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Early administration of methylprednisolone promotes survival in rats with intra-abdominal sepsis
Abstract:
We determined how the following drugs affected survival of 350-gm Sprague-Dawley rats subjected to intra-abdominal sepsis according to the method of Wichterman et al (J Surg Res 29:189-201, 1980): gentamicin (4.5 mg/kg/day), clindamycin (30 mg/kg/day), naloxone (2 mg/kg/hr), or methylprednisolone given either as a continuous infusion (2 mg/kg/hr) or as a bolus (30 mg/kg). A control group received only saline in a volume equal to the drug vehicle volume. Treatment was started immediately after cecal ligation and puncture. Drugs not given by bolus were infused by Alzet mini-pump (Model 2001) for 7 days. Percent of original population surviving at 10 days was (size of original population): saline--48% (92), antibiotics--86% (43), naloxone--30% (43), continuous methylprednisolone--14% (43), bolus methylprednisolone--93% (45). Survival of animals receiving either antibiotics or bolus methylprednisolone was significantly increased over the control population.
Insights
Antibiotics and bolus methylprednisolone significantly improved survival in rats with abdominal sepsis. Continuous methylprednisolone and naloxone did not enhance survival rates in this sepsis model.
Area of Science:
- Surgical Research
- Pharmacology
- Critical Care Medicine
Background:
- Intra-abdominal sepsis is a life-threatening condition requiring effective treatment.
- Evaluating therapeutic interventions is crucial for improving patient outcomes.
- Rodent models are essential for preclinical assessment of sepsis treatments.
Purpose of the Study:
- To evaluate the efficacy of gentamicin, clindamycin, naloxone, and methylprednisolone in a rat model of intra-abdominal sepsis.
- To compare the survival rates associated with different drug administration methods (continuous infusion vs. bolus).
Main Methods:
- Sprague-Dawley rats underwent cecal ligation and puncture to induce sepsis.
- Animals received immediate treatment with saline (control), antibiotics (gentamicin/clindamycin), naloxone, or methylprednisolone (continuous or bolus).
- Drug delivery utilized Alzet mini-pumps for continuous infusions over 7 days, except for bolus administrations.
Main Results:
- Survival rates at 10 days were: saline (48%), antibiotics (86%), naloxone (30%), continuous methylprednisolone (14%), and bolus methylprednisolone (93%).
- Both antibiotic therapy and bolus methylprednisolone administration significantly increased survival compared to the saline control group.
- Continuous methylprednisolone infusion and naloxone treatment showed reduced survival rates compared to controls.
Conclusions:
- Antibiotics and high-dose bolus methylprednisolone are effective in improving survival in this rat model of intra-abdominal sepsis.
- The route and method of drug administration significantly impact treatment efficacy in sepsis.
- Further research is warranted to explore the mechanisms behind methylprednisolone's differential effects based on administration method.