Justin Hotz

Evaluating Risk Factors for Pediatric Post-extubation Upper Airway Obstruction Using a Physiology-based Tool

RATIONALE Subglottic edema is the most common cause of pediatric extubation failure, but few studies have confirmed risk factors or prevention strategies. This may be due to subjective assessment of stridor or inability to differentiate supraglottic from subglottic disease. OBJECTIVES Objective 1 was to assess the utility of calibrated respiratory inductance plethysmography (RIP) and esophageal manometry to identify clinically significant post-extubation upper airway obstruction (UAO) and differentiate subglottic from supraglottic UAO. Objective 2 was to identify risk factors for subglottic UAO, stratified by cuffed versus uncuffed endotracheal tubes (ETTs). METHODS We conducted a single-center prospective study of children receiving mechanical ventilation. UAO was defined by inspiratory flow limitation (measured by RIP and esophageal manometry) and classified as subglottic or supraglottic based on airway maneuver response. Clinicians performed simultaneous blinded clinical UAO assessment at the bedside. MEASUREMENTS AND MAIN RESULTS A total of 409 children were included, 98 of whom had post-extubation UAO and 49 (12%) of whom were subglottic. The reintubation rate was 34 (8.3%) of 409, with 14 (41%) of these 34 attributable to subglottic UAO. Five minutes after extubation, RIP and esophageal manometry better identified patients who subsequently received UAO treatment than clinical UAO assessment (P < 0.006). Risk factors independently associated with subglottic UAO included low cuff leak volume or high preextubation leak pressure, poor sedation, and preexisting UAO (P < 0.04) for cuffed ETTs; and age (range, 1 mo to 5 yr) for uncuffed ETTs (P < 0.04). For uncuffed ETTs, the presence or absence of preextubation leak was not associated with subglottic UAO. CONCLUSIONS RIP and esophageal manometry can objectively identify subglottic UAO after extubation. Using this technique, preextubation leak pressures or cuff leak volumes predict subglottic UAO in children, but only if the ETT is cuffed.

The Relationship between High Flow Nasal Cannula Flow Rate and Effort of Breathing in Children

Objective To use an objective metric of effort of breathing to determine optimal high flow nasal cannula (HFNC) flow rates in children <3 years of age. Study design Single‐center prospective trial in a 24‐bed pediatric intensive care unit of children <3 years of age on HFNC. We measured the percent change in pressure•rate product (PRP) (an objective measure of effort of breathing) as a function of weight‐indexed flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/minute. For a subgroup of patients, 2 different HFNC delivery systems (Fisher & Paykel [Auckland, New Zealand] and Vapotherm [Exeter, New Hampshire]) were compared. Results Twenty‐one patients (49 titration episodes) were studied. The most common diagnoses were bronchiolitis and pneumonia. Overall, there was a significant difference in the percent change in PRP from baseline (of 0.5 L/kg/minute) with increasing flow rates for the entire cohort (P < .001) with largest change at 2.0 L/kg/min (−21%). Subgroup analyses showed no significant difference in percent change in PRP from baseline when comparing the 2 different HFNC delivery systems (P = .12). Patients ≤8 kg experienced a larger percent change in PRP as HFNC flow rates were increased (P = .001) than patients >8 kg. Conclusions The optimal HFNC flow rate to reduce effort of breathing in infants and young children is approximately 1.5–2.0 L/kg/minute with more benefit seen in children ≤8 kg.

Respiratory inductance plethysmography calibration for pediatric upper airway obstruction: an animal model

Background:We sought to determine optimal methods of respiratory inductance plethysmography (RIP) flow calibration for application to pediatric postextubation upper airway obstruction.Methods:We measured RIP, spirometry, and esophageal manometry in spontaneously breathing, intubated Rhesus monkeys with increasing inspiratory resistance. RIP calibration was based on: ΔµVao ≈ M[ΔµVRC + K(ΔµVAB)] where K establishes the relationship between the uncalibrated rib cage (ΔµVRC) and abdominal (ΔµVAB) RIP signals. We calculated K during (i) isovolume maneuvers during a negative inspiratory force (NIF), (ii) quantitative diagnostic calibration (QDC) during (a) tidal breathing, (b) continuous positive airway pressure (CPAP), and (c) increasing degrees of upper airway obstruction (UAO). We compared the calibrated RIP flow waveform to spirometry quantitatively and qualitatively.Results:Isovolume calibrated RIP flow tracings were more accurate (against spirometry) both quantitatively and qualitatively than those from QDC (P < 0.0001), with bigger differences as UAO worsened. Isovolume calibration yielded nearly identical clinical interpretation of inspiratory flow limitation as spirometry.Conclusion:In an animal model of pediatric UAO, isovolume calibrated RIP flow tracings are accurate against spirometry. QDC during tidal breathing yields poor RIP flow calibration, particularly as UAO worsens. Routine use of a NIF maneuver before extubation affords the opportunity to use RIP to study postextubation UAO in children.

Risk Factors for Pediatric Extubation Failure: The Importance of Respiratory Muscle Strength

Objective: Respiratory muscle weakness frequently develops during mechanical ventilation, although in children there are limited data about its prevalence and whether it is associated with extubation outcomes. We sought to identify risk factors for pediatric extubation failure, with specific attention to respiratory muscle strength. Design: Secondary analysis of prospectively collected data. Setting: Tertiary care PICU. Patients: Four hundred nine mechanically ventilated children. Interventions: Respiratory measurements using esophageal manometry and respiratory inductance plethysmography were made preextubation during airway occlusion and on continuous positive airway pressure of 5 and pressure support of 10 above positive end-expiratory pressure 5 cm H2O, as well as 5 and 60 minutes postextubation. Measurements and Main Results: Thirty-four patients (8.3%) were reintubated within 48 hours of extubation. Reintubation risk factors included lower maximum airway pressure during airway occlusion (aPiMax) preextubation, longer length of ventilation, postextubation upper airway obstruction, high respiratory effort postextubation (pressure rate product, pressure time product, tension time index), and high postextubation phase angle. Nearly 35% of children had diminished respiratory muscle strength (aPiMax ⩽ 30 cm H2O) at the time of extubation, and were nearly three times more likely to be reintubated than those with preserved strength (aPiMax > 30 cm H2O; 14% vs 5.5%; p = 0.006). Reintubation rates exceeded 20% when children with low aPiMax had moderately elevated effort after extubation (pressure rate product > 500), whereas children with preserved aPiMax had reintubation rates greater than 20% only when postextubation effort was very high (pressure rate product > 1,000). When children developed postextubation upper airway obstruction, reintubation rates were 47.4% for those with low aPiMax compared to 15.4% for those with preserved aPiMax (p = 0.02). Multivariable risk factors for reintubation included acute neurologic disease, lower aPiMax, postextubation upper airway obstruction, higher preextubation positive end-expiratory pressure, higher postextubation pressure rate product, and lower height. Conclusions: Neuromuscular weakness at the time of extubation was common in children and was independently associated with reintubation, particularly when postextubation effort was high.

Delivery of Epinephrine in the Vapor Phase for the Treatment of Croup.

Objectives: The Vapotherm system delivers high humidity to the airway of patients by using semipermeable tubules where heated liquid water is in contact with air. The humidified air is conducted to the patient via a heated tube. Preliminary clinical observations in infants with croup suggested that epinephrine added to the water supplying the humidity was delivered successfully in the vapor phase. The purpose of this study was to evaluate the efficiency of the delivery of epinephrine in the vapor phase and to develop the feasibility criteria for a clinical pilot study. Design: Thirty milligrams of epinephrine in a 1-L bag of sterile water was used as the humidification source for a Vapotherm 2000i. The output of the heated circuit was condensed and collected into a small Erlenmeyer flask via a metal coil while the whole collection system was submerged in an ice slurry to maintain the outflow temperature from the flask between 0°C and 2°C. The in vitro system was tested at 40°C with flows of 5, 10, and 15 L/min and L-epinephrine concentrations of 15, 30, and 60 mg/L. Each test was duplicated at each of the six conditions. Setting: Academic children’s hospital research laboratory. Patients: None. Interventions: None. Measurements and Main Results: The system recovered more than 90% of the water vapor from the fully saturated air at 40°C. The epinephrine concentration recovery quantified by ultraviolet-visible spectrophotometry was 23.9% (27.5–20.4%) (mean and range) of the initial concentration. At flows of 5, 10, and 15 L/min, the delivery of epinephrine would be 1.8, 3.6, and 4.2 &mgr;g/min, respectively, which is in the therapeutic range used for parenteral infusion in young children. Conclusions: The Vapotherm system can be used to deliver epinephrine in pharmacological doses to the respiratory system as a vapor and thus as an alternative to droplets by conventional nebulization.

Mainstream capnography system for nonintubated children in the postanesthesia care unit: Performance with changing flow rates, and a comparison to side stream capnography

Monitoring of exhaled carbon dioxide (CO2) in nonintubated patients is challenging. We compared the precision of a mainstream mask capnography to side stream sampling nasal cannula capnography. In addition, we compared the effect of gas flow rates on the measured exhaled CO2 between mainstream mask and side stream nasal cannula capnography.

