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7. Recommendations for research

Introduction

7.1 Research into methods of counteracting the effects of the chemicals considered in this report has, in some cases, been underway since their use during the First World War. Rapid advances are perhaps unlikely and before discussing possible approaches the issues requiring operational research are discussed.

7.2 In cases of poisoning by nerve agents and hydrogen cyanide, treatments exist but have to be given as quickly as possible after poisoning to be effective. It is appreciated that in the setting of a terrorist incident there is likely to be a delay between exposure to a toxic substance and administration of therapy. Reducing this interval is very important. It is recommended that operational research is undertaken with a view to achieving this.

7.3 It is made clear in several sections of this report that assisted respiration and oxygen are mainstays of effective patient management. It is appreciated that providing such assistance in a mass casualty situation will be very difficult and that these difficulties may be added to by the need for decontamination of patients before admission to hospital. However, it is recommended that operational research designed to reduce the interval between exposure and access to this form of care be undertaken. Research into how best to provide assisted respiration and supplementary oxygen to as many patients as possible is also recommended.

Specific recommendations

(i) Oxime therapy in nerve agent poisoning

A systematic investigation should be undertaken of the t½ of aging and reactivation of inhibited human erythrocytic acetylcholinesterase using the three oximes, P2S, obidoxime and HI-6. The nerve agents used should include tabun, sarin, soman, VX and cyclosarin. The study design should include a time course of reactivation, at various different concentrations of nerve agent and no means should be used to inhibit aging.

A systematic investigation should be undertaken of the antidotal efficacy of the three oximes, P2S, obidoxime and HI-6 in soman, cyclosarin and tabun poisoning. This would need to be carried out in primates, and could not usefully be done in any other animal. Non cholinesterase-reactivating effects of bis-pyridinium compounds (obidoxime, HI-6, HLö-7 and bis-pyridinium non-oximes) should be further studied, especially in soman poisoning but also in tabun poisoning. (In the latter reactivation with most oximes in vitro is slow and this raises the question of whether non-cholinesterase reactivating effects are responsible for the benefit sometimes observed in vivo).

The studies recommended should be carried out without pyridostigmine pretreatment and should be continued for a clinically relevant time to model the circumstances that are likely to prevail in the event of a nerve agent exposure in a civilian population in the UK.

(ii) Antidotes for cyanide poisoning

Further work is recommended on the antidote hydroxocobalamin. This offers, in principle, a low toxicity alternative to the conventional antidotes: dicobalt edetate and sodium nitrite. Much work has been done on the use of hydrocobalamin in victims of smoke exposure where both hydrogen cyanide and carbon monoxide may play a part in any poisoning. Less is known about the efficacy of hydroxocobalamin in pure hydrogen cyanide poisoning. The need for rapid confirmation of cyanide poisoning prior to treatment is recognised and research into better means of detecting exposure to cyanide is recommended,

(iii) Treatment for exposure to lung damaging agents

Much work is underway on the pathophysiology and treatment of pulmonary oedema. This is especially so in the field of post traumatic pulmonary insufficiency or adult respiratory distress syndrome. Despite many years of work in this area no simple and effective means of reversing the process has appeared and treatment continues to depend largely upon supportive care with carefully controlled ventilation as needed. Free radical scavenging agents have been examined in some detail and it may be that recent advances in understanding of how free radicals damage cells will allow advances to be made. Before any specific recommendations for research can be made an in depth review of this area is needed: this is recommended.

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