Respiratory Progression Scale for Pediatric Patients: Evaluation as a Severity Metric and Outcome Measure in Severe Acute Respiratory Illness (¹).

In this exploratory report (¹), a subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network (²) modified the World Health Organization (WHO) Clinical Progression Scale for patients with acute viral respiratory illness during PICU admission. The PALISI network group first presents details of scale development followed by testing in three separate datasets: the Pediatric Intensive Care Influenza (PICFLU) study; the PICFLU Vaccine Effectiveness (PICFLU-VE) study; and the Overcoming COVID-19 public health surveillance registry. Read the article and examine the informative alluvial plots. This clinical progression scale for pediatrics could become an outcome measure in randomized controlled trials (RCT) of therapy for viral lower respiratory tract infective illness

Miranda M, Ray S, Boot E, et al: Variation in Early Pediatric Intensive Care Management Strategies and Duration of Invasive Mechanical Ventilation for Acute Viral Bronchiolitis in the United Kingdom: A Retrospective Multicenter Cohort Study (³).

My next Editor’s Choice article describes a multicenter retrospective study of infants receiving invasive mechanical ventilation (IMV) for bronchiolitis in the United Kingdom (³). Previously, some of the authors reported a three-center retrospective cohort of 462 infants undergoing IMV for bronchiolitis over the period 2012−2016 (⁴). The authors identified between-center variations in both practice and outcomes and suggested that these findings could be further tested through implementing “optimal care bundles.” The U.K. group has not reached the point of such a prospective study but has extended its review from three to 13 centers: now studying a population of 350 infants receiving IMV for bronchiolitis in 2019. The authors again report factors associated with duration of IMV and the results of sedation practices will be of interest to our community. (Please read these findings alongside the 2022 Society of Critical Care Medicine [SCCM)] clinical practice guidelines [CPG] on sedatives during IMV; in particular, read through Table 1 in the CPG [⁵]). The U.K. researchers found variation in sedation practices during IMV for bronchiolitis in the 13 centers in the United Kingdom in 2019. If this difference exists today–this is four years later–it suggests another opportunity for a U.K.-wide pragmatic trial which, after all, is its research expertise (⁶). The authors are now advocating for RCTs during IMV for bronchiolitis with simultaneous study of multiple questions: standard versus restricted fluid management; nasal versus oral endotracheal intubation; and alpha-2 agonists versus benzodiazepines. Perhaps the clinical progression scale for acute viral respiratory illness described in my first Editor’s Choice article will also have a role (¹).

Pryce P, Gangopadhyay M, Edwards JD: Parental Adverse Childhood Experiences and Post-PICU Stress in Children and Parents (⁷).

My third Editor’s Choice article (⁷) continues the theme of parental mental health that has been a focus at PCCM, with recent contributions on screening for factors influencing parental psychological vulnerability (^8,9) and the protracted consequence of posttraumatic stress disorder (PTSD) in parents of critically ill children (^10,11). In an observational study carried out in 2021, the authors collected data from 145 parents and examined associations between a parent’s history of adverse childhood experiences and their own post-PICU PTSD symptoms (⁷). There is an accompanying editorial by a clinical psychologist (and PCCM Editorial Board member), Dr. Gillian Colville, who asks us to think more about the social determinants of health and the growing literature on risk and protective factors related to development of psychological difficulties (¹²). Also read Dr Colville’s report of 20 years as an embedded psychologist within the PICU in this month’s issue (¹³).

Campos-Mino S, Figueiredo-Delgado A, Zarate P, et al; Nutrition Committee, Latin American Society of Pediatric Intensive Care (SLACIP): Malnutrition and Nutrition Support in Latin American PICUs: The Nutrition in PICU (NutriPIC) Study (¹⁴).

My fourth Editor’s Choice article comes from the Latin American Society of Pediatric Intensive Care (SLACIP) and is a point prevalence study of malnutrition and nutritional support in 41 PICUs in 13 Latin American countries on one day in 2021 (¹⁴). SLACIP identified 311 children on the day of study who, in general, had adequate enteral nutritional support but half the children did not receive recommended levels of calories and protein.

