Resuscitation arterial waveform quantification and outcomes in pediatric bidirectional Glenn and Fontan patients.

BACKGROUND: Resuscitation with chest compressions and positive pressure ventilation in Bidirectional Glenn (BDG) or Fontan physiology may compromise passive venous return and accentuate neurologic injury. We hypothesized that arterial pressure and survival would be better in BDG than Fontan patients. METHODS: Secondary analyses of the Pediatric Intensive Care Quality of CPR and Improving Outcomes from Pediatric Cardiac Arrest databases. P-values were considered significant if < 0.05. RESULTS: In total, 64 patients had either BDG (42/64, 66%) or Fontan (22/64, 34%) anatomy. Return of spontaneous circulation was achieved in 76% of BDG patients versus 59% of Fontan patients and survival with favorable neurologic outcome in 22/42 (52%) BDG versus 6/22 (27%) Fontan patients, p = 0.067. Twelve of 24 (50%) BDG and 2/7 (29%) Fontan patients who survived to discharge suffered new morbidity as defined by worsening Functional Status Score. More BDG patients achieved adequate DBP (≥25 mmHg for neonates and infants; ≥ 30 mmHg for children) than Fontan patients (21/23 (91%) vs. 5/11 (46%), p = 0.007). CONCLUSIONS: Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after CPR, likely driven by inadequate diastolic blood pressure during resuscitation. One half of the BDG patients who survived to hospital discharge had new neurologic morbidity. BACKGROUND: Cardiac arrest in patients with congenital heart disease (CHD) may present challenges to resuscitation based on the unique cardiovascular physiology resulting from surgical palliation. Recent resuscitation guidelines for CHD patients highlight the lack of data surrounding these special patient populations.1 Univentricular heart disease is palliated by a series of cardiac surgeries that stepwise result in passive pulmonary perfusion from the systemic venous system directly to the pulmonary vascular bed. The bidirectional Glenn (BDG) palliation directly anastomoses the superior vena cava (SVC) to the pulmonary arterial system and leaves normal inferior vena cava (IVC) venous return to the heart.2 The Fontan palliation baffles IVC flow directly to the pulmonary vascular bed which relieves cyanosis due to right to left shunting, but requires systemic ventricular preload to be directly dependent upon pulmonary vascular resistance and intrathoracic pressures.3 IMPACT STATEMENT: Hemodynamic waveforms from 2 large prospective observational studies now allow for exploration of physiology during cardiopulmonary resuscitation for unique anatomy associated with single ventricle congenital heart disease. Fewer patients with Fontan physiology (46%) achieved an adequate diastolic blood pressure (defined as ≥ 25 mmHg for neonates and infants and ≥ 30 mmHg for children) than bidirectional Glenn patients during cardiopulmonary resuscitation (91%, p = 0.007). Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after cardiopulmonary resuscitation. Of the bidirectional Glenn patients who survived, 50% developed a new morbidity as quantified by the Functional Status Score.

Accuracy of free-breathing multi-parametric SASHA in identifying T1 and T2 elevations in pediatric orthotopic heart transplant patients.

T1/T2 parametric mapping may reveal patterns of elevation ("hotspots") in myocardial diseases, such as rejection in orthotopic heart transplant (OHT) patients. This study aimed to evaluate the diagnostic accuracy of free-breathing (FB) multi-parametric SAturation recovery single-SHot Acquisition (mSASHA) T1/T2 mapping in identifying hotspots present on conventional Breath-held Modified Look-Locker Inversion recovery (BH MOLLI) T1 and T2-prepared balanced steady-state free-precession (BH T2p-bSSFP) maps in pediatric OHT patients. Pediatric OHT patients underwent noncontrast 1.5T CMR with BH MOLLI T1 and T2p-bSSFP and prototype FB mSASHA T1/T2 mapping in 8 short-axis slices. FB and BH T1/T2 hotspots were segmented using semi-automated thresholding (ITK-SNAP) and their 3D coordinate locations were collected (3-Matic, Materialise, Leuven, Belgium). Receiver operator characteristic curve analysis and measures of central tendency were utilized. 40 imaging datasets from 23 pediatric OHT patients were obtained. FB mSASHA yielded a sensitivity of 82.8% for T1 and 80% for T2 maps when compared to the standard BH MOLLI, as well as 100% specificity for both T1 and T2 maps. When identified on both FB and BH maps, hotspots overlapped in all cases, with an average long axis offset between FB and BH hotspot centers of 5.8 mm (IQR 3.5-8.2) on T1 and 5.9 mm (IQR 3.5-8.2) on T2 maps. FB mSASHA T1/T2 maps can identify hotspots present on conventional BH T1/T2 maps in pediatric patients with OHT, with high sensitivity, specificity, and overlap in 3D space. Free-breathing mapping may improve patient comfort and facilitate OHT assessment in younger patient populations.

Outcomes and characteristics of cardiac arrest in children with pulmonary hypertension: A secondary analysis of the ICU-RESUS clinical trial.

