Effect of pentaglobin and piperacillin on survival in a rat model of faecal peritonitis: importance of intervention timings.

Abstract

Faecal peritonitis is a progressive pathophysiological condition which may lead to multiple organ failure and death. The reason for the associated morbidity and mortality could be attributed to the fact that some of the subtle alterations in cellular function that occur during the early stage of peritonitis are unidentified and consequently missed, leading to inadequate or delayed intervention. Recent studies have shown that early treatment with antibiotic and antisera containing antibodies to lipopolysaccharide (immunoglobulin) improve the survival rate in these patients. The present investigation was undertaken to study the effect of pentaglobin and piperacillin with particular attention to time lag of drug intervention on animal survival following experimental peritonitis. Experimental peritonitis was produced by inoculating 1 ml/kg of faecal suspension (2:1 w/v in saline) into the peritoneal cavity. Two groups of animals were treated with pentaglobin (4 ml/kg) or piperacillin (1000 mg/kg) respectively, whereas rats in another group received both drugs simultaneously. The first dose of each drug was given at 4 h, 6 h, 8 h and 12 h after faecal inoculation followed by 3 additional doses at 8-h intervals. For biochemical studies, separate groups of animals were used in which the treatment was started 4 h after faecal inoculation and the animals were killed at 12 h after the treatment. Both piperacillin and pentaglobin prolonged survival time of animals which received the treatment within 6 h of faecal insult. The combination of pentaglobin plus piperacillin produced better results as compared to the individual effect. There was a significant decrease in serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and increase in catalase following faeces-induced septicaemia, suggesting a significant increase in oxidative stress. The changes in enzyme levels were significantly attenuated by both the drugs. The findings suggest that intervention with a combination of pentaglobin and antibiotics within 6 h of peritonitis might significantly improve survival rate in rat.