Please read the article because it serves as the starting point from which to review contemporary questions about enteral nutrition in the PICU: 1) What is happening worldwide; 2) What about fellowship education in this subject area; 3) What are the new techniques for feeding tube placement; 4) What can be done during noninvasive respiratory support; and 4) What is the up-to-date clinical science? The article also adds to the international work that PCCM has recently published from South Africa, Malawi, Kenya, India, Thailand, Malaysia, and Singapore. (For more information about the international reports, look at the website (https://journals.lww.com/pccmjournal/pages/collectiondetails.aspx?TopicalCollectionId=26): select the “Collections” drop-down menu, and click on the items in the “Editor’s Choice” section for an overview, issue-by-issue.)

After reading my fourth Editor’s Choice article (¹⁴), by way of an educational review, move onto the 2019 world survey of 920 PICU practitioners in 57 countries that asked about barriers to delivery of enteral nutrition (¹⁵). Then read the 2019 survey of North American pediatric critical care fellowship programs, with 20 program directors and 60 fellows, which found that nutrition education was “highly underrepresented” in curricula (¹⁶). Next, review the report on postpyloric feeding tube placement under ultrasound guidance (^17,18). Look at the 2018−2019, four-center European PICU report of feeding practices and energy balance in 190 children receiving noninvasive respiratory support (^19,20). Last, search out two articles that address mechanistic aspects of adequacy of enteral nutrition in critically ill patients receiving IMV support: one brief report about anticholinergic drug burden (²¹), and the other a Concise Clinical Science Review about the Zonulin pathway in gastrointestinal dysfunction (²²).

Finally, before moving through the rest of this issue of PCCM from our authors, reviewers, and editors, read the PCCM Narrative Essay called “Shared Vulnerabilities” (²³). I have also written a foreword to the December 2023 issue that will give some insight into PCCM’s processes and metrics this year (²⁴).

November 2023 and a new venture for Pediatric Critical Care Medicine (PCCM): a whole issue focused on cardiac intensive care. The Associate Editor for cardiac critical care, Dr. Paul A. Checchia, has written a Foreword for the issue that focuses on two example themes in PCCM and Cardiac Critical Care Research (¹). Our expectation is that the broad range in cardiac-related reading material will be welcomed (e.g., pharmacology and toxicology, laboratory measurement, airway management, extracorporeal life support, outcomes and psychosocial care, implementation science, and clinical trials). My task is not to detract from this month’s cardiac emphasis and perspective, but to highlight three Editor’s Choice articles that will also make non-cardiac intensive care clinicians want to read and engage with the cardiac intensive care research reports this November. Because this is a special month, I will add to each of my three choices additional material that would normally fall within the educational content found in the section called PCCM Connections for Readers. Therefore, this month I will use my main highlights as a guide to further reading about extracorporeal cardiopulmonary resuscitation (E-CPR), durable vascular access in neonates, and point-of-care ultrasound (POCUS).

Lasa JJ, Guffey D, Bhalala U, et al: Critical Care Unit Characteristics and Extracorporeal Cardiopulmonary Resuscitation Survival in the Pediatric Cardiac Population: Retrospective Analysis of the Virtual Pediatric System Database (²).

There are 650 patients with cardiac disease who underwent E-CPR between 2010 and 2018 in the U.S. Virtual Pediatric System (VPS, LLC) database. The authors report associations between PICU type (i.e., general mixed versus solely cardiac), unit bed capacity, patient category (i.e., surgical, or medical cardiac patient), and outcomes.

PCCM Connections for Readers: There are two other E-CPR-related articles in the November issue. First, there is an Extracorporeal Life Support Organization (ELSO) registry study of 567 patients without congenital cardiac disease who underwent E-CPR between 2017 and 2019 (³). As you read this material, compare the VPS and the ELSO studies. In the ELSO study, the authors examined patient-level factors associated with greater or lesser odds of in-hospital mortality. Next, there is a single-center, retrospective study of 87 patients with a range of diagnoses who underwent E-CPR between 2014 and 2020. The authors focused on the relationship between the timing of resuscitation-dosing of epinephrine and the associated immediate hemodynamic outcomes (e.g., afterload) and extracorporeal membrane oxygenation (ECMO) pump parameters after cannulation (⁴). There is a very helpful editorial accompanying the article (⁵); also go back to the 2020 systematic review of E-CPR (⁶).

