Background

The use of midazolam for the treatment of status epilepticus in children has generally been shown to be well tolerated and safe. Furthermore, encouraging efficacy has been observed when pediatric patients with status epilepticus have received continuous intravenous infusions of midazolam.

Case presentation

A 9-year-old girl was treated with high-dose, continuous intravenous infusion of midazolam for the management of refractory status epilepticus. The patient developed a severe hyperchloremic, non-anion gap metabolic acidosis and resultant hemodynamic compromise, necessitating significant inotropic support and the initiation of a vasopressor infusion. We speculate that this complication was due to the preparation of parenteral midazolam with hydrochloric acid. The midazolam infusion was stopped, and, in less than 5 hours, the patient's metabolic acidosis resolved. The patient's inotropic and vasopressor infusions could only be weaned after discontinuing the use of high-dose midazolam.

Conclusions

Although this complication was observed in only 1 pediatric patient with cortical dysplasia, caution and close clinical and laboratory surveillance should be exercised when administering continuous intravenous infusions of midazolam to pediatric patients.

Objective

Cardiopulmonary bypass (CPB) is a requisite for correction of congenital heart disease by open-heart surgery and induces a systemic inflammatory response that can lead to complications such as acute lung injury and acute kidney injury. In addition, blood transfusions are commonly required for this type of surgery, and they may further exacerbate this inflammatory response and increase morbidity and mortality. We hypothesized that, in contrast to red blood cells, intraoperative cell saver (CS) blood transfusions attenuate the post-CPB proinflammatory cytokine response.

Methods

Serum cytokine concentrations of IL-10, IL-1RA, IL-6, IL-8, and TNF-α were measured at four time points (preoperatively and postoperatively on postoperative days 0, 1, and 2).

Results

Anti-inflammatory IL-10 levels were significantly lower in the CS group on POD 0 than in the control group (mean 1083.2 pg/mL vs 2080.2 pg/mL, 95%CI 357.4-1636.6, p = .0026). Of the clinical parameters measured, mean BUN and creatinine levels on POD 2 were significantly lower in the CS group (13.79 vs 21.88, p = .004 and 0.45 vs 0.55, p = .055, respectively). In addition, the duration of milrinone use decreased by 80% in the CS group (0.20, 95%CI 0.04, 0.94; p = .048), the median time to extubation in hours was significantly lower in the CS group (3.5 vs 6.5; 95%CI -38.00, -0.50; p = .026), and hospital length of stay was decreased by 60% in the CS group (p = .003).

Conclusions

CS transfusions in children may lower postoperative anti-inflammatory IL-10 levels, possibly due to an overall decrease in proinflammatory state, and may be associated with improvements in renal and pulmonary functions.

Fluid restriction and diuretic management are mainstays in the postoperative management of cardiac patients, at risk of volume overload and its deleterious effects on primary cardiac function and multi-organ systems. The importance of fluid homeostasis is further emphasized among orthotopic heart transplant recipients (OHT). We sought to investigate the relationship between postoperative volume overload, mortality, and allograft dysfunction among pediatric OHT recipients within 1-year of transplantation. This is a retrospective cohort study from a single pediatric OHT center. Children under 21 years undergoing cardiac transplantation between 2010 and 2018 were included. Cumulative fluid overload (cFO) was assessed as percent fluid accumulation adjusted for preoperative body weight. Greater than 10% cFO defined those with postoperative cFO and a comparison of postoperative cFO vs. no postoperative cFO (< 5%) is reported. 102 pediatric OHT recipients were included. Early cFO at 72 h post-OHT occurred in 14% and overall cFO at 1-week post-OHT occurred in 23% of patients. Risk factors for cFO included younger age, lower weight, and postoperative ECMO. Early cFO was associated with postoperative mortality at 1-year, OR 8.6 (95% CI 1.4, 51.6), p = 0.04, independent of age and weight. There was no significant relationship between cFO and allograft dysfunction, measured by rates of clinical rejection and cardiopulmonary filling pressures within 1-year of transplant. Early postoperative volume overload is prevalent and associated with increased risk of death at 1-year among pediatric OHT recipients. It may be an important postoperative marker of transplant survival, and this relationship warrants further clinical investigation.

Many infants with complex congenital heart disease (CHD) do not develop the skills to feed orally and are discharged home on gastrostomy tube or nasogastric feeds. We aimed to identify risk factors for failure to achieve full oral feeding and evaluate the efficacy of oral motor intervention for increasing the rate of discharge on full oral feeds by performing a prospective study in the neonatal and cardiac intensive care units of a tertiary children's hospital. 23 neonates born at ≥37weeks gestation and diagnosed with single-ventricle physiology requiring a surgical shunt were prospectively enrolled and received oral motor intervention therapy. 40 historical controls were identified. Mean length of stay was 53.7days for the control group and 40.9days for the study group (p=0.668). 13/23 patients who received oral motor intervention therapy (56.5%) and 18/40 (45.0%) controls were on full oral feeds at discharge, a difference of 11.5% (95% CI -13.9% to 37.0%, p=0.378). Diagnosis of hypoplastic left heart syndrome, longer intubation and duration of withholding enteral feeds, and presence of gastroesophageal reflux disease were predictors of poor oral feeding on univariate analysis. Although we did not detect a statistically significant impact of oral motor intervention, we found clinically meaningful differences in hospital length of stay and feeding tube requirement. Further research should be undertaken to evaluate methods for improving oral feeding in these at-risk infants.

