17 results on '"Glas GJ"'
Search Results
2. Nebulized Heparin in Burn Patients with Inhalation Trauma-Safety and Feasibility
- Author
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Glas, GJ, Horn, J, Binnekade, JM, Hollmann, MW, Muller, J, Cleffken, B, Colpaert, K, Dixon, B, Juffermans, NP, Knape, P, Levi, MM, Loef, BG, Mackie, DP, Malbrain, MLNG, Preckel, B, Reidinga, AC, van der Sluijs, KF, Schultz, MJ, Glas, GJ, Horn, J, Binnekade, JM, Hollmann, MW, Muller, J, Cleffken, B, Colpaert, K, Dixon, B, Juffermans, NP, Knape, P, Levi, MM, Loef, BG, Mackie, DP, Malbrain, MLNG, Preckel, B, Reidinga, AC, van der Sluijs, KF, and Schultz, MJ
- Abstract
BACKGROUND: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. METHODS: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. RESULTS: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. CONCLUSION: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients.
- Published
- 2020
3. Nebulized Cl-esterase inhibitor treatment does not attenuate pulmonary complement activation in a rat model of severe Streptococcus pneumoniae pneumonia
- Author
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De Beer, FM, Glas, GJ, Beurskens, CJ, Horn, J, Schultz, MJ, and Lagrand, WK
- Published
- 2014
- Full Text
- View/download PDF
4. Studienprotokoll und -design einer prospektiven multizentrischen Observationsstudie zur Beatmungsbehandlung bei brandverletzten Patienten (Local Assessment of MaNAgement in BuRn Patients - LAMiNAR)
- Author
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Horter, J, Rennekampff, HO, Glas, GJ, Hernekamp, JF, Kremer, T, Hirche, C, Kneser, U, Horter, J, Rennekampff, HO, Glas, GJ, Hernekamp, JF, Kremer, T, Hirche, C, and Kneser, U
- Published
- 2016
5. Nebulized heparin for patients under mechanical ventilation: an individual patient data meta-analysis
- Author
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Glas, GJ, Neto, AS, Horn, J, Cochran, A, Dixon, B, Elamin, EM, Faraklas, I, Dissanaike, S, Miller, AC, Schultz, MJ, Glas, GJ, Neto, AS, Horn, J, Cochran, A, Dixon, B, Elamin, EM, Faraklas, I, Dissanaike, S, Miller, AC, and Schultz, MJ
- Abstract
Pulmonary coagulopathy is a characteristic feature of lung injury including ventilator-induced lung injury. The aim of this individual patient data meta-analysis is to assess the effects of nebulized anticoagulants on outcome of ventilated intensive care unit (ICU) patients. A systematic search of PubMed (1966-2014), Scopus, EMBASE, and Web of Science was conducted to identify relevant publications. Studies evaluating nebulization of anticoagulants in ventilated patients were screened for inclusion, and corresponding authors of included studies were contacted to provide individual patient data. The primary endpoint was the number of ventilator-free days and alive at day 28. Secondary endpoints included hospital mortality, ICU- and hospital-free days at day 28, and lung injury scores at day seven. We constructed a propensity score-matched cohort for comparisons between patients treated with nebulized anticoagulants and controls. Data from five studies (one randomized controlled trial, one open label study, and three studies using historical controls) were included in the meta-analysis, compassing 286 patients. In all studies unfractionated heparin was used as anticoagulant. The number of ventilator-free days and alive at day 28 was higher in patients treated with nebulized heparin compared to patients in the control group (14 [IQR 0-23] vs. 6 [IQR 0-22]), though the difference did not reach statistical significance (P = 0.459). The number of ICU-free days and alive at day 28 was significantly higher, and the lung injury scores at day seven were significantly lower in patients treated with nebulized heparin. In the propensity score-matched analysis, there were no differences in any of the endpoints. This individual patient data meta-analysis provides no convincing evidence for benefit of heparin nebulization in intubated and ventilated ICU patients. The small patient numbers and methodological shortcomings of included studies underline the need for high-quality well-p
- Published
- 2016
6. HEPBURN - investigating the efficacy and safety of nebulized heparin versus placebo in burn patients with inhalation trauma: study protocol for a multi-center randomized controlled trial
- Author
-
Glas, GJ, Muller, J, Binnekade, JM, Cleffken, B, Colpaert, K, Dixon, B, Juffermans, NP, Knape, P, Levi, MM, Loef, BG, Mackie, DP, Malbrain, M, Schultz, MJ, van der Sluijs, KF, Glas, GJ, Muller, J, Binnekade, JM, Cleffken, B, Colpaert, K, Dixon, B, Juffermans, NP, Knape, P, Levi, MM, Loef, BG, Mackie, DP, Malbrain, M, Schultz, MJ, and van der Sluijs, KF
- Abstract
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.
