Open Access Article: 25 Years of Pediatric Critical Care Medicine: An Evolving Journey with the WFPICCS
Our president, Jeffrey P. Burns, and past presidents, Brenda M. Morrow, Andrew C. Argent, and Niranjan Kissoon, have written an insightful paper reflecting on the advancements and milestones in pediatric critical care over the past 25 years.
Don’t miss learning about the contributions and evolving role of the WFPICCS in shaping the field, especially the impact of the PCCM and World Congress.
Read the article HERE
Pediatric Critical Care Medicine Journal
The journal Pediatric Critical Care Medicine is the Federation’s official journal. The journal covers a full range of scientific content. Additionally, the journal includes abstracts of selected articles published in Chinese, French, Italian, Japanese, Portuguese and Spanish translations – making news of advances in the field available to pediatric and neonatal intensive and critical care practitioners worldwide. Read More about The Journal Subscriber to the Journal Here
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Editor’s Choice
The Pediatric Critical Care Medicine (PCCM) Editor-in-Chief, Robert C. Tasker, MBBS, MD, FRCP highlights three articles he wants to draw readers’ attention to in each issue.
We will be posting these on our website each month, and invite you to come back and peruse these monthly.
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” November 2024
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” October 2024
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” August 2024
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” September 2024
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” June 2024
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” July 2024
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” April 2024
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” May 2024
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” January and February 2024
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” March 2024
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” December 2023
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” November 2023
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” October 2023
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” September 2023
PCCM Editor-in-Chief, Robert C. Tasker’s “Editor’s Choices” August 2023
Editor’s Choice Articles for December 2024
Pediatric Critical Care Medicine. 25(12):1086-1088, December 2024.
Pediatric Critical Care Medicine. 25(12):1089-1095, December 2024.
OBJECTIVE:To describe the use of nuclear medicine cerebral perfusion studies as an ancillary test for brain death/death by neurologic criteria (BD/DNC) in infants aged under 1 year.
DESIGN:Retrospective case series.
SETTING:Single-center, quaternary, academic children’s hospital in the United States.
PATIENTS:Patients younger than 1 year of age whose evaluation for BD/DNC included a nuclear medicine cerebral perfusion study as an ancillary test, 2005–2022.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:Ten infants were identified from local databases. Mechanisms of brain injury included hypoxic-ischemic injury (8/10), traumatic brain injury (1/10), and intracranial hemorrhage (1/10). Testable components of the first BD/DNC examination were consistent with BD/DNC in all patients. Apnea testing was consistent with BD/DNC in 5 of 10 patients and deferred or terminated prematurely in 5 of 10 patients. All patients underwent ancillary testing with a nuclear medicine scan to assess cerebral perfusion using 99m Tc-ethyl cysteinate dimer ( 99m Tc-ECD). Indications were inability to complete the apnea test (5/10), presence of a confounder to the clinical examination (3/10), and clinician discretion (2/10). Nine studies were consistent with BD/DNC. The patient whose ancillary test was inconsistent with BD/DNC had their examination limited by the inability to assess the pupillary reflex and subsequently underwent withdrawal of life-sustaining technology.
CONCLUSIONS:Radionuclide cerebral perfusion studies using 99m Tc-ECD were used in our setting to support the determination of BD/DNC in infants aged younger than 1 year of age.
Aziz, Omer MRCPCH; Main, Thomas B. N. MRCPCH; Hannon, Faith R. MRCPCH; Fraser, James I. FRCPCH
Abstract
OBJECTIVES:
In the United Kingdom, the starting point for diagnosing and confirming death using neurologic criteria (DNC) is when death is suspected to have occurred following devastating brain injury in patients on an ICU who remain deeply comatose, have absent brainstem reflexes and are apneic with their lungs mechanically ventilated but in whom circulation and other bodily functions persist. In this report, we describe the U.K. experience of diagnosing DNC in children.
DESIGN:
Retrospective review of data collected by the U.K. National Health Service Blood and Transplant Potential Donor Audit.
SETTING AND PATIENTS:
U.K. children from birth to younger than 18 years old with suspected DNC between April 1, 2015, and April 1, 2023.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
A total of 824 children were suspected of DNC and 565 of 824 (68.6%) proceeded to have testing. Overall, 393 of 565 (69.5%) of the tested patients were cared for on a PICU, 164 of 565 (29%) on an adult ICU, three of 565 (0.5%) on a neonatal ICU, and the other five of 565 (1%) in other locations. After testing, 548 of 565 (97%) were confirmed as having died using neurologic criteria. During 2020 to 2023, we estimate that DNC occurred in 6.2% of all PICU deaths. Of 393 of 565 children undergoing testing on the PICU, 15 were younger than 2 months, 45 between 2 months to 1 year, and 31 between 1 and 2 years.
CONCLUSIONS:
During the 8 years, 2015–2023, out of 824 children younger than 18 years old suspected of being dead using neurologic criteria, close to one-in-three did not proceed to formal testing. In 2020–2023, DNC in U.K. PICUs accounted for 6.2% of all death. Last, in young children up to 2 years old, the average experience of diagnosing and confirming DNC across each of the 30 U.K. PICUs was one patient every other year.
Paice, Kelli MD1,2; Tang Girdwood, Sonya MD, PhD2,3,4; Mizuno, Tomoyuki PhD2,4; Pavia, Kathryn MD1,2; Punt, Nieko MSc5,6; Tang, Peter PhD4,7; Dong, Min PhD2,4; Curry, Calise BA3; Jones, Rhonda MBA8; Gibson, Abigayle BS1; Vinks, Alexander A. PharmD, PhD2,4; Kaplan, Jennifer MD, MS1,4
Abstract
OBJECTIVES:
To determine the frequency of early meropenem concentration target attainment (TA) in critically ill children with severe sepsis; to explore clinical, therapeutic, and pharmacokinetic factors associated with TA; and to assess how fluid resuscitation and volume status relate to early TA.
DESIGN:
Retrospective analysis of prospective observational cohort study.
SETTING:
PICU in a single academic quaternary care children’s hospital.
PATIENTS:
Twenty-nine patients starting meropenem for severe sepsis (characterized as need for positive pressure ventilation, vasopressors, or ≥ 40 mL/kg bolused fluid), of which 17 were newly escalated to PICU level care.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Concentration-time profiles were analyzed using modeling software employing opportunistic sampling, Bayesian estimation, and a population pharmacokinetic model. Time above four times minimum inhibitory concentration (T > 4×MIC), using the susceptibility breakpoint of 1 µg/mL, was determined for each patient over the first 24 hours of meropenem therapy, as well as individual clearance and volume of distribution (Vd) estimates. Twenty-one of 29 patients met a target of 40%T > MIC 4 μg/mL. Reaching TA, vs. not, was associated with lower meropenem clearance. We failed to identify a difference in Vd or an association between the TA group and age, weight, creatinine-based estimated glomerular filtration rate (eGFR), or the amount of fluid administered. eGFR was, however, negatively correlated with overall T > MIC.
CONCLUSIONS:
Eight of 29 pediatric patients with early severe sepsis did not meet the selected TA threshold within the first 24 hours of meropenem therapy. Higher clearance was associated with failure to meet targets. Identifying patients likely to have higher meropenem clearance could help with dosing regimens.
Editor’s Choice Articles for November 2024
Pediatric Critical Care Medicine. 25(11):985-987, November 2024.
Baker, David R. MD1; Glau, Christie L. MD1; Himebauch, Adam S. MD, MSCE1; Arnoldi, Sara MD2; Rosenblatt, Sam MD, MSEd1; Keim, Garrett MD1; Loscalzo, Steven M. MD1; Weber, Mark D. MSN, RN, CRNP-AC, FCCM1; Cohen, Meryl MD, MSEd3; Quartermain, Michael D. MD3; Kaplan, Summer L. MD, MS4; Sutton, Robert M. MD, MSCE1; Nishisaki, Akira MD, MSCE1; Conlon, Thomas W. MD1
Abstract
OBJECTIVES:
To evaluate the impact of point-of-care ultrasound (POCUS) use on clinicians within a PICU and to assess infrastructural elements of our POCUS program development.
DESIGN:
Retrospective observational study.
SETTING:
Large academic, noncardiac PICU in the United States.
SUBJECTS:
Patients in a PICU who had diagnostic POCUS performed.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Between January 1, 2017, and December 31, 2022, 7201 diagnostic POCUS studies were ordered; 1930 (26.8%) had a quality assurance (QA) record generated in an independent POCUS QA database. The cardiac domain was most frequently imaged (81.0% of ordered studies, 81.2% of reviewed studies). POCUS images changed clinician understanding of pathophysiology in 563 of 1930 cases (29.2%); when this occurred, management was changed in 318 of 563 cases (56.5%). Cardiac POCUS studies altered clinician suspected pathophysiology in 30.1% of cases (472/1568), compared with 21.5% (91/362) in noncardiac studies (p = 0.06). Among cases where POCUS changed clinician understanding, management changed more often following cardiac than noncardiac POCUS (p = 0.02). Clinicians identified a need for cardiology consultation or complete echocardiograms in 294 of 1568 cardiac POCUS studies (18.8%). Orders for POCUS imaging increased by 94.9%, and revenue increased by 159.4%, from initial to final study year. QA database use by both clinicians and reviewers decreased annually as QA processes evolved in the setting of technologic growth and unit expansion.
CONCLUSIONS:
Diagnostic POCUS imaging in the PICU frequently yields information that alters diagnosis and changes management. As PICU POCUS use increased, QA processes evolved resulting in decreased use of our initial QA database. Modifications to QA processes are likely necessary as clinical contexts change over time.
Linz, Matthew S. MD1; Booth, Lauren D. MSN, CRNP2; Milstone, Aaron M. MD, MHS3,4,5; Stockwell, David C. MD, MBA2,5; Sick-Samuels, Anna C. MD, MPH3,4,5
Abstract
OBJECTIVES:
Previously, we implemented a comprehensive decision support tool, a “New Fever Algorithm,” to support the evaluation of PICU patients with new fever or instability. This tool was associated with a decline in culture rates without safety concerns. We assessed the impact of the algorithm on testing practices by identifying the proportion of cultures pre- vs. post-implementation that were discordant with algorithm guidance and may have been avoidable.
DESIGN:
Retrospective evaluation 12 months pre- vs. post-quality improvement intervention.
SETTING:
Single-center academic PICU and pediatric cardiac ICU.
SUBJECTS:
All admitted patients.
INTERVENTIONS:
Implementing the “New Fever Algorithm” in July 2020.
MEASUREMENTS AND MAIN RESULTS:
Patient medical records were reviewed to categorize indications for all blood, respiratory, and urine cultures. Among cultures obtained for new fever or new clinical instability, we assessed specific testing patterns that were discordant from the algorithm’s guidance such as blood cultures obtained without documented concern for sepsis without initiation of antibiotics, respiratory cultures without respiratory symptoms, urine cultures without a urinalysis or pyuria, and pan-cultures (concurrent blood, respiratory, and urine cultures). Among 2827 cultures, 1950 (69%) were obtained for new fever or instability. The proportion of peripheral blood cultures obtained without clinical concern for sepsis declined from 18.6% to 10.4% (p < 0.0007). Respiratory cultures without respiratory symptoms declined from 41.5% to 27.4% (p = 0.01). Urine cultures without a urinalysis did not decline (from 27.6% to 25.1%). Urine cultures without pyuria declined from 83.0% to 73.7% (p = 0.04). Pan-cultures declined from 22.4% to 10.6% (p < 0.0001). Overall, algorithm-discordant testing declined from 39% to 30% (p < 0.0001).
CONCLUSIONS:
The majority of cultures obtained were for new fever or instability and introduction of the “New Fever Algorithm” was associated with reductions in algorithm-discordant testing practices and pan-cultures. There remain opportunities for improvement and additional strategies are warranted to optimize testing practices for in this complex patient population.
Cai, Tengyi MLabMed1,2; Emery-Corbin, Samantha J. PhD3,4; McCafferty, Conor PhD1,2; Van Den Helm, Suelyn BBiomedSciAdvHons1,2; Letunica, Natasha BSc1; Attard, Chantal PhD1,2; Barton, Rebecca MD1,2,5; Horton, Stephen PhD2,6; Bottrell, Steve BAppSc6; Schultz, Bradley BAppSc6; MacLaren, Graeme MBBS, MSc, FCCM7; Chiletti, Roberto MD8,9; Best, Derek BN8,9; Johansen, Amy MANP (Research)8,9; Newall, Fiona PhD1,2,5; Butt, Warwick MBBS, FRACP, FJFICM2,8,9; d’Udekem, Yves MD, PhD10; Dagley, Laura F. PhD3,4; Yousef, Jumana M. PhD3,4; Monagle, Paul MBBS, MD, FRACP, FRCPA, FCCP1,2,5,11; Ignjatovic, Vera PhD1,2,12,13
Abstract
OBJECTIVE:
To characterize surface-bound proteins and to measure the thickness of fibrin fibers bound to extracorporeal membrane oxygenation (ECMO) circuits used in children.
DESIGN:
Single-center observational prospective study, April to November 2021.
SETTING:
PICU, Royal Children’s Hospital, Melbourne, Australia.
PATIENTS:
Patients aged less than 18 years on venoarterial ECMO and without preexisting disorder.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
ECMO circuits were collected from six patients. Circuit samples were collected from five different sites, and subsequently processed for proteomic and scanning electron microscopy (SEM) studies. The concentration of proteins bound to ECMO circuit samples was measured using a bicinchoninic acid protein assay, whereas characterization of the bound proteome was performed using data-independent acquisition mass spectrometry. The Reactome Over-representation Pathway Analyses tool was used to identify functional pathways related to bound proteins. For the SEM studies, ECMO circuit samples were prepared and imaged, and the thickness of bound fibrin fibers was measured using the Fiji ImageJ software, version 1.53c (https://imagej.net/software/fiji/). Protein binding to ECMO circuit samples and fibrin networks showed significant intra-circuit and interpatient variation. The median (range) total protein concentration was 19.0 (0–76.9) μg/mL, and the median total number of proteins was 2011 (1435–2777). A total of 933 proteins were commonly bound to ECMO circuit samples from all patients and were functionally involved in 212 pathways, with signal transduction, cell cycle, and metabolism of proteins being the top three pathway categories. The median intra-circuit fibrin fiber thickness was 0.20 (0.15–0.24) μm, whereas the median interpatient fibrin fiber thickness was 0.18 (0.15–0.21) μm.
CONCLUSIONS:
In this report, we have characterized proteins and fiber fibrin thickness bound to ECMO circuits in six children. The techniques and approaches may be useful for investigating interactions between blood, coagulation, and the ECMO circuit and have the potential for circuit design.
Editor’s Choice Articles for October 2024
Pediatric Critical Care Medicine. 25(10):877-879, October 2024.
Pediatric Critical Care Medicine. 25(10):889-898, October 2024.
OBJECTIVES:To examine career trajectory and academic profile of Pediatric Critical Care Medicine (PCCM) physicians, with special focus on gender differences.
DESIGN:Observational cross-sectional study of PCCM fellowship graduates using publicly available data.
SETTING:Publicly available databases including National Provider Identifier registry, American Board of Pediatrics, Doximity, official hospital websites, and Scopus.
SUBJECTS:Two thousand one hundred twenty-nine PCCM fellowship graduates employed in clinical positions in U.S. practice locations.
INTERVENTION:None.