BACKGROUND: Previous studies have identified pulmonary hypertension (PH) as a relatively common diagnosis in children with in-hospital cardiac arrest (IHCA), and preclinical laboratory studies have found poor outcomes and low systemic blood pressures during CPR for PH-associated cardiac arrest. The objective of this study was to determine the prevalence of PH among children with IHCA and the association between PH diagnosis and intra-arrest physiology and survival outcomes. METHODS: This was a prospectively designed secondary analysis of patients enrolled in the ICU-RESUS clinical trial (NCT02837497). The primary exposure was a pre-arrest diagnosis of PH. The primary survival outcome was survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline). The primary physiologic outcome was event-level average diastolic blood pressure (DBP) during CPR. RESULTS: Of 1276 patients with IHCAs during the study period, 1129 index IHCAs were enrolled; 184 (16.3%) had PH and 101/184 (54.9%) were receiving inhaled nitric oxide at the time of IHCA. Survival with favorable neurologic outcome was similar between patients with and without PH on univariate (48.9% vs. 54.4%; p = 0.17) and multivariate analyses (aOR 0.82 [95%CI: 0.56, 1.20]; p = 0.32). There were no significant differences in CPR event outcome or survival to hospital discharge. Average DBP, systolic BP, and end-tidal carbon dioxide during CPR were similar between groups. CONCLUSIONS: In this prospective study of pediatric IHCA, pre-existing PH was present in 16% of children. Pre-arrest PH diagnosis was not associated with statistically significant differences in survival outcomes or intra-arrest physiologic measures.

Native T1 mapping detects both acute clinical rejection and graft dysfunction in pediatric heart transplant patients.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is emerging as an important tool for cardiac allograft assessment. Native T1 mapping may add value in identifying rejection and in assessing graft dysfunction and myocardial fibrosis burden. We hypothesized that CMR native T1 values and features of textural analysis of T1 maps would identify acute rejection, and in a secondary analysis, correlate with markers of graft dysfunction, and with fibrosis percentage from endomyocardial biopsy (EMB). METHODS: Fifty cases with simultaneous EMB, right heart catheterization, and 1.5 T CMR with breath-held T1 mapping via modified Look-Locker inversion recovery (MOLLI) in 8 short-axis slices and subsequent quantification of mean and peak native T1 values, were performed on 24 pediatric subjects. A single mid-ventricular slice was used for image texture analysis using nine gray-level co-occurrence matrix features. Digital quantification of Masson trichrome stained EMB samples established degree of fibrosis. Markers of graft dysfunction, including serum brain natriuretic peptide levels and hemodynamic measurements from echocardiography, catheterization, and CMR were collated. Subjects were divided into three groups based on degree of rejection: acute rejection requiring new therapy, mild rejection requiring increased ongoing therapy, and no rejection with no change in treatment. Statistical analysis included student's t-test and linear regression. RESULTS: Peak and mean T1 values were significantly associated with acute rejection, with a monotonic trend observed with increased grade of rejection. Texture analysis demonstrated greater spatial heterogeneity in T1 values, as demonstrated by energy, entropy, and variance, in cases requiring treatment. Interestingly, 2 subjects who required increased therapy despite low grade EMB results had abnormal peak T1 values. Peak T1 values also correlated with increased BNP, right-sided filling pressures, and capillary wedge pressures. There was no difference in histopathological fibrosis percentage among the 3 groups; histopathological fibrosis did not correlate with T1 values or markers of graft dysfunction. CONCLUSION: In pediatric heart transplant patients, native T1 values identify acute rejection requiring treatment and may identify graft dysfunction. CMR shows promise as an important tool for evaluation of cardiac grafts in children, with T1 imaging outperforming biopsy findings in the assessment of rejection.

Characterization of Inhaled Nitric Oxide Use for Cardiac Indications in Pediatric Patients.

OBJECTIVES: Characterize the use of inhaled nitric oxide (iNO) for pediatric cardiac patients and assess the relationship between patient characteristics before iNO initiation and outcomes following cardiac surgery. DESIGN: Observational cohort study. SETTING: PICU and cardiac ICUs in seven Collaborative Pediatric Critical Care Research Network hospitals. PATIENTS: Consecutive patients, less than 18 years old, mechanically ventilated before or within 24 hours of iNO initiation. iNO was started for a cardiac indication and excluded newborns with congenital diaphragmatic hernia, meconium aspiration syndrome, and persistent pulmonary hypertension, or when iNO started at an outside institution. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred seven patients with iNO initiation based on cardiac dysfunction. Cardiac dysfunction patients were administered iNO for a median of 4 days (2-7 d). There was significant morbidity with 51 of 407 (13%) requiring extracorporeal membrane oxygenation and 27 of 407 (7%) requiring renal replacement therapy after iNO initiation, and a 28-day mortality of 46 of 407 (11%). Of the 366 (90%) survivors, 64 of 366 patients (17%) had new morbidity as assessed by Functional Status Scale. Among the postoperative cardiac surgical group (n = 301), 37 of 301 (12%) had a superior cavopulmonary connection and nine of 301 (3%) had a Fontan procedure. Based on echocardiographic variables prior to iNO (n = 160) in the postoperative surgical group, right ventricle dysfunction was associated with 28-day and hospital mortalities (both, p < 0.001) and ventilator-free days (p = 0.003); tricuspid valve regurgitation was only associated with ventilator-free days (p < 0.001), whereas pulmonary hypertension was not associated with mortality or ventilator-free days. CONCLUSIONS: Pediatric patients in whom iNO was initiated for a cardiac indication had a high mortality rate and significant morbidity. Right ventricular dysfunction, but not the presence of pulmonary hypertension on echocardiogram, was associated with ventilator-free days and mortality.

