High-Flow Nasal Cannula Reduces Effort of Breathing But Not Consistently via Positive End-Expiratory Pressure.

BACKGROUND: High-flow nasal cannula (HFNC) therapy reduces the effort of breathing in patients with bronchiolitis, but the mechanisms are not understood. Theorized mechanisms include dead space washout and positive end-expiratory pressure (PEEP) application. RESEARCH QUESTION: What are the mechanisms of action of HFNC therapy in patients with bronchiolitis? STUDY DESIGN AND METHODS: Prospective, single-center study of children 3 years of age or younger with bronchiolitis from January 2020 through March 2021. Flow was titrated between 0.5 and 2 L/kg/min. Electrical impedance tomography measured end-expiratory lung impedance (EELZ) change as an end-expiratory lung volume (EELV) change surrogate and change in tidal impedance difference (ΔZ) as a tidal volume (VT) surrogate. A subset showed manometry measuring esophageal pressure change (ΔPes; transpulmonary pressure surrogate) and pressure rate product (PRP; effort of breathing metric). We hypothesized that EELV and VT would not change and that effort would reduce via respiratory rate (not ΔPes). Measurements were reported as the difference from 0.5 L/kg/min. RESULTS: We studied 22 patients in total, 10 with esophageal manometry. Median EELZ increased by 0.36 arbitrary unit (AU), 2.42 AU, and 4.8 AU at 1 L/kg/min, 1.5 L/kg/min, and 2 L/kg/min (P = .01, 2 L/kg/min vs 0.5 L/kg/min), which corresponded to a median increase in EELV of 1.8 mL/kg between 0.5 and 2 L/kg/min. Seven patients showed an increase in EELZ of > 5 AU, 12 showed no change in EELZ (± 5 AU), and three showed a decrease in EELZ of > 5 AU. ΔZ (ie, VT) did not change from 0.5 L/kg/min to 2 L/kg/min (median change, 0.29 AU; P = .48). Median PRP decreased by 78 cm H2O/min from 0.5 L/kg/min to 2 L/kg/min (P = .02), with all patients demonstrating a reduction in PRP, with a nonsignificant change in ΔPes (P = .68). INTERPRETATION: Increasing HFNC in children with bronchiolitis reduces the effort of breathing, but no consistent increase occurs in end-expiratory lung volume and no significant change occurs in VT or transpulmonary pressure. This suggests that PEEP application is not the primary mechanism of action of HFNC in children with bronchiolitis.

A Phase II randomized controlled trial for lung and diaphragm protective ventilation (Real-time Effort Driven VENTilator management).

Lung Protective Mechanical Ventilation (MV) of critically ill adults and children is lifesaving but it may decrease diaphragm contraction and promote Ventilator Induced Diaphragm Dysfunction (VIDD). An ideal MV strategy would balance lung and diaphragm protection. Building off a Phase I pilot study, we are conducting a Phase II controlled clinical trial that seeks to understand the evolution of VIDD in critically ill children and test whether a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)) can balance lung and diaphragm protective ventilation to reduce time on MV. REDvent systematically adjusts PEEP, FiO2, inspiratory pressure, tidal volume and rate, and uses real-time measures from esophageal manometry to target normal levels of patient effort of breathing. This trial targets 276 children with pulmonary parenchymal disease. Patients are randomized to REDvent vs. usual care for the acute phase of MV (intubation to first Spontaneous Breathing Trial (SBT)). Patients in either group who fail their first SBT will be randomized to REDvent vs usual care for weaning phase management (interval from first SBT to passing SBT). The primary clinical outcome is length of weaning, with several mechanistic outcomes. Upon completion, this study will provide important information on the pathogenesis and timing of VIDD during MV in children and whether this computerized protocol targeting lung and diaphragm protection can lead to improvement in intermediate clinical outcomes. This will form the basis for a larger, Phase III multi-center study, powered for key clinical outcomes such as 28-day ventilator free days. Clinical Trials Registration: NCT03266016.

Symptomatic catheter-associated thrombosis in pediatric trauma patients: Choose your access wisely.

