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PubMed1984

Specific removal of digoxin by hemoperfusion through agarose polyacrolein microsphere polyacrolein microsphere beads-antidigoxin antibodies (APAMB-AD).

The efficacy of a new, biocompatible, specific immunosorbent for hemoperfusive removal of digoxin is described. The sorbent contains antidigoxin antibodies covalently bound to polyacrolein microspheres, 0.2 mu diam. Thousands of microspheres are matrix-encapsulated in crosslinked agarose to form beads of 500 to 800 mu diam. Digoxin intoxicated dogs showed heart block, ventricular and atrial tachycardia and extended runs of PVCs. During hemoperfusion the abnormal ECG abated; at 2 h of hemoperfusion the ECG tracings returned to normal. Up to 25% of the total digoxin burden was removed. The numbers of the blood cells and the content of a battery of relevant soluble components of the blood remained constant. Dogs were alive and well after the hemoperfusion. Non hemoperfused dogs, which received antiarrythmic agents, did not survive the intoxication. This is the first report of a practical hemoperfusive system for the specific removal of digoxin from whole blood.

Acrolein↗
PubMed1996

Delayed peak serum valproic acid in massive divalproex overdose--treatment with charcoal hemoperfusion.

BACKGROUND: Increased clearance and apparent clinical improvement in valproic acid overdose has been reported following in-series hemodialysis/hemoperfusion therapy. We report a case of divalproex sodium and chlorpheniramine overdose treated with charcoal hemoperfusion and multiple-dose activated charcoal. CASE REPORT: A 32-year-old female presented alert three hours postingestion of her own medication. Serum valproic acid was 105 micrograms/mL. No anticholinergic toxicity was seen. Despite three doses of activated charcoal over 14 hours, serum valproic acid continued to rise. Whole bowel irrigation and multiple-dose activated charcoal were commenced 17 h postingestion when serum valproic acid was 1380 micrograms/mL. Charcoal hemoperfusion was instituted three hours later when serum valproic acid had not fallen and the patient remained obtunded. RESULTS: Initial extraction ratio of the hemoperfusion cartridge was 0.54 with plasma clearance of 54.5 mL/min. Valproic acid elimination half-life was 3 h during the 190 min hemoperfusion cycle. Posthemoperfusion elimination half-life was 4.8 h with continued multiple-dose activated charcoal dosing. The clinical condition improved during hemoperfusion. CONCLUSION: Enteric coated valproic acid preparations may cause delayed toxicity in overdose, particularly with coingested anticholinergic medications. In our case, charcoal hemoperfusion appeared to increase valproic acid clearance.

Adult↗
PubMed1978

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↗
PubMed1983

[Artificial liver support system: removal of bilirubin and bile acids by hemoperfusion with ionex-column].

Removal of toxic substances from the circulating blood of patients with severe hepatic failures may be life-saving, however, the substances should be clarified. IONEX is a new resin specially designed to adsorb bilirubin in the blood. The adsorption of bilirubin from the blood to IONEX was 2 to 3 times than that to the activated charcoal beads in vitro. Direct hemoperfusion with IONEX column was performed using 6 jaundiced dogs. Removal rate of bilirubin after 90 minutes direct hemoperfusion ranged from 49% (IONEX 70 gm) maximum to 9% (IONEX 24.1 gm) minimum. It has been found that the removal of bilirubin is disturbed by thrombus formation on the IONEX fibers. To prevent the platelet loss and aggregate formation during hemoperfusion with IOENX, Prostaglandin (PGE1 or PGI2) was administered continuously into the arterial line of the extracorporeal circulation using IONEX column during 90 min. direct hemoperfusion. Thrombus formation in the IONEX column was little observed and the platelet losses were also not observed. The average removal rate of bilirubin from the blood of the jaundiced dogs was as much as 40% (IONEX 70 gm) and that of bile acid was 61% in mean value. Using PGI2, slight hypotension could not be avoided in dog. In 7 patients with severe jaundice, direct hemoperfusion was performed. Mean removal rate of bilirubin and bile acids from the blood of these patients was 21% and 31.2% respectively after 60 to 90 minutes direct hemoperfusion with activated charcoal and IONEX.

