Mitogen-activated protein kinases in the intensive care unit: prognostic potential.
OBJECTIVE
To evaluate the prognostic significance of the activational status of p38, specifically progression to multiple organ dysfunction syndrome (MODS), in a group of severely injured trauma patients.


BACKGROUND
To date, therapeutic manipulation of the host immunoinflammatory response has not affected the outcome of patients with MODS. A major concern is the inability to identify the patient most at risk so as to enable early intervention.


METHODS
Nineteen trauma patients underwent bronchoalveolar lavage (BAL). Cells obtained were plated, stimulated with lipopolysaccharide (LPS), and then harvested at varying time points after stimulation. p38 was evaluated by Western blot.


RESULTS
Nineteen patients were categorized into two groups according to baseline and LPS-stimulated p38 activation in cells obtained by BAL. Group 1 demonstrated a 10-fold increase in p38 activation with LPS treatment over unstimulated controls. Group 2 had high baseline levels of p38 that were unresponsive to subsequent LPS stimulation. Both groups were similar with respect to age, gender, shock (systolic blood pressure < 90), Injury Severity Score, APACHE II, lactate levels, base deficit, blood transfusions, and the cell differential of BAL fluid. However, patients in group 2 had a greater incidence of progression to MODS as defined by the Marshall MOD score, a longer duration of mechanical ventilation, a longer stay in the intensive care unit, and a longer overall hospital stay than group 1.


CONCLUSIONS
These results demonstrate the prognostic significance of p38 activation in predicting outcome in critically ill trauma patients. Furthermore, these results demonstrate that trauma populations identical by current scoring systems contain a mixture of patients with markedly different outcomes as identified by p38 activation. Measurement of p38 may enable early identification of a subgroup of patients at increased risk for MODS to permit effective therapeutic intervention.
Rosengart
Matthew R
MR
Department of Surgery, University of Washington, Seattle, USA. rosengar@u.washington.edu
Nathens
Avery B
AB
Arbabi
Saman
S
Neff
Margaret J
MJ
Garcia
Iris
I
Martin
Thomas R
TR
Maier
Ronald V
RV
D018806:APACHE; D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D015331:Cohort Studies; D003422:Critical Care / Q000379:methods; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008070:Lipopolysaccharides / Q000494:pharmacology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis*; D009102:Multiple Organ Failure / Q000175:diagnosis* / Q000401:mortality*; D009104:Multiple Trauma / Q000175:diagnosis* / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012737:Sex Factors; D016019:Survival Analysis
D015415:Biomarkers; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases