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

Background: Faecal peritonitis is a progressive pathophysiological conditio n which may lead to multiple organ failure and death The reason for the ass ociated morbidity and mortality could be attributed to the fact that some o f the subtle alterations in cellular function that occur during the early s tage of peritonitis are unidentified and consequently missed, leading to in adequate or delayed intervention. Recent studies have shown that early trea tment with antibiotic and antisera containing antibodies to lipopolysacchar ide (immunoglobulin) improve the survival rate in these patients. The prese nt investigation was undertaken to study the effect of pentaglobin and pipe racillin with particular attention to time lag of drug intervention on anim al survival following experimental peritonitis. Methods: Experimental peritonitis was produced by inoculating 1 ml/kg of fa ecal 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 simulta neously. The first dose of each drug was given at 4 h, 6 h, 8 h and 12 h af ter faecal inoculation followed by 3 additional doses at 8-h intervals. For biochemical studies, separate groups of animals were used in which the tre atment was started 4 h after faecal inoculation and the animals were killed at 12 h after the treatment. Results: Both piperacillin and pentaglobin prolonged survival time of anima ls which received the treatment within 6 h of faecal insult. The combinatio n of pentaglobin plus piperacillin produced better results as compared to t he individual effect. There was a significant decrease in serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and increase in catalas e following faeces-induced septicaemia, suggesting a significant increase i n oxidative stress. The changes in enzyme levels were significantly attenua ted by both the drugs. Conclusion: The findings suggest that intervention with a combination of pe ntaglobin and antibiotics within 6 h of peritonitis might significantly imp rove survival rate in rat.