MEASUREMENTS AND MAIN RESULTS:Physician demographic characteristics included gender and time since fellowship completion. Current career and academic characteristics included employment data, publication productivity (h-index), and academic rank. Data from 2129 career PCCM physicians was included, with recent graduates showing a notable increase in female representation. Workplace characteristics revealed that most PCCM physicians worked in university-affiliated hospitals, with higher percentages of female physicians working in university-affiliated hospitals compared with male physicians. The study also highlighted significant gender disparities in academic metrics, with male physicians having higher h-indices (3 vs. 2; p < 0.001) and more publications (6 vs. 4; p < 0.001) than their female counterparts across various career phases. Additionally, the analysis showed gender differences in academic rank, with a higher proportion of female faculty holding assistant and associate professor ranks (58.2% vs. 47.5%; p < 0.001), while a greater percentage of male faculty held the rank of professor (20.2% vs. 11.1%; p < 0.001). Multiple variable regression analysis identified both male gender and time since fellowship graduation as independently associated with a physician’s h-index, while only time since fellowship graduation was linked to current academic rank.
CONCLUSIONS:This is the first analysis of career and academic characteristics of practicing PCCM physicians, additionally studying the association of gender and career trajectory. Gender discrepancy was seen in employment hospital characteristics, h-indices, and academic rank. Additional studies are required to further explore the impact of gender on career trajectory.
Liesse, Kelly M. MD1,2; Malladi, Lakshmee MD1; Dinh, Tu C. MD1; Wesp, Brendan M. MD1; Kam, Brittni N. MD1; Turturice, Benjamin A. MD, PhD3; Pyke-Grimm, Kimberly A. PhD, RN, CPHON4; Char, Danton S. MD5; Hollander, Seth A. MD1,2
Abstract
OBJECTIVE:
Pediatric deaths often occur within hospitals and involve balancing aggressive treatment with minimization of suffering. This study first investigated associations between clinical/demographic features and the level of intensity of various therapies these patients undergo at the end of life (EOL). Second, the work used these data to develop a new, broader spectrum for classifying pediatric EOL trajectories.
DESIGN:
Retrospective, single-center study, 2013–2021.
SETTING:
Four hundred sixty-one bed tertiary, stand-alone children’s hospital with 112 ICU beds.
PATIENTS:
Patients of age 0–26 years old at the time of death.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Of 1111 included patients, 85.7% died in-hospital. Patients who died outside the hospital were older. Among the 952 in-hospital deaths, most occurred in ICUs (89.5%). Clustering analysis was used to distinguish EOL trajectories based on the presence of intensive therapies and/or an active resuscitation attempt at the EOL. We identified five simplified categories: 1) death during active resuscitation, 2) controlled withdrawal of life-sustaining technology, 3) natural progression to death despite maximal therapy, 4) discontinuation of nonsustaining therapies, and 5) withholding/noninitiation of future therapies. Patients with recent surgical procedures, a history of organ transplantation, or admission to the Cardiovascular ICU had more intense therapies at EOL than those who received palliative care consultations, had known genetic conditions, or were of older age.
CONCLUSIONS:
In this retrospective study of pediatric EOL trajectories based on the intensity of technology and/or resuscitation discontinued at the EOL, we have identified associations between these trajectories and patient characteristics. Further research is needed to investigate the impact of these trajectories on families, patients, and healthcare providers.
Jones, Gareth A.L. MD1; Wiegand, Martin PhD2,3; Ray, Samiran1,3,4; Gould, Doug W. PhD5; Agbeko, Rachel PhD6,7; Giallongo, Elisa MSc5; Charles, Walton N. MBBS5; Orzol, Marzena MSc5; O’Neill, Lauran BSc1; Lampro, Lamprini MSc5; Lillie, Jon MD8,9; Pappachan, John MD10; Ramnarayan, Padmanabhan MD11,12; Harrison, David A. PhD5; Mouncey, Paul R. MSc5; Peters, Mark J. PhD1,3,4,11; for the Oxy-PICU Investigators of the Pediatric Critical Care Society Study Group
Abstract
OBJECTIVES:
A conservative oxygenation strategy, targeting peripheral oxygen saturations (Spo2) between 88% and 92% in mechanically ventilated children in PICU, was associated with a shorter duration of organ support and greater survival compared with Spo2 greater than 94% in our recent Oxy-PICU trial. Spo2 monitors may overestimate arterial oxygen saturation (Sao2) in patients with higher levels of skin pigmentation compared with those with less skin pigmentation. We investigated if ethnicity was associated with changes in distributions of Spo2 and Fio2 and outcome.
DESIGN:
Post-hoc analysis of a pragmatic, open-label, multicenter randomized controlled trial.
SETTING:
Fifteen PICUs across the United Kingdom and Scotland.
PATIENTS:
Children aged 38 weeks corrected gestational age to 15 years accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange.
METHODS:
Hierarchical regression models for Spo2 and Fio2, and ordinal models for the primary trial outcome of a composite of the duration of organ support at 30 days and death, were used to examine the effects of ethnicity, accounting for baseline Spo2, Fio2, and mean airway pressure and trial allocation.
MEASUREMENTS AND MAIN RESULTS:
Ethnicity data were available for 1577 of 1986 eligible children, 1408 (89.3%) of which were White, Asian, or Black. Spo2 and Fio2 distributions did not vary according to Black or Asian ethnicity compared with White children. The trial primary outcome measure also did not vary significantly with ethnicity. The point estimate for the treatment effect of conservative oxygenation in Black children was 0.64 (95% CI, 0.33–1.25) compared with 0.84 (0.68–1.04) in the overall trial population.
CONCLUSIONS:
These data do not suggest that the association between improved outcomes and conservative oxygenation strategy in mechanically ventilated children in PICU is modified by ethnicity.
Editor’s Choice Articles for September 2024
Pediatric Critical Care Medicine. 25(9):779-783, September 2024.
Bhalla, Anoopindar K. MD, MsCI1,2; Klein, Margaret J. MS1; Hotz, Justin RRT1; Kwok, Jeni JD1; Bonilla-Cartagena, Jennifer E. BA1; Baron, David A. MS1; Kohler, Kristen RRT-NPS, RRT-ACCS1; Bornstein, Dinnel RRT1; Chang, Daniel RRT1; Vu, Kennedy RRT1; Armenta-Quiroz, Anabel RRT1; Nelson, Lara P. MD1,2; Newth, Christopher J.L. MD, FRACP1,2; Khemani, Robinder G. MD, MsCI1,2
Abstract
OBJECTIVES:
We sought to evaluate the association between the carbon dioxide (co2) ventilatory equivalent (VEqco2 = minute ventilation/volume of co2 produced per min), a marker of dead space that does not require a blood gas measurement, and mortality risk. We compared the strength of this association to that of physiologic dead space fraction (VD/Vt = [Paco2–mixed-expired Pco2]/Paco2) as well as to other commonly used markers of dead space (i.e., the end-tidal alveolar dead space fraction [AVDSf = (Paco2–end-tidal Pco2)/Paco2], and ventilatory ratio [VR = (minute ventilation × Paco2)/(age-adjusted predicted minute ventilation × 37.5)]).
DESIGN:
Retrospective cohort data, 2017–2023.
SETTING:
Quaternary PICU.
PATIENTS:
One hundred thirty-one children with acute respiratory distress syndrome.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
All dead space markers were calculated at the same 1-minute timepoint for each patient within the first 72 hours of using invasive mechanical ventilation. The 131 children had a median (interquartile range, IQR) age of 5.8 (IQR 1.4, 12.6) years, oxygenation index (OI) of 7.5 (IQR 4.6, 14.3), VD/Vt of 0.47 (IQR 0.38, 0.61), and mortality was 17.6% (23/131). Higher VEqco2 (p = 0.003), VD/Vt (p = 0.002), and VR (p = 0.013) were all associated with greater odds of mortality in multivariable models adjusting for OI, immunosuppressive comorbidity, and overall severity of illness. We failed to identify an association between AVDSf and mortality in the multivariable modeling. Similarly, we also failed to identify an association between OI and mortality after controlling for any dead space marker in the modeling. For the 28-day ventilator-free days outcome, we failed to identify an association between VD/Vt and the dead space markers in multivariable modeling, although OI was significant.
CONCLUSIONS:
VEqco2 performs similarly to VD/Vt and other surrogate dead space markers, is independently associated with mortality risk, and may be a reasonable noninvasive surrogate for VD/Vt.
Lenz, Kyle B. MD1; McDade, Jessica MD1; Petrozzi, Mariagrazia MD1; Dervan, Leslie A. MD, MS1; Beckstead, Rylee MS2; Banks, Russell K. MS2; Reeder, Ron W. PhD, MS2; Meert, Kathleen L. MD3; Zimmerman, Jerry MD, PhD1; Killien, Elizabeth Y. MD, MPH1
Abstract
OBJECTIVES:
Social determinants of health (SDOH) are associated with disparities in disease severity and in-hospital outcomes among critically ill children. It is unknown whether SDOH are associated with later outcomes. We evaluated associations between SDOH measures and mortality, new functional morbidity, and health-related quality of life (HRQL) decline among children surviving septic shock.
DESIGN:
Secondary analysis of the Life After Pediatric Sepsis Evaluation (LAPSE) prospective cohort study was conducted between 2014 and 2017.
SETTING:
Twelve academic U.S. PICUs were involved in the study.
PATIENTS:
Children younger than 18 years with community-acquired septic shock were involved in the study.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
We assessed associations between race, ethnicity, income, education, marital status, insurance, language, and home U.S. postal code with day 28 mortality, new functional morbidity at discharge per day 28, and HRQL decline using logistic regression. Of 389 patients, 32% (n = 98) of families had household income less than $50,000 per year. Median Pediatric Risk of Mortality (PRISM) score was 11 (interquartile range 6, 17). We found that English language and Area Deprivation Index less than 50th percentile were associated with higher PRISM scores. Mortality was 6.7% (n = 26), new functional morbidity occurred in 21.8% (n = 78) of patients, and HRQL decline by greater than 10% occurred in 31.0% of patients (n = 63). We failed to identify any association between SDOH measures and mortality, new functional morbidity, or HRQL decline. We are unable to exclude the possibility that annual household income greater than or equal to $50,000 was associated with up to 81% lesser odds of mortality and, in survivors, more than three-fold greater odds of HRQL decline by greater than 10%.
CONCLUSIONS:
In this secondary analysis of the 2014–2017 LAPSE dataset, we failed to identify any association between SDOH measures and in-hospital or postdischarge outcomes following pediatric septic shock. This finding may be reflective of the high illness severity and single disease (sepsis) of the cohort, with contribution of clinical factors to functional and HRQL outcomes predominating over prehospital and posthospital SDOH factors.
Killien, Elizabeth Y. MD, MPH1,2; Ohman, Robert T. MD, MPH1; Dervan, Leslie A. MD, MS1,3; Smith, Mallory B. MD, MS4; Rivara, Frederick P. MD, MPH2,5; Watson, R. Scott MD, MPH1,2
Abstract
OBJECTIVES:
To determine factors associated with health-related quality of life (HRQL) decline among pediatric acute respiratory distress syndrome (PARDS) survivors.
DESIGN:
Retrospective cohort study.
SETTING:
Academic children’s hospital.
PATIENTS:
Three hundred fifteen children 1 month to 18 years old with an unplanned PICU admission from December 2011 to February 2017 enrolled in the hospital’s Outcomes Assessment Program.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Pre-admission baseline and median 6-week post-discharge HRQL were assessed using the Pediatric Quality of Life Inventory or the Functional Status II-R. Patients meeting retrospectively applied Second Pediatric Acute Lung Injury Consensus Conference criteria for PARDS were identified, and PARDS severity was classified using binary (mild/moderate, severe) and trichotomous (mild, moderate, severe) categorization for noninvasive ventilation and invasive mechanical ventilation (IMV). PARDS occurred in 41 of 315 children (13.0%). Clinically important HRQL decline (≥ 4.5 points) occurred in 17 of 41 patients (41.5%) with PARDS and 64 of 274 without PARDS (23.4%). On multivariable generalized linear regression adjusted for age, baseline Pediatric Overall Performance Category, maximum nonrespiratory Pediatric Logistic Organ Dysfunction score, diagnosis, length of stay, and time to follow-up, PARDS was associated with HRQL decline (adjusted relative risk [aRR], 1.70; 95% CI, 1.03–2.77). Four-hour and maximum PARDS severity were the only factors associated with HRQL decline. HRQL decline occurred in five of 18 patients with mild PARDS at 4 hours, five of 13 with moderate PARDS (aRR 2.35 vs. no PARDS [95% CI, 1.01–5.50]), and seven of ten with severe PARDS (aRR 2.56 vs. no PARDS [95% CI, 1.45–4.53]). The area under the receiver operating characteristic curve for discrimination of HRQL decline for IMV patients was 0.79 (95% CI, 0.66–0.91) for binary and 0.80 (95% CI, 0.69–0.93) for trichotomous severity categorization.
CONCLUSIONS:
HRQL decline is common among children surviving PARDS, and risk of decline is associated with PARDS severity. HRQL decline from baseline may be an efficient and clinically meaningful endpoint to incorporate into PARDS clinical trials.
Editor’s Choice Articles for August 2024
Tasker, Robert C. MBBS, MD, FRCP1,2,3
Ip, Pui Yin Florence MBBS1,2; Periasamy, Uvaraj MBBS2,3,4; Staffa, Steven J. MS2,3; Zurakowski, David MS, PhD2,3; Kantor, David B. MD, PhD2,3,4
Abstract
OBJECTIVES:
To evaluate management changes and outcomes in critically ill children after formal echocardiography.
DESIGN:
Retrospective cohort study between January 1, 2011, and December 31, 2020.
SETTING:
Tertiary care children’s hospital.
PATIENTS:
Patients from 1 to 18 years who had formal echocardiography within 72 hours of ICU admission and who were intubated and on vasoactive infusions at the time of the study. Patients were stratified into two cardiac function groups: 1) near-normal cardiac function and 2) depressed cardiac function.
METHODS:
Clinical variables were abstracted from the electronic medical record and placed in time sequence relative to echocardiography. Vasoactive and fluid management strategies in place before echocardiography were associated with markers of tissue perfusion and volume overload. Management changes after echocardiography were characterized and associated with outcomes.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Among patients eventually found to have depressed cardiac function, the use of vasoconstrictors was associated with worse lactate clearance and oxygen extraction ratio. Use of vasoconstrictors in this cohort was also associated with a more liberal fluid management strategy, evidence of increased lung water, and a worse Spo2/Fio2. An echocardiogram demonstrated depressed cardiac function was likely to be followed by management changes that favored inotropes and more conservative fluid administration. Patients with depressed cardiac function who were switched to inotropes were more likely to be extubated and to wean off vasoactive support compared with those patients who remained on vasoconstrictors.
CONCLUSIONS:
Among patients with depressed cardiac function, alterations in management strategy after echocardiography are associated with shortened duration of intensive care interventions.
Rodriguez, Katherine M. MD1,2,3; Vaught, Jordan MD1,2; Salz, Lisa MS, LCGC3; Foley, Jennifer RN, BSN1; Boulil, Zaineb MS1; Van Dongen-Trimmer, Heather M. CPNP, DNP4; Whalen, Drewann5; Oluchukwu, Okonkwo MD5,6; Liu, Kuang Chuen MD5,6; Burton, Jennifer MS, LCGC5,6; Syngal, Prachi MD5,6; Vargas-Shiraishi, Ofelia7; Kingsmore, Stephen F. MD, DSc3; Sanford Kobayashi, Erica MD3,4,7; Coufal, Nicole G. MD, PhD1,2,3
Abstract
OBJECTIVES:
Analysis of the clinical utility of rapid whole-genome sequencing (rWGS) outside of the neonatal period is lacking. We describe the use of rWGS in PICU and cardiovascular ICU (CICU) patients across four institutions.
