Arch watch: current approaches and opportunities for improvement.

Coarctation of the aorta (CoA) is a ductus arteriosus (DA)-dependent form of congenital heart disease (CHD) characterized by narrowing in the region of the aortic isthmus. CoA is a challenging diagnosis to make prenatally and is the critical cardiac lesion most likely to go undetected on the pulse oximetry-based newborn critical CHD screen. When undetected CoA causes obstruction to blood flow, life-threatening cardiovascular collapse may result, with a high burden of morbidity and mortality. Hemodynamic monitoring practices during DA closure (known as an "arch watch") vary across institutions and existing tools are often insensitive to developing arch obstruction. Novel measures of tissue oxygenation and oxygen deprivation may improve sensitivity and specificity for identifying evolving hemodynamic compromise in the newborn with CoA. We explore the benefits and limitations of existing and new tools to monitor the physiological changes of the aorta as the DA closes in infants at risk of CoA.

Social Drivers of Health and Pediatric Extracorporeal Membrane Oxygenation Outcomes.

BACKGROUND: Relationships between social drivers of health (SDoH) and pediatric health outcomes are highly complex with substantial inconsistencies in studies examining SDoH and extracorporeal membrane oxygenation (ECMO) outcomes. To add to this literature with emerging novel SDoH measures, and to address calls for institutional accountability, we examined associations between SDoH and pediatric ECMO outcomes. METHODS: This single-center retrospective cohort study included children (<18 years) supported on ECMO (2012-2021). SDoH included Child Opportunity Index (COI), race, ethnicity, payer, interpreter requirement, urbanicity, and travel-time to hospital. COI is a multidimensional estimation of SDoH incorporating traditional (eg, income) and novel (eg, healthy food access) neighborhood attributes ([range 0-100] higher indicates healthier child development). Outcomes included in-hospital mortality, ECMO run duration, and length of stay (LOS). RESULTS: 540 children on ECMO (96%) had a calculable COI. In-hospital mortality was 44% with median run duration of 125 hours and ICU LOS 29 days. Overall, 334 (62%) had cardiac disease, 92 (17%) neonatal respiratory failure, 93 (17%) pediatric respiratory failure, and 21 (4%) sepsis. Median COI was 64 (interquartile range 32-81), 323 (60%) had public insurance, 174 (34%) were from underrepresented racial groups, 57 (11%) required interpreters, 270 (54%) had urban residence, and median travel-time was 89 minutes. SDoH including COI were not statistically associated with outcomes in univariate or multivariate analysis. CONCLUSIONS: We observed no significant difference in pediatric ECMO outcomes according to SDoH. Further research is warranted to better understand drivers of inequitable health outcomes in children, and potential protective mechanisms.

Administration of Milrinone Following Tetralogy of Fallot Repair Increases Postoperative Volume Administration Without Improving Cardiac Output.