Inhaled Nitric Oxide Use and Outcomes in Critically Ill Children With a History of Prematurity.

BACKGROUND: Inhaled nitric oxide (INO) is used to treat hypoxic respiratory failure without clear evidence of benefit. Future trials to evaluate its use will be designed based on an understanding of the populations in which this therapy is provided and with outcomes based on patient characteristics, for example, a history of premature birth. METHODS: This was a multi-center prospective observational study that evaluated subjects in the pediatric ICU who were treated with INO for a respiratory indication, excluding those treated in the neonatal ICU or treated for birth-related disease. We used logistic regression to evaluate characteristics associated with mortality and duration of mechanical ventilation. Specifically, we compared subjects born early preterm (<32 weeks post-conceptual age), late preterm (32-37 weeks post-conceptual age), and full term. RESULTS: A total of 163 children (median age [interquartile range], 1.8 [0.7-6.0] y) were included, 41 (25.2%) had a history of preterm birth (18 born early preterm and 23 born late preterm). INO was initiated for less-severe lung disease in the early preterm versus late preterm versus full-term subjects (median mean airway pressures, 16 vs 19 vs 19 cm H2O; P = .03), although the oxygenation index and oxygenation saturation index did not differ. The early preterm subjects had more ventilator-free days (median, 18.0, 7.0, 4.5 d; P = .02) and lower 28-d mortality (0, 26.1, 32.0%; P = .007). Lower respiratory tract disease, but not a history of prematurity, was independently associated with lower mortality. CONCLUSIONS: INO was used differently in early preterm subjects. Clinical trials that evaluate INO use should have standardized oxygenation deficit thresholds for initiation of therapy and should consider stratifying by early preterm status.

Common carotid artery imaging after vessel sparing decannulation from Extracorporeal Membrane Oxygenation (ECMO) support.

INTRODUCTION: In 2008, Children's National Hospital adopted a simple vessel sparing technique (VST) for neck extra corporeal membrane (ECMO) cannulation/decannulation that is technically simple and reproducible. In this study, we review a cohort of patients decannulated from venous-arterial (VA) ECMO using a VST with the goal of understanding flow dynamics and anatomic changes of the common carotid artery (CCA) after repair with a VST. METHODS: Patients supported with ECMO at a single, tertiary care center between 2008 and 2019 were identified. Patients were included in the analysis if they survived VA ECMO including VST decannulation and neck vessel imaging was completed with either magnetic resonance angiogram (MRA) or computerized tomography angiogram (CTA) post decannulation. The right CCA was assessed for patency and arteriopathy. Complications and feasibility of repeat ECMO cannulation via the neck vessels were also investigated. RESULTS: Three hundred and nineteen patients were identified as having received ECMO support in either the PICU or CICU between 2008 and 2019, of which 76 survived VA ECMO support via neck cannulation. Neck vessel imaging was obtained in 21 patients. Ten had imaging demonstrating a normal right CCA. The CCA was occluded in 3 and stenotic in 5. Vessel wall defects were present in 4. No definitive complication was associated with any of the arterial abnormalities. Repeat right CCA cannulation was achieved in 6/7 patients who needed additional VA ECMO support. CONCLUSIONS: Repair of the right CCA with a simple VST can be achieved safely and consistently during VA ECMO support in pediatric patients. Vascular imaging of the right CCA was normal in almost half and repeat cannulation was achieved in most when pursued. Stenosis and vessel wall defects were common, thus neck vessel imaging post decannulation may be warranted for all patients with a right CCA repair after ECMO support.

Plasma and Urinary FGF-2 and VEGF-A Levels Identify Children at Risk for Severe Bleeding after Pediatric Cardiopulmonary Bypass: A Pilot Study.

