The Influence Of Extracorporeal Membrane Oxygenation And With Inline Continuous Renal Replancement Therapy On The Pulmonary Function And The Inflammatory Reaction

ARDS is characterized by the acute onset of hypoxemia and bilateral pulmonary infiltrates that are consistent with pulmonary edema but without evidence of left heart failure.The use of positive-pressure ventilation,although potentially lifesaving in patients with ARDS,may cause ventilator-associated lung injury.Lung-protective ventilation strategies mitigate ventilator-associated lung injury and oxygen toxicity.However,even with the use of this strategy,mortality from ARDS remains high.ECMO may be initiated as salvage therapy in patients with profound gas-exchange abnormalities when positive-pressure ventilation cannot maintain adequate oxygenation or carbon dioxide excretion to support life.Within the first few hours of ECMO,there was the inflammatory complication of ECMO.The mechanisms are not well established.The CRRT indications for ECMO patients are renal failure,hypervolemia,edema,and severe electrolyte disturbances.CRRT had been proved to remove the inflammatory cytokines in both animal studies and clinic researches,and it also used to managed the fluid overload.The change of inflammatory reaction during the CRRT in conjunction with ECMO is rarely mentioned.Recently,ECMO rescuing the post-trauma ARDS patients are reported,due to the need for limited heparinisation,its use in trauma patients has been more restricted.In our clinic practice,used ECMO in the trauma inducing ARDS,help to improve the patients outcome.In our research,we first tested the efficacy and safety of the inclusion of a CRRT machine in the ECMO circuit in vitro and in vivo.And secondly,we evaluated the contribution of cannulation or VV-ECMO or CRRT+ECMO based on observation of pulmonary inflammatory reaction and parenchymal construction in a porcine model of low tidal volume(VT)ventilation.We found VV-ECMO+CRRT preserved the lung parenchyma better than ECMO along by eliminating the systemic cytokines.Third,we established a post-trauma ARDS porcine model as the result of lung constitution and systemic ischemia-reperfusion.We further investgated the effect of cannulation and VV-ECMO and CRRT+ECMO in this model.And we were noticed the ECMO+CRRT would help the recover the lung in the post-trauma ARDS porcine model.At the same time,we investgated the ECMO theraphy in the ARDS patients,we concluded the clinic experience.PART ?Continuous renal replacement therapy combined venovenous extracorporeal membrane oxygenation circuit in vitro and in vivoPurpose:We had evaluated the way of connecting hemofiltration along with the ECMO circuit.Methods:we designed 4 methods to connecting CRRT to ECMO.The two devices was tested in a closed circuit primed using colloids.We varied the ECMO blood flow and the CRRT location,recording the pressures in the two devices.The systems were then used in the experimental surgery laboratory on a pig,and further evaluated the advantages and disadvantages of the connecting mannaers.Results:Connecting CRRT to ECMO before centrifugal pump,the CRRT did not operate.Connecting CRRT to ECMO between centrifugal pump and oxygenator,the ECMO circuit need to be cut.Connecting CRRT to ECMO before and after oxygenator,it would reduce the blood flow that passing through the oxygenator.Connecting CRRT to ECMO after oxygenator,we used the arterial cannula to replace the venous cannula,and there was no influence on the pressure and oxygenation.Conclusions:Connecting CRRT to ECMO,was the most practicable and economic method,and could used in the clinic practice.PART II Continuous renal replacement therapy preserved lungs from venovenous extracorporeal membrane oxygenation in a porcine modelPurpose:Pulmonary changes in venovenous extracorporeal membrane oxygenation(VV-ECMO)are rarely established.This study compared VV-ECMO and cannulation contribution based on observation of pulmonary inflammatory reaction and parenchymal construction in a porcine model of low tidal volume(VT)ventilation.We also evaluated the effect when added continuous renal replacement therapy(CRRT)to ECMO circuit in the third group,as CRRT would reduce ECMO inducing systemic cytokines releasing.Methods:18 pigs with low VT ventilation were randomly divided into three groups(group 1=cannulation;group 2=VV-ECMO;group 3=VV-ECMO+CRRT)for 24hours.Hemodynamic and ventilation parameters were recorded.We assessed plasma and alveolar cytokines,expression of pulmonary inflammatory genes,histopathological grading and ultrastructural changes of lungs.Results:Inspiratory volume increased and Pa02 decreased in group 1.Systemic cytokine levels increased in group 2 and partly dropped in group 3.At 24hr,broncho-alveolar lavage fluid(BLAF)TNF-a and IL-6 levels in group 2 was remarkably higher than those of group 1 and 3.Pulmonary mRNA expression of cytokines did not differ among groups.We observed an increase scores in pulmonary