| Ibuprofen, methylprednisolone, and gentamicin as conjoint therapy in septic shock. | |
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MedLine Citation:
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PMID: 3840416 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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-PGF1 alpha, 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 greater than 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 less than 0.05) plasma iTxB2 from 995 +/- 78 (n = 16) to 714 +/- 48 (n = 18) pg/ml and i6-keto-PGF1 alpha 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-PGF1 alpha. Ibuprofen reduced the fecal peritonitis-induced iTxB2 and i6-keto-PGF1 alpha synthesis to nondetectable levels (less than 200 pg/ml). The latter results demonstrate that methylprednisolone-sodium succinate is less effective than ibuprofen in inhibiting arachidonic acid metabolism and suggest other salutary actions. These composite observations provide evidence that conjoint therapy with steroidal and nonsteroidal anti-inflammatory agents, and antibiotics in septic shock may be beneficial. |
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Authors:
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W C Wise; P V Halushka; R G Knapp; J A Cook |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulatory shock Volume: 17 ISSN: 0092-6213 ISO Abbreviation: Circ. Shock Publication Date: 1985 |
Date Detail:
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Created Date: 1985-12-13 Completed Date: 1985-12-13 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0414112 Medline TA: Circ Shock Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 59-71 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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6-Ketoprostaglandin F1 alpha
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blood Animals Disease Models, Animal Drug Therapy, Combination Female Gentamicins / administration & dosage* Ibuprofen / administration & dosage* Indomethacin / pharmacology Methylprednisolone / administration & dosage* Peritonitis / blood, drug therapy Rats Shock, Septic / blood, drug therapy* Thromboxane B2 / blood |
| Grant Support | |
ID/Acronym/Agency:
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GM27673/GM/NIGMS NIH HHS; HL29566/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Gentamicins; 15687-27-1/Ibuprofen; 53-86-1/Indomethacin; 54397-85-2/Thromboxane B2; 58962-34-8/6-Ketoprostaglandin F1 alpha; 83-43-2/Methylprednisolone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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