Hemodynamic Effects of a High-Frequency Oscillatory Ventilation Open-Lung Strategy in Critically Ill Children With Acquired or Congenital Cardiac Disease.

OBJECTIVES: To study the hemodynamic consequences of an open-lung high-frequency oscillatory ventilation (HFOV) strategy in patients with an underlying cardiac anomaly with or without intracardiac shunt or primary pulmonary hypertension with severe lung injury. DESIGN: Secondary analysis of prospectively collected data. SETTING: Medical-surgical PICU. PATIENTS: Children less than 18 years old with cardiac anomalies (± intracardiac shunt) or primary pulmonary hypertension. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 52 subjects were analyzed, of whom 39 of 52 with cardiac anomaly (23/39 with intracardiac shunt) and 13 of 52 with primary pulmonary hypertension. Fourteen patients were admitted postoperatively, and 26 patients were admitted with acute respiratory failure. Five subjects (9.6%) were canulated for ECMO (of whom four for worsening respiratory status). Ten patients (19.2%) died during PICU stay. Median conventional mechanical ventilation settings prior to HFOV were peak inspiratory pressure 30 cm H 2 O (27-33 cm H 2 O), positive end-expiratory pressure 8 cm H 2 O (6-10 cm H 2 O), and F io2 0.72 (0.56-0.94). After transitioning to HFOV, there was no negative effect on mean arterial blood pressure, central venous pressure, or arterial lactate. Heart rate decreased significantly over time ( p < 0.0001), without group differences. The percentage of subjects receiving a fluid bolus decreased over time ( p = 0.003), especially in those with primary pulmonary hypertension ( p = 0.0155) and without intracardiac shunt ( p = 0.0328). There were no significant differences in the cumulative number of daily boluses over time. Vasoactive Infusion Score did not increase over time. Pa co2 decreased ( p < 0.0002) and arterial pH significantly improved ( p < 0.0001) over time in the whole cohort. Neuromuscular blocking agents were used in all subjects switched to HFOV. Daily cumulative sedative doses were unchanged, and no clinically apparent barotrauma was found. CONCLUSIONS: No negative hemodynamic consequences occurred with an individualized, physiology-based open-lung HFOV approach in patients with cardiac anomalies or primary pulmonary hypertension suffering from severe lung injury.

Performance of acute respiratory distress syndrome definitions in a high acuity paediatric intensive care unit.

BACKGROUND: For years, paediatric critical care practitioners used the adult American European Consensus Conference (AECC) and revised Berlin Definition (BD) for acute respiratory distress syndrome (ARDS) to study the epidemiology of paediatric ARDS (PARDS). In 2015, the paediatric specific definition, Paediatric Acute Lung Injury Consensus Conference (PALICC) was developed. The use of non-invasive metrics of oxygenation to stratify disease severity were introduced in this definition, although this potentially may lead to a confounding effect of disease severity since it is more common to place indwelling arterial lines in sicker patients. We tested the hypothesis that PALICC outperforms AECC/BD in our high acuity PICU, which employs a liberal use of indwelling arterial lines and high-frequency oscillatory ventilation (HFOV). METHODS: We retrospectively collected data from children < 18 years mechanically ventilated for at least 24 h in our tertiary care, university-affiliated paediatric intensive care unit. The primary endpoint was the difference in the number of PARDS cases between AECC/BD and PALICC. Secondary endpoints included mortality and ventilator free days. Performance was assessed by the area under the receiver operating characteristics curve (AUC-ROC). RESULTS: Data from 909 out of 2433 patients was eligible for analysis. AECC/BD identified 35 (1.4%) patients (mortality 25.7%), whereas PALICC identified 135 (5.5%) patients (mortality 14.1%). All but two patients meeting AECC/Berlin criteria were also identified by PALICC. Almost half of the cohort (45.2%) had mild, 33.3% moderate and 21.5% severe PALICC PARDS at onset. Highest mortality rates were seen in patients with AECC acute lung injury (ALI)/mild Berlin and severe PALICC PARDS. The AUC-ROC for Berlin was the highest 24 h (0.392 [0.124-0.659]) after onset. PALICC showed the highest AUC-ROC at the same moment however higher than Berlin (0.531 [0.345-0.716]). Mortality rates were significantly increased in patients with bilateral consolidations (9.3% unilateral vs 26.3% bilateral, p = 0.025). CONCLUSIONS: PALICC identified more new cases PARDS than the AECC/Berlin definition. However, both PALICC and Berlin performed poorly in terms of mortality risk stratification. The presence of bilateral consolidations was associated with a higher mortality rate. Our findings may be considered in future modifications of the PALICC criteria.

