Treatment of vancomycin overdose using high-efficiency dialysis membranes

Two children underwent acute hemodialysis using high-efficiency dialysis membranes for vancomycin intoxication (plasma levels 238 μg/ml and 182 μg/ml). During a 3-h treatment, plasma vancomycin removal was on average 60%, with a calculated vancomycin half-life (t _1/2) of 2 h. This is in contrast to a recent report using charcoal hemoperfusion for vancomycin intoxication (plasma level of 137 μg/ml), which resulted in a 40% relative plasma clearance and a calculated vancomycin t _1/2 of 12.5 h for a 4-h treatment. The choice of optimal modality for clearing a toxin should take into account the availability of equipment, protein or lipid binding of the toxin, and inherent risks of charcoal hemofiltration (large extracorporeal circuit, reversible hypocalcemia, heat loss, reversible coagulation defects) versus risks of high-efficiency hemodialysis (large extracorporeal circuit). Received: 6 July 1998 / Revised: 28 January 1999 / Accepted: 1 February 1999     

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

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

Hyperoxalemia in renal failure and the role of hemoperfusion and hemodialysis in primary oxalosis

Measurement of oxalate levels in 14 patients with chronic renal failure, treated by maintenance hemodialysis, revealed elevated plasma oxalate concentrations in all patients 1,075.7 +/- (SEM) 253 micrograms/dl. In 7 of these subjects the oxalate concentration was more than three times higher than the upper limit of normal. Furthermore, a strong positive correlation (r = 0.75) between serum creatinine and plasma oxalate concentration was found. A combination of hemodialysis and hemoperfusion procedure was carried out in a dialysis patient with primary oxalosis as a cause of renal failure. The average oxalate clearance of the hemodialyzer during seven hemodialysis/hemoperfusion procedures was 91 ml/min and that of the charcoal detoxifier was 24 ml/min. The amount of oxalate removed during 4 1/2 h of the hemodialysis/hemoperfusion procedure was 429 mg. This amount was calculated to be produced in about 87 h, with an oxalate generation rate of 4.9 mg/h.     

Sequential and simultaneous "in series" hemodialysis and hemoperfusion in the management of theophylline intoxication

Hemodialysis and hemoperfusion have been evaluated, and both are effective in removing theophylline. We report two consecutive cases of theophylline intoxication in which the sequential treatment of charcoal hemoperfusion and hemodialysis is contrasted to the simultaneous "in series" treatment of hemodialysis and charcoal hemoperfusion. Analysis of the two methodologies shows that the combined in series technique offers several advantages, including increased extraction efficiency, decreased time of hemoperfusion cartridge saturation, and rapid correction of electrolyte and acid-base abnormalities, and that it is well tolerated clinically. Simultaneous hemodialysis and charcoal hemoperfusion should be considered in cases of extreme theophylline intoxication.     

Coated carbon hemoperfusion provides limited clearance of protein-bound solutes

This study assessed the capacity of a cartridge containing coated granular carbon to clear protein-bound solutes. Clearances for test solutes were measured while an albumin solution representing plasma was pumped from a 10 L reservoir through the cartridge at a rate of 200 mL/min for 5 h. Clearance values for phenol red, phenytoin, and indican were well below the limit imposed by the plasma flow and declined with time. The clearance of phenol red, which was the most tightly bound solute, fell from 38 +/- 12 to 17 +/- 2 mL/min. Additional studies revealed that the cartridge contained enough carbon to absorb all the protein-bound test solutes, but that the rate of their clearance was limited by the inability of granular carbon to take up solutes rapidly at a low concentration. The rate of solute uptake at low concentration was shown to be much greater when carbon was in powdered rather than granular form. A device in which approximately 50 g of powdered carbon was recirculated in the dialysate compartment of hollow fiber kidneys cleared phenol red and phenytoin more rapidly than the hemoperfusion cartridge containing 300 g of coated granular carbon. These results indicate that hemoperfusion over coated granular carbon provides limited clearance of protein-bound solutes.     

