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.

Anticoagulation practices associated with bleeding and thrombosis in pediatric extracorporeal membrane oxygenation; a multi-center secondary analysis.

To determine associations between anticoagulation practices and bleeding and thrombosis during pediatric extracorporeal membrane oxygenation (ECMO), we performed a secondary analysis of prospectively collected data which included 481 children (<19 years), between January 2012 and September 2014. The primary outcome was bleeding or thrombotic events. Bleeding events included a blood product transfusion >80 ml/kg on any day, pulmonary hemorrhage, or intracranial bleeding, Thrombotic events included pulmonary emboli, intracranial clot, limb ischemia, cardiac clot, and arterial cannula or entire circuit change. Bleeding occurred in 42% of patients. Five percent of subjects thrombosed, of which 89% also bled. Daily bleeding odds were independently associated with day prior activated clotting time (ACT) (OR 1.03, 95% CI= 1.00, 1.05, p=0.047) and fibrinogen levels (OR 0.90, 95% CI 0.84, 0.96, p <0.001). Thrombosis odds decreased with increased day prior heparin dose (OR 0.88, 95% CI 0.81, 0.97, p=0.006). Lower ACT values and increased fibrinogen levels may be considered to decrease the odds of bleeding. Use of this single measure, however, may not be sufficient alone to guide optimal anticoagulation practice during ECMO.

Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy.

OBJECTIVES: To determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock. DESIGN: Multicenter, double-blinded, randomized controlled trial. SETTING: One academic medical ICU and four community ICUs. PATIENTS: Of 167 adult patients within 24 hours of vasopressor initiation for septic shock, 126 consented to participation, and 124 received study drug and were included in analysis. INTERVENTIONS: IV vitamin C (10 mg/mL in normal saline) administered as a 1,000-mg bolus over 30 minutes followed by continuous infusion of 250 mg/hr for 96 hours or placebo of equal volumes of normal saline. MEASUREMENTS AND MAIN RESULTS: Of 124 subjects receiving study drug and included in analysis, 60 received vitamin C and 64 placebo. The primary outcome of all-cause 28-day mortality (vitamin C, 26.7%; placebo, 40.6%; p = 0.10) was lower in the vitamin C arm but did not reach statistical significance. Initiation of renal replacement therapy was higher in the vitamin C arm (vitamin C, 16.7%; placebo, 3.3%; p = 0.015), as was volume of fluid administration within 6 hours of study drug initiation (vitamin C, 1.07 L; placebo, 0.76 L; p = 0.03). There were no statistically significant differences in other secondary outcomes. In post hoc subgroup analysis, there was a decrease in 28-day mortality in the vitamin C arm among patients requiring positive-pressure ventilation at the time of enrollment (vitamin C, 36.3%; placebo, 60.0%; p = 0.05). This trial is registered at clinicaltrials.gov under identifier NCT03338569. CONCLUSIONS: Vitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.

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.

Dynamic PEEP Study: A Non-invasive Diagnostic Exam to Assess for Effective PEEP in Children with Severe BPD.

OBJECTIVE: Tracheobronchomalacia (TBM) is common in neonates with bronchopulmonary dysplasia (BPD) and is associated with higher morbidity. This study evaluates the value of a CT protocol to assess the degree of TBM and gauge the adequacy of prescribed PEEP. STUDY DESIGN: Four infants with severe BPD on invasive mechanical ventilation underwent a chest CT protocol, including limited reduced-dose expiratory scans with varying PEEP levels. RESULTS: Baseline PEEP was adjusted in all subjects after performing the Dynamic PEEP CT. In two infants, the PEEP was increased due to significant TBM and in the other two without signs of TBM PEEP was decreased. The clinical course improved in all patients after adjusting PEEP. CONCLUSION: A "Dynamic PEEP" study may be reliable and non-invasive imaging modality for the evaluation of adequate ventilator settings in infants with severe BPD who are not optimal candidates for bronchoscopy.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

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.

Association Between Diastolic Blood Pressure During Pediatric In-Hospital Cardiopulmonary Resuscitation and Survival.

BACKGROUND: On the basis of laboratory cardiopulmonary resuscitation (CPR) investigations and limited adult data demonstrating that survival depends on attaining adequate arterial diastolic blood pressure (DBP) during CPR, the American Heart Association recommends using blood pressure to guide pediatric CPR. However, evidence-based blood pressure targets during pediatric CPR remain an important knowledge gap for CPR guidelines. METHODS: All children ≥37 weeks' gestation and <19 years old in Collaborative Pediatric Critical Care Research Network intensive care units with chest compressions for ≥1 minute and invasive arterial blood pressure monitoring before and during CPR between July 1, 2013, and June 31, 2016, were included. Mean DBP during CPR and Utstein-style standardized cardiac arrest data were collected. The hypothesis was that DBP ≥25 mm Hg during CPR in infants and ≥30 mm Hg in children ≥1 year old would be associated with survival. Primary outcome was survival to hospital discharge. Secondary outcome was survival to hospital discharge with favorable neurological outcome, defined as Pediatric Cerebral Performance Categories 1 to 3 or no worse than prearrest baseline. Multivariable Poisson regression models with robust error estimates were used to estimate the relative risk of outcomes. RESULTS: Blinded investigators analyzed blood pressure waveforms during CPR from 164 children, including 60% <1 year old, 60% with congenital heart disease, and 54% after cardiac surgery. The immediate cause of arrest was hypotension in 67%, respiratory decompensation in 44%, and arrhythmia in 19%. Median duration of CPR was 8 minutes (quartiles, 3 and 27 minutes). Ninety percent survived the event, 68% with return of spontaneous circulation and 22% by extracorporeal life support. Forty-seven percent survived to hospital discharge, and 43% survived to discharge with favorable neurological outcome. Maintaining mean DBP ≥25 mm Hg in infants and ≥30 mm Hg in children ≥1 year old occurred in 101 of 164 children (62%) and was associated with survival (adjusted relative risk, 1.7; 95% confidence interval, 1.2-2.6; P=0.007) and survival with favorable neurological outcome (adjusted relative risk, 1.6; 95% confidence interval, 1.1-2.5; P=0.02). CONCLUSIONS: These data demonstrate that mean DBP ≥25 mm Hg during CPR in infants and ≥30 mm Hg in children ≥1 year old was associated with greater likelihood of survival to hospital discharge and survival with favorable neurological outcome.