Severe bleeding after cardiothoracic surgery with cardiopulmonary bypass (CPB) is associated with increased morbidity and mortality in adults and children. Fibroblast Growth Factor-2 (FGF-2) and Vascular Endothelial Growth Factor-A (VEGF-A) induce hemorrhage in murine models with heparin exposure. We aim to determine if plasma and urine levels of FGF-2 and VEGF-A in the immediate perioperative period can identify children with severe bleeding after CPB. We performed a prospective, observational biomarker study in 64 children undergoing CPB for congenital heart disease repair from June 2015 - January 2017 in a tertiary pediatric referral center. Primary outcome was severe bleeding defined as ≥ 20% estimated blood volume loss within 24-hours. Independent variables included perioperative plasma and urinary FGF-2 and VEGF-A levels. Analyses included comparative (Wilcoxon rank sum, Fisher's exact, and Student's t tests) and discriminative (receiver operator characteristic [ROC] curve) analyses. Forty-eight (75%) children developed severe bleeding. Median plasma and urinary FGF-2 and VEGF-A levels were elevated in children with severe bleeding compared to without bleeding (preoperative: plasma FGF-2 = 16[10-35] vs. 9[2-13] pg/ml; urine FGF-2= 28[15-76] vs. 14.5[1.5-22] pg/mg; postoperative: plasma VEGF-A = 146[34-379] vs. 53 [0-134] pg/ml; urine VEGF-A = 132 [52-257] vs. 45[0.1-144] pg/mg; all p < 0.05). ROC curve analyses of combined plasma and urinary FGF-2 and VEGF-A levels discriminated severe postoperative bleeding (AUC: 0.73-0.77) with mean sensitivity and specificity above 80%. We conclude that the perioperative plasma and urinary levels of FGF-2 and VEGF-A discriminate risk of severe bleeding after pediatric CPB.

Association between time of day and CPR quality as measured by CPR hemodynamics during pediatric in-hospital CPR.

INTRODUCTION: Patients who suffer in-hospital cardiac arrest (IHCA) are less likely to survive if the arrest occurs during nighttime versus daytime. Diastolic blood pressure (DBP) as a measure of chest compression quality was associated with survival from pediatric IHCA. We hypothesized that DBP during CPR for IHCA is lower during nighttime versus daytime. METHODS: This is a secondary analysis of data collected from the Pediatric Intensive Care Quality of Cardiopulmonary Resuscitation Study. Pediatric or Pediatric Cardiac Intensive Care Unit patients who received chest compressions for ≥1 min and who had invasive arterial BP monitoring were enrolled. Nighttime was defined as 11:00PM to 6:59AM and daytime as 7:00AM until 10:59PM. Primary outcome was attainment of DBP ≥ 25 mmHg in infants <1 year and ≥30 mmHg in older children. Secondary outcomes were mean DBP, ROSC, and survival to hospital discharge. Univariable and multivariate analyses evaluated the relationships between time (nighttime vs. daytime) and outcomes. RESULTS: Between July 1, 2013 and June 30, 2016, 164 arrests met all inclusion/exclusion criteria: 45(27%) occurred at nighttime and 119(73%) during daytime. Average DBPs achieved were not different between groups (DBP: nighttime 28.3 mmHg[25.3, 36.5] vs. daytime 29.6 mmHg[21.8, 38.0], p = 0.64). Relative risk of DBP threshold met during nighttime vs. daytime was 1.27, 95%CI [0.80, 1.98], p = 0.30. There was no significant nighttime vs. daytime difference in ROSC (28/45[62%] vs. 84/119[71%] p = 0.35) or survival to hospital discharge (16/45[36%] vs. 61/119[51%], p = 0.08). CONCLUSIONS: In this cohort of pediatric ICU patients with IHCA, there was no significant difference in DBP during CPR between nighttime and daytime.

Survival and Hemodynamics During Pediatric Cardiopulmonary Resuscitation for Bradycardia and Poor Perfusion Versus Pulseless Cardiac Arrest.

OBJECTIVES: The objective of this study was to compare survival outcomes and intra-arrest arterial blood pressures between children receiving cardiopulmonary resuscitation for bradycardia and poor perfusion and those with pulseless cardiac arrests. DESIGN: Prospective, multicenter observational study. SETTING: PICUs and cardiac ICUs of the Collaborative Pediatric Critical Care Research Network. PATIENTS: Children (< 19 yr old) who received greater than or equal to 1 minute of cardiopulmonary resuscitation with invasive arterial blood pressure monitoring in place. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 164 patients, 96 (59%) had bradycardia and poor perfusion as the initial cardiopulmonary resuscitation rhythm. Compared to those with initial pulseless rhythms, these children were younger (0.4 vs 1.4 yr; p = 0.005) and more likely to have a respiratory etiology of arrest (p < 0.001). Children with bradycardia and poor perfusion were more likely to survive to hospital discharge (adjusted odds ratio, 2.31; 95% CI, 1.10-4.83; p = 0.025) and survive with favorable neurologic outcome (adjusted odds ratio, 2.21; 95% CI, 1.04-4.67; p = 0.036). There were no differences in diastolic or systolic blood pressures or event survival (return of spontaneous circulation or return of circulation via extracorporeal cardiopulmonary resuscitation). Among patients with bradycardia and poor perfusion, 49 of 96 (51%) had subsequent pulselessness during the cardiopulmonary resuscitation event. During cardiopulmonary resuscitation, these patients had lower diastolic blood pressure (point estimate, -6.68 mm Hg [-10.92 to -2.44 mm Hg]; p = 0.003) and systolic blood pressure (point estimate, -12.36 mm Hg [-23.52 to -1.21 mm Hg]; p = 0.032) and lower rates of return of spontaneous circulation (26/49 vs 42/47; p < 0.001) than those who were never pulseless. CONCLUSIONS: Most children receiving cardiopulmonary resuscitation in ICUs had an initial rhythm of bradycardia and poor perfusion. They were more likely to survive to hospital discharge and survive with favorable neurologic outcomes than patients with pulseless arrests, although there were no differences in immediate event outcomes or intra-arrest hemodynamics. Patients who progressed to pulselessness after cardiopulmonary resuscitation initiation had lower intra-arrest hemodynamics and worse event outcomes than those who were never pulseless.

