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Background: Mechanically ventilated patients are at risk of developing inspiratory muscle weakness (IMW), which is associated with failure to wean and poor outcomes. Inspiratory muscle training (IMT) is a recommended intervention during and after extubation but has not been widely adopted in Dutch intensive care units (ICUs)., Objectives: The objective of this study was to explore the potential, barriers, and facilitators for implementing IMT as treatment modality for mechanically ventilated patients., Methods: This mixed-method, proof-of-concept study was conducted in a large academic hospital in the Netherlands. An evidence-based protocol for assessing IMW and training was applied to patients ventilated for ≥24 h in the ICU during an 8-month period in 2021. Quantitative data on completed measurements and interventions during and after ICU-stay were collected retrospectively and were analysed descriptively. Qualitative data were collected through semistructured interviews with physiotherapists executing the new protocol. Interview data were transcribed and thematically analysed., Findings: Of the 301 screened patients, 11.6% (n = 35) met the inclusion criteria. Measurements were possible in 94.3% of the participants, and IMW was found in 78.8% of the participants. Ninety-six percent started training in the ICU, and 88.5% continued training after transfer to the ward. Follow-up measurements were achieved in 73.1% of the patients with respiratory muscle weakness. Twelve therapists were interviewed, of whom 41.7% regularly worked in the ICU. When exploring reasons for protocol deviation, three themes emerged: "professional barriers", "external factors", and "patient barriers"., Conclusions: Implementation of measurements of and interventions for IMW showed to be challenging in this single centre study. Clinicians' willingness to change their handling was related to beliefs regarding usefulness, effectiveness, and availability of time and material. We recommend that hospitals aiming to implement IMT during or after ventilator weaning consider these professional and organisational barriers for implementation of novel, evidence-based interventions into daily clinical practice., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Increased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2·0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1·3 g/kg per day)., Methods: The PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m 2 , kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1·3 kcal/mL and 0·06 g of protein/mL (ie, standard protein) or 1·3 kcal/mL and 0·10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants., Findings: Between Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35·8%) of 935 patients were female and 600 (64·2%) were male. 465 (49·7%) of 935 were assigned to the standard protein group and 470 (50·3%) were assigned to the high protein group. 430 (92·5%) of 465 patients in the standard protein group and 419 (89·1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of -0·05 (95% CI -0·10 to -0·01; p=0·031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0·38 (SE 0·02) in the standard protein group and 0·42 (0·02) in the high protein group (hazard ratio 1·14, 95% CI 0·92 to 1·40; p=0·22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1·76, 95% CI 1·06 to 2·92; p=0·030). Incidence of other adverse events did not differ between groups., Interpretation: High enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission., Funding: Netherlands Organisation for Healthcare Research and Development and Belgian Health Care Knowledge Centre., Competing Interests: Declaration of interests EDW receives honoraria for scientific lectures from Baxter Healthcare, Nutricia–Danone, and Nestlé. ARHvZ receives grants from AOP Pharma, Nutricia–Danone, Fresenius Kabi, PAION, and Rousselot; receives consulting fees from AOP Pharma, Medcaptain, and PAION; receives honoraria for lectures from Abbott, AOP Pharma, Baxter, Nestlé, Nutricia–Danone, Fresenius Kabi, GE Healthcare, and Dutch Medical Food; receives support for travel from Nutricia–Danone and Dutch Medical Food; is a member of the adult intensive care unit patient nutrition guideline committee of the European Society for Clinical Nutrition and Metabolism, the executive team of SepsisNet Netherlands, and the executive team of the Netherlands Society for Parenteral and Enteral Nutrition; and is the European Society of Intensive Care Medicine Section Feeding, Rehabilitation Endocrinology and Metabolism chair. ZP receives grants from Fresenius Kabi, Nestlé, and Baxter; receives consulting fees from Fresenius Kabi, Nestlé, Baxter, Faraday Pharmaceuticals, and Bioage Pharmaceuticals; and receives honoraria for lectures from Baxter, Nestlé, Fresenius Kabi, and Nutricia. MCGvdP receives grants from the Netherlands Organisation of Health Research and Development and the Belgian Health Care Knowledge Centre; receives in-kind support from Nutricia; receives consulting fees from Nutricia and Nestlé; and receives honoraria for lectures and support for travel from Nutricia. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Neurological complications in COVID-19 patients admitted to an intensive care unit (ICU) have been previously reported. As the pandemic progressed, therapeutic strategies were tailored to new insights. This study describes the incidence, outcome, and types of reported neurological complications in invasively mechanically ventilated (IMV) COVID-19 patients in relation to three periods during the pandemic., Methods: IMV COVID-19 ICU patients from the Dutch Maastricht Intensive Care COVID (MaastrICCht) cohort were included in a single-center study (March 2020 - October 2021). Demographic, clinical, and follow-up data were collected. Electronic medical records were screened for neurological complications during hospitalization. Three distinct periods (P1, P2, P3) were defined, corresponding to periods with high hospitalization rates. ICU survivors with and without reported neurological complications were compared in an exploratory analysis., Results: IMV COVID-19 ICU patients (n=324; median age 64 [IQR 57-72] years; 238 males (73.5%)) were stratified into P1 (n=94), P2 (n=138), and P3 (n=92). ICU mortality did not significantly change over time (P1=38.3%; P2=41.3%; P3=37.0%; p=.787). The incidence of reported neurological complications during ICU admission gradually decreased over the periods (P1=29.8%; P2=24.6%; P3=18.5%; p=.028). Encephalopathy/delirium (48/324 (14.8%)) and ICU-acquired weakness (32/324 (9.9%)) were most frequently reported and associated with ICU treatment intensity. ICU survivors with neurological complications (n=53) were older (p=.025), predominantly male (p=.037), and had a longer duration of IMV (p<.001) and ICU stay (p<.001), compared to survivors without neurological complications (n=132). A multivariable analysis revealed that only age was independently associated with the occurrence of neurological complications (OR adj =1.0541; 95% CI=1.0171-1.0925; p=.004). Health-related quality-of-life at follow-up was not significantly different between survivors with and without neurological complications (n = 82, p=.054)., Conclusions: A high but decreasing incidence of neurological complications was reported during three consecutive COVID-19 periods in IMV COVID-19 patients. Neurological complications were related to the intensity of ICU support and treatment, and associated with prolonged ICU stay, but did not lead to significantly worse reported health-related quality-of-life at follow-up., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by central hypoventilation, leading to the majority of patients being dependent on ventilatory support during sleep. This condition is often accompanied by various associated symptoms, due to a PHOX2B gene variant involved in neuronal crest cell migration. This study is the first to review the characteristics and outcomes in children with CCHS on long-term mechanical ventilation in the Netherlands. We performed a retrospective study of all CCHS patients treated in the 4 Centers of Home Mechanical Ventilation of the University Medical Centers in the Netherlands from 2000 till 2022 by collecting information from the electronic medical records, documented during follow-up. We included 31 patients, out of which 27 exhibited a known genetic profile associated with CCHS, while no PHOX2B variant was identified in the remaining patients. Among the 27 patients with known genetic profiles, 10 patients had a non-polyalanine repeat expansion mutation (NPARM), followed by 20/27, 20/25, and 20/26 polyalanine repeat expansion mutations (PARMs) in descending order. The most common presentation involved respiratory failure or apneas during the neonatal period with an inability to wean off ventilation. The majority of patients required ventilatory support during sleep, with four patients experiencing life-threatening events related to this dependency. Daily use of ventilatory support varied among different genetic profiles. All genotypes reported comorbidities, with Hirschsprung's disease and cardiac arrhythmias being the most reported comorbidities. Notably, Hirschprung's disease was exclusively observed in patients with a 20/27 PHOX2B variant., Conclusion: Our study results suggest that in our cohort, the genotype is not easily associated to the phenotype in CCHS. Consistent with these findings and international literature, we recommend a thorough annual evaluation for all patients with CCHS to ensure optimal management and follow-up., What Is Known: • The majority of CCHS patients are dependent on ventilatory support. • Variants in the PHOX2B gene are responsible for the characteristics of CCHS., What Is New: • This study provides insight into the clinical course and long-term outcomes of CCHS patients in the Netherlands. • In CCHS, the genotype is not easily associated with the phenotype, requiring a thorough life-long follow-up for all patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation)., Objective: To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease., Design, Setting, and Participants: Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021., Interventions: Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685)., Main Outcomes and Measures: The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels., Results: Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P = .92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups., Conclusions and Relevance: In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery., Trial Registration: anzctr.org.au Identifier: ACTRN12617000821392.