- Published
- 2014
7. Ventilation practices in burn patients-an international prospective observational cohort study.
- Author
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Schultz MJ, Horn J, Hollmann MW, Preckel B, Glas GJ, Colpaert K, Malbrain M, Neto AS, Asehnoune K, de Abreu MG, Martin-Loeches I, Pelosi P, Sjöberg F, Binnekade JM, Cleffken B, Juffermans NP, Knape P, Loef BG, Mackie DP, Enkhbaatar P, Depetris N, Perner A, Herrero E, Cachafeiro L, Jeschke M, Lipman J, Legrand M, Horter J, Lavrentieva A, Glas G, Kazemi A, Guttormsen AB, Huss F, Kol M, Wong H, Starr T, De Crop L, de Oliveira Filho W, Manoel Silva Junior J, Grion CMC, Jeschke MG, Burnett M, Mondrup F, Ravat F, Fontaine M, Asehoune K, Floch RL, Jeanne M, Bacus M, Chaussard M, Lehnhardt M, Mikhail BD, Gille J, Sharkey A, Trommel N, Reidinga AC, Vieleers N, Tilsley A, Onarheim H, Bouza MT, Agrifoglio A, Fredén F, Palmieri T, and Painting LE
- Abstract
Background: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28)., Methods: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume ( V
T ) was defined as VT ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between VT and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma., Results: A total of 160 patients from 28 ICUs in 16 countries were included. Low VT was used in 74% of patients, median VT size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma ( p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high VT ( p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2 O; 80% of patients had maximum airway pressures <30 cmH2 O., Conclusion: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low VT was not associated with a reduction in VFD-28., Trial Registration: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014., (© The Author(s) 2021. Published by Oxford University Press.)- Published
- 2021
- Full Text
- View/download PDF
8. Transesophageal Versus Surface Electromyography of the Diaphragm in Ventilated Subjects.
- Author
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Lokin JL, Dulger S, Glas GJ, and Horn J
- Subjects
- Electromyography, Humans, Pilot Projects, Respiration, Artificial, Diaphragm, Interactive Ventilatory Support
- Abstract
Background: Detection of diaphragmatic muscle activity during invasive ventilation may provide valuable information about patient-ventilator interactions. Transesophageal electromyography of the diaphragm ([Formula: see text]) is used in neurally adjusted ventilatory assist. This technique is invasive and can only be applied with one specific ventilator. Surface electromyography of the diaphragm ([Formula: see text]) is noninvasive and can potentially be applied with all types of ventilators. The primary objective of our study was to compare the ability of diaphragm activity detection between [Formula: see text] and [Formula: see text]., Methods: In this single-center pilot study, [Formula: see text] and [Formula: see text] recordings were obtained simultaneously for 15 min in adult subjects in the ICU who were invasively ventilated. The number of breathing efforts detected by [Formula: see text] and [Formula: see text] were determined. The percentage of detected breathing efforts by [Formula: see text] compared with [Formula: see text] was calculated. Temporal and signal strength relations on optimum recordings of 10 breaths per subject were also compared. The Spearman correlation coefficient was used to determine the correlation between [Formula: see text] and [Formula: see text]. Agreement was calculated by using Bland-Altman statistics., Results: Fifteen subjects were included. The [Formula: see text] detected 3,675 breathing efforts, of which 3,162 (86.0%) were also detected by [Formula: see text]. A statistically significant temporal correlation (r = 0.95, P < .001) was found between [Formula: see text] and [Formula: see text] in stable recordings. The mean difference in the time intervals between both techniques was 10.1 ms, with limits of agreement from -410 to 430 ms., Conclusions: Analysis of our results showed that [Formula: see text] was not reliable for breathing effort detection in subjects who were invasively ventilated compared with [Formula: see text]. In stable recordings, however, [Formula: see text] and [Formula: see text] had excellent temporal correlation and good agreement. With optimization of signal stability, [Formula: see text] may become a useful monitoring tool., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2020 by Daedalus Enterprises.)
