title: Metabolic correlates of oxygen debt predict posttrauma early acute respiratory distress syndrome and the related cytokine response.
abstract: BACKGROUND
  The purpose of this study was to quantify the relationship between negative base excess (base deficit) and lactate as correlates of oxygen debt and the probability of the early acute respiratory distress syndrome (ARDS) response and with regard to the mediator and metabolic response characteristic of this disease.
  
  
  METHODS
  Eighty patients with multiple trauma were studied (514 samples) during their intensive care unit courses (Injury Severity Score 27.6+/-8.8, 36% deaths). Simultaneous samples of arterial base excess and lactate as correlates of oxygen debt, and enzyme-linked immunosorbent assay-measured mixed venous cytokines were obtained daily. At each sample period, the patient was categorized as having ARDS or non-ARDS.
  
  
  RESULTS
  Twenty-nine patients (36%; 19 deaths) developed ARDS over the period studied: 17 in postinjury days 1 to 4 (EARLY ARDS) and 12 in postinjury days 5 or later (LATE ARDS). Patients subsequently developing ARDS had evidence of ischemic acidosis on or within the first 24 hours after hospital admission (lower base excess -7.1 mmol/L and higher lactate 5.2 mmol/L in ARDS versus base excess -3.8 mmol/L and lactate 3.6 mmol/L in non-ARDS; p < 0.05). Patients with EARLY ARDS showed even lower (p < 0.05) initial 24 hour mean base excess and higher lactate (base excess -9.1 mmol/L and lactate 6.4 mmol/L) compared with LATE ARDS (base excess -4.3 mmol/L and lactate 3.3 mmol/L). In EARLY ARDS, this degree of ischemic acidosis was followed by a greater mean IL-6 response in the postinjury days 1 to 4 (323 pg/mL) compared with the LATE ARDS response (141 pg/mL) (p < 0.05) or compared with the non-ARDS IL-6 response (67 pg/mL; p < 0.001). In addition, in EARLY ARDS, mean IL-8 levels in postinjury days 1 to 4 (264 pg/mL) were higher than in LATE ARDS (168 pg/mL) (p < 0.05) and the mean IL-1 response in postinjury days 1 to 4 of EARLY ARDS (65 pg/mL) was greater than non-ARDS (32 pg/mL) (p < 0.05). Derivation of probability curves suggests a critical threshold of base excess -6.6 mmol/L or greater for an increased risk of EARLY ARDS.
  
  
  CONCLUSIONS
  These data suggest that the maximum posttrauma oxygen debt (quantified by the ischemia correlates of negative base excess and lactate) is a critical primary determinant of the later fulminant autoinflammatory EARLY ARDS response mediated by the host's endogenous cytokine mediators.
authors.affiliation: Department of Surgery and Anatomy, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark 07103, USA.
authors.forename: D
authors.initials: D
authors.lastname: Rixen
authors.forename: J H
authors.initials: JH
authors.lastname: Siegel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016638:Critical Illness; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015601:Injury Severity Score; D007378:Interleukins / Q000097:blood; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D010101:Oxygen Consumption; D011237:Predictive Value of Tests; D012128:Respiratory Distress Syndrome / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha
chemical_list: D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid