Venovenous Extracorporeal Membrane Oxygenation Initiation for Pediatric Acute Respiratory Distress Syndrome With Cardiovascular Instability is Associated With an Immediate and Sustained Decrease in Vasoactive-Inotropic Scores.

OBJECTIVE: To determine the association of venovenous extracorporeal membrane oxygenation (VV-ECMO) initiation with changes in vasoactive-inotropic scores (VISs) in children with pediatric acute respiratory distress syndrome (PARDS) and cardiovascular instability. DESIGN: Retrospective cohort study. SETTING: Single academic pediatric ECMO center. PATIENTS: Children (1 mo to 18 yr) treated with VV-ECMO (2009-2019) for PARDS with need for vasopressor or inotropic support at ECMO initiation. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas values, VIS, mean airway pressure (mPaw), and oxygen saturation (Sp o2 ) values were recorded hourly relative to the start of ECMO flow for 24 hours pre-VV-ECMO and post-VV-ECMO cannulation. A sharp kink discontinuity regression analysis clustered by patient tested the difference in VISs and regression line slopes immediately surrounding cannulation. Thirty-two patients met inclusion criteria: median age 6.6 years (interquartile range [IQR] 1.5-11.7), 22% immunocompromised, and 75% had pneumonia or sepsis as the cause of PARDS. Pre-ECMO characteristics included: median oxygenation index 45 (IQR 35-58), mPaw 32 cm H 2o (IQR 30-34), 97% on inhaled nitric oxide, and 81% on an advanced mode of ventilation. Median VIS immediately before VV-ECMO cannulation was 13 (IQR 8-25) with an overall increasing VIS trajectory over the hours before cannulation. VISs decreased and the slope of the regression line reversed immediately surrounding the time of cannulation (robust p < 0.0001). There were pre-ECMO to post-ECMO cannulation decreases in mPaw (32 vs 20 cm H 2o , p < 0.001) and arterial P co2 (64.1 vs 50.1 mm Hg, p = 0.007) and increases in arterial pH (7.26 vs 7.38, p = 0.001), arterial base excess (2.5 vs 5.2, p = 0.013), and SpO 2 (91% vs 95%, p = 0.013). CONCLUSIONS: Initiation of VV-ECMO was associated with an immediate and sustained reduction in VIS in PARDS patients with cardiovascular instability. This VIS reduction was associated with decreased mPaw and reduced respiratory and/or metabolic acidosis as well as improved oxygenation.

Diastolic Blood Pressure Threshold During Pediatric Cardiopulmonary Resuscitation and Survival Outcomes: A Multicenter Validation Study.

OBJECTIVES: Arterial diastolic blood pressure (DBP) greater than 25 mm Hg in infants and greater than 30 mm Hg in children greater than 1 year old during cardiopulmonary resuscitation (CPR) was associated with survival to hospital discharge in one prospective study. We sought to validate these potential hemodynamic targets in a larger multicenter cohort. DESIGN: Prospective observational study. SETTING: Eighteen PICUs in the ICU-RESUScitation prospective trial from October 2016 to March 2020. PATIENTS: Children less than or equal to 18 years old with CPR greater than 30 seconds and invasive blood pressure (BP) monitoring during CPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Invasive BP waveform data and Utstein-style CPR data were collected, including prearrest patient characteristics, intra-arrest interventions, and outcomes. Primary outcome was survival to hospital discharge, and secondary outcomes were return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Multivariable Poisson regression models with robust error estimates evaluated the association of DBP greater than 25 mm Hg in infants and greater than 30 mm Hg in older children with these outcomes. Among 1,129 children with inhospital cardiac arrests, 413 had evaluable DBP data. Overall, 85.5% of the patients attained thresholds of mean DBP greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in older children. Initial return of circulation occurred in 91.5% and 25% by placement on extracorporeal membrane oxygenator. Survival to hospital discharge occurred in 58.6%, and survival with favorable neurologic outcome in 55.4% (i.e. 94.6% of survivors had favorable neurologic outcomes). Mean DBP greater than 25 mm Hg for infants and greater than 30 mm Hg for older children was significantly associated with survival to discharge (adjusted relative risk [aRR], 1.32; 1.01-1.74; p = 0.03) and ROSC (aRR, 1.49; 1.12-1.97; p = 0.002) but did not reach significance for survival to hospital discharge with favorable neurologic outcome (aRR, 1.30; 0.98-1.72; p = 0.051). CONCLUSIONS: These validation data demonstrate that achieving mean DBP during CPR greater than 25 mm Hg for infants and greater than 30 mm Hg for older children is associated with higher rates of survival to hospital discharge, providing potential targets for DBP during CPR.

The Temporal Association of the COVID-19 Pandemic and Pediatric Cardiopulmonary Resuscitation Quality and Outcomes.

