king, t - my toolbox for canine and feline intoxications

Proceedings of VetFest 2020 King, T - My toolbox for canine and feline intoxications

j8-4DRq4My toolbox for canine and feline intoxications

Terry King Veterinary Specialist Services

34 Gogg’s Road Jindalee Qld 4074 [email protected]

Most aspects of traditional decontamination have lost some favour in human medicine as a first line of defence with intoxications, as other modalities (haemodialysis, plasmaphoresis, mechanical ventilation, etc) & antidotes (fomepizole, digitoxin-specific Abs, 2-PAM) become more mainstream. Yet, the types of intoxications in small animals together with financial & other limitations make the continued use of emesis, gastric lavage and activated charcoal still warranted in veterinary toxicology. Even so, timing is crucial and there are indications and contraindications depending on the status of the patient and the type of intoxicant. Emetics used have a see-sawing history of favour & disfavour and there are toxin-specific scenarios that need to be considered.

The role of antidotes is quite restricted to a minority of toxins, hence in most cases of overdose, survival is crucially dependent on supportive care.

Further, antidotes to toxins do not negate the necessity for decontamination in many intoxications.

Knowledge of the pathophysiology, toxic doses of, and treatments prepares the clinician to deal with the emergency poisoned pet and ready access to the materials and medicaments for decontamination, antidotal and supportive therapy is paramount in providing medical care for toxin cases.

Primary treatment of an intoxicated patient involves decontamination & detoxification - emesis, gastric lavage, activated charcoal, etc. As very few intoxicants have a specific antidote, symptomatic & supportive care are imperative and provide the mainstay of treatment after decontamination.

Survival of the intoxicated small animal patient involves prioritising supportive care – establish & monitor the airway, ensure normoxia, preserve body temperature, correct any hypotension (+/- volume expansion) or hypertension, appropriate acid-base & electrolyte status, deal with any hyperexcitability +/- seizure activity, and monitor and treat dysrhythmias.

Fluid therapy aids in drug excretion (if renally excreted), perfusion, prevents dehydration, helps to diurese nephrotoxicants, vasodilates renal vessels (esp. NSAID’s, cardiac medications). A balanced isotonic ‘replacement’ crystalloid solution (e.g. Saline 0.9%, LRS/Hartmann’s, Plasmalyte 148) at 1.5–3 times maintenance rates (4-10mls/kg/hr). Saline (0.9% NaCl) would be a prudent choice if hypercalcaemia results (Vitamin D Tablets/Topicals), while buffered solutions (LRS, P-148) are preferred in acidosis. Care should be taken not to fluid overload, especially if the patient has underlying cardio-pulmonary disease.

Gastrointestinal support is provided to prevent vomition of activated charcoal, to counteract some toxins gastric irritation +/- gastric ulceration effects (NSAID’s, corrosives). Medicants include anti-emetics (Metoclopramide 1-2mg/kg/day CRI; Maropitant 1mg/kg SC/IV SID; Dolasetron/Ondansetron 0.1-1.0mg/kg IV SID-QID), gastric pH-modifiers (H2 blockers – Ranitidine 1-2mg/kg IV,SC,PO BID (moderate P450 inhibition); Famotidine 1mg/kg IV,SC

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SID/BID (low P450 inhibition), proton-pump inhibitors (Esomeprazole 1.0mg/kg IV BID, Omeprazole 1mg/kg PO BID), anti-ulcerogenics (Sucralfate 0.5-1.0gram PO TID).

Neurological support is given for the stimulatory effects (agitation, tremors, seizures) as with amphetamines & SSRI anti-depressants or sedatory effects (drowsiness, severe sedation, coma) of some toxicants. Examples include anti-convulsants for seizures (Diazepam 0,5-1.0mg/kg IV increments to effect; Phenobarbitone 4-20mg/kg IV to effect, Levetiracetam 20-60mg/kg IV,PO TID), sedatives/anxiolytics (ACP 0.05-0.1mg/kg SC,IM,IV to effect; Chlorpromazine 0.2-0.5mg/kg SC,IM,IV to effect TID; Butorphanol 0.2-0.8mg/kg SC,IM,IV to effect PRN), muscle relaxants for pyrethrins, tremorgenic mycotoxins (Methocarbamol 44-220mg/kg IV,PO to effect PRN, 330mg/kg/day CRI), and reversal agents such as Naloxone (opiates; also baclofen) 11-22ug/kg SC,IM,IV to effect PRN; Yohimbine (alpha2’s) 0.1mg/kg IV; Atipamezole (alpha2’s) 50ug/kg IM.

Cardiovascular Support is essential in the face of cardiotoxicity – SSRI anti-depressants, Amphetamines (ADD’s); Chocolate (Theobromine); Caffeine; Albuterol (Sympathomimetic); Beta-Blockers; Ca++ Channel Blockers; Oleander (Cardiac Glycoside). Clinical signs can hypo/hypertension; brady/tachycardia; arrhythmias. Monitoring employs ECG, BP measurements. Treatment involves IVF’s; Anti-arrhythmics (e.g. Lignocaine); Beta-Blockers (tachyarrhythmias); Sedatives (hypertension, tachycardia) Anti-Hypertensives (e.g. Hydralazine 0.5-2.0mg/kg PO BID/TID, Amlodipine, Nitroprusside).

