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The effect of hemoperfusion over uncoated and polymer-coated charcoal on hematological levels in the conscious rat.

An investigation has been made of the suitability of a rat hemoperfusion system for the evaluation of hematological changes induced by charcoal hemoperfusion. The investigation studied the influence on erythrocyte, leucocyte and thrombocyte levels of repeated hemoperfusion over Norit RBX1 charcoal, hemoperfusion over polymer-coated Norit RBX1 and hemoperfusion over uncoated spherical charcoal. Controls included animals subjected to hemoperfusion through empty columns and animals cannulated only. The results indicate that changes in erythrocyte and leucocyte levels are due principally to passage of blood through the extracorporeal circuit rather than contact with the adsorbent but that changes in thrombocyte levels are dependent on the type of charcoal and the nature and extent of polymer coating. The investigation suggests that the rat hemoperfusion system is a suitable procedure for the assessment of the compatibility of adsorbents to be used in hemoperfusion.

Acrylonitrile↗

Plasmatic TXB2 and 6-keto-PGF1 alpha levels during charcoal hemoperfusion in chronic renal failure patients.

6 patients with end-stage renal disease underwent hemoperfusion with charcoal columns, for 60 min. Blood samples anticoagulated with 2% EDTA/aspirin solution were obtained from arteriovenous fistulas in the basal condition, 5 min after a bolus injection of heparin (7,500 U), at the end of hemoperfusion, and 30 min after. The study was repeated few days later, in the same patients, two hours after 100 mg aspirin by mouth. TXB2 and 6-keto-PGF1 alpha were assayed with RIA in unextracted (U) and extracted (E) and chromatographed platelet poor plasma (PPP). Platelet counts before and after hemoperfusion were also performed. Low levels of the two prostaglandins were found in plasma; this could be related to the procedures for collection and processing of plasma samples; no significant differences were observed between extracted and unextracted samples: there were slightly higher levels of 6-keto-PGF1 alpha in unextracted samples. After charcoal hemoperfusion there was only a slight and not significant increase of TXB2 and 6-keto-PGF1 alpha; low dose aspirin did not modify significantly plasma levels of the two prostaglandins before hemoperfusion but it reduced TXB2 and 6-keto-PGF1 alpha levels after charcoal hemoperfusion. The platelet count fell (-22%) after charcoal hemoperfusion with heparin alone and in similar manner after low-dose aspirin pretreatment (-24%, 7%).

6-Ketoprostaglandin F1 alpha↗

Hemoperfusion is ineffectual in severe chloroquine poisoning.

OBJECTIVES: To study the toxicokinetics in severe chloroquine poisoning, and to evaluate the efficacy of hemoperfusion. DESIGN: Case report on one observation. SETTING: Medical intensive care unit (ICU) of the University Medical Center Utrecht, The Netherlands. PATIENT HISTORY: A previously healthy, 52-yr-old woman ingested 100 tablets containing 100 mg chloroquine base 1 hr before admission. At admission, she was drowsy, agitated, hypotensive, and in respiratory distress. Shortly thereafter, she was resuscitated from cardiac arrest. After hemodynamic and respiratory stabilization, the patient was transferred to the medical ICU. TOXICOKINETICS EVALUATION: During the course of her stay at the ICU, blood samples were taken for the determination of chloroquine and the metabolite desethylchloroquine concentration. Hemoperfusion was started 3.5 hrs after ingestion of the chloroquine tablets. MEASUREMENTS AND MAIN RESULTS: The following toxicokinetics data during this severe chloroquine poisoning were calculated: apparent volume of the central compartment 181 L, apparent volume of distribution 1137 L, half-life in the distribution phase 6.4 hrs, half-life in the elimination phase 392.8 hrs, and total body clearance 2.01 L/hour. The average extraction ratio during hemoperfusion was 0.07, 0.28, and 0.25, in plasma, erythrocytes and whole blood, respectively. The total amount of chloroquine removed by hemoperfusion was only 480 mg (5.3% of the amount ingested). Simulation of a hemoperfusion session over 5 hrs by using a column with an optimal extraction ratio of 1.0 would have removed 1,816 mg chloroquine, only 18.2% of the amount ingested. This limited contribution of hemoperfusion to the total clearance makes it ineffective. CONCLUSION: Hemoperfusion is not effective in severe chloroquine poisoning, even when started (relatively) early in the course of the intoxication. Toxicokinetic evaluation of a chloroquine poisoning should be based on the evaluation of plasma and whole blood concentrations.