Physicians are experiencing epidemic levels of work-related stress and burnout. Determine efficacy of mindfulness meditation delivered as a hybrid (in-person and digital) format to reduce perceived stress in pediatric residents. Pediatric residents (n = 66) were block randomized to a hybrid Mindful Awareness Practices (MAPs) intervention, comprised of one in-person 60-min session and 6-week access to a digitally delivered MAPs curriculum (n = 27) or wait-list control (n = 39). Perceived Stress Scale (PSS) was administered at baseline and post-intervention as the primary outcome measure. A priori secondary outcomes were measured using the Abbreviated Maslach Burnout Inventory-9, Beck Depression Inventory, Beck Anxiety Inventory, UCLA Loneliness Scale, and Pittsburgh Sleep Quality Index. After the first session, 58% participated at least one digital session (M = 2.0; SD = 1.3). MAPs participants showed significant decrease in PSS compared to controls, with between-group mean difference of 2.20 (95% CI 0.47-3.93) at post-intervention (effect size 0.91; 0.19-1.62). No secondary outcome group differences were detected. Exposure to a hybrid mindfulness intervention was associated with improvement in perceived stress among pediatric residents.Trial Registration: NCT03613441.

Background: Bleeding is a common complication of extracorporeal membrane oxygenation (ECMO) for pediatric cardiac patients. We aimed to identify anticoagulation practices, cardiac diagnoses, and surgical variables associated with bleeding during pediatric cardiac ECMO by combining two established databases, the Collaborative Pediatric Critical Care Research Network (CPCCRN) Bleeding and Thrombosis in ECMO (BATE) and the Extracorporeal Life Support Organization (ELSO) Registry. Methods: All children (<19 years) with a primary cardiac diagnosis managed on ECMO included in BATE from six centers were analyzed. ELSO Registry criteria for bleeding events included pulmonary or intracranial bleeding, or red blood cell transfusion >80 ml/kg on any ECMO day. Bleeding odds were assessed on ECMO Day 1 and from ECMO Day 2 onwards with multivariable logistic regression. Results: There were 187 children with 114 (61%) bleeding events in the study cohort. Biventricular congenital heart disease (94/187, 50%) and cardiac medical diagnoses (75/187, 40%) were most common, and 48 (26%) patients were cannulated directly from cardiopulmonary bypass (CPB). Bleeding events were not associated with achieving pre-specified therapeutic ranges of activated clotting time (ACT) or platelet levels. In multivariable analysis, elevated INR and fibrinogen were associated with bleeding events (OR 1.1, CI 1.0-1.3, p = 0.02; OR 0.77, CI 0.6-0.9, p = 0.004). Bleeding events were also associated with clinical site (OR 4.8, CI 2.0-11.1, p < 0.001) and central cannulation (OR 1.75, CI 1.0-3.1, p = 0.05) but not with cardiac diagnosis, surgical complexity, or cannulation from CPB. Bleeding odds on ECMO day 1 were increased in patients with central cannulation (OR 2.82, 95% CI 1.15-7.08, p = 0.023) and those cannulated directly from CPB (OR 3.32, 95% CI 1.02-11.61, p = 0.047). Conclusions: Bleeding events in children with cardiac diagnoses supported on ECMO were associated with central cannulation strategy and coagulopathy, but were not modulated by achieving pre-specified therapeutic ranges of monitoring assays.