Antidotes can be specific & non-specific, with examples of Ethylene Glycol toxin (Ethanol; Fomepizole), Organophosphates & Organocarbamates (Atropine, 2-PAM), Anticoagulant Rodenticides (Vitamin K1), Opioids (Naloxolone), Digoxin-specific Ab fragments (Oleander, Digoxin), ILE (Intra-Venous Lipid Emulsion) for lipid soluble intoxicants (Avermectins; Pyrethrins, etc) and Hepatoprotectants (N-Acetylcysteine; SAMe; Silymarin) for Hepatoxicants (Cycads; Xylitol; Paracetamol; Aphlatoxins; NSAID’s; Amanita mushrooms; Blue-green algae, etc)

Rapid access to details of unfamiliar toxins helps direct further management of the emergency. A veterinary practice ‘toolbox’ for intoxications includes antivenenes against possible arachnid and elapid envenomations, blood products, known antidotes for likely common and uncommon intoxications, current recommended medicants for emesis and decontamination, and remedies for supportive care and management of symptoms and potential adverse effects that may arise until the intoxicant is nullified.

EMETICS FOR CATS Hydromorphone Medetomidine 20 mcg/kg IV/IM with the reversal agent Atipamezole 80 mcg/kg IM Xylazine 0.44 mg/kg IM/SC with the reversal agent Yohimbine 0.1-0.5 mg/kg IV Tranexamic Acid 100 mg IV per cat (off-label)

EMETICS FOR DOGS Apomorphine 0.03-0.04 mg/kg IV/IM or 0.08 mg/kg SC or 0.25mg/kg CONJUNCTIVALLY with possible reversal agents Naloxone 0.4 mg/kg IV (for oversedation) and Maropitant 1mg/kg IV (for cessation of emesis) Hydrogen Peroxide 3% 1-2 mL/kg PO with maximum 2 doses Tranexamic Acid 50 mg/kg IV can be repeated 2-3 times if needed (off-label)

ACTIVATED CHARCOAL ABSORBENT Activated Charcoal (AC) is best given as soon as possible after ingestion of the intoxicant.

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1-5g/kg body weight, or at least ten times that of the ingested dose of intoxicant, often given with Sorbitol as a cathartic to decrease transit time through the GIT. Toxicants that have delayed release (e.g. sustained release tablets) or that undergo enterohepatic circulation may be still salvageable with the use of activated charcoal +/- catharsis up to six or more hours after ingestion. Administered in situations where life-threatening toxicity is not easily treated by supportive care +/- a specific antidote.

Multiple Dose Activated Charcoal or MDAC (also called GI dialysis) involves repeated doses of AC to increase the whole-body elimination of an intoxicant that undergoes enterohepatic or entero-gastrointestinal cycling. Used with ingested intoxicants with prolonged elimination half-life. Used where there is a small volume of distribution (<1 L/kg body weight) suggesting that sequestration is not a feature. Phenobarbitone, Theophylline, Paracetamol, Digoxin, Piroxicam, Sotalol, TCA’s, Yellow Oleander

ANTI-VENENES Tick anti-toxin, Red back spider antitoxin, Snake antivenene – univalent, polyvalent – brown, black, tiger etc

BLOOD PRODUCTS for Transfusion Therapy Stored Whole Blood/Packed Red Cells for haemorrhagic loss Fresh Whole Blood/Fresh Frozen Plasma for coagulopathies

VITAMIN K1 (Phytomenadione) 10mg/mL for Rodenticide Ingestion/Intoxication & Acute Toxic Liver Failure Traditionally, initial dose of 5mg/kg IM/SC q12 hours, converting to 5mg/kg PO (SID or divided BID given with food) as soon as possible. Continue for 4-6 weeks depending on identified rodenticide +/- coagulation monitoring IV protocol 5mg/kg diluted in D5W to 20mLs and protected from light given slowly IV over 15 minutes was shown to normalise coagulation times within one hour in 4 dogs with rodenticide coagulopathy (AVJ 2020, Vol 98, No 6). However, 2/4 dogs showed a mild anaphylactoid reaction (responsive to antihistamines) to the polyoxyethylated fatty acid derivatives used as a solubiliser in the formulation

N-ACETYLCYSTEINE for Paracetamol Intoxication in Cats/Acute Hepatic Toxicity in Dogs Reduces methaemoglobinaemia by restoring glutathione levels. Reduces oxidative injury to the liver Loading dose 140-280 mg/kg IV Bolus (in 5% Glucose) over 20-30 minutes, then 70mg/kg q6 hr for 6 additional doses

