Document Detail

Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial.
MedLine Citation:
PMID:  10404912     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Studies have shown that an inflammatory response may be elicited by mechanical ventilation used for recruitment or derecruitment of collapsed lung units or to overdistend alveolar regions, and that a lung-protective strategy may reduce this response.
OBJECTIVE: To test the hypothesis that mechanical ventilation induces a pulmonary and systemic cytokine response that can be minimized by limiting recruitment or derecruitment and overdistention.
DESIGN AND SETTING: Randomized controlled trial in the intensive care units of 2 European hospitals from November 1995 to February 1998, with a 28-day follow-up.
PATIENTS: Forty-four patients (mean [SD] age, 50 [18] years) with acute respiratory distress syndrome were enrolled, 7 of whom were withdrawn due to adverse events.
INTERVENTIONS: After admission, volume-pressure curves were measured and bronchoalveolar lavage and blood samples were obtained. Patients were randomized to either the control group (n = 19): tidal volume to obtain normal values of arterial carbon dioxide tension (35-40 mm Hg) and positive end-expiratory pressure (PEEP) producing the greatest improvement in arterial oxygen saturation without worsening hemodynamics; or the lung-protective strategy group (n = 18): tidal volume and PEEP based on the volume-pressure curve. Measurements were repeated 24 to 30 and 36 to 40 hours after randomization.
MAIN OUTCOME MEASURES: Pulmonary and systemic concentrations of inflammatory mediators approximately 36 hours after randomization.
RESULTS: Physiological characteristics and cytokine concentrations were similar in both groups at randomization. There were significant differences (mean [SD]) between the control and lung-protective strategy groups in tidal volume (11.1 [1.3] vs 7.6 [1.1] mL/kg), end-inspiratory plateau pressures (31.0 [4.5] vs 24.6 [2.4] cm H2O), and PEEP (6.5 [1.7] vs 14.8 [2.7] cm H2O) (P<.001). Patients in the control group had an increase in bronchoalveolar lavage concentrations of interleukin (IL) 1beta, IL-6, and IL-1 receptor agonist and in both bronchoalveolar lavage and plasma concentrations of tumor necrosis factor (TNF) alpha, IL-6, and TNF-alpha, receptors over 36 hours (P<.05 for all). Patients in the lung-protective strategy group had a reduction in bronchoalveolar lavage concentrations of polymorphonuclear cells, TNF-alpha, IL-1beta, soluble TNF-alpha receptor 55, and IL-8, and in plasma and bronchoalveolar lavage concentrations of IL-6, soluble TNF-alpha receptor 75, and IL-1 receptor antagonist (P<.05). The concentration of the inflammatory mediators 36 hours after randomization was significantly lower in the lung-protective strategy group than in the control group (P<.05).
CONCLUSIONS: Mechanical ventilation can induce a cytokine response that may be attenuated by a strategy to minimize overdistention and recruitment/derecruitment of the lung. Whether these physiological improvements are associated with improvements in clinical end points should be determined in future studies.
V M Ranieri; P M Suter; C Tortorella; R De Tullio; J M Dayer; A Brienza; F Bruno; A S Slutsky
Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA     Volume:  282     ISSN:  0098-7484     ISO Abbreviation:  JAMA     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-07-20     Completed Date:  1999-07-20     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  54-61     Citation Subset:  AIM; IM    
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MeSH Terms
Cytokines / metabolism*
Inflammation Mediators / metabolism*
Middle Aged
Positive-Pressure Respiration
Respiration, Artificial* / adverse effects
Respiratory Distress Syndrome, Adult / immunology*,  therapy*
Respiratory Function Tests
Reg. No./Substance:
0/Cytokines; 0/Inflammation Mediators
Comment In:
JAMA. 1999 Jul 7;282(1):77-8   [PMID:  10404916 ]
JAMA. 2003 Jul 23;290(4):461; author reply 461-2   [PMID:  12876085 ]
JAMA. 2000 Feb 23;283(8):1003-4   [PMID:  10697056 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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