Reduced anticoagulation targets in extracorporeal life support (RATE):study protocol for a randomized controlled trial

BackgroundAlthough life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT).However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome.MethodsWe will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2–2.5 times baseline aPTT, 1.5–2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months.DiscussionWe hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO.Trial registrationClinicalTrials.gov NCT04536272. Registered on 2 September 2020. Netherlands Trial Register NL796

International Survey on Mechanical Ventilation During Extracorporeal Membrane Oxygenation

The optimal ventilation strategy for patients on extracorporeal membrane oxygenation (ECMO) remains uncertain. This survey reports current mechanical ventilation strategies adopted by ECMO centers worldwide. An international, multicenter, cross-sectional survey was conducted anonymously through an internet-based tool. Participants from North America, Europe, Asia, and Oceania were recruited from the extracorporeal life support organization (ELSO) directory. Responses were received from 48 adult ECMO centers (response rate 10.6%). Half of these had dedicated ventilation protocols for ECMO support. Pressure-controlled ventilation was the preferred initial ventilation mode for both venovenous ECMO (VV-ECMO) (60%) and venoarterial ECMO (VA-ECMO) (34%). In VV-ECMO, the primary goal was lung rest (93%), with rescue therapies commonly employed, especially neuromuscular blockade (93%) and prone positioning (74%). Spontaneous ventilation was typically introduced after signs of pulmonary recovery, with few centers using it as the initial mode (7%). A quarter of centers stopped sedation within 3 days after ECMO initiation. Ventilation strategies during VA-ECMO focused less on lung-protective goals and transitioned to spontaneous ventilation earlier. Ventilation strategies during ECMO support differ considerably. Controlled ventilation is predominantly used initially to provide lung rest, often facilitated by sedation and neuromuscular blockade. Few centers apply "awake ECMO" early during ECMO support, some utilizing partial neuromuscular blockade.</p

International Survey on Mechanical Ventilation During Extracorporeal Membrane Oxygenation

The optimal ventilation strategy for patients on extracorporeal membrane oxygenation (ECMO) remains uncertain. This survey reports current mechanical ventilation strategies adopted by ECMO centers worldwide. An international, multicenter, cross-sectional survey was conducted anonymously through an internet-based tool. Participants from North America, Europe, Asia, and Oceania were recruited from the extracorporeal life support organization (ELSO) directory. Responses were received from 48 adult ECMO centers (response rate 10.6%). Half of these had dedicated ventilation protocols for ECMO support. Pressure-controlled ventilation was the preferred initial ventilation mode for both venovenous ECMO (VV-ECMO) (60%) and venoarterial ECMO (VA-ECMO) (34%). In VV-ECMO, the primary goal was lung rest (93%), with rescue therapies commonly employed, especially neuromuscular blockade (93%) and prone positioning (74%). Spontaneous ventilation was typically introduced after signs of pulmonary recovery, with few centers using it as the initial mode (7%). A quarter of centers stopped sedation within 3 days after ECMO initiation. Ventilation strategies during VA-ECMO focused less on lung-protective goals and transitioned to spontaneous ventilation earlier. Ventilation strategies during ECMO support differ considerably. Controlled ventilation is predominantly used initially to provide lung rest, often facilitated by sedation and neuromuscular blockade. Few centers apply "awake ECMO" early during ECMO support, some utilizing partial neuromuscular blockade.</p

Effect of nocturnal sound reduction on the incidence of delirium in intensive care unit patients: an interrupted time series analysis

INTRODUCTION: Delirium in critically-ill patients is a common multifactorial disorder that is associated with various negative outcomes. It is assumed that sleep disturbances can result in an increased risk of delirium. This study hypothesized that implementing a protocol that reduces overall nocturnal sound levels improves quality of sleep and reduces the incidence of delirium in Intensive Care Unit (ICU) patients. METHODS: This interrupted time series study was performed in an adult mixed medical and surgical 24-bed ICU. A pre-intervention group of 211 patients was compared with a post-intervention group of 210 patients after implementation of a nocturnal sound-reduction protocol. Primary outcome measures were incidence of delirium, measured by the Intensive Care Delirium Screening Checklist (ICDSC) and quality of sleep, measured by the Richards-Campbell Sleep Questionnaire (RCSQ). Secondary outcome measures were use of sleep-inducing medication, delirium treatment medication, and patient-perceived nocturnal noise. RESULTS: A significant difference in slope in the percentage of delirium was observed between the pre- and post-intervention periods (-3.7% per time period, p=0.02). Quality of sleep was unaffected (0.3 per time period, p=0.85). The post-intervention group used significantly less sleep-inducing medication (p<0.001). Nocturnal noise rating improved after intervention (median: 65, IQR: 50-80 versus 70, IQR: 60-80, p=0.02). CONCLUSIONS: The incidence of delirium in ICU patients was significantly reduced after implementation of a nocturnal sound-reduction protocol. However, reported sleep quality did not improve