High-flux hemodialysis--an effective alternative to hemoperfusion in the treatment of carbamazepine intoxication

Carbamazepine intoxication is associated with seizures, coma, arrhythmias and death. In acute intoxication, charcoal hemoperfusion is employed for removal of the drug. This can be associated with thrombocytopenia, coagulopathy, hypothermia and hypocalcemia. Alternatively, we used high-efficiency hemodialysis with a batch dialysis system (Genius), lowering not only serum levels of carbamazepine but removing a considerable amount of the drug as measured in the dialysate. This treatment regimen was compared to treatment by hemoperfusion. A 3.5-hour high-flux hemodialysis was as effective as a 2-hour hemoperfusion. We conclude that high-efficiency hemodialysis is a safe and effective alternative for treating life-threatening carbamazepine intoxication.     

Accelerated removal of deferoxamine mesylate-chelated aluminum by charcoal hemoperfusion in hemodialysis patients

Although deferoxamine mesylate (DFO) is effective in removing aluminum (Al) in hemodialysis patients, treatment with this drug is associated with a number of adverse effects. In order to limit the exposure of patients to DFO-Al complexes, the efficacy of colloidin-coated microencapsulated charcoal cartridges added in series to conventional dialyzers was investigated. The clearances of Al by the sorbent system were initially 116 +/- 4.7 mL/min, but decreased to 42.5 +/- 6.6 mL/min after 120 minutes of treatment. Thereafter, the Al clearances remained constant. In contrast, the Al clearances of the dialyzer were 29.5 +/- 1.8 mL/min initially and did not change during the treatment period. Both the percent and absolute decrease in Al levels after four hours of dialysis were greater with the dialyzers plus carbon cartridges than with the dialyzers alone. This resulted in an increase in the minimum net Al removal from 1,862 +/- 174 micrograms/treatment to 3,007 +/- 43 micrograms/treatment (P less than 0.05). Treatment with sorbent hemoperfusion should be considered in selected hemodialysis patients being treated with DFO for Al overload.     

Deferoxamine and coated charcoal hemoperfusion to remove aluminum in dialysis patients

We studied the in vitro and in vivo characteristics of aluminum (Al) removal by coated charcoal hemoperfusion (HP) in combination with intravenous deferoxamine (DFO). DFO enhanced the clearance of Al by HP in vitro after 180 minutes of perfusion with a solution containing 403.3 +/- 14.0 ng/ml of Al at 150 ml/min. The Al clearance was 139 +/- 1.0 ml/min with DFO and 49 +/- 10.0 ml/min (P less than 0.001) without DFO. Addition of DFO enhanced in vitro Al removal from 5.5 +/- 0.9 mg to 10.0 +/- 1.2 mg (P less than 0.05). During our in vivo studies, an HP device was in series in the dialysis circuit after a Cuprophan hemodialyzer. Eight patients with Al toxicity were studied on twelve occasions. Patients received DFO (40 mg/kg) 40 hours before the study. The total Al clearance with the combined hemodialysis (HD) and HP devices was higher than that obtained by the dialyzer alone at 30 minutes (62 +/- 4.9 ml/min vs. 25 +/- 2.5 ml/min, P less than 0.02) and after 180 to 210 minutes (32 +/- 3.0 ml/min vs. 19 +/- 2.9 ml/min, P less than 0.02). After 120 minutes the Al clearance by the HP device alone was significantly lower than the initial Al clearance by HP. Combined HD plus HP removed 2.9 +/- 0.4 mg of Al, whereas the total removal of Al by HD alone was 1.5 +/- 0.3 mg (P less than 0.01).     

