Survival of primates in LD100 septic shock following steroid/antibiotic therapy

L. B. Hinshaw, L. T. Archer, B. K. Beller-Todd, J. J. Coalson, D. J. Flournoy, R. Passey, Bruce Benjamin, G. L. White

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Abstract

This study was designed to determine the effect of steroid/antibiotic treatment on the survival of baboons subjected to LD100 Escherichia coli shock. Fourteen baboons (Papio c. cynocephalus), randomly divided into three groups, were anesthetized and administered 2-hr infusions of LD100 viable E. coli. Group A received E. coli alone; Group B was administered E. coli followed by infusions of both gentamicin sulfate (GS) (18 mg/kg) and methylprednisolone sodium succinate (MPSS) (75 mg/kg) during a 12-hr period. Group C was given E. coli plus GS (18 mg/kg) alone. Groups B and C baboons were also given GS intramuscularly, 4.5 mg/kg at 12 hr and twice daily for 3 days. Insensible fluid loss during the intial 12-hr period was replaced by minimal volumes of saline. Fully treated baboons (Group B) received steroid after 0.7 × 1010 organisms/kg body wt had been administered. All fully treated baboons survived; however, all animals of Groups A and C died within 42 hr. Systemic hypotension observed in every baboon within 2 hr was reversed in Group B animals. Hypoglycemia, hypoinsulinemia, anuria, and extensive adrenal pathology were prevented by steroid/antibiotic treatment. Serum creatinine and blood urea nitrogen concentrations increased in all baboons but returned to normal in the fully treated group. Increased survival may have been due in part to augmented antibacterial activity elicited by (a) improved peripheral distribution of the antibiotic and (b) stimulation of the bone marrow by the steroid. Findings demonstrate that the lethal pathophysiology of E. coli-induced shock is effectively prevented by combined steroid and antibiotic therapy.

Original languageEnglish
Pages (from-to)151-170
Number of pages20
JournalJournal of Surgical Research
Volume28
Issue number2
DOIs
StatePublished - 1 Jan 1980

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Papio
Septic Shock
Primates
Steroids
Anti-Bacterial Agents
Escherichia coli
Gentamicins
Therapeutics
Shock
Papio cynocephalus
Methylprednisolone Hemisuccinate
Anuria
Blood Urea Nitrogen
Hypoglycemia
Hypotension
Creatinine
Bone Marrow
Pathology
Serum

Cite this

Hinshaw, L. B., Archer, L. T., Beller-Todd, B. K., Coalson, J. J., Flournoy, D. J., Passey, R., ... White, G. L. (1980). Survival of primates in LD100 septic shock following steroid/antibiotic therapy. Journal of Surgical Research, 28(2), 151-170. https://doi.org/10.1016/0022-4804(80)90158-4
Hinshaw, L. B. ; Archer, L. T. ; Beller-Todd, B. K. ; Coalson, J. J. ; Flournoy, D. J. ; Passey, R. ; Benjamin, Bruce ; White, G. L. / Survival of primates in LD100 septic shock following steroid/antibiotic therapy. In: Journal of Surgical Research. 1980 ; Vol. 28, No. 2. pp. 151-170.
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Hinshaw, LB, Archer, LT, Beller-Todd, BK, Coalson, JJ, Flournoy, DJ, Passey, R, Benjamin, B & White, GL 1980, 'Survival of primates in LD100 septic shock following steroid/antibiotic therapy', Journal of Surgical Research, vol. 28, no. 2, pp. 151-170. https://doi.org/10.1016/0022-4804(80)90158-4

Survival of primates in LD100 septic shock following steroid/antibiotic therapy. / Hinshaw, L. B.; Archer, L. T.; Beller-Todd, B. K.; Coalson, J. J.; Flournoy, D. J.; Passey, R.; Benjamin, Bruce; White, G. L.

In: Journal of Surgical Research, Vol. 28, No. 2, 01.01.1980, p. 151-170.

Research output: Contribution to journalArticle

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N2 - This study was designed to determine the effect of steroid/antibiotic treatment on the survival of baboons subjected to LD100 Escherichia coli shock. Fourteen baboons (Papio c. cynocephalus), randomly divided into three groups, were anesthetized and administered 2-hr infusions of LD100 viable E. coli. Group A received E. coli alone; Group B was administered E. coli followed by infusions of both gentamicin sulfate (GS) (18 mg/kg) and methylprednisolone sodium succinate (MPSS) (75 mg/kg) during a 12-hr period. Group C was given E. coli plus GS (18 mg/kg) alone. Groups B and C baboons were also given GS intramuscularly, 4.5 mg/kg at 12 hr and twice daily for 3 days. Insensible fluid loss during the intial 12-hr period was replaced by minimal volumes of saline. Fully treated baboons (Group B) received steroid after 0.7 × 1010 organisms/kg body wt had been administered. All fully treated baboons survived; however, all animals of Groups A and C died within 42 hr. Systemic hypotension observed in every baboon within 2 hr was reversed in Group B animals. Hypoglycemia, hypoinsulinemia, anuria, and extensive adrenal pathology were prevented by steroid/antibiotic treatment. Serum creatinine and blood urea nitrogen concentrations increased in all baboons but returned to normal in the fully treated group. Increased survival may have been due in part to augmented antibacterial activity elicited by (a) improved peripheral distribution of the antibiotic and (b) stimulation of the bone marrow by the steroid. Findings demonstrate that the lethal pathophysiology of E. coli-induced shock is effectively prevented by combined steroid and antibiotic therapy.

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Hinshaw LB, Archer LT, Beller-Todd BK, Coalson JJ, Flournoy DJ, Passey R et al. Survival of primates in LD100 septic shock following steroid/antibiotic therapy. Journal of Surgical Research. 1980 Jan 1;28(2):151-170. https://doi.org/10.1016/0022-4804(80)90158-4