Antimalarials↗

Imipramine poisoning in a child: lack of efficacy of resin hemoperfusion.

A three-year-old boy ingested up to 1,500 mg of the tricyclic antidepressant imipramine (Tofranil). He entered our facility within two hours of discovery, and multiple resuscitative efforts, which proved unsuccessful, followed. Resin hemoperfusion was used in an effort to remove imipramine from the systemic circulation. Serum concentrations of imipramine and its major metabolite desipramine were determined from serum drawn before, during, and after hemoperfusion. Serum concentrations of imipramine and desipramine did not change appreciably. No improvement in the clinical condition was noted during the hemoperfusion period, which was due in part to the fact that our patient was clinically brain dead upon arrival in our intensive care unit. Our subsequent literature review documents that this case represents the first reported use of hemoperfusion in a pediatric tricyclic antidepressant ingestion, hemoperfusion removes an insignificant portion of the total amount of tricyclic antidepressant ingested, and some pediatric literature misleadingly suggests that hemoperfusion may be useful in such patients. Physicians treating tricyclic antidepressant ingestion cases should avoid using hemoperfusion; standard supportive care remains the essential management response.

Child, Preschool↗

Comparative efficacy of hemodialysis and hemoperfusion in severe theophylline intoxication.

OBJECTIVE: To determine the comparative efficacy of hemoperfusion and hemodialysis for severe theophylline toxicity in concurrent case series. METHODS: A 10-year, prospective, observational study was performed of consecutive patients referred to a regional poison control center with severe theophylline intoxication in whom either hemodialysis or hemoperfusion was used. The primary outcomes were 1) incidence of major theophylline toxicity (convulsions or life-threatening cardiac dysrhythmias) during or after each procedure, 2) calculated theophylline clearance, and 3) procedure-related complications. RESULTS: Over the study period, 56 patients underwent hemodialysis or hemoperfusion as treatment of severe theophylline intoxication. Overall mean age was 40.5 +/- 22.9 years. Mean peak serum theophylline concentration was 103.3 +/- 39.1 micrograms/mL (range 36 to 245 micrograms/mL). Thirty patients (54%) were victims of acute theophylline intoxication, while 18 (32%) had chronic overmedication and 8 (14%) had acute-on-therapeutic intoxication. Thirty-nine patients (70%) underwent hemodialysis, while 17 (30%) underwent hemoperfusion. There were no significant intergroup differences in age (39.4 vs 43.0 yr), peak serum theophylline concentration (99.5 vs 112.1 micrograms/mL), time to procedure (8.4 vs 6.3 hr), or duration of procedure (4.1 vs 3.7 hr). Thirty-three percent of the patients undergoing hemodialysis had major toxicity during or after the procedure, compared with 18% of those who received hemoperfusion (p = NS). Post-procedure serum theophylline concentrations were 26.9 vs 30.4 micrograms/mL, corresponding to drug clearance rates of 185.1 and 294.8 mL/kg/hr (p = 0.03). Procedural complications occurred in 3 patients who received hemoperfusion and consisted of bleeding diatheses and hypocalcemia. No complications occurred in patients receiving hemodialysis (p = 0.007). CONCLUSIONS: These data confirm that hemoperfusion provides a higher theophylline clearance rate than hemodialysis. However, hemodialysis appears to have comparable efficacy in reducing the morbidity of severe theophylline intoxication and is associated with a lower rate of procedural complications.

Acute Disease↗

Elimination of 2-arachidonoylglycerol action by direct hemoperfusion through immobilized polymyxin B fibers: an experimental study in conscious guinea pigs.