Adsorption↗
PubMed1982

Hemoperfusion in acute intoxication. Clinical experience with 48 cases.

Hemoperfusion was performed on 58 occasions to treat 48 patients with severe intoxication, of which 23 had taken on overdose of barbiturate or meprobamate. With one exception they all showed remarkable improvement during the treatment. In addition in many other intoxications patients greatly benefited from hemoperfusion, as with salicylate, paracetamol, quinidine, propranolol and mushroom intoxications. Hemoperfusion was of doubtful value or ineffective in intoxications due to tricyclic antidepressants, phenothiazine, digoxin and methanol. Four of the patients (7%) died. More side effects are seen during hemoperfusion than during hemodialysis. The disposable supplies of hemoperfusion are more costly than those for hemodialysis. Therefore if both kinds of treatment are equally effective, one has to prefer hemodialysis. Unfortunately intoxications exist, which do not respond to either hemoperfusion or hemodialysis.

Adult↗
PubMed1988

Removal of methotrexate, leucovorin, and their metabolites by combined hemodialysis and hemoperfusion.

This article documents the case of a patient with severe renal failure immediately after having been given high-dose methotrexate; the patient was effectively treated with repeated hemodialysis, charcoal hemoperfusion, leucovorin, and thymidine. The methotrexate plasma concentration was reduced from 390 mumol/L to 7 mumol/L as a result of 24.5 hours of hemodialysis along with 39.5 hours of hemoperfusion. Although a rebound in the plasma methotrexate concentration occurred the first three times that hemodialysis and/or hemoperfusion was stopped, reinstitution of the procedure was always effective in further lowering methotrexate concentrations. The patient was subsequently managed with leucovorin and thymidine rescue. Simultaneous measurements before and after the hemodialysis-hemoperfusion apparatus and before and after the hemoperfusion device alone revealed a percent decrease in the concentration of d-leucovorin of 36% and 79%; 1-leucovorin, 82% and 75%; 5-methyltetrahydrofolate, 52% and 64%; methotrexate, 73% and 37%; and 7-hydroxymethotrexate, 21% and 24%, respectively. Gastrointestinal and hematologic toxicities were completely prevented, and serum creatinine normalized within 24 days.

Adolescent↗
PubMed1978

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↗
PubMedDate not supplied

Charcoal hemoperfusion for theophylline overdose: case report and proposal for predicting treatment time.

Charcoal hemoperfusion is effective in the treatment of theophylline overdose. Estimation of the time required for charcoal hemoperfusion has been based on personal experience and judgment. We used pharmacokinetic data from a patient and from case reports to generate a formula for predicting treatment time. Pharmacokinetic parameters were calculated using model-independent analysis of concentration-time curves from two treatments of charcoal hemoperfusion. These values were compared with published data and incorporated into a formula that was derived from the elimination rate constant to estimate treatment time of charcoal hemoperfusion: Time (min) = (ln conci-ln concd)/0.0057, where the concentration of theophylline is in mumol/L. The formula may be valid in patients in whom the serum theophylline concentration is less than or equal to 516 mumol/L or 92 mg/L. It may be used as a guide to estimate the length of charcoal hemoperfusion in the treatment of theophylline toxicity. Its validation requires implementation and evaluation in future cases.

Adult↗
PubMed1986

Specific hemoperfusion through agarose acrobeads.