Mills M, Chanani N, Wolf M, et al: Durable Vascular Access in Neonates in the Cardiac ICU: A Novel Technique for Tunneled Femoral Central Venous Catheters (⁷).

My next Editor’s Choice article describes a two-puncture approach to place a tunneled femoral central venous line in neonates in the cardiac intensive care unit. The authors designed this technique and placed this form of vascular access in 161 patients between 2017 and 2021. The report comes with technical aspects, equipment list, a training video, and performance and morbidity data. There is a thoughtful editorial accompanying the article, with interesting history of medicine details (⁸).

PCCM Connections for Readers: There is one other recent technical note about venous access that will be of interest alongside the above report. You may recall that clinicians from three tertiary care units in the United States caring for infants with congenital heart disease described their experience of real-time, ultrasound-guided umbilical vein cannulation–incidentally, a beautifully illustrated account (⁹).

Maxson IN, Su E, Brown KA, et al; Pediatric Research Collaborative on Critical Ultrasound (PeRCCUS), a subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: A Program of Assessment Model for Point-of-Care Ultrasound Training for Pediatric Critical Care Providers: A Comprehensive Approach to Enhance Competency-Based Point-of-Care Ultrasound Training (¹⁰).

My third Editor’s Choice article is about competency with POCUS and how we incorporate training at the bedside. During the last three years we have published reports about using POCUS for each of the following: assessing fluid responsiveness in mechanically ventilated and hemodynamically unstable neonates (¹¹); identifying likely etiology of acute respiratory failure in children (^12,13); placing umbilical venous cannulas in neonates with congenital heart disease (⁹); and, in this month’s issue, quantifying the akinetic heart at unexpected cardiac arrest (¹⁴). We now have a position paper and call to action by the PeRCCUS (Pediatric Research Collaborative on Critical Ultrasound) subgroup of the PALISI (Pediatric acute lung injury and Sepsis Investigators) network (¹⁵). It is well worth a read by all educators: look closely at the framework presented in the Figures and Tables.

PCCM Connections for Readers: There are two themes that will be relevant connections for readers. First, the educational dimension for cardiac intensive care higher professional training. In 2022, PCCM published details of the cardiac critical care fellowship curriculum and the entrustable professional activity (EPA) levels needed for clinical and administrative competency (^16–18). The PeRCCUS group has now added more EPAs to that list. Second, we can consider the new PeRCCUS article as a natural progression of the 2021 debate about regulating critical care ultrasound by pediatric critical care practitioners (^19,20).

My three Editor’s Choices for the October issue of Pediatric Critical Care Medicine (PCCM) highlight important aspects of what is understood by brain involvement during critical illness. We now use a range in terminologies, but what do they mean and what is their significance? So, my three choices are: first, sepsis and “encephalopathy”; second, sepsis and “acute disorders of consciousness”; and third, outcome after “acquired brain injury.” The PCCM Connections for Readers focuses on team continuity during prolonged PICU admission.

Sanchez-Pinto LN, Bennet T, Stroup EK, et al: Derivation, Validation, and Clinical Relevance of a Pediatric Sepsis Phenotype With Persistent Hypoxemia, Encephalopathy, and Shock (¹).

In my first Editor’s Choice we return to the topic of time course and trajectory in sepsis and septic shock (^2–5), but with the added nuance of a phenotype that includes the term “encephalopathy.” However, what is meant by “encephalopathy” in this context? Our authors identified encephalopathy retrospectively using a Glasgow Coma Scale (GCS) score that was most frequently in the category 10 to 12 (^1,6), which would be classified as a moderate severity injury in traumatic brain injury (TBI).

The 2012–2018 cohort has over 15,000 pediatric patients with sepsis-associated multiple organ dysfunction syndrome (MODS) and the encephalopathy phenotype was present in 1-in-3 cases (¹). Please read the report as well because the accompanying editorial which, together, provide important details about the meaning and trajectory of such brain symptomatology during sepsis-associated MODS (⁷).

