Effects of hemoperfusion rate and time of initiation of ACAC charcoal hemoperfusion on the survival of fulminant hepatic failure rats.
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Albumins↗
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Solute, amino acid, and hormone changes with coated charcoal hemoperfusion in uremia.
This investigation assesses the effect of two-hour activated charcoal hemoperfusion using a column containing 300 g of acrylic hydrogel-coated activated charcoal either alone or combined with hemodialysis on small and "middle molecule" removal in uremic patients. Comparison was made with standard five-hour hemodialysis. Two patients with dialysis encephalopathy were treated with four-hour combined hemoperfusion/hemodialysis without beneficial clinical effects. Hemoperfusion increased the clearance rates of creatinine and urate when combined with dialysis. Hemoperfusion alone removed 1.3 +/- 0.6 g (mean +/- SD) of creatinine and 0.6 +/- 0.2 g of urate, while combined hemoperfusion/hemodialysis removed 1.7 +/- 0.6 g of creatinine and 1.0 +/- 0.5 g of urate in a two-hour period. Both treatment schedules removed less solute than standard five-hour hemodialysis but were associated with comparable "middle molecule" removal. Hemoperfusion accounted for additional amino acid removal when combined with hemodialysis, while hemoperfusion alone produced significant reduction only in the amino acid cystine. Changes in the hormones thyroxine, triiodothyronine, human growth hormone, and insulin were noted during the procedures. Acceptable falls in platelet counts and fibrinogen occurred with hemoperfusion. Coated charcoal hemoperfusion may prove to have a role in the management of uremic patients, although the acrylic hydrogel-coated charcoal hemoperfusion device requires combination with techniques allowing fluid and electrolyte removal.
Amino Acids↗
Hemoperfusion removal of digoxin from dogs.
Removal of digoxin by XAD-4 hemoperfusion columns was tested after four dogs were given 0.06 mg/kg of digoxin i.v. Dogs were perfused for 4 to 5 hr at a flow of 105 ml/min through a 100 gm XAD-4 column 16 hr after the dose. Pharmacokinetic analysis of digoxin levels was performed with a three-compartment model. The apparent postdistribution t1/2 was 16.0 +/- 2.9 (S.D.) hr and decreased to 7.1 +/- 2.1 hr during perfusion. Digoxin perfusion clearance was 46 ml/min. An average of 51 microgram of digoxin was recovered from used columns. CP of digoxin calculated from the total R was 127.5 +/- 13 ml/min or 2.3 times greater than plasma flow. With the use of 3H-digoxin, canine blood was found to contain 2.5 times as much digoxin as did plasma. After perfusion there was an increase in serum digoxin levels in all dogs. Computer analysis showed that the increase in plasma digoxin levels immediately after hemoperfusion occurred because the central compartment, which was depleted of digoxin during hemoperfusion, was refilled from peripheral compartments. This study demonstrated that (1) XAD-4 hemoperfusion doubles the rate of removal of digoxin from dogs, (2) dog whole blood contains more than twice as much digoxin than does plasma, so that hemoperfusion clearance exceeds plasma flow, and (3) a multicompartmental pharmacokinetic model explains the increase in serum digoxin concentrations observed at the completion of hemoperfusion.
Animals↗
Hemoperfusion for methotrexate removal.
Removal of methotrexate by Amberlite XAD-4 hemoperfusion was determined in a patient with metastatic breast carcinoma. During 4 hr of hemoperfusion the plasma concentration of methotrexate fell from 5.5 x 10(-7) M TO 3.1 x 10(-7) M. After hemoperfusion methotrexate concentration increased as a consequence of multicompartmental pharmacokinetics to 5.5 x 10(-7) M and then slowly declined. Plasma methotrexate clearance decreased from 79 ml/min 30 min into hemoperfusion to 28 ml/min at the conclusion. In vitro clearance of methotrexate by 17 artificial kidneys, Amberlite XAD-4, and uncoated charcoal was determined. Uncoated charcoal had the greatest clearance of methotrexate of all the devices tested. We conclude that: (1) Amberlite XAD-4 transiently reduces plasma methotrexate concentration; (2) in vitro, charcoal hemoperfusion is more effective than XAD-4 in removing methotrexate; (3) as a consequence of the multicompartmental pharmacokinetics of methotrexate a postperfusion rebound in plasma methotrexate concentration is to be expected.
Charcoal↗
Effect of hemoperfusion of clearance of gentamicin, cephalothin, and clindamycon from plasma of normal dogs.
