Estimation of inspiratory effort using airway occlusion maneuvers in ventilated children: a secondary analysis of an ongoing randomized trial testing a lung and diaphragm protective ventilation strategy.

BACKGROUND: Monitoring respiratory effort in ventilated patients is important to balance lung and diaphragm protection. Esophageal manometry remains the gold standard for monitoring respiratory effort but is invasive and requires expertise for its measurement and interpretation. Airway pressures during occlusion maneuvers may provide an alternative, although pediatric data are limited. We sought to determine the correlation between change in esophageal pressure during tidal breathing (∆Pes) and airway pressure measured during three airway occlusion maneuvers: (1) expiratory occlusion pressure (Pocc), (2) airway occlusion pressure (P0.1), and (3) respiratory muscle pressure index (PMI) in children. We also sought to explore pediatric threshold values for these pressures to detect excessive or insufficient respiratory effort. METHODS: Secondary analysis of physiologic data from children between 1 month and 18 years of age with acute respiratory distress syndrome enrolled in an ongoing randomized clinical trial testing a lung and diaphragm protective ventilation strategy (REDvent, R01HL124666). ∆Pes, Pocc, P0.1, and PMI were measured. Repeated measure correlations were used to investigate correlation coefficients between ∆Pes and the three measures, and linear regression equations were generated to identify potential therapeutic thresholds. RESULTS: There were 653 inspiratory and 713 expiratory holds from 97 patients. Pocc had the strongest correlation with ∆Pes (r = 0.68), followed by PMI (r = 0.60) and P0.1 (r = 0.42). ∆Pes could be reliably estimated using the regression equation ∆Pes = 0.66 [Formula: see text] Pocc (R2 = 0.82), with Pocc cut-points having high specificity and moderate sensitivity to detect respective ∆Pes thresholds for high and low respiratory effort. There were minimal differences in the relationship between Pocc and ∆Pes based on age (infant, child, adolescent) or mode of ventilation (SIMV versus Pressure Support), although these differences were more apparent with P0.1 and PMI. CONCLUSIONS: Airway occlusion maneuvers may be appropriate alternatives to esophageal pressure measurement to estimate the inspiratory effort in children, and Pocc represents the most promising target. TRIAL REGISTRATION: NCT03266016; August 23, 2017.

Effort and work-of-breathing parameters strongly correlate with increased resistance in an animal model.

BACKGROUND: Effort of Breathing (EOB) calculations may be a reliable alternative to Work of Breathing (WOB) calculations in which Respiratory Inductance Plethysmography (RIP) replaces spirometry. We sought to compare EOB and WOB measurements in a nonhuman primate model of increasing extrathoracic inspiratory resistance simulating upper airway obstruction (UAO). METHODS: RIP, spirometry, and esophageal manometry were measured in spontaneously breathing, intubated Rhesus monkeys utilizing 11 calibrated resistors randomly applied for 2-min. EOB was calculated breath-by-breath as Pressure Rate Product (PRP) and Pressure Time Product (PTP). WOB was calculated from the Pressure-Volume curve based on spirometry (WOBSPIR) or RIP flow (WOBRIP). RESULTS: WOB, PRP and PTP showed similar linear increases when exposed to higher levels of resistive loads. When comparing WOBSPIR to WOBRIP, a similar strong correlation was seen for both signals as resistance increased and there were no statistically significant differences. CONCLUSION: EOB and WOB parameters utilizing esophageal manometry and RIP, independent of spirometry, showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. This allows several potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available. IMPACT: EOB and WOB parameters showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. There was a strong correlation between spirometry-based WOB versus RIP-based WOB. To date, it has remained untested as to whether EOB is a reliable alternative for WOB and if RIP can replace spirometry in these measurements. Our results enable additional potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available. Where spirometry is not available, there is no need to apply a facemask post extubation to a spontaneously breathing, non-intubated infant to make objective EOB measurements.