BACKGROUND: Phosphodiesterase inhibitors are known to relieve symptoms in the setting of heart failure, although their effects in restrictive ventricular physiology have been poorly characterized. We explored the association between the use of milrinone and volume administration during the first 72 hours following surgical repair of tetralogy of Fallot (TOF). METHODS: We reviewed all cases of primary surgical repair of TOF with pulmonary stenosis or atresia at Boston Children's Hospital between 2011 and 2020. To adjust for baseline differences between patients who did and did not receive milrinone, we matched patients with similar propensity scores in a 1:1 ratio (use of milrinone versus not). We then compared the need for volume administration during the first 72 hours postoperatively, vital signs, and measures of cardiac output between the matched cohorts. Additionally, in the group of patients receiving milrinone, linear regression modeling was used to explore the relationship between total dose of milrinone and total volume administration. RESULTS: Among 351 included patients, 134 received perioperative milrinone. A total of 212 patients (106 per group) were matched based on anatomic and surgical risks using a propensity score. After propensity matching, compared with nonmilrinone-treated patients, milrinone-treated patients were given postoperative volume more frequently (66% vs 52%; difference 14% [95% confidence interval, CI, 1%-27%]; P = .036). Milrinone-treated patients had a slower recovery of tachycardia during the first 12 hours (difference in slope 0.30 [95% CI, 0.14-0.47] beats per minute [BPM]/h; P < .001), and the intergroup difference peaked at 12 hours postoperatively (8 [95% CI, 5-12] BPM). Milrinone administration was not associated with improved cardiac output, including arteriovenous oxyhemoglobin saturation difference. In propensity-matched patients receiving milrinone, the total volume administered during the first 72 postoperative hours was significantly associated with the cumulative dose of postoperative milrinone ( r = 0.20; 95% CI, 0.01-0.38; P = .036). Based on the slope of the regression line, for every 1000 µg/kg of milrinone (equivalent to ~0.25 µg/kg/min for 72 hours) administered in the first 72 postoperative hours, an estimated 11.0 (95% CI, 0.6-21.4) mL/kg additional volume was administered. CONCLUSIONS: The use of milrinone within the first 72 hours following TOF repair is associated with more frequent administration of volume, a positive association between a higher total dose of postoperative milrinone and the amount of postoperative volume administered, a higher heart rate, and a lower blood pressure, but is not associated with improved cardiac output.

Impact of Dexmedetomidine Infusion on Opioid and Benzodiazepine Doses in Ventilated Pediatric Patients in the Cardiac Intensive Care Unit.

INTRODUCTION: Dexmedetomidine (DEX) is frequently used as an adjunct agent for prolonged sedation in the intensive care unit (ICU), though its effect on concomitant opioids or benzodiazepines infusions is unclear. We explored the impact of DEX on concomitant analgosedation in a cohort of ventilated pediatric patients in a cardiac ICU, with stratification of patients according to duration of ventilation (< 5 versus ≥ 5 days) following DEX initiation. METHODS: We conducted a retrospective analysis on ventilated patients receiving a DEX infusion ≥ 24 h and at least one other sedative/analgesic infusion (January 2011-June 2021). We evaluated trends of daily doses of opioids and benzodiazepines from 24 h before to 72 h following DEX initiation, stratifying patients based on ventilation duration after DEX initiation (< 5 versus ≥ 5 days). RESULTS: After excluding 1146 patients receiving DEX only, 1073 patients were included [median age 234 days (interquartile range 90, 879)]. DEX was associated with an opioid infusion in 99% of patients and a benzodiazepine infusion in 62%. Among patients ventilated for < 5 days (N = 761), opioids increased in the first 24 h following DEX initiation [+ 1.12 mg/kg/day (95% CI 0.96, 1.23), P < 0.001], then decreased [- 0.90 mg/kg/day (95% CI - 0.89, - 0.71), P < 0.001]; benzodiazepines slowly decreased [- 0.20 mg/kg/day (95% CI - 0.21, - 0.19), P < 0.001]. Among patients ventilated for ≥ 5 days (N = 312), opioid administration doubled [+ 2.09 mg/kg/day (95% CI 1.82, 2.36), P < 0.001] in the first 24 h, then diminished minimally [- 0.18 mg/kg/day (95% CI - 0.32, - 0.04), P = 0.015] without returning to baseline; benzodiazepine administration decreased minimally [- 0.03 mg/kg/day (95% CI - 0.05, - 0.01), P = 0.010]. Similar trends were confirmed when adjusting for age, gender, surgical complexity, recent major invasive procedures, duration of mechanical ventilation before DEX initiation, extubation within 72 h following DEX initiation, mean hourly DEX dose, and use of neuromuscular blocking infusion. CONCLUSION: While in patients ventilated < 5 days opioids initially increased and then quickly decreased in the 72 h following DEX initiation, among patients ventilated ≥ 5 days opioids doubled, then decreased only minimally; benzodiazepines decreased minimally in both groups, although more slowly in the long-ventilation cohort. These findings may inform decision-making on timing of DEX initiation in ventilated patients already being treated with opioid or benzodiazepine infusions.

