Noninvasive Surrogate for Physiologic Dead Space Using the Carbon Dioxide Ventilatory Equivalent: Testing in a Single-Center Cohort, 2017-2023.

OBJECTIVES: We sought to evaluate the association between the carbon dioxide (co2) ventilatory equivalent (VEqco2 = minute ventilation/volume of co2 produced per min), a marker of dead space that does not require a blood gas measurement, and mortality risk. We compared the strength of this association to that of physiologic dead space fraction (VD/Vt = [Paco2-mixed-expired Pco2]/Paco2) as well as to other commonly used markers of dead space (i.e., the end-tidal alveolar dead space fraction [AVDSf = (Paco2-end-tidal Pco2)/Paco2], and ventilatory ratio [VR = (minute ventilation × Paco2)/(age-adjusted predicted minute ventilation × 37.5)]). DESIGN: Retrospective cohort data, 2017-2023. SETTING: Quaternary PICU. PATIENTS: One hundred thirty-one children with acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All dead space markers were calculated at the same 1-minute timepoint for each patient within the first 72 hours of using invasive mechanical ventilation. The 131 children had a median (interquartile range, IQR) age of 5.8 (IQR 1.4, 12.6) years, oxygenation index (OI) of 7.5 (IQR 4.6, 14.3), VD/Vt of 0.47 (IQR 0.38, 0.61), and mortality was 17.6% (23/131). Higher VEqco2 (p = 0.003), VD/Vt (p = 0.002), and VR (p = 0.013) were all associated with greater odds of mortality in multivariable models adjusting for OI, immunosuppressive comorbidity, and overall severity of illness. We failed to identify an association between AVDSf and mortality in the multivariable modeling. Similarly, we also failed to identify an association between OI and mortality after controlling for any dead space marker in the modeling. For the 28-day ventilator-free days outcome, we failed to identify an association between VD/Vt and the dead space markers in multivariable modeling, although OI was significant. CONCLUSIONS: VEqco2 performs similarly to VD/Vt and other surrogate dead space markers, is independently associated with mortality risk, and may be a reasonable noninvasive surrogate for VD/Vt.

Association between Age and Mortality in Pediatric and Adult Acute Respiratory Distress Syndrome.

Rationale: The epidemiology, management, and outcomes of acute respiratory distress syndrome (ARDS) differ between children and adults, with lower mortality rates in children despite comparable severity of hypoxemia. However, the relationship between age and mortality is unclear.Objective: We aimed to define the association between age and mortality in ARDS, hypothesizing that it would be nonlinear.Methods: We performed a retrospective cohort study using data from two pediatric ARDS observational cohorts (n = 1,236), multiple adult ARDS trials (n = 5,547), and an adult observational ARDS cohort (n = 1,079). We aligned all datasets to meet Berlin criteria. We performed unadjusted and adjusted logistic regression using fractional polynomials to assess the potentially nonlinear relationship between age and 90-day mortality, adjusting for sex, PaO2/FiO2, immunosuppressed status, year of study, and observational versus randomized controlled trial, treating each individual study as a fixed effect.Measurements and Main Results: There were 7,862 subjects with median ages of 4 years in the pediatric cohorts, 52 years in the adult trials, and 61 years in the adult observational cohort. Most subjects (43%) had moderate ARDS by Berlin criteria. Ninety-day mortality was 19% in the pediatric cohorts, 33% in the adult trials, and 67% in the adult observational cohort. We found a nonlinear relationship between age and mortality, with mortality risk increasing at an accelerating rate between 11 and 65 years of age, after which mortality risk increased more slowly.Conclusions: There was a nonlinear relationship between age and mortality in pediatric and adult ARDS.

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.

Noninvasive Ventilation for Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study.