A 30-Minute Spontaneous Breathing Trial Misses Many Children Who Go On to Fail a 120-Minute Spontaneous Breathing Trial.

BACKGROUND: The optimal length of spontaneous breathing trials (SBTs) in children is unknown. RESEARCH QUESTIONS: What are the most common reasons for SBT failure in children, and when do they occur? Can clinical parameters at the 30-min mark of a 120-min SBT predict outcome? STUDY DESIGN AND METHODS: We performed a secondary analysis of a clinical trial in pediatric ARDS, in which 2-h SBTs are conducted daily. SBT failure is based on objective criteria, including esophageal manometry for effort of breathing, categorized as passage, early failure (≤ 30 min), or late failure (30-120 min). Spirometry was used to calculate respiratory rate (RR), tidal volume (Vt), and rapid shallow breathing index (RSBI), in addition to pulse oximetry and capnography. Predictive models evaluated parameters at 30 min against SBT outcome, using receiver operating characteristic plots and area under the curve. RESULTS: We included 100 children and 305 SBTs, with 42% of SBTs being successful, 32% failing within 30 min, and 25% failing between 30 and 120 min. Of the patients passing SBTs at 30 min, 40% went on to fail by 120 min. High respiratory effort (esophageal manometry) was present in > 80% of failed SBTs. At the 30-min mark, there were no clear thresholds for RR, Vt, RSBI, Fio2, oxygen saturation, or capnography that could reliably predict SBT outcome. Multivariable modeling identified RR (P < .001) and RSBI > 7 (P = .034) at 30 min, pre-SBT inspiratory pressure level (P = .009), and pre-SBT retractions (P = .042) as predictors for SBT failure, but this model performed poorly in an independent validation set with the receiver operating characteristic plot crossing the reference line (area under the curve, 0.67). INTERPRETATION: A 30-min SBT may be too short in children recovering from pediatric ARDS because many go on to fail between 30 and 120 min. Reassuring values of Vt, RR, and gas exchange at 30 min do not reliably predict SBT passage at 2 h, likely because they do not capture the effort of breathing. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03266016; URL: www. CLINICALTRIALS: gov.

A Network Meta-analysis of Dexamethasone for Preventing Postextubation Upper Airway Obstruction in Children.

Rationale: Periextubation corticosteroids are commonly used in children to prevent upper airway obstruction (UAO). However, the best timing and dose combination of corticosteroids is unknown. Objectives: To compare effectiveness of different corticosteroid regimens in preventing UAO and reintubation. Methods: MEDLINE, CINAHL, and Embase search identified randomized trials in children using corticosteroids to prevent UAO. All studies used dexamethasone. The studies were categorized based on timing of initiation of dexamethasone (early use: >12 h before extubation) and the dose (high dose: ⩾0.5 mg/kg/dose). We performed Bayesian network meta-analysis with studies grouped into four regimens: high dose, early use (HE); low dose, early use (LE); high dose, late use (HL); and low dose, late use. Results: Eight trials (n = 903) were included in the analysis. For preventing UAO (odds ratio; 95% credible interval), HE (0.13; 0.04-0.36), HL (0.39; 0.19-0.74), and LE (0.15; 0.04-0.58) regimens appear to be more effective than no dexamethasone (low certainty). HE and LE had the highest probability of being the top-ranked regimens for preventing UAO (surface under the cumulative ranking curve 0.901 and 0.808, respectively). For preventing reintubation, the effect estimate was imprecise for all four dexamethasone regimens compared with no dexamethasone (very low certainty). HE and LE were the top-ranked regimens (surface under the cumulative ranking curve 0.803 and 0.720, respectively) for preventing reintubation. Sensitivity analysis showed that regimens that started >12 hours before extubation were likely more effective than regimens started >6 hours before extubation. Conclusions: Periextubation dexamethasone can prevent postextubation UAO in children, but effectiveness is highly dependent on timing and dosing regimen. Early initiation (ideally >12 h before extubation) appears to be more important than the dose of dexamethasone. Ultimately, the specific steroid strategy should be personalized, considering the potential for adverse events associated with dexamethasone and the individual risk of UAO and reintubation.