Predicting favorable response to intravenous morphine in pediatric critically ill cardiac patients.

INTRODUCTION: Analgesia and sedation are integral to the care of critically ill children. However, the choice and dose of the analgesic or sedative drug is often empiric, and models predicting favorable responses are lacking. We aimed to compute models to predict a patient's response to intravenous morphine. METHODS: We retrospectively analyzed data from consecutive patients admitted to the Cardiac Intensive Care Unit (January 2011-January 2020) who received at least one intravenous bolus of morphine. The primary outcome was a decrease in the State Behavioral Scale (SBS) ≥1 point; the secondary outcome was a decrease in the heart rate Z-score (zHR) at 30 min. Effective doses were modeled using logistic regression, Lasso regression, and random forest modeling. RESULTS: A total of 117,495 administrations of intravenous morphine among 8140 patients (median age 0.6 years [interquartile range [IQR] 0.19, 3.3]) were included. The median morphine dose was 0.051 mg/kg (IQR 0.048, 0.099) and the median 30-day cumulative dose was 2.2 mg/kg (IQR 0.4, 15.3). SBS decreased following 30% of doses, did not change following 45%, and increased following 25%. The zHR significantly decreased after morphine administration (median delta-zHR -0.34 [IQR-1.03, 0.00], p < 0.001). The following factors were associated with favorable response to morphine: A concomitant infusion of propofol, higher prior 30-day cumulative dose, being invasively ventilated and/or on vasopressors. Higher morphine dose, higher zHR pre-morphine, an additional analgosedation bolus ±30 min around the index bolus, a concomitant ketamine or dexmedetomidine infusion, and showing signs of withdrawal syndrome were associated with unfavorable response. Logistic regression (area under the receiver operating characteristic [ROC] curve [AUC] 0.900) and machine learning models (AUC 0.906) performed comparably, with a sensitivity of 95%, specificity of 71%, and negative predictive value of 97%. CONCLUSIONS: Statistical models identify 95% of effective intravenous morphine doses in pediatric critically ill cardiac patients, while incorrectly suggesting an effective dose in 29% of cases. This work represents an important step toward computer-aided, personalized clinical decision support tool for sedation and analgesia in ICU patients.

Injectable Oxygen Microparticles Boost Radiation-Mediated In Situ Vaccination and Systemic Antitumor Immune Responses.

PURPOSE: The aim of this work was to determine whether intratumoral injections of a liquid oxygen solution are effective at boosting radiation-induced abscopal effects. METHODS AND MATERIALS: A liquid oxygen solution, comprising slow-release polymer-shelled oxygen microparticles, was fabricated and injected intratumorally to locally elevate tumor oxygen levels before and after treatment with radiation therapy. Changes in tumor volume were monitored. In a subset of studies, CD8-positive cells were depleted and the experiments were repeated. Histologic analyses of the tumor tissues were performed to quantify the concentration of infiltrating immune cells. RESULTS: Daily intratumoral injections of oxygen-filled microparticles significantly retarded primary and secondary tumor growth, boosted infiltration of cytotoxic T cells, and improved overall survival when used as an adjuvant to radiation therapy. The findings also demonstrated that efficacy requires both radiation and oxygen, suggesting that they act synergistically to enhance in situ vaccination and systemic antitumor immune responses. CONCLUSIONS: This study demonstrated the potential advantages of intratumoral injections of a liquid oxygen solution as a strategy to boost radiation-induced abscopal effects, and the findings warrant future efforts toward clinical translation of the injectable liquid oxygen solution.

Insight into the Role of the Child Opportunity Index on Surgical Outcomes in Congenital Heart Disease.