Effect of Endotracheal Tube Size, Respiratory System Mechanics, and Ventilator Settings on Driving Pressure.

OBJECTIVES: We sought to investigate factors that affect the difference between the peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions (resistive pressure) during pressure controlled ventilation across a range of endotracheal tube sizes, respiratory mechanics, and ventilator settings. DESIGN: In vitro study. SETTING: Research laboratory. PATIENTS: None. INTERVENTIONS: An in vitro bench model of the intubated respiratory system during pressure controlled ventilation was used to obtain the difference between peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions across a range of endotracheal tubes sizes (3.0-8.0 mm). Measurements were taken at combinations of pressure above positive end-expiratory pressure (10, 15, and 20 cm H2O), airway resistance (no, low, high), respiratory system compliance (ranging from normal to extremely severe), and inspiratory time at constant positive end-expiratory pressure (5 cm H2O). Multiple regression analysis was used to construct models predicting resistive pressure stratified by endotracheal tube size. MEASUREMENTS AND MAIN RESULTS: On univariate regression analysis, respiratory system compliance (ß -1.5; 95% CI, -1.7 to -1.4; p < 0.001), respiratory system resistance (ß 1.7; 95% CI, 1.5-2.0; p < 0.001), pressure above positive end-expiratory pressure (ß 1.7; 95% CI, 1.4-2.0; p < 0.001), and inspiratory time (ß -0.7; 95% CI, -1.0 to -0.4; p < 0.001) were associated with resistive pressure. Multiple linear regression analysis showed the independent association between increasing respiratory system compliance, increasing airway resistance, increasing pressure above positive end-expiratory pressure, and decreasing inspiratory time and resistive pressure across all endotracheal tube sizes. Inspiratory time was the strongest variable associated with a proportional increase in resistive pressure. The contribution of airway resistance became more prominent with increasing endotracheal tube size. CONCLUSIONS: Peak inspiratory pressures measured during pressure controlled ventilation overestimated plateau pressure irrespective of endotracheal tube size, especially with decreased inspiratory time or increased airway resistance.

Tidal volume and mortality in mechanically ventilated children: a systematic review and meta-analysis of observational studies*.

OBJECTIVE: To determine whether tidal volume is associated with mortality in critically ill, mechanically ventilated children. DATA SOURCES: MEDLINE, EMBASE, and CINAHL databases from inception until July 2013 and bibliographies of included studies without language restrictions. STUDY SELECTION: Randomized clinical trials and observational studies reporting mortality in mechanically ventilated PICU patients. DATA EXTRACTION: Two authors independently selected studies and extracted data on study methodology, quality, and patient outcomes. Meta-analyses were performed using the Mantel-Haenszel random-effects model. Heterogeneity was quantified using I. Study quality was assessed using the Newcastle-Ottawa Score for cohort studies. DATA SYNTHESIS: Out of 142 citations, seven studies met the inclusion criteria, and additional two articles were identified from references of the found articles. One was excluded. These eight studies included 1,756 patients. Mortality rates ranged from 13% to 42%. There was no association between tidal volume and mortality when tidal volume was dichotomized at 7, 8, 10, or 12 mL/kg. Comparing patients ventilated with tidal volume less than 7 mL/kg and greater than 10 mL/kg or greater than 12 mL/kg and tidal volume less than 8 mL/kg and greater than 10 mL/kg or greater than 12 mL/kg also showed no association between tidal volume and mortality. Limiting the analysis to patients with acute lung injury/acute respiratory distress syndrome did not change these results. Heterogeneity was observed in all pooled analyses. CONCLUSIONS: A relationship between tidal volume and mortality in mechanically ventilated children could not be identified, irrespective of the severity of disease. The significant heterogeneity observed in the pooled analyses necessitates future studies in well-defined patient populations to understand the effects of tidal volume on patient outcome.

Lung behavior during a staircase high-frequency oscillatory ventilation recruitment maneuver.