Objective: Use of lung-protective mechanical ventilation (MV) by applying lower tidal volumes is recommended in patients suffering from acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Recent data suggest that lung-protective MV may benefit non-ALI/ARDS patients as well. This study analyzed tidal volume settings in three ICUs in The Netherlands to determine the effect of feedback and education concerning use of lung-protective MV.Design and Setting: Observational study in one academic and two nonacademic "closed format" ICUs.Patients: Intubated mechanically ventilated subjects.Interventions: Feedback and education concerning lung-protective MV with special attention to the importance of closely adjusting tidal volumes to predicted body weight (PBW).Results: Tidal volumes declined significantly within 6 months after intervention (from 9.8+/-2.0 at baseline to 8.1+/-1.7 ml/kg PBW) as the percentage of undesirable ventilation data points, defined as tidal volumes greater than 8 ml/kg PBW (84% vs. 48%). There were no differences between patients meeting the international definition criteria for ALI/ARDS and those not. Only four patients received tidal volumes less than 6 ml/kg PBW. Lower tidal volumes were still used after 12 months. Tidal volumes in patients on mandatory MV and patients breathing on spontaneous modes were similar.Conclusions: Feedback and education improve physician compliance in use of lung-protective MV. [ABSTRACT FROM AUTHOR]

Objective: Invasively ventilated patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) potentially benefit from tracheostomy. The aim of this study was to determine the practice of tracheostomy during the first wave of the pandemic in 2020 in the Netherlands, to ascertain whether timing of tracheostomy had an association with outcome, and to identify factors that had an association with timing., Methods: Secondary analysis of the 'PRactice of VENTilation in COVID-19' (PRoVENT-COVID) study, a multicenter observational study, conducted from March 1, 2020 through June 1, 2020 in 22 Dutch intensive care units (ICU) in the Netherlands. The primary endpoint was the proportion of patients receiving tracheostomy; secondary endpoints were timing of tracheostomy, duration of ventilation, length of stay in ICU and hospital, mortality, and factors associated with timing., Results: Of 1023 patients, 189 patients (18.5%) received a tracheostomy at median 21 [17 to 28] days from start of ventilation. Timing was similar before and after online publication of an amendment to the Dutch national guidelines on tracheostomy focusing on COVID-19 patients (21 [17-28] vs. 21 [17-26] days). Tracheostomy performed ≤ 21 days was independently associated with shorter duration of ventilation (median 26 [21 to 32] vs. 40 [34 to 47] days) and higher mortality in ICU (22.1% vs. 10.2%), hospital (26.1% vs. 11.9%) and at day 90 (27.6% vs. 14.6%). There were no patient demographics or ventilation characteristics that had an association with timing of tracheostomy., Conclusions: Tracheostomy was performed late in COVID-19 patients during the first wave of the pandemic in the Netherlands and timing of tracheostomy possibly had an association with outcome. However, prospective studies are needed to further explore these associations. It remains unknown which factors influenced timing of tracheostomy in COVID-19 patients., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier España, S.L.U.)

Background: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches., Methods: PRoVENT-COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342., Findings: Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent class analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO 2 /FiO 2 , pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0·10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0-15 vs 5, 0-17; p=0·016) and more frequent venous thrombotic events (109 [32%] of 336 patients vs 176 [26%] of 671 patients; p=0·048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1·64, 95% CI 1·17-2·29 for ventilatory ratio; 1·82, 1·24-2·66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4·65, 95% CI 1·87-11·6 for ventilatory ratio in replication cohort 1; 1·89, 1·05-3·37 for ventilatory ratio in replication cohort 2)., Interpretation: At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality., Funding: Amsterdam UMC., Competing Interests: Declaration of interests LDJB reports grants from the Dutch Lung Foundation (Young Investigator grant), grants from the Dutch Lung Foundation and Health Holland (Public–Private Partnership grant), grants from the Dutch Lung Foundation (Dirkje Postma Award), grants from the IMI COVID19 iniative, and grants from Amsterdam UMC fellowship, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Data on the course of severe COVID-19 in inflammatory bowel disease (IBD) patients remains limited. We aimed to determine the incidence rate and clinical course of severe COVID-19 in the heavily affected South-Limburg region in the Netherlands., Methods: All COVID-19 patients admitted to the only two hospitals covering the whole South-Limburg region between February 27, 2020 and January 4, 2021 were included. Incidence rates for hospitalization due to COVID-19 were determined for the IBD (n = 4980) and general population (n = 597,184) in South-Limburg., Results: During a follow-up of 4254 and 510,120 person-years, 20 IBD patients (0.40%; 11 ulcerative colitis (UC), 9 Crohn's disease (CD)) and 1425 (0.24%) patients from the general population were hospitalized due to proven COVID-19 corresponding to an incidence rate of 4.7 (95% Confidence interval (CI) 3.0-7.1) and 2.8 (95% CI 2.6-2.9) per 1000 patient years, respectively (Incidence rate ratio: 1.68, 95% CI 1.08-2.62, p = 0.019). Median age (IBD: 63.0 (IQR 58.0-75.8) years vs. general population: 72.0 (IQR 62.0-80.0) years, p = 0.10) and mean BMI (IBD: 24.4 (SD 3.3) kg/m2 vs. general population 24.1 (SD 4.9) kg/m2, p = 0.79) at admission were comparable in both populations. As for course of severe COVID-19, similar rates of ICU admission (IBD: 12.5% vs. general population: 15.7%, p = 1.00), mechanical ventilation (6.3% vs. 11.2%, p = 1.00) and death were observed (6.3% vs. 21.8%, p = 0.22)., Conclusion: We found a statistically significant higher rate of hospitalization due to COVID-19 in IBD patients in a population-based setting in a heavily impacted Dutch region. This finding reflects previous research that showed IBD patients using systemic medication were at an increased risk of serious infection. However, although at an increased risk of hospitalization, clinical course of severe COVID-19 was comparable to hospitalized patients without IBD., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AvB has served as speaker, adviser and/or principal investigator for AbbVie, Arandal, Arena, Celgene, Ferring, Galapagos, Janssen, MSD, Pfizer, Roche, Takeda, TEVA, and received research grants from TEVA, Eurostars funding, ZonMW, all outside the submitted work. MP reports grants and non-financial support from Falk Pharma, grants from European commission, grants from ZONMW (Dutch national research fund), grants and non-financial support from Takeda, grants and non-financial support from Johnson and Johnson, grants and non-financial support from Abbvie, non-financial support from Ferring, non-financial support from Immunodiagnostics, non-financial support from MSD, all outside the submitted work. DJ reports grants from Top Knowledge Institute (Well on Wheat), grants from Horizon 2020 DISCOvERIE, grants from NWO-CCC Partnership program (Carbokinetics), all outside the submitted work. ARA, RC, ML and MRC have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aim: In critically ill mechanically ventilated children, midazolam is used first line for sedation, however its exact sedative effects have been difficult to quantify. In this analysis, we use parametric time-to-event (PTTE) analysis to quantify the effects of midazolam in critically ill children., Methods: In the PTTE analysis, data was analyzed from a published study in mechanically ventilated children in which blinded midazolam or placebo infusions were administered during a sedation interruption phase until, based on COMFORT-B and NISS scores, patients became undersedated and unblinded midazolam was restarted. Using NONMEM® v.7.4.3., restart of unblinded midazolam was analysed as event. Patients in the trial were divided into internal and external validation cohorts prior to analysis., Results: Data contained 138 events from 79 individuals (37 blinded midazolam; 42 blinded placebo). In the PTTE model, the baseline hazard was best described by a constant function. Midazolam reduced the hazard for restart of unblinded midazolam due to undersedation by 51%. In the blinded midazolam group, time to midazolam restart was 26 h versus 58 h in patients with low versus high disease severity upon admission (PRISM II < 10 versus > 21), respectively. For blinded placebo, these times were 14 h and 33 h, respectively. The model performed well in an external validation with 42 individuals., Conclusion: The PTTE analysis effectively quantified the effect of midazolam in prolonging sedation and also the influence of disease severity on sedation in mechanically ventilated critically ill children, and provides a valuable tool to quantify the effect of sedatives. Clinical trial number and registry URL: Netherlands Trial Register, Trial NL1913 (NTR2030), date registered 28 September 2009 https://www.trialregister.nl/trial/1913 ., (© 2021. The Author(s).)

Background: The lateral abdominal wall muscles are recruited with active expiration, as may occur with high breathing effort, inspiratory muscle weakness, or pulmonary hyperinflation. The effects of critical illness and mechanical ventilation on these muscles are unknown. This study aimed to assess the reproducibility of expiratory muscle (i.e., lateral abdominal wall muscles and rectus abdominis muscle) ultrasound and the impact of tidal volume on expiratory muscle thickness, to evaluate changes in expiratory muscle thickness during mechanical ventilation, and to compare this to changes in diaphragm thickness., Methods: Two raters assessed the interrater and intrarater reproducibility of expiratory muscle ultrasound (n = 30) and the effect of delivered tidal volume on expiratory muscle thickness (n = 10). Changes in the thickness of the expiratory muscles and the diaphragm were assessed in 77 patients with at least two serial ultrasound measurements in the first week of mechanical ventilation., Results: The reproducibility of the measurements was excellent (interrater intraclass correlation coefficient: 0.994 [95% CI, 0.987 to 0.997]; intrarater intraclass correlation coefficient: 0.992 [95% CI, 0.957 to 0.998]). Expiratory muscle thickness decreased by 3.0 ± 1.7% (mean ± SD) with tidal volumes of 481 ± 64 ml (P < 0.001). The thickness of the expiratory muscles remained stable in 51 of 77 (66%), decreased in 17 of 77 (22%), and increased in 9 of 77 (12%) patients. Reduced thickness resulted from loss of muscular tissue, whereas increased thickness mainly resulted from increased interparietal fasciae thickness. Changes in thickness of the expiratory muscles were not associated with changes in the thickness of the diaphragm (R2 = 0.013; P = 0.332)., Conclusions: Thickness measurement of the expiratory muscles by ultrasound has excellent reproducibility. Changes in the thickness of the expiratory muscles occurred in 34% of patients and were unrelated to changes in diaphragm thickness. Increased expiratory muscle thickness resulted from increased thickness of the fasciae., (Copyright © 2021, the American Society of Anesthesiologists, Inc. All Rights Reserved.)

