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Evaluation of a new coated charcoal for hemoperfusion in uremia.

A new coated charcoal for hemoperfusion in uremia was investigated in 14 patients with end stage renal disease who underwent hemoperfusion or combined hemodialysis-hemoperfusion (39 seances). Investigations concerned removal of small molecules, coagulation and hematological status and amino acids and some hormones equilibrium. Clinical observations were also made in all patients. The methacrylate-coated charcoal enabled the removal of "toxins" up to 5000 daltons and the total solute removal did not significantly differ from previous hemoperfusion systems. However, the new coating membrane showed improved biocompatibility, in terms of clinical side effects and/or platelet and fibrinogen alterations.

Biocompatible Materials↗

In vitro adsorption spectrum of plasma amino acids by coated charcoal hemoperfusion.

In order to clarify whether coated charcoal hemoperfusion is capable of normalizing amino acid disturbances in hepatic coma, in vitro adsorption and in vitro hemoperfusion studies were carried out. We have found that collodion-coated activated charcoal beads preferentially removed much more aromatic acids (AAA) than branched chain amino acids (BCAA). In the in vitro adsorption experiment with 50 microM amino acid standards aqueous solution, 99% of AAAs were removed by charcoal while only 50 to 81% of BCAAs were removed. As the concentration of amino acids in solution was doubled from microM to 100 microM, BCAA removal was halved while about 90% of AAA was still being removed. In vitro hemoperfusion with heparinized blood from hepatic failure rats, the clearance and the removal of AAAs were significantly greater than those of BCAAs. Consequently, the molar ratio of BCAA over AAA was markedly improved from the initial 1.09 to 3.87 after 60 min of hemoperfusion. Thus, we have demonstrated the preferential adsorption of aromatic amino acids by collodion-coated charcoal beads. The correction of BCAA/AAA molar ratio is also demonstrated.

Adsorption↗

Hemoperfusion in theophylline neurotoxicity.

Four patients with severe theophylline toxicity (theophylline levels of 60 to 180 micrograms/ml) are reported. Three patients with neurotoxicity were treated with hemoperfusion. Two of these were hemoperfused early after the onset of seizures; they recovered with no neurologic deficit. In the third patient hemoperfusion was delayed for 16 hours after uncontrolled seizures; severe brain damage resulted. The fourth patient, who had the highest peak theophylline level but no seizures, was successfully treated with conservative management and peritoneal dialysis. The role of hemoperfusion in severe theophylline intoxication is discussed.

Age Factors↗

Influence of hemoperfusion with XAD-4 resin on the concentration of biologic constituents in the blood.

13 patients, who had been subjected to hemoperfusion with Amberlite XAD-4 resin (Haemoresin, Fa. Braun), because of acute intoxications, were examined for the adsorption of bioactive material from the blood. A mean treatment period of four hours at a blood flow rate of 200 ml/min. resulted in a marked thrombocyte decrease by 43% and changes in the concentrations of proteins, complement components C3 and C4 (16-26%) triglycerides (33%), aldosterone (33%) and testosterone (20%). Low molecular weight substances and electrolytes, however, were only slightly or not affected. Thus hemoperfusion system with its poor biocompatibility and inability to remove BUN, electrolytes and water is only suitable for short-term treatment and cannot be used without detailed control of possible side effects and perhaps substitution for treatment of chronic renal or hepatic failure. Hemoperfusion has proved an efficient method of treating various exogenous intoxications. The adsorption of biologically active material from the blood constitutes several side effects which contraindicate long-term treatment, above all of endogenous intoxications such as chronic renal failure and hepatic failure. With the type of adsorber used - various charcoal preparations, resins etc. such as uncoated material or coated with different substances - these side effects vary and have not yet been investigated in a systematic, comparative and comprehensive way. The present investigations are meant to check the adsorption behaviour of Amberlite XAD-4 Resin in vivo towards some selected blood constituents and the influence of hemoperfusion on the concentrations.

Adolescent↗

Fixed-bed charcoal hemoperfusion. Treatment of drug overdose.

