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.

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.

Application of Multiplex Polymerase Chain Reaction for Pathogen Identification and Antibiotic Use in Children With Respiratory Infections in a PICU.

OBJECTIVES: To compare the pathogen identification rate and use of antibiotics before and after the implementation of multiplex polymerase chain reaction testing in children with respiratory infections in a PICU. DESIGN: Single-center, pre-post study. SETTING: PICU of Osaka Women's and Children's Hospital, Osaka, Japan. PATIENTS: Consecutive children with respiratory infections who were admitted to the PICU between December 2017 and November 2018 (premultiplex polymerase chain reaction period) and between March 2019 and February 2020 (postmultiplex polymerase chain reaction period). INTERVENTIONS: Conventional rapid antigen tests and bacterial culture tests were performed throughout the study period. Multiplex polymerase chain reaction testing using the FilmArray respiratory panel (BioFire Diagnostics, Salt Lake City, UT) was conducted to detect 17 viruses and three bacterial pathogens. During the postmultiplex polymerase chain reaction period, we did not recommend prescribing antibiotics for stable children, depending on the virus species and laboratory test results. MEASUREMENTS AND MAIN RESULTS: Ninety-six and 85 children were enrolled during the pre- and postmultiplex polymerase chain reaction periods, respectively. Rapid antigen tests identified pathogens in 22% of the children (n = 21) during the premultiplex polymerase chain reaction period, whereas rapid antigen tests and/or multiplex polymerase chain reaction testing identified pathogens in 67% of the children (n = 57) during the postmultiplex polymerase chain reaction period (p < 0.001). The most commonly identified pathogen using multiplex polymerase chain reaction testing was human rhino/enterovirus. Bacterial pathogens were identified in 50% of the children (n = 48) and 60% of the children (n = 51) during the pre- and postmultiplex polymerase chain reaction periods (p = 0.18). There were no differences in antibiotic use (84% vs 75%; p = 0.14), broad-spectrum antibiotic use (33% vs 34%; p = 0.91), or the duration of antibiotic use within 14 days of admission (6.0 vs 7.0 d; p = 0.45) between the pre- and postmultiplex polymerase chain reaction periods. CONCLUSIONS: Although the pathogen identification rate, especially for viral pathogens, increased using multiplex polymerase chain reaction testing, antibiotic use did not reduce in children with respiratory infections in the PICU. Definitive identification of bacterial pathogens and implementation of evidence-based antimicrobial stewardship programs employing multiplex polymerase chain reaction testing are warranted.

Occurrence and Risk Factors for Unplanned Catheter Removal in a PICU: Central Venous Catheters Versus Peripherally Inserted Central Venous Catheters.

OBJECTIVES: We aimed to identify the occurrence and risk factors for unplanned catheter removal due to catheter-associated complications and the effects on catheter survival probability in a PICU. DESIGN: Retrospective, single-center, observational study of cases involving conventional central venous catheters or peripherally inserted central venous catheters. SETTING: The PICU of a tertiary children's hospital. PATIENTS: Consecutive PICU patients with central venous catheters between April 2016 and February 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified unplanned catheter removals that were related to central line-associated bloodstream infection, thrombosis, and mechanical complications. During the study period, 582 central venous catheters and 474 peripherally inserted central venous catheters were identified. The median durations of catheter placement were 4.0 days for central venous catheters and 13.0 days for peripherally inserted central venous catheters (p < 0.001), and unplanned catheter removals due to catheter-associated complications were in 52 (8.9%) central venous catheter cases and 132 (27.8%) peripherally inserted central venous catheter cases (p < 0.001) (15.0 and 16.0 per 1,000 catheter-days, respectively [p = 0.75]). Unplanned catheter removal was associated with a peripheral catheter tip position among both central venous catheters and peripherally inserted central venous catheters (p < 0.001 and p = 0.001), and it was associated with surgical patient status among peripherally inserted central venous catheters (p = 0.009). In contrast, the use of ultrasound-guided insertion was associated with a lower occurrence of unplanned catheter removal among peripherally inserted central venous catheters (p = 0.01). With regard to catheter survival probability, there was no significant difference between central venous catheters and peripherally inserted central venous catheters (p = 0.23). However, peripherally inserted central venous catheters had a lower occurrence of central line-associated bloodstream infection than central venous catheters (p = 0.03), whereas there was no significant difference in the rates of thrombosis (p = 0.29) and mechanical complications (p = 0.84) between central venous catheters and peripherally inserted central venous catheters. CONCLUSIONS: In a PICU, peripherally inserted central venous catheters had lower occurrence of central line-associated bloodstream infection than central venous catheters; however, similar catheter survival probabilities were observed between both catheters. A central catheter tip position for both catheters and ultrasound-guided insertion for peripherally inserted central venous catheters may help limit unplanned catheter removal due to catheter-associated complications.