Inhaled Nitric Oxide Use in Pediatric Hypoxemic Respiratory Failure.

OBJECTIVES: To characterize contemporary use of inhaled nitric oxide in pediatric acute respiratory failure and to assess relationships between clinical variables and outcomes. We sought to study the relationship of inhaled nitric oxide response to patient characteristics including right ventricular dysfunction and clinician responsiveness to improved oxygenation. We hypothesize that prompt clinician responsiveness to minimize hyperoxia would be associated with improved outcomes. DESIGN: An observational cohort study. SETTING: Eight sites of the Collaborative Pediatric Critical Care Research Network. PATIENTS: One hundred fifty-one patients who received inhaled nitric oxide for a primary respiratory indication. MEASUREMENTS AND MAIN RESULTS: Clinical data were abstracted from the medical record beginning at inhaled nitric oxide initiation and continuing until the earliest of 28 days, ICU discharge, or death. Ventilator-free days, oxygenation index, and Functional Status Scale were calculated. Echocardiographic reports were abstracted assessing for pulmonary hypertension, right ventricular dysfunction, and other cardiovascular parameters. Clinician responsiveness to improved oxygenation was determined. One hundred thirty patients (86%) who received inhaled nitric oxide had improved oxygenation by 24 hours. PICU mortality was 29.8%, while a new morbidity was identified in 19.8% of survivors. Among patients who had echocardiograms, 27.9% had evidence of pulmonary hypertension, 23.1% had right ventricular systolic dysfunction, and 22.1% had an atrial communication. Moderate or severe right ventricular dysfunction was associated with higher mortality. Clinicians responded to an improvement in oxygenation by decreasing FIO2 to less than 0.6 within 24 hours in 71% of patients. Timely clinician responsiveness to improved oxygenation with inhaled nitric oxide was associated with more ventilator-free days but not less cardiac arrests, mortality, or additional morbidity. CONCLUSIONS: Clinician responsiveness to improved oxygenation was associated with less ventilator days. Algorithms to standardize ventilator management may improve signal to noise ratios in future trials enabling better assessment of the effect of inhaled nitric oxide on patient outcomes. Additionally, confining studies to more selective patient populations such as those with right ventricular dysfunction may be required.

Ventilation Rates and Pediatric In-Hospital Cardiac Arrest Survival Outcomes.

OBJECTIVES: The objective of this study was to associate ventilation rates during in-hospital cardiopulmonary resuscitation with 1) arterial blood pressure during cardiopulmonary resuscitation and 2) survival outcomes. DESIGN: Prospective, multicenter observational study. SETTING: Pediatric and pediatric cardiac ICUs of the Collaborative Pediatric Critical Care Research Network. PATIENTS: Intubated children (≥ 37 wk gestation and < 19 yr old) who received at least 1 minute of cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure and ventilation rate (breaths/min) were manually extracted from arterial line and capnogram waveforms. Guideline rate was defined as 10 ± 2 breaths/min; high ventilation rate as greater than or equal to 30 breaths/min in children less than 1 year old, and greater than or equal to 25 breaths/min in older children. The primary outcome was survival to hospital discharge. Regression models using Firth penalized likelihood assessed the association between ventilation rates and outcomes. Ventilation rates were available for 52 events (47 patients). More than half of patients (30/47; 64%) were less than 1 year old. Eighteen patients (38%) survived to discharge. Median event-level average ventilation rate was 29.8 breaths/min (interquartile range, 23.8-35.7). No event-level average ventilation rate was within guidelines; 30 events (58%) had high ventilation rates. The only significant association between ventilation rate and arterial blood pressure occurred in children 1 year old or older and was present for systolic blood pressure only (-17.8 mm Hg/10 breaths/min; 95% CI, -27.6 to -8.1; p < 0.01). High ventilation rates were associated with a higher odds of survival to discharge (odds ratio, 4.73; p = 0.029). This association was stable after individually controlling for location (adjusted odds ratio, 5.97; p = 0.022), initial rhythm (adjusted odds ratio, 3.87; p = 0.066), and time of day (adjusted odds ratio, 4.12; p = 0.049). CONCLUSIONS: In this multicenter cohort, ventilation rates exceeding guidelines were common. Among the range of rates delivered, higher rates were associated with improved survival to hospital discharge.

