Lung-Protective Ventilation for Pediatric Acute Respiratory Distress Syndrome: A Nonrandomized Controlled Trial.

OBJECTIVES: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS. DESIGN: Multicenter prospective before-and-after comparison design study. SETTING: Twenty-one PICUs. PATIENTS: Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation. INTERVENTIONS: The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to Fio2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets. MEASUREMENTS AND MAIN RESULTS: There were 285 of 693 (41·1%) and 408 of 693 (58·9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0·001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/Fio2 combinations were associated with reduced mortality. CONCLUSIONS: Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence.

Lung-Protective Mechanical Ventilation Strategies in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: Reduced morbidity and mortality associated with lung-protective mechanical ventilation is not proven in pediatric acute respiratory distress syndrome. This study aims to determine if a lung-protective mechanical ventilation protocol in pediatric acute respiratory distress syndrome is associated with improved clinical outcomes. DESIGN: This pilot study over April 2016 to September 2019 adopts a before-and-after comparison design of a lung-protective mechanical ventilation protocol. All admissions to the PICU were screened daily for fulfillment of the Pediatric Acute Lung Injury Consensus Conference criteria and included. SETTING: Multidisciplinary PICU. PATIENTS: Patients with pediatric acute respiratory distress syndrome. INTERVENTIONS: Lung-protective mechanical ventilation protocol with elements on peak pressures, tidal volumes, end-expiratory pressure to FIO2 combinations, permissive hypercapnia, and permissive hypoxemia. MEASUREMENTS AND MAIN RESULTS: Ventilator and blood gas data were collected for the first 7 days of pediatric acute respiratory distress syndrome and compared between the protocol (n = 63) and nonprotocol groups (n = 69). After implementation of the protocol, median tidal volume (6.4 mL/kg [5.4-7.8 mL/kg] vs 6.0 mL/kg [4.8-7.3 mL/kg]; p = 0.005), PaO2 (78.1 mm Hg [67.0-94.6 mm Hg] vs 74.5 mm Hg [59.2-91.1 mm Hg]; p = 0.001), and oxygen saturation (97% [95-99%] vs 96% [94-98%]; p = 0.007) were lower, and end-expiratory pressure (8 cm H2O [7-9 cm H2O] vs 8 cm H2O [8-10 cm H2O]; p = 0.002] and PaCO2 (44.9 mm Hg [38.8-53.1 mm Hg] vs 46.4 mm Hg [39.4-56.7 mm Hg]; p = 0.033) were higher, in keeping with lung protective measures. There was no difference in mortality (10/63 [15.9%] vs 18/69 [26.1%]; p = 0.152), ventilator-free days (16.0 [2.0-23.0] vs 19.0 [0.0-23.0]; p = 0.697), and PICU-free days (13.0 [0.0-21.0] vs 16.0 [0.0-22.0]; p = 0.233) between the protocol and nonprotocol groups. After adjusting for severity of illness, organ dysfunction and oxygenation index, the lung-protective mechanical ventilation protocol was associated with decreased mortality (adjusted hazard ratio, 0.37; 95% CI, 0.16-0.88). CONCLUSIONS: In pediatric acute respiratory distress syndrome, a lung-protective mechanical ventilation protocol improved adherence to lung-protective mechanical ventilation strategies and potentially mortality.

The longitudinal course of pediatric acute respiratory distress syndrome and its time to resolution: A prospective observational study.

Background: The longitudinal course of patients with pediatric acute respiratory distress syndrome (PARDS) is not well described. In this study, we describe the oxygenation index (OI) and oxygen saturation index (OSI) in mild, moderate, and severe PARDS over 28 days and provide pilot data for the time to resolution of PARDS (T res), as a short-term respiratory-specific outcome, hypothesizing that it is associated with the severity of PARDS and clinical outcomes. Methods: This prospective observational study recruited consecutive patients with PARDS. OI and OSI were trended daily over 28 days. T res (defined as OI < 4 or OSI < 5.3 on 2 consecutive days) were described based on PARDS severity and analyzed with Poisson and logistic regression to determine its association with conventional outcomes [mechanical ventilation (MV) duration, intensive care unit (ICU) and hospital length of stay, 28-day ventilator-free days (VFD), and 28-day ICU-free days (IFD)]. Results: There were 121 children included in this study, 33/121(27.3%), 44/121(36.4%), and 44/121(36.4%) in the mild, moderate, and severe groups of PARDS, respectively. OI and OSI clearly differentiated mild, moderate, and severe groups in the first 7days of PARDS; however, this differentiation was no longer present after 7days. Median T res was 4 (interquartile range: 3, 6), 5 (4, 7), and 7.5 (7, 11.5) days; p < 0.001 for the mild, moderate, and severe groups of PARDS, respectively. T res was associated with increased MV duration, ICU and hospital length of stay, and decreased VFD and IFD. Conclusion: The oxygenation defect in PARDS took progressively longer to resolve across the mild, moderate, and severe groups. T res is a potential short-term respiratory-specific outcome, which may be useful in addition to conventional clinical outcomes but needs further validation in external cohorts.