Background and Aims: The COVID-19 risk and disease course in inflammatory bowel disease [IBD] patients remains uncertain. Therefore, we aimed to assess the clinical presentation, disease course, and outcomes of COVID-19 in IBD patients. Second, we determined COVID-19 incidences in IBD patients and compared this with the general population., Methods: We conducted a multicentre, nationwide IBD cohort study in The Netherlands and identified patients with COVID-19. First, we assessed the COVID-19 disease course and outcomes. Second, we compared COVID-19 incidences between our IBD study cohort and the general Dutch population., Results: We established an IBD cohort of 34 763 patients. COVID-19 was diagnosed in 100/34 763 patients [0.29%]; 20/100 of these patients [20%] had severe COVID-19 defined as admission to the intensive care unit, mechanical ventilation, and/or death. Hospitalisation occurred in 59/100 [59.0%] patients and 13/100 [13.0%] died. All patients who died had comorbidities and all but one were ≥65 years old. In line, we identified ≥1 comorbidity as an independent risk factor for hospitalisation (odds ratio [OR] 4.20, 95% confidence interval [CI] 1.58-11.17,; p = 0.004). Incidences of COVID-19 between the IBD study cohort and the general population were comparable (287.6 [95% CI 236.6-349.7] versus 333.0 [95% CI 329.3-336.7] per 100000 patients, respectively; p = 0.15)., Conclusions: Of 100 cases with IBD and COVID-19, 20% developed severe COVID-19, 59% were hospitalised and 13% died. A comparable COVID-19 risk was found between the IBD cohort [100/34 763 = 0.29%] and the general Dutch population. The presence of ≥1 comorbidities was an independent risk factor for hospitalisation due to COVID-19., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as an invasive fungal disease, often affecting previously immunocompetent, mechanically ventilated, intensive care unit (ICU) patients. Incidence rates of 3.8%-33.3% have been reported depending on the geographic area, with high (47%) mortality., Objectives: Here, we describe a single-centre prospective case series with CAPA cases from both the first (March-May, n = 5/33) and second (mid-September through mid-December, n = 8/33) COVID-19 wave at a 500-bed teaching hospital in the Netherlands., Patients/methods: In the first COVID-19 wave, a total of 265 SARS-CoV-2 PCR-positive patients were admitted to our hospital of whom 33 needed intubation and mechanical ventilation. In the second wave, 508 SARS-CoV-2 PCR-positive patients were admitted of whom 33 needed mechanical ventilation. Data were prospectively collected., Results: We found a significant decrease in COVID-19 patients needing mechanical ventilation in the ICU in the second wave (p < .01). From these patients, however, a higher percentage were diagnosed with CAPA (24.2% vs 15.2%), although not significant (p = .36). All CAPA patients encountered in the second wave received dexamethasone. Mortality between both groups was similarly high (40%-50%). Moreover, we found environmental TR 34 /L98H azole-resistant Aspergillus fumigatus isolates in two separate patients., Conclusions: In this series, 19.7% (n = 13/66) of mechanically ventilated SARS-CoV-2 patients were diagnosed with CAPA. In addition, we found a significant reduction in COVID-19 patients needing mechanical ventilation on the ICU in the second wave. Numbers are too small to determine whether there is a true difference in CAPA incidence in mechanically ventilated patients between the two waves, and whether it could be attributed to dexamethasone SARS-CoV-2 therapy., (© 2021 The Authors. Mycoses published by Wiley-VCH GmbH.)