Functional outcomes among survivors of pediatric in-hospital cardiac arrest are associated with baseline neurologic and functional status, but not with diastolic blood pressure during CPR.

AIM: Diastolic blood pressure (DBP) during cardiopulmonary resuscitation (CPR) is associated with survival following pediatric in-hospital cardiac arrest. The relationship between intra-arrest haemodynamics and neurological status among survivors of pediatric cardiac arrest is unknown. METHODS: This study represents analysis of data from the prospective multicenter Pediatric Intensive Care Quality of cardiopulmonary resuscitation (PICqCPR) Study. Primary predictor variables were median DBP and median systolic blood pressure (SBP) over the first 10min of CPR. The primary outcome measure was "new substantive morbidity" determined by Functional Status Scale (FSS) and defined as an increase in the FSS of at least 3 points or increase of 2 in a single FSS domain. Univariable analyses were completed to investigate the relationship between new substantive morbidity and BPs during CPR. RESULTS: 244 index CPR events occurred during the study period, 77 (32%) CPR events met all inclusion criteria as well as having both DBP and FSS data available. Among 77 survivors, 32 (42%) had new substantive morbidity as measured by the FSS score. No significant differences were identified in DBP (median 30.5mmHg vs. 30.9mmHg, p=0.5) or SBP (median 76.3mmHg vs. 63.0mmHg, p=0.2) between patients with and without new substantive morbidity. Children who developed new substantive morbidity were more likely to have lower pre-arrest FSS than those that did not (median [IQR]: 7.5 [6.0-9.0] versus 9.0 [7.0-13.0], p=0.01). CONCLUSION: New substantive morbidity determined by FSS after a pediatric IHCA was associated with baseline functional status, but not DBP during CPR.

Survival and Cardiopulmonary Resuscitation Hemodynamics Following Cardiac Arrest in Children With Surgical Compared to Medical Heart Disease.

OBJECTIVES: To assess the association of diastolic blood pressure cutoffs (≥ 25 mm Hg in infants and ≥ 30 mm Hg in children) during cardiopulmonary resuscitation with return of spontaneous circulation and survival in surgical cardiac versus medical cardiac patients. Secondarily, we assessed whether these diastolic blood pressure targets were feasible to achieve and associated with outcome in physiology unique to congenital heart disease (single ventricle infants, open chest), and influenced outcomes when extracorporeal cardiopulmonary resuscitation was deployed. DESIGN: Multicenter, prospective, observational cohort analysis. SETTING: Tertiary PICU and cardiac ICUs within the Collaborative Pediatric Critical Care Research Network. PATIENTS: Patients with invasive arterial catheters during cardiopulmonary resuscitation and surgical cardiac or medical cardiac illness category. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hemodynamic waveforms during cardiopulmonary resuscitation were analyzed on 113 patients, 88 surgical cardiac and 25 medical cardiac. A similar percent of surgical cardiac (51/88; 58%) and medical cardiac (17/25; 68%) patients reached the diastolic blood pressure targets (p = 0.488). Achievement of diastolic blood pressure target was associated with improved survival to hospital discharge in surgical cardiac patients (p = 0.018), but not medical cardiac patients (p = 0.359). Fifty-three percent (16/30) of patients with single ventricles attained the target diastolic blood pressure. In patients with an open chest at the start of chest compressions, 11 of 20 (55%) attained the target diastolic blood pressure. In the 33 extracorporeal cardiopulmonary resuscitation patients, 16 patients (48%) met the diastolic blood pressure target with no difference between survivors and nonsurvivors (p = 0.296). CONCLUSIONS: During resuscitation in an ICU, with invasive monitoring in place, diastolic blood pressure targets of greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in children can be achieved in patients with both surgical and medical heart disease. Achievement of diastolic blood pressure target was associated with improved survival to hospital discharge in surgical cardiac patients, but not medical cardiac patients. Diastolic blood pressure targets were feasible to achieve in 1) single ventricle patients, 2) open chest physiology, and 3) extracorporeal cardiopulmonary resuscitation patients.

The association of immediate post cardiac arrest diastolic hypertension and survival following pediatric cardiac arrest.

