Paediatric Acute Respiratory Distress Syndrome Neuromuscular Blockade study (PAN-study): a phase IV randomised controlled trial of early neuromuscular blockade in moderate-to-severe paediatric acute respiratory distress syndrome.

BACKGROUND: Paediatric 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). METHODS: This 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 REGISTRATION: ClinicalTrials.gov NCT02902055 . Registered on September 15, 2016.

Long-term consequences of the posterior reversible encephalopathy syndrome in eclampsia and preeclampsia: a review of the obstetric and nonobstetric literature.

This review summarizes the long-term consequences of the posterior reversible encephalopathy syndrome (PRES) that have been described in the obstetric literature (eclampsia and preeclampsia) and compares these with data from the nonobstetric literature. Preeclampsia is characterized by new-onset hypertension and proteinuria after the 20th week of pregnancy. Neurological symptoms include headache; visual deficits; confusion; seizures; and, in the most severe cases, intracranial hemorrhage. Eclampsia is an acute cerebral complication of preeclampsia, defined as the occurrence of tonic-clonic seizures in pregnant or recently postpartum women. With severe preeclampsia, in conjunction with neurological symptoms, or eclampsia, neuroimaging changes consistent with PRES can be seen. Posterior reversible encephalopathy syndrome is a specific clinicoradiological syndrome presenting with headaches, visual impairment, seizures, and altered mental status. Characteristic neuroimaging features are consistent with cerebral edema predominantly in the parietal and occipital lobes. In addition to preeclampsia/eclampsia, PRES has been associated with various conditions in the nonobstetric population, that is, severe hypertension, transplantation, or autoimmune disease, in combination with immunosuppressive therapy or high-dose chemotherapy for various malignant conditions. Long-term sequelae of both preeclampsia/eclampsia and other PRES-related conditions are poorly described. After eclampsia or preeclampsia, nonspecific white matter lesions may be found on magnetic resonance imaging, which may or may not be related to the PRES episode. Previously (pre)eclamptic women report cognitive failures; however, no neurocognitive impairment has been shown so far. Various nonobstetric PRES-related conditions have been described with long-term neuroimaging abnormalities as well as cognitive problems, epilepsy, or visual impairment. Although no firm conclusions can be drawn because of the heterogeneity of reported cases, some general comments can be made. Because most persistent long-term problems are present in the nonobstetric population, the main determinant for these long-term problems may be the underlying condition that gave rise to the PRES episode. In addition, most reports suggest that late diagnosis or inadequate therapy may contribute, emphasizing the need for early recognition, adequate treatment, follow-up, and support.