OBJECTIVES: The COVID-19 pandemic resulted in adaptations to pediatric resuscitation systems of care. The objective of this study was to determine the temporal association between the pandemic and pediatric in-hospital cardiac arrest (IHCA) process of care metrics, cardiopulmonary resuscitation (cardiopulmonary resuscitation) quality, and patient outcomes. DESIGN: Multicenter retrospective analysis of a dataset comprising observations of IHCA outcomes pre pandemic (March 1, 2019 to February 29, 2020) versus pandemic (March 1, 2020 to February 28, 2021). SETTING: Data source was the ICU-RESUScitation Project ("ICU-RESUS;" NCT028374497), a prospective, multicenter, cluster randomized interventional trial. PATIENTS: Children (≤ 18 yr) who received cardiopulmonary resuscitation while admitted to the ICU and were enrolled in ICU-RESUS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 429 IHCAs meeting inclusion criteria, occurrence during the pandemic period was associated with higher frequency of hypotension as the immediate cause of arrest. Cardiac arrest physiology, cardiopulmonary resuscitation quality metrics, and postarrest physiologic and quality of care metrics were similar between the two periods. Survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline) occurred in 102 of 195 subjects (52%) during the pandemic compared with 140 of 234 (60%) pre pandemic ( p = 0.12). Among survivors, occurrence of IHCA during the pandemic period was associated with a greater increase in Functional Status Scale (FSS) (i.e., worsening) from baseline (1 [0-3] vs 0 [0-2]; p = 0.01). After adjustment for confounders, IHCA survival during the pandemic period was associated with a greater increase in FSS from baseline (+1.19 [95% CI, 0.35-2.04] FSS points; p = 0.006) and higher odds of a new FSS-defined morbidity (adjusted odds ratio, 1.88 [95% CI, 1.03-3.46]; p = 0.04). CONCLUSIONS: Using the ICU-RESUS dataset, we found that relative to the year prior, pediatric IHCA during the first year of the COVID-19 pandemic was associated with greater worsening of functional status and higher odds of new functional morbidity among survivors.

Weight-Based Versus Flat Dosing of Epinephrine During Cardiac Arrest in the PICU: A Multicenter Survey.

OBJECTIVES: Pediatric Advanced Life Support (PALS) guidelines include weight-based epinephrine dosing recommendations of 0.01 mg/kg with a maximum of 1 mg, which corresponds to a weight of 100 kg. Actual practice patterns are unknown. DESIGN: Multicenter cross-sectional survey regarding institutional practices for the transition from weight-based to flat dosing of epinephrine during cardiopulmonary resuscitation in PICUs. Exploratory analyses compared epinephrine dosing practices with several institutional characteristics using Fisher exact test. SETTING: Internet-based survey. SUBJECTS: U.S. PICU representatives (one per institution) involved in resuscitation systems of care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 137 institutions surveyed, 68 (50%) responded. Most responding institutions are freestanding children's hospitals or dedicated children's hospitals within combined adult/pediatric hospitals (67; 99%); 55 (81%) are academic and 41 (60%) have PICU fellowship programs. Among respondents, institutional roles include PICU medical director (13; 19%), resuscitation committee member (23; 34%), and attending physician with interest in resuscitation (21; 31%). When choosing between weight-based and flat dosing, 64 respondents (94%) report using patient weight, 23 (34%) patient age, and five (7%) patient pubertal stage. Among those reporting using weight, 28 (44%) switch at 50 to less than 60 kg, 17 (27%) at 60 to less than 80 kg, five (8%) at 80 to less than 100 kg, and eight (12%) at greater than or equal to 100 kg. Among those reporting using age, four (17%) switch at 14 to less than 16 years, five (22%) at 16 to less than 18, and six (26%) at greater than or equal to 18. Twenty-nine respondents (43%) report using ideal body weight when dosing epinephrine in obese patients. Using patient age in choosing epinephrine dosing is more common in institutions that require Advanced Cardiac Life Support (ACLS) certification for some/all code team responders compared with institutions that do not require ACLS certification (52% vs 22%; p = 0.02). CONCLUSIONS: The majority of PICUs surveyed report epinephrine dosing practices that are inconsistent with PALS guidelines.

Pediatric Resuscitation Practices During the Coronavirus Disease 2019 Pandemic.