Background: The majority of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are admitted to the Intensive Care Unit (ICU) for mechanical ventilation. The role of multi-organ failure during ICU admission as driver for outcome remains to be investigated yet., Design and Setting: Prospective cohort of mechanically ventilated critically ill with SARS-CoV-2 infection., Participants and Methods: 94 participants of the MaastrICCht cohort (21% women) had a median length of stay of 16 days (maximum of 77). After division into survivors (n = 59) and non-survivors (n = 35), we analysed 1555 serial SOFA scores using linear mixed-effects models., Results: Survivors improved one SOFA score point more per 5 days (95% CI: 4-8) than non-survivors. Adjustment for age, sex, and chronic lung, renal and liver disease, body-mass index, diabetes mellitus, cardiovascular risk factors, and Acute Physiology and Chronic Health Evaluation II score did not change this result. This association was stronger for women than men (P-interaction = 0.043)., Conclusions: The decrease in SOFA score associated with survival suggests multi-organ failure involvement during mechanical ventilation in patients with SARS-CoV-2. Surviving women appeared to improve faster than surviving men. Serial SOFA scores may unravel an unfavourable trajectory and guide decisions in mechanically ventilated patients with SARS-CoV-2., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the practice of ventilation management in patients with COVID-19. We aimed to describe the practice of ventilation management and to establish outcomes in invasively ventilated patients with COVID-19 in a single country during the first month of the outbreak., Methods: PRoVENT-COVID is a national, multicentre, retrospective observational study done at 18 intensive care units (ICUs) in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The primary outcome was a combination of ventilator variables and parameters over the first 4 calendar days of ventilation: tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and ICU complications. Patient-centred outcomes were ventilator-free days at day 28, duration of ventilation, duration of ICU and hospital stay, and mortality. PRoVENT-COVID is registered at ClinicalTrials.gov (NCT04346342)., Findings: Between March 1 and April 1, 2020, 553 patients were included in the study. Median tidal volume was 6·3 mL/kg predicted bodyweight (IQR 5·7-7·1), PEEP was 14·0 cm H 2 O (IQR 11·0-15·0), and driving pressure was 14·0 cm H 2 O (11·2-16·0). Median respiratory system compliance was 31·9 mL/cm H 2 O (26·0-39·9). Of the adjunctive treatments for refractory hypoxaemia, prone positioning was most often used in the first 4 days of ventilation (283 [53%] of 530 patients). The median number of ventilator-free days at day 28 was 0 (IQR 0-15); 186 (35%) of 530 patients had died by day 28. Predictors of 28-day mortality were gender, age, tidal volume, respiratory system compliance, arterial pH, and heart rate on the first day of invasive ventilation., Interpretation: In patients with COVID-19 who were invasively ventilated during the first month of the outbreak in the Netherlands, lung-protective ventilation with low tidal volume and low driving pressure was broadly applied and prone positioning was often used. The applied PEEP varied widely, despite an invariably low respiratory system compliance. The findings of this national study provide a basis for new hypotheses and sample size calculations for future trials of invasive ventilation for COVID-19. These data could also help in the interpretation of findings from other studies of ventilation practice and outcomes in invasively ventilated patients with COVID-19., Funding: Amsterdam University Medical Centers, location Academic Medical Center., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To determine whether children with asymptomatic carriage of rhinovirus in the nasopharynx before elective cardiac surgery have an increased risk of prolonged PICU length of stay., Study Design: Prospective, single-center, blinded observational cohort study., Setting: PICU in a tertiary hospital in The Netherlands., Patients: Children under 12 years old undergoing elective cardiac surgery were enrolled in the study after informed consent of the parents/guardians., Interventions: The parents/guardians filled out a questionnaire regarding respiratory symptoms. On the day of the operation, a nasopharyngeal swab was obtained. Clinical data were collected during PICU admission, and PICU/hospital length of stay were reported. If a patient was still intubated 3 days after operation, an additional nasopharyngeal swab was collected. Nasopharyngeal swabs were tested for rhinovirus and other respiratory viruses with polymerase chain reaction., Measurements and Main Results: Of the 163 included children, 74 (45%) tested rhinovirus positive. Rhinovirus-positive patients did not have a prolonged PICU length of stay (median 2 d each; p = 0.257). Rhinovirus-positive patients had a significantly shorter median hospital length of stay compared with rhinovirus-negative patients (8 vs 9 d, respectively; p = 0.006). Overall, 97 of the patients (60%) tested positive for one or more respiratory virus. Virus-positive patients had significantly shorter PICU and hospital length of stay, ventilatory support, and nonmechanical ventilation. Virus-negative patients had respiratory symptoms suspected for a respiratory infection more often. In 31% of the children, the parents reported mild upper respiratory complaints a day prior to the cardiac surgery, this was associated with postextubation stridor, but no other clinical outcome measures., Conclusions: Preoperative rhinovirus polymerase chain reaction positivity is not associated with prolonged PICU length of stay. Our findings do not support the use of routine polymerase chain reaction testing for respiratory viruses in asymptomatic children admitted for elective cardiac surgery., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Purpose: Since the SARS-CoV-2 pandemic, countries are overwhelmed by critically ill Coronavirus disease 2019 (COVID-19) patients. As ICU capacity becomes limited we characterized critically ill COVID-19 patients in the Netherlands., Methods: In this case series, COVID-19 patients admitted to the ICU of the Jeroen Bosch Hospital were included from March 9 to April 7, 2020. COVID-19 was confirmed by a positive result by a RT-PCR of a specimen collected by nasopharyngeal swab. Clinical data were extracted from medical records., Results: The mean age of the 50 consecutively included critically ill COVID-19 patients was 65 ± 10 years, the mean BMI was 29 ± 4.7 and 66% were men. Seventy-eight percent of patients had ≥1 comorbidity, 34% had hypertension. Ninety-six percent of patients required mechanical ventilation and 80% were ventilated in prone position. Venous thromboembolism was recognized in 36% of patients. Seventy-four percent of patients survived and were successfully discharged from the ICU, the remaining 26% died (median follow up 86 days). The length of invasive ventilation in survivors was 15 days (IQR 12-31)., Conclusions: The survival rate of COVID-19 critically ill patients in our population is considerably better than previously reported. Thrombotic complications are commonly found and merit clinical attention., Trial Registration Number: NL2020.07.04.01., Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected patients. Although it has been suggested that ARBs might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation, and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking. METHODS: The PRAETORIAN-COVID trial is a multicenter, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2-infected patients (n = 651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020). SUMMARY: The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation, and death in hospitalized SARS-CoV-2-infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Frailty is an important predictor for the prognosis of intensive care unit (ICU) patients. This study examined changes in frailty in the year after ICU admission, and its associated factors., Materials and Methods: Prospective cohort study including adult ICU patients admitted between July 2016-December 2017. Frailty was measured using the Clinical Frailty Scale (CFS), before ICU admission, at hospital discharge, and three and 12 months after ICU admission. Multivariable linear regression was used to explore factors associated with frailty changes., Results: Frailty levels changed among 1300 ICU survivors, with higher levels at hospital discharge and lower levels in the following months. After one year were 42% of the unplanned, and 27% of the planned patients more frail. For both groups were older age, longer hospital length of stay, and discharge location associated with being more frail. Male sex, higher education level and mechanical ventilation were associated with being less frail in the planned patients., Conclusion: One year after ICU admission, 42% and 27% of the unplanned and planned ICU patients, respectively, were more frail. Insight in the associated factors will help to identify patients at risk, and may help in informing patients and their family members., Registration: ClinicalTrials.gov database (NCT03246334)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Viral bronchiolitis is the most common cause of respiratory failure requiring invasive ventilation in young children. Bacterial co-infections may complicate and prolong paediatric intensive care unit (PICU) stay. Data on prevalence, type of pathogens and its association with disease severity are limited though. These data are especially important as bacterial co-infections may be treated using antibiotics and could reduce disease severity and duration of PICU stay. We investigated prevalence of bacterial co-infection and its association with disease severity and PICU stay., Methods: Retrospective cohort study of the prevalence and type of bacterial co-infections in ventilated children performed in a 14-bed tertiary care PICU in The Netherlands. Children less than 2 years of age admitted between December 2006 and November 2014 with a diagnosis of bronchiolitis and requiring invasive mechanical ventilation were included. Tracheal aspirates (TA) and broncho-alveolar lavages (BAL) were cultured and scored based on the quantity of bacteria colony forming units (CFU) as: co-infection (TA > 10 ^5 /BAL > 10 ^4 CFU), low bacterial growth (TA < 10 ^5 /BAL < 10 ^4 CFU), or negative (no growth). Duration of mechanical ventilation and PICU stay were collected using medical records and compared against the presence of co-infection using univariate and multivariate analysis., Results: Of 167 included children 63 (37.7%) had a bacterial co-infection and 67 (40.1%) low bacterial growth. Co-infections occurred within 48 h from intubation in 52 out 63 (82.5%) co-infections. H.influenza (40.0%), S.pneumoniae (27.1%), M.catarrhalis (22.4%), and S.aureus (7.1%) were the most common pathogens. PICU stay and mechanical ventilation lasted longer in children with co-infections than children with negative cultures (9.1 vs 7.7 days, p = 0.04 and 8.1vs 6.5 days, p = 0.02)., Conclusions: In this large study, bacterial co-infections occurred in more than a third of children requiring invasive ventilation for bronchiolitis and were associated with longer PICU stay and mechanical ventilation. These findings support a clinical trial of antibiotics to test whether antibiotics can reduce duration of PICU stay.

Background: Pertussis causes severe disease in young unvaccinated infants, with preterms potentially at highest risk. We studied pertussis in hospitalized infants as related to gestational age (GA) and vaccination history., Methods: Medical record data of 0-2y old patients hospitalized for pertussis during 2005-2014 were linked to vaccination data. Multivariable logistic regression was used to study the association between GA and vaccination history on the clinical disease course. We compared vaccine effectiveness (VE) against hospitalization for pertussis between term and preterm infants (i.e., <37w GA) using the screening method as developed by Farrington., Results: Of 1187 records, medical data from 676 were retrieved. Of these, 12% concerned preterms, whereas they are 8% of Dutch birth cohorts. Median age at admission was 3 m for preterms and 2 m for terms (p < 0.001). Preterms more often had received pertussis vaccination (62% vs 44%; p = 0.01) and more often had coinfections (37% vs 21%; p = 0.01). Preterms tended more often to have complications, to require artificial respiration or to need admittance to the intensive care unit (ICU). Preterms had longer ICU stays (15d vs 9d; p = 0.004). Vaccinated preterms and terms had a lower median length of hospital stay and lower crude risks of apneas and the need for artificial respiration, additional oxygen, and ICU admittance than those not vaccinated. After adjustment for presence of coinfections and age at admittance, these differences were not significant, except the lower need of oxygen treatment in vaccinated terms. Effectiveness of the first vaccination against pertussis hospitalizations was 95% (95% CI 93-96%) and 73% (95% CI 20-91%) in terms and preterms, respectively. Effectiveness of the second dose of the primary vaccination series was comparable in both groups (86 and 99%, respectively)., Conclusions: Infants hospitalized for pertussis suffer from severe disease. Preterms were overrepresented, with higher need for intensive treatment and less VE of first vaccination. These findings stress the need for alternative prevention, in particular prenatal vaccination of mothers, to reduce pertussis in both groups.

Objective: To evaluate the feasibility and safety of exercise testing and to describe the physiological response to exercise of patients in the Intensive Care Unit (ICU)., Design: A prospective observational multicenter study., Setting: Two mixed medical-surgical ICUs., Participants: Patients (N=37; with no primary neurological disorders, 59% men; median age 50y; ICU length of stay 14.5d; Acute Physiology and Chronic Health Evaluation IV 73.0) who had been mechanically ventilated for more than 48 hours and were hemodynamically stable enough to perform physical exercise., Interventions: A passive or active incremental exercise test, depending on muscle strength, on a bed-based cycle ergometer., Main Outcome Measures: Feasibility and safety were evaluated based on protocol adherence and adverse events. Physiological responses to exercise quantified as changes in respiratory frequency (RF), oxygen uptake (Vo 2 ), carbon dioxide output (Vco 2 ), respiratory exchange ratio (RER), and blood lactate., Results: Thirty-seven patients of whom 18 were mechanically ventilated underwent the exercise test. The active incremental test was performed by 28, and the passive test by 9 participants. Thirty-three (89%) accomplished the test according to the protocol and 1 moderate severe adverse event (bradycardia; heart rate 44) occurred shortly after the test. RF, Vo 2 , Vco 2 , and lactate increased significantly, whereas RER did not change during the active incremental exercise test. No changes were observed during the passive exercise test., Conclusions: It is safe and feasible to perform exercise testing on a bed-based cycle ergometer in patients who are critically ill and a physiological response could be measured. Future research should investigate the clinical value of exercise testing in daily ICU practice and whether exercise capacity and its limiting factors could be determined by incremental exercise testing., (Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background/objectives: In order to identify critically ill patients with high nutritional risk the modified NUTrition Risk in the Critically ill (mNUTRIC)-score was developed. This score aims to identify patients that will benefit from nutritional interventions. Few data are available on its validity. In The Netherlands, the MUST-score, a nutritional assessment tool for non-ICU patients, is commonly used in the ICU. To validate the mNUTRIC-score in Dutch ICU patients and compare its prognostic performance with the MUST-score., Subjects/methods: A single-center retrospective cohort study among 475 mechanically ventilated patients. Prognostic performance of the mNUTRIC and MUST-scores were assessed and compared for discriminative abilities for 28-day mortality and prolonged mechanical ventilation (>2 days)., Results: The discriminative ability of the mNUTRIC-score for 28-day mortality is (ROC-AUC) 0.768 (95% CI 0.722-0.814) with an associated LR+ of 1.73 (95% CI 1.53-1.95) and LR- of 0.24 (95% CI 0.14-0.39) when comparing low with high (>4) scores. Comparing low with high MUST-scores (>1) a ROC-AUC of 0.513 (95% CI 0.445-0.587) and LR+ of 1.05 (95%CI 0.77-1.45) and LR- of 0.97 (95% CI 0.71-1.17) for mortality were found. The discriminative ability for prolonged ventilation was 0.666 (95% CI 0.616-0.716) and 0.532 (95% CI 0.469-0.594) for the mNUTRIC and MUST-scores, respectively., Conclusions: The prognostic performance of the mNUTRIC-score for 28-day mortality is fair and comparable to other validation studies. The association with prolonged ventilation was not confirmed by our results. The mNUTRIC-score has better performance than the commonly used MUST-score. Therefore, we suggest abandoning use of the MUST-score and to recommend introduction of the mNUTRIC-score for the nutritional risk assessment of critically ill patients.