OBJECTIVES: The worldwide practice and impact of noninvasive ventilation (NIV) in pediatric acute respiratory distress syndrome (PARDS) is unknown. We sought to describe NIV use and associated clinical outcomes in PARDS. DESIGN: Planned ancillary study to the 2016/2017 prospective Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study. SETTING: One hundred five international PICUs. PATIENTS: Patients with newly diagnosed PARDS admitted during 10 study weeks. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children were categorized by their respiratory support at PARDS diagnosis into NIV or invasive mechanical ventilation (IMV) groups. Of 708 subjects with PARDS, 160 patients (23%) received NIV at PARDS diagnosis (NIV group). NIV failure rate (defined as tracheal intubation or death) was 84 of 160 patients (53%). Higher nonrespiratory pediatric logistic organ dysfunction (PELOD-2) score, Pa o2 /F io2 was less than 100 at PARDS diagnosis, immunosuppression, and male sex were independently associated with NIV failure. NIV failure was 100% among patients with nonrespiratory PELOD-2 score greater than 2, Pa o2 /F io2 less than 100, and immunosuppression all present. Among patients with Pa o2 /F io2 greater than 100, children in the NIV group had shorter total duration of NIV and IMV, than the IMV at initial diagnosis group. We failed to identify associations between NIV use and PICU survival in a multivariable Cox regression analysis (hazard ratio 1.04 [95% CI, 0.61-1.80]) or mortality in a propensity score matched analysis ( p = 0.369). CONCLUSIONS: Use of NIV at PARDS diagnosis was associated with shorter exposure to IMV in children with mild to moderate hypoxemia. Even though risk of NIV failure was high in some children, we failed to identify greater hazard of mortality in these patients.

Mechanical Power Is Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: Mechanical power (MP) transferred from the ventilator to the lungs has been proposed as a summary variable that may impact mortality in children with acute respiratory distress syndrome (ARDS). To date, no study has shown an association between higher MP and mortality in children with ARDS. DESIGN: Secondary analysis of a prospective observational study. SETTING: Single-center, tertiary, academic PICU. PATIENTS: Five hundred forty-six intubated children with ARDS enrolled between January 2013 and December 2019 receiving pressure-controlled ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Higher MP was associated with increased mortality (adjusted hazard ratio [HR] 1.34 per 1 sd increase, 95% CI 1.08-1.65; p = 0.007). When assessing the contribution of individual components of MP, only positive end-expiratory pressure (PEEP) was associated with mortality (HR 1.32; p = 0.007), whereas tidal volume, respiratory rate, and driving pressure (ΔP = [peak inspiratory pressure (PIP)-PEEP]) were not. Finally, we tested whether there remained an association when specific terms were removed from the MP equation by calculating MP from static strain (remove ΔP), MP from dynamic strain (remove PEEP), and mechanical energy (remove respiratory rate). MP from static strain (HR 1.44; p < 0.001), MP from dynamic strain (HR 1.25; p = 0.042), and mechanical energy (HR 1.29; p = 0.009) were all associated with mortality. MP was associated with ventilator-free days only when using MP normalized to predicted body weight, but not when using measured weight. CONCLUSIONS: Higher MP was associated with mortality in pediatric ARDS, and PEEP appears to be the component most consistently driving this association. As higher PEEP is used in sicker patients, the association between MP and mortality may reflect a marker of illness severity rather than MP itself being causal for mortality. However, our results support future trials testing different levels of PEEP in children with ARDS as a potential means to improve outcome.

The end-tidal alveolar dead space fraction for risk stratification during the first week of invasive mechanical ventilation: an observational cohort study.

