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Application of a rat model of streptococcal shock to evaluate on-line hemoperfusion and removal of circulating superantigens.

OBJECTIVE: To evaluate the efficacy of on-line hemoperfusion for the removal of circulating superantigens in a rat model of streptococcal shock. DESIGN: In vitro and experimental animal studies. SETTING: University research laboratories. INTERVENTIONS: Chemically modified polystyrene-based composite fiber reinforced with polypropylene was formulated in discs and used to evaluate the removal of superantigenic toxins from culture supernatants in vitro, and from blood in vivo. MEASUREMENTS AND MAIN RESULTS: Incubation of streptococcal supernatant with a single disc reduced the concentration of the superantigen streptococcal pyrogenic exotoxin A from 90.9 +/- 12.7 ng/mL with the control fiber to 32.5 +/- 3.6 ng/mL with active fiber (p <.001). The active discs also brought about a dose-dependent reduction in mitogenic activity that was highly significant (counts reduced from 82,133 +/- 2747 using three control discs to 26,307 +/- 3547 with three active discs [p <.001]). Beginning 6 hrs after infection, animals were hemoperfused for 3 hrs over columns containing control or active fiber. At the end of the treatment period, there was a significant decrease in the number of circulating bacteria in the active group (3.5 x 10(4) vs. 3.1 x 10(3) colony-forming units/mL, p<.05). However, bacterial counts subsequently increased and by 15 hrs and at all subsequent time points, the number of circulating bacteria was no different between the two groups. There was a highly significant and sustained difference in circulating streptococcal pyrogenic exotoxin A levels between the groups. Streptococcal pyrogenic exotoxin A levels at 9 hrs were 19.9 ng/mL in the controls vs. 2.1 ng/mL in the active group (p =.05). Animals perfused over active fibers had a highly significant survival advantage compared with control or nonperfused groups (p <.01). CONCLUSIONS: Hemoperfusion and on-line removal of superantigens merits further study as a possible treatment strategy for streptococcal shock syndromes. The mechanism by which the fibers are operating requires further investigation.

Animals↗

Digoxin removal from an anephric patient by hemoperfusion over XAD-4.

Removal of digoxin by hemoperfusion over Amberlite XAD-4 was determined in a functionally anephric patient. During four hours of hemoperfusion, 50.45 microgram of digoxin were removed by the column and serum digoxin concentrations decreased by 0.2 ng/ml after the post-hemoperfusion reequilibration was complete.

Digoxin↗

The use of hemoperfusion as an adjunct to hemodialysis.

Studies are reported on the use of short dialysis, sequential ultrafiltration/short dialysis and hemoperfusion in chronic renal failure. Short dialysis (less than 12 hours/week) is a satisfactory regime with good patient acceptance, adequate small and middle molecule clearance and control of fluid and blood pressure. Sequential ultrafiltration in the first hour improves fluid removal and reduces the side effects of dialysis. The addition of hemoperfusion increases clearance of small and middle molecules and has little effect on the osmolality of the serum. Thus, it does not increase the side effects of dialysis. Preliminary results suggest that hemoperfusion may be useful in the treatment of chronic renal failure in combination with ultrafiltration and dialysis.

Carbon↗

Acid citrate dextrose reduces platelet retention during in vitro and in vivo dog hemoperfusion: a comparative study of different charcoal adsorbers.

Hemoperfusion through charcoal adsorbers has often been proposed for use in exogenous and endogenous intoxication. A serious drawback of this technique is the often encountered loss of platelets and leucocytes. In vitro hemoperfusion studies with heparinized human blood and in vivo hemoperfusion of heparinized Labrador dogs through different types of charcoal adsorbers (Becton-Dickinson [B-D], Gambro, Haemocol) clearly demonstrated that addition of the anticoagulant acid citrate dextrose (ACD) might reduce the loss of platelets. ACD seemed to have no distinct influence on leucocyte retention.