DESIGN:
Ambidirectional multisite cohort study.
SETTING:
Four tertiary children’s hospitals.
PATIENTS:
Children 0–18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
A total of 133 patients underwent clinical, phenotype-driven rWGS analysis, 36 prospectively. A molecular diagnosis was identified in 79 patients (59%). Median (interquartile range [IQR]) age was 6 months (IQR 1.2 mo–4.6 yr). Median time for return of preliminary results was 3 days (IQR 2–4). In 79 patients with a molecular diagnosis, there was a change in ICU management in 19 patients (24%); and some change in clinical management in 63 patients (80%). Nondiagnosis changed management in 5 of 54 patients (9%). The clinical specialty ordering rWGS did not affect diagnostic rate. Factors associated with greater odds ratio (OR [95% CI]; OR [95% CI]) of diagnosis included dysmorphic features (OR 10.9 [95% CI, 1.8–105]) and congenital heart disease (OR 4.2 [95% CI, 1.3–16.8]). Variables associated with greater odds of changes in management included obtaining a genetic diagnosis (OR 16.6 [95% CI, 5.5–62]) and a shorter time to genetic result (OR 0.8 [95% CI, 0.76–0.9]). Surveys of pediatric intensivists indicated that rWGS-enhanced clinical prognostication (p < 0.0001) and contributed to a decision to consult palliative care (p < 0.02).
CONCLUSIONS:
In this 2016–2023 multiple-PICU/CICU cohort, we have shown that timely genetic diagnosis is feasible across institutions. Application of rWGS had a 59% (95% CI, 51–67%) rate of diagnostic yield and was associated with changes in critical care management and long-term patient management.
Ahmed, Nasim MBBS1,2; Russo, Larissa MS3; Kuo, Yen-Hong PhD4,5
Abstract
OBJECTIVES:
To compare levetiracetam and phenytoin as prophylaxis for the short-term development of status epilepticus (SE) during care of pediatric patients with acute severe traumatic brain injury (TBI).
DESIGN:
Nonprespecified secondary analysis using propensity score matching.
SETTING:
We used the Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT NCT04077411) dataset (2014–2017).
SUBJECTS:
Patients less than 18 years old with Glasgow Coma Scale Score less than or equal to 8 who received levetiracetam or phenytoin as a prophylactic anticonvulsant therapy.
INTERVENTION:
None.
MEASUREMENT AND MAIN RESULTS:
Of the 516 total patients who qualified for the case-control study, 372 (72.1%) patients received levetiracetam, and 144 (27.9%) received phenytoin. After propensity score matching, the pair-matched analysis with 133 in each group failed to identify an association between levetiracetam versus phenytoin use and occurrent of SE (3.8% vs. 0.8%, p = 0.22), or mortality (i.e., in-hospital, 30-d and 60-d). However, on closer inspection of the statistical testing, we cannot exclude the possibility that selecting levetiracetam rather than phenytoin for prophylaxis was associated with the following: up to a mean difference of 7.3% greater prevalence of SE; up to a mean difference of 13.9%, 12.1%, and 13.9% greater mortality during the hospital stay, and 30-, and 60-days after hospital arrival, respectively. Last, analysis of 6 months Glasgow Outcome Scale Extended score in those without premorbid comorbidities, there was an association between favorable outcomes and use of phenytoin rather than levetiracetam prophylaxis.
CONCLUSIONS:
In ADAPT, the decision to use prophylactic levetiracetam versus phenytoin failed to show an association with occurrence of subsequent SE, or mortality. However, we are unable to exclude the possibility that selecting levetiracetam rather than phenytoin for prophylaxis was associated with greater prevalence of SE and mortality. We are unable to make any recommendation about one prophylactic anticonvulsant medication over the other, but recommend that further larger, contemporary studies in severe pediatric TBI are carried out.
Editor’s Choice Articles for July 2024
Pediatric Critical Care Medicine. 25(7):588-590, July 2024.
Brohan, Orlane MD1; Chenouard, Alexis MD, PhD1; Gaultier, Aurélie2; Tonna, Joseph E. MD, MS3; Rycus, Peter MPH3; Pezzato, Stefano MD4; Moscatelli, Andrea MD4; Liet, Jean-Michel MD, PhD1; Bourgoin, Pierre MD1; Rozé, Jean-Christophe MD, PhD1,5; Léger, Pierre-Louis MD, PhD6,7; Rambaud, Jérôme MD, PhD6,7; Joram, Nicolas MD, PhD1,7
Abstract
OBJECTIVES:
Extracorporeal life support can lead to rapid reversal of hypoxemia but the benefits and harms of different oxygenation targets in severely ill patients are unclear. Our primary objective was to investigate the association between the Pao2 after extracorporeal membrane oxygenation (ECMO) initiation and mortality in neonates treated for respiratory failure.
DESIGN:
Retrospective analysis of the Extracorporeal Life Support Organization (ELSO) Registry data, 2015–2020.
PATIENTS:
Newborns supported by ECMO for respiratory indication were included.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Pao2 24 hours after ECMO initiation (H24 Pao2) was reported. The primary outcome was 28-day mortality. We identified 3533 newborns (median age 1 d [interquartile range (IQR), 1–3]; median weight 3.2 kg [IQR, 2.8–3.6]) from 198 ELSO centers, who were placed on ECMO. By 28 days of life, 731 (20.7%) had died. The median H24 Pao2 was 85 mm Hg (IQR, 60–142). We found that both hypoxia (Pao2 < 60 mm Hg) and moderate hyperoxia (Pao2 201–300 mm Hg) were associated with greater adjusted odds ratio (aOR [95% CI]) of 28-day mortality, respectively: aOR 1.44 (95% CI, 1.08–1.93), p = 0.016, and aOR 1.49 (95% CI, 1.01–2.19), p value equals to 0.045.
CONCLUSIONS:
Early hypoxia or moderate hyperoxia after ECMO initiation are each associated with greater odds of 28-day mortality among neonates requiring ECMO for respiratory failure.
Whitney, Jane E. MD, MSCE1,2; Johnson, Grace M. BS1,3; Varisco, Brian M. MD4,5; Raby, Benjamin A. MD, MPH2,3; Yehya, Nadir MD, MSCE6,7
Abstract
OBJECTIVES:
The Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model (PARDSEVERE) used age and three plasma biomarkers measured within 24 hours of pediatric acute respiratory distress syndrome (ARDS) onset to predict mortality in a pilot cohort of 152 patients. However, longitudinal performance of PARDSEVERE has not been evaluated, and it is unclear whether the risk model can be used to prognosticate after day 0. We, therefore, sought to determine the test characteristics of PARDSEVERE model and population over the first 7 days after ARDS onset.
DESIGN:
Secondary unplanned post hoc analysis of data from a prospective observational cohort study carried out 2014–2019.
SETTING:
University-affiliated PICU.
PATIENTS:
Mechanically ventilated children with ARDS.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Between July 2014 and December 2019, 279 patients with ARDS had plasma collected at day 0, 266 at day 3 (11 nonsurvivors, two discharged between days 0 and 3), and 207 at day 7 (27 nonsurvivors, 45 discharged between days 3 and 7). The actual prevalence of mortality on days 0, 3, and 7, was 23% (64/279), 14% (38/266), and 13% (27/207), respectively. The PARDSEVERE risk model for mortality on days 0, 3, and 7 had area under the receiver operating characteristic curve (AUROC [95% CI]) of 0.76 (0.69–0.82), 0.68 (0.60–0.76), and 0.74 (0.65–0.83), respectively. The AUROC data translate into prevalence thresholds for the PARDSEVERE model for mortality (i.e., using the sensitivity and specificity values) of 37%, 27%, and 24% on days 0, 3, and 7, respectively. Negative predictive value (NPV) was high throughout (0.87–0.90 for all three-time points).
CONCLUSIONS:
In this exploratory analysis of the PARDSEVERE model of mortality risk prediction in a population longitudinal series of data from days 0, 3, and 7 after ARDS diagnosis, the diagnostic performance is in the “acceptable” category. NPV was good. A major limitation is that actual mortality is far below the prevalence threshold for such testing. The model may, therefore, be more useful in cohorts with higher mortality rates (e.g., immunocompromised, other countries), and future enhancements to the model should be explored.
Karsies, Todd MD, MPH, FCCP1; Shein, Steven L. MD, FCCM2; Diaz, Franco MD3,4,5; Vasquez-Hoyos, Pablo MD3,6; Alexander, Robin MS7; Pon, Steven MD8; González-Dambrauskas, Sebastián MD3,9; with the Bronchiolitis And COdetectioN (BACON) Study Investigators; for the Bronchiolitis Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network and the Red Colaborativa Pediátrica de Latinoamérica Network
Abstract
OBJECTIVES:
To determine the prevalence of respiratory bacterial codetection in children younger than 2 years intubated for acute lower respiratory tract infection (LRTI), primarily viral bronchiolitis, and identify the association of codetection with mechanical ventilation duration.
DESIGN:
Prospective observational study evaluating the prevalence of bacterial codetection (moderate/heavy growth of pathogenic bacterial plus moderate/many polymorphonuclear neutrophils) and the impact of codetection on invasive mechanical ventilation (IMV) duration.
SETTING:
PICUs in 12 high and low/middle-income countries.
PATIENTS:
Children younger than 2 years old requiring intubation and ICU admission for LRTI and who had a lower respiratory tract culture obtained at the time of intubation between December 1, 2019, and November 30, 2020.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Of the 472 analyzed patients (median age 4.5 mo), 55% had a positive respiratory culture and 29% (n = 138) had codetection. 90% received early antibiotics starting at a median of 0.36 hours after respiratory culture. Median (interquartile range) IMV duration was 151 hours (88, 226), and there were 28 deaths (5.3%). Codetection was more common with younger age, a positive respiratory syncytial virus test, and an admission diagnosis of bronchiolitis; it was less common with an admission diagnosis of pneumonia, with admission to a low-/middle-income site, and in those receiving vasopressors. When adjusted for confounders, codetection was not associated with longer IMV duration (adjusted relative risk 0.854 [95% CI 0.684–1.065]). We could not exclude the possibility that codetection might be associated with a 30-hour shorter IMV duration compared with no codetection, although the CI includes the null value.
CONCLUSIONS:
Bacterial codetection was present in almost a third of children younger than 2 years requiring intubation and ICU admission for LRTI, but this was not associated with prolonged IMV. Further large studies are needed to evaluate if codetection is associated with shorter IMV duration.
Editor’s Choice Articles for June 2024
Tasker, Robert C. MBBS, MD, FRCP1,2,3
Straka, Nadine MB BCh BAO, MPH1,2; França, Urbano L. PhD1,2; Franks, Jennifer D. BA1; McManus, Michael L. MD, MPH1,2
OBJECTIVES:To identify and geolocate pediatric post-acute care (PAC) facilities in the United States.
DESIGN:Cross-sectional survey using both online resources and telephone inquiry.
SETTING:All 50 U.S. states surveyed from June 2022 to May 2023. Care sites identified via state regulatory agencies and the Centers for Medicare & Medicaid Services.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:Number, size, and type of facility, scope of practice, and type of care provided. One thousand three hundred fifty-five facilities were surveyed; of these, 18.6% (252/1355) were pediatric-specific units or adult facilities accepting some pediatric patients. There were 109 pediatric-specific facilities identified within 39 U.S. states. Of these, 38 were freestanding with all accepting children with tracheostomies, 97.4% (37/38) accepting those requiring mechanical ventilation via tracheostomy, and 81.6% (31/38) accepting those requiring parenteral nutrition. The remaining 71 facilities were adult facilities with embedded pediatric units or children’s hospitals with 88.7% (63/71), 54.9% (39/71), and 54.9% (39/71), accepting tracheostomies, mechanical ventilation via tracheostomy, and parenteral nutrition, respectively. Eleven states lacked any pediatric-specific PAC units or facilities.
CONCLUSIONS:The distribution of pediatric PAC is sparse and uneven across the United States. We present an interactive map and database describing these facilities. These data offer a starting point for exploring the consequences of pediatric PAC supply.
Thirnbeck, Caitlin K. DO, MPH1; Espinoza, Elizabeth T. DNP, CPNP-AC, C-NPT2; Beaman, Elizabeth A. BS3; Rozen, Alexis L.4; Dukes, Kimberly C. PhD5,6; Singh, Hardeep MD, MPH7; Herwaldt, Loreen A. MD5,8; Landrigan, Christopher P. MD, MPH9,10; Reisinger, Heather Schacht PhD5,11; Cifra, Christina L. MD, MS12,13
Abstract
OBJECTIVES:
For patients requiring transfer to a higher level of care, excellent interfacility communication is essential. Our objective was to characterize verbal handoffs for urgent interfacility transfers of children to the PICU and compare these characteristics with known elements of high-quality intrahospital shift-to-shift handoffs.
DESIGN:
Mixed methods retrospective study of audio-recorded referral calls between referring clinicians and receiving PICU physicians for urgent interfacility PICU transfers.
SETTING:
Academic tertiary referral PICU.
PATIENTS:
Children 0–18 years old admitted to a single PICU following interfacility transfer over a 4-month period (October 2019 to January 2020).
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
We reviewed interfacility referral phone calls for 49 patients. Referral calls between clinicians lasted a median of 9.7 minutes (interquartile range, 6.8–14.5 min). Most referring clinicians provided information on history (96%), physical examination (94%), test results (94%), and interventions (98%). Fewer clinicians provided assessments of illness severity (87%) or code status (19%). Seventy-seven percent of referring clinicians and 6% of receiving PICU physicians stated the working diagnosis. Only 9% of PICU physicians summarized information received. Interfacility handoffs usually involved: 1) indirect references to illness severity and diagnosis rather than explicit discussions, 2) justifications for PICU admission, 3) statements communicating and addressing uncertainty, and 4) statements indicating the referring hospital’s reliance on PICU resources. Interfacility referral communication was similar to intrahospital shift-to-shift handoffs with some key differences: 1) use of contextual information for appropriate PICU triage, 2) difference in expertise between communicating clinicians, and 3) reliance of referring clinicians and PICU physicians on each other for accurate information and medical/transport guidance.
CONCLUSIONS:
Interfacility PICU referral communication shared characteristics with intrahospital shift-to-shift handoffs; however, communication did not adhere to known elements of high-quality handovers. Structured tools specific to PICU interfacility referral communication must be developed and investigated for effectiveness in improving communication and patient outcomes.
Atreya, Mihir R. MD, MPH1,2; Bennett, Tellen D. MD, MS3; Geva, Alon MD, MPH4,5; Faustino, E. Vincent S. MD, MHS6; Rogerson, Colin M. MD, MPH7; Lutfi, Riad MD7; Cvijanovich, Natalie Z. MD8; Bigham, Michael T. MD9; Nowak, Jeffrey MD10; Schwarz, Adam J. MD11; Baines, Torrey MD12; Haileselassie, Bereketeab MD, MHS13; Thomas, Neal J. MD, MSc14; Luo, Yuan PhD15,16; Sanchez-Pinto, L. Nelson MD, MBI15,16; for the Novel Data-Driven Sepsis Phenotypes in Children Study and the Genomics of Pediatric Septic Shock Investigators
Abstract
OBJECTIVES:
Identification of children with sepsis-associated multiple organ dysfunction syndrome (MODS) at risk for poor outcomes remains a challenge. We sought to the determine reproducibility of the data-driven “persistent hypoxemia, encephalopathy, and shock” (PHES) phenotype and determine its association with inflammatory and endothelial biomarkers, as well as biomarker-based pediatric risk strata.