AIM: In-hospital cardiac arrest occurs in >5000 children each year in the US and almost half will not survive to discharge. Animal data demonstrate that an immediate post-resuscitation burst of hypertension is associated with improved survival. We aimed to determine if systolic and diastolic invasive arterial blood pressures immediately (0-20 min) after return of spontaneous circulation (ROSC) are associated with survival and neurologic outcomes at hospital discharge. METHODS: This is a secondary analysis of the Pediatric Intensive Care Quality of CPR (PICqCPR) study of invasively measured blood pressures during intensive care unit CPR. Patients were eligible if they achieved ROSC and had at least one invasively measured blood pressure within the first 20 min following ROSC. Post-ROSC blood pressures were normalized for age, sex and height. "Immediate hypertension" was defined as at least one systolic or diastolic blood pressure >90th percentile. The primary outcome was survival to hospital discharge. RESULTS: Of 102 children, 70 (68.6%) had at least one episode of immediate post-CPR diastolic hypertension. After controlling for pre-existing hypotension, duration of CPR, calcium administration, and first documented rhythm, patients with immediate post-CPR diastolic hypertension were more likely to survive to hospital discharge (79.3% vs. 54.5%; adjusted OR = 2.93; 95%CI, 1.16-7.69). CONCLUSIONS: In this post hoc secondary analysis of the PICqCPR study, 68.6% of subjects had diastolic hypertension within 20 min of ROSC. Immediate post-ROSC hypertension was associated with increased odds of survival to discharge, even after adjusting for covariates of interest.

Clinical Determination of Brain Death in Children Supported by Extracorporeal Membrane Oxygenation.

BACKGROUND/OBJECTIVE: Children supported by extracorporeal membrane oxygenation (ECMO) are at risk of catastrophic neurologic injury and brain death. Timely determination of brain death is important for minimizing psychological distress for families, resource allocation, and organ donation. Reports of successful determination of brain death in pediatric patients supported by ECMO are limited. The determination of brain death by clinical criteria requires apnea testing, which has historically been viewed as challenging in patients supported by ECMO. We report eight pediatric patients who underwent a total of 14 brain death examinations, including apnea testing, while supported by veno-arterial ECMO (VA-ECMO), resulting in six cases of clinical determination of brain death. METHODS: We performed a retrospective review of the medical records of pediatric patients who underwent brain death examination while supported by VA-ECMO between 2010 and 2018 at a single tertiary care children's hospital. RESULTS: Eight patients underwent brain death examination, including apnea testing, while supported by VA-ECMO. Six patients met criteria for brain death, while two had withdrawal of technical support after the first examination. During the majority of apnea tests (n = 13/14), the ECMO circuit was modified to achieve hypercarbia while maintaining oxygenation and hemodynamic stability. The sweep flow was decreased prior to apnea testing in ten brain death examinations, carbon dioxide was added to the circuit during three examinations, and ECMO pump flows were increased in response to hypotension during two examinations. CONCLUSIONS: Clinical determination of brain death, including apnea testing, can be performed in pediatric patients supported by ECMO. The ECMO circuit can be effectively modified during apnea testing to achieve a timely rise in carbon dioxide while maintaining oxygenation and hemodynamic stability.

End-tidal carbon dioxide during pediatric in-hospital cardiopulmonary resuscitation.

BACKGROUND: Based on laboratory cardiopulmonary resuscitation (CPR) investigations and limited adult data, the American Heart Association Consensus Statement on CPR Quality recommends titrating CPR performance to achieve end-tidal carbon dioxide (ETCO2) >20 mmHg. AIMS: We prospectively evaluated whether ETCO2 > 20 mmHg during CPR was associated with survival to hospital discharge. METHODS: Children ≥37 weeks gestation in Collaborative Pediatric Critical Care Research Network intensive care units with chest compressions for ≥1 min and ETCO2 monitoring prior to and during CPR between July 1, 2013 and June 31, 2016 were included. ETCO2 and Utstein-style cardiac arrest data were collected. Multivariable Poisson regression models with robust error estimates were used to estimate relative risk of outcomes. RESULTS: Blinded investigators analyzed ETCO2 waveforms from 43 children. During CPR, the median ETCO2 was 23 mmHg [quartiles, 16 and 28 mmHg], median ventilation rate was 29 breaths/min [quartiles, 24 and 35 breaths/min], and median duration of CPR was 5 min [quartiles, 2 and 16 min]. Return of spontaneous circulation occurred after 71% of CPR events and 37% of patients survived to hospital discharge. For children with mean ETCO2 during CPR > 20 mmHg, the adjusted relative risk for survival was 0.92 (0.41, 2.08), p = 0.84. The median mean ETCO2 among children who survived to hospital discharge was 20 mmHg [quartiles; 15, 28 mmHg] versus 23 mmHg [16, 28 mmHg] among non-survivors. CONCLUSION: Mean ETCO2 > 20 mmHg during pediatric in-hospital CPR was not associated with survival to hospital discharge, and ETCO2 was not different in survivors versus non-survivors.

Chest compression rates and pediatric in-hospital cardiac arrest survival outcomes.