Adsorption↗

The thin-film adsorber hemoperfusion device: development and evaluation of clearance characteristics.

A novel hemoperfusion device was developed by embedding powered activated charcoal in thin (150 micrometer) films of cellulose nitrate. These films were sprinkled with small particles of granular charcoal and wound into spools, which were then placed in a plastic housing. The use of powdered charcoal exploits the enormous rate-of-uptake advantage of powered charcoal over the granular sorbents found in other hemoperfusion devices. The granular carbon sprinkled on the films was primarily to provide spacing between adjacent film layers for adequate fluid flow; the granules did enhance long-term uptake in addition. Clearance tests with this novel "thin-film adsorber," using sodium salicylate, sodium barbital, and creatinine, showed that its rate of solute adsorption, particularly at early times, was consistently very high. This type of hemoperfusion device is a promising alternative to the granular-sorbent types of devices currently available, especially when maximal solute removal during the early stages of treatment is mandated.

Adsorption↗

The thin-film adsorber hemoperfusion device: detailed mass transfer and flow characteristics.

Further testing and evaluation of the thin-film adsorber (TFA) type of hemoperfusion device is reported here to complement an earlier paper describing the development of these devices and clearance tests performed with them. The present paper describes the results of pressure drop tests, flow uniformity tests, and detailed studies of the mass transfer characteristics of the components of the TFA units. The TFA units consist of powdered activated charcoal embedded in thin films of cellulose nitrate. These films are sprinkled with small particles of granular charcoal and then wound into spools, which are then placed in a plastic housing. The use of powdered charcoal exploits the enormous rate-of-uptake advantage of powdered charcoal over the granular sorbents used in other hemoperfusion devices. The present tests showed that the pressure drops in the TFA devices are intrinsically low, but that their priming volumes are only marginally acceptable. Significant flow nonuniformities also exist. Despite this, the overall mass transfer resistance values for the TFA devices are lower than those for available commercial hemoperfusion units. Measurements of diffusion coefficients in the carbon and in the carbon-loaded polymer film showed that in the carbon-loaded film, the slowest diffusion step involves the carbon particles themselves. Other tests disclosed that the liquid external to the film (i.e., in the flow spaces) offers even greater mass transfer resistance than does the carbon-loaded film. Further evaluations of the TFA type of device are suggested, particularly concerning its thrombogenic properties.

Adsorption↗

Lidocaine removal during resin hemoperfusion for phenobarbital intoxication.

A deeply comatose patient with severe phenobarbital intoxication was hemoperfused with an Amerlite XAD-4 column. She was receiving lidocaine for ventricular ectopy. The rate of lidocaine infusion had to be increased to control ventricular arrhythmias during hemoperfusion. Plasma clearance for lidocaine by the column was 122 ml/min at initiation and 75 ml/min at 2 h. These findings suggest that an increment in lidocaine infusion may be needed during resin hemoperfusion in patients receiving this drug because of its removal by the column.

Female↗

A new DNA immune adsorbent for hemoperfusion in SLE therapy: a clinical trial.

This investigation studied the preparation and clinical trial of DNA immunoadsorbent for hemoperfusion in systemic lupus erythematosus (SLE) therapy. DNA was complexed with blue tetrazolium (BT), then mixed with collodion, and finally adsorbed on macroporous spherical polymeric adsorbent. The percentage of DNA thus immobilized was 98-98.5%, and no release was detected during hemoperfusion. A patient with severe SLE was treated with the above adsorbent in hemoperfusion. The patient was in coma, with high anti-DNA antibody and abnormal immune complex levels, which fell sharply from 56.34% to 0.8% after 2.5 h of whole-blood hemo perfusion. There were no major clinical complications, and 2 weeks later, her proteinuria level became normal and immune complex levels were sustained. She was then discharged from the hospital and has been in good health for more than 1 year.