BACKGROUND: The end-tidal alveolar dead space fraction (AVDSf = [PaCO2-PETCO2]/PaCO2) is a metric used to estimate alveolar dead space. Higher AVDSf on the first day of mechanical ventilation is associated with mortality and fewer ventilator-free days. It is not clear if AVDSf is associated with length of ventilation in survivors, how AVDSf performs for risk stratification beyond the first day of ventilation, or whether AVDSf adds predictive value to oxygenation (oxygenation index [OI]) or severity of illness (Pediatric Risk of Mortality [PRISM III]) markers. METHODS: Retrospective single-center observational cohort study of children and young adults receiving invasive mechanical ventilation. In those with arterial or capillary blood gases, AVDSf was calculated at the time of every blood gas for the first week of mechanical ventilation. RESULTS: There were 2335 children and young adults (median age 5.8 years [IQR 1.2, 13.2]) enrolled with 8004 analyzed AVDSf values. Higher AVDSf was associated with mortality and longer length of ventilation in survivors throughout the first week of ventilation after controlling for OI and PRISM III. Higher OI was not associated with increased mortality until ≥ 48 h of ventilation after controlling for AVDSf and PRISM III. When using standardized variables, AVDSf effect estimates were generally higher than OI for mortality, whereas OI effect estimates were generally higher than AVDSf for the length of ventilation in survivors. An AVDSf > 0.3 was associated with a higher mortality than an AVDSf < 0.2 within each pediatric acute respiratory distress syndrome severity category. The maximum AVDSf within 12 h of intensive care unit admission demonstrated good risk stratification for mortality (AUC 0.768 [95% CI 0.732, 0.803]). AVDSf did not improve mortality risk stratification when added to PRISM III but did improve mortality risk stratification when added to the gas exchange components of PRISM III (minimum 12-h PaO2 and maximum 12-h PCO2) (p < 0.00001). CONCLUSIONS: AVDSf is associated with mortality and length of ventilation in survivors throughout the first week of invasive mechanical ventilation. Some analyses suggest AVDSf may better stratify mortality risk than OI, whereas OI may better stratify risk for prolonged ventilation in survivors than AVDSf.

Mechanical power in pediatric acute respiratory distress syndrome: a PARDIE study.

BACKGROUND: Mechanical power is a composite variable for energy transmitted to the respiratory system over time that may better capture risk for ventilator-induced lung injury than individual ventilator management components. We sought to evaluate if mechanical ventilation management with a high mechanical power is associated with fewer ventilator-free days (VFD) in children with pediatric acute respiratory distress syndrome (PARDS). METHODS: Retrospective analysis of a prospective observational international cohort study. RESULTS: There were 306 children from 55 pediatric intensive care units included. High mechanical power was associated with younger age, higher oxygenation index, a comorbid condition of bronchopulmonary dysplasia, higher tidal volume, higher delta pressure (peak inspiratory pressure-positive end-expiratory pressure), and higher respiratory rate. Higher mechanical power was associated with fewer 28-day VFD after controlling for confounding variables (per 0.1 J·min-1·Kg-1 Subdistribution Hazard Ratio (SHR) 0.93 (0.87, 0.98), p = 0.013). Higher mechanical power was not associated with higher intensive care unit mortality in multivariable analysis in the entire cohort (per 0.1 J·min-1·Kg-1 OR 1.12 [0.94, 1.32], p = 0.20). But was associated with higher mortality when excluding children who died due to neurologic reasons (per 0.1 J·min-1·Kg-1 OR 1.22 [1.01, 1.46], p = 0.036). In subgroup analyses by age, the association between higher mechanical power and fewer 28-day VFD remained only in children < 2-years-old (per 0.1 J·min-1·Kg-1 SHR 0.89 (0.82, 0.96), p = 0.005). Younger children were managed with lower tidal volume, higher delta pressure, higher respiratory rate, lower positive end-expiratory pressure, and higher PCO2 than older children. No individual ventilator management component mediated the effect of mechanical power on 28-day VFD. CONCLUSIONS: Higher mechanical power is associated with fewer 28-day VFDs in children with PARDS. This association is strongest in children < 2-years-old in whom there are notable differences in mechanical ventilation management. While further validation is needed, these data highlight that ventilator management is associated with outcome in children with PARDS, and there may be subgroups of children with higher potential benefit from strategies to improve lung-protective ventilation. TAKE HOME MESSAGE: Higher mechanical power is associated with fewer 28-day ventilator-free days in children with pediatric acute respiratory distress syndrome. This association is strongest in children <2-years-old in whom there are notable differences in mechanical ventilation management.