Fixed-bed activated charcoal cartridges were used for hemoperfusion in the treatment of 54 patients with overdose of one or more drugs, including barbiturate, glutethimide, ethchloryvnol, meprobamate, methyprylon, methaqualone, salicylate, and diazepam. The most dramatic improvement was noticed in patients with phenobarbitol intoxication; they were admitted in stage 3-4 coma and were either awake or arousable by verbal communication at the end of 1 1/2 to 3 1/2 hours of hemoperfusion. Other intoxications improved slowly and required longer duration of treatment. The clearance rates of the drugs with hemoperfusion were greater than those usually achieved with hemodialysis. The data demonstrate the efficacy and usefulness of charcoal hemoperfusion for the management of drug overdose.

Adolescent↗

Severe meprobamate intoxication treated by hemoperfusion over amberlite resin.

A 36-year-old female was treated successfully by hemoperfusion over Amberlite XAD-4 resin after ingestion of 40 gm of meprobamate. Hemoperfusion was started five hours after the ingestion. At that time the patient was in deep coma. The patient was treated by hemoperfusion for five hours, at the end of which time she was awake. Meprobamate clearance over the resin was about 290 mg/min. There were no bleeding complications. It is concluded that hemoperfusion over amberlite XAD-4 resin is a highly effective method in the treatment of severe cases of meprobamate intoxication.

Adult↗

Use of mechanical devices for distal hemoperfusion during balloon catheter coronary angioplasty.

Previous attempts to protect the dependent myocardium during balloon catheter coronary angioplasty in animals and humans have had generally unsatisfactory results. This paper summarizes the authors' experience in investigating commercially available mechanical pumps for distal coronary hemoperfusion during balloon angioplasty. Both roller and piston pumps can attain adequate distal perfusion without significant side effects in the majority of patients. Our goal was to suppress angina for at least 5 min to prolong balloon inflation in awake patients. Minor T-wave changes without concomitant angina pectoris can be expected when the distal coronary bed is perfused with hypothermic blood. Side branch occlusion by the inflated balloon prevents effective protection of the corresponding part of the dependent myocardium during distal hemoperfusion, which may result in persistent angina and ST-T changes uncorrected by increasing the hemoperfusion rate. Distal coronary diffuse spasm, rare and transient, was the only immediate complication of this procedure. It is suggested that intense local wall stimulation could occur with a higher flow rate (jet effect). Improved balloon catheter pressure/flow characteristics and on-line continuous mechanical pumps should soon make distal coronary hemoperfusion through balloon catheters an accepted clinical technique.

Adult↗

Removing substances from blood by affinity chromatography. II. Removing bilirubin from the blood of jaundiced rats by hemoperfusion over albumin-conjugated agarose beads.

In vitro studies indicate that bilirubin and other albumin-bound substances can be efficiently removed from plasma by filtration over albumin-conjugated agarose beads. The effectiveness of this technique in vivo was investigated in rats by using a closed extracorporeal hemoperfusion system. Five Gunn rats whose endogenous bilirubin pool had been labeled with [(3)H]bilirubin and five Sprague Dawley rats with surgically created biliary obstruction were chosen as models of unconjugated and conjugated hyperbilirubinemia. Indocyanine green was injected into rats and its removal also studied. In the Gunn rats, 98% of the bilirubin was removed from plasma during the initial pass over the column as determined isotopically and chemically. Plasma bilirubin levels fell more than 70% from 8.2+/-1.6 mg/100 ml (mean+/-SD) to 2.6+/-0.5 mg/100 ml during a 1-h hemoperfusion. An average of 1,061 mug of bilirubin was recovered from the columns, representing 22.5+/-4.2% of the total exchangeable bilirubin pool and 96+/-36.4% of the plasma pool. Results were similar in the rats with biliary obstruction and in those given indocyanine green. Normal Sprague Dawley rats experience minimal changes in formed blood elements, electrolytes, and proteins as the result of hemoperfusion. When the total volume of the column did not exceed 51% of the estimated blood volume of the animal, the survival rate was 100% in 20 studies, and the procedure was without observable ill effect. Extrapolation of both in vitro and in vivo data to man suggests that extracorporeal hemoperfusion over albumin-agarose columns may be a practical means of assisting hepatic excretory function.