- Published
- 2020
- Full Text
- View/download PDF
9. Changes in ventilator settings and ventilation-induced lung injury in burn patients-A systematic review.
- Author
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Glas GJ, Horn J, van der Hoeven SM, Hollmann MW, Cleffken B, Colpaert K, Juffermans NP, Knape P, Loef BG, Mackie DP, Malbrain M, Muller J, Reidinga AC, Preckel B, and Schultz MJ
- Subjects
- Barotrauma, Humans, Positive-Pressure Respiration methods, Respiration, Artificial methods, Smoke Inhalation Injury therapy, Tidal Volume, Ventilator-Induced Lung Injury epidemiology, Burns therapy, Respiration, Artificial trends, Ventilator-Induced Lung Injury prevention & control
- Abstract
Objective: Ventilation strategies aiming at prevention of ventilator-induced lung injury (VILI), including low tidal volumes (V
T ) and use of positive end-expiratory pressures (PEEP) are increasingly used in critically ill patients. It is uncertain whether ventilation practices changed in a similar way in burn patients. Our objective was to describe applied ventilator settings and their relation to development of VILI in burn patients., Data Sources: Systematic search of the literature in PubMed and EMBASE using MeSH, EMTREE terms and keywords referring to burn or inhalation injury and mechanical ventilation., Study Selection: Studies reporting ventilator settings in adult or pediatric burn or inhalation injury patients receiving mechanical ventilation during the ICU stay., Data Extraction: Two authors independently screened abstracts of identified studies for eligibility and performed data extraction., Data Synthesis: The search identified 35 eligible studies. VT declined from 14 ml/kg in studies performed before to around 8 ml/kg predicted body weight in studies performed after 2006. Low-PEEP levels (<10 cmH2 O) were reported in 70% of studies, with no changes over time. Peak inspiratory pressure (PIP) values above 35 cmH2 O were frequently reported. Nevertheless, 75% of the studies conducted in the last decade used limited maximum airway pressures (≤35 cmH2 O) compared to 45% of studies conducted prior to 2006. Occurrence of barotrauma, reported in 45% of the studies, ranged from 0 to 29%, and was more frequent in patients ventilated with higher compared to lower airway pressures., Conclusion: This systematic review shows noticeable trends of ventilatory management in burn patients that mirrors those in critically ill non-burn patients. Variability in available ventilator data precluded us from drawing firm conclusions on the association between ventilator settings and the occurrence of VILI in burn patients., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
10. Nebulized Heparin in Burn Patients with Inhalation Trauma-Safety and Feasibility.
- Author
-
Glas GJ, Horn J, Binnekade JM, Hollmann MW, Muller J, Cleffken B, Colpaert K, Dixon B, Juffermans NP, Knape P, Levi MM, Loef BG, Mackie DP, Malbrain MLNG, Preckel B, Reidinga AC, van der Sluijs KF, and Schultz MJ
- Abstract
Background: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin., Methods: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility., Results: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations., Conclusion: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients., Competing Interests: The authors declare no conflict of interest.