Adult↗

Development of a potassium-specific adsorbent for direct hemoperfusion.

Direct hemoperfusion (DHP) over an exchange resin for sodium is capable of rapidly lowering an elevated serum potassium level but has not been used clinically because of subsequent electrolyte abnormalities. After the completion of detailed in vitro studies, we developed a sodium/calcium/magnesium exchange resin mixture specifically to remove potassium from the blood. The mixture, which consisted of exchange resins for sodium (48%), calcium (48%), and magnesium (4%), gave the most satisfactory results in vitro. DHP through these resin-mixture columns for 2 h reduced elevated plasma potassium levels (6.7 +/- 1.1 to 3.5 +/- 0.6 mEq/L, p < 0.001) in anephric dogs without including any significant change in the levels of sodium, calcium, magnesium, albumin, total protein, or cholesterol. The platelet losses and changes in the plasma free hemoglobin levels observed were similar to those found with activated charcoal hemoperfusion. These results suggest that this resin hemoperfusion may be useful in patients with acute hyperkalemia.

Animals↗

LDL hemoperfusion--a new procedure for LDL apheresis: biocompatibility results from a first pilot study in hypercholesterolemic atherosclerosis patients.

Current lipid apheresis techniques can remove atherogenic lipoproteins only from plasma. The initial mandatory separation of plasma and blood cells renders the extracorporeal circuit complex. We recently described the first clinical application of a new lipid adsorber that adsorbs low-density lipoprotein (LDL) and lipoprotein (a) (Lp[a]) directly from whole blood. In continuation of our work, this paper describes the clinical biocompatibility of this new LDL hemoperfusion system. In a 2 center phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation protocol consisted of an initial heparin bolus followed by an acid citrate dextrose-A (ACD-A) infusion during the treatment. One patient blood volume was treated per session. All sessions were clinically uneventful. No signs of hemolysis or extracorporeal clot formation could be detected, and cell counts remained virtually constant. In a subgroup of patients (n = 4-6), further biocompatibility parameters were studied. Activation of leukocytes (elastase release), thrombocytes (beta-thromboglobulin [beta-TG] extrusion), and monocytes (interleukin (IL)-1beta and IL-6) were minimal. Complement activation (C3a and C5a generation) was negligible. The chosen anticoagulation protocol was both safe (constant ionized calcium levels) and effective (low thrombin-antithrombin formation). In summary, within the scope of a first pilot study, this new LDL hemoperfusion procedure combined the features of excellent clinical tolerance, good biocompatibility, and ease of handling. Phase III clinical trials will have to show whether these encouraging preliminary results can be corroborated in a larger patient population.

Acrylic Resins↗

Polymyxin B-immobilized fiber hemoperfusion after emergency surgery in patients with chronic renal failure.

The purpose of this study was to evaluate the effect of direct hemoperfusion using a Polymyxin B (PMX) immobilized fiber column in septic patients with chronic renal failure after emergency surgery. Twenty-four renal failure patients, including 19 dialysis patients, with sepsis or septic shock were treated with direct hemoperfusion after emergency surgery. The 24 consecutive patients included nine with necrotic enterocolitis, six with colonic perforation due to diverticulitis, three with ruptured suture after colectomy, one with duodenal perforation, four with blood access infection, and one with an infected abdominal aortic aneurysm. The acute physiology and chronic health evaluation II score ranged from 13 to 26 (19 +/- 3). After completion of the first and the second hemoperfusion, mean blood pressure was significantly elevated from 69 +/- 12 mm Hg to 89 +/- 15 mm Hg and from 78 +/- 14 mm Hg to 95 +/- 13 mm Hg, respectively (P < 0.01). In addition, the catecholamine dosage needed to maintain the circulation could be decreased markedly after the treatment. The blood concentration of endotoxin in patients with Gram-negative sepsis, before and after the treatment, significantly decreased from 36 +/- 19 pg/mL to 19 +/- 19 pg/mL (P < 0.05). PMX was effective in patients with Gram-positive sepsis as well as Gram-negative sepsis. The 28-day mortality rate in patients who had emergency abdominal surgery was 10% (2/20), whereas that in patients with dialysis access infection was 50% (2/4). There was a significant difference in the Sequential Organ Failure Assessment (SOFA) score of all patients before and after treatment using PMX (9.2 +/- 3.3 vs. 7.5 +/- 3.5, P < 0.05). Furthermore, the SOFA score of survivors decreased significantly after PMX treatment (8.4 +/- 3.5 vs. 6.7 +/- 2.6, P < 0.01). Our results suggest that the early application of PMX may prevent multiple organ failure and improve survival in patients with chronic renal failure and sepsis/septic shock after emergency abdominal surgery, regardless of the type of pathogenic bacteria involved.