Use of hemodialysis and hemoperfusion in poisoned patients

Extracorporeal removal techniques such as hemodialysis, charcoal hemoperfusion, and peritoneal dialysis have been used to remove toxins from the body. To define trends in the use of these techniques for toxin removal, we analyzed the 19,351 cases requiring extracorporeal removal reported to U.S. poison centers from 1985-2005. The number of such patients who received hemodialysis, excluding those with other medical indications, (normalized per million calls) increased from 231 to 707 whereas hemoperfusion decreased from 53 to 12 in the years 1985-2005. Peritoneal dialysis decreased from 2.2 in 1985 to 1.6 in 1991. The most common toxins removed by hemodialysis were lithium and ethylene glycol. There were more dialysis treatments for poisonings with valproate and acetaminophen in 2001-2005 than for methanol and theophylline, although hemodialysis for acetaminophen removal is generally not recommended. Theophylline was the most common toxin removed by hemoperfusion from 1985-2000, but carbamazepine became the most frequent toxin for removal during 2001-2005. Our study shows that the profile of toxins and the type of extracorporeal technique used to remove the toxins have changed over the years.     

Extracorporeal removal of toxic valproic acid levels in children

Toxic ingestion of valproic acid is difficult to treat as no antidote exists and hemodialysis has been considered ineffective for clearance due to high protein binding of this drug. Recent reports suggest that protein binding of valproic acid is saturated at toxic levels, thereby allowing for removal of free drug by extracorporeal circuits. We describe our experiences in two children with toxic blood levels of valproic acid, in whom we were able to achieve effective clearances by extracorporeal removal without charcoal hemoperfusion. In an 18-year-old girl with initial valproic acid levels of 663 μg/ml (therapeutic 46–88 μg/ml), the elimination constant (k_el) increased five- to eightfold from 0.04/h pre dialysis and 0.06/h post dialysis to 0.31/h during high-flux hemodiafiltration. In the same time periods, drug half-life reduced from 15.96 h pre dialysis and 21 h post dialysis to 2.23 h during hemodiafiltration. In a younger 18-month-old child with initial levels of 922 μg/ml, k_el was fivefold higher at 0.25/h during conventional hemodialysis, compared with 0.05/h after dialysis. Similarly, the drug half-life was 2.9 h during dialysis and 12.9 h after dialysis. Both conventional hemodialysis and high-flux hemodiafiltration are effective treatment modalities that should be offered to all pediatric patients with valproic acid ingestion and neurological compromise. Received: 3 October 2001 / Revised: 8 January 2002 / Accepted: 13 January 2002     

Present and Future Uses of Hemoperfusion with Sorbents

International interest in the clinical uses of hemoperfusion has increasingly grown in the last ten years and, as a result, sorbent hemoperfusion has emerged as first-line management in several areas. This center and many others have shown that there is a clear role for hemoperfusion in severe self-poisoning. Plasma extraction ratios for most drugs are significantly higher for hemoperfusion over both resin (0.8) and activated charcoal (0.5; CHP) than for hemodialysis (0.27), under similar conditions of blood flow, plasma drug concentrations, etc. Using appropriate pharmacokinetic models in the analysis of plasma drug profiles, it has been shown that CHP can increase drug elimination rate constants and whole body clearance rates in experimentally intoxicated animals. Enhancement of drug elimination broadens the scope of sorbent hemoperfusion to other areas of application, such as the removal of anticancer drugs (e.g., methotrexate, adriamycin) after cancer chemotherapy. Evaluation of the role of hemoperfusion in hepatic encephalopathy or uremia is limited by the lack of knowledge regarding specific toxic molecules in these syndromes. Nevertheless, in the authors' series of ten patients with fulminant hepatic failure, four survived, in contradistinction to an 80–90% mortality for untreated patients, and virtually all awoke from deep coma. Accompanying reversal of coma, there were significant changes in plasma and cerebrospinal fluid amino acids and in cerebrospinal fluid cyclic AMP concentrations. This suggests that hemoperfusion over charcoal in hepatic encephalopathy may be a useful technique. In this series of uremic patients, although hemoperfusion with charcoal has been shown capable of adsorbing putative uremic toxins including middle molecules up to the present, hemoperfusion alone is only marginally superior to standard hemodialysis. Fouremia, it is likely that multiple specific sorbents will be required, and several compounds for urea and creatinine sorption are presently under investigation.     