Nine normal dogs were divided into three groups of three. Group 1 was given an overdose of gentamicin; group 2, cephalothin; and group 3, clindamycin. Group 1 had hemoperfusion with Amberlite XE-336, and groups 2 and 3 with Amberlite XAD-4 resin adsorbents, for 6 hr with a blood flow rate of 300 ml/min. The plasma clearance and removal rates of antibiotics by the hemoperfusion columns were high. The clearance rate of gentamicin from plasma (mean +/- standard deviation) ranged from 59 +/- 30 to 199 +/- 6 ml/min, of cephalothin from 66 +/- 14 to 157 +/- 8 ml/min, and of clindamycin from 55 +/- 9 to 125 +/- 16 ml/min. Of the total dose of antibiotic administered, the hemoperfusion columns removed 67% from theplasma in group 1, 41% in group 2, and 18% in group 3. The fact that antibiotics may be rapidly removed from the blood during hemoperfusion should be considered in calculation of the therapeutic dose of antibiotic required for patients who receive this preocedure. Also, hemoperfusion can effectively and rapidly remove certain antibiotics from the blood of patients who have had a potentially toxic overdose.
Animals↗
Digoxin removal from a patient with renal failure by hemoperfusion with Amberlite XAD-4 resin.
A digitoxic patient with severe renal failure underwent two hemoperfusion treatments with Amberlite XAD-4 resin. Digoxin clearances calculated from plasma flow rates and plasma digoxin concentrations, as well as from the amount of digoxin eluted from the used columns, were superior to those previously described for peritoneal dialysis, hemodialysis and charcoal hemoperfusion. There was a temporary improvement in the patient's life-threatening digitoxic cardiac rhythm with the first hemoperfusion, and a permanent improvement after the second hemoperfusion. It is submitted that hemoperfusion with this resin may significantly lessen manifestations of digoxin poisoning and may hasten digoxin elimination in digitoxic patients with renal failure.
Aged↗
Influence of hemoperfusion on the concentrations of calcitonin, testosterone and cortisol in blood plasma.
The influence of hemoperfusion with a cellulose-acetate-coated charcoal column (Adsorba 300-C, Gambro, Lund, Sweden) on plasma concentrations of calcitonin, testosterone and cortisol was studied in five psoriatic patients during 12 treatment periods. Calcitonin, testosterone and cortisol were effectively removed from blood plasma by the charcoal column with average plasma clearances of 34.0, 14.5 and 27.6 ml/min, respectively, at 30 minutes of hemoperfusion, and 4.9, 15.4 and 24.4 ml/min, respectively, at 180 minutes of hemoperfusion. After three hours of hemoperfusion, significant decreases of testosterone and cortisol were found in peripheral venous blood, while calcitonin fell insignificantly. It remains to be elucidated whether long-term use of hemoperfusion would require a detailed control of possible effects on the endocrine status of patients.
Acetates↗
[Is hemoperfusion effective in the treatment of digoxin intoxication? (author's transl)].
Digitalis therapy is frequently accompanied by adverse drug reactions. Severe digitalis intoxications are still a problem. Therapeutical methods, which could be used in the case of a life threatening digoxin intoxication, are known, but not yet generally available. Hemodialysis has only a minor effect on digoxin excretion. This study was planned to test the hypothesis that hemoperfusion across dextran-cocoated charcoal or the resin Amberlite XAD 4 could be more effective in the therapy of digoxin intoxications. The ability of hemoperfusion to eliminate digoxin was tested in a patient who had to undergo treatment beacuse of a severe bromcarbamide intoxication. Additionally we compared the effect of several modifications on this method in 12 dogs, which had received 0.05 mg/kg body weight per day for three days prior to the experiment. Although hemoperfusion across Amberlite XAD 4 may eliminate as much digoxin as normal human kidneys during the few hours of treatment, the amount of digoxin removed after all is only a small percentage of the total body pool. Thus compared to the risks of hemoperfusion as an invasive treatment its effect is small. According to our results, hemoperfusion cannot be recommended as a standard therapy of severe digoxin intoxications.
Adult↗
[Treatment of the experimental chronic digitalisintoxication by hemoperfusion (author's transl)].