OBJECTIVE: To use neighborhood-level Child Opportunity Index (COI) measures to investigate disparities in congenital heart surgery postoperative outcomes and identify potential targets for intervention. STUDY DESIGN: In this single-institution retrospective cohort study, children <18 years old who underwent cardiac surgery between 2010 and 2020 were included. Patient-level demographics and neighborhood-level COI were used as predictor variables. COI-a composite US census tract-based score measuring educational, health/environmental, and social/economic opportunities-was dichotomized as lower (<40th percentile) vs higher (≥40th percentile). Cumulative incidence of hospital discharge was compared between groups using death as a competing risk, adjusting for clinical characteristics associated with outcomes. Secondary outcomes included hospital readmission and death within 30 days. RESULTS: Among 6247 patients (55% male) with a median age of 0.8 years (IQR, 0.2-4.3), 26% had lower COI. Lower COI was associated with longer hospital lengths of stay (adjusted HR, 1.2; 95% CI, 1.1-1.2; P < .001) and an increased risk of death (adjusted OR, 2.0; 95% CI. 1.4-2.8; P < .001), but not hospital readmission (P = .6). At the neighborhood level, lacking health insurance coverage, food/housing insecurity, lower parental literacy and college attainment, and lower socioeconomic status were associated with longer hospital length of stay and increased risk of death. At the patient-level, public insurance (adjusted OR, 1.4; 95% CI, 1.0-2.0; P = .03) and caretaker Spanish language (adjusted OR 2.4; 95% CI, 1.2-4.3; P < .01) were associated with an increased risk of death. CONCLUSIONS: Lower COI is associated with longer length of stay and higher early postoperative mortality. Risk factors identified including Spanish language, food/housing insecurity, and parental literacy serve as potential intervention targets.

Clinical risk prediction score for postoperative accelerated junctional rhythm and junctional ectopic tachycardia in children with congenital heart disease.

BACKGROUND: Accelerated junctional rhythm (AJR) and junctional ectopic tachycardia (JET) are common postoperative arrhythmias associated with morbidity/mortality. Studies suggest that pre- or intraoperative treatment may improve outcomes, but patient selection remains a challenge. OBJECTIVES: The purpose of this study was to describe contemporary outcomes of postoperative AJR/JET and develop a risk prediction score to identify patients at highest risk. METHODS: This was a retrospective cohort study of children aged 0-18 years undergoing cardiac surgery (2011-2018). AJR was defined as usual complex tachycardia with ≥1:1 ventricular-atrial association and junctional rate >25th percentile of sinus rate for age but <170 bpm, whereas JET was defined as a rate >170 bpm. A risk prediction score was developed using random forest analysis and logistic regression. RESULTS: Among 6364 surgeries, AJR occurred in 215 (3.4%) and JET in 59 (0.9%). Age, heterotaxy syndrome, aortic cross-clamp time, ventricular septal defect closure, and atrioventricular canal repair were independent predictors of AJR/JET on multivariate analysis and included in the risk prediction score. The model accurately predicted the risk of AJR/JET with a C-index of 0.72 (95% confidence interval 0.70-0.75). Postoperative AJR and JET were associated with prolonged intensive care unit and hospital length of stay, but not with early mortality. CONCLUSION: We describe a novel risk prediction score to estimate the risk of postoperative AJR/JET permitting early identification of at-risk patients who may benefit from prophylactic treatment.

Low-Fouling Zwitterionic Polymeric Colloids as Resuscitation Fluids for Hemorrhagic Shock.