Adult↗

Regional flow adjusted hemoperfusion during coronary angioplasty: circulatory support/myocardial protection.

Routine percutaneous transluminal coronary angioplasty catheters are adequate and demonstrate high success rates in balloon angioplasty with stable patients. Active hemoperfusion seems to offer an advantage in patients with hemodynamic instability. Active hemoperfusion provides myocardial protection during coronary interventions and can be applied in conjunction with routine angioplasty equipment. When compared with other devices demonstrating clinical utility in a supported angioplasty setting, this flow adjustable active antegrade hemoperfusion pump appears reliable, simple to use, cost-effective, and requires much less instrumentation than the more bulky CPS systems.

Angioplasty, Balloon, Coronary↗

Acute hemolysis with acute renal failure in a patient with valproic acid poisoning treated with charcoal hemoperfusion.

Hemoperfusion consists of the passage of anticoagulated blood through a column containing adsorbent particles. It was introduced in 1940 and refined from 1950 to 1970, and then introduced clinically for the treatment of acute intoxications between 1970 and 1980. Life-threatening valproic acid toxicity is an indication for coated charcoal hemoperfusion usually accomplished without complications, but we report a case of acute severe intravascular hemolysis during the time of hemoperfusion with coated charcoal column.

Acute Kidney Injury↗

Clinical evaluation of diagnostic hemoperfusion for in vivo enrichment of bacteria and fungi in comparison with a conventional blood culture technique.

The hemoperfusion module, a newly developed technique for recovering pathogenic microorganisms from patients suffering from septicemia, was compared with conventional blood cultures. The module was interconnected with the extracorporeal circulation of 92 predominantly hemodialyzed patients. Nearly 12 liters of flowing blood (up to 200 ml min-1; mean running time, 60 min) came in contact with the coated charcoal. Of 99 modules examined, 44 (44.7%) yielded positive cultures and contained 54 potentially pathogenic bacteria or fungi (22 species). Only 32 of 190 (16.8%) conventional blood cultures were positive and contained 37 microorganisms (10 species). Even when patients were receiving antibiotic treatment, the frequency of isolation was significantly higher in hemoperfusion (21 of 44 modules positive, 47.7%) than in conventional blood cultures (10 of 88 cultures positive, 11.4%). In contrast, 23 of 55 modules (41.8%) and 22 of 102 conventional blood cultures (21.6%) were positive when patients were not treated with antibiotics prior to blood sampling. Altogether, hemoperfusion modules appeared to be superior to and more sensitive than the conventional blood cultures used and seemed to be a valuable tool for detecting septicemia.

Adult↗

Hemoperfusion with polymyxin B-immobilized fiber attenuates the increased plasma levels of thrombomodulin and von Willebrand factor from patients with septic shock.