In 5 adult dogs experimental chronic digitalis intoxication was produced by oral administration of different digitalis-types (digoxin, beta-methyl-, beta-acetyl-digoxin, digitoxin). 18 to 24 hours after the last application of digitalis, charcoal hemoperfusion was performed in Dipidolor-N2O-anesthesia and serum digitalis-concentrations in the arterial and venous lines of the hemoperfusion system were determined by RIA J125. The Ecg was registered continuously as a simple clinical parameter of cardiac digitalis intoxication. Initial multiple cardiac arrhythmias (AVII degree, SAII degree, tachycardia of the atrium) subsided in the dogs with digoxin, beta-methyl- and beta-acetyl-digoxin during hemocolperfusion within 130 to 160 min. The disturbances of rhythm persisted up to 200 min after onset of hemoperfusion in the dog intoxicated by digitoxin. The clearances of digoxin and derivatives (35.8--43.1 ml/min) are higher than the digitoxin clearance (17--23.2 ml/min) which is supposed to be the reason for cardiac detoxication in the digoxin-intoxicated dogs. Hemoperfusion using polymer coated charcoal appears to be effective for the elimination of digoxin leading to a marked improvement of cardiac arrhythmias. By contrast digitoxin induced cardiac arrhythmias are not influenced during hemoperfusion.
Animals↗
[Hemoperfusion with coated activated charcoal for treating acute poisoning by remedies, plant protectants, and fungi. III. Fungi (author's transl)].
Four patients with foudroyant liver dystrophy due to ingestion of fungi of the Amanita phalloides species were treated by hemoperfusion with coated activated charcoal. Three patients survived the poisoning. One patient died in a coma due to hepatic disintegration with cardiac and respiratory insufficiency. One female patient suffering from hemolytic syndrome and acute anuresis due to ingestion of fungi of the Paxillus involutus species recovered completely after treatment of combinated hemodialysis and hemoperfusion. The first hemoperfusion in the patients with Amanita phalloides poisoning were performed two to three days after ingestion of the fungus. At that time there were only traces of amanitines in the blood of one of the surviving patients. These Amanita phalloides toxins were only detected in the first 24-hour urine in the other 3 patients. It is thus not to be expected that toxicologically relevant quanities of the toxins will be eliminated from the blood by hemoperfusion carried out two to three days following ingestion of the fungus, Amanita phalloides. No coherence of restitutio ad integrum and hemoperfusion could be pointed out in the female patients suffering from hemolytic syndrom and anuresis due to Paxillus involutus.
Adult↗
Efficacy of gut lavage, hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication.
Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents. Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1-2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1-2 ppm, the clearance values for hemoperfusion were some 5-7 times higher than those for hemodialysis. In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquats less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.
Adult↗
[Carbromal intoxication: influence of hemodialysis and hemoperfusion].
It has been demonstrated with an in vitro model that hemoperfusion through Amberlite XAD4 or coated charcoal containing cartridges eliminates carbromal and its ureid derivatives more efficiently than hemodialysis. The following clearancs were measured in vitro (blood flow: 200 ml/min): Coil dialyser (1 m2): 55-85 ml/min, charcoal hemoperfusion 100-125 ml/min, Amberlite XAD4 hemoperfusion: 200 ml/min. The data of one patient who had been hemoperfused after the ingestion of 35 g Carbromal with the Haemocol cartridge (SMith & Nephews) are depicted. Our results permit to draw the conclusion that hemoperfusion at this time is the most efficient means to eliminate Carbromal from intoxicated patients.
Charcoal↗
[Hemoperfusion with coated activated charcoal for treating acute poisoning by remedies, plant protectants, and fungi (author's transl)].
From the clinico-toxicological standpoint, the most important plant protectants are the insecticides (bipyridylium compounds). In vitro trials and investigations on poisoned patients have shown that it is fundamentally possible to eliminate such plant protectants from the blood by hemoperfusion with coated activated charcoal. With both the lipophilic alkyl phosphate, nitrostigmine (E605 forte), and by the two hydrophilic alkyl phosphates, demetone-S-methyl sulfoxide (Metasystox R) and dimethoate (Roxion), it was possible to measure hemoperfusion clearance values around 60 to 85 ml/min at a blood flow rate of 100 ml/min. Only the two hydrophilic alkyl phosphates were able to be eliminated by hemodialysis, the clearance values being, however, lower. Thus in severe alkyl phosphate intoxications the use of hemoperfusion may considered alongside the standard therapy. The bipyridylium compounds, paraquat (Gramoxone) and diquat (Reglone), are readily dialysed, but can be better eliminated from the blood by hemoperfusion. This therapeutic measure must be initiated as rapidly as possible independent of the clinical picture, for only when hemoperfusion is begun prior to the fixation of paraquat or diquat at tissue are there any prospects of success.