Colloids, known as volume expanders, have been used as resuscitation fluids for hypovolemic shock for decades, as they increase plasma oncotic pressure and expand intravascular volume. However, recent studies show that commonly used synthetic colloids have adverse interactions with human biological systems. In this work, a low-fouling amine(N)-oxide-based zwitterionic polymer as an alternative volume expander with improved biocompatibility and efficacy is designed. It is demonstrated that the polymer possesses antifouling ability, resisting cell interaction and deposition in major organs, and is rapidly cleared via renal filtration and hepatic circulation, reducing the risk of long-term side effects. Furthermore, in vitro and in vivo studies show an absence of adverse effects on hemostasis or any acute safety risks. Finally, it is shown that, in a head-to-head comparison with existing colloids and plasma, the zwitterionic polymer serves as a more potent oncotic agent for restoring intravascular volume in a hemorrhagic shock model. The design of N-oxide-based zwitterionic polymers may lead to the development of alternative fluid therapies to treat hypovolemic shock and to improve fluid management in general.

A microfluidic device for real-time on-demand intravenous oxygen delivery.

SignificanceThe treatment of hypoxemia that is refractory to the current standard of care is time-sensitive and requires skilled caregivers and use of specialized equipment (e.g., extracorporeal membrane oxygenation). Most patients experiencing refractory hypoxemia will suffer organ dysfunction, and death is common in this cohort. Here, we describe a new strategy to stabilize and support patients using a microfluidic device that administers oxygen gas directly to the bloodstream in real time and on demand using a process that we call sequential shear-induced bubble breakup. If successful, the described technology may help to avoid or decrease the incidence of ventilator-related lung injury from refractory hypoxemia.

Patch augmentation of small ascending aorta during stage I procedure reduces the risk of morbidity and mortality.

OBJECTIVES: Hypoplastic left heart syndrome (HLHS) with aortic atresia (AA) patients are prone to coronary insufficiency due to a small ascending aorta. Prophylactic patch augmentation of the small ascending aorta during the stage I procedure (S1P) may reduce the risk of coronary insufficiency as marked by ventricular dysfunction, need for extracorporeal membrane oxygenator (ECMO) support or mortality. METHODS: Retrospective analysis of patients with HLHS with AA who underwent an S1P was completed. Baseline ascending aorta size, right ventricular (RV) function and outcome variables of transplant-free survival, ECMO support after the stage 1 operation and RV function at the time of the bidirectional Glenn and latest follow-up were collected. RESULTS: Between January 2010 and April 2020, 11 patients underwent prophylactic ascending aorta augmentation at the time of the S1P as a planned portion of the procedure. A total of 125 patients underwent S1P during this period as a comparison. Overall survival was 100% for the augmented group and 74% for the control group (P = 0.66). A composite end point of transplant-free survival, no post-S1P ECMO and less than moderate RV dysfunction was created. At the time of BDG, this composite end point was 100% for the augmented group and 61.8% for the control group (P = 0.008) and at most recent follow-up was 100% for the augmented group and 59.3% for control (P = 0.007). Eight patients required a rescue procedure for the clinical evidence of coronary insufficiency following S1P that included ascending aorta patch augmentation or stent placement. When comparing these rescue versus prophylactic ascending aortic augmentations, there were also differences in the composite outcome 100% for augmented and 60% for rescue (P = 0.009) and at the time of most recent follow-up 100% for augmented and 50% for rescue (P = 0.029). CONCLUSIONS: Prophylactic patch augmentation of the ascending aorta in HLHS patients with AA may reduce the risk of mortality, ECMO and reduced RV function. Patients not initially undergoing augmentation but then requiring a rescue procedure have particularly poor outcomes. Patch augmentation for smaller ascending aortic diameters should be considered and further clinical experience may help delineate aorta diameter threshold for augmentation.

Safety of Prolonged Inhalation of Hydrogen Gas in Air in Healthy Adults.

