Carbromal intoxication--hemodialysis or hemoperfusion?
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Biomedical subjects
Publications and source records attributed to H W Leber.
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Ten patients were treated with 10 g essential amino acids per day orally; 9 patients received 9.5 g of a mixture of essential amino acids (Lys, Thr, Try, His, Tyr) and ketoanalogues of Ile, Leu, Phe, Val, Met per day and a control group of 11 patients received no supplementation. All patients were on a liberal food intake amounting to 1g protein/kg body weight and 31 kcal/kg body weight daily. Before and three months after the beginning of supplementation the following parameters were measured: serum concentrations of albumin, transferrin, urea, creatinine, blood haemoglobin content and haematocrit, activities of the enzymes delta-aminolevulinic acid dehydrase and porpho-bilinogen desaminase, and globin synthesis in peripheral red blood cells. After treatment with either essential amino acids or keto acids a significant stimulation of globin synthesis occurred. None of the other parameters was altered. It is concluded that in well-nourished patients supplements of essential amino acids or keto acids are ineffective.
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It has been demonstrated with an in vitro model that hemoperfusion through Amberlite XAD4 or coated charcoal containing cartridges eliminates carbromal and its ureid derivatives more efficiently than hemodialysis. The following clearancs were measured in vitro (blood flow: 200 ml/min): Coil dialyser (1 m2): 55-85 ml/min, charcoal hemoperfusion 100-125 ml/min, Amberlite XAD4 hemoperfusion: 200 ml/min. The data of one patient who had been hemoperfused after the ingestion of 35 g Carbromal with the Haemocol cartridge (SMith & Nephews) are depicted. Our results permit to draw the conclusion that hemoperfusion at this time is the most efficient means to eliminate Carbromal from intoxicated patients.
Male rats weighing 100-130 g were treated orally with a daily dose of 1 X 10 mg Legalon (active principle: silymarin)/100 g b.w. daily for 4 or 10 days. 4 and 10 days after the beginning of the pretreatment a significant increase of the activity of the mixed function oxidation system (Cytochrome P-450, aminopyrine demethylation, p-nitroanisole demethylation) was observed. No alteration of the body weight, the liver wet weight, the microsomal protein content, the cytochrome b5 content and the activities of glucose-6-phosphatase (G-6-Pase) and of a glucoronidase (4-methylumbelliferone) took place after the Legalon treatment. 4 h after the oral administration of 0.5 ml CCl4/kg b.w. the activity of the mixed function oxidation system and of the G-6-Pase was markedly decreased. This effect could not be prevented by the oral administration of 1 X 10 mg Legalon/100 g b.w. 6 h prior to CCl4 application. In human subjects the treatment with daily doses of 3 X 70 mg Legalon during 28 days had no influence on the metabolism of aminopyrine and phenylbutazone. From our results it is concluded that Legalon despite its effects in experimental animals has no influence on drug metabolism in man, when applied in therapeutic amounts.
Globin synthesis was measured by incubating washed packed red cells with a balanced amino acid mixture and 14C-Histidine. After globin had been isolated from the haemolysate the 14C-incorporation rate per 10 mg globin per min was estimated. With regard to globin synthesis no differences existed between patients on chronic intermittent haemodialysis therapy (n equals 41), patitents suffering from secondary anaemia due to chronic infection, rheumatism or malignant diseases (n equals 21) and healthy subjects (n equals 37). Patients with acute bleeding on the other hand, had significant higher 14C-incorporation rates caused by an increase of the reticulocyte count mu1 blood (n equals 13). When substances retained in renal failure were added to the incubation mixture a marked inhibition took place with guanidinosuccinic acid, methylguanidine and fraction containing peptides with a molecular weight between 1200-1400 present in uraemic serum and normal urine, but not in serum from patients without renal failure.
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Since no information exists concerning porphyrin metabolism in uraemic patients we have measured the activities of delta-aminolaevulinic acid dehydrase (D-ALA-D) and porphobilinogen desaminase (PBG-D) in reticulocytes from uraemic patients, anaemic patients without uraemia and in healthy subjects. Despite a severe anaemia uraemic patients had the same amount of reticulocytes/mul blood. In uraemic patients D-ALA-D activity was reduced to about 20% compared to healthy subjects, PBG-D in uraemia was decreased to about 70%. It is concluded that porphyrin metabolism is altered in uraemic patients.
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