Effect Of 3%NaCl, Mannitol And Their Combination As An Adjunctive Treatment On E.Coil Meningitis In Rabbits

Background:Despite of advances in antibiotic treatment, bacterial meningitis(BM) remains a devastating disease in children. How to optimize the outcome of BM is still a big challenge. Intravenous infusion of man-nitol with the ability of decreasing intracranial pressure(ICP) rapidly,is considered to be the'gold standard' for the treatment of increased ICP. However, several side effects limit the clinical use of it in patients, such as ICP rebound, aggravated brain edema, and hypovolemia. Compared with mannitol therapy, hypertonic saline (HTS) produces a more rapid volume expansion, increases systemic blood pressure, and microvascular perfusion. It also decreases the rising of ICP and possesses signi-ficant anti-inflammatory capabilities. These features make HTS an attractive therapeutic agent to attenuate brain edema and neuronal injury in BM.In the present study, we evaluated the efficacy of 3%NaCl and mannitol and their combination as an adjunctive therapy in attenuating cerebral edema and brain damage in experimental Escherichia coli Meningitis in rabbits, hoping to provid evidence for useness of these two drug in the clinincal setting of BMMetheod: rabbits were fandomly divided into 8 groups:control group, meningitis group(model group), Ampicilin group,Ampicilin+mannitol group(M group), Ampicilin+3%NaCl group(H group), Ampicilin+ mannitol followed by 3%NaCl(MH group),Ampicilin+3%NaCl followed by mannitol(HM group), Ampicilin+hypertonic solution mixed with mannitol and 3%NaCl (Mix group).After been inoculated intracistenrnally saline or E.Coil, rabbits were monitored ICP, MAP, serum osmotic pressure, serum sodium, chlorine, kalium, and determined the leukocytic count, concentration of protein,TNF-α,IL-1,IL-10 in CSF. The content of water, Evans blue and of brain were also determined.Results:1.changes in ICP:In the infected group ICP were significantly higher than the control group(P<0.01). Adjunctive treatment with 3%NaCl,mannitol and their combination can inhibit the increase of ICP.mannitol decreases ICP rapidly (P<0.05), while ICP in H group was reduced gradually and maintained stably(P<0.01,or P<0.01). In MH group ICP decreased as qucikly as mannitol,and maintained so stable as 3%NaCl(P<0.05). The lowest lever of ICP in HM group appeared in 1h, and the ICP in mixed group were higher than other adjunctive treatment from 30min to 4h(P<0.05,or P<0.01).While at the last hour, there were no significent difference in the five adjunctive group(P>0.05).2. changes in MAP and CPP:The MAP and CPP in M group were significantly lower than the control group(P<0.05, or p<0.01), while there were no significant difference of MAP and CPP in the other groups (P>0.05). 3.change in serum osmotic pressure and serum sodium, chlorine, kalium:The serum osmotic pressure in the adjunctive treatment groups are significantly higher than the control,model and ampicilin group(p<0.01),but there were no siginificant difference when the five adjunctive treatment groups compared with each other. There were no significant difference of serum sodium and chlorine in control,model, ampicilin,and M group,while the that levers in H group was quickly increased at 30min, higer than the control, model,ampicilin and M group (P<0.05),then decended at 3h with no significant difference compared to control group.There were no significant difference of serum sodium and chlorine in control,MH,HM,and mixed group. There also no significant changes of serum kalium in the eight groups.4.the leukocytic count and concentration of protein in CSF:The number of leukocytes and the protein content of CSF in the infected groups was significantly higher than that of the contril group(P<0.01)。the adjunctive therapy can significantly decreased the leukocyte count and the concentration of protein in CSF(P<0.05,or P<0.01).5.The concentration of TNF-α, IL-1, IL-10 in CSF:The concentration of TNF-α,IL-1,IL-10 were significantly higher than the control groups(P<0.01). The adjunctive treatment can also significantly decrease the contents of THF-α,IL-1 in CSF(P<0.05,or P<0.01),and the concentration of IL-10 in H group was quite higher than the other groups(p<0.01).6.The water,Evans blue content of brain:the water and Evans blue content in model and ampicilin groups were quite higher than the control group(P<0.01).The adjunctive therapy were benificial to decreased the water and Evans blun content of brain (P<0.05,or P<0.01). The water content in H group and MH group were the lowest lever with no significent difference to the control group.7.pathomorphosm:In the adjunctive treatment groups, brain swelling and necrosis were less compared with model and ampicilin group.Conclusion:3%NaCl,mannitol and their combination owned the effective ability to attenuated the imflamtion and brain edema in short-term induced by Ampicillin.3%NaCl reduced ICP graudally and maintained stably,with the strong power of anti-imflamtion.infusing mannitol followed by 3%NaCl can reduce ICP quicky and maintain it stably,without electrolyte disturbances and hypovolemia.