Effects of hemodialysis and hemoperfusion on inflammatory factors and nuclear transcription factors in peripheral blood cell of multiple organ dysfunction syndrome.

OBJECTIVE: To investigate the effects of hemodialysis (HD) and hemoperfusion (HP) on inflammatory factors and nuclear transcription factors in peripheral blood cell of multiple organ dysfunction syndrome (MODS) patients. PATIENTS AND METHODS: 92 cases of MODS patients undergoing maintained hemodialysis in our hospital were randomly divided into the control group and observation group. The control group was treated with conventional hemodialysis (HD), the observation group was treated with hemoperfusion combined therapy (HD+HP) based on the control group. The levels of serum creatinine (SCR), serum total cholesterol (TC), blood urea nitrogen (BUN) and serum albumin (Alb) were compared and analyzed between two groups before and after treatment. The levels of NK-κB p65 in the white cell of peripheral blood were compared between two groups before and after treatment by Western blot. The levels of inflammatory factors TNF-α and IL-6 in peripheral blood were detected between two groups before and after treatment using ELISA method. RESULTS: Compared with the control group, the levels of Scr, BUN and TC were significantly decreased, while the level of Alb was significantly increased (p < 0.05). The level of cytoplasm NK-κB p65 protein in peripheral blood was significantly increased in the observation group, while the level of nuclear NK-κB p65 in peripheral blood was significantly decreased (p < 0.05). CONCLUSIONS: Hemodialysis combined with hemoperfusion in treating MODS patients could significantly improve the biochemical indicators, effectively remove the inflammatory mediums, and significantly inhibit the activation of NK-κB.

Therapeutic efficacies of different hemoperfusion frequencies in patients with organophosphate poisoning.

OBJECTIVE: We tested therapeutic efficacies of different hemoperfusion frequencies in patients with acute severe organophosphate poisoning (ASOP). PATIENTS AND METHODS: 36 patients with ASOP were enrolled in this study and divided into two groups. Patients in the repeated hemoperfusion group (n=20) received 3-4 hemoperfusions within 48 hours after poisoning, while other patients (n=16) received 1 hemoperfusion. The therapeutic efficacies were compared using the following outcomes: dosage of atropine, time to awake from coma, time for normalization of cholinesterase levels, appearance of intermediate myasthenia syndrome, and survival rates. RESULTS: Compared with patients who receive one hemoperfusion, patients with repeated hemoperfusion had a significantly less atropine use, shorter time of awakening from coma, higher cure rates, shorter time until normalization of cholinesterase levels, lower appearance of intermediate myasthenia syndrome, and higher survival rates. CONCLUSIONS: Early repeated hemoperfusion is more efficient than single hemoperfusion in treating organophosphate poisoning.

Utilidad de la hemoperfusión en el tratamiento del paciente séptico grave. Actualización / Usefulness of haemoperfusion in the treatment of the severe septic patient: an update

La hemoperfusión es un procedimiento extracorpóreo que consiste en la retirada de endotoxina y/o mediadores inflamatorios por un mecanismo de adsorción durante el paso de la sangre por un filtro específico. La mayor parte de los estudios publicados han empleado la polimixina B como adsorbente. Este tratamiento se basa en la premisa de que la eliminación de endotoxina y mediadores de la circulación atenúa la respuesta inflamatoria en la sepsis. Se revisan las bases teóricas y los resultados clínicos publicados con el uso de la hemoperfusión. Si bien la mayoría de los estudios que emplean esta técnica presentan resultados positivos, existen dudas acerca de la idoneidad de los métodos empleados (grupos pequeños, baja calidad en el diseño de los estudios, mortalidad excesiva en los grupos control). También existen inconsistencias en la base teórica de su uso (ausencia de beneficios tras la eliminación de endotoxina por otros mecanismos, discrepancias en el momento de iniciar la terapia, aparente utilidad en enfermedades sin elevación de endotoxina). Los autores opinan que la hemoperfusión es prometedora en el tratamiento de la sepsis, pero requiere su confirmación en estudios bien diseñados antes de ser incluida en los protocolos habituales de tratamiento(AU)

