Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions

Clinically,it is highly challenging to promote recovery in patients with acute liver failure(ALF)and acute-on-chronic liver failure(ACLF).Despite recent advances in understanding the underlying mechanisms of ALF and ACLF,standard medical therapy remains the primary therapeutic approach.Liver transplantation(LT)is considered the last option,and in several cases,it is the only intervention that can be lifesaving.Unfortunately,this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant.Another option is to restore impaired liver function with artificial extracorporeal blood purification systems.The first such systems were developed at the end of the 20th century,providing solutions as bridging therapy,either for liver recovery or LT.They enhance the elimination of metabolites and substances that accumulate due to compromised liver function.In addition,they aid in clearance of molecules released during acute liver decompensation,which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy,multiple-organ failure,and other complications of liver failure.As compared to renal replacement therapies,we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems.Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging.The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins.Furthermore,conventional methods such as plasma exchange are being re-evaluated,and novel adsorption filters are increasingly being used for liver indications.These strategies are very promising for the treatment of liver failure.Nevertheless,the best method,system,or device has not been developed yet,and its probability of getting developed in the near future is also low.Furthermore,little is known about the effects of liver support systems on the overall and transplant-free survival of these patients,and further investigation using randomized controlled trials and meta-analyses is needed.This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy.It focuses on general principles of their function,and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF.In addition,we have outlined the basic advantages and disadvantages of each system.

Research on Nursing Effect of Individualized Nursing Intervention on Critically Ill Patients with Continuous Blood Purification

Objective:This paper aims to investigate the value of individualized care for critically ill patients receiving continuous blood purification therapy.Methods:89 cases of critically ill patients who were treated from June 2021 to June 2023 were randomly divided into groups,with individualized care in group A and routine care in group B.The differences in clinical indicators,purification effect,quality of life,and complications of blood purification were compared between the groups.Results:Heart rate,respiration,body temperature,and other indicators in group A were better than those in group B,P<0.05.C-reactive protein(CRP),β2-microglobulin(β2-MG),blood urea nitrogen(BUN),and phosphorus(P)in group A were lower than those in group B,P<0.05.Group A had higher quality of life than Group B,P<0.05.The complication rate of blood purification in Group A was lower than that in Group B,P<0.05.Conclusion:During continuous blood purification in critically ill patients,individualized nursing intervention can enhance the effect of blood purification,improve the physiological indicators of patients,and reduce the complications of blood purification,which is highly effective and feasible.

Treatment of hyperbilirubinemia with blood purification in China

The incidence of hyperbilirubinemia is high clinically, which is difficult to cure by medication, surgery or interventional therapies. Non-bioartificial liver is the main alternative in the blood purification for hyperbilirubinemia, which includes plasma exchange, hemoperfusion, hemodialysis, molecular adsorbent recycling system and so on. The research results and clinical experiences in China show that these methods are effective in lowering high levels of bilirubin with fewer side effects. The hyperbilirubinemias of different causes, with different complications or accompanying different diseases can be treated by different methods. Bioartificial liver, hybrid artificial liver support system and adsorbent membrane material have also been studied and their development in reducing hyperbilirubinemias has been achieved. This article gives a brief overview on the actuality and research improvement in blood purification for hyperbilirubinemia in China.

Application of bedside continuous blood purification in patients with multiple organ dysfunction syndromes

BACKGROUND:The complications of systemic inflammatory response syndrome(SIRS)include acute lung injury,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS).In recent years,how to clear inflammatory mediators has become a hot topic in critical care medicine.Researchers hypothesize that continuous blood purification(CBP) can effectively eliminate a variety of inflammatory mediators which participate in the occurrence of MODS and adjust the immune imbalance.This study aimed to observe the effects of CBP in MODS patients.METHODS:In this retrospective clinical study,a total of 38 MODS patients,18 males and 20 females,were enrolled.After conventional therapy,all the patients received CBP.Biochemistry,blood gas analysis,oxygenation index,mean arterial blood pressure(MAP),acute physiology and chronic health evaluation(APACHE) II scores were monitored.RESULTS:After CBP,the vital signs of patients were rapidly stable,and electrolyte disorders and acid-base imbalance were corrected.Renal function,blood gas,oxygenation index were all improved.MAP was increased,and APACHE II score was significantly decreased.All patients had good tolerance,stable hemodynamics,and no obvious adverse reaction on CBP compared with pre-CBP.CONCLUSION:CBP can effectively clean toxins,correct electrolyte acid-base balance,and improve systemic inflammatory response syndrome and the organ function of MODS patients.