Ischemia-reperfusion injury is common in critically ill patients, and directed therapies are lacking. Inhaled hydrogen gas diminishes ischemia-reperfusion injury in models of shock, stroke, and cardiac arrest. The purpose of this study was to investigate the safety of inhaled hydrogen gas at doses required for a clinical efficacy study. DESIGN: Prospective, single-arm study. SETTING: Tertiary care hospital. PATIENTS/SUBJECTS: Eight healthy adult participants. INTERVENTIONS: Subjects underwent hospitalized exposure to 2.4% hydrogen gas in medical air via high-flow nasal cannula (15 L/min) for 24 (n = 2), 48 (n = 2), or 72 (n = 4) hours. MEASUREMENTS AND MAIN RESULTS: Endpoints included vital signs, patient- and nurse-reported signs and symptoms (stratified according to clinical significance), pulmonary function testing, 12-lead electrocardiogram, mini-mental state examinations, neurologic examination, and serologic testing prior to and following exposure. All adverse events were verified by two clinicians external to the study team and an external Data and Safety Monitoring Board. All eight participants (18-30 yr; 50% female; 62% non-Caucasian) completed the study without early termination. No clinically significant adverse events occurred in any patient. Compared with baseline measures, there were no clinically significant changes over time in vital signs, pulmonary function testing results, Mini-Mental State Examination scores, neurologic examination findings, electrocardiogram measurements, or serologic tests for hematologic (except for clinically insignificant increases in hematocrit and platelet counts), renal, hepatic, pancreatic, or cardiac injury associated with hydrogen gas inhalation. CONCLUSIONS: Inhalation of 2.4% hydrogen gas does not appear to cause clinically significant adverse effects in healthy adults. Although these data suggest that inhaled hydrogen gas may be well tolerated, future studies need to be powered to further evaluate safety. These data will be foundational to future interventional studies of inhaled hydrogen gas in injury states, including following cardiac arrest.

Modeling severe functional impairment or death following ECPR in pediatric cardiac patients: Planning for an interventional trial.

AIM: We aimed to characterize extracorporeal CPR (ECPR) outcomes in our center and to model prediction of severe functional impairment or death at discharge. METHODS: All ECPR events between 2011 and 2019 were reviewed. The primary outcome measure was severe functional impairment or death at discharge (Functional Status Score [FSS] ≥ 16). Organ dysfunction was graded using the Pediatric Logistic Organ Dysfunction Score-2, neuroimaging using the modified Alberta Stroke Program Early Computed Tomography Score. Multivariable logistic regression was used to model FSS ≥ 16 at discharge. RESULTS: Of the 214 patients who underwent ECPR, 182 (median age 148 days, IQR 14-827) had an in-hospital cardiac arrest and congenital heart disease and were included in the analysis. Of the 110 patients who underwent neuroimaging, 52 (47%) had hypoxic-ischemic injury and 45 (41%) had hemorrhage. In-hospital mortality was 52% at discharge. Of these, 87% died from the withdrawal of life-sustaining therapies; severe neurologic injury was a contributing factor in the decision to withdraw life-sustaining therapies in 50%. The median FSS among survivors was 8 (IQR 6-8), and only one survivor had severe functional impairment. At 6 months, mortality was 57%, and the median FSS among survivors was 6 (IQR 6-8, n = 79). Predictive models identified FSS at admission, single ventricle physiology, extracorporeal membrane oxygenation (ECMO) duration, mean PELOD-2, and worst mASPECTS (or DWI-ASPECTS) as independent predictors of FSS ≥ 16 (AUC = 0.931) and at 6 months (AUC = 0.924). CONCLUSION: Mortality and functional impairment following ECPR in children remain high. It is possible to model severe functional impairment or death at discharge with high accuracy using daily post-ECPR data up to 28 days. This represents a prognostically valuable tool and may identify endpoints for future interventional trials.

Development of Care Curves Following the Stage 1 Palliation: A Comparison of Intensive Care Among 5 Centers.