2,2'-Dipyridyl↗
[Hemoperfusion with coated activated charcoal for treating acute poisoning by remedies, plant protectants, and fungi. I. Remedies (author's transl)].
Hemoperfusion with coated activated charcoal is a novel procedure for treating acute poisoning. It enables the elimination of both, water-soluble and liposoluble toxins. Hemoperfusion with coated activated charcoal has proved to be superior to hemodialysis in the treatment of barbiturate or bromocarbamide poisoning both under experimental conditions as well as in the ward. Analogous statements may be made for the therapy of glutethimide poisoning. Methaqualone, on the other hand, could not be eliminated sufficiently well in animal trials. Intoxications by "mild" analgetics, such as paracetamol and acetylsalicylic acid, may be treated successfully with hemoperfusion. Treatment of acetylsalicylic acid poisoning is equally effective with hemoperfusion as with hemodialysis. Prospects for the success of hemoperfusion in treating intoxication from tricyclic antidepressants and neuroliptics are slight. It is simply the danger of antidepressant poisoning that justifies using this method of treatment in the first few hours after ingestion in order to reduced the flow of the psychopharmaceutical substance into the tissue.
Acetaminophen↗
Digoxin and digitoxin elimination in man by charcoal hemoperfusion.
Since there is no widely used causal means of reducing the severity of massive digitalis intoxication the capability of hemoperfusion with coated activated charcoal to remove toxicologically relevant amounts of digoxin and digitoxin was evaluated in vitro and in man. At a blood flow rate of 100 ml/min the digoxin clearance by hemoperfusion in vitro was 51 +/- 8 ml/min in comparison to 24.3 +/- 11.3 ml/min by hemodialysis. The average hemoperfusion clearance of digitoxin was 31.7 +/- 13.4 ml/min, whereas almost no digitoxin was removed by hemodialysis. These clearance values point to the ability of hemoperfusion of eliminating digitalis glycosides from the blood. They do not clarify the essential question whether it is possible to lower the toxic concentrations in the tissues.
Charcoal↗
Treatment of severe drug overdosage with charcoal hemoperfusion.
Mortality from severe poisoning remains excessively high in patients managed conservatively. In this report, charcoal hemoperfusion was used as a therapeutic aid to active drug removal in 10 patients (9 of whom were in Grade IV coma) intoxicated with a variety of drugs and a further 3 patients poisoned with the highly lethal herbicide, paraquat. All 10 patients who ingested drugs recovered. One of the 3 patients ingesting paraquat survived. The hemoperfusion treatments were associated with demonstrated drug removal. Complications associated with hemoperfusion were minor. Decreases in platelet levels were observed but were not accompanied by clinically important bleeding. The technique of hemoperfusion is simple and provides a therapeutic aid in the care of the severely poisoned patient.
Adolescent↗
Adsorptive capacities of hemoperfusion devices in clinical use.
Five different hemoperfusion devices have been used in the treatment of patients, intoxicated with barbiturates. The changes in drug clearance values which occurred during hemoperfusion varied according to the device used. Even after very long periods of hemoperfusion, however, drug clearance values never fell to zero. Using data collected from comparable cases, it has been shown that the rate of uptake of drug from the blood is independent of the amount of adsorbent in the columns, those containing 100 gm charcoal having the same efficiency as the conventional 300 gm. The prime factor which determines the rate of drug uptake has been shown to be the arterial plasma drug concentrations. Other factors, such as the deposition of cellular debris and proteins as hemoperfusion progresses, are also thought to influence the efficiency of drug removal.
Adsorption↗
Albumin-coated Amberlite XAD-7 resin for hemoperfusion in acute liver failure. Part II: in vivo evaluation.
Albumin-coated Amberlite XAD-7 has been previously shown to be blood compatible in in vitro hemoperfusion experiments whith human blood. In this study, the preliminary results are reported on single hemoperfusions with albumin-coated XAD-7 resin in four patients with acute liver failure. The mean platelet count was 116+/-SE 16.3% of the initial arterial value and the mean white cell count was 96+/-SE 6.5% of initial at the end of four hours of hemoperfusion. Removal of bilirubin, phenols and substances in the middle molecular weight range by the resin was demonstrated. These preliminary results suggest albumin-coated Amberlite XAD-7 resin to be blood compatible and capable of removing protein-bound and middle molecular weight substances from patients with acute liver failure. Further clinical evaluation of repeated resin hemoperfusion is required to determine whether this treatment will be beneficial to patient survival.
Acrylic Resins↗