Management strategy of prevention and control of nosocomial infection of COVID-19 in blood purification center

There are many patients in the blood purification center who need maintenance hemodialysis to maintain life. Those patients generally havelow resistance and are easily exposed to coronavirus because they go back and forth the hospital and residence three times a week andclosely contact with family, caregivers, community personnel, people in various means of transportation, medical staff, and other patientsvisiting hospital. Therefore, the blood purification center has become a high‑risk environment for the spread of COVID-19 infection. In viewof this, our center quickly responded to the formulation and implementation of infection prevention and control measures suitable for thecharacteristics of the blood purification center and continuous renal replacement therapy (CRRT) emergency plan for fever and suspectedpatients. According to these measures, we have a positive effect on preventing and controlling nosocomial infection in the blood purificationcenter.

Research Progress of Continuous Blood Purification in the Treatment of Severe Sepsis in Children

Pediatric sepsis is the most common disease in pediatric critical illness,because the main reason for the disease is that children's immune level is not high or the immune system is not perfect,when children's lung,abdominal cavity and blood system are infected,it will cause systemic inflammation and immune dysfunction.Early clinical symptoms are mainly irregular and intermittent fever.When the disease develops to severe sepsis,the children will suffer from acute heart failure,oliguria,respiratory alkalosis and even multiple organ failure.The incidence of death is high.It is reported that the incidence rate of sepsis in children can reach 0.3%,and the mortality rate is 50%.High incidence rate,high mortality rate and high treatment cost are the biggest problems in the pediatric field.In the past,the clinical hope of clearing away heat and toxin,promoting blood circulation and removing stasis,strengthening inflammation and other methods in traditional Chinese medicine,but the treatment effect is not ideal.With the improvement of modem medical understanding of sepsis,continuous blood purification therapy is introduced into the treatment of children with severe sepsis.In order to further explore the effect of continuous blood purification in the treatment of children with severe sepsis,the author summarizes the clinical practice experience and relevant literature,hoping to provide reference for relevant medical staff。

Mathematical Simulation of Blood Purification for Leukemia by Immobilized L-asparaginase

Plasma was purified in an immobilized L-asparaginase column. The predicted results are in good agreement with experimental data. It is indicated that the mathematical model is suitable for the mass transfer and reaction of blood purification.

Treatment of a patient with aconitine poisoning using veno-arterial membrane oxygenation:A case report

BACKGROUND Aconitine poisoning is highly prone to causing malignant arrhythmias.The elimination of aconitine from the body takes a considerable amount of time,and during this period,patients are at a significant risk of death due to malignant arrhythmias associated with aconitine poisoning.CASE SUMMARY A 30-year-old male patient was admitted due to accidental ingestion of aconitinecontaining drugs.Upon arrival at the emergency department,the patient intermittently experienced malignant arrhythmias including ventricular tachycardia,ventricular fibrillation,ventricular premature beats,and cardiac arrest.Emergency interventions such as cardiopulmonary resuscitation and defibrillation were promptly administered.Additionally,veno-arterial extracorporeal membrane oxygenation(VA-ECMO)therapy was initiated.Successful resuscitation was achieved before ECMO placement,but upon initiation of ECMO,the patient experienced recurrent malignant arrhythmias.ECMO was utilized to maintain hemodynamics and respiration,while continuous blood purification therapy for toxin clearance,mechanical ventilation,and hypothermic brain protection therapy were concurrently administered.On the third day of VA-ECMO support,the patient’s respiratory and hemodynamic status stabilized,with only frequent ventricular premature beats observed on electrocardiographic monitoring,and echocardiography indicated recovery of cardiac contractile function.On the fourth day,a significant reduction in toxin levels was observed,along with stable hemodynamic and respiratory functions.Following a successful pump-controlled retrograde trial occlusion test,ECMO assistance was terminated.The patient gradually improved postoperatively and achieved recovery.He was discharged 11 days later.CONCLUSION VA-ECMO can serve as a bridging resuscitation technique for patients with reversible malignant arrhythmias.

