The Alteration And Significance Of Neutrophil Function In The Treatment Of Multiple Organ Dysfunction Syndrome With High Volume Hemofiltration

MODS is one of the major reasons for the death of critical patients.Themechanisms of MODS is kept unclear,the hypothesis of "two-hit" has become mostpopular by now.When the body suffers from two hits,a lot of pro-inflammatory andanti-inflammatory mediaors will be produced,which would cause overwhelminginflammation response;then,the body can not maintain the homeostasis,and wouldresult in the presence of SIRS/MODS and death at last.The polymorphonuclearneutrophil(PMN) plays an important role in the process of MODS,when penetratingtarget tissue,it releases many mediators by oxidative burst,such as hydrogen peroxideanion or cytokines or protein enzymes,then causes tissue injury.Continuous renalreplace therapy(CRRT) is not only conceived as a replacement of the lost kidneyfunction,but plays an important role in the therapy of serious inflammation asimmunomodulatory treatment,which can remove many soluble pro-inflammatory andanti-inflammatory mediators attributed to SIRS/MODS.It has been accepted widelythat high volume hemofitrition(HVHF) can remove these mediators more effectivelythan other hemofiltrition techniques.In this study, a pig model with MODS wasestablished at first,then the process of MODS and the function of neutrophil wasinvestigated;and the influence of HVHF on MODS and the neutrophil function wasstudied. In first part of the research,a new pig MODS model was successfullyestablished with the combined factors of hemorrhagic shock and endotoxemia.Methods: 15 pigs were randomly divided into two groups which were subjected to theMODS group(group M, n=9), and the control group(group N, n=6). In group M,afteranesthesia, mean arterial pressure was decreased to 50+5 mmHg for 1.5-2 hour. Then60% of the lost blood and the double volume of equilibrium liquid were transfusedback into the pigs for resuscitation. The next morning, 1.5mg/kg of endotoxin (O11B4)was given via vein which persisting for 24h.The control group only receivedanesthesia and operation without suffering from hemorrhagic shock and 第 5 页第二军医大学硕士学位论文 普通外科专业endotoxemia.All living animals were sacrificed after seven days.During the study,theheart rate,respiratory rate, arterial blood pressure were supervised, blood specimenswere collected everyday for serum ALT, AST, Cr, BUN,blood regular test and bloodgas analysis. The results showed that eight pigs developed MODS in group M,themorbidity was 88.9%.Two pigs with two organs failure ,four pigs with three organsfailure,two pigs with four or more organs failure. The mortality was 77.8%. Themorbidity and mortality were zero in group N.The difference was significant betweenthe two groups.The pig MODS model was successfully established by the use of"double-hit" method in the study. This model has high morbidity, high mortality,highrepetition, and much simulates the clinical features of classical MODS. In second part,the role of high volume hemofiltration in the treatment of MODSwas studied.Ten pigs(group HF) which were randomly introduced into the studyreceived combined factors of hemorrhagic shock and endotoxemia as group M.HVHFbegan after one hour of the infusion of endotoxin being finished,and persisted 12hours everyday for three days,the filter was changed everyday,the ultrafiltration ratewas 3L/h. All living animals were sacrificed after seven days.During the study,theheart rate,respiratory rate, arterial blood pressure were supervised, blood specimenswere collected everyday for serum ALT, AST, Cr, BUN,blood regular test and bloodgas analysis. The results showed that the morbidity of MODS was 20% in groupHF,the mortality was 20%,which decreased significantly compared to group Mrespectively.Conclusion:In the early stage of the development from SIRS toMODS,HVHF could play an important role in the treatment of MODS andsignificantly reduce the morbidity and mortality of MODS...