Hemodialysis, hemoperfusion

After a valproate overdose a 27-year-old man developed seizures, hypernatremia, respiratory failure, metabolic acidosis, liver failure, and bone marrow depression (125). His plasma valproic acid concentration was 1414 pg/ml. Treatment with hemodialysis was effective in enhancing valproic acid clearance, while hemoperfu-sion was relatively less effective, because of saturation of the column. Overall, the half-Ufe of the drug was reduced from over 20 hours before treatment to less than 3 hours during hemodialysis/hemoperfusion drug removal was probably favored by saturation of drug binding to plasma proteins, which resulted in a low unbound fraction (32% at the start of treatment). He was comatose for 5 days but recovered fully thereafter. 

Enhanced fecal excretion Hemodialysis Hemoperfusion Prussian blue [7]... 

D. Enhanced elimination. Hemodialysis, hemoperfusion, peritoneal dialysis, and repeat-dose charcoal are not effective in removing anticholinergic agents. 

D. Enhanced elimination. There is no role for hemodialysis, hemoperfusion, repeat-dose charcoal, hemodiafiltration, or other enhanced elimination techniques. Hemodialysis may be required tor supportive care of patients with acute renal failure, and it can marginally increase the elimination of the copper-chelator complex. 

D. Enhanced elimination. There is no documented efficacy for diuresis, hemodialysis, hemoperfusion, or repeat-dose charcoal. 

C. Extracorporeal removal techniques (eg, hemodialysis, hemoperfusion, and repeat-dose activated charcoal see p 54) may enhance the clearance of phenobarbital, possibly requiring supplemental dosing to maintain therapeutic levels. 

Hollow Fiber with Sorbent Walls. A cellulose sorbent and dialy2ing membrane hoUow fiber was reported in 1977 by Enka Glan2stoff AG (41). This hoUow fiber, with an inside diameter of about 300 p.m, has a double-layer waU. The inner waU consists of Cuprophan ceUulose and is very thin, approximately 8 p.m. The outer waU, which is ca 40-p.m thick, consists mainly of sorbent substance bonded by ceUulose. The advantage of such a fiber is that it combines the principles of hemodialysis with those of hemoperfusion. Two such fibers have been made one with activated carbon in the fiber waU, and one with aluminum oxide, which is a phosphate binder (also see Dialysis). 

A variety of therapies for thallium poisoning have been suggested by neutralising thallium in the intestinal tract, hastening excretion after resorption, or decreasing absorption. Berlin-Blue (fertihexacyanate) and sodium iodide in a 1 wt % solution have been recommended. Forced diuresis hemoperfusion and hemodialysis in combination results in the elimination of up to 40% of the resorbed thaHous sulfate (39). 

Metabolism/Excretion - In the first 24 hours, approximately 75% of a dose is excreted in urine by glomerular filtration. Elimination half-life is 4 to 6 hours in adults and 2 to 3 hours in children. About 60% of an intraperitoneal dose administered during peritoneal dialysis is absorbed systemically in 6 hours. Accumulation occurs in renal failure. Serum half-life in anephric patients is approximately 7.5 days. Vancomycin is not significantly removed by hemodialysis or continuous ambulatory peritoneal dialysis, although there have been reports of increased clearance with hemoperfusion and hemofiltration. 

Hemoperfusion is like hemodialysis except that blood is circulated extracorporeally through a column with adsorbent material like resin or charcoal, which binds molecules electrostatically. The molecules likely to be removed are characterized as poorly dialyzable, lipid-soluble, protein bound. Among the indications for hemoperfusion in the management of poisoning include the presence of a poison in a patient with impairment of excretory system (i.e. damaged kidneys), intoxication of a drug known to produce delayed toxicity or metabolized to a more toxic metabolite (i.e. paraquat or methotrexate), deterioration of the clinical state of the poisoned patient despite conservative therapy (i.e. convulsions or cardiac arrhythmias following theophylline intoxication), or development of coma as a complication. 

Cutler RE, Forland SC, Hammond, P, and Evans, JR. Extracorporeal removal of drugs and poisons by hemodialysis and hemoperfusion. Annu Rev Pharmacol Toxicol 1987 27 169-191. 