Extracorporeal organ support for critically ill patients:Overcoming the past,achieving the maximum at present,and redefining the future

Extracorporeal organ support(ECOS)has made remarkable progress over the last few years.Renal replacement therapy,introduced a few decades ago,was the first available application of ECOS.The subsequent evolution of ECOS enabled the enhanced support to many other organs,including the heart[veno-arterial extracorporeal membrane oxygenation(ECMO),slow continuous ultrafiltration],the lungs(veno-venous ECMO,extracorporeal carbon dioxide removal),and the liver(blood purification techniques for the detoxification of liver toxins).Moreover,additional indications of these methods,including the suppression of excessive inflammatory response occurring in severe disorders such as sepsis,coronavirus disease 2019,pancreatitis,and trauma(blood purification techniques for the removal of exotoxins,endotoxins,or cytokines),have arisen.Multiple organ support therapy is crucial since a vast majority of critically ill patients present not with a single but with multiple organ failure(MOF),whereas,traditional therapeutic approaches(mechanical ventilation for acute respiratory failure,antibiotics for sepsis,and inotropes for cardiac dysfunction)have reached the maximum efficacy and cannot be improved further.However,several issues remain to be clarified,such as the complexity and cost of ECOS systems,standardization of indications,therapeutic protocols and initiation time,choice of the patients who will benefit most from these interventions,while evidence from randomized controlled trials supporting their use is still limited.Nevertheless,these methods are currently a part of routine clinical practice in intensive care units.This editorial presents the past,present,and future considerations,as well as perspectives regarding these therapies.Our better understanding of these methods,the pathophysiology of MOF,the crosstalk between native organs resulting in MOF,and the crosstalk between native organs and artificial organ support systems when applied sequentially or simultaneously,will lead to the multiplication of their effects and the minimization of complications arising from their use.

Continuous renal replacement therapy with oXiris®in patients with hematologically malignant septic shock:A retrospective study

BACKGROUND The mortality rate from septic shock in patients with hematological malignancies(HMs)remains significantly higher than that in patients without HMs.A longer resuscitation time would definitely be harmful because of the irreversibly immunocompromised status of the patients.Shortening the resuscitation time through continuous renal replacement therapy(CRRT)with oXiris^(■)would be an attractive strategy in managing such patients.AIM To explore the effects of CRRT and oXiris^(■)in shortening the resuscitation time and modifying the host response by reducing inflammation mediator levels.METHODS Forty-five patients with HM were diagnosed with septic shock and underwent CRRT between 2018 and 2022.Patients were divided into two groups based on the hemofilter used for CRRT(oXiris^(■)group,n=26;M150 group,n=19).We compared the number of days of negative and total fluid balance after 7 d of CRRT between the groups.The heart rate,norepinephrine dose,Sequential Organ Failure Assessment(SOFA)score,and blood lactic acid levels at different time points in the two groups were also compared.Blood levels of inflammatory mediators in the 26 patients in the oXiris^(■)group were measured to further infer the possible mechanism.RESULTS The average total fluid balance after 7 d of CRRT in the oXiris^(■)group was significantly lower than that of patients in the M150 hemofilter group.The SOFA scores of patients after CRRT with oXiris^(■)therapy were significantly lower than those before treatment on day 1(d1),d3 and d7 after CRRT;these parameters were also significantly lower than those of the control group on d7.The lac level after oXiris^(■)therapy was significantly lower than that before treatment on d3 and d7 after CRRT.There were no significant differences in the above parameters between the two groups at the other time points.In the oXiris^(■)group,procalcitonin levels decreased on d7,whereas interleukin-6 and tumor necrosis factor levels decreased significantly on d3 and d7 after treatment.CONCLUSION CRRT with oXiris^(■)hemofilter may improve hemodynamics by reducing inflammatory mediators and playing a role in shortening the resuscitation period and decreasing total fluid balance in the resuscitation phases.