Cheung C, Kernan K, Berg RA, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network: Acute Disorders of Consciousness in Pediatric Severe Sepsis and Organ Failure: Secondary Analysis of the Multicenter Phenotyping Sepsis-Induced Multiple Organ Failure Study (⁸).

My next Editor’s Choice article is a secondary analysis of data from the multicenter, prospective PHENOMS (Phenotyping Sepsis-Induced Multiple Organ Failure Study) cohort, 2015–2017 (^5,9). The authors defined “acute disorder of consciousness” as a GCS score below 12 in the absence of sedatives on the initial study day of sepsis-induced organ failure; therefore, in essence, a definition like the criterion for encephalopathy used in my first Editor’s Choice (¹).

In a population of 401 patients, 1-in-5 cases had the depressed GCS phenotype, and the authors go on to describe clinical and laboratory characteristics—another theme that we have followed closely in PCCM (^5,9–11). The editorial gives us a broad view of how we can “unravel the intricate relationship between sepsis, organ dysfunction, and neurologic manifestations in pediatric patients” (¹²).

As a reader of PCCM you may also want to review our recent material about timing of acute neurologic dysfunction in relation to sepsis recognition (^13,14) and the choice of clinical assessment (¹⁵). Finally, also consider the computational phenotype of “acute brain dysfunction” regarding database research—based on using neuroimaging or electroencephalography as part of evaluating neurologic change—which had better diagnostic performance than the GCS in sepsis (¹⁶).

Williams CN, Hall TA, Baker VA, et al: Follow-up After PICU Discharge for Patients With Acquired Brain Injury: The Role of an Abbreviated Neuropsychological Evaluation and a Return-to-School Program (¹⁷).

My third Editor’s Choice article about brain health extends the Journal’s theme on follow-up programs and PICU outcomes and is a link between neurology during PICU admission and morbidity at follow-up. For example, in 2021, there was a scoping review of instruments and methods for assessing overall health after PICU admission (¹⁸) and, in 2022, there was description of a core outcome measurement set for evaluating PICU survivorship (^19,20). The Journal also published three descriptions of structured follow-up by clinical programs in Canada, the United States, and the Netherlands (^21–24). There was the most comprehensive and detailed clinical research analysis of physical, emotional/behavioral, and neurocognitive developmental outcomes 2−4 years after PICU admission in over 600 patients from a randomized clinical trial cohort (^25,26).

Two neurocritical programs in the US describe a multidisciplinary 1-month follow-up of 289 school-aged children at-risk of cognitive impairment, because of “acquired brain injury” most commonly due to TBI with GCS 9 to 13 (¹⁷); rather like the GCS of patients in my first two Editor’s Choices (see above). Of note here, the authors describe using an abbreviated battery of neuropsychological tests that proved useful in identifying new impairments and screening for referral to specialist services. There is an accompanying editorial (²⁷).

This third Editor’s Choice article (¹⁷), when considered in conjunction with the other choices (^1,8), made me want to re-read the 1- and 3-month outcomes work of the LAPSE (Life After Pediatric Sepsis Evaluation) investigators in their 2014–2017 sepsis cohort (^28,29), and their most recent publications (i.e., one also appearing in this month’s issue (³⁰), and another with 12-month outcomes appearing later this year (³¹)). There is much to consider.

This month’s topic for educational review is a Society of Critical Care Medicine (SCCM)-endorsed Special Article from the Lucile Packard Foundation PICU continuity panel (³²). Thirty-seven experts have generated 17 consensus statements about continuity strategies for long-stay PICU patients. Please read the article and, as context, see the experts’ previous survey of contemporary practices and perceptions in US PICUs with training fellowship programs (³³) and the accompanying editorial published in June 2023 (³⁴).