DESIGN:
We retrained and validated a random forest classifier using organ dysfunction subscores in the 2012–2018 electronic health record (EHR) dataset used to derive the PHES phenotype. We used this classifier to assign phenotype membership in a test set consisting of prospectively (2003–2023) enrolled pediatric septic shock patients. We compared profiles of the PERSEVERE family of biomarkers among those with and without the PHES phenotype and determined the association with established biomarker-based mortality and MODS risk strata.
SETTING:
Twenty-five PICUs across the United States.
PATIENTS:
EHR data from 15,246 critically ill patients with sepsis-associated MODS split into derivation and validation sets and 1,270 pediatric septic shock patients in the test set of whom 615 had complete biomarker data.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
The area under the receiver operator characteristic curve of the modified classifier to predict PHES phenotype membership was 0.91 (95% CI, 0.90–0.92) in the EHR validation set. In the test set, PHES phenotype membership was associated with both increased adjusted odds of complicated course (adjusted odds ratio [aOR] 4.1; 95% CI, 3.2–5.4) and 28-day mortality (aOR of 4.8; 95% CI, 3.11–7.25) after controlling for age, severity of illness, and immunocompromised status. Patients belonging to the PHES phenotype were characterized by greater degree of systemic inflammation and endothelial activation, and were more likely to be stratified as high risk based on PERSEVERE biomarkers predictive of death and persistent MODS.
CONCLUSIONS:
The PHES trajectory-based phenotype is reproducible, independently associated with poor clinical outcomes, and overlapped with higher risk strata based on prospectively validated biomarker approaches.
Ames, Stefanie G. MD, MS1; Maddux, Aline B. MD, MSCS2; Burgunder, Lauren MD, MPH1; Meeks, Huong PhD1; Fink, Erica L. MD, MS3; Meert, Kathleen L. MD4; Zinter, Matt S. MD5; Mourani, Peter M. MD2; Carcillo, Joseph A. MD3; Carpenter, Todd MD2; Pollack, Murray M. MD6; Mareboina, Manvita7; Notterman, Daniel A. MD8; Sapru, Anil MD9; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN)
Abstract
OBJECTIVES:
To describe family healthcare burden and health resource utilization in pediatric survivors of acute respiratory distress syndrome (ARDS) at 3 and 9 months.
DESIGN:
Secondary analysis of a prospective multisite cohort study.
SETTING:
Eight academic PICUs in the United States (2019–2020).
PATIENTS:
Critically ill children with ARDS and follow-up survey data collected at 3 and/or 9 months after the event.
INTERVENTIONS:
None.
METHODS AND MEASUREMENT:
We evaluated family healthcare burden, a measure of healthcare provided by families at home, and child health resource use including medication use and emergency department (ED) and hospital readmissions during the initial 3- and 9-month post-ARDS using proxy-report. Using multivariable logistic regression, we evaluated patient characteristics associated with family healthcare burden at 3 months.
MAIN RESULTS:
Of 109 eligible patients, 74 (68%) and 63 patients (58%) had follow-up at 3- and 9-month post-ARDS. At 3 months, 46 families (62%) reported healthcare burden including (22%) with unmet care coordination needs. At 9 months, 33 families (52%) reported healthcare burden including 10 families (16%) with unmet care coordination needs. At month 3, 61 patients (82%) required prescription medications, 13 patients (18%) had ED visits and 16 patients (22%) required hospital readmission. At month 9, 41 patients (65%) required prescription medications, 19 patients (30%) had ED visits, and 16 (25%) required hospital readmission were reported. Medication use was associated with family healthcare burden at both 3 and 9 months. In a multivariable analysis, preillness functional status and chronic conditions were associated with healthcare burden at month 3 but illness characteristics were not.
CONCLUSIONS:
Pediatric ARDS survivors report high rates of healthcare burden and health resource utilization at 3- and 9-month post-ARDS. Future studies should assess the impact of improved care coordination to simplify care (e.g., medication management) and improve family burden.
Editor’s Choice Articles for May 2024
Tasker, Robert C. MBBS, MD, FRCP1,2,3
May 2024 and another month of exciting Pediatric Critical Care Medicine (PCCM) publications. There are three Editor’s Choice articles with editorials, and each article is accompanied by PCCM Connections material. The topics are clinical decision support using digital bedside data (1,2), trainee education and needs in spiritual care (3,4), and communication with parents about patient prognosis and the language we use (5,6). Finally, in addition to the PCCM Connections section of the Editor’s Choice, I have started a new section called PCCM International.
Pelletier JH, Rakkar J, Au AK, et al: Retrospective Validation of a Computerized Physiologic Equation to Predict Minute Ventilation Needs in Critically Ill Children (1).
My first Editor’s Choice article reports the use of a large electronic dataset of acid-base and ventilator parameters in children undergoing neuromuscular blockade during mechanical ventilation to validate a computerized equation to predict minute ventilation requirements. There were over 15,000 arterial blood gases in 484 patients and the investigators found that in silico their equation outperformed clinicians in real time (1). The accompanying editorial provides a helpful discussion about simulation and teaching platforms, and clinical decision support in respiratory care (2).
We then have two parallel developments in the PCCM literature that are worth reviewing. You may recall the work of the Second Pediatric Acute Lung Injury Consensus Conference and the renewed emphasis in leveraging clinical informatics and data science for improved care and research in pediatric acute respiratory distress syndrome (7,8). The other work is from the Pediatric Data Science and Analytics (PEDAL) subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators network (9). The group had a 2020 survey of clinical decision support practices (10) and, in April 2024, a Special Article about development, validation, and implementation of unsupervised machine learning models in pediatric critical care research (11). Do read them all.
Stevens PE, Rassbach CE, Qin F, Kuo KW: Spiritual Care in PICUs: A U.S. Survey of 245 Training Fellows, 2020−2021 (3).
My second Editor’s Choice article is a report of clinical fellows’ responses to a survey about spiritual care in their PICU and/or neonatal intensive care unit practices, 2020 to 2021 (3). The survey response rate was around one-third of 720 training fellows in the United States, which is far below the usual acceptable rate of 85%. However, with opinions from a total of 245 fellows, these insights cannot be ignored. For example, many fellows reported that “spiritual care was important for patients and families but (they) rarely incorporated spiritual care into their self-reported clinical practice.” This theme is discussed in the accompanying editorial (4), which considers a way forward in curricula, education, and research to “rediscover…. (see above header quote).” Of note, it has been almost 20 years since PCCM last published material about history taking and addressing parents’ spiritual needs (12,13), and so this information warrants further review and study.
Olive AM, Wagner AF, Mulhall DT, et al: Nudging During Pediatric Intensive Care Conferences With Family Members: Retrospective Analysis of Transcripts From a Single Center, 2015−2019 (5).
My third Editor’s Choice article is a retrospective study of transcripts from 70 care conferences involving clinicians and families, 2015−2019 (5). The authors examined episodes of decision-making that occurred in 63 transcripts and provide a summary of almost 1,100 instances of nudging. The accompanying editorial comments on the implications of this new research in care conferences, and there is a summary table of strategies to promote “ethically supported shared decision-making” (6).
This area of research is underrepresented in PCCM. However, for more reading material, look at my second Editor’s Choice this month (3,4), the systematic review of prognostic and goals-of-care communication in the PICU (14), and the data from the comparative trial of parent Navigator-support during and after PICU admission (15–17).
There are two PCCM Connections topics this month. The first extends the above discussion about clinical decision support (1,2). This month there are two articles about an automated, daily calculation of the pediatric Sequential Organ Failure Assessment (pSOFA) score. One article describes the external validation of the automated calculator using a single center 7-year cohort, 2015−2021 (18). The other article describes using this calculator to provide a dynamic prediction of mortality with longitudinal pSOFA scores (19). Please read the accompanying editorial, which is a tour de force with its skillful coverage of severity scoring, prognostic modeling, and biomedical informatics (20).
The second topic for PCCM Connections is covered in a PCCM Perspective about end-of-life care and the principle of “supported privacy” for families (21). That is, “creating and protecting a private space during end-of-life care in the PICU, while simultaneously sustaining unobtrusive continued presence for practical and emotional support of the family.” The summary of recommendations in the authors’ table is useful and adds to the discussions found in this month’s second and third Editor’s Choices (see above).
Our last international focus on sepsis came from Pakistan and was about biomarker-based risk-stratification (22,23). This month, PCCM publishes an article from southwest China describing the epidemiological characteristics, from 12 centers identifying sepsis or septic shock in 3.3% of over 11,000 PICU admissions, 2022−2023 (24). The accompanying editorial covers issues such as diagnosis and treatment protocols (25), which should now be seen in the context of the 2024 international consensus criteria for pediatric sepsis and septic shock (26).
Finally, this month there is another Editorial Notes, Methods, and Statistics article in the series about writing for PCCM (27–30). The new addition gives details about the variety of formats for PCCM’s Editorials and Commentaries (31). There is also guidance on paragraph-by-paragraph content and structure for new writers.
REFERENCES
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2. Geva A, Daniel DA, Akhondi-Asl A: Using the past to inform the future: How a classic respiratory physiology equation informs computer-based simulators and clinical decision support systems. Pediatr Crit Care Med. 2024; 25:466–468
3. Stevens PE, Rassbach CE, Qin F, et al.: Spiritual care in PICUs: A U.S. survey of 245 training fellows, 2020-2021. Pediatr Crit Care Med. 2024; 25:396–406
4. Gaudio J, Markovitz BP: Does the spirit move you, or does it take formal training? Pediatr Crit Care Med. 2024; 25:468–470
5. Olive AM, Wagner AF, Mulhall DT, et al.: Nudging during pediatric intensive care conferences with family members: Retrospective analysis of transcripts from a single center, 2015-2019. Pediatr Crit Care Med. 2024; 25:407–415
6. Smith TM, Basu S, Moynihan KM: A nudge or a shove – the importance of balancing parameters and training in decision-making communication. Pediatr Crit Care Med. 2024; 25:470–474
7. Sanchez-Pinto LN, Sauthier M, Rajapreyar P, et al.; Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Leveraging clinical informatics and data science to improve care and facilitate research in pediatric acute respiratory distress syndrome: From the second pediatric acute lung injury consensus conference. Pediatr Crit Care Med. 2023; 24(Suppl 2):S1–S11
8. Emeriaud G, Lopez-Fernandez YM, Iyer NP, et al.; Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Executive summary of the second international guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PALICC-2). Pediatr Crit Care Med. 2023; 24:143–168
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10. Dziorny AC, Heneghan JA, Bhat MA, et al.; Pediatric Data Science and Analytics (PEDAL) Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Clinical decision support in the PICU: Implications for design and evaluation. Pediatr Crit Care Med. 2022; 23:e392–e396
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12. Meert KL, Thurston CS, Briller SH: The spiritual needs of parents at the time of their child’s death in the pediatric intensive care unit and during bereavement: A qualitative study. Pediatr Crit Care Med. 2005; 6:420–427
13. Devictor D: Are we ready to discuss spirituality with our patients and their families? Pediatr Crit Care Med. 2005; 6:492–493
14. McSherry ML, Rissman L, Mitchell R, et al.: Prognostic and goals-of-care communication in the PICU: A systematic review. Pediatr Crit Care Med. 2023; 24:e28–e43
15. Michelson KN, Frader J, Charleston E, et al.; Navigate Study Investigators: A randomized comparative trial to evaluate a PICU navigator-based parent support intervention. Pediatr Crit Care Med. 2020; 21:e617–e627
16. Tager JB, Hinojosa JT, LiaBraaten BM, et al.; Navigate Study Investigators: Challenges of families of parents hospitalized in the PICU: A preplanned secondary analysis from the Navigate dataset. Pediatr Crit Care Med. 2024; 25:128–138
17. Rissman L, Paquette ET: Family challenges and navigator support: It is time we support our families better. Pediatr Crit Care Med. 2024; 25:180–182
18. Akhondi-Asl A, Luchette M, Mehta NM, et al.: Automated calculator for the Pediatric Sequential Organ Failure Assessment score: Development and external validation in a single-center 7-year cohort, 2015-2021. Pediatr Crit Care Med. 2024; 25:434–442
19. Akhondi-Asl A, Geva A, Burns JP, et al.: Dynamic prediction of mortality using longitudinally measured Pediatric Sequential Organ Failure Assessment scores. Pediatr Crit Care Med. 2024; 25:443–451
20. Horvat CM, Taylor WM: To improve a prediction model, give it time. Pediatr Crit Care Med. 2024; 25:483–485
21. Butler AE, Pasek T, Clark T-J, et al.: Supported privacy: An essential principle for end-of-life care for children and families in the PICU. Pediatr Crit Care Med. 2024; 25:e258–e262
22. Ishaque S, Famularo ST 3rd, Saleem AF, et al.: Biomarker-based risk stratification in pediatric sepsis from a low-middle income country. Pediatr Crit Care Med. 2023; 24:563–573
23. Mount MC, Remy KE: Help wanted for sepsis: Biomarkers in low- and middle-income countries please apply. Pediatr Crit Care Med. 2023; 24:619–621
24. Liu R, Yu Z, Xiao C, et al.: Epidemiology and clinical characteristics of pediatric sepsis in PICUs in southwest China: A prospective multicenter study. Pediatr Crit Care Med. 2024; 25:425–433
25. Kortz T, Kissoon N: From pediatric sepsis epidemiologic data to improved clinical outcomes. Pediatr Crit Care Med. 2024; 25:480–483
26. Schlapbach LJ, Watson RS, Sorce LR, et al.; Society of Critical Care Medicine Pediatric Sepsis Definition Task Force: International consensus criteria for pediatric sepsis and septic shock. JAMA. 2024; 331:665–674
27. Tasker RC: Writing for PCCM: The 3,000-word structured clinical research report. Pediatr Crit Care Med. 2021; 22:312–317
28. Tasker RC: PCCM Narratives, Letters, and Correspondence. Pediatr Crit Care Med. 2021; 22:426–427
29. Tasker RC: Writing for PCCM: Instructions for authors. Pediatr Crit Care Med. 2022; 23:651–655
30. Tasker RC: Writing for Pediatric Critical Care Medicine: Engaging with citations to references in the Chatbot Generative Pre-Trained Transformer era. Pediatr Crit Care Med. 2023; 24:862–868
31. Tasker RC: Writing for Pediatric Critical Care Medicine: Editorials and Commentaries. Pediatr Crit Care Med. 2024; 24:862–868
Editor’s Choice Articles for April 2024
Tasker, Robert C. MBBS, MD, FRCP1,2,3
Another month of top-rated specialist articles in Pediatric Critical Care Medicine (PCCM). My three April 2024 Editor’s Choice articles, each with editorials, cover familiar research themes in the Journal. For a change, alongside each of these highlights, I include some educational material usually found in the PCCM Connections section. The topics are pediatric acute respiratory distress syndrome (PARDS) (1,2), formal ethics consultation in cases of extracorporeal membrane oxygenation (ECMO) (3,4), and hemodynamics in cannulation for ECMO during active cardiopulmonary resuscitation (ECPR) (5,6).
Gertz SJ, Bhalla A, Chima RS, et al; Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology (PARDIE) Investigators and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Immunocompromised-Associated Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study (1).