Direct hemoperfusion through a network of immobilized polymyxin B fibers is used for the treatment of septic shock, but the mechanism underlying the clinical benefits remains unclear. The aims of the present study were to assess the actions of direct hemoperfusion through immobilized polymyxin B fibers on effects of exogenous endotoxin or 2-arachidonoylglycerol in conscious guinea pigs; and to examine the underlying mechanisms. In the present study, colonic motion was monitored continuously by telemetry using a force transducer attached to the taenia caecum, while blood pressure was monitored with a carotid artery catheter. To establish a hemoperfusion circuit in a freely moving, conscious guinea pig, catheters were implanted in the carotid artery and the jugular vein, tunneled subcutaneously, exteriorized at the back of the neck in contact with a lightweight tethering spring, and attached to a swivel device at the top of the cage. On the day after the operation, lipopolysaccharide (Escherichia coli, O111:B4; 1 mg/kg) or 2-arachidonoylglycerol (1 mg/kg) was given intraperitoneally (i.p.) and direct hemoperfusion through immobilized polymyxin B fibers was carried out for 2 h. The results showed that in guinea pigs treated with direct hemoperfusion through immobilized polymyxin B fibers, relaxation of colonic longitudinal muscle caused by lipopolysaccharide or 2-arachidonoylglycerol was significantly suppressed, as were decreases in blood pressure. We conclude that the actions following exogenous administration of 2-arachidonoylglycerol were eliminated by direct hemoperfusion through immobilized polymyxin B fibers. These results suggest that effectiveness of direct hemoperfusion through immobilized polymyxin B fibers in endotoxemia involves elimination of 2-arachidonoylglycerol action.

Animals↗

Biological evaluation of hemoperfusion in acute poisoning.

The efficiency of hemoperfusion in acute poisoning cannot be clinically estimated, because: (a) concomittant intestinal absorption, hepatic metabolism, and urinary excretion must be taken into account. (b) With supportive treatment alone, spontaneous recovery usually occurs in 98% of the intoxications in Intensive Care Units. The efficiency of hemoperfusion can only be estimated biologically. Measuring the blood level at the beginning and the end of hemoperfusion as well as measuring the clearances of the drug is misleading. A better method is to measure the amount of extracted drug, either indirectly by calculation (from hourly differences of arterio-venous measures of drug concentration multiplied by the blood flow) or directly by elution of the cartridge. In a practical way, if the blood level of drug is readily available after the patient is hospitalized, the optimum efficiency of hemoperfusion can be estimated beforehand, so that the decision to carry out the hemoperfusion can be maintained, postponed, or abandoned. For the most part, the experience of toxicologists has shown hemoperfusion to be ineffective for drugs with weak extracellular distribution (such as Digoxine, tricyclic drugs, heavy metals, Colchicine). Its effectiveness for certain drugs with poor in-vitro dialysance (such as Paracetamol) or with a small percentage of intestinal absorption (such as Paraquat) is still debatable. In the case of intoxications by hypnotic drugs, one hemoperfusion allows an average of 4-12% of the ingested medium and short barbiturates, and 7-17% of the ingested Meprobamate. Whether these results can be judged satisfactory, life-saving, or insignificant is largely a matter of personal standards.

Acute Disease↗

Efficacy of hemoperfusion in the therapy of bromvalerylurea (bromural) intoxication.

We have found that charcoal hemoperfusion is effective in removing bromvalerylurea (BVU) from circulation. A patient poisoned with BVU showed a marked lightening of coma after 3 h of hemoperfusion. The BVU concentration in the patient's serum was decreased significantly by hemoperfusion. In an experiment with dogs without hemoperfusion, the BVU concentration had its peak at the fourth hour after oral administration and decreased in 24 h. In an experiment with hemoperfusion, BVU concentration in dogs decreased markedly during hemoperfusion. After hemoperfusion a rebound of concentration was observed.

Adolescent↗

Hemoperfusion in a child who ingested diquat and died from pontine infarction and hemorrhage.