Agarose acrobeads were produced by encapsulating polyacrolein microspheres (acrobeads) of 0.2 micron average diameter within an agarose matrix. Crosslinked agarose acrobeads of diameters ranging from 0.5 to 0.8 mm were found to be optimal spheres for specific hemoperfusion purposes. Agarose provides the biocompatibility and mechanical strength of the agarose acrobeads. Acrobeads contain a high aldehyde-group content through which various amino ligands, i.e., proteins, antigens, antibodies, enzymes, and so on, can be covalently bound in a single step under physiological pH (or other pH). Thus, antibodies, antigens, or toxic materials may be directly removed from whole blood by hemoperfusion. During in vitro and in vivo hemoperfusion trials, the content of erythrocytes, leukocytes, and thrombocytes was essentially unaltered. Likewise, a battery of the soluble blood components (Cl-, K+, Na+, Ca2+, PO3/4-), total proteins, albumin, and C'4 component of the complement cascade, as well as the enzymes SGOT, LDH, and alkaline phosphatase, remained constant within narrow limits during the hemoperfusion procedure. The chemical and physical structure of the beads is stable; neither acrolein nor bead fragments were detected in hemoperfusion trials. Similarly, leakage of antibody bound to the agarose acrobeads into the blood is insignificant. Thus far, we have demonstrated the efficacy of the crosslinked agarose acrobeads for extracorporeal removal of "unwanted" substances from whole blood in the following systems: (a) removal of specific antigens (digoxin or paraquat removal with antidigoxin or antiparaquat antibodies bound to the acrobeads, respectively), (b) removal of specific antibody (antiBSA) removal with BSA bound to the beads), (c) removal of immune complexes (BSA-antiBSA complex removal with C1q bound to acrobeads), and (d) removal of specific metals (removal of iron with deferoxamine bound to the agarose acrobeads).

Animals↗
PubMed1988

Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure.

One hundred thirty-seven patients with fulminant hepatic failure were entered into two controlled trials of charcoal hemoperfusion carried out concurrently. In trial A, 75 patients with grade 3 encephalopathy were randomized to receive 5 or 10 h of hemoperfusion daily. Overall survival rates for the two groups were similar (51.3% vs. 50.0%) as was the frequency of major complications including cerebral edema and renal failure. In trial B, in which 62 patients with established grade 4 encephalopathy on admission were randomized to a no-perfusion group or to have 10 h of hemoperfusion daily, overall survival rates for the two groups were again similar (39.3% and 34.5%, respectively). There was in both trials a significant relationship between survival and etiology quite independent of the use or duration of hemoperfusion. Thus, percentage survival for the acetaminophen-overdose cases was 52.9%, for hepatitis A 66.7%, for hepatitis B 38.9%, for presumed non-A, non-B hepatitis 20%, and for halothane or drug reaction 12.5%. Within the etiologic subgroups survival was also influenced by the three major complications that developed, being inversely related to their frequency and combination, except in the non-A, non-B hepatitis and halothane or drug reaction subgroups, which had a high mortality throughout. In the latter cases particularly, orthotopic liver transplantation merits early consideration and in the group with better "intrinsic" survival (acetaminophen, hepatitis A and B) intensive management of complications (rather than charcoal hemoperfusion) would appear to be of major importance.

Acetaminophen↗
PubMed2003

Xenogeneic direct hemoperfusion using whole swine liver for liver failure in dogs.

BACKGROUND: We developed a new method of xenogeneic direct hemoperfusion of a bioartificial liver support system consisting of a leukocyte-adsorbent column, an immunoglobulin-adsorbent column, and the substitute unit for hepatic function. By this method, we performed xenogeneic direct hemoperfusion experiment using resected whole swine liver for treatment of a canine liver failure model, and compared the contribution of each adsorbent column both by blood analysis and from the histological point of view. MATERIALS AND METHODS: Canine liver failure model was produced by portocaval shunting and ligating the entire hepatoduodenal ligament. The xenogeneic direct hemoperfusion system was constructed using a roller pump, a leukocyte-adsorbent column, an immunoglobulin-adsorbent column, a combined device of oxygenator and warmer, the resected whole swine liver accommodated in a chamber, and a dissolved oxygen meter through which canine whole blood leaving the external jugular vein circulated in this order. RESULTS: Xenogeneic direct hemoperfusion was successfully performed for 3 h without hyperacute rejection occurring. Adequate ammonia detoxification and bile juice secretion were exhibited, and no findings of hepatocyte destruction by immunological cells and proteins were detected. Blood data showed that the immunoglobulin adsorbent were more effective than the leukocyte adsorbent in avoiding hyperacute rejection. This result indicates that hyperacute rejection has a closer relation to humoral immune responses, especially regarding removal of complements than to cellular immune responses. CONCLUSIONS: We successfully performed xenogeneic direct hemoperfusion of the whole swine liver without hyperacute rejection using our method.