Adherence to Lung-Protective Ventilation Principles in Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

OBJECTIVES: To describe mechanical ventilation management and factors associated with nonadherence to lung-protective ventilation principles in pediatric acute respiratory distress syndrome. DESIGN: A planned ancillary study to a prospective international observational study. Mechanical ventilation management (every 6 hr measurements) during pediatric acute respiratory distress syndrome days 0-3 was described and compared with Pediatric Acute Lung Injury Consensus Conference tidal volume recommendations (< 7 mL/kg in children with impaired respiratory system compliance, < 9 mL/kg in all other children) and the Acute Respiratory Distress Syndrome Network lower positive end-expiratory pressure/higher Fio2 grid recommendations. SETTING: Seventy-one international PICUs. PATIENTS: Children with pediatric acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analyses included 422 children. On pediatric acute respiratory distress syndrome day 0, median tidal volume was 7.6 mL/kg (interquartile range, 6.3-8.9 mL/kg) and did not differ by pediatric acute respiratory distress syndrome severity. Plateau pressure was not recorded in 97% of measurements. Using delta pressure (peak inspiratory pressure - positive end-expiratory pressure), median tidal volume increased over quartiles of median delta pressure (p = 0.007). Median delta pressure was greater than or equal to 18 cm H2O for all pediatric acute respiratory distress syndrome severity levels. In severe pediatric acute respiratory distress syndrome, tidal volume was greater than or equal to 7 mL/kg 62% of the time, and positive end-expiratory pressure was lower than recommended by the positive end-expiratory pressure/Fio2 grid 70% of the time. In multivariable analysis, tidal volume nonadherence was more common with severe pediatric acute respiratory distress syndrome, fewer PICU admissions/yr, non-European PICUs, higher delta pressure, corticosteroid use, and pressure control mode. Adherence was associated with underweight stature and cuffed endotracheal tubes. In multivariable analysis, positive end-expiratory pressure/Fio2 grid nonadherence was more common with higher pediatric acute respiratory distress syndrome severity, ventilator decisions made primarily by the attending physician, pre-ICU cardiopulmonary resuscitation, underweight stature, and age less than 2 years. Adherence was associated with respiratory therapist involvement in ventilator management and longer time from pediatric acute respiratory distress syndrome diagnosis. Higher nonadherence to tidal volume and positive end-expiratory pressure recommendations were independently associated with higher mortality and longer duration of ventilation after adjustment for confounding variables. In stratified analyses, these associations were primarily influenced by children with severe pediatric acute respiratory distress syndrome. CONCLUSIONS: Nonadherence to lung-protective ventilation principles is common in pediatric acute respiratory distress syndrome and may impact outcome. Modifiable factors exist that may improve adherence.

Declining Procedures in Pediatric Critical Care Medicine Using a National Database.

OBJECTIVES: To investigate the change in rate of invasive procedures (endotracheal intubation, central venous catheters, arterial catheters, and peripheral inserted central venous catheters) performed in PICUs per admission over time. Secondarily, to investigate the change in type of respiratory support over time. DESIGN: Retrospective study of prospectively collected data using the Virtual Pediatric Systems (VPS; LLC, Los Angeles, CA) database. SETTING: North American PICUs. PATIENTS: Patients admitted from January 2009 to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 902,624 admissions from 161 PICUs included in the analysis. Since 2009, there has been a decrease in rate of endotracheal intubations, central venous catheters placed, and arterial catheters placed and an increase in the rate of peripheral inserted central venous catheter insertion per admission over time after controlling for severity of illness and unit level effects. As compared to 2009, the incident rate ratio for 2017 for endotracheal intubation was 0.90 (95% CI, 0.83-0.98; p = 0.017), for central venous line placement 0.69 (0.63-0.74; p < 0.001), for arterial catheter insertion 0.85 (0.79-0.92; p < 0.001), and for peripheral inserted central venous catheter placement 1.14 (1.03-1.26; p = 0.013). Over this time period, in a subgroup with available data, there was a decrease in the rate of invasive mechanical ventilation and an increase in the rate of noninvasive respiratory support (bilevel positive airway pressure/continuous positive airway pressure and high-flow nasal oxygen) per admission. CONCLUSIONS: Over 9 years across multiple North American PICUs, the rate of endotracheal intubations, central catheter, and arterial catheter insertions per admission has decreased. The use of invasive mechanical ventilation has decreased with an increase in noninvasive respiratory support. These data support efforts to improve exposure to invasive procedures in training and structured systems to evaluate continued competency.

The Association Between Ventilatory Ratio and Mortality in Children and Young Adults.

