Prostacyclin and thromboxane A2 formation is increased in human sepsis syndrome.
Effects of cyclooxygenase inhibition.
Author(s): Bernard GR(1), Reines HD, Halushka PV, Higgins SB, Metz CA, Swindell BB, Wright
PE, Watts FL, Vrbanac JJ.
Affiliation(s): Author information:
(1)Department of Medicine, Vanderbilt School of Medicine, Nashville, Tennessee
37232.
Publication date & source: 1991, Am Rev Respir Dis. , 144(5):1095-101
Arachidonic acid metabolites, especially thromboxane-A2 and prostacyclin, have
been shown to be increased in experimental models of sepsis and the adult
respiratory distress syndrome (ARDS) and play a major pathophysiologic role. This
study was designed to determine if these metabolites are increased in human
sepsis syndrome and if inhibition of fatty acid cyclooxygenase affects their
formation and their pathophysiologic sequelae. We conducted a double-blind,
placebo-controlled trial of ibuprofen (800 mg given rectally every 4 h for three
doses) in 30 patients with sepsis syndrome defined by abnormal vital signs, the
appearance of serious infection, and at least one major organ failure. Urinary
concentrations of the metabolite of thromboxane-A2, 2,3-dinor-TxB2, and
prostacyclin, 2,3-dinor-6-keto-prostaglandin F2 alpha, were elevated 10 to 20
times normal and declined to four to five times normal by 12 h after entry in the
ibuprofen-treated group and remained elevated in the placebo-treated patients.
The urinary concentration of TxB2 and 6-keto-prostaglandin F1 alpha, which
reflect renal production of TxA2 and prostacyclin, respectively, were also
increased approximately 10-fold over normal and were subsequently decreased by
ibuprofen. Coincident with the reduction in metabolite levels, the
ibuprofen-treated group, but not the placebo-treated group, experienced a
significant decline in temperature, heart rate, and peak airway pressure, and a
trend towards more rapid reversal of shock (p = 0.12).(ABSTRACT TRUNCATED AT 250
WORDS)
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