A novel method for transpulmonary pressure estimation using fluctuation of central venous pressure.

The objective of the study is to develop a correction method for estimating the change in pleural pressure (ΔPpl) and plateau transpulmonary pressure (PL) by using the change in central venous pressure (ΔCVP). Seven children (aged < 15 years) with acute respiratory failure (PaO2/FIO2 < 300 mmHg), who were paralyzed and mechanically ventilated with a PEEP of < 10 cmH2O and had central venous catheters and esophageal balloon catheters placed for clinical purposes, were enrolled prospectively. We compared change in esophageal pressure (ΔPes), ΔCVP, and ΔPpl calculated using a corrected ΔCVP (cΔCVP-derived ΔPpl). cΔCVP-derived ΔPpl was calculated as κ × ΔCVP, where κ was the ratio of the change in airway pressure (ΔPaw) to ΔCVP during the occlusion test. cΔCVP-derived ΔPpl correlated better than ΔCVP with ΔPes (R2 = 0.48, p = 0.08 vs. R2 = 0.14, p = 0.4) with lesser bias and precision in Bland-Altman analysis. The plateau PL calculated using the cΔCVP-derived ΔPpl (17.6 ± 2.6 cmH2O) correlated well with the ΔPes-derived plateau PL (18.1 ± 2.3 cmH2O) (R2 = 0.90, p = 0.001). Our correction method can estimate ΔPpl and plateau PL from ΔCVP with a reasonable accuracy in paralyzed and mechanically ventilated pediatric patients with respiratory failure.

Post-Extubation Inhaled Nitric Oxide Therapy via High-Flow Nasal Cannula After Fontan Procedure.

In 2014, our hospital introduced inhaled nitric oxide (iNO) therapy combined with high-flow nasal cannula (HFNC) oxygen therapy after extubation following the Fontan procedure in patients with unstable hemodynamics. We report the benefits of HFNC-iNO therapy in these patients. This was a single-center, retrospective review of 38 patients who underwent the Fontan procedure between January 2010 and June 2016, and required iNO therapy before extubation. The patients were divided into two groups: patients in Epoch 1 (n = 24) were treated between January 2010 and December 2013, receiving only iNO therapy; patients in Epoch 2 (n = 14) were treated between January 2014 and June 2016, receiving iNO therapy and additional HFNC-iNO therapy after extubation. There were no significant differences between Epoch 1 and 2 regarding preoperative cardiac function, age at surgery, body weight, initial diagnosis (hypoplastic left heart syndrome, 4 vs. 2; total anomalous pulmonary venous return, 5 vs. 4; heterotaxy, 7 vs. 8), intraoperative fluid balance, or central venous pressure upon admission to the intensive care unit. Epoch 2 had a significantly shorter duration of postoperative intubation [7.2 (3.7-49) vs. 3.5 (3.0-4.6) hours, p = 0.033], pleural drainage [23 (13-34) vs. 9.5 (8.3-18) days, p = 0.007], and postoperative hospitalization [36 (29-49) vs. 27 (22-36) days, p = 0.017]. Two patients in Epoch 1 (8.3%), but none in Epoch 2, required re-intubation. Our results suggest that HFNC-iNO therapy reduces the duration of postoperative intubation, pleural drainage, and hospitalization.

Risk Factors for Healthcare-Associated Infections After Pediatric Cardiac Surgery.