Adsorption↗
PubMed1995

Clinical pilot study on high-dose intraarterial chemotherapy with direct hemoperfusion under hepatic venous isolation in patients with advanced hepatocellular carcinoma.

BACKGROUND: We recently developed a novel system of direct hemoperfusion under hepatic venous isolation in an attempt to achieve high-dose intraarterial chemotherapy for patients with malignant liver tumors. We report here the results of treatment of these patients with advanced hepatocellular carcinoma. METHODS: Adriamycin (100 to 150 mg/m2) was administered into the hepatic artery of 15 patients, under conditions of extracorporeal drug elimination by direct hemoperfusion under hepatic venous isolation. Hepatic venous isolation was accomplished mainly by the double-balloon technique with an occlusion catheter and a balloon catheter. The isolated hepatic venous blood was filtered by direct hemoperfusion and pumped to the left axillary vein. RESULTS: During 5 minutes of adriamycin infusion, the mean drug extraction ratios of the direct hemoperfusion filters were 91% +/- 9% (mean +/- SD). The amount of drug removed by the system was 26.4% +/- 16.0% of the amount of drug administered. Two patients died, one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Other side effects included hemolysis related to the system of hemoperfusion (87%), chemical hepatitis (80%), leukopenia less than 3000/mm3 (67%), alopecia (33%), and nausea and vomiting (20%). Nine (64%) of 14 evaluable patients had objective tumor responses, with a median duration of response of 6.2 months. CONCLUSIONS: This approach offers an effective therapeutic option for patients with advanced hepatocellular carcinoma.

Adult↗
PubMed1992

Combined high-efficiency hemodialysis and charcoal hemoperfusion in severe N-acetylprocainamide intoxication.

Several extracorporeal techniques have been used to remove N-acetylprocainamide (NAPA), the major metabolite of procainamide, in patients intoxicated with this substance. We report a patient with life-threatening NAPA intoxication who was rapidly and successfully treated with combined high-efficiency hemodialysis and charcoal hemoperfusion. The hemodialyzer and hemoperfusion cartridge were placed in series such that the patient's blood was dialyzed before reaching the cartridge. Overall clearance of NAPA was 153 mL/min, with clearance due to hemodialysis averaging 102 mL/min and that due to hemoperfusion averaging 88 mL/min. Thus, addition of the hemoperfusion cartridge into the extracorporeal circuit resulted in a 50% increase in clearance over that obtainable by high-efficiency hemodialysis alone. In comparison to other modalities, this technique is more effective than either hemodialysis or charcoal hemoperfusion alone and can achieve a more rapid reduction of serum NAPA levels than that observed with slow continuous hemofiltration or hemodiafiltration.

Acecainide↗
PubMed2002

Efficacy of charcoal hemoperfusion in massive carbamazepine poisoning.

BACKGROUND: Carbamazepine poisoning can be life threatening. The role and efficacy of extracorporeal drug clearance is not clearly defined. CASE REPORT: A 16-year-old male ingested 34g of slow-release carbamazepine. His course was complicated by seizures, recurrent cardiac arrests, and renalfailure. Intestinal ileus at the time of presentation prevented effective gastrointestinal decontamination. His carbamazepine concentration peaked at 93.8 mg/L (397micromol/L) 106 hours after ingestion. There was evidence suggesting ongoing absorption for 120 hours. He underwent seven episodes of charcoal hemoperfusion for a total of 109.25 hours. He subsequently made a full recovery. METHODS: The efficacy of charcoal hemoperfusion was evaluated by measuring the carbamazepine concentrations in the afferent and efferent loops of the hemoperfusion cartridge using 17 paired convenience samples. Extraction ratios were calculated and plotted against timefor each individual episode of charcoal hemoperfusion. CONCLUSION: The extraction ratio was linearly related to time, and ranged 0.46-0.02. The peak clearance was 69 mL/min. Cartridge saturation was defined as a clearance that was equal to an estimate of the patient's intrinsic clearance. In our patient, this was equivalent to an extraction ratio of 0.2 at a flow rate of 150 mL/min. By this definition, cartridge saturation appeared to occur at 7 hours. Charcoal hemoperfusion was associated with a significant reduction in the apparent half-life, which is most easily explained by clearance from the central vascular compartment, during a prolonged absorptive phase. The patient made full recovery without evidence of neurological deficit.

