PCCM Journal

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.

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.

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.

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.

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.

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.

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.

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 (V_D/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), V_D/Vt of 0.47 (IQR 0.38, 0.61), and mortality was 17.6% (23/131). Higher VEqco₂ (p = 0.003), V_D/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 V_D/Vt and the dead space markers in multivariable modeling, although OI was significant.

CONCLUSIONS:

VEqco₂ performs similarly to V_D/Vt and other surrogate dead space markers, is independently associated with mortality risk, and may be a reasonable noninvasive surrogate for V_D/Vt.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 (V_D/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), V_D/Vt of 0.47 (IQR 0.38, 0.61), and mortality was 17.6% (23/131). Higher VEqco₂ (p = 0.003), V_D/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 V_D/Vt and the dead space markers in multivariable modeling, although OI was significant.

CONCLUSIONS:

VEqco₂ performs similarly to V_D/Vt and other surrogate dead space markers, is independently associated with mortality risk, and may be a reasonable noninvasive surrogate for V_D/Vt.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.