Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study

Abstract

Background: Paediatric acute respiratory distress syndrome (PARDS) is associated with high mortality in children, but until recently no paediatric-specific diagnostic criteria existed. The Pediatric Acute Lung Injury Consensus Conference (PALICC) definition was developed to overcome limitations of the Berlin definition, which was designed and validated for adults. We aimed to determine the incidence and outcomes of children who meet the PALICC definition of PARDS.

Methods: In this international, prospective, cross-sectional, observational study, 145 paediatric intensive care units (PICUs) from 27 countries were recruited, and over a continuous 5 day period across 10 weeks all patients were screened for enrolment. Patients were included if they had a new diagnosis of PARDS that met PALICC criteria during the study week. Exclusion criteria included meeting PARDS criteria more than 24 h before screening, cyanotic heart disease, active perinatal lung disease, and preparation or recovery from a cardiac intervention. Data were collected on the PICU characteristics, patient demographics, and elements of PARDS (ie, PARDS risk factors, hypoxaemia severity metrics, type of ventilation), comorbidities, chest imaging, arterial blood gas measurements, and pulse oximetry. The primary outcome was PICU mortality. Secondary outcomes included 90 day mortality, duration of invasive mechanical and non-invasive ventilation, and cause of death.

Findings: Between May 9, 2016, and June 16, 2017, during the 10 study weeks, 23 280 patients were admitted to participating PICUs, of whom 744 (3·2%) were identified as having PARDS. 95% (708 of 744) of patients had complete data for analysis, with 17% (121 of 708; 95% CI 14-20) mortality, whereas only 32% (230 of 708) of patients met Berlin criteria with 27% (61 of 230) mortality. Based on hypoxaemia severity at PARDS diagnosis, mortality was similar among those who were non-invasively ventilated and with mild or moderate PARDS (10-15%), but higher for those with severe PARDS (33% [54 of 165; 95% CI 26-41]). 50% (80 of 160) of non-invasively ventilated patients with PARDS were subsequently intubated, with 25% (20 of 80; 95% CI 16-36) mortality. By use of PALICC PARDS definition, severity of PARDS at 6 h after initial diagnosis (area under the curve [AUC] 0·69, 95% CI 0·62-0·76) discriminates PICU mortality better than severity at PARDS diagnosis (AUC 0·64, 0·58-0·71), and outperforms Berlin severity groups at 6 h (0·64, 0·58-0·70; p=0·01).

Interpretation: The PALICC definition identified more children as having PARDS than the Berlin definition, and PALICC PARDS severity groupings improved the stratification of mortality risk, particularly when applied 6 h after PARDS diagnosis. The PALICC PARDS framework should be considered for use in future epidemiological and therapeutic research among children with PARDS.

Funding: University of Southern California Clinical Translational Science Institute, Sainte Justine Children's Hospital, University of Montreal, Canada, Réseau en Santé Respiratoire du Fonds de Recherche Quebec-Santé, and Children's Hospital Los Angeles, Department of Anesthesiology and Critical Care Medicine.

Figure 1:

Screened and enrolled patients, stratified by initial PARDS severity. As per the PALICC definition, patients normally on home ventilation were identified as having PARDS, but not included in the severity stratification.

Figure 2a (top) and b (bottom):

Berlin criteria at (a) PARDS diagnosis and (b) within 3 days of PARDS diagnosis. The size of the box represents the number of patients in each area and the cumulative total is represented on the x-axis. The diamond represents the point estimate for ICU mortality with the 95% Confidence Interval (whiskers). Bilateral = bilateral infiltrates on chest x-ray. Unilateral= unilateral infiltrate on chest x-ray. (a) Only 32% of children have an arterial blood gas with PF <300 and bilateral infiltrates on chest imaging at the time of PARDS diagnosis (patients who met All Berlin Criteria, blue). Allowing for the SF ratio to be substituted for the PF ratio in the Berlin Definition, then 72% met modified Berlin Criteria (blue + green). Bilateral infiltrates at PARDS diagnosis were not present in 25% of PARDS patients who would have otherwise met Berlin SF/PF criteria (pink). Only 3% of patients who met PARDS criteria did not have a PF ratio ≤ 300 or SF ratio ≤ 264 at PARDS diagnosis (tan). (b) In the first 3 days of PARDS diagnosis, 58% of patients met all Berlin criteria (blue), and 86.3% met Berlin criteria if SF ratio was included (blue + green). *Note only 3 patients did not have a PF ratio ≤ 300 or SF ratio ≤ 264 within the first 3 days of PARDS diagnosis, so they are not labeled on the graph (tan). None of these 3 patients died.

Figure 3:

OI/OSI versus PF/SF ratio based severity stratifications for those initially on IMV (excluding home ventilation). Each graph represents the number of patients who would fall in each severity group (bars) using hypoxemia metrics at distinct time points after PARDS diagnosis: (a) PARDS diagnosis (b) 6 hours, (c) 12 hours, and (d) 24 hours after PARDS diagnosis. ICU mortality for each group is represented with the diamond, and the whiskers represent 95% Confidence Interval around the point estimate for mortality. For PALICC OI/OSI groups: Severe = OI ≥ 16 or OSI ≥ 12.3; Moderate = OI ≥ 8 and < 16 or OSI ≥ 7.5 and < 12.3; Mild = OI ≥ 4 and < 8 or OSI ≥ 5 and < 7.5; None = OI<4 or OSI <5, or no longer on mechanical ventilation. For Berlin PF/SF groups: Severe = PF ≤ 100 or SF ≤ 150; Moderate = PF ≤ 200 and > 100 or SF ≤ 221 and > 150; Mild = PF ≤ 300 and > 200 or SF ≤ 264 and SF> 221; None = PF >300 or SF > 264, or no longer on mechanical ventilation.

Figure 4

Cumulative proportions free of intubation as a function of initial hypoxemia severity for those on NIV. Very few children are intubated after 3 days (graph cut off at this point). Hypoxemia severity is highly associated with time to intubation (p<0.002, Log-rank test). Severe = PF ≤ 100 or SF ≤ 150; Moderate = PF ≤ 200 and > 100 or SF ≤ 221 and > 150; Mild = PF ≤ 300 and > 200 or SF ≤ 264 and SF> 221. No patients were censored.