AIMS: The present study assessed whether plasma levels of thrombomodulin and von Willebrand factor (vWF) are altered in patients with septic shock and whether treatment with polymyxin B-immobilized fiber (PMX-F) affects these levels. METHODS: Twenty-four patients with septic shock and 20 normal healthy controls were included in this study. Plasma levels of thrombomodulin and vWF were measured by enzyme immunoassay (EIA). The treatments with direct hemoperfusion using PMX-F column on patients with septic shock were repeated twice for 2 h each. Healthy controls were not subjected to hemoperfusion. RESULTS: 13 of 24 patients with septic shock survived (survival rate was 54.2%). Levels of blood endotoxin decreased significantly from 41.2 +/- 4.8 pg/ml at baseline to 13.2 +/- 3.6 pg/ml after direct hemoperfusion. Systolic blood pressure increased significantly from 82 +/- 6 mm Hg at baseline to 118 +/- 12 mm Hg after treatment. The patients with septic shock demonstrated significantly increased plasma levels of thrombomodulin (p < 0.001) and vWF (p < 0.001) compared with those in healthy controls. These increased levels of plasma thrombomodulin and vWF in patients with septic shock decreased significantly after treatment with PMX-F (p < 0.01). CONCLUSION: These data suggest that plasma thrombomodulin and vWF may be related to septic shock and that PMX-F is effective in reducing these factors in patients with septic shock.

Adult↗

Fixed-bed uncoated charcoal hemoperfusion in the treatment of intoxications: animal and patient studies.

We examined the efficacy of a new, fixed-bed, uncoated charcoal device in experimentally intoxicated dogs and in drug-intoxicated as well as chemically poisoned patients. In the animal studies, 4 h of hemoperfusion resulted in a significant decrease in the blood level of phenobarbital, salicylate, pentobarbital and glutethimide. The drug clearances varied between 97 +/- 10 and 129 +/- 6 ml/min. However, the total amount of drug removed was higher for phenobarbital and salicylate which have a small apparent volume of distribution (AVD) than for pentobarbital and glutethimide which have an AVD greater than total body water. We next treated 14 patients suffering from a wide variety of intoxications. Patients intoxicated with phenobarbital, methsuximide, chlordane and Amanita muscaria all showed a significant improvement in their clinical status. Patients intoxicated with ethchlorvynol, glutethimide, methaqualone, podophyllin and fluoroacetamide did not improve. Charcoal hemoperfusion may be useful in patients poisoned with drugs characterized by an AVD smaller than total body water. No major complications were encountered during the hemoperfusions.

Adolescent↗

Aluminum removal with hemodialysis, hemofiltration and charcoal hemoperfusion in uremic patients after desferrioxamine infusion. A comparison of efficiency.

In order to compare the effectiveness of aluminum removal in uremic patients during extracorporeal treatment, 17 patients with endstage renal failure were given a desferrioxamine infusion of 40 mg/kg body weight after an ordinary dialysis treatment. Forty-eight hours later 7 patients were treated with hemodialysis, 6 with hemofiltration and 4 with a combination of hemodialysis and hemoperfusion. The clearance of aluminum was measured at different intervals. It was found that the aluminum clearance was 75 +/- 18 ml/min in hemofiltration compared to 30 +/- 10 ml/min in hemodialysis (p less than 0.001). A combination of hemodialysis and hemoperfusion with a charcoal column containing 100 g activated charcoal in series gave a total aluminum clearance of 56 +/- 11 ml/min. The total amount of aluminum in the ultrafiltrate after hemofiltration was found to be approximately 3 times as high (1,728 +/- 156 micrograms) as the total amount of aluminum in the hemodialysis water that had passed a single pass system during a 4-hour dialysis (576 +/- 104 micrograms). Our results indicate that hemofiltration or a combination of hemodialysis and hemoperfusion should be used to remove aluminum in patients with signs of severe aluminum accumulation such as encephalopathy or painful bone disease, because these methods are 2-3 times as effective as ordinary hemodialysis. In patients where aluminum has been accumulated but no severe symptoms occur hemodialysis gives a significant clearance of the aluminum desferrioxamine complex.

Aluminum↗

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.

Albumins↗