BACKGROUND: The ventilatory ratio (VR) is a dead-space marker associated with mortality in mechanically ventilated adults with ARDS. The end-tidal alveolar dead space fraction (AVDSf) has been associated with mortality in children. However, AVDSf requires capnography measurements, whereas VR does not. We sought to examine the prognostic value of VR, in comparison to AVDSf, in children and young adults with acute hypoxemic respiratory failure. METHODS: We conducted a retrospective study of prospectively collected data from 180 mechanically ventilated children and young adults with acute hypoxemic respiratory failure. VR was calculated as (minute ventilation × [Formula: see text])/(age-adjusted predicted minute ventilation × 37.5). AVDSf was calculated as [Formula: see text]. RESULTS: VR and AVDSf had a moderate correlation (rho 0.31, P < .001). VR was similar between survivors at 1.22 (interquartile range [IQR] 1.0-1.52) and nonsurvivors at 1.30 (IQR 0.96-1.95) (P = .2). AVDSf was lower in survivors at 0.12 (IQR 0.03-0.23) than nonsurvivors at 0.24 (IQR 0.13-0.33) (P < .001). In logistic regression and competing risk regression analyses, VR was not associated with mortality or rate of extubation at any given time (competing risk death; all P > .3). An AVDSf in the highest 2 quartiles, in comparison to the lowest quartile (AVDSf < 0.06), was associated with higher mortality after adjustment for oxygenation index and severity of illness (AVDSf ≥ 0.15-0.26: odds ratio 3.58, 95% CI 1.02-12.64, P = .047, and AVDSf ≥ 0.26: odds ratio 3.91 95% CI-1.03-14.83, P = .045). At any given time after intubation, a child with an AVDSf ≥ 0.26 was less likely to be extubated than a child with an AVDSf < 0.06, after adjustment for oxygenation index and severity of illness (AVDSf ≥ 0.26: subdistribution hazard ratio 0.55, 95% CI 0.33-0.94, P = .03). CONCLUSIONS: VR should not be used for prognostic purposes in children and young adults. AVDSf added prognostic information to the severity of oxygenation defect and overall severity of illness in children and young adults, consistent with previous research.

Body Habitus and Risk of Mortality in Pediatric Sepsis and Septic Shock: A Retrospective Cohort Study.

OBJECTIVE: To investigate the association between body habitus and mortality in critically ill children with sepsis or septic shock. STUDY DESIGN: This was a retrospective cohort study of prospectively collected data of children admitted to US pediatric intensive care units (PICUs) with a primary or secondary diagnosis of sepsis or septic shock. We separated body habitus into underweight, normal weight, overweight, and obese. Outcomes were mortality (primary), treatment with invasive mechanical ventilation (secondary), and time to PICU discharge for survivors (secondary). Multivariable analyses using mixed-effects logistic regression and shared frailty models clustered by unit and adjusted for confounding variables were used to assess the association between body habitus and outcomes. RESULTS: There were 7038 children with sepsis or septic shock. Mortality was 10.1% (n = 714) and 52.9% (n = 3720) required invasive mechanical ventilation. Body habitus was not associated with mortality after controlling for hospital level effects and confounding variables. Children who were overweight and obese had greater odds of invasive mechanical ventilation (overweight OR 1.23 [95% CI 1.05-1.45], P = .011 and obese OR 1.57 [95% CI 1.37-1.80], P < .001) compared with children of normal weight. In survivors treated with invasive mechanical ventilation, children who were obese had a longer time to PICU discharge than children of normal weight (obese hazard ratio for discharge 0.84 [95% CI, 0.77-0.92], P < .0001). CONCLUSIONS: There was no association between body habitus and mortality in critically ill children with sepsis. Children who were overweight and obese were more likely to receive invasive mechanical ventilation and mechanically ventilated survivors who were obsese had a longer time to PICU discharge.

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.

