A. N. P. van Heijst

Therapeutic Problems in Cyanide Poisoning

In three patients with severe acute cyanide poisoning, a cyanosis was observed instead of the bright pink skin coloration often mentioned as a sign in textbooks. Treatment of cardiopulmonary insufficiency is as essential as antidotal therapy and the use of sodium nitrite and 4-DMAP is not without risk as, in practice, the methemoglobin-level induced is difficult to control.

Charcoal Hemoperfusion in the Treatment of two Cases of Acute Carbamazepine Poisoning

Charcoal hemoperfusion is effective in the treatment of acute carbamazepine (CBZ) poisoning, its efficacy depending on the metabolic capacity of the patient involved. This was assessed in two cases of CBZ poisoning in which CBZ and its metabolite carbamazepine-10,11-epoxide (CBZO) were monitored. One patient had not been treated with CBZ or other enzyme-inducing drugs before the overdose ingestion. The CBZO/CBZ plasma concentration ratio of this patient was 0.15 +/- 0.01 (mean +/- s.d.), indicating a normal metabolic capacity. The average clearance values obtained with the Haemocol were 85 ml/min for CBZ and 81 ml/min for CBZO. The other patient had been on long-term treatment with anticonvulsive drugs before. The CBZO/CBZ ratio was 1.58 +/- 0.16, indicating a high metabolic capacity and, consequently, a high intrinsic clearance. The average clearances obtained with the Adsorba 300 C were 129 ml/min for CBZ and 133 ml/min for CBZO. Saturation of a charcoal column can occur during a four hours treatment, in particular if the plasma CBZO concentration is high. CBZ and CBZO were also monitored in erythrocytes. The erythrocyte/plasma concentration ratios of CBZ were 0.90 +/- 0.11 (mean +/- s.d.) and 1.36 +/- 0.10. CBZO was 30-40 per cent more concentrated in erythrocytes than was CBZ. The erythrocyte/plasma concentration ratios of CBZO were 1.36 +/- 0.10 and 1.80 +/- 0.23.

Toxicokinetic aspects of thallium poisoning. Methods of treatment by toxin elimination

The elimination techniques which are used in the treatment of thallium poisoning are evaluated in toxicokinetic perspective. Prussian Blue therapy and forced diuresis are effective in the treatment of acute as well as subacute thallium intoxications. Both elimination techniques can be applied without danger from neurological side effects. Generally, the combined use of these techniques is recommended. Since obstipation as well as renal impairment are common in thallium poisoning, extracorporal elimination techniques are of additional importance. In particular, charcoal haemoperfusion has proven to be successful in the elimination of thallium from the body, especially in the early phase of the intoxication.

An evaluation of the efficacy of charcoal haemoperfusion in the treatment of three cases of acute thallium poisoning

The efficacy of intermittent charcoal haemoperfusion in combination with forced diuresis and Prussian Blue therapy was evaluated in three cases of thallium poisoning. At a blood flow of 300 ml/min the average blood clearance values obtained with haemoperfusion were 72 ± 11 ml/min (mean±SD) at a starting blood concentration above 2 mg/l and 120 ± 23 ml/min (mean ± SD) below this blood level. As a result of the combined intensive treatment, the thallium half-lives in blood observed during the period monitored were only 25–41 h.Removal of thallium by haemoperfusion is faster per unit of time than simultaneous excretion by forced diuresis. When forced diuresis was combined with intermittent (4–20 h intervals) haemoperfusion therapy, the total elimination by each technique was about equivalent over the period of combined treatment.Saturation of the Adsorba 300 C columns occurred during treatment. As a result, the clearance obtained did decrease to half the initial value in 2–3 h. As this decrease in efficacy is related to the blood concentration, haemoperfusion is more efficient at lower blood concentrations. This is in contradistinction to forced diuresis, of which the excretion is proportional to the blood concentration.

Buformin concentrations in a case of fatal lactic acidosis

SummaryA fatal case of lactic acidosis in a 84 year old diabetic woman taking buformin is reported. Buformin concentrations in serum, other body fluids and tissues were measured by gas chromatography. Serum buformin concentration at admission was 5.5 mg/1. Postmortem concentrations were: in serum 3.2mg/l; in lung 2.8mg/kg wet weight; in heart 3.0mg/kg; in pericardial fluid 3.5 mg/1; in liver 5.2 mg/kg; in bile 6.3 mg/1; and in kidney 98 mg/kg.

Chronic Cyanide Poisoning in Relation to Blindness and Tropical Neuropathy

Within a group of 20 patients showing optic atrophy and macula degeneration, 14 patients could be examined for neurological and audiometric defects. In 6 patients neurological signs and symptoms were observed. Nine patients reported loss of hearing and in 3 of them a severe perceptive deafness was seen in the audiogram. In 3 of the 14 patients a combination of severe neurologic and audiologic symptoms developed and in two of them a high thiocyanate concentration in serum was observed. The occurrence of perceptive deafness and posterior column sensory loss in the lower extremities in four of the patients made the diagnosis of polyneuropathy the most plausible. Although a similarity to chronic myelopathies caused by nutritional cyanide poisoning cannot be denied, the mean thiocyanate concentration in plasma 24 mumol/L (1.39 mg/L), and the cyanide levels in the blood 0.09 mumol/L (2.3 micrograms/L) were substantially lower than those found in other individuals during periods of extreme drought in which food only consisted of the bitter variety of cassava. The role of cyanide in the etiopathology of this polyneuropathy is unknown.

Massive Theophylline Intoxication: Effects of Charcoal Haemoperfusion on Plasma and Erythrocyte Theophylline Concentrations

1 The results of a charcoal haemoperfusion on plasma and erythrocyte theophylline concentrations are described in a patient, intentionally intoxicated with a sustained-release theophylline formulation. 2 It is demonstrated that the charcoal-filled Gambro Adsorba 300-C column is effective in removing theophylline. 3 This effectiveness is based on pharmacokinetic parameters, which are presented. 4 The necessity of measuring plasma and erythrocyte theophylline concentrations is outlined. Calculations based on plasma theophylline concentrations only can lead to an underestimation of the effectiveness.

Biocompatibility of haemoperfusion

To evaluate the influence of haemoperfusion on haemodynamics, complement system, leucocyte and thrombocyte concentration, a controlled study was performed in three groups of five dogs each. During the first 30 min of haemoperfusion with columns containing cellulose-coated activated charcoal, a significant decrease of mean aortic pressure, cardiac output and stroke volume was observed, while heart rate and total systemic resistance decreased. A comparable phenomenon, although to a much lesser extent, was observed during perfusion using columns containing polystyrene resin. Perfusion with columns containing cellulose-coated activated charcoal caused a significant decrease in total haemolytic complement, indicating activation of the complement system. A significant decrease in the leucocyte and thrombocyte concentration due to sequestration of granulocytes and thrombocytes in the columns was observed during the first 30 min of perfusion in both groups. Pulmonary leucostasis, without decrease of arterial oxygen tension, occurred during perfusion with columns containing cellulose-coated activated charcoal. Both the simultaneous occurrence and the transient character of the haemodynamic changes, complement activation and sequestration of granulocytes and thrombocytes in the perfusion column suggest a relationship between these various changes. The results stress the importance of close monitoring of the haemodynamic parameters of the intoxicated patient, particularly during the early phase of haemoperfusion.

A Specific Method for the Analysis of Buformin in Pre- and Post- Mortem Human Material

As for many other drugs, also current and essential information on the disposition of biguanides in man are scarce.