BACKGROUND: Traumatic injury and the presence of a central venous catheter are 2 of the strongest risk factors for venous thromboembolism in children. The purpose of this study was to determine the incidence of symptomatic, catheter-associated thrombosis in critically injured children. We hypothesized that femoral venous catheters are associated with a greater rate of thrombotic complications when compared with all other central venous access points. METHODS: We reviewed a retrospective cohort (2006-2016) of injured children (≤18 years) admitted to a pediatric intensive care unit with central access placed ≤7 days from admission. Symptomatic, catheter-associated thrombosis was determined by radiographic evidence. Poisson regression was used to compare the incidence of catheter-associated thrombosis per 1,000 catheter days between femoral and nonfemoral catheters. All comparisons were 2-tailed with α = 0.05. RESULTS: We examined 209 pediatric trauma patients with central access (65% femoral, 19% subclavian, 11% arm vein, and 5% internal jugular). Femoral catheters were removed earlier (median [interquartile range] 4 [2-7] vs 8 [3-12] days, P < .001) and were larger in diameter (5 Fr [4-7] vs 4 Fr [4-4], P < .001) when compared with all other catheters. Catheter-associated thrombosis was more frequent in femoral versus nonfemoral catheters (18.4 vs 3.5 per 1,000 catheter days, P = .01). CONCLUSION: Femoral venous catheters are associated with a greater incidence of symptomatic, catheter-associated thrombosis in pediatric trauma patients. When central venous access is indicated for injured children, the femoral site should be avoided. If a femoral venous catheter is necessary, use of a smaller catheter should be considered.

Measurements Obtained From Esophageal Balloon Catheters Are Affected by the Esophageal Balloon Filling Volume in Children With ARDS.

BACKGROUND: Esophageal balloon inflation volume may affect the accuracy of transpulmo-nary pressure estimates in adults, but the effect is unknown in pediatrics. Using a combination bench and human study, we sought to determine a range of optimal filling volumes for esophageal balloon catheters and to derive a technique to inflate catheters to yield the most accurate estimates of pleural pressure. METHODS: In the laboratory study, we evaluated 4 pediatric and adult esophageal balloon catheters, a liquid-filled catheter, and a micro-tip catheter, both with and without a model esophagus. We compared the measured esophageal pressure for each type of catheter within a pressurized chamber. Esophageal balloon catheters were also tested by manipulating the esophageal balloon inflation volume, and we attempted to derive a filling-volume technique that would assure accuracy. We then tested the feasibility of this technique in 5 mechanically ventilated pediatric subjects with ARDS. RESULTS: In the laboratory study, smaller inflation volumes underestimated the chamber pressure at higher chamber pressures, and larger inflation volumes overestimated the chamber pressure at lower chamber pressures. Using an optimal filling-volume technique resulted in a mean total error that ranged from -0.53 to -0.10 cm H2O. The optimal filling-volume values for the pediatric catheters were 0.2-0.6 mL, and 0.4-0.8 mL for the adult catheters. When correctly positioned and calibrated, the micro-tip transducer and liquid-filled catheters were within ± 1 cm H2O of chamber pressure for all ranges of pressure. In the clinical study, high variability in measured esophageal pressure and subsequent transpulmonary pressure during exhalation and during inhalation was observed within the manufacturer's recommended esophageal balloon inflation ranges. CONCLUSIONS: Manufacturer-recommended esophageal balloon inflation ranges do not assure accuracy. Individual titration of esophageal balloon volume may improve accuracy. Better esophageal catheters are needed to provide reliable esophageal pressure measurements in children.

Volume and Pressure Delivery During Pediatric High-Frequency Oscillatory Ventilation.