OBJECTIVES: While most pediatric coronavirus disease 2019 cases are not life threatening, some children have severe disease requiring emergent resuscitative interventions. Resuscitation events present risks to healthcare provider safety and the potential for compromised patient care. Current resuscitation practices and policies for children with suspected/confirmed coronavirus disease 2019 are unknown. DESIGN: Multi-institutional survey regarding inpatient resuscitation practices during the coronavirus disease 2019 pandemic. SETTING: Internet-based survey. SUBJECTS: U.S. PICU representatives (one per institution) involved in resuscitation system planning and oversight. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 130 institutions surveyed, 78 (60%) responded. Forty-eight centers (62%) had admitted coronavirus disease 2019 patients; 26 (33%) reported code team activation for patients with suspected/confirmed coronavirus disease 2019. Sixty-seven respondents (86%) implemented changes to inpatient emergency response systems. The most common changes were as follows: limited number of personnel entering patient rooms (75; 96%), limited resident involvement (71; 91%), and new or refined team roles (74; 95%). New or adapted technology is being used for coronavirus disease 2019 resuscitations in 58 centers (74%). Most institutions (57; 73%) are using enhanced personal protective equipment for all coronavirus disease 2019 resuscitation events; 18 (23%) have personal protective equipment policies dependent on the performance of aerosol generating procedures. Due to coronavirus disease 2019, most respondents are intubating earlier during cardiopulmonary resuscitation (56; 72%), utilizing video laryngoscopy (67; 86%), pausing chest compressions during laryngoscopy (56; 72%), and leaving patients connected to the ventilator during cardiopulmonary resuscitation (56; 72%). Responses were varied regarding airway personnel, prone cardiopulmonary resuscitation, ventilation strategy during cardiopulmonary resuscitation without an airway in place, and extracorporeal cardiopulmonary resuscitation. Most institutions (46; 59%) do not have policies regarding limitations of resuscitation efforts in coronavirus disease 2019 patients. CONCLUSIONS: Most U.S. pediatric institutions rapidly adapted their resuscitation systems and practices in response to the coronavirus disease 2019 pandemic. Changes were commonly related to team members and roles, personal protective equipment, and airway and breathing management, reflecting attempts to balance quality resuscitation with healthcare provider safety.

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.

Prevalence and Outcomes of Pediatric In-Hospital Cardiac Arrest Associated With Pulmonary Hypertension.

OBJECTIVES: In adult in-hospital cardiac arrest, pulmonary hypertension is associated with worse outcomes, but pulmonary hypertension-associated in-hospital cardiac arrest has not been well studied in children. The objective of this study was to determine the prevalence of pulmonary hypertension among children with in-hospital cardiac arrest and its impact on outcomes. DESIGN: Retrospective single-center cohort study. SETTING: PICU of a quaternary care, academic children's hospital. PATIENTS: Children (<18 yr old) receiving greater than or equal to 1 minute of cardiopulmonary resuscitation (cardiopulmonary resuscitation) for an index in-hospital cardiac arrest with an echocardiogram in the 48 hours preceding in-hospital cardiac arrest, excluding those with cyanotic congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 284 in-hospital cardiac arrest subjects, 57 (20%) had evaluable echocardiograms, which were analyzed by a cardiologist blinded to patient characteristics. Pulmonary hypertension was present in 20 of 57 (35%); nine of 20 (45%) had no prior pulmonary hypertension history. Children with pulmonary hypertension had worse right ventricular systolic function, measured by fractional area change (p = 0.005) and right ventricular global longitudinal strain (p = 0.046); more right ventricular dilation (p = 0.010); and better left ventricular systolic function (p = 0.001). Children with pulmonary hypertension were more likely to have abnormal baseline functional status and a history of chronic lung disease or acyanotic congenital heart disease and less likely to have sepsis or acute kidney injury. Children with pulmonary hypertension were more likely to have an initial rhythm of pulseless electrical activity or asystole and were more frequently treated with inhaled nitric oxide (80% vs 32%; p < 0.001) at the time of cardiopulmonary resuscitation. On multivariable analysis, pulmonary hypertension was not associated with event survival (14/20 [70%] vs 24/37 [65%]; adjusted odds ratio, 1.30 [CI95, 0.25-6.69]; p = 0.77) or survival to discharge (8/20 [40%] vs 10/37 [27%]; adjusted odds ratio, 1.17 [CI95, 0.22-6.44]; p = 0.85). CONCLUSIONS: Pulmonary hypertension physiology preceding pediatric in-hospital cardiac arrest may be more common than previously described. Among this cohort with a high frequency of inhaled nitric oxide treatment during cardiopulmonary resuscitation, pulmonary hypertension was not associated with survival outcomes.

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.

Hemodynamic-Directed Cardiopulmonary Resuscitation Improves Neurologic Outcomes and Mitochondrial Function in the Heart and Brain.