Haemoperfusion is an extracorporeal technique that removes endotoxin and/or inflammatory mediators by means of an adsorptive mechanism during the passage of the blood through a porous filter. Most of the studies in the literature use polymyxin B as the adsorptive agent. This treatment is based on the assumption that the removal of endotoxin and inflammatory mediators from the circulation attenuates the inflammatory response in sepsis. This review summarizes the theoretical basis, and the experimental and clinical results published to date with the use of haemoperfusion. Although most of the studies show positive results, some doubts have arisen about the suitability of the methods described (small number of cases, low quality of the experimental design, and excessive mortality in the control groups). There are also some inconsistencies regarding the theoretical basis of its use (lack of positive effects after the removal of endotoxin from the circulation using alternative mechanisms, discrepancies regarding the best moment to initiate the therapy, unexplained beneficial effects in the absence of increased endotoxin levels). It is the opinion of the authors that haemoperfusion represents a promising therapy for the treatment of sepsis, but consider that its usefulness requires confirmation in well designed studies before being included in protocols(AU)

Descripción de los efectos hemodinámicos y respiratorios del tratamiento mediante hemoperfusión con polimixina B en pacientes con shock séptico de origen abdominal / Description of the hemodynamic and respiratory effects of hemoperfusion treatment with polymyxin B in patients with abdominal septic shock

En 11 de los 13 pacientes se realizaron 2 ciclos completos con el cartucho de polimixina y, en los otros 2, un solo ciclo. Tras este tratamiento, la presión arterial media (PAM) se incrementó (p = 0,003), disminuyó la necesidad de noradrenalina (p = 0,003) y la relación PO2/FiO2 aumentó (p = 0,02). La utilización precoz de hemoperfusión con polimixina en pacientes con shock séptico de origen intraabdominal puede mejorar de manera significativa las funciones hemodinámica y respiratoria. El objetivo de este estudio es describir la evolución hemodinámica, la dependencia a drogas inotrópicas y vasoactivas y analizar la relación PO2/FiO2 en 13 pacientes con shock séptico de origen abdominal después de emplear el tratamiento con hemoperfusión de polimixina. El tratamiento con hemoperfusión de polimixina es una terapia indicada para pacientes con sepsis grave o shock séptico de origen abdominal que no responden adecuadamente a la terapia convencional(AU)

The objective of this study is to describe the hemodynamic effects, inotropic and vasoactive drug dependence, and to analyze the PO2/FiO2 ratio in 13 patients with septic shock of abdominal origin after hemoperfusion treatment with polymyxin-B. Treatment with polymyxin hemoperfusion therapy is indicated for patients with severe sepsis/septic shock of abdominal origin who do not respond adequately to conventional therapy. Two complete cycles with polymyxin cartridge were performed on 11 of the 13 patients, and a single cycle on the other O2. After treatment, the mean airway pressure (MAP) was increased (P=.003), the need for norepinephrine decreased (P=.003), and the PO2/FiO2 ratio increased (P=.02). The use of polymyxin hemoperfusion in patients with septic shock of intra-abdominal origin can significantly improve hemodynamic and respiratory functions(AU)

The lipid- and lipoprotein- [LDL-Lp(a)] apheresis techniques. Updating.