A 2 1/2 year old boy accidentally ingested the herbicide diquat. Progressive neurologic dysfunction preceded his death 143 hours after poisoning. Brain stem infarction and purpura were noted at post mortem and closely resembled the brain stem pathology in 3 of 7 adults who died after diquat ingestion. Renal, gastrointestinal and pulmonary involvement in this child also resembled that seen in adults after ingestion of diquat. Hemoperfusion was performed six times in an effort to lower the body diquat burden. Cellulose-coated, activated charcoal was first employed 40 hours postingestion and removed diquat from serum with clearances of 104 and 39 ml/minute at the initiation of hemoperfusion and 6 hours later, respectively. Serum diquat concentrations decreased rapidly during charcoal hemoperfusion. However, marked rebound in serum diquat concentrations were noted between charcoal treatments, indicating extensive sequestration of diquat by tissues. Thrombocytopenia and hypocalcemia, the major complications of charcoal hemoperfusion, were easily treated. Unlike charcoal, Amberlite XAD-4 resin hemoperfusion did not remove diquat from serum. Charcoal hemoperfusion may temporarily reduce serum diquat concentrations. Whether the early institution and daily performance of charcoal hemoperfusion will minimize diquat-induced damage to brain and other organs is not clear from this case and will only be determined in future studies.

Adolescent↗

Meprobamate kinetics during and after terminated hemoperfusion in acute intoxications.

We report four cases of severe meprobamate intoxication. Maximal plasma levels reached 800 (176), 816 (180), 863 (190) and 923 mumol/l (203 mg/l). All patients survived without sequelae including one patient resuscitated from cardiac arrest. The clinical course was complicated by coma, hypotension, and hypothermia in all patients. Three cases were treated with charcoal hemoperfusion with mean hemoperfusion clearance ranging from 134-164 ml/min compared to 174 ml/min in one case treated with resin filter and the same blood flow of 200 ml/min. In two cases, a mean renal meprobamate clearance of 15 and 23 ml/min was calculated comprising only 9-15% of the hemoperfusion clearance. The amount of meprobamate removed by hemoperfusion ranged from 1.6-6.2 g. In one case, the half-life of plasma meprobamate during hemoperfusion was 2.6 hours compared to 8.3 hours after hemoperfusion. Thus the half-life was reduced more than 3-fold. These data show that hemoperfusion may be indicated in severe meprobamate intoxication.

Adult↗

Effects of hemoperfusion adsorption and/or plasma exchange in treatment of severe viral hepatitis: a comparative study.

AIM: Non-bioartificial liver has been applied to clinic for quite a long time, but the reported efficacy has been very different. The aim of this study was to compare the efficacy and safety of hemoperfusion adsorption, plasma exchange and plasma exchange plus hemoperfusion adsorption in treatment of severe viral hepatitis. METHODS: Seventy-five patients with severe viral hepatitis were treated with hemoperfusion adsorption therapy (24 cases), plasma exchange therapy (17 cases) and plasma exchange plus hemoperfusion adsorption therapy (34 cases). The data of liver function, renal function, blood routine test, prothrombin time (PT) and prothrombin activity (PTa) pre- and post-therapy were analyzed. RESULTS: Clinical symptoms of patients improved after treatment. The levels of aminotransferase, total bilirubin, direct bilirubin decreased significantly after 3 therapies (P<0.05 or P<0.01). PT, the level of total serum protein decreased significantly and PTa increased significantly after plasma exchange therapy and plasma exchange plus hemoperfusion adsorption therapy (P<0.05 or P<0.01). The side effects were few and mild in all patients. CONCLUSION: Three therapies were effective in the treatment of severe viral hepatitis. Plasma exchange therapy and plasma exchange plus hemoperfusion adsorption therapy are better than hemoperfusion adsorption therapy.

Adult↗

Biological evaluation of hemoperfusion in acute poisoning.