This Special Article adds to the Journal’s compendium on pediatric chronic critical illness. I recommend the scoping review on case definition of pediatric chronic critical illness (³⁵) and the description of prevalence in a single center (³⁶). Next, consider reading about an overlapping entity called pediatric complex chronic condition (or medical complexity); it has variable identification in US PICUs (³⁷), yet accounts for high-frequency PICU utilization (³⁸). Finally, read the qualitative analysis of clinical care strategies that support parents of children with complex chronic conditions, particularly during their child’s end-of-life care in the PICU (^39,40).

The September 2023 issue and this year has already proven to be important for improving our understanding of pediatric acute respiratory distress syndrome (PARDS); Pediatric Critical Care Medicine (PCCM) has published 16 articles so far. Therefore, my three Editor’s Choice articles this month highlight yet more PCCM material about PARDS by covering the use of noninvasive ventilation (NIV), the trajectory in cytokine profile during illness, and a new look at lung mechanics. The PCCM Connections for Readers give us the opportunity to focus on some clinical biomarkers of severity and mortality risk during critical illness.

Emeriaud G, Pons-Odena M, Bhalla AK, et al; Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology (PARDIE) Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Noninvasive Ventilation for Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study (¹).

Whether to use noninvasive respiratory support during the development of PARDS has been debated for several years. The discussion was featured in the 2015 Pediatric Acute Lung Injury Consensus Conference (PALICC-1) guidance and was still ongoing in the 2023 PALICC-2 report (^2,3). However, in early 2023, PCCM published a systematic review and meta-analysis of NIV support in PARDS (⁴). The Journal also published a Concise Clinical Physiology Review on PARDS pathophysiology that described the differential detrimental effect of spontaneous breathing in mild versus severe PARDS, and the potential for developing ventilator-induced lung injury (VILI) and, so-called, patient self-inflicted lung injury (P-SILI) (⁵).

The PARDS Incidence and Epidemiology (PARDIE) investigators now report a planned ancillary study of their 2016/2017 prospective cohort in which 160 of 708 PARDS cases underwent NIV at the time of PARDS diagnosis (¹). These are unique data, albeit from 6 years ago–but this is as good it gets. Our editorialists even go so far as to say that the PARDIE-NIV work is a “game changer” for decision-making in clinical practice (⁶), and it may even lead to more clinical research into the entity they call “NIV-induced lung injury” (which may be P-SILI).

Ardila SM, Weeks HM, Dahmer MK, et al; Biomarkers in Children with Acute Lung Injury and Randomized Evaluation for Sedation Titration for Respiratory Failure (RESTORE) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: A Targeted Analysis of Serial Cytokine Measures and Nonpulmonary Organ System Failure in Children With Acute Respiratory Failure: Individual Measures and Trajectories Over Time (⁷).

My next Editor’s Choice article is a secondary analysis of data from the Biomarkers in Acute Lung Injury (BALI) ancillary study–a component of the Randomized Evaluation for Sedation Titration for Respiratory Failure (RESTORE) trial–which included some sepsis patients, but of note there were over 350 patients with PARDS (⁸). The new report by the BALI-RESTORE investigators focuses on trajectories in clinical state and inflammatory cytokines (⁷). Of note, the work adds to PCCM’s ongoing literature about trajectories and phenotype. Review, for example, other reports on trajectory-based phenotype: in sepsis, related to changes in C-reactive protein and ferritin levels (^9,10); or in prolonged shock, related to changes in vasoactive inotrope score and cytokines (^11,12); or in moderate to severe PARDS, related to persistence of hypoxemia (¹³).

Taking all this work together, we have the making of a coherent narrative about patient trajectory in an inflammation-shock-PARDS continuum (^7–13). I wonder whether this axis will converge with another research narrative within PCCM: the literature about machine learning and dynamic modeling of real-time criticality, deterioration, and mortality risk (^14–20).

Cruces P, Moreno D, Reveco S, et al: Plateau Pressure and Driving Pressure in Volume- and Pressure-Controlled Ventilation: Comparison of Frictional and Viscoelastic Resistive Components in Pediatric Acute Respiratory Distress Syndrome (²¹).

