Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome

Wiedemann, Herbert; Arroliga, Alejandro C.; Komara, John J.; Denver, V. A.; Welsh, Carolyn H.; Fulkerson, W. J.; MacIntyre, Neil R.; Mallatratt, Lee; Sebastian, Mark; Sladen, Robert N.; Wilcox, C.I.; Brower, Roy G.; Thompson, David C.; Morris, Alan H.; Clemmer, Terry P.; Davis, Rebecca; Orme, James F.; Lawton, Charles B.; D'Hulst, Janice; Smith, Carolyn; Jefferson, Thomas; Gottlieb, Jonathan E.; Girod, Aimee; Matthay, Michael A.; Daniel, Brian; Kallet, Richard H; Luce, John M.; Gryzner, Michael A.; Abraham, Edward; Piedalue, Fran; Kalous, Dawn; Walberg, Christine; Lockrem, John D.; McIntyre, Robert C.; Parsons, Polly E.; Stevens, Christopher J; Silverman, Henry; Corral, Wanda; Toews, Galen B.; Arnoldi, Deborah; Bartlett, Robert H.; Dechert, Ron; Watts, Charles M.; Lanken, Paul N.; Anderson, Harry L.; Finkel, Barbara; Hanson, C. William; Hudson, Leonard D.; Lee, Claudette; Maier, Ronald V.; Steinberg, Kenneth P.; Wheeler, Arthur P.; Bernard, Gordon R.; Stone, Libby; Schoenfeld, David; Thompson, B. Taylor; Ancukiewicz, Marek; Hayden, Douglas; Molay, Francine; Ringwood, Nancy; Wenzlow, Gail; Gail, Dorothy B.; Bosken, Carol H.; Harabin, A. L.; Randall, Pamela; Waclawiw, Myron A.; Paradise, Carolyn; Dahlberg, Steve; Spragg, Roger G.; Boyett, James M.; Kelley, Jason; Secundy, Marion Gray; Leeper, Kenneth V.; Slutsky, Arthur S.; Hyera, Thomas M.; Emerson, Scott S.; Garcia, Joe G.N.; Pingleton, Susan K.; Shasby, Michael; Sibbald, William J.

doi:10.1097/00003246-200201000-00001

Cited by 198 publications

(12 citation statements)

References 25 publications

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“…The prognostic value of estimated Vd/Vt was then validated in two recent prospectively collected ALI/ARDS databases, namely Mayo Clinic [20] and ARDS-network [21-23]. Inclusion criteria were patients ventilated for three or more days.…”

Section: Methodsmentioning

confidence: 99%

Bedside quantification of dead-space fraction using routine clinical data in patients with acute lung injury: secondary analysis of two prospective trials

Siddiki

Kojičić

et al. 2010

Crit Care

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IntroductionDead-space fraction (Vd/Vt) has been shown to be a powerful predictor of mortality in acute lung injury (ALI) patients. The measurement of Vd/Vt is based on the analysis of expired CO2 which is not a part of standard practice thus limiting widespread clinical application of this method. The objective of this study was to determine prognostic value of Vd/Vt estimated from routinely collected pulmonary variables.MethodsSecondary analysis of the original data from two prospective studies of ALI patients. Estimated Vd/Vt was calculated using the rearranged alveolar gas equation: Vd/Vt=1−[(0.86×V˙CO2est)/(VE×PaCO2)] where V˙CO2est is the estimated CO2 production calculated from the Harris Benedict equation, minute ventilation (VE) is obtained from the ventilator rate and expired tidal volume and PaCO2 from arterial gas analysis. Logistic regression models were created to determine the prognostic value of estimated Vd/Vt.ResultsOne hundred and nine patients in Mayo Clinic validation cohort and 1896 patients in ARDS-net cohort demonstrated an increase in percent mortality for every 10% increase in Vd/Vt in a dose response fashion. After adjustment for non-pulmonary and pulmonary prognostic variables, both day 1 (adjusted odds ratio-OR = 1.07, 95%CI 1.03 to 1.13) and day 3 (OR = 1.12, 95% CI 1.06 to 1.18) estimated dead-space fraction predicted hospital mortality.ConclusionsElevated estimated Vd/Vt predicts mortality in ALI patients in a dose response manner. A modified alveolar gas equation may be of clinical value for a rapid bedside estimation of Vd/Vt, utilizing routinely collected clinical data.

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Section: Methodsmentioning

confidence: 99%

Bedside quantification of dead-space fraction using routine clinical data in patients with acute lung injury: secondary analysis of two prospective trials

Siddiki

Kojičić

et al. 2010

Crit Care

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“…Dellinger 1998 [168], Gerlach 2003 [169], Mehta 2001 [170], Michael 1998 [171], Park 2003 [172], Taylor 2004 [173], Troncy 1998 [174], Matthay 2011 [175], Gao 2012 [176], Perkins 2006 [177], Paine 2012 [178], Presneill 2002 [179], Abraham 1996 [180], Abraham 1999 [181], Bone 1989 [182], Holcroft 1986 [183], Rossignon 1990 [184], Slotman 1992 [185], Vincent 2001 [186], Craig 2011 [187], McAuley 2014 [188], Truwit 2014 [189], Anzueto 1996 [190], Gregory 1997 [191], Kesecioglu 2009 [192], Markart 2007 [193], Spragg 2003 [194], Spragg 2004 [195], Spragg 2011 [196], Tsangaris 2007 [197], Weg 1994 [198], Willson 2015 [199], Cornet 2014 [200], Liu 2008 [201], Bernard 1997 [202], Jepsen 1992 [203], Ortolani 2000 [204], Suter 1994 [205], ARDS Network 2000 [206], ARDS Network 2002 [207]…”