The efficiency of Hemoperfusion in acute poisoning cannot be clinically estimated, because: a) concomitant intestinal absorption, hepatic metabolism and urinary excretion must be taken into account. b) with supportive treatment alone, spontaneous recovery usually occurs in 98% of the intoxications in Intensive Care Units. The efficiency of hemoperfusion can only be estimated biologically. Measuring the blood level at the beginning and the end of hemoperfusion as well as measuring the clearances of the drug is misleading. A better method is to measure the amount of extracted drug, either indirectly by calculation (form hourly differences of arterio-venous measures of drug concentration multiplied by the blood flow) or directly by elution of the cartridge. In a practical way, if the blood level of drug is readily available after the patient is hospitalized, the optimum efficiency of hemoperfusion can be estimated beforehand, so that the decision to carry out the hemoperfusion can be maintained, postponed or abandoned. For the most part, the experience of toxicologists has shown hemoperfusion to be ineffective for drugs with weak extra-cellular distribution (such as Digitoxin, Tricyclic drugs, Heavy Metals, Colchicine). Its effectiveness for certain drugs, with poor in vitro dialysance (such as Paracetamol) or with small percentage of intestinal absorption (such as Paraquat) is still debatable. In the case of intoxications by hypnotic drugs, one hemoperfusion allows an average of 4 - 12% of the ingested medium and short barbiturates, 7 - 17% of the ingested Meprobamate. Whether these results can be judged satisfactory, life-saving or insignificant is largely a matter of personal standards.

Barbiturates↗

Hemoperfusion with alpha-amanitin: an in vitro study.

The authors carried out sixteen hemoperfusions with alpha-amanitin in vitro in a closed system using active charcoal, Amberlite XAD-2 and Amberlite XAD-4 in hemoperfusion capsules. As a perfusion solution 4 liters of 0.9% NaCl solution was used. The alpha-amanitin concentration in the solution was 8.3 +/- 0.36 mg/L. Individual hemoperfusion lasted 5 hours. Two hundred and forty minutes of Amberlite XAD-2 hemoperfusion led to the zero values of alpha-amanitin concentration in 0.9% NaCl solution. When using active charcoal the adsorption capacity of the hemoperfusion capsule was already exhausted at 120 min. The results gathered suggest that the most effective alpha-amanitin hemoperfusion in vitro was obtained with Amberlite XAD-2 and the least effective with active charcoal. The authors recommend the use of hemoperfusion with Amberlite XAD-2 for acute intoxication with Amanita phalloides in humans up to 24-36 hours after poisoning.

Adsorption↗

Hemoperfusion in acute camphor poisoning.

After ingestion of an unknown dose of a 10% camphor spirit (maximum dose 200 ml), a 54-year-old female was found in coma, having developed grand-mal-like seizures and respiratory failure. For detoxification, gastric lavage and hemoperfusion with amberlite XAD4 were performed. During hemoperfusion, seizures ceased, but no marked influence on the clinical course of the intoxication--especially on grade of coma--was observed. For further evaluation of the efficacy of treatment, camphor plasma elimination kinetics during hemoperfusion were compared to plasma elimination kinetics determined in a volunteer after an oral dose of 200 mg of camphor. Although the plasma compartment was almost completely (89%-95%) cleared of camphor by hemoperfusion, only a total of 35 mg of camphor was removed due to its high apparent volume of distribution (estimated 2-4 l/kg). The plasma elimination half-life was not affected by hemoperfusion, which may be explained by the saturation of metabolizing enzymes, still incomplete absorption, or metabolic interference of isopropanol. In the case presented here, neither the clinical course of the intoxication nor plasma level data gave evidence for a pronounced beneficial effect of hemoperfusion.

Acute Disease↗

Therapy of digoxin intoxication in dogs by specific hemoperfusion through agarose polyacrolein microsphere beads-antidigoxin antibodies.

The usefulness of a new biocompatible, specific immunosorbent, Agarose-Polyacrolein Microsphere Beads--Antidigoxin antibodies (APAMB-AD) for hemoperfusive removal of digoxin in digoxin intoxicated dogs is described. The sorbent contains antidigoxin antibodies covalently bound to polyacrolein microspheres, 0.2 micron in diameter. Thousands of microspheres are matrix-encapsulated in cross-linked agarose to form beads 500 to 800 micron in diameter. The sorbent removes digoxin specifically, leaving other components of the blood intact, in contrast to the nonspecific sorbents (charcoal and ion exchange resins) currently in use. Digoxin-intoxicated dogs looked ill, vomited, and their ECGs showed malignant arrhythmias which were reversed during the first hour of hemoperfusion. By 2 hours of hemoperfusion, the ECG tracings returned to the preintoxication state. Up to 27% of the total body digoxin burden was removed. The sorbent is biocompatible. Neither the formed elements nor a battery of the routinely assayed soluble components of the blood or complement (C'4) were altered significantly during the hemoperfusion trials. The dogs tolerated the hemoperfusion well and all survived the intoxication. Nonhemoperfused dogs or dogs whose blood was hemoperfused through beads lacking antidigoxin did not survive the digoxin intoxication.