My first Editor’s Choice article is a report using the 2016/2017 PARDS incidence and epidemiology (PARDIE) cohort. The accompanying editorial (2) is helpful because it reviews last year’s articles using the PARDIE dataset: the association between platelet transfusion and diuretic use with unfavorable outcome (7); and the association between immunosuppression and noninvasive ventilation (NIV) failure (8,9). The PARDIE investigators delve deeper into the 2016/2017 dataset and compare 105 patients with ICC-associated PARDS with another 603 patients with severe PARDS without ICC. Platelet transfusion, diuretic use, and NIV-failure feature in the latest report (1). And of particular interest is how these factors could now add to our interpretation of the 2023 guidance in the Second Pediatric Acute Lung Injury Consensus Conference (10,11): should we consider ICC-associated PARDS as a separate clinical entity, and what about the utility of NIV-trials in such children?
Siegel B, Taylor LS, Alizadeh F, et al: Formal Ethics Consultation in Extracorporeal Membrane Oxygenation Patients: A Single-Center Retrospective Cohort of a Quaternary Pediatric Hospital (3).
My second Editor’s Choice article is a single-center review of formal ethics consultation in ECMO patients, 2012−2021 (3). This work is about 27 of 605 ECMO patients who were referred for ethics consultation, with a focus on frequent ethical themes that occur. The accompanying editorial provides a helpful discussion on how to maximize the benefits of ethics consultation (4). Read this material with the 2023 systematic review on prognostic and goals of care communication in the pediatric intensive care unit (12), and the 2022 reports on ECMO candidacy decisions (13–15).
Yates AR, Naim MY, Reeder RW, et al: Early Cardiac Arrest Hemodynamics, End-Tidal Co2, and Outcomes in Pediatric Extracorporeal Cardiopulmonary Resuscitation: Secondary Analysis of the ICU-RESUScitation Project Dataset (2016-2021) (5).
My third Editor’s Choice article is a secondary analysis of the ICU-Resuscitation project (ICU-RESUS) dataset, with a focus on invasive arterial waveform data in 97 patients undergoing ECPR. The potential usefulness of such monitoring in gauging pathophysiology is covered in the accompanying editorial (6). For a broader view, read this work from 2016−2021 with the recent ECPR data from the Extracorporeal Life Support Organization dataset (2017−2021) (16), and the Virtual Pediatric System database (2010−2018) (17).
There are two other PCCM Connections educational items this month. The first is a Special Article from the Pediatric Data Science and Analytics (PEDAL) subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators network (18). The PEDAL article combines a scoping review on the use of supervised machine learning applications in PCCM research with a position paper on the standard needed for future PCCM articles using machine learning (19).
The second item is a Professional Organization research perspective from the Sedation Consortium on Endpoints and Procedures for Treatment, Education and Research (SCEPTER) IV Workshop (20). The SCEPTER group has defined 25 consensus statements to improve the methodology of clinical studies involving analgesia and sedation in practices such as the PICU. Read these statements along with the Society of Critical Care Medicine clinical practice guidelines published in 2022 (21), because they relate to adding more to our evidence base.
Finally, we have the return of the PCCM Narrative. This month I am pleased to present n essay from a 3rd year medical student giving us a touching piece called “Superhero” (22).
1. Gertz SJ, Bhalla A, Chima RS, et al.; Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology (PARDIE) Investigators and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Immunocompromised-associated pediatric acute respiratory distress syndrome: Experience from the 2016/2017 pediatric acute respiratory distress syndrome incidence and epidemiology prospective cohort study. Pediatr Crit Care Med. 2024; 25:288–300
2. Marraro GA, Chen Y-F, Spada C: So, what about acute respiratory distress syndrome in immunocompromised pediatric patients? Pediatr Crit Care Med. 2024; 25:375–377
3. Siegel B, Taylor LS, Alizadeh F, et al.: Formal ethics consultation in extracorporeal membrane oxygenation patients: A single-center retrospective cohort of a quaternary pediatric hospital. Pediatr Crit Care Med. 2024; 25:301–311
4. Kirsch RE: Extracorporeal membrane oxygenation ethics: What is your question? Pediatr Crit Care Med. 2024; 25:377–379
5. Yates AR, Naim MY, Reeder RW, et al.: Early cardiac arrest hemodynamics, end-tidal Co2, and outcomes in pediatric extracorporeal cardiopulmonary resuscitation: Secondary analysis of the ICU-RESUScitation project dataset (2016-2021). Pediatr Crit Care Med. 2024; 25:312–322
6. Kobayashi RL, Sperotto F, Alexander PMA: Targeting hemodynamics of cardiopulmonary resuscitation to cardiac physiology–the next frontier for resuscitation science? Pediatr Crit Care Med. 2024; 25:380–382
7. Hamil GS, Remy KE, Slain KN, et al.; Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology (PARDIE) Investigators and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Association of interventions with outcomes in children at-risk for pediatric acute respiratory distress syndrome: A pediatric acute respiratory distress syndrome incidence and epidemiology study. Pediatr Crit Care Med. 2023; 24:574–583
8. 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. Pediatr Crit Care Med. 2023; 24:715–726
9. Milesi C, Baleine J, Mortamet G, et al.: Noninvasive ventilation in pediatric acute respiratory distress syndrome: “Another dogma bites the dust.”. Pediatr Crit Care Med. 2023; 24:783–785
10. Carroll CL, Napolitano N, Pons-Odena M, et al.; Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Noninvasive respiratory support for pediatric acute respiratory distress syndrome: From the second pediatric acute lung injury consensus conference. Pediatr Crit Care Med. 2023; 24(12 Suppl 2):S135–S147
11. Emerieaud G, Lopez-Fernandez YM, Iyer NP, et al.; Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Executive summary of the second international guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PALICC-2). Pediatr Crit Care Med. 2023; 24:143–168
12. McSherry ML, Rissman L, Mitchell R, et al.: Prognostic and goals-of-care communication in the PICU: A systematic review. Pediatr Crit Care Med. 2023; 24:e28–e43
13. Moynihan KM, Jansen M, Siegel B, et al.: Extracorporeal membrane oxygenation candidacy decisions: An argument for a process-based longitudinal approach. Pediatr Crit Care Med. 2022; 23:e434–e439
14. Kingsley J, Markovitz B: To cannulate or not to cannulate: Are we asking the wrong question? Pediatr Crit Care Med. 2022; 23:759–761
15. Zinter MS, McArthur J, Duncan C, et al.; Hematopoietic Cell Transplant and Cancer Immunotherapy Subgroup of the PALISI Network: Candidacy for extracorporeal life support in children after hematopoietic cell transplantation: A position paper from the pediatric acute lung injury and sepsis investigators network’s hematopoietic cell transplant and cancer immunotherapy subgroup. Pediatr Crit Care Med. 2022; 23:205–213
16. Beni CE, Rice-Townsend SE, Esangbedo ID, et al.: Outcome of extracorporeal cardiopulmonary resuscitation in pediatric patients with congenital cardiac disease: Extracorporeal Life Support Organization Registry study. Pediatr Crit Care Med. 2023; 24:927–936
17. 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. Pediatr Crit Care Med. 2023; 24:910–918
18. Randolph AG, Bembea MM, Cheifetz IM, et al.; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Evolution of an investigator-initiated research network. Pediatr Crit Care Med. 2022; 23:1056–1066
19. Heneghan JA, Walker SB, Fawcett A, et al.; The Pediatric Data Science and Analytics (PEDAL) subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network: Use of supervised machine learning applications in pediatric critical care medicine research. Pediatr Crit Care Med. 2024; 25:364–374
20. Jackson SS, Lee JJ, Jackson WM, et al.: Sedation research in critically ill pediatric patients: Proposals for future study design from the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV workshop. Pediatr Crit Care Med. 2024; 25:e193–e204
21. Smith HAB, Besunder JB, Betters KA, et al.: 2022 Society of Critical Care Medicine clinical practice guidelines 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. Pediatr Crit Care Med. 2022; 23:e74–e110
22. Friend TH: Superhero. Pediatr Crit Care Med. 2024; 25:362–363
Editor’s Choice Articles for March 2024
Tasker, Robert C. MBBS, MD, FRCP1–3
March 2024 and another month of amazing content in Pediatric Critical Care Medicine (PCCM). Please take the time to read my three Editor’s Choice articles, each with editorials. First is an article about prognostic modeling in critically ill children in a low- and middle-income (LMIC) PICU in Cambodia (1,2). The second is a single-center analysis of noninvasive neurally adjusted ventilatory assist (NIV-NAVA) in infants with bronchiolitis (3,4). The third is a two-center PICU study about a machine learning model designed to improve the conventional clinical criteria to predict need for intubation in the PICU (5,6).
Chandna A, Keang S, Vorlark M, et al: A Prognostic Model for Critically Ill Children in Locations With Emerging Critical Care Capacity (1).
My first editor’s choice article from Cambodia used a dataset of over 1,300 children (1,500 admission) in a PICU, 2018 to 2020. There were close to 100 deaths, and the authors examined the performance of nine existing severity of illness mortality prediction scores, and then derived their own prediction model for their resource constrained setting. The accompanying editorial provides an international perspective with a commentary on the various risk-prediction models available and what the study adds to the literature (2).
This new work from Cambodia (1,2) is now the next piece of a contemporary narrative within PCCM focused on PICU practice in LMIC settings. For example, we have had articles about utility of Pediatric Index of Mortality scoring (7), resource inequities among facilities (8), pediatric acute respiratory distress syndrome diagnosis and prevalence (9,10), sepsis biomarkers (11,12), and sepsis definitions that are appropriate for children worldwide (13). Also look at the deeper insight provided by our PCCM editorial commentaries on LMIC settings about monitoring outcomes (14), development of services when resources are scarce (15), and centralization of practices (16).
Lepage-Farrell A, Tabone L, Plante V, et al: Noninvasive Neurally Adjusted Ventilatory Assist in Infants With Bronchiolitis: Respiratory Outcomes in a Single-Center, Retrospective Cohort, 2016−2018 (3).
My second editor’s choice article is from investigators at a PICU in Canada who report their experience of using NIV-NAVA in 64 of 205 bronchiolitis patients aged under 2 years. In this report, NIV-NAVA was used after failure of first-tier NIV support (i.e., continuous positive airway pressure or high-flow nasal oxygen [HFNO]) during the two winters, 2016−2018. Six of the NIV-NAVA patients deteriorated to the point of needing invasive mechanical ventilation (IMV). The researchers give a detailed account of respiratory effort physiology with quantitative electrical activity of the diaphragm (Edi) from 2 hours before to 2 hours after starting NIV-NAVA.
This work extends two themes in PCCM: bronchiolitis and diaphragmatic electrophysiology. Regarding bronchiolitis respiratory support, by way of recalling what was published in 2023, we had a systematic review and network meta-analyses on HFNO and other NIV therapies in bronchiolitis (17); two quality improvement studies of “protocolized NIV” in bronchiolitis (18–20); and a multicenter, retrospective study of variations in early PICU management during IMV (21,22). Regarding diaphragmatic electrophysiology, in 2021 PCCM had a descriptive study of transcutaneous electromyography (23,24), and in 2023 there was a retrospective report about the range in Edi measurements in the PICU population (25,26) from the current researchers in Canada (3). Add to all this material the editorial that accompanies the new report (4). It gives a helpful discussion about bringing together bronchiolitis clinical care with diaphragmatic electrophysiology data in a potential protocolized trial (4) (n.b., elsewhere in PCCM we call these pragmatic trials (27,28)).
Chanci D, Grunwell JR, Rafiel A, et al: Development and Validation of a Model for Endotracheal Intubation and Mechanical Ventilation Prediction in PICU Patients (5).
My third editor’s choice article focuses on the problem of predicting need for endotracheal intubation and IMV in PICU patients. Here, the authors use large datasets to develop and validate an automated machine learning model for decision-support. This material is state-of-the-art for the PICU, so also read the accompanying editorial (6). There are two other editorials that have been part of the Journal’s narrative on machine learning: one gives details about evaluating machine learning models for clinical prediction problems (29); the other is about clinical deterioration detection using machine learning (30). These, together with this March’s editorial (6), serve as an education in this theme of research.
In the April 2024 issue, the PEDAL (pediatric data science and analytics) subgroup of the PALISI (pediatric acute lung injury and sepsis investigators) network (31) have a scoping review as part of a Special Article on the use of supervised machine learning applications in PCCM research (32). This PEDAL subgroup position paper will be the standard for future PCCM articles on machine learning in the PICU.
The PCCM Connections this month highlights two educational items. The first is in the new and improved Editorial Notes, Methods, and Statistics section article comments on the problem of measurement error in PCCM research (33). This commentary is very important for those reading and reporting research in PCCM as it describes the standard now required for considering error, precision, bias, noise, and differences between measurements and scales presented in our tables and figures. As an example, the authors write about data using point of care ultrasound (POCUS) measurements. They illustrate their material with one of the other studies published this month (34). Here, POCUS was used in under 5-year-olds to measure the laryngeal air column width around a cuffed endotracheal tube before extubation. These millimeter measurements (to 2 decimal places) were then related to risk of postextubation stridor.
Finally, the second educational item highlighted in PCCM Connections is a Clinical Science commentary about the cold stress response in acute brain injury and critical illness (35). The authors from the Safar Center for Resuscitation Research, Pittsburgh, write an outstanding and beautifully illustrated commentary and, in PCCM’s 25th year, it shows how far the field has progressed since the Safar group’s 2000 (volume number 1) publication on secondary brain damage after traumatic injury (36).