Purpose: Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate the attributable effect of CMV reactivation on mortality in immunocompetent ARDS patients., Methods: We prospectively studied immunocompetent ARDS patients who tested seropositive for CMV and remained mechanically ventilated beyond day 4 in two tertiary intensive care units in the Netherlands from 2011 to 2013. CMV loads were determined in plasma weekly. Competing risks Cox regression was used with CMV reactivation status as a time-dependent exposure variable. Subsequently, in sensitivity analyses we adjusted for the evolution of disease severity until onset of reactivation using marginal structural modeling., Results: Of 399 ARDS patients, 271 (68%) were CMV seropositive and reactivation occurred in 74 (27%) of them. After adjustment for confounding and competing risks, CMV reactivation was associated with overall increased ICU mortality (adjusted subdistribution hazard ratio (SHR) 2.74, 95% CI 1.51-4.97), which resulted from the joint action of trends toward an increased mortality rate (direct effect; cause specific hazard ratio (HR) 1.58, 95% CI 0.86-2.90) and a reduced successful weaning rate (indirect effect; cause specific HR 0.83, 95% CI 0.58-1.18). These associations remained in sensitivity analyses. The population-attributable fraction of ICU mortality was 23% (95% CI 6-41) by day 30 (risk difference 4.4, 95% CI 1.1-7.9)., Conclusion: CMV reactivation is independently associated with increased case fatality in immunocompetent ARDS patients who are CMV seropositive.

Background & Aims: Adequate nutritional intake is essential during pediatric intensive care admission. We investigated whether achievement of energy intake goals at day 4 after admission and route of nutrition were associated with improved outcome., Methods: Observational study using prospectively acquired data. Patients receiving enteral and/or parenteral nutrition were included. The energy intake target range at day 4 after admission was 90-110% of resting energy expenditure +10%. Acute malnutrition was defined as weight-for-age <-2 SD. Clinical outcome measures were length of stay, days on ventilator, duration of antibiotics and number of new infections. Data as median (min-max)., Results: Of 325 subjects (age 0.14 (0.0-18.0) year), 19% were acutely malnourished upon admission. Median 86% of energy goals were administered via the enteral route. With enteral energy intake, 7% of patients were fed within the target range, 50% were fed below and 43% were fed above the target range. In a subgroup (n = 223) the acutely malnourished proportion at discharge (26%) was not significantly different from that upon admission (22%). Whether the energy intake was below, within or above the target range did not affect changes in clinical outcome, nor did the route of nutrition., Conclusions: Acute malnutrition was highly prevalent upon admission and at discharge. With our nutritional protocol we achieved high rates of (enteral) energy intake. A high percentage of our population received enteral energy above the target energy range. However, there was no association between the amount of energy intake or route of nutrition and clinical outcome., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: Cytomegalovirus reactivation may complicate critical illness in latent carriers of the virus, even in patients who were previously immunocompetent. Patients with acute respiratory distress syndrome are considered to be prone for reactivation. Prophylactic antiviral therapy in immunocompetent cytomegalovirus seropositive patients admitted to the ICU with acute respiratory distress syndrome has therefore been proposed. We assessed cytomegalovirus seroprevalence as a risk factor for morbidity and mortality in patients with acute respiratory distress syndrome., Design: Prospective observational cohort study. We used the number of days alive and free of mechanical ventilation on day 28 as a composite outcome measure and used multivariable ordinal logistic regression analyses to adjust for potential confounders., Setting: ICUs of two tertiary care hospitals in The Netherlands., Patients: We included all newly admitted patients with acute respiratory distress syndrome who received mechanical ventilation for at least 4 days. Patients with known immunocompromise and those receiving antiviral treatment prior to ICU admission were excluded., Interventions: None., Measurements and Main Results: Over a 2-year period, 306 patients were included, 209 (68%) of whom were cytomegalovirus seropositive. Cytomegalovirus reactivation occurred in 53 of these cases (26%). One hundred patients (33%) died or continued to be mechanically ventilated by day 28. After adjustment for confounding, cytomegalovirus seroprevalence was not associated with the primary outcome (crude odds ratio, 1.09; 95% CI, 0.70-1.70; adjusted odds ratio, 1.01; 95% CI, 0.64-1.59). Seroprevalence was also not associated with poor outcome in any of the prespecified subgroup analyses. However, a significant association was found in a post hoc subgroup of patients who had developed acute respiratory distress syndrome in a setting of septic shock (adjusted odds ratio, 2.86; 95% CI, 1.32-6.23). The time course of pulmonary markers in survivors was comparable between the two serogroups., Conclusions: Cytomegalovirus seroprevalence is not associated with prolonged mechanical ventilation or increased mortality in critically ill patients with acute respiratory distress syndrome, with possible exception of patients presenting with septic shock. Therefore, a prevention strategy targeting an unselected cohort of seropositive patients with acute respiratory distress syndrome is unlikely to show any meaningful benefit.

Objective: Neonatal resuscitation is often retrospectively documented, which can lead to inaccuracy and incomplete recording of delivery room management. In this study, we assessed the accuracy and completeness of neonatal resuscitation documentation in our neonatal intensive care unit., Methods: Recordings of physiological parameters and video data were performed in the delivery room and used to deduct the clinical condition of the infant, the interventions done and their effect on the infant's condition. The data from the recordings were compared with the documentation on neonatal stabilisation in the medical records (paper or digital)., Results: Recordings of 54 infants were compared with the documentation in their medical records. In 93% of the medical records delivery room management was documented. The clinical condition of the infant at birth was documented in 76% and 1 min Apgar scores in 98%. Respiratory support was correctly documented in 83%, heart rate in 37% and oxygen saturation in 13%. In 57% use of supplemental oxygen and its indication were correctly reported. Seven infants were intubated and this was correctly documented in 57%. Apgar scores were compared between the recordings and the medical records. At 1 min, 5 min and 10 min after birth the Apgar score, given by the researcher using the recordings, was similar to the scores in the medical records in 33%, 44% and 53%, respectively., Conclusions: Accurate and complete documentation of neonatal resuscitation continues to be a challenge. Recordings of physiological parameters and video imaging can improve documentation by providing detailed information., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Pulmonary coagulopathy is a hallmark of lung injury following inhalation trauma. Locally applied heparin attenuates lung injury in animal models of smoke inhalation. Whether local treatment with heparin benefits patients with inhalation trauma is uncertain. The present trial aims at comparing a strategy using frequent nebulizations of heparin with standard care in intubated and ventilated burn patients with bronchoscopically confirmed inhalation trauma., Methods: The Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized HEParin versus Placebo in BURN Patients with Inhalation Trauma (HEPBURN) is an international multi-center, double-blind, placebo-controlled, two-arm study. One hundred and sixteen intubated and ventilated burn patients with confirmed inhalation trauma are randomized to nebulizations of heparin (the nebulized heparin strategy) or nebulizations of normal saline (the control strategy) every four hours for 14 days or until extubation, whichever comes first. The primary endpoint is the number of ventilator-free days, defined as days alive and breathing without assistance during the first 28 days, if the period of unassisted breathing lasts for at least 24 consecutive hours., Discussion: As far as the authors know, HEPBURN is the first randomized, placebo-controlled trial, powered to investigate whether local treatment with heparin shortens duration of ventilation of intubated and ventilated burn patients with inhalation trauma., Trial Registration: NCT01773083 (http://www.clinicaltrials.gov), registered on 16 January 2013.Recruiting. Randomisation commenced on 1 January 2014.