Background Comparison of care among centers is currently limited to major end points, such as mortality, length of stay, or complication rates. Creating "care curves" and comparing individual elements of care over time may highlight modifiable differences in intensive care among centers. Methods and Results We performed an observational retrospective study at 5 centers in the United States to describe key elements of postoperative care following the stage 1 palliation. A consecutive sample of 502 infants undergoing stage 1 palliation between January 2009 and December 2018 were included. All electronic health record entries relating to mandatory mechanical ventilator rate, opioid administration, and fluid intake/outputs between postoperative days (POD) 0 to 28 were extracted from each institution's data warehouse. During the study period, 502 patients underwent stage 1 palliation among the 5 centers. Patients were weaned to a median mandatory mechanical ventilator rate of 10 breaths/minute by POD 4 at Center 5 but not until POD 7 to 8 at Centers 1 and 2. Opioid administration peaked on POD 2 with extreme variance (median 6.9 versus 1.6 mg/kg per day at Center 3 versus Center 2). Daily fluid balance trends were variable: on POD 3 Center 1 had a median fluid balance of -51 mL/kg per day, ranging between -34 to 19 mL/kg per day among remaining centers. Intercenter differences persist after adjusting for patient and surgical characteristics (P<0.001 for each end point). Conclusions It is possible to detail and compare individual elements of care over time that represent modifiable differences among centers, which persist even after adjusting for patient factors. Care curves may be used to guide collaborative quality improvement initiatives.

Socioeconomic and Racial and/or Ethnic Disparities in Multisystem Inflammatory Syndrome.

OBJECTIVES: To characterize the socioeconomic and racial and/or ethnic disparities impacting the diagnosis and outcomes of multisystem inflammatory syndrome in children (MIS-C). METHODS: This multicenter retrospective case-control study was conducted at 3 academic centers from January 1 to September 1, 2020. Children with MIS-C were compared with 5 control groups: children with coronavirus disease 2019, children evaluated for MIS-C who did not meet case patient criteria, children hospitalized with febrile illness, children with Kawasaki disease, and children in Massachusetts based on US census data. Neighborhood socioeconomic status (SES) and social vulnerability index (SVI) were measured via a census-based scoring system. Multivariable logistic regression was used to examine associations between SES, SVI, race and ethnicity, and MIS-C diagnosis and clinical severity as outcomes. RESULTS: Among 43 patients with MIS-C, 19 (44%) were Hispanic, 11 (26%) were Black, and 12 (28%) were white; 22 (51%) were in the lowest quartile SES, and 23 (53%) were in the highest quartile SVI. SES and SVI were similar between patients with MIS-C and coronavirus disease 2019. In multivariable analysis, lowest SES quartile (odds ratio 2.2 [95% confidence interval 1.1-4.4]), highest SVI quartile (odds ratio 2.8 [95% confidence interval 1.5-5.1]), and racial and/or ethnic minority background were associated with MIS-C diagnosis. Neither SES, SVI, race, nor ethnicity were associated with disease severity. CONCLUSIONS: Lower SES or higher SVI, Hispanic ethnicity, and Black race independently increased risk for MIS-C. Additional studies are required to target interventions to improve health equity for children.

Avoidable Serum Potassium Testing in the Cardiac ICU: Development and Testing of a Machine-Learning Model.

