The beagle dog has been employed as the experimental model for the active detoxification of drugs administered in overdose. Comparison is mode between haemodialysis, hoemoperfusion and forced diuresis and these together compared with more conventional supportive therapy, using this breed. By reference to haemodialysis, a well established technique for the treatment of renal failure, an attempt has been made to define the permissible tolerance in changes of adverse potential. Because the drugs investigated can have adverse effects in their own right on the variables normally studied during toxicological evaluation, the changes observed consequent upon perfusion are often not as severe as they appear on preliminary inspection. Indeed, the response by an individual dog when used as its own control seems to vary sufficiently from the part in common with the original experimental procedure that its use does not assist in defining safety limits more closely. Hoemoperfusion in the context of acute poisoning therapy is designed for single use situations, so these results should not be extended to hoemoperfusion as a repetitive procedure, or as an adjunct to haemodialysis. Furthermore these results refer to experimental conditions in dogs, which appear to be more susceptible than man to platelet changes. In addition, a disproportion is introduced since the quantity of adsorbent and the flow rate employed are more appropriate to a 70 kg man than to a 12 kg dog. The high survival rate of control animals appears to confirm the belief that many cases of over-dosage will recover with good supportive treatment, and that more active treatment should be kept for patients with established high blood drug levels or additional complications. Forced diuresis, used routinely in man In the treatment of some drug overdosages, shows minimal efficacy in the dog when compared with haemodialysis and, especially, to haemoperfusion. Clinically forced diuresis is not without hazard and the procedure of alkaline diuresis con lead to protracted recovery. Whilst some differences between dog and man must be expected, the experimental evidence presented does not support the need for forced diuresis. The possibility of haemoperfusion as a treatment of paraquat poisoning has been investigated. Therapeutic benefit can be attained and the procedures recorded suggest that haemoperfusion could assist an understanding of the toxic kinetics. However, perfusion needs to be instituted rapidly, and at present is unlikely to reverse cases already suffering from massive organ damage.
|Date of Award||1980|