- Published
- 2020
- Full Text
- View/download PDF
11. Age-dependent differences in pulmonary host responses in ARDS: a prospective observational cohort study.
- Author
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Schouten LR, van Kaam AH, Kohse F, Veltkamp F, Bos LD, de Beer FM, van Hooijdonk RT, Horn J, Straat M, Witteveen E, Glas GJ, Wieske L, van Vught LA, Wiewel MA, Ingelse SA, Cortjens B, van Woensel JB, Bos AP, Walther T, Schultz MJ, and Wösten-van Asperen RM
- Abstract
Background: Results from preclinical studies suggest that age-dependent differences in host defense and the pulmonary renin-angiotensin system (RAS) are responsible for observed differences in epidemiology of acute respiratory distress syndrome (ARDS) between children and adults. The present study compares biomarkers of host defense and RAS in bronchoalveolar lavage (BAL) fluid from neonates, children, adults, and older adults with ARDS., Methods: In this prospective observational study, we enrolled mechanical ventilated ARDS patients categorized into four age groups: 20 neonates (< 28 days corrected postnatal age), 29 children (28 days-18 years), 26 adults (18-65 years), and 17 older adults (> 65 years of age). All patients underwent a nondirected BAL within 72 h after intubation. Activities of the two main enzymes of RAS, angiotensin converting enzyme (ACE) and ACE2, and levels of biomarkers of inflammation, endothelial activation, and epithelial damage were determined in BAL fluid., Results: Levels of myeloperoxidase, interleukin (IL)-6, IL-10, and p-selectin were higher with increasing age, whereas intercellular adhesion molecule-1 was higher in neonates. No differences in activity of ACE and ACE2 were seen between the four age groups., Conclusions: Age-dependent differences in the levels of biomarkers in lungs of ARDS patients are present. Especially, higher levels of markers involved in the neutrophil response were found with increasing age. In contrast to preclinical studies, age is not associated with changes in the pulmonary RAS.
- Published
- 2019
- Full Text
- View/download PDF
12. Selective decontamination of the digestive tract halves the prevalence of ventilator-associated pneumonia compared to selective oral decontamination.
- Author
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Bos LD, Stips C, Schouten LR, van Vught LA, Wiewel MA, Wieske L, van Hooijdonk RT, Straat M, de Beer FM, Glas GJ, Visser CE, de Jonge E, Juffermans NP, Horn J, and Schultz MJ
- Subjects
- Administration, Oral, Anti-Bacterial Agents therapeutic use, Cohort Studies, Critical Illness therapy, Female, Humans, Intensive Care Units, Male, Pneumonia, Ventilator-Associated drug therapy, Pneumonia, Ventilator-Associated epidemiology, Prospective Studies, Decontamination methods, Gastrointestinal Tract, Oropharynx, Pneumonia, Ventilator-Associated prevention & control
- Published
- 2017
- Full Text
- View/download PDF
13. Nebulized C1-Esterase Inhibitor does not Reduce Pulmonary Complement Activation in Rats with Severe Streptococcus Pneumoniae Pneumonia.