OBJECTIVES: Healthcare-associated infections after pediatric cardiac surgery are significant causes of morbidity and mortality. We aimed to identify the risk factors for the occurrence of healthcare-associated infections after pediatric cardiac surgery. DESIGN: Retrospective, single-center observational study. SETTING: PICU at a tertiary children's hospital. PATIENTS: Consecutive pediatric patients less than or equal to 18 years old admitted to the PICU after cardiac surgery, between January 2013 and December 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All the data were retrospectively collected from the medical records of patients. We assessed the first surgery during a single PICU stay and identified four common healthcare-associated infections, including bloodstream infection, surgical site infection, pneumonia, and urinary tract infection, according to the definitions of the Centers for Disease Control and Prevention and National Healthcare Safety Network. We assessed the pre-, intra-, and early postoperative potential risk factors for these healthcare-associated infections via multivariable analysis. In total, 526 cardiac surgeries (394 patients) were included. We identified 81 cases of healthcare-associated infections, including, bloodstream infections (n = 30), surgical site infections (n = 30), urinary tract infections (n = 13), and pneumonia (n = 8). In the case of 71 of the surgeries (13.5%), at least one healthcare-associated infection was reported. Multivariable analysis indicated the following risk factors for postoperative healthcare-associated infections: mechanical ventilation greater than or equal to 3 days (odds ratio, 4.81; 95% CI, 1.89-12.8), dopamine use (odds ratio, 3.87; 95% CI, 1.53-10.3), genetic abnormality (odds ratio, 2.53; 95% CI, 1.17-5.45), and delayed sternal closure (odds ratio, 3.78; 95% CI, 1.16-12.8). CONCLUSIONS: Mechanical ventilation greater than or equal to 3 days, dopamine use, genetic abnormality, and delayed sternal closure were associated with healthcare-associated infections after pediatric cardiac surgery. Since the use of dopamine is an easily modifiable risk factor, and may serve as a potential target to reduce healthcare-associated infections, further studies are needed to establish whether dopamine negatively impacts the development of healthcare-associated infections.

Estimating the change in pleural pressure using the change in central venous pressure in various clinical scenarios: a pig model study.

BACKGROUND: We have previously reported a simple correction method for estimating pleural pressure (Ppl) using central venous pressure (CVP). However, it remains unclear whether this method is applicable to patients with varying levels of intravascular volumes and/or chest wall compliance. This study aimed to investigate the accuracy of our method under different conditions of intravascular volume and chest wall compliance. RESULTS: Ten anesthetized and paralyzed pigs (43.2 ± 1.8 kg) were mechanically ventilated and subjected to lung injury by saline lung lavage. Each pig was subjected to three different intravascular volumes and two different intraabdominal pressures. For each condition, the changes in the esophageal pressure (ΔPes) and the estimated ΔPpl using ΔCVP (cΔCVP-derived ΔPpl) were compared to the directly measured change in pleural pressure (Δd-Ppl), which was the gold standard estimate in this study. The cΔCVP-derived ΔPpl was calculated as κ × ΔCVP, where "κ" was the ratio of the change in airway pressure to the change in CVP during the occlusion test. The means and standard deviations of the Δd-Ppl, ΔPes, and cΔCVP-derived ΔPpl for all pigs under all conditions were 7.6 ± 4.5, 7.2 ± 3.6, and 8.0 ± 4.8 cmH2O, respectively. The repeated measures correlations showed that both the ΔPes and cΔCVP-derived ΔPpl showed a strong correlation with the Δd-Ppl (ΔPes: r = 0.95, p < 0.0001; cΔCVP-derived ΔPpl: r = 0.97, p < 0.0001, respectively). In the Bland-Altman analysis to test the performance of the cΔCVP-derived ΔPpl to predict the Δd-Ppl, the ΔPes and cΔCVP-derived ΔPpl showed almost the same bias and precision (ΔPes: 0.5 and 1.7 cmH2O; cΔCVP-derived ΔPpl: - 0.3 and 1.9 cmH2O, respectively). No significant difference was found in the bias and precision depending on the intravascular volume and intraabdominal pressure in both comparisons between the ΔPes and Δd-Ppl, and cΔCVP-derived ΔPpl and Δd-Ppl. CONCLUSIONS: The CVP method can estimate the ΔPpl with reasonable accuracy, similar to Pes measurement. The accuracy was not affected by the intravascular volume or chest wall compliance.

Fundamental concepts and the latest evidence for esophageal pressure monitoring.

Transpulmonary pressure is an essential physiologic concept as it reflects the true pressure across the alveoli, and is a more precise marker for lung stress. To calculate transpulmonary pressure, one needs an estimate of both alveolar pressure and pleural pressure. Airway pressure during conditions of no flow is the most widely accepted surrogate for alveolar pressure, while esophageal pressure remains the most widely measured surrogate marker for pleural pressure. This review will cover important concepts and clinical applications for esophageal manometry, with a particular focus on how to use the information from esophageal manometry to adjust or titrate ventilator support. The most widely used method for measuring esophageal pressure uses an esophageal balloon catheter, although these measurements can be affected by the volume of air in the balloon. Therefore, when using balloon catheters, it is important to calibrate the balloon to ensure the most appropriate volume of air, and we discuss several methods which have been proposed for balloon calibration. In addition, esophageal balloon catheters only estimate the pleural pressure over a certain area within the thoracic cavity, which has resulted in a debate regarding how to interpret these measurements. We discuss both direct and elastance-based methods to estimate transpulmonary pressure, and how they may be applied for clinical practice. Finally, we discuss a number of applications for esophageal manometry and review many of the clinical studies published to date which have used esophageal pressure. These include the use of esophageal pressure to assess lung and chest wall compliance individually which can provide individualized information for patients with acute respiratory failure in terms of setting PEEP, or limiting inspiratory pressure. In addition, esophageal pressure has been used to estimate effort of breathing which has application for ventilator weaning, detection of upper airway obstruction after extubation, and detection of patient and mechanical ventilator asynchrony.

Estimation of change in pleural pressure in assisted and unassisted spontaneous breathing pediatric patients using fluctuation of central venous pressure: A preliminary study.

BACKGROUND: It is important to evaluate the size of respiratory effort to prevent patient self-inflicted lung injury and ventilator-induced diaphragmatic dysfunction. Esophageal pressure (Pes) measurement is the gold standard for estimating respiratory effort, but it is complicated by technical issues. We previously reported that a change in pleural pressure (ΔPpl) could be estimated without measuring Pes using change in CVP (ΔCVP) that has been adjusted with a simple correction among mechanically ventilated, paralyzed pediatric patients. This study aimed to determine whether our method can be used to estimate ΔPpl in assisted and unassisted spontaneous breathing patients during mechanical ventilation. METHODS: The study included hemodynamically stable children (aged <18 years) who were mechanically ventilated, had spontaneous breathing, and had a central venous catheter and esophageal balloon catheter in place. We measured the change in Pes (ΔPes), ΔCVP, and ΔPpl that was calculated using a corrected ΔCVP (cΔCVP-derived ΔPpl) under three pressure support levels (10, 5, and 0 cmH2O). The cΔCVP-derived ΔPpl value was calculated as follows: cΔCVP-derived ΔPpl = k × ΔCVP, where k was the ratio of the change in airway pressure (ΔPaw) to the ΔCVP during airway occlusion test. RESULTS: Of the 14 patients enrolled in the study, 6 were excluded because correct positioning of the esophageal balloon could not be confirmed, leaving eight patients for analysis (mean age, 4.8 months). Three variables that reflected ΔPpl (ΔPes, ΔCVP, and cΔCVP-derived ΔPpl) were measured and yielded the following results: -6.7 ± 4.8, - -2.6 ± 1.4, and - -7.3 ± 4.5 cmH2O, respectively. The repeated measures correlation between cΔCVP-derived ΔPpl and ΔPes showed that cΔCVP-derived ΔPpl had good correlation with ΔPes (r = 0.84, p< 0.0001). CONCLUSIONS: ΔPpl can be estimated reasonably accurately by ΔCVP using our method in assisted and unassisted spontaneous breathing children during mechanical ventilation.

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).