The Association Between Inhaled Nitric Oxide Treatment and ICU Mortality and 28-Day Ventilator-Free Days in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: To investigate the association between inhaled nitric oxide treatment and ICU mortality and 28-day ventilator-free days in pediatric acute respiratory distress syndrome. DESIGN: Retrospective cohort study. A propensity score for inhaled nitric oxide treatment was developed and used in the analysis. SETTING: Two quaternary care PICUs. PATIENTS: Children with pediatric acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 499 children enrolled in this study with 143 (28.7%) receiving inhaled nitric oxide treatment. Children treated with inhaled nitric oxide were more likely to have a primary diagnosis of pneumonia (72% vs 54.8%; p < 0.001), had a higher initial oxygenation index (median 16.9 [interquartile range, 10.1-27.3] vs 8.5 [interquartile range, 5.8-12.2]; p < 0.001), and had a higher 72-hour maximal Vasoactive-Inotrope Score (median 15 [interquartile range, 6-25] vs 8 [interquartile range, 0-17.8]; p < 0.001) than those not receiving inhaled nitric oxide. Mortality was higher in the inhaled nitric oxide treatment group (25.2% vs 16.3%; p = 0.02), and children in this group had fewer 28-day ventilator-free days (10 d [interquartile range, 0-18 d] vs 17 d (interquartile range 5.5-22 d]; p < 0.0001). We matched 176 children based on propensity score for inhaled nitric oxide treatment. In the matched cohort, inhaled nitric oxide treatment was not associated with mortality (odds ratio, 1.3 [95% CI, 0.56-3.0]) or 28-day ventilator-free days (incidence rate ratio, 0.91 [95% CI, 0.80-1.04]). These results remained consistent in the entire study cohort when the propensity score for inhaled nitric oxide treatment was used for either inverse probability weighting or stratification in regression modeling with the exception that subjects treated with inhaled nitric oxide were more likely to have 0 ventilator-free days (p ≤ 0.02). In secondary analysis stratified by oxygenation response, inhaled nitric oxide treatment was not associated with mortality or 28-day ventilator-free days in children with a positive oxygenation response (all p > 0.2) CONCLUSIONS:: Treatment with inhaled nitric oxide in pediatric acute respiratory distress syndrome is not associated with improvement in either mortality or ventilator-free days and may be associated with harm. Further prospective trials are required to define the role of inhaled nitric oxide treatment in pediatric acute respiratory distress syndrome.

Positive End-Expiratory Pressure Lower Than the ARDS Network Protocol Is Associated with Higher Pediatric Acute Respiratory Distress Syndrome Mortality.

RATIONALE: The ARDS Network (ARDSNet) used a positive end-expiratory pressure (PEEP)/FiO2 model in many studies. In general, pediatric intensivists use less PEEP and higher FiO2 than this model. OBJECTIVES: To evaluate whether children managed with PEEP lower than recommended by the ARDSNet PEEP/FiO2 model had higher mortality. METHODS: This was a multicenter, retrospective analysis of patients with pediatric acute respiratory distress syndrome (PARDS) managed without a formal PEEP/FiO2 protocol. Four distinct datasets were combined for analysis. We extracted time-matched PEEP/FiO2 values, calculating the difference between PEEP level and the ARDSNet-recommended PEEP level for a given FiO2. We analyzed the median difference over the first 24 hours of PARDS diagnosis against ICU mortality and adjusted for confounding variables, effect modifiers, or factors that may have affected the propensity to use lower PEEP. MEASUREMENTS AND MAIN RESULTS: Of the 1,134 patients with PARDS, 26.6% were managed with lower PEEP relative to the amount of FiO2 recommended by the ARDSNet protocol. Patients managed with lower PEEP experienced higher mortality than those who were managed with PEEP levels in line with or higher than recommended by the protocol (P < 0.001). After adjustment for hypoxemia, inotropes, comorbidities, severity of illness, ventilator settings, nitric oxide, and dataset, PEEP lower than recommended by the protocol remained independently associated with higher mortality (odds ratio, 2.05; 95% confidence interval, 1.32-3.17). Findings were similar after propensity-based covariate adjustment (odds ratio, 2.00; 95% confidence interval, 1.24-3.22). CONCLUSIONS: Patients with PARDS managed with lower PEEP relative to FiO2 than recommended by the ARDSNet model had higher mortality. Clinical trials targeting PEEP management in PARDS are needed.