Background: In adult patients who are critically ill and mechanically ventilated, daily interruption of sedation (DSI) is an effective method of improving sedation management, resulting in a decrease of the duration of mechanical ventilation, the length of stay in the intensive care unit (ICU) and the length of stay in the hospital. It is a safe and effective approach and is common practice in adult ICUs. For critically ill children it is unknown if DSI is effective and feasible. The aim of this multicenter randomized controlled trial is to evaluate the safety and efficacy of daily sedation interruption in critically ill children., Methods/design: Children between 0 and 18 years of age who require mechanical ventilation, with an expected duration of at least 48 h and need for sedative infusion, will be included. After enrollment patients will be randomly assigned to DSI in combination with protocolized sedation (intervention group) or protocolized continuous sedation (control group). A sedation protocol that contains an algorithm for increasing and weaning of sedatives and analgesics will be used. The sedative infusion will be restarted if the patient becomes uncomfortable or agitated according to the sedation protocol. The primary endpoint is the number of ventilator-free days at 28 days., Trial Registration: NTR2030.

Background and Purpose: We assessed the first evaluation at a large ventilation clinic in the Netherlands to: (i) determine what proportion of patients with motor neuron disease would benefit from earlier referral; and (ii) examine the patient preferences regarding ventilatory support., Methods: Observational study at a single centre with a catchment area of 7.6 million inhabitants. Data on disease status, the referral process and patients' preferences regarding ventilatory support were collected during the first home ventilation services (HVS) assessment and analysed for correlation with the presence of daytime hypercapnia and suspected nocturnal hypoventilation. The latter conditions require immediate (within 48 h) or subacute (within 3 weeks) initiation of ventilatory support., Results: Vital capacity (in percentage of predicted value, VC%pred) was assessed by referring physicians in 84% of the 217 referred patients; the mean VC%pred was 69% (SD 16). One-hundred and ninety-one patients attended the first HVS assessment without ventilatory support, at a median of 21 days following referral: 18% had respiratory failure (daytime hypercapnia), 19% had normocapnia but were suspected of nocturnal hypoventilation, and 63% had normocapnia without symptoms. Following the HVS assessment, 25 patients (13%) declined home mechanical ventilation; this occurred more often in patients with (14/70) compared with patients without respiratory impairment (11/121; P < 0.05)., Conclusion: A meaningful proportion of patients who desire ventilatory support are referred to a ventilation clinic after already developing respiratory failure. Future studies could examine means, including more sensitive respiratory measures, to detect those patients who could benefit from earlier referral., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Background: The 2010 guidelines for cardiopulmonary resuscitation allow 5 seconds to give 2 breaths to deliver sufficient chest compressions and to keep perfusion pressure high. This study aims to determine whether the recommended short interruption for ventilations by trained lay rescuers and first responders can be achieved and to evaluate its consequence for chest compressions and survival., Methods and Results: From a prospective data collection of out-of-hospital cardiac arrest, we used automatic external defibrillator recordings of cardiopulmonary resuscitation by rescuers who had received a standard European Resuscitation Council basic life support and automatic external defibrillator course. Ventilation periods and total compressions delivered per minute during each 2 minutes of cardiopulmonary resuscitation cycle were measured, and the chest compression fraction was calculated. Neurological intact survival to discharge was studied in relation to these factors and covariates. We included 199 automatic external defibrillator recordings. The median interruption time for 2 ventilations was 7 seconds (25th-75th percentile, 6-9 seconds). Of all rescuers, 21% took <5 seconds and 83% took <10 seconds for a ventilation period; 97%, 88%, and 63% of rescuers were able to deliver >60, >70, and >80 chest compressions per minute, respectively. The median chest compression fraction was 65% (25th-75th percentile, 59%-71%). Survival was 25% (49 of 199), not associated with long or short ventilation pauses when controlled for covariates., Conclusions: The great majority of rescuers can give 2 rescue breaths in <10 seconds and deliver at least 70 compressions in a minute. Longer pauses for ventilations are not associated with worse outcome. Guidelines may allow longer pauses for ventilations with no detriment to survival.

Background: Readmission within 48 hours is a leading performance indicator of the quality of care in an intensive care unit., Objective: To investigate variables that might be associated with readmission to a surgical intensive care unit., Methods: Demographic characteristics, severity-of-illness scores, and survival rates were collected for all patients admitted to a surgical intensive care unit between 1995 and 2000. Long-term survival and quality of life were determined for patients who were readmitted within 30 days after discharge from the unit. Quality of life was measured with the EuroQol-6D questionnaire. Multivariate logistic analysis was used to calculate the independent association of expected covariates., Results: Mean follow-up time was 8 years. Of the 1682 patients alive at discharge, 141 (8%) were readmitted. The main causes of readmission were respiratory decompensation (48%) and cardiac conditions (16%). Compared with the total sample, patients readmitted were older, mostly had vascular (39%) or gastrointestinal (26%) disease, and had significantly higher initial severity of illness (P = .003, .007) and significantly more comorbid conditions (P = .005). For all surgical classifications except general surgery, readmission was independently associated with type of admission and need for mechanical ventilation. Long-term mortality was higher among patients who were readmitted than among the total sample. Nevertheless, quality-of-life scores were the same for patients who were readmitted and patients who were not., Conclusion: The adverse effect of readmission to the intensive care unit on survival appears to be long-lasting, and predictors of readmission are scarce.

Background: Acute admission to an intensive care unit (ICU) of cancer patients is considered with increasing frequency due to a better life expectancy and more aggressive therapies. The aim of this study was to determine the characteristics and outcomes of cancer patients with unplanned admissions to general ICUs, and to compare these with outcomes of critically ill patients without cancer., Material and Methods: All unplanned ICU admissions in the Netherlands collected in the National Intensive Care Evaluation registry between January 2007 and January 2011 were analyzed., Results and Conclusion: Of the 140,154 patients with unplanned ICU admission 10.9% had a malignancy. Medical cancer patients were more severely ill on ICU admission in comparison with medical non-cancer patients, as reflected by higher needs for mechanical ventilation (50.8% vs. 46.4%, p < 0.001) and vasopressors within 24 hours after admission (41.5% vs. 33.0%, p < 0.001), higher Acute Physiology and Chronic Health Evaluation (APACHE) IV scores (88.1 vs. 67.5, p < 0.001) and a longer ICU stay (5.1 vs. 4.6 days, p < 0.001). In contrast, surgical cancer patients only displayed a modestly higher APACHE IV score on admission when compared with non-cancer surgical patients, whereas the other afore mentioned parameters were lower in the surgical cancer patients group. In-hospital mortality was almost twice as high in medical cancer patients (40.6%) as in medical patients without cancer (23.7%). In-hospital mortality of surgical cancer patients (17.4%) was slightly higher than in patients without cancer (14.6%). These data indicate that unplanned ICU admission is associated with a high mortality in patients with cancer when admitted for medical reasons.

Objective: Deep hypothermic circulatory arrest (DHCA) and antegrade cerebral perfusion (ACP) are 2 cardiopulmonary bypass techniques applied in aortic arch repair. In recent literature, cerebral effects of both techniques have received most attention, whereas the consequences for other organs have not been thoroughly investigated. Therefore, in this study, the impact of duration of DHCA and ACP on postoperative recovery was analyzed in a cohort of neonates undergoing aortic arch reconstruction., Methods: All consecutive neonates who underwent aortic arch reconstruction from 2004 to 2009 were included in this retrospective study. Length of stay on the intensive care unit (ICU-LOS), duration of mechanical ventilation, inotrope score, and areas under the curve (AUC) for lactate and creatinine were compared with respect to durations of DHCA and ACP, respectively. Correction for confounders was performed using multivariable linear regression., Results: Eighty-three neonates were included, with a 30-day mortality of 4.8%. Longer duration of DHCA was associated with longer ICU-LOS both in univariable and multivariable analyses. Similarly, duration of mechanical ventilation and lactate and creatinine AUCs increased with duration of DHCA. Inotrope score was only associated with DHCA duration in univariable analysis. Duration of ACP did not affect any of the outcome parameters., Conclusions: Increasing duration of DHCA, but not ACP, during neonatal aortic arch reconstruction prolongs short-term postoperative recovery. This suggests all efforts should be made to reduce the duration of DHCA to the shortest period possible, which may be achieved by exclusive use of ACP or a combination of the 2 perfusion techniques., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Minimal access aortic valve replacement (AVR) has been demonstrated to have beneficial effects over median sternotomy. Minimal extracorporeal circulation (MECC) has been shown to have less deleterious effects than conventional cardiopulmonary bypass. We describe for the first time AVR via upper J-shaped partial sternotomy compared to median sternotomy using MECC., Methods: Prospectively collected pre-operative, intra-operative, post-operative and follow-up data from 104 consecutive patients who underwent minimal access AVR were compared to 72 consecutive patients undergoing median sternotomy using MECC during the same period (January 2007 to December 2009)., Results: No significant differences were found in patient's characteristics or intra-operative data with the exception of pre-existing pulmonary disease. The mean cardiopulmonary bypass (86 ± 18 min vs. 78 ± 15 min, p = 0.0079) and cross-clamp times (65 ± 13 min vs. 59 ± 12 min, p = 0.0013) were significantly shorter in the median sternotomy group. Mediastinal blood loss (397 ± 257 ml vs. 614 ± 339 ml, p < 0.0001) and ventilation time (8 ± 6.9 h vs. 11 ± 16.5 h, p = 0.0054) were significantly less in the minimal access group. No differences were seen in transfusion requirements, inotropic support, intensive care unit (ICU) stay, total hospital stay, post-operative haemoglobin drop, major events or mortality. Quality of life scores after discharge demonstrated less pain with a quicker recovery and return to daily activities in patients receiving J-shaped sternotomy., Conclusions: Minimal access AVR using MECC is feasible and provides excellent clinical results. Less pain and quicker recovery was experienced among patients in this group.