1. Chandna A, Keang S, Vorlark M, et al.: A prognostic model for critically ill children in locations with emerging critical care capacity. Pediatr Crit Care Med. 2024; 25:189–200
2. Carter MJ, Ranjit S: Prognostic markers in pediatric critical care: Data from the diverse majority. Pediatr Crit Care Med. 2024; 25:271–273
3. Lepage-Farrell A, Tabone L, Plante V, et al.: Noninvasive neurally adjusted ventilatory assist in infants with bronchiolitis: Respiratory outcomes in a single-center, retrospective cohort, 2016-2018. Pediatr Crit Care Med. 2024; 25:201–211
4. Keim G, Nishisaki A: Improving noninvasive ventilation for bronchiolitis: It is here to stay! Pediatr Crit Care Med. 2024; 25:274–275
5. Chanci D, Grunwell JR, Rafiel A, et al.: Development and validation of a model for endotracheal intubation and mechanical ventilation prediction in PICU patients. Pediatr Crit Care Med. 2024; 25:212–221
6. Fackler J, Ghobadi K, Gurses AP: Algorithms at the bedside: Moving past development and validation. Pediatr Crit Care Med. 2024; 25:276–278
7. Solomon LJ, Naidoo KD, Appel I, et al.: Pediatric index of mortality 3–an evaluation of function among ICUs in South Africa. Pediatr Crit Care Med. 2021; 22:813–821
8. Abbas Q, Shahbaz FF, Hussain MZH, et al.: Evaluation of the resources and inequities among pediatric critical care facilities in Pakistan. Pediatr Crit Care Med. 2023; 24:e611–e620
9. Morrow BM, Agulnik A, Brunow de Carvalho W, et al.; Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Diagnosis, management, and research considerations for pediatric acute respiratory distress syndrome in resource-limited settings: From the second pediatric acute lung injury consensus conference. Pediatr Crit Care Med. 2023; 24(Suppl 2):S148–S159
10. Morrow BM, Lozano Ray E, McCulloch M, et al.: Pediatric acute respiratory distress syndrome in South African PICUs: A multisite point-prevalence study. Pediatr Crit Care Med. 2023; 24:1063–1071
11. Ishaque S, Famularo ST 3rd, Saleem AF, et al.: Biomarker-based risk stratification in pediatric sepsis from a low-middle income country. Pediatr Crit Care Med. 2023; 24:563–573
12. Mount MC, Remy KE: Help wanted for sepsis: Biomarkers in low- and middle-income countries please apply. Pediatr Crit Care Med. 2023; 24:619–621
13. Carrol ED, Ranjit S, Menon K, et al.; Society of Critical Care Medicine’s Pediatric Sepsis Definition Taskforce: Operationalizing appropriate sepsis definitions in children worldwide: Considerations for the pediatric sepsis definition taskforce. Pediatr Crit Care Med. 2023; 24:e263–e271
14. Slater A: Monitoring the outcome of children admitted to intensive care in middle-income countries: What will it take? Pediatr Crit Care Med. 2021; 22:850–852
15. Argent AC: Pediatric intensive care development when resources are scarce and demand is potentially very high. Pediatr Crit Care Med. 2023; 24:525–527
16. Argent AC: Centralization of pediatric critical care services–it seems to work in Australia and New Zealand Is it right for all? Pediatr Crit Care Med. 2022; 23:952–954
17. Gutierrez Moreno M, Del Villar Guerra P, Medina A, et al.: High-flow oxygen and other noninvasive respiratory support therapies in bronchiolitis: Systematic review and network meta-analyses. Pediatr Crit Care Med. 2023; 24:133–142
18. Huang JX, Colwell B, Vadlaputi P, et al.: Protocol-driven initiation and weaning of high-flow nasal cannula for patients with bronchiolitis: A quality improvement initiative. Pediatr Crit Care Med. 2023; 24:112–122
19. Marx MHM, Shein SL: Deaf ears, blind eyes, and driverless cars. Pediatr Crit Care Med. 2023; 24:177–179
20. Maue DK, Ealy A, Hobson MJ, et al.: Improving outcomes for bronchiolitis patients after implementing a high-flow nasal cannula holiday and standardizing discharge criteria in a PICU. Pediatr Crit Care Med. 2023; 24:233–242
21. 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. Pediatr Crit Care Med. 2023; 24:1010–1021
22. Straube TL, Rotta AT: Sedation, relaxation, and a tube in the nose: Which are associated with longer mechanical ventilation woes? Early management strategies and outcomes in critical bronchiolitis. Pediatr Crit Care Med. 2023; 24:1086–1089
23. van Leuteren RW, de Waal CG, de Jongh FH, et al.: Diaphragm activity pre and post extubation in ventilated critically ill infants and children measured with transcutaneous electromyography. Pediatr Crit Care Med. 2021; 22:950–959
24. Morris IS, Goligher EC: What can we learn from monitoring diaphragm activity in infants? Pediatr Crit Care Med. 2021; 22:1003–1005
25. Plante V, Poirier C, Guay H, et al.: Elevated diaphragmatic tonic activity in PICU patients: Age-specific definitions, prevalence, and associations. Pediatr Crit Care Med. 2023; 24:447–457
26. van Leuteren RW, Bem RA: Measuring expiratory diaphragm activity: An electrifying tool to guide positive end-expiratory pressure strategy in critically ill children? Pediatr Crit Care Med. 2023; 24:515–517
27. Peters MJ, Ramnarayan P, Scholefield BR, et al.; United Kingdom Paediatric Critical Care Society Study Group (PCCS-SG): The United Kingdom paediatric critical care society study group: The 20-year journey toward pragmatic, randomized clinical trials. Pediatr Crit Care Med. 2022; 23:1067–1075
28. Ramnarayan P, Peters MJ: Commentary on the first-line support for assistance in breathing in children trials on noninvasive respiratory support: Taking a closer look. Pediatr Crit Care Med. 2022; 23:1084–1088
29. Sanchez-Pinto LN, Bennett TD: Evaluation of machine learning models for clinical prediction problems. Pediatr Crit Care Med. 2022; 23:405–408
30. Bennett TD: Pediatric deterioration detection using machine learning. Pediatr Crit Care Med. 2023; 24:347–349
31. Randolph AG, Bembea MM, Cheifetz IM, et al.; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Pediatric Acute Lung Injury and Sepsis Investigators (PALISI): Evolution of an investigator-initiated network. Pediatr Crit Care Med. 2022; 23:1056–1066
32. Heneghan JA, Walker SB, Fawcett A, et al.: The pediatric data science and analytics subgroup of the pediatric acute lung injury and sepsis investigators network: Use of supervised machine learning applications in pediatric critical care medicine research. Pediatr Crit Care Med. 2023 Dec 7. [online ahead of print]
33. Luchette M, Akhondi-Asl A: Measurement error. Pediatr Crit Care Med. 2024; 25:e140–e148
34. Burton L, Loberger J, Baker M, et al.: Pre-extubation ultrasound measurement of in situ cuffed endotracheal tube laryngeal air column width difference: Single-center pilot study of relationship with post-extubation stridor in under 5 year olds. Pediatr Crit Care Med. 2024; 25:222–230
35. Jackson TC, Herrmann JR, Fink EL, et al.: Harnessing the promise of the cold stress response for acute brain injury and critical illness in infants and children. Pediatr Crit Care Med. 2024; 25:259–270
36. Kochanek PM, Clark RSB, Ruppel RA, et al.: Biochemical, cellular, and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: Lessons learned from the bedside. Pediatr Crit Care Med. 2000; 1:4–19
Editor’s Choice Articles for February 2024
Tasker, Robert C. MBBS, MD, FRCP1,2,3
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?
1. Buchman TG, Tasker RC: Fair use of augmented intelligence and artificial intelligence in the preparation and review of submissions to the Society of Critical Care Medicine journals. Crit Care Med. 2024; 25:85–87
2. Tasker RC: Writing for Pediatric Critical Care Medicine: Engaging with citations to references in the Chatbot Generative Pre-Trained Transformer era. Pediatr Crit Care Med. 2023; 24:862–868
3. 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. Pediatr Crit Care Med. 2024; 25:92–105
4. 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). Pediatr Crit Care Med. 2024; 25:118–127
5. Harley A, George S, Phillips N, et al.: Resuscitation with early adrenaline infusion for children with septic shock–a randomized pilot trial: The RESPOND ED randomized clinical trial. Pediatr Crit Care Med. 2024; 25:106–117
6. Ista E, van Dijk M: Moving away from randomized controlled trials to hybrid implementation studies for complex interventions in the PICU. Pediatr Crit Care Med. 2024; 25:177–180
7. Smith HAB, Besunder JB, Betters KA, et al.: 2022 society of critical care medicine clinical practice guidelines 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. Pediatr Crit Care Med. 2022; 23:e74–e110
8. 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. Pediatr Crit Care Med. 2023; 24:636–651
9. Shime N, MacLaren G: ICU liberation bundles and the legend of three arrows. Pediatr Crit Care Med. 2023; 24:703–705
10. Randolph AG, Bembea MM, Cheifetz IM, et al.; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Pediatric acute lung injury and sepsis investigators (PALISI: Evolution of an investigator-initiated research network. Pediatr Crit Care Med. 2022; 23:1056–1066
11. Woods-Hill CZ, Wolfe H, Malone S, et al.; Excellence in Pediatric Implementation Science (ECLIPSE) for the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Implementation science research in pediatric critical care medicine. Pediatr Crit Care Med. 2023; 24:943–951
12. Tasker RC: 2023 in review. Pediatr Crit Care Med. 2023; 24:711–714
13. Peters MJ, Ramnarayan P, Scholefield BR, et al.; United Kingdom Paediatric Critical Care Society Study Group (PCCS-SG): The United Kingdom Paediatric Critical Care Society Study Group: The 20-year journey toward pragmatic, randomized clinical trials. Pediatr Crit Care Med. 2022; 23:1067–1075
14. Ramnarayan P, Peters MJ: Commentary on the first-line support for assistance in breathing in children trials on noninvasive respiratory support: Taking a closer look. Pediatr Crit Care Med. 2022; 23:1084–1088
15. Obonyo NG, Olupot-Olupot P, Mpoya A, et al.: A clinical and physiological prospective observational study on the management of pediatric shock in the post-fluid expansion as supportive therapy trial era. Pediatr Crit Care Med. 2022; 23:502–513
16. Schlapbach LJ, Kisssoon N: Resuscitating children with sepsis and impaired perfusion with maintenance fluid: An evolving concept. Pediatr Crit Care Med. 2022; 23:563–565
17. Carrol ED, Ranjit S, Menon K, et al.; Society of Critical Care Medicine’s Pediatric Sepsis Definition Taskforce: Operationalizing appropriate sepsis definitions in children worldwide: Considerations for the pediatric sepsis definitions taskforce. Pediatr Crit Care Med. 2023; 24:e263–e271
18. Levy RA, Reiter PD, Spear M, et al.: Peripheral vasoactive administration in critically ill children with shock: A single-center retrospective cohort study. Pediatr Crit Care Med. 2022; 23:618–625
19. Peshimam N, Bruce-Hickman K, Crawford K, et al.: Peripheral and central/intraosseous vasoactive infusions during and after pediatric critical care transport: Retrospective cohort study of extravasation injury. Pediatr Crit Care Med. 2022; 23:626–634
20. Madden K: Peripheral vasopressors – are we avoiding the central issue altogether? Pediatr Crit Care Med. 2022; 23:665–667
21. Equey L, Agyeman PKA, Veraguth R, et al.; Swiss Pediatric Sepsis Study Group: Serum ascorbic acid and thiamine concentrations in sepsis: Secondary analysis of the Swiss pediatric sepsis study. Pediatr Crit Care Med. 2022; 23:390–394
22. Fathi A, Downey C, Rabiee Gohar A: Vitamin C deficiency in critically ill children: Prospective observational cohort study. Pediatr Crit Care Med. 2022; 23:395–398
23. Akkuzu E, Yavuz S, Ozcan S, et al.: Prevalence and time course of thiamine deficiency in critically ill children: A multicenter, prospective cohort study in Turkey. Pediatr Crit Care Med. 2022; 23:399–404
24. Mehta NM: Resuscitation with vitamins C and B1 in pediatric sepsis–hold on to your “HAT”. Pediatr Crit Care Med. 2022; 23:385–389
25. McWhinney B, Ungerer J, LeMarsey R, et al.: Serum levels of vitamin C and thiamine in children with suspected sepsis – a prospective observational cohort study. Pediatr Crit Care Med. 2024; 25:171–176
26. Schlapbach LJ, Raman S, Buckley D, et al.; Rapid Acute Paediatric Infection Diagnosis in Suspected Sepsis (RAPIDS) Study Investigators: Resuscitation with vitamin C, hydrocortisone, and thiamine in children with septic shock–a multicenter randomized pilot study: The respond PICU randomized clinical trial. Pediatr Crit Care Med. 2024; 25:159–170
27. Kamps NN, Banks R, Reeder RW, et al.; Life After Pediatric Sepsis Evaluation (LAPSE) Investigators: The association of early corticosteroid therapy with clinical and health-related quality of life outcomes in children with septic shock. Pediatr Crit Care Med. 2022; 23:687–697
28. Menon K: Associations between early corticosteroids, pediatric septic shock, and outcomes: not a simple analysis. Pediatr Crit Care Med. 2022; 23:749–751
29. Klowak JA, Bijelic V, Barrowman N, et al.; Genomics of Pediatric Septic Shock Investigators: The association of corticosteroids and pediatric sepsis biomarker risk model (PERSEVERE)-II biomarker risk stratification with mortality in pediatric septic shock. Pediatr Crit Care Med. 2023; 24:186–193
30. Zimmerman JJ: The classic critical care conundrum encounters precision medicine. Pediatr Crit Care Med. 2023; 24:251–253
Editor’s Choice Articles for January 2024
Tasker, Robert C. MBBS, MD, FRCP1,2,3
It’s January 2024 and the 25th 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)?
1. 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. Pediatr Crit Care Med. 2024; 25:4–14
2. 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. Pediatr Crit Care Med. 2024; 25:15–23
3. 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. Pediatr Crit Care Med. 2024; 25:24–36
4. Thiagarajan RR: Quality of cardiopulmonary resuscitation in children with cardiac and noncardiac disease: Comparing apples and oranges?. Pediatr Crit Care Med. 2024; 25:72–73
5. Butt W: Extracorporeal organ support and anticoagulation with antiplatelet medication. Pediatr Crit Care Med. 2024; 25:74–76
6. Killien EY: Predicting fluid responsiveness in critically ill children: So many tools and so few answers. Pediatr Crit Care Med. 2024; 25:77–80
7. Cashen K, Reeder RW, Ahmed T, et al.; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) and National Heart Lung and Blood Institute ICU-RESUScitation Project Investigators: Sodium bicarbonate use during pediatric cardiopulmonary resuscitation: A secondary analysis of the ICU-RESUScitation project trial. Pediatr Crit Care Med. 2022; 23:784–792
8. Morgan RW, Wolfe HA, Reeder RW, et al.: The temporal association of the COVID-19 pandemic and pediatric cardiopulmonary resuscitation quality and outcomes. Pediatr Crit Care Med. 2022; 23:908–918
9. Tasker RC: Writing for PCCM: Instructions for authors. Pediatr Crit Care Med. 2022; 23:651–655
10. Su E, Soni NJ, Blaivas M, et al.: Regulating critical care ultrasound, it is all in the interpretation. Pediatr Crit Care Med. 2021; 22:e253–e258
11. Conlon TW, Kantor DB, Hirshberg EL, et al.: A call to action for the pediatric critical care community. Pediatr Crit Care Med. 2021; 22:e410–e414
12. Maxson IN, Su E, Brown KA, et al.: 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. Pediatr Crit Care Med. 2024; 24:e511–e519
13. Bronicki RA, Tume SC, Flores S, et al.: The cardiovascular system in severe sepsis: Insight from a cardiovascular simulator. Pediatr Crit Care Med. 2022; 23:464–472
14. Bronicki RA, Tume SC, Flores S, et al.: The cardiovascular system in cardiogenic shock: Insight from a cardiovascular simulator. Pediatr Crit Care Med. 2024; 24:937–942
15. Dhillon GS, Kleinman ME, Staffa SJ, et al.; American Heart Association’s Get With The Guidelines – Resuscitation (GWTG-R) Investigators: Caclium administration during cardiopulmonary resuscitation for in-hospital cardiac arrest in children with heart disease is associated with worse survival – A report from the American Heart Association’s Get With The Guidelines-Resuscitation (GWTG-R) registry. Pediatr Crit Care Med. 2022; 23:860–871
16. Savorgnan F, Acosta S: Calclium chloride is given to sicker patients during cardiopulmonary resuscitation events. Pediatr Crit Care Med. 2022; 23:938–940
17. DelSignore L: Sodium bicarbonate and poor outcomes in cardiopulmonary resuscitation: Coincidence or culprit? Pediatr Crit Care Med. 2022; 23:848–851
18. Gray JM, Raymond TT, Atkins DL, et al.; pediRES-Q Investigators: Inappropriate shock delivery is common during pediatric in-hospital cardiac arrest. Pediatr Crit Care Med. 2023; 24:e390–e396
Editor’s Choice Articles for December 2023
Tasker, Robert C. MBBS, MD, FRCP1,2,3
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
WHAT FACTORS ARE ASSOCIATED WITH DURATION OF INVASIVE MECHANICAL VENTILATION FOR VIRAL BRONCHIOLITIS
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).