OBJECTIVES: To create a machine-learning model identifying potentially avoidable blood draws for serum potassium among pediatric patients following cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Tertiary-care center. PATIENTS: All patients admitted to the cardiac ICU at Boston Children's Hospital between January 2010 and December 2018 with a length of stay greater than or equal to 4 days and greater than or equal to two recorded serum potassium measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected variables related to potassium homeostasis, including serum chemistry, hourly potassium intake, diuretics, and urine output. Using established machine-learning techniques, including random forest classifiers, and hyperparameter tuning, we created models predicting whether a patient's potassium would be normal or abnormal based on the most recent potassium level, medications administered, urine output, and markers of renal function. We developed multiple models based on different age-categories and temporal proximity of the most recent potassium measurement. We assessed the predictive performance of the models using an independent test set. Of the 7,269 admissions (6,196 patients) included, serum potassium was measured on average of 1 (interquartile range, 0-1) time per day. Approximately 96% of patients received at least one dose of IV diuretic and 83% received a form of potassium supplementation. Our models predicted a normal potassium value with a median positive predictive value of 0.900. A median percentage of 2.1% measurements (mean 2.5%; interquartile range, 1.3-3.7%) was incorrectly predicted as normal when they were abnormal. A median percentage of 0.0% (interquartile range, 0.0-0.4%) critically low or high measurements was incorrectly predicted as normal. A median of 27.2% (interquartile range, 7.8-32.4%) of samples was correctly predicted to be normal and could have been potentially avoided. CONCLUSIONS: Machine-learning methods can be used to predict avoidable blood tests accurately for serum potassium in critically ill pediatric patients. A median of 27.2% of samples could have been saved, with decreased costs and risk of infection or anemia.

Shock Index, Coronary Perfusion Pressure, and Rate Pressure Product As Predictors of Adverse Outcome After Pediatric Cardiac Surgery.

OBJECTIVES: To determine whether shock index, coronary perfusion pressure, or rate pressure product in the first 24 hours after congenital heart surgery are independent predictors of subsequent clinically significant adverse outcomes. DESIGN: A retrospective cohort study. SETTING: A tertiary care center. PATIENTS: All patients less than 18 years old who underwent cardiac surgery at Boston Children's Hospital between January 1, 2010, and December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Shock index (heart rate/systolic blood pressure), coronary perfusion pressure (diastolic blood pressure-right atrial pressure), and rate pressure product (heart rate × systolic blood pressure) were calculated every 5 seconds, and the median value for the first 24 hours of cardiac ICU admission for each was used as a predictor. The composite, primary outcome was the occurrence of any of the following adverse events in the first 7 days following cardiac ICU admission: cardiopulmonary resuscitation, extracorporeal cardiopulmonary resuscitation, mechanical circulatory support, unplanned surgery, heart transplant, or death. The association of each variable of interest with this outcome was tested in a multivariate logistic regression model. Of the 4,161 patients included, 296 (7%) met the outcome within the specified timeframe. In a multivariate regression model adjusted for age, surgical complexity, inotropic and respiratory support, and organ dysfunction, shock index greater than 1.83 was significantly associated with the primary outcome (odds ratio, 6.6; 95% CI, 4.4-10.0), and coronary perfusion pressure greater than 35 mm Hg was protective against the outcome (odds ratio, 0.5; 0.4-0.7). Rate pressure product was not found to be associated with the outcome. However, the predictive ability of the shock index and coronary perfusion pressure models were not superior to their component hemodynamic variables alone. CONCLUSIONS: Both shock index and coronary perfusion pressure may offer predictive value for adverse outcomes following cardiac surgery in children, although they are not superior to the primary hemodynamic variables.

Hyperbaric polymer microcapsules for tunable oxygen delivery.

Over the past decade, there have been many attempts to engineer systems capable of delivering oxygen to overcome the effects of both systemic and local hypoxia that occurs as a result of traumatic injury, cell transplantation, or tumor growth, among many others. Despite progress in this field, which has led to a new class of oxygen-generating biomaterials, most reported techniques lack the tunability necessary for independent control over the oxygen flux (volume per unit time) and the duration of delivery, both of which are key parameters for overcoming tissue hypoxia of varying etiologies. Here, we show that these critical parameters can be effectively manipulated using hyperbarically-loaded polymeric microcapsules (PMC). PMCs are micron-sized particles with hollow cores and polymeric shells. We show that oxygen delivery through PMCs is dependent on its permeability through the polymeric shell, the shell thickness, and the pressure gradient across the shell. We also demonstrate that incorporating an intermediate oil layer between the polymeric shell and the gas core prevents rapid outgassing by effectively lowering the resultant pressure gradient across the polymeric membrane following depressurization.