OBJECTIVE: Identify variables independently associated with delivered tidal volume (VT) and measured mean airway pressure during high-frequency oscillatory ventilation across the range of pediatric endotracheal tube sizes. DESIGN: In vitro study. SETTING: Research laboratory. INTERVENTIONS: An in vitro bench model of the intubated pediatric respiratory system during high-frequency oscillatory ventilation was used to obtain delivered VT and mean airway pressure (in the distal lung) for various endotracheal tube sizes. Measurements were taken at different combinations of ventilator set mean airway pressure (Paw), amplitude (ΔP), frequency, and test lung compliance. Multiple regression analysis was used to construct multivariable models predicting delivered VT and mean airway pressure. MEASUREMENTS AND MAIN RESULTS: Variables independently associated with higher delivered VT for all endotracheal tube sizes include higher ΔP (p < 0.001), lower frequency (p < 0.001), and higher test lung compliance (p < 0.001). A multiplicative interaction between frequency and ΔP magnifies the delivered VT when ΔP is high and frequency is low (p < 0.001). Delivered mean airway pressure becomes lower than set Paw as ΔP increases (p < 0.001) and frequency increases (p < 0.05). Ventilator set Paw is the largest determinant of delivered mean airway pressure; however, increasing ΔP resulted in a lower delivered mean airway pressure. For example, in a 4.0 mm ID endotracheal tube, increasing ΔP by 10 cm H2O resulted in an average decrease of delivered mean airway pressure by 4.5%. CONCLUSIONS: This is the first study to quantify the interaction between ΔP and frequency in delivered VT and the effect of ΔP and frequency on delivered mean airway pressure. These results demonstrate the need to measure or estimate VT and delivered pressures during high-frequency oscillatory ventilation and may be useful in determining optimal strategies for lung protective ventilation during high-frequency oscillatory ventilation.

Procalcitonin to Detect Suspected Bacterial Infections in the PICU.

OBJECTIVES: Nonspecific clinical symptoms frequently lead to suspicion of bacterial infection in critically ill children. Clinicians send bacterial cultures for suspected infection and begin an empiric course of antibiotics while microbiology results are pending. We investigated whether the biomarker procalcitonin could be useful to predict confirmed bacterial infection in critically ill children in the PICU, before culture results are available. DESIGN: Prospective, blinded single-center study. SETTING: Tertiary PICU and cardiothoracic ICU. PATIENTS: There were one hundred forty-four patients with suspected bacterial infections that had bacterial cultures sent by clinicians. INTERVENTIONS: Procalcitonin samples were obtained at three time intervals: as close to the time of the initial culture as possible (up to 12 hr after) and 24 and 72 hours after the initial culture. Patients were stratified into clinical outcome groups based on microbiology results and clinical symptoms using Centers for Disease Control and Prevention criteria. These assignments were blinded to procalcitonin levels. Primary outcome was the presence of culture-proven bacterial infection. MEASUREMENTS AND MAIN RESULTS: There was a statistically significant difference in initial and subsequent median procalcitonin values between patients with confirmed bacterial infections and patients with low suspicion of bacterial infection (p < 0.02). However, there was extremely high variability in procalcitonin values among all groups. Procalcitonin had only a fair ability to predict bacterial infection, with area under the curve of receiver operating characteristic plots ranging between 0.63 and 0.71. When using serial procalcitonin values to predict bacterial infection, positive likelihood ratios were near 1 and negative likelihood ratios were between 0.3 and 0.4. CONCLUSIONS: Procalcitonin levels were higher in children with documented confirmed bacterial infection as compared with those with low suspicion of infection. However, neither single nor serial procalcitonin measurements were able to predict the presence or absence of confirmed bacterial infection with enough certainty to be clinically useful as to recommend initiating or withholding antibiotics.

Increase in oxygen consumption after albuterol inhalation in ventilated infants and children.

OBJECTIVE: To determine if inhaled albuterol (salbutamol) increases oxygen consumption (V'O2) in children and, if so, the duration of this effect. DESIGN: Oxygen consumption was measured by indirect calorimetry using the Argon dilution technique with a respiratory mass spectrometer. After measurement of baseline values, albuterol was administered and subsequent measurements were performed at 10 minutes, 1 hour, 2 hours, 3 hours, and 4 hours. SETTING: Multidisciplinary PICU in a university teaching hospital. PATIENTS: Eleven intubated infants and children (five girls, six boys) with a mean age of 20 months (range, 1 mo to 8 yr) and a mean weight of 10.7 kg (range, 3.1-23 kg) who required therapeutic albuterol inhalations. INTERVENTION: Nine hundred micrograms of albuterol (10 puffs) was administered by a metered-dose inhaler into a spacer through the inspiratory arm of the ventilator circuit near to the patient, during 10 mechanically assisted breaths. MEASUREMENTS AND MAIN RESULTS: All children showed an increase in V'O2 within 10 minutes (mean increase 48.6%). The increased V'O2 was still elevated (42.3% above baseline) at 1 hour, but 3 hours after albuterol inhalation, the V'O2 was back to baseline in all patients. Heart rate increased significantly at 10 minutes, 1 hour, and 2 hours after inhalation. CONCLUSION: There is a large increase in V'O2 after albuterol inhalation. This effect lasts up to 3 hours.