Artificial and bioartificial liver support:A review of perfusion treatment for hepatic failure patients

Liver transplantation and blood purification therapy,including plasmapheresis,hemodiafiltration,and bioartificial liver support,are the available treatments for patients with severe hepatic failure.Bioartificial liver support,in which living liver tissue is used to support hepatic function,has been anticipated as an effective treatment for hepatic failure.The two mainstream systems developed for bioartificial liver support are extracorporeal whole liver perfusion(ECLP)and bioreactor systems.Comparing various types of bioartificial liver in view of function,safety,and operability,we concluded that the best efficacy can be provided by the ECLP system.Moreover,in our subsequent experiments comparing ECLP and apheresis therapy,ECLP offers more ammonia metabolism than HD and HF.In addition,ECLP can compensate amino acid imbalance and can secret bile.A controversial point with ECLP is the procedure is labor intensive,resulting in high costs.However,ECLP has the potential to reduce elevated serum ammonia levels of hepatic coma patients in a short duration.When these problems are solved,bioartificial liver support,especially ECLP,can be adopted as an option in ordinary clinical therapy to treat patients with hepatic failure.

Regional citrate anticoagulation in critically ill patients during continuous blood purification

Objectives To evaluate the safety and define the contraindication of regional citrate anticoagulation treatment on various critically ill patients being treated by continuous blood purification, who also had bleeding tendencies. Methods Forty critically ill patients being treated by continuous blood purification (CBP) were involved in this study. Due to their bleeding tendencies, regional citrate anticoagulation treatment was given to all of them. Those with hepatic function impairment (n=10) were classified as Group A, those with hypoxemia were classified as Group B (n=10), and the others as Group C (n=20). Blood samples were collected before treatment, and at 4, 12, 24, 36, and 48 hour intervals during CBP. These samples then were used arterial blood gas analysis, whole blood activated clotting time (WBACT) pre- and post-filter, and serum ionized calcium examination. Results WBACT pre-filter showed little fluctuant through the 48hr period of CBP, and WBACT post-filter showed obvious prolongation than that of the pre-filter (P<0.05) at all time points. Metabolic acidosis was found in Group A patients before CBP, and improved during CBP. Normal acid-base conditions of patients were disturbed and deteriorated in Group B during CBP, but not in Group C. Serum ionized calcium was maintained at a normal range during CBP in Group A and C patients, but declined significantly in Group B patients (vs. pre-treatment, P<0.05). Conclusions Regional citrate anticoagulation can be safely used in conjunction with CBP treatment for patients with hepatic function impairment , but may induce acidosis and a decline in serum ionized calcium when used with hypoxemic patients.

Blood purification for sepsis:an overview

Sepsis is a life-threatening organ failure exacerbated by a maladaptive infection response from the host,and is one of the major causes of mortality in the intensive care unit.In recent decades,several extracorporeal blood purification techniques have been developed to manage sepsis by acting on both the infectious agents themselves and the host immune response.This research aims to summarize recent progress on extracorporeal blood purification technologies applied for sepsis,discuss unanswered questions on renal replacement therapy for septic patients,and present a decision-making strategy for practitioners.

High performance of a unique mesoporous polystyrene-based adsorbent for blood purification

A multi-functional polystyrene based adsorbent(NKU-9)with a unique mesoporous and a high surface area was prepared by suspension polymerization for removal of therapeutic toxins in blood purification.The adsorbent produced had an almost equal amount of mesopore distribution in the range from 2 to 50 nm.The adsorption of serum toxins with different molecular weights were examined by in vitro adsorption assays and compared with some clinical currently used adsorbents such as HA-330,Cytosorb and BL-300 which are produced by China,America and Japan,respectively.Test results indicated that the adsorption rate for pentobarbital by NKU-9 was 81.24%which is nearly as high as HA-330(81.44%).The latter adsorbent is currently used for acute detoxification treatment in China.To reach adsorption equilibrium,NKU-9 was faster than HA-330,which implies short treatment time.For the removal of middle molecular toxins such as b2-microglobulin(98.88%),NKU-9 performed better adsorptive selectivity than Cytosorb(92.80%).In addition,NKU-9 showed high performance for the removal of albumin-bound toxins(e.g.,bilirubin),and its adsorption rate for total bilirubin(80.79%)in plasma was 8.4%higher than that of anion exchange resin BL-300 which is currently used to eliminate bilirubin in clinic.Therefore,our results indicate that the newly developed adsorbent with a wide distribution and almost equal amount of mesopores is a multifunctional adsorbent for high efficient removal of serum toxins with different molecular weights which might be an excellent blood purification adsorbent especially to treat diseases that conventional medical methods are low or not efficient.