Procainamide toxicity in a patient with acute renal failure

A patient developed acute renal failure while receiving oral procainamide (PA). This lead to severe PA and N-acetyl procainamide (NAPA) toxicity. Rebound of NAPA plasma levels postdialysis prolonged the toxicity, which was treated with hemodialysis, hemoperfusion, and combined hemodialysis-hemoperfusion. Because of the potential for PA and NAPA toxicity in patients with renal insufficiency, especially in patients with changing renal function due to acute renal failure, it is recommended that the use of PA be curtailed in this population and that another substitute antiarrhythmic agent be used.     

Effects of hemoperfusion plus high-flux hemodialysis in a patient with methotrexate toxicity

Acute methotrexate toxicity resulting from methotrexate-induced renal fáilue is a medical emergency requiring extracorporeal removal of methotrexate. The optimum method of methotrexate removal has not yet been established. We report a case of osteosarcoma with lung metastasis that was treated with high-dose methotrexate as adjuvant chemotherapy. Although no problems occurred after the first 5 courses of methotrexate, methotrexate-induced renal failure and methotrexate toxicity appeared after the sixth course. The patient was treated, either with hemoperfusion plus high-flux hemodialysis, or hemoperfusion alone, and pre- and post-treatment serum methotrexate concentrations were monitored. The reduction in methotrexate by hemoperfusion alone for 2 hours was 54%, compared to a mean reduction of 59% by hemoperfusion combined with high-flux hemodialysis, for 3 hours. Rebound increases in methotrexate levels were small (less than 1 μmol/L) with either method. The combination of hemoperfusion and hemodialysis resulted in good control of volume status, as well as improvement in serum chemistry values.     

Chlorpropamide overdose in renal failure: management with charcoal hemoperfusion

A potentially lethal chlorpropamide overdose in a patient with chronic renal failure on long-term hemodialysis was treated by two courses of charcoal hemoperfusion. Hemoperfusion shortened the half-life clearance of the drug from a mean value of 93.6 to 3.4 hours. Calculation of the fractional extraction indicated that hemoperfusion reduced the body burden of the drug by 24% and 19% (mean values) during the first and second hours of treatment, respectively. We conclude that charcoal hemoperfusion should be considered a definitive therapeutic option in such cases.     

Extracorporeal management of valproic acid overdose: a large regional experience

BACKGROUND: Valproic acid intoxication is common in North America. Although extra-corporeal therapy has been proposed as beneficial in managing significant exposures, evidence to support its use is limited to isolated case reports. A systematic review has not been performed. METHODS: All cases of valproic acid overdose in Ontario, Canada, reported to the Hospital for Sick Children Poison Information Centre (PIC) between January 1st and July 31st 2002 were reviewed. Patients with valproic acid levels > 100 microg/mL were divided into two groups: those treated with and without extra-corporeal therapy. All hospital-measured valproic acid levels and additional clinical information including elimination half-life and clearance were obtained for patients treated with extra-corporeal therapy. RESULTS: There were 28,362 calls to the PIC, of which 139 related to valproic acid poisoning. Thirty-two patients had peak levels > 100 microg/mL. 26 patients were managed conservatively and 6 with extra-corporeal therapy. Survival was 100% in both groups. Patients who received extra-corporeal therapy had higher peak levels (p=0.005), were more frequently treated with charcoal (P=0.006), required intensive care admission (P=0.019), intubation (P<0.001), and vasopressors (P=0.004). Valproic acid elimination was enhanced about tenfold through extra-corporeal methods. Complications included tonic-clonic seizures in 1 patient who received hemodialysis, and thrombocytopenia in 1 patient who underwent hemoperfusion. CONCLUSION: Hemodialysis and hemoperfusion are safe, effective adjuncts in the management of serious valproic acid intoxication and should be considered for patients with hemodynamic or neurological instability. Further study is needed to determine whether hemodialysis alone versus combined hemodialysis-hemoperfusion is more effective for this condition.     