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 New Trick for an Old Dog: L-Epinephrine Delivered Continuously in the Vapor Phase.

Inhaled L-epinephrine is a known treatment of severe croup and postextubation upper airway obstruction. L-epinephrine can be delivered continuously in the vapor phase, but the indications, safety, and efficacy of this novel practice have yet to be evaluated. Theoretical risks are tachycardia, hypertension, and dysrhythmias. The study objective was to describe patient characteristics and vital sign changes related to continuous vaporized L-epinephrine use in critically ill children with the hypothesis that it can be practically and safely administered to children with subglottic edema and lower airway obstruction. DESIGN: Retrospective cohort study. SETTING: PICU and cardiothoracic ICU in a tertiary academic children's hospital. PATIENTS: Patients age 0-21 years treated with continuous vaporized L-epinephrine from 2013 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Continuous vaporized L-epinephrine was administered 140 times to 129 subjects via a high-flow nasal oxygen device. The median age was 10.6 months (1.3; interquartile range, 4.8-17.1 mo). The most common indications were lower respiratory tract obstruction (45%), postextubation subglottic edema (31%), and croup (16%). Eighty-eight percent had no escalation of respiratory support within 24 hours of initiation of continuous vaporized L-epinephrine, 5% progressed to require endotracheal intubation, and 3% were reintubated within 24 hours of initiation of continuous vaporized L-epinephrine following an extubation attempt. After starting continuous vaporized L-epinephrine, 85% of subjects had a decrease in heart rate and 80% had a decrease in respiratory rate. Six subjects had an increase in heart rate, and eight had an increase in blood pressure of more than 20% from baseline. These subjects did not receive interventions specific to these vital sign changes, including discontinuation of continuous vaporized L-epinephrine. CONCLUSIONS: Continuous vaporized L-epinephrine was safely administered to critically ill children with most subjects demonstrating a decrease in heart rate, blood pressure, and respiratory rate.

Direction and Magnitude of Change in Plateau From Peak Pressure During Inspiratory Holds Can Identify the Degree of Spontaneous Effort and Elastic Workload in Ventilated Patients.

OBJECTIVES: Inspiratory holds with measures of airway pressure to estimate driving pressure (elastic work) are often limited to patients without respiratory effort. We sought to evaluate if measures of airway pressure during inspiratory holds could be used for patients with spontaneous respiratory effort during mechanical ventilation to estimate the degree of spontaneous effort and elastic work. DESIGN: We compared the direction and degree of change in airway pressure during inspiratory holds versus esophageal pressure through secondary analysis of physiologic data. SETTING: ICUs at Children's Hospital Los Angeles. PATIENTS: Children with pediatric acute respiratory distress syndrome with evidence of spontaneous respiration while on pressure control or pressure support ventilation. INTERVENTIONS: Inspiratory hold maneuvers. MEASUREMENTS AND MAIN RESULTS: From airway pressure, we defined "plateau - peak pressure" as Pmusc, index, which was divided into three categories for analysis (< -1 ["negative"], between -1 and 1 ["neutral"], and > 1 cm H2O ["positive"]). A total of 30 children (age 36.8 mo [16.1-70.3 mo]) from 65 study days, comprising 118 inspiratory holds were included. Pmusc, index was "negative" in 29 cases, was "neutral" in 17 cases, and was "positive" in 72 cases. As Pmusc, index went from negative to neutral to positive, there was larger negative deflection in esophageal pressure -5.0 (-8.2 to 1.9), -5.9 (-7.6 to 4.3), and -10.7 (-18.1 to 7.9) cm H2O (p < 0.0001), respectively. There was a correlation between max negative esophageal pressure and Pmusc, index (r = -0.52), and when Pmusc, index was greater than or equal to 7 cm H2O, the max negative esophageal pressure was greater than 10 cm H2O. There was a stronger correlation between Pmusc, index and markers of elastic work from esophageal pressure (r = 0.84). CONCLUSIONS: The magnitude of plateau minus peak pressure during an inspiratory hold is correlated with the degree of inspiratory effort, particularly for those with high elastic work. It may be useful to identify patients with excessively high effort or high driving pressure.