Section: Resultsmentioning

confidence: 99%

The clinical practice guideline for the management of ARDS in Japan

et al. 2017

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BackgroundThe Japanese Society of Respiratory Care Medicine and the Japanese Society of Intensive Care Medicine provide here a clinical practice guideline for the management of adult patients with ARDS in the ICU.MethodThe guideline was developed applying the GRADE system for performing robust systematic reviews with plausible recommendations. The guideline consists of 13 clinical questions mainly regarding ventilator settings and drug therapies (the last question includes 11 medications that are not approved for clinical use in Japan).ResultsThe recommendations for adult patients with ARDS include: we suggest against early tracheostomy (GRADE 2C), we suggest using NPPV for early respiratory management (GRADE 2C), we recommend the use of low tidal volumes at 6-8 mL/kg (GRADE 1B), we suggest setting the plateau pressure at 30cmH20 or less (GRADE2B), we suggest using PEEP within the range of plateau pressures less than or equal to 30cmH2O, without compromising hemodynamics (Grade 2B), and using higher PEEP levels in patients with moderate to severe ARDS (Grade 2B), we suggest using protocolized methods for liberation from mechanical ventilation (Grade 2D), we suggest prone positioning especially in patients with moderate to severe respiratory dysfunction (GRADE 2C), we suggest against the use of high frequency oscillation (GRADE 2C), we suggest the use of neuromuscular blocking agents in patients requiring mechanical ventilation under certain circumstances (GRADE 2B), we suggest fluid restriction in the management of ARDS (GRADE 2A), we do not suggest the use of neutrophil elastase inhibitors (GRADE 2D), we suggest the administration of steroids, equivalent to methylprednisolone 1-2mg/kg/ day (GRADE 2A), and we do not recommend other medications for the treatment of adult patients with ARDS (GRADE1B; inhaled/intravenous β2 stimulants, prostaglandin E1, activated protein C, ketoconazole, and lisofylline, GRADE 1C; inhaled nitric oxide, GRADE 1D; surfactant, GRADE 2B; granulocyte macrophage colony-stimulating factor, N-acetylcysteine, GRADE 2C; Statin.)ConclusionsThis article was translated from the Japanese version originally published as the ARDS clinical practice guidelines 2016 by the committee of ARDS clinical practice guideline (Tokyo, 2016, 293p, available from http://www.jsicm.org/ARDSGL/ARDSGL2016.pdf). The original article, written for Japanese healthcare providers, provides points of view that are different from those in other countries.Electronic supplementary materialThe online version of this article (doi:10.1186/s40560-017-0222-3) contains supplementary material, which is available to authorized users.

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“…Nevertheless, the significant reduction of free 2-ClFA (18:0 Cl) by KYC and ABAH, provides support for the notion that MPO activity plays an important role in fueling the formation of 2-ClFA (18:0 Cl) in sepsis. Bioactive chlorinated lipids have been implicated as potential mediators of ARDS, a devastating complication of sepsis that results in extremely high mortality (3,21,42,57). Although our understanding of the pathologic events contributing to the development of ARDS occurring in septic subjects continues to evolve, it is clear that pulmonary barrier dysfunction, secondary to neutrophil recruitment, and activation and excessive free radical production (26) are the major contributing processes.…”

Section: Discussionmentioning

confidence: 99%

Myeloperoxidase instigates proinflammatory responses in a cecal ligation and puncture rat model of sepsis

Liu

Wang

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

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Myeloperoxidase (MPO)-derived hypochlorous (HOCl) reacts with membrane plasmalogens to yield α-chlorofatty aldehydes such as 2-chlorofatty aldehyde (2-ClFALD) and its metabolite 2-chlorofatty acid (2-ClFA). Recent studies showed that 2-ClFALD and 2-ClFA serve as mediators of the inflammatory responses to sepsis by as yet unknown mechanisms. Since no scavenger for chlorinated lipids is available and based on the well-established role of the MPO/HOCl/chlorinated lipids axis in inflammatory responses, we hypothesized that treatment with MPO inhibitors (N-acetyl lysyltyrosylcysteine amide or 4-aminobenzoic acid hydrazide) would inhibit inflammation and proinflammatory mediator expression induced by cecal ligation and puncture (CLP). We employed intravital microscopy to quantify in vivo inflammatory responses in Sham and CLP rats with or without MPO inhibition. Small intestines, mesenteries, and lungs were collected to assess changes in MPO positive staining and lung injury, respectively, as well as free 2-ClFA and proinflammatory mediators levels. CLP caused neutrophil infiltration, 2-ClFA generation, acute lung injury, leukocyte-/platelet-endothelium interactions (LPECA), mast cell activation (MCA), plasminogen activator inhibitor-1 (PAI-1) production, and the expression of several cytokines, chemokines, and vascular endothelial growth factor, changes that were reduced by MPO inhibition. Pretreatment with a PAI-1 inhibitor or MC stabilizer prevented CLP-induced LECA and MCA, and abrogated exogenous 2-CLFALD-induced inflammatory responses. Thus, we provide evidence that MPO instigates these inflammatory changes in CLP and that chlorinated lipids may serve as a mechanistic link between the enzymatic activity of MPO and PAI-1- and mast cell-dependent adhesive interactions, providing a rationale for new therapeutic interventions in sepsis.

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Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome

Cited by 198 publications

References 25 publications

Bedside quantification of dead-space fraction using routine clinical data in patients with acute lung injury: secondary analysis of two prospective trials

Bedside quantification of dead-space fraction using routine clinical data in patients with acute lung injury: secondary analysis of two prospective trials

The clinical practice guideline for the management of ARDS in Japan

Myeloperoxidase instigates proinflammatory responses in a cecal ligation and puncture rat model of sepsis

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