High Early Fluid Input After Aneurysmal Subarachnoid Hemorrhage: Combined Report of Association With Delayed Cerebral Ischemia and Feasibility of Cardiac Output–Guided Fluid Restriction

Background: Guidelines on the management of aneurysmal subarachnoid hemorrhage (aSAH) recommend euvolemia, whereas hypervolemia may cause harm. We investigated whether high early fluid input is associated with delayed cerebral ischemia (DCI), and if fluid input can be safely decreased using transpulmonary thermodilution (TPT). Methods: We retrospectively included aSAH patients treated at an academic intensive care unit (2007-2011; cohort 1) or managed with TPT (2011-2013; cohort 2). Local guidelines recommended fluid input of 3 L daily. More fluids were administered when daily fluid balance fell below +500 mL. In cohort 2, fluid input in high-risk patients was guided by cardiac output measured by TPT per a strict protocol. Associations of fluid input and balance with DCI were analyzed with multivariable logistic regression (cohort 1), and changes in hemodynamic indices after institution of TPT assessed with linear mixed models (cohort 2). Results: Cumulative fluid input 0 to 72 hours after admission was associated with DCI in cohort 1 (n=223; odds ratio [OR] 1.19/L; 95% confidence interval 1.07-1.32), whereas cumulative fluid balance was not. In cohort 2 (23 patients), using TPT fluid input could be decreased from 6.0 ± 1.0 L before to 3.4 ± 0.3 L; P =.012), while preload parameters and consciousness remained stable. Conclusion: High early fluid input was associated with DCI. Invasive hemodynamic monitoring was feasible to reduce fluid input while maintaining preload. These results indicate that fluid loading beyond a normal preload occurs, may increase DCI risk, and can be minimized with TPT

COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study

Background: 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. Methods: We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. Findings: Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. Interpretation: Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. Funding: EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health

Probiotics for prevention of nosocomial infections: efficacy and adverse effects

PURPOSE OF REVIEW: In this era of increasing antimicrobial resistance, use of probiotics in infection prevention has brought new perspective. However, in 2008 the, until then considered, safe use of probiotics became an important topic after publication of a trial showing excess mortality in patients on probiotic prophylaxis. In this article, we review the concept of infection prevention by probiotics and the present knowledge of the efficacy of probiotics in prevention of infections among patients with abdominal diseases and in intensive care. Safety issues of probiotics will be discussed extensively. RECENT FINDINGS: Over 30 clinical trials with probiotics to prevent infections have been published, some of which were prematurely stopped recently. Studies with critically ill patients and patients with abdominal diseases showed conflicting results regarding the effects of probiotics on infection rates, as did meta-analyses. These studies are difficult to compare because different probiotics were used which all have different efficacy and safety profiles. SUMMARY: The efficacy of probiotics in infection prevention among critically ill patients is still not unequivocally determined. The safety profile differs per probiotic strain and should not be generalized towards other strains and patient populations. A well designed and well powered clinical trial with clear endpoints to demonstrate efficacy is warranted

Clinical course and complications following diagnostic bronchoalveolar lavage in critically ill mechanically ventilated patients

BACKGROUND: Flexible, fibreoptic bronchoscopy (FFB) and bronchoalveolar lavage (BAL) have been used for diagnostic purposes in critically ill ventilated patients. The additional diagnostic value compared to tracheal aspirations in ventilator-associated pneumonia (VAP) has been questioned. Nevertheless, BAL can provide extra information for the differential diagnosis of respiratory disease and good antibiotic stewardship. These benefits should outweigh potential hazards caused by the invasiveness of this diagnostic technique. The focus of the present study was on the clinical course and complications of patients following BAL procedures up to 24 h. METHODS: Hundred sixty-four FFB guided BAL procedures for suspected pneumonia were analysed in an observational study. The clinical course of patients was monitored by respiratory and haemodynamic data before BAL, 1 and 24 h after BAL. Complications were defined and registered. Factors associated with complications were analysed by logistic regression. RESULTS: CLINICAL COURSE: a decrease in average pO2/FiO2 ratio 1 h after BAL from 29 kPa (218 mmHg) to 25 kPa (189 mmHg) (p 25 % PaO2/FiO2 ratio 1 h after BAL was found in 29 % of patients; no bleeding or pneumothorax were registered. Haemodynamic complications: there were no cases of hypertension and cardiac rhythm disturbances; haemodynamic instability within the first 24 h after BAL was recorded in 22 %; this was correlated with a cardiovascular diagnosis at admission (OR 2.9; 95 % CI 1.2 - 6.7) and the presence of cardiovascular co-morbidity (OR 3.5; 95 % CI 1.5 - 8.3). The incidence of bacteraemia was 7 %. There was no case of procedure related death. DISCUSSION: Frequently occurring haemodynamic and respiratory instability but no cases of cardiac rhythm disturbances, bleeding, pneumothorax or procedure related death were attributable to diagnostic FFB and BAL. The procedures should be conducted under careful supervision by experienced physicians. Only a randomized controlled trial that compares diagnostic FFB and BAL with a non-invasive strategy could ultimately establish the safety profile and clinical utility of these procedures in critically ill ventilated patients