pro-inflammatory cells infiltration and interstitial thickened in group 2.Epitheliumin of blood-air barrier after ECMO was swollen.In group 3,the pulmonary parenchyma and blood-air barrier construction were well preserved.Conclusions:In a pig model of low VT ventilation,either VV-ECMO or VV-ECMO+CRRT assured adequate oxygenation and carbon dioxide removal.VV-ECMO+CRRT preserved the lung parenchyma better than ECMO along by eliminating the systemic cytokines.PART ?Continuous renal replacement therapy connecting to venovenous extracorporeal membrane oxygenation in a post-trauma ARDS porcine modelStudy I:Establishment of the post-trauma ARDS porcine model Purpose:we aimed to establish a post-trauma ARDS porcine model,which was easy to perform and well reproduced.Methods:12 pigs were randomly divided into three groups.In each group,we used weighty fell on the chest of the pig(group A=0.2kg/(kg weight);group B=0.4kg/(kg weight);group C= 0.6kg/(kg weight)).Then the pig underwent the systemic ischemia-reperfusion and observed for 24hours.Hemodynamic and ventilation parameters were recorded.We assessed CT score after trauma,and the histopathological changes of lungs.Results:there was no remarkably difference of suivival time between groups.The morbility of Group C was 75%.The animals in Group A all survived.And in Group A,the light changes of oxygenation index,CT score and the pathohistology were observed.In Group B,the oxygenation index was between 200 to 300.The CT score indicated that the half lung was contused.And there was mild to severe inflammatory infiltration and exudate in the lung parenchyma.Conclusion:Group B was similar with the changes of pathophysiology in post-trauma ARDS.Study ?:The influence of VV-ECMO and W-ECMO+CRRT in post-trauma ARDS porcine modelPurpose:The clinic research of W-ECMO in the post-trauma was rare,and there was no animal research in this research aspect.This study compared VV-ECMO and cannulation contribution based on observation of pulmonary inflammatory reaction and parenchymal construction in a post-trauma porcine model of low tidal volume(VT)ventilation.We further evaluated the effect when added continuous renal replacement therapy(CRRT)to ECMO circuit in the third group.Method:18 pigs with low VT ventilation were randomly divided into three groups(model group =cannulation;model +ECMO group=VV-ECMO;model +ECMO+CRRT group =W-ECMO+CRRT)for 24hours.Hemodynamic and ventilation parameters were recorded.We assessed total protein of the BALF,pulmonary MPO activity and wet to dry ratio.We also observed the survival time and histopathological changes of lungs.Results:The survival time and rate did not significantly differ between groups.The hemodynamics was more stable in the model +ECMO group.In model +ECMO group,the pneumodynamics and the pulmonary compliance was improved in the model group while there was no remarkably difference of plateau airway pressure and pulmonary vascular permeability index(PVPI)between model group and model +ECMO group.In model +ECMO+CRRT group,the plateau airway pressure and PVPI were lower than that of the other groups.Both model +ECMO and model +ECMO+CRRT group could provide sufficient oxygenation and carbon dioxide exchange.The BALF proteinic level was increased in model +ECMO group than that of model group.The pulmonary wet to dry ratio of model +ECMO+CRRT group reduced than that of model +ECMO group.In model +ECMO+CRRT group,organization of alveolar exudate and the interstitial thickening were less severe than that of the other groups.Conclusions:In a post-trauma pig model of low V T ventilation,both VV-ECMO and VV-ECMO+CRRT assured adequate oxygenation and carbon dioxide removal of the injure animals,while improved the hemodynamic parameters.VV-ECMO connecting with CRRT improved the ventilation parameters and pulmonary edema in the post-trauma animals.PART IVThe influence of initiating venovenous extracorporeal membrane oxygenation with continuous renal replacement therapy on the pulmonary fuction of ARDS patientsPurpose:Extracorporeal membrane oxygenation(ECMO)is a supportive therapy used for severe acute respiratory distress syndrome(ARDS).We present clinical parameter and organ fuction in a cohort of 9 ARDS patients whom were treated with ECMO.Method:Data of all ARDS patients were prospectively collected between 2010 and 2013.Clinical parameters of patients treated with were evaluated.Result:There was 9 ARDS patients receiving ECMO or ECMO+CRRT.After initating ECMO,the oxygenation inproved,comparing with that before ECMO.There was no different between the WEC,PLT,coagulation and organic function of before or after ECMO.Conclusion:ECMO or ECMO+CRRT had improved the ARDS patients oxygenation,so that the failed lungs could have some time to recover.The system would also protect the kidney.And there was no obeviously aggravating of the coagulation and liver fuction after the initiong ECMO or ECMO+CRRT,while the inflammory reaction did not differ between before and after ECMO.