Background and Objective: In pharmacological research, arm occlusion pressure is used to study haemodynamic effects of drugs. However, arm occlusion pressure might be an indicator of static filling pressure of the arm. We hypothesised that arm occlusion pressure can be used to predict fluid loading responsiveness., Methods: Twenty-four patients who underwent cardiac surgery were studied during their first 2 h in the ICU. The lungs were ventilated mechanically and left ventricular function was supported as necessary. Arm occlusion pressure was defined as the radial artery pressure after occluding arterial flow for 35 s by a blood pressure cuff inflated to 50 mmHg above SBP. The cuff was positioned around the arm in which a radial artery catheter had been inserted. Measurements were performed before (baseline) and after fluid loading (500 ml hydroxyethyl starch 6%). Patients whose cardiac output increased by at least 10% were defined as responders., Results: In responders (n = 17), arm occlusion pressure, mean arterial pressure and central venous pressure increased and stroke volume variation and pulse pressure variation decreased. In non-responders (n = 7), arm occlusion pressure and central venous pressure increased, and pulse pressure variation decreased. Mean arterial pressure, stroke volume variation and heart rate did not change significantly. The area under the curve to predict fluid loading responsiveness for arm occlusion pressure was 0.786 (95% confidence interval 0.567-1.000), at a cut-off of 21.9 mmHg, with sensitivity of 71% and specificity of 88% in predicting fluid loading responsiveness. Prediction of responders with baseline arm occlusion pressure was as good as baseline stroke volume variation and pulse pressure variation., Conclusion: Arm occlusion pressure was a good predictor of fluid loading responsiveness in our group of cardiac surgery patients and offers clinical advantages over stroke volume variation and pulse pressure variation.

Background: Pulmonary coagulopathy is intrinsic to pneumonia and other forms of acute lung injury. We hypothesized patients with burn injuries and inhalation trauma to have similar alterations in pulmonary coagulation and fibrinolysis., Methods: We performed a prospective study on changes in pulmonary and systemic thrombin generation and fibrinolytic activity in patients with burn injuries and inhalation trauma requiring mechanical ventilation. Nondirected bronchial lavage was performed on alternate days. Patients requiring mechanical ventilation for nonpulmonary reasons who did not meet the North American European Consensus Conference criteria for acute lung injury functioned as control patients., Results: We studied 13 patients with burn injuries and inhalation trauma and 15 control patients. On admission, patients with burn injuries and inhalation trauma showed a significant increase in thrombin generation in the airways compared with control patients, as reflected by increased lavage fluid levels of thrombin-antithrombin complexes and fibrin degradation products, and decreased lavage fluid levels of activated protein C and antithrombin. Simultaneously, burn patients showed a significant decrease in fibrinolytic activity, as reflected by decreased lavage fluid levels of plasminogen activator activity. Pulmonary coagulopathy persisted throughout the period of mechanical ventilation and was accompanied by similar changes in systemic coagulation and fibrinolysis. There was no significant correlation between changes in coagulation and fibrinolysis and the extent of burn injury., Conclusions: Patients with burn injuries and inhalation trauma requiring mechanical ventilation show a distinct and sustained procoagulant and antifibrinolytic shift in the pulmonary compartment. Pulmonary coagulopathy could be an important therapeutic target in these patients.

Objective: This study describes the clinical course, treatment, and outcome of 13 critically ill children due to infection with new influenza A H1N1, admitted to 2 pediatric intensive care units (PICUs) in the northwestern part of the Netherlands., Methods: Retrospective case series, conducted in 2 PICUs in Amsterdam, the Netherlands., Results: A total of 13 children with a new influenza A H1N1 infection were admitted at 2 Dutch PICUs. The majority of these children were 12 to 16 years old and had an underlying disease. All children required mechanical ventilatory support. Shock was present in 7 of 13 (54%) children. Two children were transferred to a supraregional PICU with facilities for extracorporeal membrane oxygenation., Conclusions: In a Dutch cohort of 13 critically ill children due to infection with new influenza (H1N1), respiratory (100%) and circulatory (54%) failure characterized the course of this infection in most of these children. All children survived.

Objective: To clarify the process of end-of-life decision-making in culturally different neonatal intensive care units (NICUs)., Study Design: Review of medical files of newborns >22 weeks gestation who died in the delivery room (DR) or the NICU during 12 months in 4 NICUs (Chicago, Milwaukee, Montreal, and Groningen). We categorized deaths using a 2-by-2 matrix and determined whether mechanical ventilation was withdrawn/withheld and whether the child was dying despite ventilation or physiologically stable but extubated for neurological prognosis., Results: Most unstable patients in all units died in their parents' arms after mechanical ventilation was withdrawn. In Milwaukee, Montreal, and Groningen, 4% to 12% of patients died while receiving cardiopulmonary resuscitation. This proportion was higher in Chicago (31%). Elective extubation for quality-of-life reasons never occurred in Chicago and occurred in 19% to 35% of deaths in the other units. The proportion of DR deaths in Milwaukee, Montreal, and Groningen was 16% to 22%. No DR deaths occurred in Chicago., Conclusions: Death in the NICU occurred differently within and between countries. Distinctive end-of-life decisions can be categorized separately by using a model with uniform definitions of withholding/withdrawing mechanical ventilation correlated with the patient's physiological condition. Cross-cultural comparison of end-of-life practice is feasible and important when comparing NICU outcomes.

Objective: To determine tracheostomy-management practices in Dutch intensive care units (ICUs) and post-ICU step-down facilities., Methods: We surveyed the physician medical directors of all Dutch nonpediatric ICUs that have > or = 5 beds suitable for mechanical ventilation. The survey asked for demographic information about the hospital and ICU setting, and for information and opinions about tracheostomy management in the ICU and step-down facilities, and the use of tracheostomy-management guidelines., Results: Forty-four of the 69 ICUs responded. Sixty-four percent of the respondent ICUs only deflate the cuff when the patient is breathing spontaneously, without assistance from the ventilator. Fifty-nine percent do not routinely change the tracheostomy tube. Almost half use inner cannulas in tracheostomy tubes. Overall, intensivists were most often involved in the follow-up of discharged tracheostomized patients. In the nonacademic hospitals, specialized ICU nurses were more often involved (P = .05). Sixty-four percent indicated they have no guideline for managing discharged tracheostomized patients. There was a diversity of opinion (median visual-analog-scale score 5.0, 95% confidence interval 3.0 to 8.0) on whether the tracheostomy tube should be removed "at once" or after "down-sizing.", Conclusions: There were large differences in tracheostomy management among Dutch ICUs. ICU and post-ICU tracheostomy-management guidelines are lacking and needed.

Objective: To describe the incidence of acute respiratory distress syndrome (ARDS) in mechanically ventilated children and to study whether ARDS is underrecognized in this patient population., Design and Setting: Retrospective observational study in a single-center bed pediatric intensive care unit serving two Dutch provinces., Patients: 533 mechanically ventilated children aged 0-16 years, all of whom met the North-American European Consensus Conference criteria for ARDS., Measurements and Results: Chest radiographs were screened for the novel presence of bilateral infiltrates, in patients with bilateral infiltrates the PaO2/FIO2 ratio was calculated on two separate consecutive measurements. If below 200, the patient was classified as having ARDS. Left ventricular dysfunction was ruled out by echocardiography. The incidence was calculated by obtaining the number of children aged 0-16 years in our region. For each patient it was noted whether the patient was currently considered to have ARDS. Forty-one patients (7.7%) met the criteria for ARDS, with an incidence of 2.2 per 100,000 per year. The mortality rate was 20.4%. Thirty patients (73.1%) had primary ARDS, mainly from viral lower respiratory tract disease. Only ten patients (24.4%) currently had ARDS., Conclusions: The incidence of pediatric ARDS is low compared to that of adult ARDS, and further underestimated as most patients were diagnosed by their underlying diseases.