Frequency and Risk Factors for Reverse Triggering in Pediatric Acute Respiratory Distress Syndrome during Synchronized Intermittent Mandatory Ventilation.

Rationale: Reverse triggering (RT) occurs when respiratory effort begins after a mandatory breath is initiated by the ventilator. RT may exacerbate ventilator-induced lung injury and lead to breath stacking.Objectives: We sought to describe the frequency and risk factors for RT among patients with acute respiratory distress syndrome (ARDS) and identify risk factors for breath stacking.Methods: We performed a secondary analysis of physiologic data from children on synchronized intermittent mandatory pressure-controlled ventilation enrolled in a single-center randomized controlled trial for ARDS. When children had a spontaneous effort on esophageal manometry, waveforms were recorded and independently analyzed by two investigators to identify RT.Results: We included 81,990 breaths from 100 patient-days and 36 patients. Overall, 2.46% of breaths were RTs, occurring in 15/36 patients (41.6%). A higher tidal volume and a minimal difference between neural respiratory rate and set ventilator rate were independently associated with RT (P = 0.001) in multivariable modeling. Breath stacking occurred in 534 (26.5%) of 2,017 RT breaths and in 14 (93.3%) of 15 patients with RT. In multivariable modeling, breath stacking was more likely to occur when total airway Δpressure (peak inspiratory pressure - positive end-expiratory pressure [PEEP]) at the time patient effort began, peak inspiratory pressure, PEEP, and Δpressure were lower and when patient effort started well after the ventilator-initiated breath (higher phase angle) (all P < 0.05). Together, these parameters were highly predictive of breath stacking (area under the curve, 0.979).Conclusions: Patients with higher tidal volume who have a set ventilator rate close to their spontaneous respiratory rate are more likely to have RT, which results in breath stacking >25% of the time.Clinical trial registered with ClinicalTrials.gov (NCT03266016).

Ventilator Liberation in the Pediatric ICU.

Despite the accepted importance of minimizing time on mechanical ventilation, only limited guidance on weaning and extubation is available from the pediatric literature. A significant proportion of patients being evaluated for weaning are actually ready for extubation, suggesting that weaning is often not considered early enough in the course of ventilation. Indications for extubation are often not clear, although a trial of spontaneous breathing on CPAP without pressure support seems an appropriate prerequisite in many cases. Several indexes have been developed to predict weaning and extubation success, but the available literature suggests they offer little or no improvement over clinical judgment. New techniques for assessing readiness for weaning and predicting extubation success are being developed but are far from general acceptance in pediatric practice. While there have been some excellent physiologic, observational, and even randomized controlled trials on aspects of pediatric ventilator liberation, robust research data are lacking. Given the lack of data in many areas, a determined approach that combines systematic review with consensus opinion of international experts could generate high-quality recommendations and terminology definitions to guide clinical practice and highlight important areas for future research in weaning, extubation readiness, and liberation from mechanical ventilation following pediatric respiratory failure.

Real-Time Effort Driven Ventilator Management: A Pilot Study.