Therapeutic plasmapheresis allows the extracorporeal removal of plasmatic lipoproteins (Lipid-apheresis) (LA). It can be non selective (non specific), semi - selective or selective low density lipoprotein-lipoprotein(a) (specific [LDL- Lp(a)] apheresis) (Lipoprotein apheresis, LDLa). The LDL removal rate is a perfect parameter to assess the system efficiency. Plasma-Exchange (PEX) cannot be considered either specific nor, selective. In PEX the whole blood is separated into plasma and its corpuscular components usually through centrifugation or rather filtration. The corpuscular components mixed with albumin solution plus saline (NaCl 0.9%) solution at 20%-25%, are then reinfused to the patient, to substitute the plasma formerly removed. PEX eliminates atherogenic lipoproteins, but also other essential plasma proteins, such as albumin, immunoglobulins, and hemocoagulatory mediators. Cascade filtration (CF) is a method based on plasma separation and removal of plasma proteins through double filtration. During the CF two hollow-fiber filters with pores of different diameter are used to eliminate the plasma components of different weight and molecular diameter. A CF system uses a first polypropylene filter with 0.55 µm diameter pores and a second one of diacetate of cellulose with 0.02 µm pores. The first filter separates the whole blood, and the plasma is then perfused through a second filter which allows the recovery of molecules with a diameter lower than 0.02 µm, and the removal of molecules larger in diameter as apoB100-containing lipoproteins. Since both albumin and immunoglobulins are not removed, or to a negligible extent, plasma-expanders, substitution fluids, and in particular albumin, as occurs in PEX are not needed. CF however, is characterized by lower selectivity since removes also high density lipoprotein (HDL) particles which have an antiatherogenic activity. In the 80's, a variation of Lipid-apheresis has been developed which allows the LDL-cholesterol (LDLC) (-61%) and Lp(a) (-60%) removal from plasma through processing 3 liters of filtered plasma by means of lipid-specific thermofiltration, LDL immunoadsorption, heparin-induced LDL precipitation, LDL adsorption through dextran sulphate. More recently (90's) the DALI®, and the Liposorber D® hemoperfusion systems, effective for apoB100- containing lipoproteins removal have been developed. All the above mentioned systems are established LDL-apheresis techniques referable to the generic definition of LDLa. However, this last definition cannot describe in an appropriate manner the removal of another highly atherogenic lipoprotein particle: the Lp(a). Thus it would be better to refer the above mentioned techniques to the wider scientific and technical concept of lipoprotein apheresis.

Beyond dialysis: current and emerging blood purification techniques.

Extracorporeal blood purification using various techniques and hardware is a major part of the modern day practice of clinical nephrology. Although the various modalities of hemodialysis and hemofiltration are the most commonly used extracorporeal therapies in clinical nephrology, blood purification using other techniques have become necessary to remove pathogenic, toxic, or waste substances not easily cleared by hemodialysis or hemofiltration due to factors such as molecular size, protein binding, and lipid solubility. The following review is an up to date summary of extracorporeal therapies, beyond hemodialysis and hemofiltration, in current clinical use as practiced by nephrologists and others in the United States and beyond. This comprises therapeutic apheresis (plasma exchange and cytapheresis), plasma adsorption, hemoperfusion, and the bio-artificial devices.

Use of hemodialysis and hemoperfusion in poisoned patients.

Extracorporeal removal techniques such as hemodialysis, charcoal hemoperfusion, and peritoneal dialysis have been used to remove toxins from the body. To define trends in the use of these techniques for toxin removal, we analyzed the 19,351 cases requiring extracorporeal removal reported to U.S. poison centers from 1985-2005. The number of such patients who received hemodialysis, excluding those with other medical indications, (normalized per million calls) increased from 231 to 707 whereas hemoperfusion decreased from 53 to 12 in the years 1985-2005. Peritoneal dialysis decreased from 2.2 in 1985 to 1.6 in 1991. The most common toxins removed by hemodialysis were lithium and ethylene glycol. There were more dialysis treatments for poisonings with valproate and acetaminophen in 2001-2005 than for methanol and theophylline, although hemodialysis for acetaminophen removal is generally not recommended. Theophylline was the most common toxin removed by hemoperfusion from 1985-2000, but carbamazepine became the most frequent toxin for removal during 2001-2005. Our study shows that the profile of toxins and the type of extracorporeal technique used to remove the toxins have changed over the years.

The future of extracorporeal support.

Extracorporeal therapy has expanded significantly over the past few decades from solely artificial renal replacement therapy. In patients with multiple organ dysfunction syndrome, it becomes necessary to provide multiple organ support therapy. Technological advances have opened the door to a multifaceted intervention directed at supporting the function of multiple organs through the treatment of blood. Indications for "old" therapies such as hemofiltration and adsorption have been expanded, and using these therapies in combination further enhances blood detoxification capabilities. Furthermore, new devices are constantly in development. Nanotechnology allows us to refine membrane characteristics and design innovative monitoring/biofeedback devices. Miniaturization is leading down the path of wearable/implantable devices. With the incorporation of viable cells within medical devices, these instruments become capable not only of detoxification but synthetic functions as well, bringing us closer to the holy grail of complete replacement of organ function. This article provides a brief overview of current and future direction in extracorporeal support in the critical care setting.