Adolescent↗
PubMed1977

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↗
PubMed1980

Removal of cimetidine by peritoneal dialysis, hemodialysis, and charcoal hemoperfusion.

Dialysis clearance of cimetidine in patients receiving peritoneal dialysis, hemodialysis, and hemoperfusion was compared in stable and seriously ill patients. Two methods of determining dialysis clearance were employed, one of which was the method employed for cimetidine previously in the literature. Cimetidine clearance was lowest for peritoneal dialysis (5 ml/min), intermediate for hemodialysis (28 ml/min), and greatest for hemoperfusion (85 ml/min). Using both methods to calculate dialysis clearance, we found that cimetidine clearance during dialysis has been overestimated. In addition, pharmacokinetic analysis revealed that peritoneal and hemodialysis apparently removed cimetidine from the central compartment only, whereas hemoperfusion apparently removed drug from the peripheral compartment as well. A possible mechanism to explain this difference is based on the observation that hemodynamic changes occur during hemodialysis that may not be seen during hemoperfusion. No dosage adjustment need be made when patients receiving cimetidine undergo any form of dialysis; hemoperfusion may be of some benefit in removing drug from the central as well as tissue compartments in an acute overdose situation.

Aged↗
PubMed1999

Valproic acid toxicokinetics: serial hemodialysis and hemoperfusion.

The toxicity and pharmacokinetic properties of a drug determine whether hemodialysis and/or hemoperfusion are indicated in acute intoxications. Valproic acid is considered unremovable by hemodialysis because of the high protein binding of 90%-95%. A 27-year-old male with a history of seizures was admitted to the emergency room because of coma, hypernatriemia, and respiratory failure caused by an intoxication with a large dose of valproic acid. At admission, the plasma valproic acid level was 1414 mg/L (9.9 mmol/L) (therapeutic range: 50-100 mg/L (350-700 micromol/ L). The anion gap was 26 mmol/L (normal <12-14 mmol/L) and corresponded fairly well with this valproic acid level. Because of the potential toxicity of this high valproic acid level serial hemodialysis and hemoperfusion was performed. The first session was done with a charcoal column and the second session with a resin column. The patient recovered during the course of treatment. The valproic acid plasma clearances during treatment were: 80 mL/min (hemodialysis); 40 mL/min (hemoperfusion by charcoal) and 80 mL/min (hemoperfusion by resin, only in the first hour). The protein binding of valproic acid in plasma was only 32% at the start and was 54% at the end of the two sessions. In this specific case of a severe valproic acid intoxication, saturated protein binding resulted in an increased fraction of unbound valproic acid. This made hemodialysis an effective treatment, while hemoperfusion was relatively less effective because of saturation of the column. In conclusion, the toxicokinetics of valproate are quite different from the pharmacokinetics at therapeutic levels. The anion gap and protein binding are important parameters in toxicokinetics.

Adult↗
PubMed1980

Hemoperfusion with Amberlite resin in the treatment of self-poisoning.

Ten patients with various intoxications were treated with resin hemoperfusion. Three of four patients with grade IV coma due to tricyclic antidepressant (TCA) poisoning could be extubated during or on termination of hemoperfusion. Clearance values of 135--185 and 190--200 ml/min were obtained for amitriptyline and nortriptyline, respectively. One patient with severe chloral hydrate poisoning could be extubated after less than one hour's hemoperfusion. A clearance of 140 ml/min was obtained in a uremic patient with AV block II due to digitoxin intoxication. Four patients with mushroom poisoning were treated with combined hemoperfusion-hemodialysis. A transient fall in platelet count was seen in all patients. Resin hemoperfusion is of definite value in selected, severe cases of self-poisoning with psychotropic drugs such as TCA and possibly in cases of mushroom poisoning where the prognosis with hemodialysis and supportive therapy is doubtful.

Adult↗