1. 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. Pediatr Crit Care Med. 2023; 24:998–1009
2. Randolph AG, Bembea MM, Cheifetz IM, et al.; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Pediatric acute lung injury and sepsis investigators (PALISI): Evolution of an investigator-initiated research group. Pediatr Crit Care Med. 2022; 23:1056–1066
3. 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. Pediatr Crit Care Med. 2023; 24:1010–1021
4. Mitting RB, Peshimam N, Lillie J, et al.: Invasive mechanical ventilation for acute viral bronchiolitis: Retrospective multicenter cohort study. Pediatr Crit Care Med. 2021; 22:231–240
5. Smith HAB, Besunder JB, Betters KA, et al.: 2022 Society of Critical Care Medicine clinical practice guidelines 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. Pediatr Crit Care Med. 2022; 23:e74–e110
6. Peters MJ, Ramnarayan P, Scholefield BR, et al.; United Kingdom Paediatric Critical Care Society Study Group (PCCS-SG): The United Kingdom Paediatric Critical Care Society Study Group: The 20-year journey toward pragmatic, randomized clinical trials. Pediatr Crit Care Med. 2022; 23:1067–1075
7. Pryce P, Gangopadhyay M, Edwards JD: Parental adverse childhood experiences and post-PICU stress in children and parents. Pediatr Crit Care Med. 2023; 24:1022–1032
8. Woolgar FA, Wilcoxon L, Pathan N, et al.: Screening for factors influencing parental psychological vulnerability during a child’s PICU admission. Pediatr Crit Care Med. 2022; 23:286–295
9. Garofano JS, Kudchadkar SR: The blurred lines between mental and somatic healthcare: Screening caregiver psychological vulnerability to improve clinical care. Pediatr Crit Care Med. 2022; 23:330–332
10. Whyte-Nesfield M, Kaplan D, Eldridge PS, et al.: Pediatric critical care-associated parental traumatic stress: Beyond the first year. Pediatr Crit Care Med. 2023; 24:93–101
11. Colville G: Is it time for the “trauma-informed” PICU? Pediatr Crit Care Med. 2023; 24:171–173
12. Colville G: ACEs high: Parents’ own history of childhood adversity is associated with their increased risk of PTSD after PICU. Pediatr Crit Care Med. 2023; 24:1089–1091
13. Colville GA: Mental health provision in PICU: An analysis of referrals to an embedded psychologist over 20 years at a single center. Pediatr Crit Care Med. 2023; 24:e592–e601
14. 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. Pediatr Crit Care Med. 2023; 24:1033–1042
15. Tume LN, Eveleens RD, Verbruggen SCAT, et al.; ESPNIC Metabolism, Endocrine and Nutrition section: Barriers to delivery of enteral nutrition in pediatric intensive care: A world survey. Pediatr Crit Care Med. 2020; 21:e661–e671
16. De Souza BJ, Callif C, Staffa SJ, et al.: Current state of nutrition education in pediatric critical care medicine fellowship programs in the United States and Canada. Pediatr Crit Care Med. 2020; 21:e769–e775
17. Osawa I, Tsuboi N, Nozawa H, et al.: Ultrasound-guided postpyloric feeding tube placement in critically ill pediatric patient. Pediatr Crit Care Med. 2021; 22:e324–e328
18. Albert BD: Postpyloric feeding tube placement under ultrasound guidance: Is it moving forward? Pediatr Crit Care Med. 2021; 22:514–516
19. Tume LN, Eveleens RD, Mayordomo-Colunga J, et al.; ESPNIC Metabolism, Endocrine and Nutrition Section and the Respiratory Failure Section: Enteral feeding of children on noninvasive respiratory support: A four-center European study. Pediatr Crit Care Med. 2021; 22:e192–e202
20. Varkey A, Carroll CL: Can I just reflux and grow? Feeding critically ill children receiving respiratory support. Pediatr Crit Care Med. 2021; 22:339–341
21. Martinez EE, Dang H, Franks J, et al.: Association between anticholinergic drug burden and adequacy of enteral nutrition in critically ill, mechanically ventilated pediatric patients. Pediatr Crit Care Med. 2021; 22:1083–1087
22. Martinez EE, Mehta NM, Fasano A: The Zonulin pathway as a potential mediator of gastrointestinal dysfunction in critical illness. Pediatr Crit Care Med. 2022; 23:e424–e428
23. Rissman L: Shared vulnerabilities. Pediatr Crit Care Med. 2023; 24:1084–1085
24. Tasker RC: 2023 in review. Pediatr Crit Care Med. 2023; 24:81–83
Editor’s Choice Articles for November 2023
Tasker, Robert C. MBBS, MD, FRCP1,2,3
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).
1. Checchia PA: Pediatric Critical Care Medicine and cardiac critical care research. Pediatr Crit Care Med. 2023; 24:887–889
2. 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. Pediatr Crit Care Med. 2023; 24:910–918
3. Beni CE, Rice-Townsend SE, Esangbedo ID, et al.: Outcome of extracorporeal cardiopulmonary resuscitation in pediatric patients without congenital cardiac disease: Extracorporeal Life Support Organization registry study. Pediatr Crit Care Med. 2023; 24:927–936
4. Kucher NM, Marquez AM, Guerguerian AM, et al.: Epinephrine dosing use during extracorporeal cardiopulmonary resuscitation: Single-center retrospective cohort. Pediatr Crit Care Med. 2023; 24:e531–e539
5. Butt W: Cardiopulmonary resuscitation, epinephrine and extracorporeal membrane oxygenation: Finding the right balance. Pediatr Crit Care Med. 2023; 24:975–978
6. Esangbedo ID, Brunetti MA, Campbell FM, et al.: Pediatric extracorporeal cardiopulmonary resuscitation A systematic review. Pediatr Crit Care Med. 2020; 21:e934–e943
7. 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. Pediatr Crit Care Med. 2023; 24:919–926
8. Su E, Bhargava V, Gil DV, et al.: The path to durable access in critically ill children: Not a straight line. Pediatr Crit Care Med. 2023; 24:969–972
9. Kozyak BW, Fraga MV, Juliano CE, et al.: Real-time ultrasound guidance for umbilical venous cannulation in neonates with congenital heart disease. Pediatr Crit Care Med. 2022; 23:e257–e266
10. 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. Pediatr Crit Care Med. 2023; 24:e511–e519
11. Oulego-Erroz I, Terroba-Seara S, Alonso-Quintela P, et al.: Respiratory variation in aortic blood flow velocity in hemodynamically unstable, ventilated neonates A pilot study of fluid responsiveness. Pediatr Crit Care Med. 2021; 22:380–391
12. DeSanti RL, Al-Subu AM, Cowan EA, et al.: Point-of-care ultasound to diagnose the etiology of acute respiratory failure at admission to the PICU. Pediatr Crit Care Med. 2021; 22:722–732
13. Conlon T, Keim G: Pathophysiology versus etiology using lung ultrasound Clinical correlation required. Pediatr Crit Care Med. 2021; 22:761–763
14. Su E, Dutko A, Ginsburg S, et al.: Death and ultrasound evidence of the akinetic heart in pediatric cardiac arrest. Pediatr Crit Care Med. 2023; 24:e568–e572
15. Randolph AG, Bembea MM, Cheifetz IM, et al.; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Evolution of an investigator-initiated research network. Pediatr Crit Care Med. 2022; 23:1056–1066
16. Werho DK, DeWitt AG, Owens ST, et al.: Establishing entrustable professional activities in pediatric cardiac critical care. Pediatr Crit Care Med. 2022; 23:54–59
17. Tabbutt S, Krawczeski C, McBride M, et al.: Standardized training for physicians practicing pediatric cardiac critical care. Pediatr Crit Care Med. 2022; 23:60–64
18. Checchia PA: It is time to raise the bar with a board. Pediatr Crit Care Med. 2022; 23:74–75
19. Su E, Soni NJ, Blaivas M, et al.: Regulating critical care ultrasound, it is all in the interpretation. Pediatr Crit Care Med. 2021; 22:e253–e258
20. Conlon TW, Kantor DB, Hirshberg EL, et al.: A call to action for the pediatric critical care community. Pediatr Crit Care Med. 2021; 22:e410–e414
Editor’s Choice Articles for October 2023
Tasker, Robert C. MBBS, MD, FRCP1,2,3
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).
1. 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. Pediatr Crit Care Med. 2023; 24:795–806
2. Trujillo Rivera EA, Patel AK, Zeng-Treitler Q, et al.: Severity trajectories of pediatric inpatients using the criticality index. Pediatr Crit Care Med. 2021; 22:e19–e32
3. Rivera EAT, Patel AK, Chamberlain JM, et al.: Criticality: A new concept of severity of illness for hospitalized children. Pediatr Crit Care Med. 2021; 22:e33–e43
4. Perizes EN, Chong G, Sanchez-Pinto LN: Derivation and validation of vasoactive inotrope score trajectory groups in critically ill children with shock. Pediatr Crit Care Med. 2022; 23:1017–1026
5. Horvat CM, Fabio A, Nagin DS, et al.; on behalf of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network: Mortality risk in pediatric sepsis based on C-reactive protein and ferritin levels. Pediatr Crit Care Med. 2022; 23:968–979
6. Matics TJ, Sanchez-Pinto LN: Adaptation and validation of a pediatric sequential organ failure assessment score and evaluation of the Sepsis-3 definitions in critically ill children. JAMA Pediatr. 2017; 171:e172352
7. Balcarcel D, Fitzgerald JC, Alcamo AM: Unmasking critical illness: using machine learning and biomarkers to see what lies beneath. Pediatr Crit Care Med. 2023; 24:869–871
8. Cheung C, Kernan KF, 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. Pediatr Crit Care Med. 2023; 24:840–848
9. Dean MJ for the Collaborative Pediatric Critical Care Research Network (CPCCRN) investigators: Evolution of the collaborative pediatric critical care research network (CPCCRN). Pediatr Crit Care Med. 2022; 23:1049–1055
10. Badke CM, Marsillio LE, Carroll MS, et al.: Development of a heart rate variability risk score to predict organ dysfunction and death in critically ill children. Pediatr Crit Care Med. 2021; 22:e437–e447
11. Badke CM, Carroll MS, Weese-Mayer DE, et al.: Association between heart rate variability and inflammatory biomarkers in critically ill children. Pediatr Crit Care Med. 2022; 23:e289–e294
12. Miksa M: Beyond survival: Insights from the Phenotyping Sepsis-Induced Multiple Organ Failure study on the neurological impact of pediatric sepsis. Pediatr Crit Care Med. 2023; 24:877–880
13. Alcamo AM, Weiss SL, Fitzgerald JC, et al.; Sepsis Prevalence, Outcomes and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Outcomes associated with timing of neurologic dysfunction onset relative to pediatric sepsis recognition. Pediatr Crit Care Med. 2022; 23:593–605
14. Smith CM: Late-onset neurologic dysfunction in pediatric sepsis – what brains might learn from kidneys and persistent acute kidney injury. Pediatr Crit Care Med. 2022; 23:659–661
15. Kirschen MP, Smith KA, Snyder M, et al.: Serial neurologic assessment in pediatrics (SNAP): A new tool for bedside neurologic assessment of critically ill children. Pediatr Crit Care Med. 2021; 22:483–495
16. Alcamo AM, Barren GJ, Becker AE, et al.: Validation of a computational phenotype to identify acute brain dysfunction in pediatric sepsis. Pediatr Crit Care Med. 2022; 23:1027–1036
17. 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. Pediatr Crit Care Med. 2023; 24:807–817
18. Carlton EF, Pinto N, Smith M, et al.; POST-PICU Investigators of the PALISI Network and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network: Overall health following pediatric critical illness: A scoping review of instruments and methodology. Pediatr Crit Care Med. 2021; 22:1061–1071
19. Pinto NP, Maddux AB, Dervan LA, et al.; POST-PICU Investigators of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN): A core outcome measurement set for pediatric critical care. Pediatr Crit Care Med. 2022; 23:893–907
20. LaRosa JM, Scholefield BR, Kudchadkar SR: Measure to improve like PROs: Patient-related outcomes in survivors of pediatric critical illness. Pediatr Crit Care Med. 2022; 23:946–949
21. Ducharme-Crevier L, La KA, Francois T, et al.: PICU follow-up clinic: Patient and family outcomes 2 months after discharge. Pediatr Crit Care Med. 2021; 22:935–943
22. Smith M, Grassia K, Zimmerman JJ: Acknowledging the importance of follow-up after childhood critical illness. Pediatr Crit Care Med. 2021; 22:998–1000
23. Hickey E, Johnson T, Kudchadkar SR, et al.: Persistence matters! Hurdles and high points of PICU follow-up clinic. Pediatr Crit Care Med. 2022; 23:e397–e399
24. De Sonnaville ESV, van Woensel JBM, van Goudoever JB, et al.; Emma Children’s Hospital Amsterdam UMC Follow Me Program Consortium: Structured multidisciplinary follow-up after pediatric intensive care: A model for continuous data-driven health care innovation. Pediatr Crit Care Med. 2023; 24:484–498
25. Verlinden I, Guiza F, Dulfer K, et al.: Physical, emotional/behavioral, and neurocognitive developmental outcome from 2 to 4 years after PICU admission: A secondary analysis of the early versus late parenteral nutrition randomized controlled trial cohort. Pediatr Crit Care Med. 2022; 23:580–592
26. Maddux AB, Fink EL: The post-PICU growth curve. Pediatr Crit Care Med. 2022; 23:656–658
27. Colville G: Building bridges: Integration of PICU follow-up with aftercare in the community. Pediatr Crit Care Med. 2023; 24:871–874
28. Wong HR, Reeder RW, Banks R, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN) and the Life After Pediatric Sepsis Evaluation (LAPSE) Investigators: Biomarkers for estimating risk of hospital mortality and long-term quality-of-life morbidity after surviving pediatric septic shock: A secondary analysis of the Life After Pediatric Sepsis Evaluation investigation. Pediatr Crit Care Med. 2021; 22:8–15
29. Kamps NN, Banks R, Reeder RW, et al.: The association of early corticosteroid therapy with clinical and health-related quality of life outcomes in children with septic shock. Pediatr Crit Care Med. 2022; 23:687–697
30. Stenson EK, Banks RK, Reeder RW, et al.: Fluid balance and its association with mortality and health-related quality of life: A nonprespecified secondary analysis of the Life After Pediatric Sepsis Evaluation. Pediatr Crit Care Med. 2023; 24:829–839
31. Workman JK, Reeder RW, Banks RK, et al.: Change in functional status during hospital admission and long-term health-related quality of life among pediatric septic shock survivors. Pediatr Crit Care Med. 2023 Jun 22. [online ahead of print]
32. Edwards JD, Wocial LD, Madrigal VN, et al.: Continuity strategies for long-stay PICU patients: Consensus statements from the Lucile Packard Foundation PICU continuity panel. Pediatr Crit Care Med. 2023; 24:849–861
33. Williams EP, Madrigal VN, Leone TA, et al.: Primary intensivists and nurses for long-stay patients: A survey of practices and perceptions at academic PICUs. Pediatr Crit Care Med. 2023; 24:436–446
34. Gouda SR, Hoehn KS: Walking a tightrope: Balancing continuity for long-stay patients and wellness for clinicians in an ever-evolving landscape. Pediatr Crit Care Med. 2023; 24:512–514
35. Zorko DJ, McNally JD, Rochwerg B, et al.; International Pediatric Chronic Critical Illness Collaborative: Defining pediatric chronic critical illness: A scoping review. Pediatr Crit Care Med. 2023; 24:e91–e103
36. Shappley RKH, Noles DL, Spentzas T: Pediatric chronic critical illness: Validation, prevalence, and impact in a children’s hospital. Pediatr Crit Care Med. 2021; 22:e636–e639
37. Heneghan JA, Goodman DM, Ramgopal S: Variable identification of children with medical complexity in United States PICUs. Pediatr Crit Care Med. 2023; 24:56–61
38. Heneghan JA, Akande M, Goodman DM, et al.: High-frequency utilization of the PICU. Pediatr Crit Care Med. 2022; 23:e230–e239
39. Bogetz JF, Revette A, DeCourcey DD: Clinical care strategies that support parents of children with complex chronic conditions. Pediatr Crit Care Med. 2021; 22:595–602
40. Pinto NP, Morrison WE: Supporting children with complex chronic conditions and their families at the end of life. Pediatr Crit Care Med. 2021; 22:669–671
Editor’s Choice Articles for September 2023
Tasker, Robert C. MBBS, MD, FRCP1,2,3
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).