Objective: Acute respiratory tract infection is a common reason for hospitalization in children with Down syndrome (CDS) and is characterized by a high morbidity. The severe course of disease in CDS may be related to a higher incidence of acute lung injury (ALI). This study evaluated the incidence of ALI and acute respiratory distress syndrome (ARDS) in mechanically ventilated CDS., Design and Setting: Retrospective cohort study in a pediatric ICU., Patients and Participants: Cases were all mechanically ventilated CDS admitted to our unit between January 1998 and July 2005. All mechanically ventilated patients without Down syndrome from January 1998 to January 2001 served as controls. Postoperative patients (cases and controls) and those with a cardiac left to right shunt were excluded., Measurements and Results: The main outcome measure was the incidence of ALI and ARDS. The criteria for ALI were met in 14 of 24 CDS (58.3%) in 41 of 317 of controls (12.9%; OR 9.4, 95% CI 3.9-22.6). The criteria for ARDS were met in 11 of 24 CDS (46%) and in 21 of 317 of controls (7%; OR 11.9, 95% CI 4.8-29.8). None of the CDS with ALI died; in the control group ten patients with ALI died., Conclusions: CDS had a significantly higher incidence of ALI and ARDS than children without Down syndrome. The explanation for this remains to be elucidated; further study is necessary before clinical implications become clear.

Background: The characteristics, incidence and risk factors for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) may depend on definitions and geography., Methods: A prospective, 3-day point-prevalence study was performed by a survey of all intensive care units (ICU) in the Netherlands (n=96). Thirty-six ICU's responded (37%), reporting on 266 patients, of whom 151 were mechanically ventilated. The questionnaire included criteria and potential risk factors for ALI/ARDS, according to the North American-European Consensus Conference (NAECC) or the lung injury score (LIS>or=2.5)., Results: Agreement between definitions was fair (kappa 0.31-0.42, P=0.001). ALI/ARDS was characterized, regardless of definition, by radiographic densities, low oxygenation ratios, high inspiratory O(2) and airway pressure requirements. Depending on definitions, ALI and ARDS accounted for about 12-33% and 7-9% of ICU admissions per year, respectively, constituting 21-58% (ALI) and 13-16% (ARDS) of all mechanically ventilated patients. The annual incidences of ALI and ARDS are 29.3 (95%CI 18.4-40.1) and 24.0 (95%CI 14.2-33.8) by NAECC, respectively, and are, respectively, 83.6 (95%CI 65.3-101.9) and 20.9 (95%CI 11.7-30.1) by LIS per 100,000. Risk factors for ALI/ARDS were aspiration, pneumonia, sepsis and chronic alcohol abuse (the latter only by NAECC)., Conclusion: The effect of definitions of ALI/ARDS on mechanical ventilation in the Netherlands is small. Nevertheless, the incidence of ALI/ARDS may be higher than in other European countries but lower than in the USA, and the incidence of ALI by LIS may overestimate compared to that by NAECC. Aspiration, pneumonia, sepsis and chronic alcohol abuse are major risk factors, largely independent of definitions.

Objective: To describe the pattern of defecation in critically ill ventilated patients and the influence of selective decontamination (SDD) and other medication., Design: Descriptive cohort study., Setting: Mixed surgical-medical ICU in a university Hospital., Patients: Ventilated patients with a length of stay >or=7 days taking part in a study on SDD., Measurements: Daily registration of defecation, SOFA (sepsis-related organ failure assessment score) score, administration of dopamine, noradrenaline, morphine and other medications., Results: The first defecation occurred after a mean of 6.2 days. Patients with defecation within 6[Symbol: see text]days had lower mean SOFA scores, received more cisapride and lactulose and less dopamine, noradrenaline and morphine, and had a shorter duration of mechanical ventilation and ICU stay. On 57% of the days, no stools were produced; on 31% diarrhea, and on 12%, normal stools. Patients receiving SDD had more days with normal stools and less with diarrhea. Diarrhea was preceded by the administration of lactulose in the majority of patients., Conclusion: Time to first defecation correlated with severity of illness, vasoactive medication, administration of morphine, cisapride and lactulose, duration of mechanical ventilation and length of stay. Diarrhea seemed at least partially iatrogenic.

Objectives: To assess outcome of assisted ventilation in cystic fibrosis (CF) patients with acute respiratory failure (ARF), to identify risk factors associated with poor outcome and to compare long-term outcome of CF children who were mechanically ventilated for ARF with unventilated CF controls., Design: Retrospective cohort study., Setting: Two large CF centres in the Netherlands., Patients: CF patients who required assisted ventilation for ARF and unventilated CF controls., Interventions: None., Measurements and Results: Thirty-one CF patients required assisted ventilation for ARF between January 1990 and March 2005. All five children (under 2 years of age) and seven adults (27%) survived. In the total population, age was a statistically significant risk factor for poor outcome (p=0.02). In adult CF patients who required invasive mechanical ventilation, acute on chronic respiratory failure was associated with poor outcome. In children who required mechanical ventilation for ARF, lung function and CF related complications 5 years later were not significantly different compared with controls matched for age, gender and genotype., Conclusions: CF patients younger than 2 years old, who are ventilated because of ARF, have a good prognosis and their long-term outcome seems identical to unventilated CF controls. ARF in adult CF patients still is associated with high mortality, especially among patients with acute on chronic respiratory failure.

The incidence of nosocomial infection in neonatal intensive care units (NICUs) is high compared with other wards. However, no definitions for hospital-acquired infection are available for NICUs. The aim of this study was to measure the incidence of such infections and to identify risk factors in the NICU of the VU University Medical Center, which serves as a level III regional NICU. For this purpose, a prospective surveillance was performed in 1998-2000. We designed definitions by adjusting the current definitions of the Centers for Disease Control and Prevention (CDC) for children <1 year of age. Birth weight was stratified into four categories and other baseline risk factors were dichotomized. Analysis of risk factors was performed by Cox regression with time-dependent variables. The relationship between the Clinical Risk Index for Babies (CRIB) and nosocomial infection was investigated. Furthermore, for a random sample of cases, we determined whether bloodstream infection and pneumonia would also have been identified with the CDC definitions. Seven hundred and forty-two neonates were included in the study. One hundred and ninety-one neonates developed 264 infections. Bloodstream infection (N=138, 14.9/1000 patient-days) and pneumonia (N=69, 7.5/1000 patient-days) were the most common infections. Of bloodstream infections, 59% were caused by coagulase-negative staphylococci; in 21% of neonates, blood cultures remained negative. In 25% of pneumonias, Enterobacteriaceae were the causative micro-organisms; 26% of cultures remained negative. Compared with the Nosocomial Infections Surveillance System (NNIS) of the CDC, our device utilization ratios and device-associated nosocomial infection rates were high. The main risk factors for bloodstream infection were birth weight [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.45-2.17] and parenteral feeding with hospital-pharmacy-produced, all-in-one mixture 'Minimix' (HR 3.69, 95%CI 2.03-6.69); administration of intravenous antibiotics (HR 0.39, 95%CI 0.26-0.56) was a protective risk factor. The main risk factors for pneumonia were low birth weight (HR 1.37, 95%CI 1.01-1.85) and mechanical ventilation (HR 9.69, 95%CI 4.60-20.4); intravenous antibiotics were protective (HR 0.37, 95%CI 0.21-0.64). In a subcohort of 232 very-low-birthweight neonates, the CRIB was not predictive for infection. With the CDC criteria, only 75% (21/28) of bloodstream infections and 87.5% of pneumonias (21/24) would have been identified. In conclusion, our local nosocomial infection rates are high compared with those of NICUs participating in the NNIS. This can be partially explained by: (1) the use of our definitions for nosocomial infection, which are more suitable for this patient category; and (2) the high device utilization ratios.

Objective: To identify demographic, clinical, and laboratory variables predictive for a concurrent bacterial pulmonary infection in ventilated infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) and investigate antimicrobial drug use., Design and Setting: Retrospective, observational study in a 14-bed pediatric intensive care unit., Patients: 82 infants younger than 1 year of age with a virologically confirmed RSV LRTD during 1996-2001, of whom 65 were mechanically ventilated., Results: Microbiological data were available from 38 ventilated infants, 10 of whom had a positive blood culture (n=1) or endotracheal aspirate (n=9) obtained upon admission to the pediatric intensive care unit (PICU). Infants with a positive culture had a lower mean gestational age but were otherwise demographically comparable to those with negative culture results. Infants with a positive culture were ventilated 4 days longer. Indicators for a concurrent bacterial infection were comparable between ventilated and nonventilated infants. Antimicrobial drugs were used in 95.1% of infants (100% of ventilated infants) with a mean duration of 7.8+/-0.3 days. The moment of initiation and duration of antimicrobial drug treatment varied considerably., Conclusions: We observed in ventilated infants a low occurrence of concurrent bacterial pulmonary infection, but infants with positive cultures needed prolonged ventilatory support. Improvement in the diagnosis of a pulmonary bacterial infection is warranted to reduce the overuse of antimicrobial drugs among ventilated infants with RSV LRTD and to restrict these drugs to the proper patients.

Respiratory insufficiency due to respiratory muscle weakness is a common complication of many neuromuscular diseases. The prevalence of respiratory failure in facioscapulohumeral muscular dystrophy (FSHD) is unknown. The authors identified 10 FSHD patients on nocturnal ventilatory support at home, representing approximately 1% of the Dutch FSHD population. Severe muscle disease, wheelchair dependency, and kyphoscoliosis appeared to be risk factors for respiratory failure.