The place of early haemoperfusion with polymyxin B fibre column in the treatment of sepsis.

Direct haemoperfusion with polymyxin B-immobilized fibre (PMX-F) is a promising treatment for Gram-negative sepsis in critically ill patients. Indeed, it has been used routinely in Japan for a decade. Recent evidence presented in this journal suggests that PMX-F can have a positive impact on outcome in patients with sepsis, although other reports in the literature have presented confusing or even conflicting results. This commentary considers whether the available evidence allows us to establish an appropriate role for PMX-F treatment in sepsis and what further work is needed.

Activated charcoal microcapsules and their applications.

Activated charcoal, long known to the ancients as a substance of therapeutic value in a variety of maladies, has recently been "rediscovered" to be of great value in medical applications. Activated charcoal hemoperfusion is effective in blood purification for removal of various circulating toxic materials and waste metabolites, directly. However, particulate release and platelet adhesion prevent its continued clinical use. Polymeric coatings or microencapsulation of charcoal within polymers have improved their blood compatibility. Chitosan encapsulated activated charcoal (ACCB) beads have been extensively investigated in our group for the removal of various toxins such as urea, creatinine, uric acid, bilirubin, etc. This article highlights various methods of microencapsulation procedures of activated charcoal and the importance of this novel material for a variety of biomedical applications. Further, this review provides an insight to the future perspectives for using them in clinical practice.

Haemoperfusion: a useful therapy for a severely poisoned patient?

Although it is many years since a haemodialysis and haemoperfusion over uncoated and later coated charcoal columns have been used for the treatment of intoxicated patients, the clinical efficacy of these extracorporeal techniques in the treatment of severely poisoned patients remains a matter of debate. Some of the reasons for this controversy may be the indiscriminate use of haemoperfusion in any form of intoxication, the lack of well-controlled studies and the wrong interpretation of the high haemoperfusion clearance values sometimes obtained. Simple pharmacokinetic principles are applied to this type of treatment and some practical guidelines as to how and when haemoperfusion should be applied or presented are reviewed. The limited place of haemoperfusion in the treatment of severe poisoning, its further declining use in the future, at least in its present design, and some promising new treatments are emphasized.

Haemoperfusion in the management of end-stage renal disease.

Haemoperfusion, mainly in the form of activated charcoal haemoperfusion, has been investigated for the treatment of end-stage renal disease. Short-term studies have demonstrated that charcoal haemoperfusion devices in combination with haemodialysis are safe, produce reversal of certain symptoms of uraemia, but do little to define the role of haemoperfusion in the management of end-stage renal disease. Long-term studies, however, have demonstrated that reduction in dialysis time may be achievable with the addition of charcoal haemoperfusion to dialysis or ultrafiltration in the routine management of the dialysis patient. However, since charcoal as an adsorbent fails to remove important uraemic toxins such as water, urea, electrolytes, phosphate and sulphate, haemoperfusion does require the addition of dialysis or ultrafiltration for the removal of such toxins. In future, haemoperfusion will probably consist of sorbents added to an ultrafiltration or dialysis device to form a hybrid artificial organ that will combine sorbents suitable for removal of urea, phosphate, etc., and will be a useful treatment in the routine management of end-stage renal disease.

Hemoperfusion in 1981.

The present status of hemoperfusion using the principle of artificial cells is described in detail using coated charcoal hemoperfusion as an example. The laboratory and clinical results show that in 1981 increasing numbers of new commercial models are approaching the efficiency and blood compatibility of the ACAC laboratory system. The results of hemoperfusion for uremia, acute intoxication and hepatic coma are analyzed. Other approaches are briefly discussed.

Blood purification by haemoperfusion.

Blood purification by haemoperfusion is considered, principally in terms of the European effort. The development of the different approaches which have emerged and the assessment of adsorbents and devices are described. The application of haemoperfusion is examined in the areas of acute poisoning, liver failure and uraemia.