- Author
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de Beer F, Lagrand W, Glas GJ, Beurskens CJ, van Mierlo G, Wouters D, Zeerleder S, Roelofs JJ, Juffermans NP, Horn J, and Schultz MJ
- Subjects
- Animals, Bronchoalveolar Lavage Fluid chemistry, Case-Control Studies, Complement C4 metabolism, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Interleukin-6 analysis, Lung metabolism, Lung pathology, Male, Pneumonia metabolism, Pneumonia microbiology, Rats, Rats, Sprague-Dawley, Severity of Illness Index, Tumor Necrosis Factor-alpha analysis, Complement Activation drug effects, Complement C1 Inhibitor Protein pharmacology, Pneumonia pathology, Streptococcus pneumoniae pathogenicity
- Abstract
Complement activation plays an important role in the pathogenesis of pneumonia. We hypothesized that inhibition of the complement system in the lungs by repeated treatment with nebulized plasma-derived human C1-esterase inhibitor reduces pulmonary complement activation and subsequently attenuates lung injury and lung inflammation. This was investigated in a rat model of severe Streptococcus pneumoniae pneumonia. Rats were intra-tracheally challenged with S. pneumoniae to induce pneumonia. Nebulized C1-esterase inhibitor or saline (control animals) was repeatedly administered to rats, 30 min before induction of pneumonia and every 6 h thereafter. Rats were sacrificed 20 or 40 h after inoculation with bacteria. Brochoalveolar lavage fluid and lung tissue were obtained for measuring levels of complement activation (C4b/c), lung injury and inflammation. Induction of pneumonia was associated with pulmonary complement activation (C4b/c at 20 h 1.24 % [0.56-2.59] and at 40 h 2.08 % [0.98-5.12], compared to 0.50 % [0.07-0.59] and 0.03 % [0.03-0.03] in the healthy control animals). The functional fraction of C1-INH was detectable in BALF, but no effect was found on pulmonary complement activation (C4b/c at 20 h 0.73 % [0.16-1.93] and at 40 h 2.38 % [0.54-4.19]). Twenty hours after inoculation, nebulized C1-esterase inhibitor treatment reduced total histology score, but this effect was no longer seen at 40 h. Nebulized C1-esterase inhibitor did not affect other markers of lung injury or lung inflammation. In this negative experimental animal study, severe S. pneumoniae pneumonia in rats is associated with pulmonary complement activation. Repeated treatment with nebulized C1-esterase inhibitor, although successfully delivered to the lungs, does not affect pulmonary complement activation, lung inflammation or lung injury., Competing Interests: The authors declare that they have no competing interests.
- Published
- 2016
- Full Text
- View/download PDF
14. Nebulized heparin for patients under mechanical ventilation: an individual patient data meta-analysis.
- Author
-
Glas GJ, Serpa Neto A, Horn J, Cochran A, Dixon B, Elamin EM, Faraklas I, Dissanaike S, Miller AC, and Schultz MJ
- Abstract
Pulmonary coagulopathy is a characteristic feature of lung injury including ventilator-induced lung injury. The aim of this individual patient data meta-analysis is to assess the effects of nebulized anticoagulants on outcome of ventilated intensive care unit (ICU) patients. A systematic search of PubMed (1966-2014), Scopus, EMBASE, and Web of Science was conducted to identify relevant publications. Studies evaluating nebulization of anticoagulants in ventilated patients were screened for inclusion, and corresponding authors of included studies were contacted to provide individual patient data. The primary endpoint was the number of ventilator-free days and alive at day 28. Secondary endpoints included hospital mortality, ICU- and hospital-free days at day 28, and lung injury scores at day seven. We constructed a propensity score-matched cohort for comparisons between patients treated with nebulized anticoagulants and controls. Data from five studies (one randomized controlled trial, one open label study, and three studies using historical controls) were included in the meta-analysis, compassing 286 patients. In all studies unfractionated heparin was used as anticoagulant. The number of ventilator-free days and alive at day 28 was higher in patients treated with nebulized heparin compared to patients in the control group (14 [IQR 0-23] vs. 6 [IQR 0-22]), though the difference did not reach statistical significance (P = 0.459). The number of ICU-free days and alive at day 28 was significantly higher, and the lung injury scores at day seven were significantly lower in patients treated with nebulized heparin. In the propensity score-matched analysis, there were no differences in any of the endpoints. This individual patient data meta-analysis provides no convincing evidence for benefit of heparin nebulization in intubated and ventilated ICU patients. The small patient numbers and methodological shortcomings of included studies underline the need for high-quality well-powered randomized controlled trials.