OBJECTIVES: Less than half of the thousands of children who suffer in-hospital cardiac arrests annually survive, and neurologic injury is common among survivors. Hemodynamic-directed cardiopulmonary resuscitation improves short-term survival, but its impact on longer term survival and mitochondrial respiration-a potential neurotherapeutic target-remains unknown. The primary objectives of this study were to compare rates of 24-hour survival with favorable neurologic outcome after cardiac arrest treated with hemodynamic-directed cardiopulmonary resuscitation versus standard depth-guided cardiopulmonary resuscitation and to compare brain and heart mitochondrial respiration between groups 24 hours after resuscitation. DESIGN: Randomized preclinical large animal trial. SETTING: A large animal resuscitation laboratory at a large academic children's hospital. SUBJECTS: Twenty-eight 4-week-old female piglets (8-11 kg). INTERVENTIONS: Twenty-two swine underwent 7 minutes of asphyxia followed by ventricular fibrillation and randomized treatment with either hemodynamic-directed cardiopulmonary resuscitation (n = 10; compression depth titrated to aortic systolic pressure of 90 mm Hg, vasopressors titrated to coronary perfusion pressure ≥ 20 mm Hg) or depth-guided cardiopulmonary resuscitation (n = 12; depth 1/3 chest diameter, epinephrine every 4 min). Six animals (sham group) underwent anesthesia and instrumentation without cardiac arrest. The primary outcomes were favorable neurologic outcome (swine Cerebral Performance Category ≤ 2) and mitochondrial maximal oxidative phosphorylation utilizing substrate for complex I and complex II (OXPHOSCI+CII) in the cerebral cortex and hippocampus. MEASUREMENTS AND MAIN RESULTS: Favorable neurologic outcome was more likely with hemodynamic-directed cardiopulmonary resuscitation (7/10) than depth-guided cardiopulmonary resuscitation (1/12; p = 0.006). Hemodynamic-directed cardiopulmonary resuscitation resulted in higher intra-arrest coronary perfusion pressure, aortic pressures, and brain tissue oxygenation. Hemodynamic-directed cardiopulmonary resuscitation resulted in higher OXPHOSCI+CII (pmol oxygen/s × mg/citrate synthase) in the cortex (6.00 ± 0.28 vs 3.88 ± 0.43; p < 0.05) and hippocampus (6.26 ± 0.67 vs 3.55 ± 0.65; p < 0.05) and higher complex I respiration (pmol oxygen/s × mg) in the right (20.62 ± 1.06 vs 15.88 ± 0.81; p < 0.05) and left ventricles (20.14 ± 1.40 vs 14.17 ± 1.53; p < 0.05). CONCLUSIONS: In a model of asphyxia-associated pediatric cardiac arrest, hemodynamic-directed cardiopulmonary resuscitation increases rates of 24-hour survival with favorable neurologic outcome, intra-arrest hemodynamics, and cerebral and myocardial mitochondrial respiration.

Pediatric In-Hospital Cardiac Arrest Secondary to Acute Pulmonary Embolism.

OBJECTIVES: Pulmonary embolism is a rarely reported and potentially treatable cause of cardiac arrest in children and adolescents. The objective of this case series is to describe the course of five adolescent patients with in-hospital cardiac arrest secondary to pulmonary embolism. DESIGN: Case series. SETTING: Single, large academic children's hospital. PATIENTS: All patients under the age of 18 years (n = 5) who experienced an in-hospital cardiac arrest due to apparent pulmonary embolism from August 1, 2013, to July 31, 2017. INTERVENTIONS: All five patients received systemic thrombolytic therapy (IV tissue plasminogen activator) during cardiac arrest or periarrest during ongoing resuscitation efforts. MEASUREMENTS AND MAIN RESULTS: Five adolescent patients, 15-17 years old, were treated for pulmonary embolism-related cardiac arrests during the study period. These accounted for 6.3% of all children and 25% of adolescents (12-17 yr old) receiving at least 5 minutes of in-hospital cardiopulmonary resuscitation during the study period. All five had venous thromboembolism risk factors. Two patients had known, extensive venous thrombi at the time of cardiac arrest, and one was undergoing angiography at the time of arrest. The diagnoses of pulmonary embolism were based on clinical suspicion, bedside echocardiography (n = 4), and low end-tidal CO2 levels relative to arterial CO2 values (n = 5). IV tissue plasminogen activator was administered during cardiopulmonary resuscitation in three patients and after the return of spontaneous circulation, in the setting of severe hemodynamic instability, in the other two patients. Four of five patients were successfully resuscitated and survived to hospital discharge. CONCLUSIONS: Pulmonary embolism was recognized as the etiology of multiple adolescent cardiac arrests in this single-center series and may be more common than previously reported. Recognition, high-quality cardiopulmonary resuscitation, and treatment with thrombolytic therapy resulted in survival in four of five patients.

Variability in the implementation of rapid response teams at academic American pediatric hospitals.

Pediatric rapid response teams have become standard over the past decade, but are organized heterogeneously at US academic hospitals, with rare financial support. To compare rapid response team efficacy, pediatric hospitals should agree on standard outcome measures, whether it be a standard definition of floor arrest or of clinical deterioration.