Friso M de Beer1,2,3, Luuk Wieske4,5,6, Gerard van Mierlo7, Diana Wouters7, Sacha Zeerleder8,7, Lieuwe D Bos4,5, Nicole P Juffermans4,5, Marcus J Schultz4,5,9,10, Tom van der Poll11,12, Wim K Lagrand4,5, Janneke Horn4,5. 1. Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. frisodebeer@hotmail.com. 2. Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. frisodebeer@hotmail.com. 3. Department of Anesthesiology, Amsterdam UMC, University of Amsterdam, Mail stop H1-118,Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. frisodebeer@hotmail.com. 4. Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 5. Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 6. Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 7. Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands. 8. Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 9. Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand. 10. Nuffield Department of Medicine, University of Oxford, Oxford, UK. 11. Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 12. Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Abstract
BACKGROUND: Mechanical ventilation can induce or even worsen lung injury, at least in part via overdistension caused by too large volumes or too high pressures. The complement system has been suggested to play a causative role in ventilator-induced lung injury. AIMS AND METHODS: This was a single-center prospective study investigating associations between pulmonary levels of complement activation products and two ventilator settings, tidal volume (VT) and driving pressure (ΔP), in critically ill patients under invasive ventilation. A miniature bronchoalveolar lavage (BAL) was performed for determination of pulmonary levels of C5a, C3b/c, and C4b/c. The primary endpoint was the correlation between BAL fluid (BALF) levels of C5a and VT and ΔP. Levels of complement activation products were also compared between patients with and without ARDS or with and without pneumonia. RESULTS: Seventy-two patients were included. Median time from start of invasive ventilation till BAL was 27 [19 to 34] hours. Median VT and ΔP before BAL were 6.7 [IQR 6.1 to 7.6] ml/kg predicted bodyweight (PBW) and 15 [IQR 11 to 18] cm H2O, respectively. BALF levels of C5a, C3b/c and C4b/c were neither different between patients with or without ARDS, nor between patients with or without pneumonia. BALF levels of C5a, and also C3b/c and C4b/c, did not correlate with VT and ΔP. Median BALF levels of C5a, C3b/c, and C4b/c, and the effects of VT and ΔP on those levels, were not different between patients with or without ARDS, and in patients with or without pneumonia. CONCLUSION: In this cohort of critically ill patients under invasive ventilation, pulmonary levels of complement activation products were independent of the size of VT and the level of ΔP. The associations were not different for patients with ARDS or with pneumonia. Pulmonary complement activation does not seem to play a major role in VILI, and not even in lung injury per se, in critically ill patients under invasive ventilation.
BACKGROUND: Mechanical ventilation can induce or even worsen lung injury, at least in part via overdistension caused by too large volumes or too high pressures. The complement system has been suggested to play a causative role in ventilator-induced lung injury. AIMS AND METHODS: This was a single-center prospective study investigating associations between pulmonary levels of complement activation products and two ventilator settings, tidal volume (VT) and driving pressure (ΔP), in critically illpatients under invasive ventilation. A miniature bronchoalveolar lavage (BAL) was performed for determination of pulmonary levels of C5a, C3b/c, and C4b/c. The primary endpoint was the correlation between BAL fluid (BALF) levels of C5a and VT and ΔP. Levels of complement activation products were also compared between patients with and without ARDS or with and without pneumonia. RESULTS: Seventy-two patients were included. Median time from start of invasive ventilation till BAL was 27 [19 to 34] hours. Median VT and ΔP before BAL were 6.7 [IQR 6.1 to 7.6] ml/kg predicted bodyweight (PBW) and 15 [IQR 11 to 18] cm H2O, respectively. BALF levels of C5a, C3b/c and C4b/c were neither different between patients with or without ARDS, nor between patients with or without pneumonia. BALF levels of C5a, and also C3b/c and C4b/c, did not correlate with VT and ΔP. Median BALF levels of C5a, C3b/c, and C4b/c, and the effects of VT and ΔP on those levels, were not different between patients with or without ARDS, and in patients with or without pneumonia. CONCLUSION: In this cohort of critically illpatients under invasive ventilation, pulmonary levels of complement activation products were independent of the size of VT and the level of ΔP. The associations were not different for patients with ARDS or with pneumonia. Pulmonary complement activation does not seem to play a major role in VILI, and not even in lung injury per se, in critically illpatients under invasive ventilation.
Authors: B Petersen; T Busch; J Gaertner; J J Haitsma; S Krabbendam; M Ebsen; B Lachmann; U X Kaisers Journal: J Physiol Pharmacol Date: 2016-12 Impact factor: 3.011
Authors: F M de Beer; H Aslami; J Hoeksma; G van Mierlo; D Wouters; S Zeerleder; J J T H Roelofs; N P Juffermans; M J Schultz; W K Lagrand Journal: Cell Biochem Biophys Date: 2014-11 Impact factor: 2.194
Authors: V Marco Ranieri; Gordon D Rubenfeld; B Taylor Thompson; Niall D Ferguson; Ellen Caldwell; Eddy Fan; Luigi Camporota; Arthur S Slutsky Journal: JAMA Date: 2012-06-20 Impact factor: 56.272