IBUPROFEN, METHYLPREDNISOLONE, AND GENTAMICIN AS CONJOINT THERAPY IN SEPTIC SHOCK

  • 1 January 1985
    • journal article
    • research article
    • Vol. 17  (1) , 59-71
Abstract
Septic shock is associated with increased metabolism of arachidonic acid to thromboxane A2 (TxA2) and prostacyclin (PGI2). The effects of ibuprofen, methylprednisolone-sodium succinate, and gentamicin alone, or in combination on survival time and, txA2 and PGI2 production in rats in a LD100 fecal peritonitis shock model were assessed. Plasma levels of TxA2 and PGI2 were measured by radioimmunoassay of their stable metabolites immunoreactive (i) TxB2 and i6-keto-PGF1a [prostaglandin F], respectively. Drugs were given 30 min before induction of fecal peritonitis. Survival times in hours were as follows: fecal peritonitis = 10.5 .+-. 0.4 (n = 50); ibuprofen (15 mg/kg) = 16.1 .+-. 0.8 (n = 8); methylprednisolone-sodium succinate (40 mg/kg) = 17.1 .+-. 0.7 (n = 22); methylprednisolone-sodium succinate (80 mg/kg) = 46.1 .+-. 10.4 (n = 25) with 8% long-term survivors (survival > 7 days); gentamicin (4 mg/kg) = 23.8 .+-. 4.4 (n = 16); methylprednisolone-sodium succinate (40 mg/kg) + ibuprofen = 20.3 .+-. 1.8 (n = 6); gentamicin + methylprednisolone-sodium succinate = 31.0 .+-. 1.6 (n = 11); gentamicin + ibuprofen = 28.5 + 2.3 (n = 12); gentamicin + methylprednisolone-sodium succinate (40 mg/kg) + ibuprofen = 46.9 .+-. 5.4 (n = 8). Treatment with the combination of gentamicin + ibuprofen + methylprednisolone-sodium succinate (80 mg/kg) resulted in a mean survival time of 116 .+-. 13.9 h with 26% long-term survivors. Methylprednisolone-sodium succinate (40 mg/kg) reduced (P < 0.05) plasma iTxB2 from 995 .+-. 78 (n = 16) to 714 .+-. 48 (n = 18) pg/ml and i6-keto-PGF1a from 4,090 .+-. 334 (n = 12) to 2,009 .+-. 119 (n = 17) pg/ml, 4 h post-FP. Methylprednisolone-sodium succinate (80 mg/kg) produced no further decrease in either iTxB2 or i6-keto-PGF1a. Ibuprofen reduced the fecal peritonitis-induced iTxB2 and i6-keto-PGF1a synthesis to nondetectable levels (< 200 pg/ml). Methylprednisolone-sodium succinate is less effective than ibuprofen in inhibiting arachidonic acid metabolism and suggest other salutary actions. Conjoint therapy with steroidal and nonsteroidal antiinflammatory agents, and antibiotics in septic shock may be beneficial.