Accuracy of Transcutaneous Carbon Dioxide Levels in Comparison to Arterial Carbon Dioxide Levels in Critically Ill Children

BACKGROUND: Widespread use of transcutaneous PCO2 (PtcCO2) monitoring is currently limited by concerns many practitioners have regarding accuracy. We compared the accuracy of PtcCO2 with that of PaCO2 measurements in critically ill children, and we investigated whether clinical conditions associated with low cardiac output or increased subcutaneous tissue affect this accuracy. METHODS: We performed a single-center prospective study of critically ill children placed on transcutaneous monitoring. RESULTS: There were 184 children enrolled with paired PaCO2 and PtcCO2 values. Subjects had a median age of 31.8 mo (interquartile range 3.5–123.3 mo). Most children were mechanically ventilated (n = 161, 87.5%), and many had cardiac disease (n = 76, 41.3%). The median PaCO2 was 44 mm Hg (interquartile range 39–51 mm Hg). The mean bias between PaCO2 and PtcCO2 was 0.6 mm Hg with 95% limits of agreement from −13.6 to 14.7 mm Hg. The PtcCO2 and PaCO2 were within ±5 mm Hg in 126 (68.5%) measurements. In multivariable modeling, cyanotic heart disease (odds ratio 3.5, 95% CI 1.2–10, P = .02) and monitor number 2 (odds ratio 3.8 95% CI 1.3–10.5, P = .01) remained associated with PtcCO2 ≥ 5 mm Hg higher than PaCO2. Serum lactate, fluid balance, renal failure, obesity, vasoactive-inotrope score, and acyanotic heart disease were not associated with high or low PtcCO2 values. In 130 children with a second paired PtcCO2 and PaCO2 measurement, predicting the second measured PaCO2 by subtracting the initial observed difference between the PtcCO2 and PaCO2 from the subsequent measured PtcCO2 decreased the mean bias between observed and predicted PaCO2 to 0.2 mm Hg and the 95% limits of agreement to −9.4 to 9.7 mm Hg. CONCLUSIONS: PtcCO2 provides an acceptable estimate of PaCO2 in many critically ill children, including those with clinical conditions that may be associated with low cardiac output or increased subcutaneous tissue, although it does not perform as well in children with cyanotic heart disease. PtcCO2 may be a useful adjunct monitoring method, but it cannot reliably replace PaCO2 measurement.

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 manufacturers 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.

Inhaled Treprostinil Drug Delivery During Mechanical Ventilation and Spontaneous Breathing Using Two Different Nebulizers

Objectives: To determine the feasibility of delivering inhaled treprostinil during mechanical ventilation and spontaneous unassisted ventilation using the Tyvaso Inhalation System and the vibrating mesh nebulizer. We sought to compare differences in fine particle fraction, and absolute inhaled treprostinil mass delivered to neonatal, pediatric, and adult models affixed with a face mask, conventional, and high-frequency ventilation between Tyvaso Inhalation System and with different nebulizer locations between Tyvaso Inhalation System and vibrating mesh nebulizer. Design: Fine particle fraction was first determined via impaction with both the Tyvaso Inhalation System and vibrating mesh nebulizer. Next, a test lung configured with neonatal, pediatric, and adult mechanics and a filter to capture medication was attached to a realistic face model during spontaneous breathing or an endotracheal tube during conventional ventilation and high-frequency oscillator ventilator. Inhaled treprostinil was then nebulized with both the Tyvaso Inhalation System and vibrating mesh nebulizer, and the filter was analyzed via high-performance liquid chromatography. Testing was done in triplicate. Independent two-sample t tests were used to compare mean fine particle fraction and inhaled mass between devices. Analysis of variance with Tukey post hoc tests were used to compare within device differences. Setting: Academic children’s hospital aerosol research laboratory. Measurements and Main Results: Fine particle fraction was not different between the Tyvaso Inhalation System and vibrating mesh nebulizer (0.78 ± 0.04 vs 0.77 ± 0.08, respectively; p = 0.79). The vibrating mesh nebulizer delivered the same or greater inhaled treprostinil than the Tyvaso Inhalation System in every simulated model and condition. When using the vibrating mesh nebulizer, delivery was highest when using high-frequency oscillator ventilator in the neonatal and pediatric models, and with the nebulizer in the distal position in the adult model. Conclusions: The vibrating mesh nebulizer is a suitable alternative to the Tyvaso Inhalation System for inhaled treprostinil delivery. Fine particle fraction is similar between devices, and vibrating mesh nebulizer delivery meets or exceeds delivery of the Tyvaso Inhalation System. Delivery for infants and children during high-frequency oscillator ventilator with the vibrating mesh nebulizer may result in higher than expected dosages.