Topical ibuprofen decreases thromboxane release from the endotoxin-stimulated burn wound

A full-thickness burn wound in adult sheep releases prostanoids when they are injected locally with E. coli endotoxin, 2 micrograms/kg, resulting in an increase in pulmonary artery pressure (Ppa) from 20 +/- 3 to 34 +/- 5 mm Hg, and a decrease in mean arterial oxygen tension (PaO2) from 88 +/- 6 to 70 +/- 5 torr; this corresponds to an increase in venous plasma TxB2 content from a baseline of 220 +/- 79 pg/ml to 440 +/- 90 pg/ml. Burn prostanoid production, measured in lymph, increased ten- to fifteen-fold for both thromboxane A2, measured as TxB2, and prostacyclin, 6-keto-PGF1 alpha. The intravenous administration of ibuprofen, 12.5 mg/kg, eliminated both the increase in Ppa and decrease in PaO2 as well as the increase in burn lymph prostanoids. However, plasma prostanoids were also decreased below baseline, a potentially deleterious effect. A topical ibuprofen cream, 5% ibuprofen in a water-soluble ester, was applied to the burn hide every 6 hrs x 4 after which endotoxin was again injected below the hide. The pulmonary dysfunction was prevented as was the increase in plasma TxB2 with the value remaining at baseline. Burn lymph levels were only increased three- to five fold. Ibuprofen levels in burn lymph were maintained at 1-2 mcg/ml. The addition of the cream to the burn, however, did increase the wound bacterial content to 10(5)-10(7) bacteria/gram of tissue compared to 10(2)-10(3) for the dry, untreated burn, probably due to softening of the burn. Topically applied ibuprofen, therefore, can decrease burn wound prostanoid production from local endotoxin, preventing lung dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)