BACKGROUND: Lung volume optimization maneuvers (LVOM) are necessary to make physiologic use of high-frequency oscillatory ventilation (HFOV), but lung behavior during such maneuvers has not been studied to determine lung volume changes after initiation of HFOV, to quantify recruitment versus derecruitment during the LVOM and to calculate the time to stabilization after a pressure change. METHODS: We performed a secondary analysis of prospectively collected data in subjects < 18 years on HFOV. Uncalibrated respiratory inductance plethysmography (RIP) tracings were used to quantify lung recruitment and derecruitment during the LVOM inflation and deflation. The time constant was calculated according to the Niemann model. RESULTS: RIP data of 51 subjects (median age 3.5 [1.7-13.3] months) with moderate-to-severe pediatric acute respiratory distress syndrome (PARDS) in 85.4% were analyzed. Lung recruitment and derecruitment occurred during the LVOM inflation phase upon start of HFOV and between and within pressure changes. At 90% of maximum inflation pressure, lung derecruitment already started during the deflation phase. Time to stable lung volume (time constant) could only be calculated in 26.2% of all pressure changes during the inflation and in 21.4% during the deflation phase, independent of continuous distending pressure (CDP). Inability to calculate the time constant was due to lack of stabilization of the RIP signal or no change in any direction. CONCLUSIONS: Significant heterogeneity in lung behavior during a staircase incremental-decremental LVOM occurred, underscoring the need for higher initial inflation pressures when transitioning from conventional mechanical ventilation (CMV) and a longer time between pressure changes to allow for equilibration.

Physiologic responses to a staircase lung volume optimization maneuver in pediatric high-frequency oscillatory ventilation.

BACKGROUND: Titration of the continuous distending pressure during a staircase incremental-decremental pressure lung volume optimization maneuver in children on high-frequency oscillatory ventilation is traditionally driven by oxygenation and hemodynamic responses, although validity of these metrics has not been confirmed. METHODS: Respiratory inductance plethysmography values were used construct pressure-volume loops during the lung volume optimization maneuver. The maneuver outcome was evaluated by three independent investigators and labeled positive if there was an increase in respiratory inductance plethysmography values at the end of the incremental phase. Metrics for oxygenation (SpO2, FiO2), proximal pressure amplitude, tidal volume and transcutaneous measured pCO2 (ptcCO2) obtained during the incremental phase were compared between outcome maneuvers labeled positive and negative to calculate sensitivity, specificity, and the area under the receiver operating characteristic curve. Ventilation efficacy was assessed during and after the maneuver by measuring arterial pH and PaCO2. Hemodynamic responses during and after the maneuver were quantified by analyzing heart rate, mean arterial blood pressure and arterial lactate. RESULTS: 41/54 patients (75.9%) had a positive maneuver albeit that changes in respiratory inductance plethysmography values were very heterogeneous. During the incremental phase of the maneuver, metrics for oxygenation and tidal volume showed good sensitivity (> 80%) but poor sensitivity. The sensitivity of the SpO2/FiO2 ratio increased to 92.7% one hour after the maneuver. The proximal pressure amplitude showed poor sensitivity during the maneuver, whereas tidal volume showed good sensitivity but poor specificity. PaCO2 decreased and pH increased in patients with a positive and negative maneuver outcome. No new barotrauma or hemodynamic instability (increase in age-adjusted heart rate, decrease in age-adjusted mean arterial blood pressure or lactate > 2.0 mmol/L) occurred as a result of the maneuver. CONCLUSIONS: Absence of improvements in oxygenation during a lung volume optimization maneuver did not indicate that there were no increases in lung volume quantified using respiratory inductance plethysmography. Increases in SpO2/FiO2 one hour after the maneuver may suggest ongoing lung volume recruitment. Ventilation was not impaired and there was no new barotrauma or hemodynamic instability. The heterogeneous responses in lung volume changes underscore the need for monitoring tools during high-frequency oscillatory ventilation.

Ventilator-induced lung injury in children: a reality?

Mechanical ventilation (MV) is inextricably linked to the care of critically ill patients admitted to the paediatric intensive care unit (PICU). Even today, little evidence supports best MV practices for life-threatening acute respiratory failure in children. However, careful attention must be paid because this life-saving technique induces pulmonary inflammation that aggravates pre-existing lung injury, a concept that is known as ventilator-induced lung injury (VILI). The delivery of too large tidal volumes (Vt) (i.e., volutrauma) and repetitive opening and closure of alveoli (i.e., atelectrauma) are two key mechanisms underlying VILI. Despite the knowledge of these mechanisms, the clinical relevance of VILI in critically ill children is poorly understood as almost all of our knowledge has been obtained from studies in adults or experimental studies mimicking the adult critical care situation. This leaves the question if VILI is relevant in the paediatric context. In fact, limited paediatric experimental data showed that the use of large, supraphysiologic Vt resulted in less inflammation and injury in paediatric animal models compared to adult models. Furthermore, the association between large Vt and adverse outcome has not been confirmed and the issue of setting positive end-expiratory pressure (PEEP) to prevent atelectrauma has hardly been studied in paediatric clinical studies. Hence, even today, the question whether or not there VILI is relevant in pediatric critical remains to be answered. Consequently, how MV is used remains thus based on institutional preferences, personal beliefs and clinical data extrapolated from adults. This signifies the need for clinical and experimental studies in order to better understand the use and effects of MV in paediatric patients with or without lung injury.