My third Editor’s Choice article about PARDS focuses on lung mechanics. For some context, during 2021 to 2023 the Journal published reports about mechanical ventilation and the potential lung exposure to the energy of mechanical power and the risk of VILI (^22–24), and about the mechanics of ventilator-driving pressure and this transmitted energy (using the “power” calculations) (^25,26). However, there has been little about airway resistance during mechanical ventilation in PARDS (^4,27).

We now have some detailed physiology of lung frictional, viscoelastic and elastic resistive components during volume-controlled and pressure-controlled ventilation in 18 PARDS patients (²¹). Please read this clinical report along with the author’s Concise Clinical Physiology Review on PARDS pathophysiology that appeared in the February 2023 issue (⁴).

This month’s special topic for educational review is biomarker research, whether related to severity of illness and mortality risk during critical illness, or whether related to severity of potential toxic exposure because of treatment during critical illness. There are three articles that bring these ideas together in the September 2023 issue.

Begin with the article reporting the association between a compound variable–the Lactate-Albumin ratio (i.e., severity biomarker)–rather than each of its components alone, with mortality and multiple organ dysfunction in over 600 PICU patients (²⁸). There is an accompanying editorial (²⁹), and it is also worth looking at a PCCM 2022 international report about lactate and severity of illness scoring (³⁰).

Next, read about the association between potentially excess oxygen exposure (i.e., severity exposure) and death in over 3,000 mechanically ventilated children (³¹). The report builds on a 2022 paper in the Journal using the same oxygen exposure metric (³²), and there is an accompanying editorial (³³). What is of real importance and concern when we consider the other PCCM literature and commentaries on excess oxygen exposure (^34–37) is that they all point in the direction of potential for toxicity and risk of harm. We must now eagerly await the findings of the United Kingdom randomized multicenter trial of conservative versus liberal oxygenation targets in critically ill children in the PICU (Oxy-PICU) (^38,39). Recruitment of over 2,000 mechanically ventilated children finished early 2023.

Finally, complete this month’s educational review by reading about hyperferritinemia (i.e., severity biomarker) in severe Dengue infection (⁴⁰). This new work not only adds to PCCM’s narrative about Dengue, but it also ties in with the other literature on trajectory in ferritin in sepsis (^9,10).

There are three excellent Editor’s Choice articles for the August 2023 issue of Pediatric Critical Care Medicine (PCCM). First, a much-awaited report from the Society of Critical Care Medicine (SCCM) ICU liberation campaign focused on a bundle of six quality improvement (QI) initiatives in the PICU. Second, a study to better understand physician experiences with families as they respond to the potential diagnosis of their child’s death by neurologic criteria (DNC). Third, a multidisciplinary evaluation of an algorithm for testing practices and approach to differential diagnosis in PICU patients with new fever or instability. The PCCM Connections for Readers focuses on practices during life support with extracorporeal membrane oxygenation (ECMO).

Lin JC, Srivastava A, Malone S, et al; Society of Critical Care Medicine’s Pediatric ICU Liberation Campaign Collaborative: Caring for Critically Ill Children With the ICU Liberation Bundle (ABCDEF): Results of the Pediatric Collaborative (¹).

SCCM’s six-component ABCDEF (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment, prevention, and management; Early mobility and exercise; Family engagement and empowerment) “Bundle” creates management goals aimed at optimizing pediatric care and family participation during critical illness. We have the benefit of the 2022 SCCM clinical practice guidelines (CPG) on “prevention and management of pain, agitation, neuromuscular blockade, and delirium in critically ill pediatric patients with consideration of the ICU environment and early mobility” (²). The new SCCM report extends the CPG by addressing PICU-wide and individual feasibility and outcomes associated with CPG implementation. Readers, please note that PCCM has published other reports about implementing QI-related bundles of care (^3–6) and, in this context, the new article is extensive and wide-reaching.

The SCCM ABCDEF bundle was implemented in 632 patients, during 6,252 days of PICU care, when there were 47 deaths. The accompanying editorial makes us pause for thought and reflect on the current findings (⁷). Overall, the pediatric SCCM ABCDEF study is important, it must be read, and we clearly need to make refinements to our clinical research in this area.