Consider forced diuresis, urine acidification, or alkalinization if specific antidotes are not available Hemodialysis or charcoal hemoperfusion may be appropriate for rapid elimination if antidotes are not available... 

Extracorporeal devices to support a compromised liver were reviewed by Allen et al. and Strain and Neubcrgcr.Various nonbiological approaches such as hemodialysis or hemoperfusion over charcoal have met with limited success, presumably because these systems inadequately replaced the synthetic and metabolic functions of the liver. Conversely, biological approaches such as hollow fiber devices, flat plate systems, perfusion beds, and suspension reactors have shown encouraging results but are difficult to implement in a clinical setting. 

Hemoperfusion and hemodialysis may be used in very severely poisoned patients. 

Table 59-3. Indications for Hemodialysis (HD) and Hemoperfusion (HP) in Drug Poisoning. ...

Generally, hemodialysis is easier to perform and is associated with fewer complications. It is ideal for low-molecular-weight, polar, water-soluble molecules such as alcohol, salicylate, or lithium. Hemoperfusion is used for drugs that are poorly soluble in water or relatively higher in protein binding. 

Hemoperfusion differs from hemodialysis in that the blood is passed over a resin or charcoal column. The drug becomes bound to the column and the clean blood returned to the body. Hemoperfusion units have adsorptive surface areas of several thousand square meters while hemodialysis devices have an effective dialysis surface limited to several square meters. Obviously, relatively sophisticated technology is required for these procedures and there is the need to prevent clotting in the circuit, which can produce complications. 

Complications of hemoperfusion include platelet and leukocyte depletion, hypocalcemia, and a mild reduction in body temperature (50). In many cases, these complications are outweighed by the fact that intoxicants are removed more rapidly by hemoperfusion than by hemodialysis. However, an additional consideration is that hemoperfusion clearance tends to decline during therapy as column efficiency declines, presumably reflecting saturation of adsorbent sites (53). In addition, intercompartmen-tal clearance from skeletal muscle and other slowly equilibrating tissues can limit the extent of drug removal by hemoperfusion and result in a rebound of blood levels and possible toxicity at the conclusion of this procedure (54). In some instances, alternative therapies have been developed that are even more efficient than hemoperfusion. For example. 

Because digoxin has a large apparent volume of distribution, plasma exchange, hemodialysis, and hemoperfusion are not effective methods of removing digoxin from the body. 

A 35-year-old woman took diphenhydramine 16 g and developed hypertension and QRS prolongation charcoal hemoperfusion and hemodialysis were used successfully (12). 

Mullins ME, Pinnick RV, Terhes JM. Life-threatening diphenhydramine overdose treated with charcoal hemoperfusion and hemodialysis. Ann Emerg Med 1999 33(l) 104-7. 

When serum methotrexate concentrations are high, leu-covorin (folinic acid) rescue may protect against renal damage. Methotrexate concentrations are only transiently lowered by hemoperfusion, and they are unaffected by peritoneal dialysis once there is acute renal insufficiency. Sustained reductions in drug concentrations and recovery of renal function have been reported after charcoal hemoperfusion followed by hemodialysis (63,64). 

ReUing MV, Stapleton FB, Ochs J, Jones DP, Meyer W, Wainer IW, Crom WR, McKay CP, Evans WE. Removal of methotrexate, leucovorin, and their metabolites by combined hemodialysis and hemoperfusion. Cancer 1988 62(5) 884-8. 

The only alternatives to glutathione donors are charcoal hemoperfusion and hemodialysis, which can be effective up to 18 hours after dosage. However, the longer the time from ingestion to treatment, the less likely the condition is to be reversible and the more likely a fatal outcome. 

The use of hemodialysis or hemoperfusion in the management of theophylline toxicity was initially controversial (SEDA-8, 11) (SEDA-9, 10) (SEDA-11, 5). In one study... 

Shannon MW. Comparative efficacy of hemodialysis and hemoperfusion in severe theophylline intoxication. Acad Emerg Med 1997 4(7) 674-8. 

Franssen EJ, van Essen GG, Portman AT, de Jong J, Go G, Stegeman CA, Uges DR. Valproic acid toxicokinetics serial hemodialysis and hemoperfusion. Ther Drug Monit 1999 21(3) 289-92. 

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