Animals↗

Efficacy of activated charcoal hemoperfusion in removing lethal doses of barbiturates and salicylate from the blood of rats and dogs.

Rats were injected intraperitoneally with lethal doses of sodium pentobarbital (115 mg/kg) or a lethal mixture of sodium salicylate (500 mg/kg) and sodium acetazolamide (25 mg/kg). Within about 20 min, part of each group was connected to an extracorporeal circuit containing uncoated activated charcoal and part to an empty control circuit. After a 90-min hemoperfusion, the treated groups showed a significantly decreased mortality (58% to 14% for pentobarbital; 100% to 0% for salicylate). Dogs were injected intravenously with lethal doses of sodium phenobarbital (175 mg/kg). One group was treated by hemoperfusion through an empty device in a control extracorporeal circuit, a second group was treated with loose-bed activated charcoal devices, and a third group with fixed-bed activated charcoal devices. For both the fixed and loose-bed devices, a 5-h hemoperfusion markedly decreased mortality (100% to less than or equal to 15%). The lethal combination of salicylate and closed-circuit methoxyflurane anesthesia was also successfully treated in dogs. This study clearly demonstrates the lifesaving potential of uncoated activated charcoal hemoperfusion.

Animals↗

The use of calcium chelating agents and prostaglandin E to eliminate platelet and white blood cell losses resulting from hemoperfusion through uncoated charcoal, albumin-agarose gel, and neutral and cation exchange resins.

Hemoperfusion through adsorbents such as charcoal, cation exchange (e.g., AG 50W-X8) and uncharged (e.g., XAD-2) resins, and albumin-agarose gel (AAG) has been proposed for use in patients with hepatic failure. However, the loss of white blood cells and, particularly, platelets caused by each of these adsorbents remains a major deterrent to their clinical use. In vitro studies demonstrate that addition of citrate, ethylenediamine tetraacetate (EDTA), or oxalate to heparinized human blood eliminated this loss of formed blood elements during hemoperfusion. The improvement in postperfusion platelet counts (per cent of preperfusion values) produced by citrate were XAD-2, 13 leads to 95 per cent; AG 50W-X8, 10 leads to 94 per cent; AAG, 17 leads to 94 per cent; and charcoal, 44 leads to 96 per cent. Prostaglandin E1 in high doses (5 mug/ml.) markedly reduced platelet losses. Lower doses were less uniformly effective. Three young rhesus monkeys were hemoperfused for 160 minutes with columns containing AAG, XAD-2, and charcoal. During the first 80 minutes, citrate and calcium were infused into the column inflow and outflow lines respectively. For all three adsorbents, average platelet counts in the monkeys (115 per cent) and column effluent (95 per cent) were unchanged from preperfusion control values during the first 80 minutes but fell promptly to 13 and 7 per cent, respectively, after the citrate infusion was stopped. Each of the monkeys tolerated the procedure without ill effects. Use of a system analogous to that described here may facilitate clinical application of the technique of hemoperfusion through a variety of adsorbents.

Albumins↗

Treatment of extrahepatic occlusive jaundice with activated charcoal hemoperfusion in dogs.

To find the feasibility of treatment for congenital bile duct atresia, we studied the usefullness of extracorporeal hemoperfusion over activated charcoal in canine obstructive jaundice. One, three and five weeks after ligation and disection of common bile duct in 5 dogs we performed the hemoperfusion over activated charcoal extracorporeally (group 3). In this animals we examined hematological and blood coagulation studies, serum electrolyte levels, kidney function tests and liver chemistries. As control in 5 animals we carried out after sham operation the perfusion without common bile duct ligation (group 2) and in 5 animals only common bile duct ligation without perfusion (group 1). In the liver chemistries we found 2 weeks after 2nd and 3rd perfusion (5 and 7 weeks after bile duct ligation) lower levels of serum bilirubin, GOT, GPT and SDH in treated group than in non-treated jaundiced animals. It suggest the effectiveness of hemoperfusion with activated charcoal in the treatment of occlusive jaundice. There were no alteration in the hematological studies, serum electrolyte levels and kidney function tests. PT and PTT was prolonged in the jaundiced animals there were no significant differences with and without hemoperfusion.

