Association between early cumulative fluid balance and successful liberation from invasive ventilation in COVID-19 ARDS patients - insights from the PRoVENT-COVID study:a national, multicenter, observational cohort analysis

BACKGROUND: Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 patients with acute respiratory distress syndrome (ARDS). METHODS: We analyzed data from the multicenter observational 'PRactice of VENTilation in COVID-19 patients' study. Patients with confirmed COVID-19 and ARDS who required invasive ventilation during the first 3 months of the international outbreak (March 1, 2020, to June 2020) across 22 hospitals in the Netherlands were included. The primary outcome was successful liberation of invasive ventilation, modeled as a function of day 3 cumulative fluid balance using Cox proportional hazards models, using the crude and the adjusted association. Sensitivity analyses without missing data and modeling ARDS severity were performed. RESULTS: Among 650 patients, three groups were identified. Patients in the higher, intermediate, and lower groups had a median cumulative fluid balance of 1.98 L (1.27-7.72 L), 0.78 L (0.26-1.27 L), and - 0.35 L (- 6.52-0.26 L), respectively. Higher day 3 cumulative fluid balance was significantly associated with a lower probability of successful ventilation liberation (adjusted hazard ratio 0.86, 95% CI 0.77-0.95, P = 0.0047). Sensitivity analyses showed similar results. CONCLUSIONS: In a cohort of invasively ventilated patients with COVID-19 and ARDS, a higher cumulative fluid balance was associated with a longer ventilation duration, indicating that restricted fluid management in these patients may be beneficial. Trial registration Clinicaltrials.gov ( NCT04346342 ); Date of registration: April 15, 2020

Importance of Occlusion Site for Thrombectomy Technique in Stroke:Comparison Between Aspiration and Stent Retriever

BACKGROUND AND PURPOSE: Thrombectomy with stent retriever and direct aspiration are equally effective in the endovascular treatment of anterior circulation acute ischemic stroke. We report efficacy and safety of initial treatment technique per occlusion segment.METHODS: For this study, we analyzed data from the MR CLEAN Registry, a prospective, observational study in all centers that perform endovascular therapy in the Netherlands. We used ordinal logistic regression analysis to compare clinical and technical results of first line direct aspiration treatment with that of stent retriever thrombectomy stratified for occlusion segment. Primary outcome measure was functional outcome at 3 months. Secondary outcome measures included reperfusion grade expressed as the extended Thrombolysis in Cerebral Infarction score, periprocedural complication risk, time to reperfusion, and mortality.RESULTS: Of the 2282 included patients, 1658 (73%) were initially treated with stent retriever and 624 (27%) with aspiration. Four hundred sixty-two patients had an occlusion of the intracranial part of the carotid artery, 1349 of the proximal middle cerebral artery, and 471 of the distal parts of the middle cerebral artery. There was no difference in functional outcome between aspiration and stent retriever thrombectomy (odds ratio, 1.0 [95% CI, 0.9-1.2]) in any of the occlusion segments (P value for interaction=0.2). Reperfusion rate was higher in the aspiration group (odds ratio, 1.4 [95% CI, 1.1-1.6]) and did not differ between occlusion segments (P value for interaction=0.6). Procedure times were shorter in the aspiration group (minutes 50 versus 65 minutes; P&lt;0.0001). There was no difference in periprocedural complications or mortality.CONCLUSIONS: In unselected patients with anterior circulation infarcts, we observed equal functional outcome of aspiration and stent retriever thrombectomy in all occlusion segments. When aspiration was the first line treatment modality, reperfusion rates were higher and procedure times shorter in all occlusion segments.</p

Determinants of Symptomatic Intracranial Hemorrhage After Endovascular Stroke Treatment:A Retrospective Cohort Study

Background: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location. Methods: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue. Results: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06-2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02-1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI, 1.16-2.78]). Conclusions: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms. Registration: URL: https://www.isrctn.com/; Unique identifier: ISRCTN10888758

Immediate versus postponed intervention for infected necrotizing pancreatitis

BACKGROUND Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, −1; 95% confidence interval [CI], −12 to 10; P=0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions

Childhood Acute Illness and Nutrition (CHAIN) Network: a protocol for a multi-site prospective cohort study to identify modifiable risk factors for mortality among acutely ill children in Africa and Asia

INTRODUCTION: Children admitted to hospitals in resource-poor settings remain at risk of both inpatient and post-discharge mortality. While known risk factors such as young age and nutritional status can identify children at risk, they do not provide clear mechanistic targets for intervention. The Childhood Acute Illness and Nutrition (CHAIN) cohort study aims to characterise the biomedical and social risk factors for mortality in acutely ill children in hospitals and after discharge to identify targeted interventions to reduce mortality. METHODS AND ANALYSIS: The CHAIN network is currently undertaking a multi-site, prospective, observational cohort study, enrolling children aged 1 week to 2 years at admission to hospitals at nine sites located in four African and two South Asian countries. The CHAIN Network supports the sites to provide care according to national and international guidelines. Enrolment is stratified by anthropometric status and children are followed throughout hospitalisation and for 6 months after discharge. Detailed clinical, demographic, anthropometric, laboratory and social exposures are assessed. Scheduled visits are conducted at 45, 90 and 180 days after discharge. Blood, stool and rectal swabs are collected at enrolment, hospital discharge and follow-up. The primary outcome is inpatient or post-discharge death. Secondary outcomes include readmission to hospital and nutritional status after discharge. Cohort analysis will identify modifiable risks, children with distinct phenotypes, relationships between factors and mechanisms underlying poor outcomes that may be targets for intervention. A nested case-control study examining infectious, immunological, metabolic, nutritional and other biological factors will be undertaken. ETHICS AND DISSEMINATION: This study protocol was reviewed and approved primarily by the Oxford Tropical Research Ethics Committee, and the institutional review boards of all partner sites. The study is being externally monitored. Results will be published in open access peer-reviewed scientific journals and presented to academic and policy stakeholders. TRIAL REGISTRATION NUMBER: NCT03208725