Charcoal Hemoperfusion for Treatment of Ethchlorvynol Overdose

Abstract: Charcoal hemoperfusion is commonly employed to treat overdose of a number of drugs. There are varying Reports of its efficacy in the treatment of ethchlorvynol overdose. Herein is Reported a case of ethchlorvynol overdose successfully treated with charcoal hemoperfusion within 5 h of ingestion of 12.5 g of the drug. The patient was deeply comatose at that time but recovered consciousness at the end of 4 h of hemoperfusion. Ethchlorvynol clearance over the charcoal varied from 118 to 147 ml/min. There were no bleeding complications. Prompt charcoal hemoperfusion may be an effective mode of treatment in cases of ethchlorvynol intoxication.     

Hemoperfusion for the Treatment of Poisoning: Technology,Determinants of Poison Clearance,and Application in Clinical Practice

Hemoperfusion is an extracorporeal treatment based on adsorption, historically reserved for the treatment of acute poisonings. Its use was popularized in the 1970s after several in vitro and animal experiments had demonstrated its efficacy, and was even preferred over hemodialysis in the management of overdosed patients. With the advent of new and more efficient dialytic modalities, hemoperfusion is now less frequently performed in the Western world. However, hemoperfusion still remains popular in developing countries. The present article reviews the technique of hemoperfusion, the factors influencing poison clearance through adsorption and its current applications.     

Repeat charcoal hemoperfusion treatments in life threatening carbamazepine overdose

A 16-month-old female experienced a massive carbamazepine ingestion resulting in a peak serum carbamazepine concentration of 55 μg/ml. Clinical manifestations included generalized seizures, coma, shock, and gastrointestinal hypomotility. Gut decontamination was attempted using multiple-dose activated charcoal and cathartics. Because of the severity of illness, charcoal hemoperfusion was initiated. The patient underwent three sessions of charcoal hemoperfusion, each utilizing a fresh cartridge, with one session immediately following the other. Serum carbamazepine and carbamazepine-10,11-epoxide concentrations decreased from 54 μg/ml to 23 μg/ml, and 30 μg/ml to 17 μg/ml, respectively, during charcoal hemoperfusion. There were no complications. The patient recovered completely and was discharged on the 4th hospital day. Charcoal hemoperfusion should be considered for life-threatening carbamazepine intoxication, especially when drug-induced gastrointestinal hypomotility prevents elimination via the gut. Received: 12 October 1998 / Revised: 11 December 1998 / Accepted: 17 December 1998     

Poison elimination methods in acute poisoning

This paper presents current ideas about the application of poison elimination methods in acute poisoning. The methods are divided into two groups: poison elimination before absorption; and enhancement of elimination after drug absorption. The former include washes, emesis, gastric lavage, and administration of activated charcoal and cathartics, while the latter include forced diuresis and extracorporeal toxin elimination such as hemodialysis or hemoperfusion. The indications, contraindications, techniques, and complications, associated with these elimination methods, except for extracorporeal toxin elimination, are discussed. In the treatment of poisoning, early and comprehensive poison elimination is important.     

Clearance of Meprobamate by Hemoperfusion Over Columns of Charcoal and Amberlite Resin

Perfusion of the blood of a patient with toxic levels of meprobamate through an activated charcoal cartridge resulted in efficient early clearance of the drug, then a decline in extraction. Perfusion through a resin column resulted in total drug extraction without a decline in clearance over four hours. Both procedures were stable with minimal disturbance in hematological values or blood chemistries. This is the first report of in vivo hemoperfusion over resin for meprobamate poisoning. The efficacy and safety of the procedure need emphasis.