OBJECTIVES: Mechanical ventilation of patients with acute respiratory distress syndrome should balance lung and diaphragm protective principles, which may be difficult to achieve in routine clinical practice. Through a Phase I clinical trial, we sought to determine whether a computerized decision support-based protocol (real-time effort-driven ventilator management) is feasible to implement, results in improved acceptance for lung and diaphragm protective ventilation, and improves clinical outcomes over historical controls. DESIGN: Interventional nonblinded pilot study. SETTING: PICU. PATIENTS: Mechanically ventilated children with acute respiratory distress syndrome. INTERVENTIONS: A computerized decision support tool was tested which prioritized lung-protective management of peak inspiratory pressure-positive end-expiratory pressure, positive end-expiratory pressure/FIO2, and ventilatory rate. Esophageal manometry was used to maintain patient effort in a physiologic range. Protocol acceptance was reported, and enrolled patients were matched 4:1 with respect to age, initial oxygenation index, and percentage of immune compromise to historical control patients for outcome analysis. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were included. Acceptance of protocol recommendations was over 75%. One-hundred twenty-eight matched historical controls were used for analysis. Compared with historical controls, patients treated with real-time effort-driven ventilator management received lower peak inspiratory pressure-positive end-expiratory pressure and tidal volume, and higher positive end-expiratory pressure when FIO2 was greater than 0.60. Real-time effort-driven ventilator management was associated with 6 more ventilator-free days, shorter duration until the first spontaneous breathing trial and 3 fewer days on mechanical ventilation among survivors (all p ≤ 0.05) in comparison with historical controls, while maintaining no difference in the rate of reintubation. CONCLUSIONS: A computerized decision support-based protocol prioritizing lung-protective ventilation balanced with reduction of controlled ventilation to maintain physiologic levels of patient effort can be implemented and may be associated with shorter duration of ventilation.

High Breath-by-Breath Variability Is Associated With Extubation Failure in Children.

OBJECTIVES: Extubation failure is multifactorial, and most tools to assess extubation readiness only evaluate snapshots of patient physiology. Understanding variability in respiratory variables may provide additional information to inform extubation readiness assessments. DESIGN: Secondary analysis of prospectively collected physiologic data of children just prior to extubation during a spontaneous breathing trial. Physiologic data were cleaned to provide 40 consecutive breaths and calculate variability terms, coefficient of variation and autocorrelation, in commonly used respiratory variables (i.e., tidal volume, minute ventilation, and respiratory rate). Other clinical variables included diagnostic and demographic data, median values of respiratory variables during spontaneous breathing trials, and the change in airway pressure during an occlusion maneuver to measure respiratory muscle strength (maximal change in airway pressure generated during airway occlusion [PiMax]). Multivariable models evaluated independent associations with reintubation and prolonged use of noninvasive respiratory support after extubation. SETTING: Acute care, children's hospital. PATIENTS: Children were included from the pediatric and cardiothoracic ICUs who were greater than 37 weeks gestational age up to and including 18 years who were intubated greater than or equal to 12 hours with planned extubation. We excluded children who had a contraindication to an esophageal catheter or respiratory inductance plethysmography bands. INTERVENTIONS: Noninterventional study. MEASUREMENTS AND MAIN RESULTS: A total of 371 children were included, 32 of them were reintubated. Many variability terms were associated with reintubation, including coefficient of variation and autocorrelation of the respiratory rate. After controlling for confounding variables such as age and neurologic diagnosis, both coefficient of variation of respiratory rate(p < 0.001) and low PiMax (p = 0.002) retained an independent association with reintubation. Children with either low PiMax or high coefficient of variation of respiratory rate had a nearly three-fold higher risk of extubation failure, and when these children developed postextubation upper airway obstruction, reintubation rates were greater than 30%. CONCLUSIONS: High respiratory variability during spontaneous breathing trials is independently associated with extubation failure in children, with very high rates of extubation failure when these children develop postextubation upper airway obstruction.

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.

The role of computer-based clinical decision support systems to deliver protective mechanical ventilation.

PURPOSE OF REVIEW: Mechanical ventilation of adults and children with acute respiratory failure necessitates balancing lung and diaphragm protective ventilation. Computerized decision support (CDS) offers advantages in circumstances where complex decisions need to be made to weigh potentially competing risks, depending on the physiologic state of the patient. RECENT FINDINGS: Significant variability in how ventilator protocols are applied still exists and clinical data show that there continues to be wide variability in ventilator management. We have developed a CDS, which we are currently testing in a Phase II randomized controlled trial. The CDS is called Real-time Effort Driven ventilator management (REDvent). We will describe the rationale and methods for development of CDS for lung and diaphragm protective ventilation, using the REDvent CDS as an exemplar. SUMMARY: Goals for achieving compliance and physiologic objectives can be met when CDS instructions are simple and explicit, provide the clinician with the underlying rule set, permit acceptable reasons for declining and allow for iterative adjustments.

