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Improved oxygenation following methylprednisolone therapy and survival in paediatric acute respiratory distress syndrome.

ABSTRACT: BACKGROUND:Methylprednisolone remains a commonly used ancillary therapy for paediatric acute respiratory distress syndrome (PARDS), despite a lack of level 1 evidence to justify its use. When planning prospective trials it is useful to define response to therapy and to identify if there is differential response in certain patients, i.e. existence of 'responders' and 'non responders' to therapy. This retrospective, observational study carried out in 2 tertiary referral paediatric intensive care units aims to characterize the change in Oxygen Saturation Index, following the administration of low dose methylprednisolone in a cohort of patients with PARDS, to identify what proportion of children treated demonstrated response, whether any particular characteristics predict response to therapy, and to determine if a positive response to corticosteroids is associated with reduced Paediatric Intensive Care Unit mortality. METHODS:All patients who received prolonged, low dose, IV methylprednisolone for the specific indication of PARDS over a 5-year period (2011-2016) who met the PALICC criteria for PARDS at the time of commencement of steroid were included (n = 78).OSI was calculated four times per day from admission until discharge from PICU (or death). Patients with ?20% improvement in their mean daily OSI within 72 hours of commencement of methylprednisolone were classified as 'responders'. Primary outcome measure was survival to PICU discharge. RESULTS:Mean OSI of the cohort increased until the day of steroid commencement then improved thereafter. 59% of patients demonstrated a response to steroids. Baseline characteristics were similar between responders and non-responders. Survival to PICU discharge was significantly higher in 'responders' (74% vs 41% OR 4.14(1.57-10.87) p = 0.004). On multivariable analysis using likely confounders, response to steroid was an independent predictor of survival to PICU discharge (p = 0.002). Non-responders died earlier after steroid administration than responders (p = 0.003). CONCLUSIONS:An improvement in OSI was observed in 60% of patients following initiation of low dose methylprednisolone therapy in this cohort of patients with PARDS. Baseline characteristics fail to demonstrate a difference between responders and non-responders. A 20% improvement in OSI after commencement of methylprednisolone was independently predictive of survival, Prospective trials are needed to establish if there is a benefit from this therapy.

SUBMITTER: Mitting RB

PROVIDER: S-EPMC6879165 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Improved oxygenation following methylprednisolone therapy and survival in paediatric acute respiratory distress syndrome.

Mitting Rebecca B RB Ray Samiran S Raffles Michael M Egan Helen H Goley Paul P Peters Mark M Nadel Simon S

PloS one 20191126 11

<h4>Background</h4>Methylprednisolone remains a commonly used ancillary therapy for paediatric acute respiratory distress syndrome (PARDS), despite a lack of level 1 evidence to justify its use. When planning prospective trials it is useful to define response to therapy and to identify if there is differential response in certain patients, i.e. existence of 'responders' and 'non responders' to therapy. This retrospective, observational study carried out in 2 tertiary referral paediatric intensiv ...[more]

PMID: 31770398

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Project description:BackgroundPaediatric acute respiratory distress syndrome (PARDS) is a manifestation of severe, life-threatening lung injury necessitating mechanical ventilation with mortality rates ranging up to 40-50%. Neuromuscular blockade agents (NMBAs) may be considered to prevent patient self-inflicted lung injury in PARDS patients, but two trials in adults with severe ARDS yielded conflicting results. To date, randomised controlled trials (RCT) examining the effectiveness and efficacy of NMBAs for PARDS are lacking. We hypothesise that using NMBAs for 48 h in paediatric patients younger than 5 years of age with early moderate-to-severe PARDS will lead to at least a 20% reduction in cumulative respiratory morbidity score 12 months after discharge from the paediatric intensive care unit (PICU).MethodsThis is a phase IV, multicentre, randomised, double-blind, placebo-controlled trial performed in level-3 PICUs in the Netherlands. Eligible for inclusion are children younger than 5 years of age requiring invasive mechanical ventilation with positive end-expiratory pressure (PEEP) ≥ 5 cm H2O for moderate-to-severe PARDS occurring within the first 96 h of PICU admission. Patients are randomised to continuous infusion of rocuronium bromide or placebo for 48 h. The primary endpoint is the cumulative respiratory morbidity score 12 months after PICU discharge, adjusted for confounding by age, gestational age, family history of asthma and/or allergy, season in which questionnaire was filled out, day-care and parental smoking. Secondary outcomes include respiratory mechanics, oxygenation and ventilation metrics, pulmonary and systemic inflammation markers, prevalence of critical illness polyneuropathy and myopathy and metrics for patient outcome including ventilator free days at day 28, length of PICU and hospital stay, and mortality DISCUSSION: This is the first paediatric trial evaluating the effects of muscular paralysis in moderate-to-severe PARDS. The proposed study addresses a huge research gap identified by the Paediatric Acute Lung Injury Consensus Collaborative by evaluating practical needs regarding the treatment of PARDS. Paediatric critical care practitioners are inclined to use interventions such as NMBAs in the most critically ill. This liberal use must be weighed against potential side effects. The proposed study will provide much needed scientific support in the decision-making to start NMBAs in moderate-to-severe PARDS.Trial registrationClinicalTrials.gov NCT02902055 . Registered on September 15, 2016.

Project description:BackgroundHow the surgical stabilization of rib fractures after trauma affects the development of acute respiratory distress syndrome and impacts survival has yet to be determined in a large database. We hypothesized that surgical stabilization of rib fractures would not decrease the incidence of acute respiratory distress syndrome.MethodsThe National Trauma Data Bank was queried for all traumatic rib fractures in 2016. Patients were divided into groups with single rib fractures, multiple rib fractures, and flail chest. Nonoperative therapy was compared with stabilization of rib fractures of 1 to 2 ribs or 3+ ribs.ResultsThere were 114,972 total patients with rib fractures meeting inclusion criteria, with 5,106 (4.4%) having flail chest, 24,726 (21.5%) having single rib fractures, and 85,140 (74.1%) having multiple rib fractures. Those with flail chest (15.9%) were most likely to get rib plating in comparison to multiple rib fractures (0.9%) and single rib fractures (0.2%); P < .001. On logistic regression, surgical stabilization of rib fractures 1 to 2 ribs (odds ratio: 0.17, 95% confidence interval: 0.10-0.28) or 3+ ribs (odds ratio: 0.17, 95% confidence interval: 0.11-0.28), with nonoperative therapy as the reference was associated with survival. Variables associated with mortality included increasing age, male sex, increasing injury severity score, decreased Glasgow coma scale, requirement of transfusions, and hypotension on admission. Surgical stabilization of rib fractures 3+ ribs (odds ratio: 2.30, 95% confidence interval: 1.58-3.37) was associated with acute respiratory distress syndrome but not 1 to 2 ribs (odd ratio: 1.55, 95% confidence interval: 0.97-2.48). On logistic regression of only patients with flail chest, stabilization of rib fractures was associated with decreased mortality but not increased risk of acute respiratory distress syndrome.ConclusionThe increased risk of acute respiratory distress syndrome should be considered in the preoperative assessment for stabilization of rib fractures.

Project description: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.

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Improved oxygenation following methylprednisolone therapy and survival in paediatric acute respiratory distress syndrome.

Publications

Improved oxygenation following methylprednisolone therapy and survival in paediatric acute respiratory distress syndrome.

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