Animals↗

Coronary artery pseudo-occlusion associated with the use of an active hemoperfusion system during PTCA.

We describe the phenomenon of coronary artery "pseudo-occlusion," which may occur when active hemoperfusion devices are utilized during percutaneous transluminal coronary angioplasty (PTCA). In such cases, contrast injected via the guiding catheter fails to opacify the coronary artery distal to the tip of the dilating catheter, thereby giving the angiographic appearance of coronary occlusion. When active hemoperfusion is terminated, contrast opacifies the vessel in a normal fashion. The cause of this observation is likely multifactorial and includes obstruction to flow by the dilating catheter, high distal pressure delivered by the dilating catheter during hemoperfusion competing with the flow of contrast injected via the guiding catheter, and wash-out of contrast at the tip of the dilating catheter by non-contrast containing blood being pumped through the system. This phenomenon must be recognized if potentially deleterious repeat dilatations are to be avoided.

Angioplasty, Balloon, Coronary↗

Hemoperfused isolated porcine slaughterhouse kidneys as a valid model for pharmacological studies.

Mammalian models of isolated perfused kidneys provide an important tool to study pharmacological, toxicological, and physiological properties of drugs, hormones, and vasoactive substances. As organs from small laboratory animals are difficult to compare to human conditions, porcine and bovine kidneys permit better approaches to simulate human conditions. We developed an alternative model for pharmacological studies using isolated hemoperfused porcine kidneys from slaughterhouse animals to reduce laboratory animal experiments. Controlled pharmacological studies were established using furosemide (2 mg/100 g organweight) as a model drug. Kidneys were hemoperfused after a preservation period of 4.6 +/- 1.7 h. In comparison to the control period, furosemide application led to significant changes in renal parameters with urine flow: 4.2/1.7 mL/min*100 g (furosemide/control), urine-sodium: 108/77.5 mmol/L, sodium excretion: 0.47/0.14 mmol/min*100 g; all differences significant, p < 0.01. The parameters stabilized to normal values as found in the control period within a period of 80 min. A second group of laboratory-harvested kidneys was examined for differences and revealed limitations of the slaughterhouse organs in parameters such as oxygen consumption. In summary, the present study demonstrates the valid use of hemoperfused slaughterhouse kidneys as a pharmacological model of renal function within the limits of the use of slaughterhouse organs, and indicates that future studies using this alternative approach could reduce animal experiments.

Animals↗

Drug intoxication: influence of hemoperfusion on human plasma fibronectin.

Fibronectin is a glycoprotein belonging to the opsonic system and able to mediate phagocytosis by the reticuloendothelial system (RES). Severe intoxications are often followed by a diminished capacity of RES-clearance. Patients with severe drug intoxications have lower concentrations of fibronectin in plasma than healthy persons. Charcoal hemoperfusion lowers plasma fibronectin by an average of 4.7 mg/dl. Initial values below 15 mg/dl did not undergo a significant decrease in the case of hemoperfusion. Regarding these findings, determination of plasma fibronectin seems a useful parameter for monitoring RES function during treatment of drug-intoxicated patients by hemoperfusion.

Adolescent↗

Effects of hemoperfusion during percutaneous transluminal coronary angioplasty on left ventricular function.

The effect of autologous blood perfusion, delivered through an angiographic power injector, on alleviating left ventricular (LV) hemodynamic deterioration during percutaneous transluminal coronary angioplasty (PTCA) was examined. LV systolic and diastolic pressures, LV peak positive and peak negative first derivative of LV pressure (dP/dt), and ST-segment shift were recorded in 9 patients with and without hemoperfusion. Hemoperfusion resulted in an improved LV hemodynamic profile during balloon occlusion, as reflected in LV systolic pressure (127 +/- 14 vs 120 +/- 15 mm Hg, p = 0.01), LV end-diastolic pressure (17 +/- 14 vs 25 +/- 6 mm Hg, p less than 0.001), peak positive (1,237 +/- 240 vs 1,149 +/- 225 mm Hg/s, p less than 0.05) and peak negative (1,666 +/- 357 vs 1,485 +/- 385 mm Hg/s, p = 0.003) dP/dt. Hemoperfusion provides substantial protection for significant LV dysfunction induced by conventional PTCA in 1-vessel angioplasty and is a feasible option to protect against potential cardiovascular collapse in high-risk PTCA.