NALOXONE for Opioid overdose Dilute 0.4mg/mL solution to 0.005-0.01mg/mL and give 0.5-1.0 mL increments per minute until signs (oversedation, respiratory depression, panting, dysphoria) subside; repeat doses sometimes necessary due to short duration of reversal effect 0.02 mg/kg IV for opioid reversal in anaesthetic arrest 1 Drop of 0.4 mg/mL solution sublingually in neonate if opioid-induced depression from premedicant in caesarean section procedure

INTRALIPID EMULSION (ILE) Lipid therapy shows great promise for lipid soluble toxicosis (fat-soluble) management, providing a “lipid sink” for rescuing the intoxicant

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ILE is the 20% lipid solution commonly used as a fat component for parenteral nutrition Initial bolus at 1.5 ml/kg then 0.25 ml/kg/min for 30-60 min Repeat dose every 4-6 hours if needed (check for hyperlipemia before repeating dose - redose only if serum clear)

ATROPINE for muscarinic signs in Organophosphate & Organocarbamate intoxications, and for bradyarrhythmias in other intoxications 0.01 mg/kg IV & 0.01 mg/kg IM and repeat PRN for OP/OC toxicosis In bradycardic patients (dogs HR <50, cats HR <120) need BP reading to monitor for reflex bradycardia secondary to severe hypertension as atropine contra-indicated here If systolic BP >180 mm Hg, consider anti-hypertensives If normotensive and bradycardic, treat with atropine at 0.01–0.02 mg/kg IM or IV

PRALIDOXIME (2-PAM) for OP poisoning to control nicotinic signs Reconstitutes anticholinesterase Effect is enhanced if used adjunctively with Atropine

ETHANOL or FOMIPAZOLE for Ethylene Glycol intoxication Ethanol competes with ethylene glycol as substrate for alcohol dehydrogenase and use if >3 hours (cats) or >8 hours (dogs) ingestion. Initial dose of 20% solution at 3mL/kg (600mg/kg) over 1 hour in saline diluted at least 1:2; subsequent hourly CRI doses of 0.5-1.0 mL/kg of 20% solution diluted 1:2 for up to 24 hours

Fomipazole (4MP or 4 Methylpyrazole) 5% Solution inhibits alcohol dehydrogenase and preferred if <3 hours ingestion (cats) or >8 hours ingestion (dogs) DOGS – Give 20 mg/kg IV initially, then 15 mg/kg IV at 12 hours and again at 24 hours then 5 mg/kg at 36 hours CATS – Give 125 mg/kg IV initially, then 31.25 mg/kg IV at 12, 24 & 36 hours

CYPROHEPTADINE for Serotonin Syndrome Alleviates signs of hyperthermia & CNS stimulation Dogs: 1.1 mg/kg PO or PR q1–6hr PRN Cats: 2–4 mg PO or PR q1–6hr PRN

PHENOTHIAZINES for Agitation/Hyperexcitability/Hyperaesthesia in Serotonin Syndrome Acepromazine at 0.05–0.1 mg/kg IV, IM, or SC OR Chlorpromazine at 0.5–1 mg/kg slow IV or IM Some serotonin receptor antagonist activity Not used in OP/OC toxicities as can enhance toxicity and duration of toxin’s effect

METHOCARBAMOL for Tremors as in Permethrin toxicity in Cats, Metaldehyde intoxication in Dogs, Serotonin Syndrome in Dogs & Cats 55–220 mg/kg slow IV to effect +/- CRI at 10-15 mg/kg/hr (suggested maximum of 330 mg/kg/day)

BENZODIAZEPINES/BARBITURATES/ANAESTHETICS for Seizure activity Diazepam OR Midazolam 0.1-1.0 mg/kg aliquots IV to effect +/- CRI Based on human extrapolations, benzodiazepines should be avoided in Serotonin Syndrome, as they may increase CNS excitation Phenobarbital at 4–16 mg/kg IV as needed Propofol at 2–6 mg/kg IV or 0.1–0.6 mg/kg/min CRI Can decrease dose by 25% if acepromazine or chlorpromazine has been administered

ESMOLOL In tachyarrhythmic patients (dogs HR >180; cats HR >220–240) not responsive to sedation, use of beta-blockers may be necessary. Dogs & Cats: 0.25-0.5 mg/kg slow IV bolus then 50-200 mcg/kg/min CRI

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ANTI-HYPERTENSIVES Amlodipine 0.2-0.4 mg/kg PO q12-24-hour PRN Loading protocol 0.2 mg/kg PO q2-4 hour for 2-3 doses until BP <160-180 mmHg

Nitroprusside CRI in D5W for emergency management of a hypertensive crisis Initial CRI dose 1 mcg/kg/min (cat) or 2-3 mcg/kg/min (dog) and titrate by 0.5-1 mcg/kg/min each 15 minutes until target blood pressure is achieved; maximum 24 hours

MISOPROSTOL for NSAID intoxication Enhances GIT mucosal defence mechanisms, reduces gastric acid secretion 2-5 mcg/kg PO q12 hour

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king, t - my toolbox for canine and feline intoxications

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