Haemoperfusion: a useful therapy for a severely poisoned patient?

Although it is many years since a haemodialysis and haemoperfusion over uncoated and later coated charcoal columns have been used for the treatment of intoxicated patients, the clinical efficacy of these extracorporeal techniques in the treatment of severely poisoned patients remains a matter of debate. Some of the reasons for this controversy may be the indiscriminate use of haemoperfusion in any form of intoxication, the lack of well-controlled studies and the wrong interpretation of the high haemoperfusion clearance values sometimes obtained. Simple pharmacokinetic principles are applied to this type of treatment and some practical guidelines as to how and when haemoperfusion should be applied or presented are reviewed. The limited place of haemoperfusion in the treatment of severe poisoning, its further declining use in the future, at least in its present design, and some promising new treatments are emphasized.

[Poisoning as a method of suicide in children and adolescents]. / Vergiftungen als Suizidmittel von Kindern und Jugendlichen.

The number of suicides by children and juveniles has remained similar or even slightly reduced in the last 5 years. This correlates with the constancy or slight reduction in the number of the under-20-years population over this period. Comparison with deaths due to suicide in Prussia (1894-1897) indicates that suicide in children and juveniles is not more common today than it was nearly a hundred years ago. Hanging and suffocation are the most frequent means, followed by poisoning. Less common are jumping from a height, shooting, drowning or stabbing. Cause of the suicide attempt is usually a disturbed relationship to a partner. Acute quarrel with parents dominates. The psychopathological background is abnormal reactions to experience and abnormal reactions to conflict. Neurosis and psychosis or infantile reactions are much less common.

[Poisoning by hypochlorite-containing disinfectants. A retrospective analysis of 594 cases of poisoning]. / Vergiftungen durch hypochlorithaltige Sanitärreiniger. Eine retrospektive Analyse von 594 Vergiftungsfällen.

Hypochlorite-containing disinfectants or bleaching fluids, if inhaled, may lead to life-threatening poisoning (56% of moderately severe cases, 5% of severe cases) through the immediate liberation of chlorine gas, if they are used together with another cleansing fluid which is very acid. A rough estimate suggests that there must be about 700 cases of such poisonings per year in the Federal Republic of Germany. The characteristic symptom is a respiratory distress syndrome when the liberated chlorine gas is inhaled. Toxic pulmonary oedema and cardiovascular failure can occur if the poisoning takes a fulminating course.

[Poisoning with leather-impregnation sprays. A retrospective analysis of 224 cases of poisoning]. / Vergiftungen durch Leder-Imprägniersprays. Eine retrospektive Analyseüber 224 Vergiftungsfälle.

Annually, there are about 100-200 intoxications in the Federal Republic of Germany caused by inhalation of leather impregnation sprays. The course of these intoxications is moderately severe in 60% and severe in 18% of the cases. The signs and symptoms are characterized by a respiratory distress syndrome which sets in about 15-60 min after spraying and which requires several days of hospitalisation in severe cases. The sprays contain about 7-11 components; their toxicity is not exclusively associated with one substance only. Lower toxicity can be achieved by preparing a basic formulation adjusted to the low-hazard components.

Acute toxicity of pyrazolones.

Pyrazolone intoxication accounts for most (52 percent) mild analgesic poisonings in West Germany. Severe and fatal intoxication with pyrazolones is, however, rare. In the German literature, only 50 cases have been described in the past 62 years; 80 to 90 percent of these were caused by aminopyrine, which was withdrawn from the West German market in 1978 and replaced by propyphenazone. Up to now, no fatal poisoning with propyphenazone has been reported. However, the signs and symptoms of severe intoxication are similar for both propyphenazone and aminopyrine. The acute toxicity of dipyrone is slightly lower than that of propyphenazone, whereas phenylbutazone and oxyphenbutazone clearly cause less severe reactions. Characteristic symptoms include impaired consciousness progressing to coma, and convulsions. In addition, arrhythmia and cardiogenic shock may occur. Severe aminopyrine intoxication may also be complicated by sudden apnea. Liver damage may develop after a latent period of about 24 hours, especially after phenylbutazone and oxyphenbutazone poisoning. Therapy involves supportive measures as well as gastric emptying by emesis or lavage, installation of medical charcoal, and induction of diarrhea or gut lavage. Although exact clinicotoxicologic data on hemoperfusion are not available as yet, distribution volumes, plasma half-lives, and endogenous plasma clearances as well as results of in vitro trials all suggest the efficacy of this procedure. Hemoperfusion with uncoated amberlite XAD-4 resin is, therefore, recommended for patients with severe pyrazolone intoxication.

[Clinical findings and treatment of paraquat poisoning in childhood]. / Klinik und Therapie der Paraquat-Intoxikation im Kindesalter.

Two of three children with Paraquat poisoning were treated with hemoperfusion. All patients survived. One patient had an acute renal failure after the intoxication. A percutaneous poisoning is discussed in one child with large skin necrosis after direct contact with Paraquat. An irreversible lung fibrosis did not set in. The prognosis for a patient with Paraquat intoxication depends on a speedy and consistent detoxication from both the bowel and from the blood by hemoperfusion. This is the only way to survive the acute intoxication and to avoid lung fibrosis, that would lead to death.