Lin JC, Srivastava A, Malone S, et al; Society of Critical Care Medicine’s Pediatric ICU Liberation Campaign Collaborative: Caring for Critically Ill Children With the ICU Liberation Bundle (ABCDEF): Results of the Pediatric Collaborative (¹).

SCCM’s six-component ABCDEF (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment, prevention, and management; Early mobility and exercise; Family engagement and empowerment) “Bundle” creates management goals aimed at optimizing pediatric care and family participation during critical illness. We have the benefit of the 2022 SCCM clinical practice guidelines (CPG) on “prevention and management of pain, agitation, neuromuscular blockade, and delirium in critically ill pediatric patients with consideration of the ICU environment and early mobility” (²). The new SCCM report extends the CPG by addressing PICU-wide and individual feasibility and outcomes associated with CPG implementation. Readers, please note that PCCM has published other reports about implementing QI-related bundles of care (^3–6) and, in this context, the new article is extensive and wide-reaching.

The SCCM ABCDEF bundle was implemented in 632 patients, during 6,252 days of PICU care, when there were 47 deaths. The accompanying editorial makes us pause for thought and reflect on the current findings (⁷). Overall, the pediatric SCCM ABCDEF study is important, it must be read, and we clearly need to make refinements to our clinical research in this area.

Paquette ED, Ross LF, Chavez J, Frader JE: Refusals of the Determination of Death by Neurologic Criteria: A Mixed Methods Study of Physician Perspectives on Refusals Cases (⁸).

My second Editor’s Choice article is about physician perspectives of parent/family refusals at the time of determination of DNC. By way of background, start with the contemporary international literature (2020 to 2023) on determination of death. For example, review the 2020 World Brain Death Project report (⁹) and the 2023 CPG for a brain-based definition of death in children and adults in Canada (¹⁰). Then consider the work about the public’s understanding of the definition and determination of death. There is a 2022 scoping review (¹¹), a 2023 national survey of public opinion in Canada (¹²), and a 2023 report of interviews in family members with relatives dying after determination of DNC (¹³). Despite these detailed articles on families at the time of death, we have heard little about physicians and their decision-making when families refuse testing for the determination of DNC (¹⁴).

PCCM publishes a report about refusals to allow examination for determination of DNC from an online survey of 80 pediatric intensivists and neurologists, with detailed phone interviews in 12 of the respondents. The clinicians describe their approaches when managing refusals, and the impact of these decisions on their medical teams. This work echoes previous PCCM publications on the topics of therapeutic alliance between parents and physicians (¹⁵) and communications about prognosis (^16–18). Our editorial writer also adds to our understanding with more context about the United States 1980 Uniform Determination of Death Act, the case of Jahi McMath, and a personal view (¹⁹).

Sick-Samuels AC, Booth LD, Milstone M, et al: A Novel Comprehensive Algorithm for Evaluation of PICU Patients With New Fever or Instability (²⁰).

My final Editor’s Choice article returns to the topic of QI in the PICU (¹). Over 2021 to 2023, the QI themes of antibiotic stewardship (^21–23), bacterial investigations (^24,25), and diagnostic accuracy (^26,27), have had extended coverage in PCCM, and all this material is worth reviewing. Now, in this latest QI report (²⁰), the authors follow PCCM’s guidance on reporting QI studies (^28,29) and describe their pre- versus postimplementation findings (4,290 versus 2,843) of an algorithm for PICU patients with new fever or clinical instability. There is an accompanying editorial (³⁰); also read another relevant article and editorial about serial tracheal aspirate cultures in the PICU (^31,32).

This month’s special topic for educational review is life support with ECMO. There are five articles about ECMO in the August 2023 issue (^33–37): an extracorporeal life support organization database study of neonates undergoing life support with either centrifugal or conventional roller pumps (³³); two articles on outcomes in specific patient populations, with one about status asthmaticus (³⁴) and the other about neonates with congenital diaphragmatic hernia (³⁵); and, last, two articles about acute care during life support–a literature review of nutrition (³⁶) and an electroencephalography study of seizure identification (³⁷).

Finally, another highlight for me in the narrative essay series is the article entitled “The Exchange” (³⁸).