Effort of breathing in children receiving high-flow nasal cannula.

OBJECTIVE: High-flow humidified nasal cannula is often used to provide noninvasive respiratory support in children. The effect of high-flow humidified nasal cannula on effort of breathing in children has not been objectively studied, and the mechanism by which respiratory support is provided remains unclear. This study uses an objective measure of effort of breathing (Pressure. Rate Product) to evaluate high-flow humidified nasal cannula in critically ill children. DESIGN: Prospective cohort study. SETTING: Quaternary care free-standing academic children's hospital. PATIENTS: ICU patients younger than 18 years receiving high-flow humidified nasal cannula or whom the medical team planned to extubate to high-flow humidified nasal cannula within 72 hours of enrollment. INTERVENTIONS: An esophageal pressure monitoring catheter was placed to measure pleural pressures via a Bicore CP-100 pulmonary mechanics monitor. Change in pleural pressure (ΔPes) and respiratory rate were measured on high-flow humidified nasal cannula at 2, 5, and 8 L/min. ΔPes and respiratory rate were multiplied to generate the Pressure.Rate Product, a well-established objective measure of effort of breathing. Baseline Pes, defined as pleural pressure at end exhalation during tidal breathing, reflected the positive pressure generated on each level of respiratory support. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients had measurements on high-flow humidified nasal cannula. Median age was 6.5 months (interquartile range, 1.3-15.5 mo). Median Pressure,Rate Product was lower on high-flow humidified nasal cannula 8 L/min (median, 329 cm H2O·min; interquartile range, 195-402) compared with high-flow humidified nasal cannula 5 L/min (median, 341; interquartile range, 232-475; p = 0.007) or high-flow humidified nasal cannula 2 L/min (median, 421; interquartile range, 233-621; p < 0.0001) and was lower on high-flow humidified nasal cannula 5 L/min compared with high-flow humidified nasal cannula 2 L/min (p = 0.01). Baseline Pes was higher on high-flow humidified nasal cannula 8 L/min than on high-flow humidified nasal cannula 2 L/min (p = 0.03). CONCLUSIONS: Increasing flow rates of high-flow humidified nasal cannula decreased effort of breathing in children, with the most significant impact seen from high-flow humidified nasal cannula 2 to 8 L/min. There are likely multiple mechanisms for this clinical effect, including generation of positive pressure and washout of airway dead space.

Infant botulism: a 30-year experience spanning the introduction of botulism immune globulin intravenous in the intensive care unit at Childrens Hospital Los Angeles.

OBJECTIVE: To report a tertiary care hospital's 30-year experience with the diagnosis, treatment, and outcome of infant botulism in the PICU before and after the availability of Botulism Immune Globulin Intravenous. METHODS: This was a retrospective medical chart review of the 67 patients who had received a diagnosis of infant botulism and were admitted to the ICU from 1976 to 2005. The ages on presentation, length of hospital stay, length of ICU stay, length of mechanical ventilation, and type of botulism toxin were recorded and compared for patients who had received Botulism Immune Globulin Intravenous and those who had not. On the basis of our results, conclusions were drawn regarding the effect of Botulism Immune Globulin Intravenous on the morbidity of infant botulism. RESULTS: Sixty-seven patients' charts were reviewed; 23 male and 29 female patients did not receive Botulism Immune Globulin Intravenous. Of patients who did not receive Botulism Immune Globulin Intravenous, the median age at presentation was 71 days, median length of hospital stay was 35 days, ICU stay was 24 days, and duration of mechanical ventilation was 17 days. A total of 40% had type A toxin, and 60% had type B toxin. There was a significant difference between patients with toxin types A and B in length of hospital stay but not length of ICU stay or mechanical ventilation. Patients with type A toxin were significantly older than patients with type B toxin. Fifteen children received Botulism Immune Globulin Intravenous. There were statistically significant differences in length of hospital stay, length of ICU stay, and length of mechanical ventilation between patients who received Botulism Immune Globulin Intravenous and those who did not. CONCLUSIONS: The use of Botulism Immune Globulin Intravenous significantly decreased the length of ICU stay, length of mechanical ventilation, and overall hospital stay in children with infant botulism.