CONTENTS Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Mode of action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Signs of Poisoning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Treatment – general . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Vitamin K1 – the antidote . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Length of treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Supportive measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Treatment – specific cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Animals exhibiting signs of intoxication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Animals suspected of consuming bait . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Prothrombin time test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Summary of treatment in domestic animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Veterinary Poisons Information Service . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 INTRODUCTION
This booklet is designed to help veterinarians recognise and effectively treat poisoning by anticoagulant rodenticides, particularly those which are generally known as the second generation anticoagulant rodenticides. It has been produced jointly by companies involved in the manufacture and distribution of rodenticides to ensure the widest knowledge of treatment regimes which are agreed to be effective for anticoagulant rodenticides. There is a range of rodenticide formulations available in the market. The signatory companies produce several types, including those containing brodifacoum, bromadiolone, difenacoum, difethialone and flocoumafen as active ingredients. Details of locally available formulations may be given by the distributor on the final pages of this booklet. Certain rodenticides contain mixtures of active compounds, and an anticoagulant may be combined with other chemicals. In poisoning incidents, where possible, establish what product the animal was exposed to, in order to ascertain whether additional treatment procedures may be required.
Animals may be exposed to anticoagulant rodenticides by two routes:1. Consumption of bait containing an anticoagulant. 2. Secondary poisoning due to consumption of rodents poisoned with an anticoagulant. MODE OF ACTION
Brodifacoum, bromadiolone, difenacoum, difethialone and flocoumafen are coumarin anticoagulants which, like warfarin, act by interfering with the synthesis of prothrombin and disturbing the normal blood clotting mechanisms. They therefore cause an increased tendency to bleed. As in warfarin poisoning, vitamin K1 (Phytomenadione) is the antidote. The major difference between warfarin and these rodenticides is that they have longer body half-lives and increase the tendency to bleeding for a longer period of time than warfarin. It is therefore important to understand that it may be necessary to continue treatment for weeks rather than days. SIGNS OF POISONING
Clinical signs are unlikely to occur within 24 hours after ingestion of formulations containing brodifacoum, bromadiolone, difenacoum, difethialone or flocoumafen and may not appear for a few days. Thereafter, signs of poisoning become rapidly more pronounced with time. Typical signs resulting from the increased tendency to bleed may include:
• bruising easily with occasional nasal or oral bleeding,• blood in faeces or urine,• excessive bleeding from minor cuts or abrasions,• laboured breathing,• pale mouth and cold gums,• anorexia, general weakness,• subcutaneous swelling; when around joints may result in lameness.
More severe cases of poisoning include massive haemorrhage (usual y internal), shock and coma. DIAGNOSIS
Diagnosis is based on a combination of clinical signs, circumstantial evidence and laboratory tests. A reliable indication of a coumarin anticoagulant effect, particularly if clinical signs are minimal, is the determination of prothrombin time. Anticoagulation with coumarins leads to an increase in prothrombin time and successful treatment will quickly return it to normal levels. Prothrombin time testing should be carried out wherever possible, at least before the start of treatment and after antidote is withdrawn. TREATMENT – GENERAL VITAMIN K1 – THE SPECIFIC ANTIDOTE Vitamin K1 (Phytomenadione) is the only antidote in al cases of coumarin anticoagulant poisoning. Other analogues of vitamin K should not be used. LENGTH OF TREATMENT Treatment should start with a single parenteral administration of vitamin K1 (2 to 5mg/kg body weight). Intravenous injection is the quickest route and should reduce prothrombin time to normal values within a few hours. Caution should be exercised in severely symptomatic animals as the site of venepuncture may bleed excessively. Always administer vitamin K1 parenteral y with the smal est diameter needle that is feasible. One parenteral dose is usual y sufficient to return prothrombin time to normal. If prothrombin time fails to normalise, parenteral administration should be repeated. Note: Some preparations of vitamin K1 are reported to induce anaphylaxis; these preparations must be injected intramuscularly or subcutaneously. Check the label instructions of the vitamin K1 preparation used. Once prothrombin time has returned to normal, oral doses of vitamin K1 (2 to 5mg/kg body weight) can be given. Dosing should continue for three to four weeks without interruption, even if symptoms have regressed. Prothrombin time should be determined again 24 to 48 hours after the antidote has been withdrawn. If the prothrombin time is elevated, treatment should be continued for a further two to three weeks. SUPPORTIVE MEASURES In cases of severe blood loss, whole blood transfusion (10 to 15ml/kg body weight) may be needed. This blood should be fresh because some clotting factors (V and VI I) are labile on storage.
Always keep anticoagulant poisoned animals calm and in a warm place in order to avoid unnecessary stress and haemorrhaging. TREATMENT – SPECIFIC CASES ANIMALS EXHIBITING SIGNS OF INTOXICATION
• col ect a blood sample and carry out a prothrombin test,• parenteral injection of vitamin K1, 2 to 5mg/kg. Use the smal est diameter needle feasible, and avoid the intravenous route in severely haemorrhagic animals,• supportive measures,• repeat prothrombin test about four hours after injection,• provided prothrombin time has normalised, start daily oral vitamin K1 treatment and continue it for three to four weeks,• carry out prothrombin test 24 to 48 hours after end of treatment, • continue treatment if signs of poisoning reappear or if prothrombin time is stil abnormal. ANIMALS SUSPECTED OF CONSUMING BAIT
• this includes animals known to have ingested the bait or animals showing evidence of ingestion such as traces of dye from the bait around the mouth or in faeces,
• induce vomiting only if ingestion is recent (less than six hours),
• observe closely for signs of poisoning (see page 2) for one week,
• test prothrombin time daily for up to three days after suspected date of ingestion,
• treat with vitamin K1 if signs of poisoning appear or if prothrombin time increases,
• prophylactic oral vitamin K1 treatment could be carried out. THE PROTHROMBIN TIME TEST
To sample for the prothrombin time test, col ect at least 1ml blood into a citrate tube. Ideal y the plasma should be separated within half an hour of col ection and the test performed within 2 hours of blood col ection. However, unfrozen samples wil usual y give clinical y useful results if examined within 24 hours. SUMMARY OF TREATMENT IN DOMESTIC ANIMALS
IMPORTANT:To be read in conjunction with the text above
TREATMENT CONDITION (signs of poisoning) a = Observe for several weeks and monitor prothrombin time b = Only where bait consumption is known to have occurred within six hours VETERINARY POISONS INFORMATION SERVICE
Formulations available: Active ingredient Product Name Brief Description
BrodifacoumBromadioloneDifenacoumDifethialoneFlocoumafen
DISCLAIMER
Although the authors of this booklet have given the advice contained herein in good faith and on the basis of the best and most recent evidence available at the time of this booklet going to print, no warranty can be given as to the correctness of the advice nor can any liability be incurred by them in respect thereof. Further, the likelihood of success of any antidote treatment will also depend on other extraneous factors over which the authors have no control and which include, for example, the general health of the affected animal, the period of time between ingestion of the anticoagulant and the beginning of the antidote treatment and the quantity of the relevant anticoagulant which has been ingested.
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