Adult↗

Life-threatening diphenhydramine overdose treated with charcoal hemoperfusion and hemodialysis.

We describe a 35-year-old woman who ingested 16 g (approximately 20 mg/kg) of diphenhydramine with resultant hypotension requiring pressor support and marked QRS prolongation. After treatment with sodium bicarbonate failed to improve cardiac status, the patient underwent emergency charcoal hemoperfusion and hemodialysis with rapid improvement in the ECG findings within the first 40 minutes of treatment and with no further need for pressors. Major texts in toxicology state that diphenhydramine is unsuitable for hemodialysis or charcoal hemoperfusion. However, our case suggests that charcoal hemoperfusion may be appropriate therapy in cases of massive diphenhydramine overdoses when standard supportive measures fail. This case represents the largest documented diphenhydramine overdose that resulted in survival.

Adult↗

Hemoperfusion and pharmacokinetic studies with methamidophos in the rat.

A gas chromatographic method for quantifying methamidophos in plasma was developed and used to study the kinetics of methamidophos in the rat and to evaluate the efficacy of hemoperfusion therapy for treating organophosphate insecticide poisoned individuals. Intravenous administration of methamidophos resulted in a plasma decay curve which corresponded to a one compartment pharmacokinetic model with the following pharmacokinetic parameters: t1/2 = 1.5 hr; Vd = 0.81 L/kg; C1 = 5.8 mL/min/kg; kel = 0.45 hr-1. Hemoperfusion with activated charcoal effectively removed methamidophos from the blood of intoxicated rats, and significantly decreased the body burden of methamidophos; 27% of the administered dose of methamidophos was removed during five hours of perfusion. Despite a rapid reduction in the body burden of the insecticide, rats were not protected against a lethal dose of the insecticide. Because of the rapid and slowly reversible inhibition of acetylcholinesterase by organophosphate insecticides, hemoperfusion alone will not improve the clinical status of organophosphate insecticide poisoned patients.

Animals↗

Effect of hemoperfusion with polymyxin B-immobilized fiber on plasma endothelin-1 and endothelin-1 mRNA in monocytes from patients with sepsis.

Hemoperfusion using polymyxin B-immobilized fiber (PMX-F) is reported to be an effective treatment for sepsis. The aim of the present study is to assess whether plasma endothelin-1 (ET-1) and ET-1 messenger RNA (mRNA) levels in peripheral-blood monocytes are altered in patients with sepsis and whether PMX-F treatment affects plasma ET-1 and monocyte ET-1 mRNA levels. Sixteen patients with sepsis and 20 healthy volunteers were included in this study. Plasma ET-1 concentration was measured by radioimmunoassay (RIA), and plasma levels of transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) were measured by enzyme-linked immunosorbent assay (ELISA). Sixteen patients with sepsis were treated with direct hemoperfusion using PMX-F columns. Blood endotoxin levels decreased significantly from 35 to 10 pg/mL after two treatments of direct hemoperfusion, each for 2 hours. Patients with sepsis showed significantly increased levels of plasma ET-1 (P < 0.001) and monocyte ET-1 mRNA (P < 0.001) compared with healthy volunteers. However, no differences in plasma levels of TGF-beta, TNF-alpha, and IL-1beta existed between patients with sepsis and healthy volunteers. Increased plasma ET-1 levels and monocyte ET-1 mRNA levels in patients with sepsis decreased significantly after PMX-F treatment (P < 0.01). These data suggest that the secretion of ET-1 from peripheral-blood monocytes may be stimulated by endotoxin, and PMX-F treatment may be effective in reducing ET-1 secretion in patients with sepsis.

APACHE↗