Minimal Change in Cardiac Index With Increasing PEEP in Pediatric Acute Respiratory Distress Syndrome.

Objective: To determine if increasing positive end expiratory pressure (PEEP) leads to a change in cardiac index in children with Pediatric Acute Respiratory Distress Syndrome ranging from mild to severe. Design: Prospective interventional study. Setting: Multidisciplinary Pediatric Intensive Care Unit in a University teaching hospital. Patients: Fifteen intubated children (5 females, 10 males) with a median age of 72 months (IQR 11, 132) and a median weight of 19.3 kg (IQR 7.5, 53.6) with a severity of Pediatric Acute Respiratory Distress Syndrome that ranged from mild to severe with a median lung injury score of 2.3 (IQR 2.0, 2.7). Measurements: Cardiac index (CI) and stroke volume (SV) were measured on baseline ventilator settings and subsequently with a PEEP 4 cmH2O higher than baseline. Change in CI and SV from baseline values was evaluated using Wilcoxon signed rank test. Results: A total of 19 paired measurements obtained. The median baseline PEEP was 8 cmH2O (IQR 8, 10) Range 6-14 cmH2O. There was no significant change in cardiac index or stroke volume with change in PEEP. Baseline median CI 4.4 L/min/m2 (IQR 3.4, 4.8) and PEEP 4 higher median CI of 4.3 L/min/m2 (IQR 3.6, 4.8), p = 0.65. Baseline median SV 26 ml (IQR 13, 44) and at PEEP 4 higher median SV 34 ml (IQR 12, 44) p = 0.63. Conclusion: There is no significant change in cardiac index or stroke volume with increasing PEEP by 4 cmH2O in a population of children with mild to severe PARDS. Clinical Trial Registration: The study is registered on Clinical trails.gov under the Identifier: NCT02354365.

Physiologic Effects of 3 Different Neonatal Volume-Targeted Ventilation Modes in Surfactant-Deficient Juvenile Rabbits.

BACKGROUND: Different brands of volume-targeted modes may vary the location of tidal volume (VT) monitoring and whether peak inspiratory pressure is adjusted based on inspiratory, expiratory, or leak-compensated VT. These variables may result in different levels of support provided to patients, especially when an endotracheal tube (ETT) leak is present. We hypothesized that there would be no differences in gas exchange, triggering, or work of breathing between volume-targeted modes of 3 different brands of equipment in a surfactant-deficient, spontaneously breathing animal model with and without an ETT leak. METHODS: Twelve rabbits (mean ± SD 1.61 ± 0.20 kg) were sedated, anesthetized, intubated, lavaged with 0.9% saline solution, and randomized in a crossover design so that each animal was supported by 3 different volume-targeted modes at identical settings with and without an ETT leak. After 30 min, arterial blood gas, VT, and esophageal and airway pressure were recorded for each condition, and pressure-rate product and percentage of successfully triggered breaths were calculated. RESULTS: Gas exchange and the pressure-rate product were not different between the ventilators in the absence of an ETT leak. When an ETT leak was introduced, volume-guarantee modes allowed a higher percentage of triggered breaths and peak inspiratory pressure, which resulted in higher minute ventilation, pH, and lower PaCO2 than the pressure-regulated volume control mode (P < .05). CONCLUSIONS: When a moderate ETT leak was present, volume-targeted modes that used proximal VT monitoring and triggering with adaptive leak compensation capabilities appeared more effective in providing ventilation support than did a ventilator that used measurements obtained from the back at the ventilator and does not have leak compensation.

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 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.

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.