- Published
- 2016
- Full Text
- View/download PDF
15. Coagulopathy and its management in patients with severe burns.
- Author
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Glas GJ, Levi M, and Schultz MJ
- Subjects
- Anticoagulants chemistry, Blood Coagulation, Blood Coagulation Disorders complications, Burns complications, Burns immunology, Coagulants chemistry, Fibrinolysis, Hemodilution, Hemostasis, Humans, Recombinant Proteins chemistry, Smoke Inhalation Injury, Blood Coagulation Disorders immunology, Blood Coagulation Disorders therapy, Burns therapy
- Abstract
Severe burn injury is associated with systemic coagulopathy. The changes in coagulation described in patients with severe burns resemble those found patients with sepsis or major trauma. Coagulopathy in patients with severe burns is characterized by procoagulant changes, and impaired fibrinolytic and natural anticoagulation systems. Both the timing of onset and the severity of hemostatic derangements are related to the severity of the burn. The exact pathophysiology and time course of coagulopathy are uncertain, but, at least in part, result from hemodilution and hypothermia. As the occurrence of coagulopathy in patients with severe burns is associated with increased comorbidity and mortality, coagulopathy could be seen as a potential therapeutic target. Clear guidelines for the treatment of coagulopathy in patients with severe burns are lacking, but supportive measures and targeted treatments have been proposed. Supportive measures are aimed at avoiding preventable triggers such as tissue hypoperfusion caused by shock, or hemodilution and hypothermia following the usually aggressive fluid resuscitation in these patients. Suggested targeted treatments that could benefit patients with severe burns include systemic treatment with anticoagulants, but sufficient randomized controlled trial evidence is lacking., (© 2016 International Society on Thrombosis and Haemostasis.)
- Published
- 2016
- Full Text
- View/download PDF
16. HEPBURN - investigating the efficacy and safety of nebulized heparin versus placebo in burn patients with inhalation trauma: study protocol for a multi-center randomized controlled trial.
- Author
-
Glas GJ, Muller J, Binnekade JM, Cleffken B, Colpaert K, Dixon B, Juffermans NP, Knape P, Levi MM, Loef BG, Mackie DP, Malbrain M, Schultz MJ, and van der Sluijs KF
- Subjects
- Administration, Inhalation, Anticoagulants adverse effects, Belgium, Clinical Protocols, Double-Blind Method, Heparin adverse effects, Humans, Intubation, Intratracheal, Lung pathology, Lung physiopathology, Netherlands, Recovery of Function, Respiration, Smoke Inhalation Injury diagnosis, Smoke Inhalation Injury physiopathology, Time Factors, Treatment Outcome, Ventilator Weaning, Anticoagulants administration & dosage, Heparin administration & dosage, Lung drug effects, Nebulizers and Vaporizers, Research Design, Respiration, Artificial, Smoke Inhalation Injury therapy
- Abstract
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.
- Published
- 2014
- Full Text
- View/download PDF
17. Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome.
- Author
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Glas GJ, Van Der Sluijs KF, Schultz MJ, Hofstra JJ, Van Der Poll T, and Levi M
- Subjects
- Animals, Anticoagulants therapeutic use, Fibrinolytic Agents therapeutic use, Humans, Inflammation Mediators metabolism, Pneumonia blood, Pneumonia immunology, Pulmonary Alveoli drug effects, Pulmonary Alveoli immunology, Respiratory Distress Syndrome drug therapy, Respiratory Distress Syndrome immunology, Ventilator-Induced Lung Injury drug therapy, Ventilator-Induced Lung Injury immunology, Fibrin metabolism, Hemostasis drug effects, Pulmonary Alveoli metabolism, Respiratory Distress Syndrome blood, Ventilator-Induced Lung Injury blood
- Abstract
Enhanced intrapulmonary fibrin deposition as a result of abnormal broncho-alveolar fibrin turnover is a hallmark of acute respiratory distress syndrome (ARDS), pneumonia and ventilator-induced lung injury (VILI), and is important to the pathogenesis of these conditions. The mechanisms that contribute to alveolar coagulopathy are localized tissue factor-mediated thrombin generation, impaired activity of natural coagulation inhibitors and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. There is an intense and bidirectional interaction between coagulation and inflammatory pathways in the bronchoalveolar compartment. Systemic or local administration of anticoagulant agents (including activated protein C, antithrombin and heparin) and profibrinolytic agents (such as plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti-inflammatory effects of these therapies in ARDS and pneumonia., (© 2012 International Society on Thrombosis and Haemostasis.)
- Published
- 2013
- Full Text
- View/download PDF
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