Near fatal percutaneous paraquat poisoning.

A fatal paraquat poisoning can occur when relatively large areas of skin are contaminated with a concentrated solution of paraquat (Gramoxone). A paraquat absorption takes place of the same magnitude as that with an equal dose per os. In the presence of mechanical or chemical lesion of the skin the percutaneous paraquat absorption is distinctly enhanced.

Successful treatment of paraquat poisoning: activated charcoal per os and "continuous hemoperfusion".

Ingestion of paraquat results in an extremely dangerous poisoning. The first aim is to clear the gastrointestinal tract by inducing emesis and performing gastric/gut lavage; as much activated charcoal as possible should be administered per os and as quickly as possible. The best measure to eliminate paraquat from blood and tissue is hemoperfusion with coated activated charcoal; it has to be performed in the sense of "continuous hemoperfusion" about 8 h/d over a period of 2-3 weeks. These measures give a chance to lower the lethality of paraquat poisoning.

Activated charcoal is as effective as fuller's earth or bentonite in paraquat poisoning.

In vitro investigations have shown that the adsorption capacity of activated charcoal ('Kohle-Compretten', 'Ultracarbon', E. Merck, Darmstadt, FRG) is just as high as that of 'Fuller's earth' (Surrey powder, Laporte Industries Ltd., Luton, GB) or 'Bentonite BP W.B. (Steetley Minerals Ltd., Milton Keynes, GB). Fuller's earth ('Fullererde') from another manufacturer has had very poor adsorption properties and is thus not suitable for the treatment of paraquat poisoning. Animal experiments have shown that the curative effect of activated charcoal given 0.5, 1, 2, and 3 h after ingestion of 200 and 300 mg paraquat/kg body weight is equally as good or even better than that of 'Fuller's earth' or 'Bentonite BP W.B' Activated charcoal is a substitute of equal value to these mineral soils.

Hemoperfusion in toxicology. Basic considerations of its effectiveness.

The indication to use hemoperfusion as a therapeutic measure in severe intoxications in man should be based on a three-step evaluation. First, the ability of an adsorbent to eliminate the poison from human blood has to be known. Second, the distribution volume has to be small and the spontaneous half-life of the poison has to be relatively long, such that lowering the toxic blood level results in a concomitant decreasing tissue concentration. Third, studies in poisoned patients have to prove that it is possible by hemoperfusion to lower the total body load to a toxicologically relevant extent.

[Unexpected metabolic acidosis in severe lye poisoning (author's transl)]. / Unerwartete metabolische Azidose bei schwerer Lauge-Intoxikation.

A woman 38 years of age suffering from severe peroral lye intoxication, without shock, developed prolonged metabolic acidosis lasting for 8 days despite substitution therapy. Metabolic acidosis was caused by lactic acid. The increased lactic acid production in the marginal regions of the corroded upper digestive tract as well as the impaired lactate removal by the injured liver were most probably responsible for this lactic acidosis.

Unexpected metabolic acidosis in severe lye poisoning.

Prolonged metabolic acidosis developed in a 38-year-old patient suffering from severe peroral liquid lye poisoning without shock syndrome. Metabolic acidosis was caused by lactic acid. The combination of increased lactic acid production in the marginal regions of the necrotic intestinal areas and impaired lactate removal by the liver were most probably responsible for this lactic acidosis.

An economical hemoperfusion system to determine in vitro clearances of various poisons with different adsorbents.

An economical hemoperfusion system for clearance studies in vitro was developped. It was ascertained, that hemoperfusion using columns which contain 13 g of adsorbent and perfused at a blood flow rate of 1.25 ml/min results in the same relative clearances as when using clinical sized columns containing 300--355 g of the absorbent and run at 100ml/min. The adsorption kinetics of toxicologically important drugs and pesticides are given as examples. To date 27 substances were tested systematically. The investigation has shown, that no adsorbent is without exception the best one, but the efficacy can vary from substance to substance.

Intoxication with pyrazolones.

1 About 50 severe or fatal (mostly accidental) cases of intoxication in children by pyrazolones have been reported in the German literature of the past 59 years. 2 Characteristic symptoms are impaired consciousness progressing to coma and convulsions. In addition, sudden apnoea and cardiac arrest may occur. Hepatic lesions may develop after a latent period of 12-24 hours. 3 Haemoperfusion seems to be the only therapeutic measure which is able to reduce the total body load of all pyrazolones to a toxicologically relevant extent. Actual clinico-toxicological data from poisoned patients are not available as yet; however, distribution volumes, plasma half-lives and endogenous plasma clearances as well as removal kinetics in vitro of aminophenazone (aminopyrine), propyphenazone, metamizole (dipyrone), phenylbutazone and oxyphenbutazone as point to the efficacy of haemoperfusion with amberlite XAD-4 resin.

Two survivors of severe paraquat intoxication by "continuous hemoperfusion".

"Continuous hemoperfusion" (8 h/day for 2--3 weeks) was performed in two patients suffering from severe paraquat intoxication. On account of paraquat plasma concentrations a fatal outcome due to pulmonary fibrosis would have been expected in both cases. However, both patients survived following "continuous hemoperfusion" therapy. Coated activated charcoal seems to have a higher affinity for paraquat than lung tissue.