1. 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. Pediatr Crit Care Med. 2023; 24:715–727
2. Carroll CL, Napolitano N, Pons-Odena M, et al.; Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Noninvasive respiratory support for pediatric acute respiratory distress syndrome: From the second pediatric acute lung injury consensus conference. Pediatr Crit Care Med. 2023; 24:S135–S147
3. Emeriaud G, Lopez-Fernandez YM, Iyer NP, et al.; Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Executive summary of the second international guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PALICC-2). Pediatr Crit Care Med. 2023; 24:143–168
4. Boghi D, Kim KW, Kim JH, et al.: Noninvasive ventilation for acute respiratory failure in pediatric patients: A systematic review and meta-analysis. Pediatr Crit Care Med. 2023; 24:123–132
5. Cruces P: Pediatric acute respiratory distress syndrome: approaches in mechanical ventilation. Pediatr Crit Care Med. 2023; 24:e104–e114
6. Milesi C, Baleine J, Mortamet G, et al.: Noninvasive ventilation in pediatric acute respiratory distress syndrome: Another dogma bites the dust. Pediatr Crit Care Med. 2023; 24:783–785
7. 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. Pediatr Crit Care Med. 2023; 24:727–737
8. Dahmer MK, Quasney MW, Sapru A, et al.; BALI and RESTORE Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Interleukin-1 receptor antagonist is associated with pediatric acute respiratory distress syndrome and worse outcomes in children with acute respiratory failure. Pediatr Crit Care Med. 2018; 19:930–938
9. Dean JM; Collaborative Pediatric Critical Care Research Network (CPCCRN) Investigators: Evolution of the collaborative pediatric critical care research network. Pediatr Crit Care Med. 2022; 23:1049–1055
10. Horvat CM, Fabio A, Nagin DS, et al.; on behalf of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network: Mortality risk in pediatric sepsis based on C-reactive protein and ferritin levels. Pediatr Crit Care Med. 2022; 23:968–979
11. Perizes EN, Ching G, Sanchez-Pinto LN: Derivation and validation of vasoactive inotrope score trajectory groups in critically ill children with shock. Pediatr Crit Care Med. 2022; 23:1017–1026
12. Badke CM, Carroll MS, Weese-Mayer DE, et al.: Association between heart rate variability and inflammatory biomarkers in critically ill children. Pediatr Crit Care Med. 2022; 23:e289–e294
13. Sanchez-Pinto LN, Bennett TD, Stroup EK, et al.: Derivation, validation, and clinical relevance of a pediatric sepsis phenotype with persistent hypoxemia, encephalopathy, and shock. Pediatr Crit Care Med. 2023 June 2. [online ahead of print]
14. Rivera EAT, Patel AK, Chamberlain JM, et al.: Criticality: A new concept of severity of illness for hospitalized children. Pediatr Crit Care Med. 2021; 22:e33–e43
15. Aczon MD, Ledbetter DR, Laksana E, et al.: Continuous prediction of mortality in the PICU: A recurrent neural network model in a single-center dataset. Pediatr Crit Care Med. 2021; 22:519–529
16. Bennett TD, Russell S, Albers DJ: Neural networks for mortality prediction: ready for prime time? Pediatr Crit Care Med. 2021; 22:578–581
17. Rivera EAT, Chamberlain JM, Patel AK, et al.: Dynamic mortality risk predictions for children in ICUs: Development and validation of machine learning tools. Pediatr Crit Care Med. 2022; 23:344–352
18. Sanchez-Pinto LN, Bennett TD: Evaluation of machine learning models for clinical prediction problems. Pediatr Crit Care Med. 2022; 23:405–408
19. Rust LOH, Gorham TJ, Bambach S, et al.: The deterioration risk index: Developing and piloting a machine learning algorithm to reduce pediatric inpatient deterioration. Pediatr Crit Care Med. 2023; 24:322–333
20. Bennett TD: Pediatric deterioration detection using machine learning. Pediatr Crit Care Med. 2023; 24:347–349
21. 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. Pediatr Crit Care Med. 2023; 24:750–760
22. Proulx F, Emeriaud G, Francois T, et al.: Oxygenation defects, ventilatory ratio, and mechanical power during severe pediatric acute respiratory distress syndrome: Longitudinal time sequence analyses in a single-center retrospective cohort. Pediatr Crit Care Med. 2022; 23:22–33
23. Khemani RG: Should we embrace mechanical power to understand the risk of ventilator-induced lung injury in children? Pediatr Crit Care Med. 2022; 23:71–74
24. Percy AG, Mai MV, Bhalla AK, et al.: Mechanical power is associated with mortality in pediatric acute respiratory distress syndrome. Pediatr Crit Care Med. 2023; 24:e307–e316
25. Diaz F, Gonzalez-Dambrauskas S, Cristiani F, et al.: Driving pressure and normalized energy transmission calculations in mechanically ventilated children without lung disease and pediatric acute respiratory distress syndrome. Pediatr Crit Care Med. 2021; 22:870–878
26. van Schelven P, Koopman AA, Burgerhof JGM, et al.: Driving pressure is associated with outcome in pediatric acute respiratory failure. Pediatr Crit Care Med. 2022; 23:e136–e144
27. Bruno F, Andreolio C, Garcia PCR, et al.: The relevance of airway resistance in children requiring mechanical ventilatory support. Pediatr Crit Care Med. 2022; 23:e483–e488
28. Ray CC, Pollack MM, Gai J, et al.: The association of the lactate-albumin ratio with mortality and multiple organ dysfunction in PICU patients. Pediatr Crit Care Med. 2023; 24:760–767
29. Butt WW: The lactate-albumin ratio predicts multi-organ dysfunction syndrome and death but is it ready to use? Pediatr Crit Care Med. 2023; 24:785–787
30. Morris KP, Kapetanstrataki M, Wilkins B, et al.: Lactate, base excess, and the pediatric index of mortality: Exploratory study of an international, multicenter dataset. Pediatr Crit Care Med. 2022; 23:e268–e276
31. Geva A, Akhondi-Asl A, Mehta NM: Validation and extension of the association between potentially excess oxygen exposure and death in mechanically ventilated children. Pediatr Crit Care Med. 2023; 24:e434–e440
32. Balcarcel DR, Coates BM, Chong G, et al.: Excessive oxygen supplementation in the first day of mechanical ventilation is associated with multiple organ dysfunction and death in critically ill children. Pediatr Crit Care Med. 2022; 23:89–98
33. Jones GAL, Peters MJ: Towards causality with liberal oxygen use? Pediatr Crit Care Med. 2022; 23:135–137
34. Beshish AG, Jahadi O, Mello A, et al.: Hyperoxia during cardiopulmonary bypass is associated with mortality in infants undergoing cardiac surgery. Pediatr Crit Care Med. 2021; 22:445–453
35. Horvat C: Statistical note: Confounding and causality in observational studies. Pediatr Crit Care Med. 2021; 22:496–498
36. Peters MJ: Linking hyperoxia and harm: Consequence or merely subsequence? Pediatr Crit Care Med. 2021; 22:501–503
37. Jones GAL, Eaton S, Orford M, et al.; Oxy-PICU Investigators of the Paediatric Critical Care Society Study Group (PCCS-SG): Randomization to a liberal versus conservative oxygenation target: Redox responses in critically ill children. Pediatr Crit Care Med. 2023; 24:e137–e146
38. Peters MJ, Ramnarayan P, Scholefield BR, et al.; United Kingdom Paediatric Critical Care Society Study Group (PCCS-SG): The United Kingdom paediatric critical care society study group: The 20-year journey toward pragmatic, randomized clinical trials. Pediatr Crit Care Med. 2022; 23:1067–1075
39. Chang I, Thomas K, O’Neill Gutierrez L, et al.: Protocol for a randomized multiple center trial of conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): Oxygen in pediatric intensive care. Pediatr Crit Care Med. 2022; 23:736–744
40. Lakshmanan C, Ranjit S, Natraj R, et al.: Hyperferritinemia in severe Dengue infection: Single-center retrospective cohort study. Pediatr Crit Care Med. 2023; 24:e409–416
Editor’s Choice Articles for August 2023
Tasker, Robert C. MBBS, MD, FRCP1,2,3
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).
1. 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. Pediatr Crit Care Med. 2023; 24:636–651
2. Smith HAB, Besunder JB, Betters KA, et al.: 2022 Society of Critical Care Medicine clinical practice guidelines 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. Pediatr Crit Care Med. 2022; 23:e74–e110
3. Jones IGR, Freidman S, Vu M, et al.: Improving daily patient goal-setting and team communications: the Liber8 glass door project. Pediatr Crit Care Med. 2023; 24:382–390
4. Geva A, Albert BD, Hamilton S, et al.: eSIMPLER: A dynamic, electronic health record-integrated checklist for clinical decision support during PICU daily rounds. Pediatr Crit Care Med. 2021; 22:898–905
5. Yang Y, Akhondi-sl A, Geva A, et al.: Implementation of an analgesia-sedation protocol is associated with reduction in midazolam usage in the PICU. Pediatr Crit Care Med. 2021; 22:e513–e523
6. Patel RV, Redivo J, Nelliot A, et al.: Early mobilization in a PICU: A qualitative sustainability analysis of PICU Up!. Pediatr Crit Care Med. 2021; 22:e233–e242
7. Shime N, MacLaren G: ICU liberation bundles and the legend of three arrows. Pediatr Crit Care Med. 2023; 24:703–705
8. Paquette ED, Ross LF, Chavez J, et al.: Refusals of the determination of death by neurologic criteria: A mixed methods study of physician perspectives on refusals cases. Pediatr Crit Care Med. 2023; 24:628–635
9. Greer DM, Shemie SD, Lewis A, et al.: Determination of brain death/death by neurologic criteria: The World Brain Death Project. JAMA. 2023; 324:1078–1097
10. Shemie SD, Wilson LC, Hornby L, et al.: A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: A 2023 clinical practice guideline. Can J Anaesth. 2023; 70:483–557
11. Zheng K, Sutherland S, Hornby L, et al.: Public understandings of the definition and determination of death: A scoping review. Transplantation Direct. 2022; 8:e1300
12. Sarti AJ, Honarmand K, Sutherland S, et al.: When is a person dead? The Canadian public’s understanding of death and death determination: A nationwide survey. Can J Anesth. 2023; 70:617–627
13. Sarti AJ, Sutherland S, Meade M, et al.: Death determination by neurologic criteria – what do families understand? Can J Anesth. 2023; 70:637–650
14. Truog RD, Morrison W, Kirschen M: What should we d when families refuse testing for brain death? AMA J Ethics. 2020; 22:e986–e994
15. Suttle M, Hall MW, Pollack MM, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN): Therapeutic alliance between bereaved parents and physicians in the PICU. Pediatr Crit Care Med. 2021; 22:e243–e252
16. Rissman L, Derrington S, Rychlik K, et al.: Parent and physician report of discussions about prognosis for critically ill children. Pediatr Crit Care Med. 2021; 22:785–794
17. McSherry ML, Kudchadkar SR: Prognostic conversations in the PICU: Are we even coming close? Pediatr Crit Care Med. 2021; 22:844–847
18. Gupta D, October TW, Wolfe AMHJ: Characteristics of prognostic statements during family conferences of critically ill children. Pediatr Crit Care Med. 2023; 24:34–40
19. Truog RD: Why do families reject the diagnosis of brain death, and how should we respond? Pediatr Crit Care Med. 2023; 24:701–703
20. Sick-Samuels AC, Booth LD, Milstone AM, et al.: A novel comprehensive algorithm for evaluation of PICU patients with new fever or instability. Pediatr Crit Care Med. 2023; 24:670–680
21. Fontela PS, Gaudreault J, Dagenais M, et al.; Canadian Critical Care Trials Group: Clinical reasoning behind antibiotic use in PICUs: A qualitative study. Pediatr Crit Care Med. 2022; 23:e126–e135
22. Madden K: Risk and resistance: Examining our antibiotic use. Pediatr Crit Care Med. 2022; 23:227–228
23. Chorafa E, Komatsiouli V, Iosifidis E, et al.: Antimicrobial stewardship programs in PICU settings: A systematic review. Pediatr Crit Care Med. 2023; 24:e20–e27
24. Woods-Hill CZ, Koontz DW, Voskertchain A, et al.: Consensus recommendations for blood culture use in critically ill children using a modified Delphi approach. Pediatr Crit Care Med. 2021; 22:774–784
25. Dewan M, Wolfe H, Stalets EL: Relentless improvement: Overcoming the “active resisters and organizational constipators” to drive change. Pediatr Crit Care Med. 2021; 22:842–844
26. Cifra CL, Custer JW, Singh H, et al.: Diagnostic errors in pediatric critical care: A systematic review. Pediatr Crit Care Med. 2021; 22:701–712
27. Wetzel RC: Diagnosis: A tricky, never-ending business. Pediatr Crit Care Med. 2021; 22:758–761
28. Bartman T, Brilli RJ: Quality improvement studies in pediatric critical care medicine. Pediatr Crit Care Med. 2021; 22:662–668
29. Inata Y, Nakagami-Yamaguchi E, Ogawa Y, et al.: Quality assessment of the literature on quality improvement in PICUs: A systematic review. Pediatr Crit Care Med. 2021; 22:553–560
30. Karube T, Karsies TJ: Can we change the culture around fever in the PICU? Pediatr Crit Care Med. 2023; 24:705–707
31. Feldman E, Shah SS, Ahn D: Low diagnostic utility of frequent serial tracheal aspirate cultures in the PICU. Pediatr Crit Care Med. 2023; 24:681–689
32. Prinzi AM, Chiotos K: Repeat tracheal aspirate cultures: A port in the storm or a sinking ship? Pediatr Crit Care Med. 2023; 24:708–710
33. Undar A, Kunselman AR, Barbaro RP, et al.: Centrifugal or roller pumps for neonatal venovenous extracorporeal membrane oxygenation: Extracorporeal life support organization database comparison of mortality and morbidity. Pediatr Crit Care Med. 2023; 24:662–669
34. Pineda EY, Sallam M, Breuer RK, et al.: Asthma cases treated with inhaled anesthetics or extracorporeal membrane oxygenation: A virtual pediatric systems database study of outcomes. Pediatr Crit Care Med. 2023; 24:e397–e402
35. O’Hara JE, Buchmiller TL, Bechard LJ, et al.: Long-term functional outcomes at 1-year after hospital discharge in critically ill neonates with congenital diaphragmatic hernia. Pediatr Crit Care Med. 2023; 24:e372–e381
36. Dennis JL, Jordan J, Rice M, et al.: Enteral nutrition during extracorporeal membrane oxygenation in the neonatal and pediatric populations: A literature review. Pediatr Crit Care Med. 2023; 24:e382–e389
37. Danzer E, Massey SL, Flohr SJ, et al.: Extracorporeal membrane oxygenation for neonates with congenital diaphragmatic hernia: Prevalence of seizures and outcomes. Pediatr Crit Care Med. 2023; 24:e224–e235
38. Bratt Carle JL: The exchange. Pediatr Crit Care Med. 2023; 24:690–691