Acrolein↗

Delayed rejection of heart allografts after extracorporeal donor-specific liver hemoperfusion. Role of Kupffer cells.

Liver allografts have a privileged status in regard to acute rejection. In this experimental study, we have analyzed the immunosuppressive effects of an extracorporeal liver hemoperfusion. In the LEW-to-BN combination of inbred rats, donor-specific liver hemoperfusion can significantly delay acute rejection of heart allografts. Analysis of the immunological status of these animals revealed a significant decrease in donor-specific lymphocytotoxic antibodies and in cytotoxic T lympholysis. Reactivity in mixed lymphocyte culture was normal. After third-party (DA) liver hemoperfusion or after donor-specific (LEW) splenic hemoperfusion, prolongation of heart allograft survival was moderate. Previous blockade of Kupffer cells suppressed the effects of donor-specific liver hemoperfusion. These results suggest that the sequestration by Kupffer cells of a clone of cytotoxic T cells and/or lymphocytotoxic antibodies may explain the immunosuppressive effects of donor-specific liver hemoperfusion.

Animals↗

Pharmacokinetics of chloral hydrate poisoning treated with hemodialysis and hemoperfusion.

In a severe case of chloral hydrate intoxication treated with combined hemodialysis and hemoperfusion the pharmacokinetics of the metabolites trichloroethanol (TCE), trichloroethanol glucuronide (TCE-Glu) and trichloroacetic acid (TCA) were studied. Indications of delayed absorption and some slowing of metabolism were found. At a blood flow rate of 200 ml/min clearances by hemodialysis and hemoperfusion, respectively, in ml/min were estimated to be 188 and 156 for TCE, 184 and 181 for TCE-Glu, 142 and 91 for TCA. Clearance by hemoperfusion declined with time. The half-lives of TCE and TCA were 3.2 and 4.3 hours during combined hemodialysis and hemoperfusion. After termination of treatment the half-life of TCE was 12.8 hours, whereas TCA was metabolized so slowly, that no reliable calculation could be performed. We conclude that hemodialysis and hemoperfusion are equally and highly efficient in the treatment of chloral hydrate poisoning, but hemoperfusion may increase the risk of gastric bleeding more than hemodialysis. Hemodialysis may therefore be preferable and should be tried in spite of low blood pressure.

Adult↗

Reversal of toxicity using avidin-based hemoperfusion: a model system in rats using biotinylated melittin.

The high-affinity interaction between avidin and biotin (Kd = 10(-15)M) can be exploited to develop specific protocols for retrieval of biotinylated drugs and toxicants from biological fluids. Melittin, the main toxic component of bee venom, was biotinylated and used as a model toxicant to determine whether avidin-based extracorporeal hemoperfusion could remove biotinylated melittin and thus alter the severity of the toxic response in rats. Melittin was biotinylated using N-hydroxysuccinimide-long-chain biotin. Biotinylated melittin produced 100% lethality in rats by 120 min following four sequential intravenous injections of 1.7 mg/kg biotinylated melittin (0, 5, 20, and 35 min). An avidin hemoperfusion column was constructed (10 mg avidin/1 ml gel) and connected via the femoral vasculature to rats intoxicated with biotinylated melittin. Controls rats were hemoperfused using avidin columns blocked with d-biotin. None of the 6 rats hemoperfused using the biotin-blocked avidin column control survived, whereas 5 of 9 of the experimental rats survived to 120 min. The difference between the two survival rates was statistically significant (p < 0.0048). Thus, avidin-based hemoperfusion improved survival following biotinylated melittin toxicity and strengthens the concept that avidin-based hemoperfusion can reverse the toxicity of biotinylated toxicants.

Animals↗