Mimivirus is not a frequent cause of ventilator-associated pneumonia in critically ill patients

Acanthamoeba polyphaga mimivirus (APMV) belongs to the amoebae-associated microorganisms. Antibodies to APMV have been found in patients with pneumonia suggesting a potential role as a respiratory pathogen. In addition, positive serology for APMV was associated with an increased duration of mechanical ventilation and intensive care unit stay in patients with ventilator-associated pneumonia. The aim of the present study was to assess the presence of APMV in bronchoalveolar lavage fluid samples of critically ill patients suspected of ventilator-associated pneumonia. The study was conducted in the intensive care unit of the Maastricht University Medical Centre. All consecutive bronchoalveolar lavage fluid samples obtained between January 2005 and October 2009 from patients suspected of ventilator-associated pneumonia were eligible for inclusion. All samples were analyzed by real-time PCR targeting the APMV. A total of 260 bronchoalveolar lavage fluid samples from 214 patients (139 male, 75 female) were included. Bacterial ventilator-associated pneumonia was confirmed microbiologically in 105 out of 260 (40%) suspected episodes of ventilator-associated pneumonia (86 patients). The presence of APMV DNA could not be demonstrated in the bacterial ventilator-associated pneumonia positive or in the bacterial ventilator-associated pneumonia negative bronchoalveolar lavage fluid samples. Although suspected, APMV appeared not to be present in critically ill patients suspected of ventilator-associated pneumonia, and APMV does not seem to be a frequent cause of ventilator-associated pneumonia

Virtual Patient Modeling and Prediction Validation for Pressure Controlled Mechanical Ventilation

Respiratory failure patients in the intensive care unit (ICU) require mechanical ventilation (MV) to support breathing and tissue oxygenation. Optimizing MV care is problematic. Significant patient variability confounds optimal MV settings and increase the risk of lung damage due to excessive pressure or volume delivery, which in turn can increase length of stay and cost, as well as mortality. Model-based care using in silico virtual patients can significantly affect ICU care, personalizing delivery and optimising care. This research presents a virtual patient model for pressure-controlled MV, an increasingly common mode of MV delivery, based on prior work applied to volume-controlled MV. This change necessitates predictions of flow and thus volume, instead of pressure, as the unspecified variable. A model is developed and validated using clinical data from five patients (N=5) during a series of PEEP (positive end expiratory pressure) changes in a recruitment maneuver (RM), creating a total of 242 predictions. Peak inspiratory volume, a measure of risk of lung damage, errors were 56 [26 95]mL (10.6 [5.3 19.1]%) for predictions of PEEP changes from 2-16cmH2O. Model fitting errors were all lower than 5%. Accurate predictions validate the model, and its potential to both personalise and optimise care. Copyright (C) 2020 The Authors

Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality

Selective decontamination of the digestive tract (SDD) has been shown to decrease the infection rate and mortality in intensive care units (ICUs); Lactobacillus plantarum 299/299v plus fibre (LAB) has been used for infection prevention and does not harbour the potential disadvantages of antibiotics. The objective was to assess whether LAB is not inferior to SDD in infection prevention. Two hundred fifty-four consecutive ICU patients with expected mechanical ventilation a parts per thousand yen48 h and/or expected ICU stay a parts per thousand yen72 h were assigned to receive SDD: four times daily an oral paste (polymyxin E, gentamicin, amphotericin B), enteral solution (same antibiotics), intravenous cefotaxime (first 4 days) or LAB: two times daily L. plantarum 299/299v with rose-hip. The primary endpoint was infection rate. A difference <12% between both groups indicated non-inferiority of LAB. The trial was prematurely stopped after a study reporting increased mortality in critically ill pancreatitis patients receiving probiotics. No significant difference in infection rate [31% in the LAB group, 24% in the SDD group (OR 1.68, 95% CI 0.91-3.08; p = 0.10)] was found. ICU mortality was 26% and not significantly different between the LAB and SDD groups. Gram-positive cocci and Pseudomonas aeruginosa were significantly more frequently isolated from surveillance cultures in the SDD group compared to the LAB group (for sputum: 18 vs. 10% and 33 vs. 14%). Significantly more Enterobacteriaceae were found in the LAB group (23 vs. 50%). No increase in antibiotic resistance was found during and after SDD or LAB use. The trial could not demonstrate the non-inferiority of LAB compared with SDD in infection prevention. Results suggest no increased ICU mortality risk in the LAB group

Prediction and estimation of pulmonary response and elastance evolution for volume-controlled and pressure-controlled ventilation

Mechanical ventilation (MV) is a core treatment for patients suffering from respiratory disease and failure. However, MV settings are not standardized due to significant inter- and intra- patient variability in response to care, leading to variability in outcome. There is thus a need to personalize MV settings. This research significantly extends a single compartment lung mechanics model with physiologically relevant basis functions, and uses it to identify patient-specific lung mechanics and predict response to changes in MV settings. Nonlinear evolution of pulmonary elastance over positive end expiratory pressure (PEEP) is modelled by a newly proposed, physiologically relevant and simplified compensatory function to enable prediction of pulmonary response for both volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV), and identified as patientspecific using each patient's data at a baseline PEEP. Predictions at higher PEEP levels test the validity of the proposed models based on errors in predicted peak inspiratory pressure (PIP) in two VCV trials and volume (PIV) in one PCV trial. A total of 210 prediction cases over 36 patients (22 VCV; 14 PCV) yielded absolute predicted PIP errors within 1.0 cmH2O (2.3%) and 3.3 cmH2O (7.3%) for 90% cases in VCV, while predicted PIV errors are within 0.073 L (16.8%) for 85% cases in PCV. In conclusion, a novel deterministic virtual patient model is presented, able to offer accurate prediction of pulmonary response across a wide range of PEEP changes for the two main MV modes used clinically, enabling predictive decision support in real-time to safely personalize and optimize care

Minimal Lung Mechanics Basis-functions for a Mechanical Ventilation Virtual Patient

Mechanical ventilation (MV) is used in the intensive care unit (ICU) to treat patients with respiratory failure. However, MV settings are not standardized due to significant inter- and intra- patient variability in response to care, leading to variability in care, outcome, and cost. There is thus a need to personalize MV. This research extends a single compartment lung mechanics model with physiologically relevant basis functions, to identify patient-specific lung mechanics and predict response to changes in MV care. The nonlinear evolution of pulmonary elastance as positive-end-expiratory pressure (PEEP) changes is captured by a physiologically relevant, simplified compensatory equation as a function of PEEP and pressure identification error at the baseline PEEP level. It allows both patient-specific and general prediction of lung elastance of higher PEEP. The prediction outcome is validated with data from two volume-controlled ventilation (VCV) trials and one pressure-controlled ventilation (PCV) trial, where the biggest PEEP prediction interval is a clinically unrealistic 20cmH(2)O, comprising 210 prediction cases over 36 patients (22 VCV; 14 PCV). Predicted absolute peak inspiratory pressure (PIP) errors are within 1.0cmH(2)O and 3.3cmH(2)O for 90% cases in the two VCV trials, while predicted peak inspiratory tidal volume (PIV) errors are within 0.073L for 85% cases in studied PCV trial. The model presented provides a highly accurate, predictive virtual patient model across multiple MV modes and delivery methods, and over clinically unrealistically large changes. Low computational cost, and fast, easy parameterization enable model-based, predictive decision support in real-time to safely personalize and optimize MV care. Copyright (C) 2021 The Authors