Expert recommendations on blood purification treatment protocol for patients with severe COVID-19

Coronavirus disease(COVID-19)was first diagnosed in Wuhan in December 2019.The World Health Organization defined the subsequent outbreak of COVID-19 worldwide as a public health emergency of international concern.Epidemiological data indicate that at least 20%of COVID-19 patients have severe disease.In addition to impairment of the respiratory system,acute kidney injury(AKI)is a major complication.Immune damage mediated by cytokine storms and concomitant AKI is a key factor for poor prognosis.Based on previous experience of blood purification for patients with severe acute respiratory syndrome and Middle East respiratory syndrome combined with clinical front-line practice,we developed a blood purification protocol for patients with severe COVID-19.This protocol is divided into four major steps.The first step is to assess whether patients with severe COVID-19 require blood purification.The second step is to prescribe a blood purification treatment for patients with COVID-19.The third step is to monitor and adjust parameters of blood purification.The fourth step is to evaluate the timing of discontinuation of blood purification.It is expected that blood purification will play a key role in effectively reducing the mortality of patients with severe COVID-19 through the standardized implemenlation of the present protocol.

毛细血管渗漏综合征的研究进展(英文)

Capillary leak syndrome(CLS) in critically ill patients is common,and the clinical manifestations of CLS include systemic edema,hypoproteinemia,effective circulating blood volume reduction and blood concentrated.The common pathogenesy is sepsis,severe trauma,cardiopulmonary bypass and so on.CLS is divided into leakage period and recovery period usually.Clinical manifestation and treatment in different period are different in each pathophysiologic process.Although the methods of treatment are more,effective treatment measures are in shortage.More therapeutic measures are studied currently which include improvement of endothelial cell function,macromolecular colloidal solution application,continuous blood purification and so on.It is a guiding value to understand the pathological mechanism,clinical manifestations,diagnosis and treatment of the CLS.

Preparation of Aminated Macroporous Polyvinyl Alcohol Resins and Evaluation for Bilirubin Adsorption

In the present study we prepared macroporous polyvinyl alcohol beads. A series of bilirubin adsorbents were generated by immobilization of eight amine agents to the beads as ligands. The adsorption of bilirubin was evaluated by in vitro static and dynamic adsorption tests. The results show that these adsorbents have excellent adsorption efficiency and capacity. Among the eight ligands, trimethylamine （TMA）, triethylamine （TEA） and 1,6- hexanediamine （HDA） showed the highest adsorption capacity. The adsorption equilibrium can be achieved in half an hour, and the adsorption percentage of bilirubin was up to 80%. Static electricity and hydrophobie interaction played the main role in bilirubin adsorption, and the adsorption was found to match the monolayer model. The excellent adsorption of these adsorbents indicates their potential in clinical treatment.

Interactions to plasm protein and application potentials of carbon nanotubes in blood-contacting medical devices

Carbon nanotubes(CNTs)have been largely investigated in various biomedical fields on the basis of their excellent physical properties and drug delivery performance.However,application capacities of CNTs in blood-contacting medical devices are given due attention though there have been increasingly accumulated experimental data showing promising potentials.Herein,we collected and showed research evidence that strong interactions of CNTs to plasm proteins are attractive and valuable features holding great application potentials for medical devices and implants used in blood-contacting environments,while blood compatibility has been a big challenge faced by this kind of devices.This review introduces the strong and nonspecific plasm protein adsorptions of CNTs due to their high purity of carbon composition and nanostructures,followed by discussions on the implication of these interactions to blood coagulation and complement activation,aiming to sort out and provide insights into the application potentials of CNTs in blood-contacting medical devices and implants in the context of anti-thrombosis and blood purification.