Characteristics and trajectory of patients with pediatric acute respiratory distress syndrome.

OBJECTIVE: This study delineates the disease trajectory of patients with pediatric acute respiratory distress syndrome (PARDS) defined by the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition, and evaluates the impact of comorbidities on outcomes. METHODS: This prospective study over November 2017-October 2019 was conducted in a single-center multidisciplinary pediatric intensive care unit (PICU) and included patients <21years of age with PARDS. Clinical history of those requiring mechanical ventilation for <3 days was interrogated and cases in which the diagnosis of PARDS were unlikely, identified. The impact of chronic comorbidities on clinical outcomes, in particular, pulmonary disease and immunosuppression, were analyzed. RESULTS: Eighty-five of 1272 PICU admissions (6.7%) met the criteria for PARDS and were included. Median age and oxygenation indexes were 2.8 (0.6, 8.3) years and 10.6 (7.6, 15.4), respectively. Overall mortality was 12 out of 85 (14.1%). Despite fulfilling criteria in 6/85 (7.1%), hypoxemia contributed by bronchospasm, mucus plugging, fluid overload, and atelectasis was quickly reversible and PARDS was unlikely in these patients. Comorbidities (57/85 [67.1%]) were not associated with worsened outcomes. However, pre-existing pulmonary disease and immunosuppression were associated with severe PARDS (12/20 [60.0%] vs 19/65 [29.2%]; P = .017), extracorporeal membrane oxygenation use (5/20 [25.0%] vs 3/65 [4.6%]; P = .016) and reduced ventilator free days (VFD) (15 [0, 19] vs 21 [6, 23]; P = .039), compared with those without them. CONCLUSION: A small percentage of children fulfilling the PALICC definition had quickly reversible hypoxemia with likely alternate pathophysiology to PARDS. Patients with pulmonary comorbidities and immunosuppression had a more severe course of PARDS compared with others.

Pertinent clinical outcomes in pediatric survivors of pediatric acute respiratory distress syndrome (PARDS): a narrative review.

The objectives of this review are to describe the limitations of commonly used clinical outcomes [e.g., mortality, ventilation parameters, need for extracorporeal membrane oxygenation (ECMO), pediatric intensive care unit (PICU) and hospital length of stay (LOS)] in pediatric acute respiratory distress syndrome (PARDS) studies; and to explore other pertinent clinical outcomes that pediatric critical care practitioners should consider in future clinical practice and research studies. These include long-term pulmonary function, risk of pulmonary hypertension (PHT), nutrition status and growth, PICU-acquired weakness, neurological outcomes and neurocognitive development, functional status, health-related quality of life (HRQOL)], health-care costs, caregiver and family stress. PubMed was searched using the following keywords or medical subject headings (MESH): "acute lung injury (ALI)", "acute respiratory distress syndrome (ARDS)", "pediatric acute respiratory distress syndrome (PARDS)", "acute hypoxemia respiratory failure", "outcomes", "pediatric intensive care unit (PICU)", "lung function", "pulmonary hypertension", "growth", "nutrition', "steroid", "PICU-acquired weakness", "functional status scale", "neurocognitive", "psychology", "health-care expenditure", and "HRQOL". The concept of contemporary measure outcomes was adapted from adult ARDS long-term outcome studies. Articles were initially searched from existing PARDS articles pool. If the relevant measure outcomes were not found, where appropriate, we considered studies from non-ARDS patients within the PICU in whom these outcomes were studied. Long-term outcomes in survivors of PARDS were not follow-up in majority of pediatric studies regardless of whether the new or old definitions of ARDS in children were used. Relevant studies were scarce, and the number of participants was small. As such, available studies were not able to provide conclusive answers to most of our clinical queries. There remains a paucity of data on contemporary clinical outcomes in PARDS studies. In addition to the current commonly used outcomes, clinical researchers and investigators should consider examining these contemporary outcome measures in PARDS studies in the future.