AIM: The primary aim of this study was to evaluate the association between chest compression rates and 1) arterial blood pressure and 2) survival outcomes during pediatric in-hospital cardiopulmonary resuscitation (CPR). METHODS: Prospective observational study of children ≥37 weeks gestation and <19 years old who received CPR in an intensive care unit (ICU) as part of the Pediatric Intensive Care Unit Quality of CPR Study (PICqCPR) of the Collaborative Pediatric Critical Care Research Network (CPCCRN). Arterial blood pressure and compression rate were determined from manually extracted arterial line waveform data during the first 10 min of CPR. The primary outcome was survival to hospital discharge. Modified Poisson regression models assessed the association between rate categories (80-<100, 100-120 [Guidelines], >120-140, >140) and outcomes. RESULTS: Compression rate data were available for 164 patients. More than half (98/164; 60%) were <1 year old. Return of circulation was achieved in 148/164 (90%); survival to hospital discharge in 77/164 (47%). Percentage of events with average rate within Guidelines was 32.9%. Compared to Guidelines, higher rate categories were associated with lower systolic blood pressures (>120-140, p = 0.010; >140, p = 0.077), but not survival. A rate between 80-<100 per minute was associated with a higher rate of survival to hospital discharge (aRR 1.92, CI95 1.13, 3.29, p = 0.017) and survival with favorable neurological outcome (aRR 2.12, CI95 1.09, 4.13, p = 0.027) compared to Guidelines. CONCLUSION: Non-compliance with compression rate Guidelines was common in this multicenter cohort. Among ICU patients, slightly lower rates were associated with improved outcomes compared to Guidelines.

Cardiopulmonary Bypass Reduces Early Thrombosis of Systemic-to-Pulmonary Artery Shunts.

BACKGROUND: Shunt thrombosis is a significant cause of morbidity and mortality after systemic-to-pulmonary artery shunt (SPS) placement. Concurrent procedures with placement of SPS may require cardiopulmonary bypass (CPB). Cardiopulmonary bypass is known to cause bleeding and platelet dysfunction in infants, which may protect from early shunt thrombosis. We hypothesized that infants undergoing SPS placement on CPB have a lower incidence of early shunt thrombosis. METHODS: Retrospective cohort study of infants undergoing SPS placement from January 2008 to December 2014 was performed. Patients with and without early shunt thrombosis and on or off CPB were compared using the Mann-Whitney U test or Fisher exact test. Multivariable regression analysis was performed to identify independent predictors of early shunt thrombosis and to assess effect of CPB independent of other factors. RESULTS: Seventy-five infants underwent SPS placement during the study period (on CPB, n = 25; off CPB, n = 50). Operative mortality was 11% (8/75). Nine (12%) patients developed early shunt thrombosis, all of whom had shunt placement off CPB. Independent risk factors for early shunt thrombosis were identified to be SPS placement off CPB ( P = .011), prematurity ( P = .034), and competitive antegrade pulmonary blood flow ( P = .038). CONCLUSION: Prematurity, competitive antegrade pulmonary blood flow, and shunt placement off CPB lead to higher risk of early shunt thrombosis. We speculate that the protection offered by use of CPB may be accounted for by the associated complex coagulopathy and platelet dysfunction associated with CPB.

Risk Factors for Major Early Adverse Events Related to Cardiac Catheterization in Children and Young Adults With Pulmonary Hypertension: An Analysis of Data From the IMPACT (Improving Adult and Congenital Treatment) Registry.

BACKGROUND: Cardiac catheterization is the gold standard for assessment and follow-up of patients with pulmonary hypertension (PH). To date, there are limited data about the factors that influence the risk of catastrophic adverse events after catheterization in this population. METHODS AND RESULTS: A retrospective multicenter cohort study was performed to measure risk of catastrophic adverse outcomes after catheterization in children and young adults with PH and identify risk factors for these outcomes. All catheterizations in children and young adults, aged 0 to 21 years, with PH at hospitals submitting data to the IMPACT (Improving Adult and Congenital Treatment) registry between January 1, 2011, and December 31, 2015, were studied. Using mixed-effects multivariable regression, we assessed the association between prespecified subject-, procedure-, and center-level covariates and the risk of death, cardiac arrest, or mechanical circulatory support during or after cardiac catheterization. A total of 8111 procedures performed in 7729 subjects at 77 centers were studied. The observed risk of the composite outcome was 1.4%, and the risk of death before discharge was 5.2%. Catheterization in prematurely born neonates and nonpremature infants was associated with increased risk of catastrophic adverse event, as was precatheterization treatment with inotropes and lower systemic arterial saturation. Secondary analyses demonstrated the following: (1) increasing volumes of catheterization in patients with PH were associated with reduced risk of composite outcome (odds ratio, 0.8 per 10 procedures; P=0.002) and (2) increasing pulmonary vascular resistance and pulmonary artery pressures were associated with increased risk (P<0.0001 for both). CONCLUSIONS: Young patients with PH are a high-risk population for diagnostic and interventional cardiac catheterization. Hospital experience with PH is associated with reduced risk, independent of total catheterization case volume.