Feasibility of an alternative, physiologic, individualized open-lung approach to high-frequency oscillatory ventilation in children.

BACKGROUND: High-frequency oscillatory ventilation (HFOV) is a common but unproven management strategy in paediatric critical care. Oscillator settings have been traditionally guided by patient age and/or weight rather than by lung mechanics, thereby potentially negating any beneficial effects. We have adopted an open-lung HFOV strategy based on a corner frequency approach using an initial incremental-decremental mean airway pressure titration manoeuvre, a high frequency (8-15 Hz), and high power to initially target a proximal pressure amplitude (∆Pproximal) of 70-90 cm H2O, irrespective of age or weight. METHODS: We reviewed prospectively collected data on patients < 18 years of age who were managed with HFOV for acute respiratory failure. We measured metrics for oxygenation, ventilation, and haemodynamics as well as the use of sedative-analgesic medications and neuromuscular blocking agents. RESULTS: Data from 115 non-cardiac patients were analysed, of whom 53 had moderate-to-severe paediatric acute respiratory distress syndrome (PARDS). Sixteen patients (13.9%) died. Frequencies≥ 8 Hz and high ∆Pproximal were achieved in all patients irrespective of age or PARDS severity. Patients with severe PARDS showed the greatest improvement in oxygenation. pH and PaCO2 normalized in all patients. Haemodynamic parameters, cumulative amount of fluid challenges, and daily fluid balance did not deteriorate after transitioning to HFOV in any age or PARDS severity group. We observed a transient increase neuromuscular blocking agent use after switching to HFOV, but there was no increase in the daily cumulative amount of continuous midazolam or morphine in any age or PARDS severity group. No patients experienced clinically apparent barotrauma. CONCLUSIONS: This is the first study reporting the feasibility of an alternative, individualized, physiology-based open-lung HFOV strategy targeting high F and high ∆Pproximal. No adverse effects were observed with this strategy. Our findings warrant further systematic evaluation.

Short-term effects of neuromuscular blockade on global and regional lung mechanics, oxygenation and ventilation in pediatric acute hypoxemic respiratory failure.

BACKGROUND: Neuromuscular blockade (NMB) has been shown to improve outcome in acute respiratory distress syndrome (ARDS) in adults, challenging maintaining spontaneous breathing when there is severe lung injury. We tested in a prospective physiological study the hypothesis that continuous administration of NMB agents in mechanically ventilated children with severe acute hypoxemic respiratory failure (AHRF) improves the oxygenation index without a redistribution of tidal volume V T toward non-dependent lung zones. METHODS: Oxygenation index, PaO2/FiO2 ratio, lung mechanics (plateau pressure, mean airway pressure, respiratory system compliance and resistance), hemodynamics (heart rate, central venous and arterial blood pressures), oxygenation [oxygenation index (OI), PaO2/FiO2 and SpO2/FiO2], ventilation (physiological dead space-to-V T ratio) and electrical impedance tomography measured changes in end-expiratory lung volume (EELV), and V T distribution was measured before and 15 min after the start of continuous infusion of rocuronium 1 mg/kg. Patients were ventilated in a time-cycled, pressure-limited mode with pre-set V T. All ventilator settings were not changed during the study. RESULTS: Twenty-two patients were studied (N = 18 met the criteria for pediatric ARDS). Median age (25-75 interquartile range) was 15 (7.8-77.5) weeks. Pulmonary pathology was present in 77.3%. The median lung injury score was 9 (8-10). The overall median CoV and regional lung filling characteristics were not affected by NMB, indicating no ventilation shift toward the non-dependent lung zones. Regional analysis showed a homogeneous time course of lung inflation during inspiration, indicating no tendency to atelectasis after the introduction of NMB. NMB decreased the mean airway pressure (p = 0.039) and OI (p = 0.039) in all patients. There were no significant changes in lung mechanics, hemodynamics and EELV. Subgroup analysis showed that OI decreased (p = 0.01) and PaO2/FiO2 increased (p = 0.02) in patients with moderate or severe PARDS. CONCLUSIONS: NMB resulted in an improved oxygenation index in pediatric patients with AHRF. Distribution of V T and regional lung filling characteristics were not affected.