Strong Relation Between an EEG Functional Connectivity Measure and Postmenstrual Age: A New Potential Tool for Measuring Neonatal Brain Maturation

Fetal and neonatal brain connectivity development is highly complex. Studies have shown that functional networks change dramatically during development. The purpose of the current study was to determine how the mean phase lag index (mPLI), a measure of functional connectivity (FC), assessed with electroencephalography (EEG), changes with postmenstrual age (PMA) during the early stages of brain development after birth. Neonates (N = 131) with PMA 27.6–45.3 weeks who underwent an EEG for a medical reason were retrospectively studied. For each recording, global FC was assessed by obtaining a whole-head average of all local PLI values (pairwise between sensor space EEG signals). Global FC results were consequently correlated with PMA values in seven frequency bands. Local results were obtained for the frequency band with the strongest global association. There was a strong negative correlation between mPLI and PMA in most frequency bands. The strongest association was found in the delta frequency band (R = −0.616, p < 0.001) which was therefore topographically explored; the strongest correlations were between pairs of electrodes with at least one electrode covering the central sulcus. Even in this heterogeneous group of neonates, global FC strongly reflects PMA. The decrease in PLI may reflect the process of segregation of specific brain regions with increasing PMA. This was mainly found in the central brain regions, in parallel with myelination of these areas during early development. In the future, there may be a role for PLI in detecting atypical FC maturation. Moreover, PLI could be used to develop biomarkers for brain maturation and expose segregation processes in the neonatal brain

Measurements of medial temporal lobe atrophy for prediction of Alzheimer's disease in subjects with mild cognitive impairment

AbstractOur aim was to compare the predictive accuracy of 4 different medial temporal lobe measurements for Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Manual hippocampal measurement, automated atlas-based hippocampal measurement, a visual rating scale (MTA-score), and lateral ventricle measurement were compared. Predictive accuracy for AD 2 years after baseline was assessed by receiver operating characteristics analyses with area under the curve as outcome. Annual cognitive decline was assessed by slope analyses up to 5 years after baseline. Correlations with biomarkers in cerebrospinal fluid (CSF) were investigated. Subjects with MCI were selected from the Development of Screening Guidelines and Clinical Criteria for Predementia AD (DESCRIPA) multicenter study (n = 156) and the single-center VU medical center (n = 172). At follow-up, area under the curve was highest for automated atlas-based hippocampal measurement (0.71) and manual hippocampal measurement (0.71), and lower for MTA-score (0.65) and lateral ventricle (0.60). Slope analysis yielded similar results. Hippocampal measurements correlated with CSF total tau and phosphorylated tau, not with beta-amyloid 1–42. MTA-score and lateral ventricle volume correlated with CSF beta-amyloid 1–42. We can conclude that volumetric hippocampal measurements are the best predictors of AD conversion in subjects with MCI

Reduced anticoagulation targets in extracorporeal life support (RATE): study protocol for a randomized controlled trial

Background: Although life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT). However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome. Methods: We will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2–2.5 times baseline aPTT, 1.5–2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months. Discussion: We hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO. Trial registration: ClinicalTrials.gov NCT04536272. Registered on 2 September 2020

Reduced anticoagulation targets in extracorporeal life support (RATE):study protocol for a randomized controlled trial

BackgroundAlthough life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT).However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome.MethodsWe will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2–2.5 times baseline aPTT, 1.5–2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months.DiscussionWe hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO.Trial registrationClinicalTrials.gov NCT04536272. Registered on 2 September 2020. Netherlands Trial Register NL796