title: Effects of methylprednisolone infusion on markers of inflammation, coagulation, and angiogenesis in early acute respiratory distress syndrome.
abstract: OBJECTIVE
  Evaluate the effects of methylprednisolone on markers of inflammation, coagulation, and angiogenesis during early acute respiratory distress syndrome.
  
  
  METHODS
  Retrospective analysis.
  
  
  METHODS
  Four intensive care units.
  
  
  METHODS
  Seventy-nine of 91 patients with available samples enrolled in a randomized, blinded controlled trial.
  
  
  METHODS
  Early methylprednisolone infusion (n = 55) compared with placebo (n = 24).
  
  
  RESULTS
  Interleukin-6, tumor necrosis factor α, vascular endothelial growth factor, protein C, procalcitonin, and proadrenomedullin were measured in archived plasma. Changes from baseline to day 3 and day 7 were compared between groups and in subgroups based on the precipitating cause of acute respiratory distress syndrome. Methylprednisolone therapy was associated with greater improvement in Lung Injury Score (p = .003), shorter duration of mechanical ventilation (p = .005), and lower intensive care unit mortality (p = .05) than control subjects. On days 3 and 7, methylprednisolone decreased interleukin-6 and increased protein C levels (all p < .0001) compared with control subjects. Proadrenomedullin levels were lower by day 3 with methylprednisolone treatment (p = .004). Methylprednisolone decreased interleukin-6 by days 3 and 7 in patients with pulmonary causes of acute respiratory distress syndrome but only at day 3 in those with extrapulmonary causes of acute respiratory distress syndrome. Protein C levels were increased with methylprednisolone on days 3 and 7 in patients with infectious and/or pulmonary causes of acute respiratory distress syndrome (all p < .0001) but not in patients with noninfectious or extrapulmonary causes of acute respiratory distress syndrome. Proadrenomedullin levels were decreased with methylprednisolone on day 3 in patients with infectious or extrapulmonary causes of acute respiratory distress syndrome (both p ≤ .008) but not in noninfectious or pulmonary acute respiratory distress syndrome. Tumor necrosis factor, vascular endothelial growth factor, and procalcitonin were elevated but not differentially affected by methylprednisolone therapy.
  
  
  CONCLUSIONS
  In early acute respiratory distress syndrome, administration of methylprednisolone was associated with improvement in important biomarkers of inflammation and coagulation and clinical outcomes. Biomarker changes varied with the precipitating cause of acute respiratory distress syndrome, suggesting that the underlying mechanisms and response to anti-inflammatory therapy may vary with the cause of acute respiratory distress syndrome.
authors: Pulmonary Section, Veterans Affairs Medical Center, Washington, DC, USA. nitin.seam@va.gov
authors: Nitin
authors: N
authors: Seam
authors: G Umberto
authors: GU
authors: Meduri
authors: Honghui
authors: H
authors: Wang
authors: Eric S
authors: ES
authors: Nylen
authors: Junfeng
authors: J
authors: Sun
authors: Marcus J
authors: MJ
authors: Schultz
authors: Margaret
authors: M
authors: Tropea
authors: Anthony F
authors: AF
authors: Suffredini
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D003422:Critical Care / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D017052:Hospital Mortality; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism*; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012016:Reference Values; D012128:Respiratory Distress Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D008775:Methylprednisolone