Among neonatal cardiomyopathies, primary endocardial fibroelastosis (pEFE) remains a mysterious disease of the endomyocardium that is poorly genetically characterized, affecting 1/5000 live births and accounting for 25% of the entire pediatric dilated cardiomyopathy (DCM) with a devastating course and grave prognosis. To investigate the potential genetic contribution to pEFE, we performed integrative genomic analysis, using whole exome sequencing (WES) and RNA-seq in a female infant with confirmed pathological diagnosis of pEFE. Within regions of homozygosity in the proband genome, WES analysis revealed novel parent-transmitted homozygous mutations affecting three genes with known roles in cilia assembly or function. Among them, a novel homozygous variant [c.1943delA] of uncertain significance in ALMS1 was prioritized for functional genomic and mechanistic analysis. Loss of function mutations of ALMS1 have been implicated in Alstrom syndrome (AS) [OMIM 203800], a rare recessive ciliopathy that has been associated with cardiomyopathy. The variant of interest results in a frameshift introducing a premature stop codon. RNA-seq of the proband's dermal fibroblasts confirmed the impact of the novel ALMS1 variant on RNA-seq reads and revealed dysregulated cellular signaling and function, including the induction of epithelial mesenchymal transition (EMT) and activation of TGFβ signaling. ALMS1 loss enhanced cellular migration in patient fibroblasts as well as neonatal cardiac fibroblasts, while ALMS1-depleted cardiomyocytes exhibited enhanced proliferation activity. Herein, we present the unique pathological features of pEFE compared to DCM and utilize integrated genomic analysis to elucidate the molecular impact of a novel mutation in ALMS1 gene in an AS case. Our report provides insights into pEFE etiology and suggests, for the first time to our knowledge, ciliopathy as a potential underlying mechanism for this poorly understood and incurable form of neonatal cardiomyopathy. KEY MESSAGE: Primary endocardial fibroelastosis (pEFE) is a rare form of neonatal cardiomyopathy that occurs in 1/5000 live births with significant consequences but unknown etiology. Integrated genomics analysis (whole exome sequencing and RNA sequencing) elucidates novel genetic contribution to pEFE etiology. In this case, the cardiac manifestation in Alstrom syndrome is pEFE. To our knowledge, this report provides the first evidence linking ciliopathy to pEFE etiology. Infants with pEFE should be examined for syndromic features of Alstrom syndrome. Our findings lead to a better understanding of the molecular mechanisms of pEFE, paving the way to potential diagnostic and therapeutic applications.

OBJECTIVES: To evaluate associations between sodium bicarbonate use and outcomes during pediatric in-hospital cardiac arrest (p-IHCA). DESIGN: Prespecified secondary analysis of a prospective, multicenter cluster randomized interventional trial. SETTING: Eighteen participating ICUs of the ICU-RESUScitation Project (NCT02837497). PATIENTS: Children less than or equal to 18 years old and greater than or equal to 37 weeks post conceptual age who received chest compressions of any duration from October 2016 to March 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Child and event characteristics, prearrest laboratory values (2-6 hr prior to p-IHCA), pre- and intraarrest hemodynamics, and outcomes were collected. In a propensity score weighted cohort, the relationships between sodium bicarbonate use and outcomes were assessed. The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Of 1,100 index cardiopulmonary resuscitation events, median age was 0.63 years (interquartile range, 0.19-3.81 yr); 528 (48.0%) received sodium bicarbonate; 773 (70.3%) achieved ROSC; 642 (58.4%) survived to hospital discharge; and 596 (54.2%) survived to hospital discharge with favorable neurologic outcome. Among the weighted cohort, sodium bicarbonate use was associated with lower survival to hospital discharge rate (adjusted odds ratio [aOR], 0.7; 95% CI, 0.54-0.92; p = 0.01) and lower survival to hospital discharge with favorable neurologic outcome rate (aOR, 0.69; 95% CI, 0.53-0.91; p = 0.007). Sodium bicarbonate use was not associated with ROSC (aOR, 0.91; 95% CI, 0.62-1.34; p = 0.621). CONCLUSIONS: In this propensity weighted multicenter cohort study of p-IHCA, sodium bicarbonate use was common and associated with lower rates of survival to hospital discharge.

AIM: To evaluate associations between characteristics of simulated point-of-care cardiopulmonary resuscitation (CPR) training with simulated and actual intensive care unit (ICU) CPR performance, and with outcomes of children after in-hospital cardiac arrest. METHODS: This is a pre-specified secondary analysis of the ICU-RESUScitation Project; a prospective, multicentre cluster randomized interventional trial conducted in 18 ICUs from October 2016-March 2021. Point-of-care bedside simulations with real-time feedback to allow multidisciplinary ICU staff to practice CPR on a portable manikin were performed and quality metrics (rate, depth, release velocity, chest compression fraction) were recorded. Actual CPR performance was recorded for children 37 weeks post-conceptual age to 18 years who received chest compressions of any duration, and included intra-arrest haemodynamics and CPR mechanics. Outcomes included survival to hospital discharge with favourable neurologic status. RESULTS: Overall, 18,912 point-of-care simulations were included. Simulation characteristics associated with both simulation and actual performance included site, participant discipline, and timing of simulation training. Simulation characteristics were not associated with survival with favourable neurologic outcome. However, participants in the top 3 sites for improvement in survival with favourable neurologic outcome were more likely to have participated in a simulation in the past month, on a weekday day, to be nurses, and to achieve targeted depth of compression and chest compression fraction goals during simulations than the bottom 3 sites. CONCLUSIONS: Point-of-care simulation characteristics were associated with both simulated and actual CPR performance. More recent simulation, increased nursing participation, and simulation training during daytime hours may improve CPR performance.