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Home , Paracetamol poisoning

What’s new in and Toxinology Guidelines?

Dr Venita Munir Editor [email protected] Therapeutic Guidelines Ltd.

▪ Not-for-profit, financially self-supporting, intellectually independent

▪ Improve patient outcomes by promoting the quality use of medicines

▪ Create and publish point-of-care guidelines

▪ Products:

▪ eTG complete (since 2002)

▪ eTG app (since 2016)

▪ books phased out (2019) Toxicology and Toxinology 3

▪ Not updated since 2012 ▪ Expert group assembled in late 2017 Toxicology and Toxinology Expert Group

Clinical Toxicologists / Emergency Physicians: Prof. Nick Buckley (NSW) Chair Prof. Geoff Isbister (NSW) Dr Sam Alfred (SA) Dr Katherine Isoardi (QLD) Dr Angela Chiew (NSW) Dr Zeff Koutsogiannis (VIC) Prof. Andrew Dawson (NSW) Dr Jess Soderstrom (WA) Prof. Andis Graudins (VIC) Specialists in Information (SPIs): Mr Kasra Ahmadi (WA) Ms Elizabeth Nguyen (NSW) Dr Dawson Macleod (VIC) Ms Carol Wylie (QLD)

General Practitioner: Dr Marion Christie (VIC) What’s new in Toxicology and Toxinology?

• 54 Existing monographs and 38 New monographs • Many topics split & linked to multiple specific topics • More structure: • Management overview • Risk assessment • Treatment • Observation & Disposition Overview of changes

• Covers more rare but highly toxic agents • More detail overall; eg: • Toxic doses and concentrations • Specific decontamination advice • Links to General approach & Toxidromes • Paediatric doses and maximums • Less emphasis on • Specific advice on duration of observation Existing monographs updated (54)

ACEIs and ARBs CCBs: dihydropyridines Hydrofluoric acid – now 5 topics CCBs: verapamil and diltiazem (toxic) Carbon monoxide Iron Potassium (oral)

Antidiabetic drugs Caustic ingestions IV inotrope infusions Snake bite

Antiepileptic drugs Clonidine Lead Sodium valproate

Antihistamines, sedating & Chloroquine, hydroxychloroquine Lithium (acute overdose) less sedating and quinine Lithium (chronic accumulation) Antipsychotics Colchicine Metformin SNRIs

Acute arsenic Cyanide Methotrexate SSRIs

Aspirin / salicylates Digoxin (acute overdose) Mirtazapine Stimulant drugs Digoxin (chronic accumulation) Baclofen Essential oils Marine envenoming Superwarfarins Marine Flecainide Nicotine Theophylline and caffeine

Benzodiazepines Gamma-hydroxybutyrate NSAIDs Toxidromes

Beta blockers General approach Opioids Tricyclic antidepressants

Bupropion Herbicides Organophosphates Warfarin New monographs (38)

Amanita phalloides mushrooms Insecticides Quetiapine

Amisulpride Insulin Sulfonylureas

Apixaban and rivaroxaban Tiagabine

Buprenorphine Lamotrigine Topiramate

Button batteries Local anaesthetics Hydrocarbons

Carbamazepine and oxcarbazepine Monoamine oxidase inhibitors Novel psychoactive substances - Overview Chlorophenoxy herbicides Olanzapine Novel stimulants

Clozapine Paraquat Novel hallucinogens

Cocaine Synthetic cannabinoid-receptor agonists

Dabigatran Poisoning from plants

Glyphosate Pregabalin and gabapentin What’s new in General Approach?

High-dose insulin euglycaemia therapy (HIET) included

Rapid cooling techniques in drug-associated hyperthermia

Sedation in challenging situations; eg stimulant , toxidromes

Seizure control; barbiturates or levitiracetam for intractable seizures

Directive advice for activated charcoal, MDAC, and whole bowel irrigation Also new in General Approach

In QT-interval prolongation • Replace potassium to high normal range (>5 mmol/L) to prevent torsades de pointes

Serum alkalinisation with IV sodium bicarbonate & gentle hyperventilation

Sodium bicarbonate 8.4% - maximum dose up to 6 mL/kg (6 mmol/kg)

Calcium gluconate 10 % for hyperkalaemia - maximum dose up to 60 mL (child max 30 mL) What’s new in the management of ?

Now 5 separate monographs • Advice for primary care providers • Immediate-release • Modified-release • Liquid in child <6 years • Unintentional repeated supratherapeutic ingestion

Based on: Chiew AL et al. Updated guidelines for the management of paracetamol poisoning Australia and NZ (pending publication MJA Nov 2019) for paracetamol poisoning

• Paracetamol and ALT concentrations for ALL at >4 hours after ingestion • 2-bag acetylcysteine regimen (instead of 3) • ‘Low-dose’ – standard 20-hour regimen • ‘High-dose’ – double dose in 2nd bag Acetylcysteine (NAC) regimens for paracetamol poisoning

Low dose • 200 mg/kg (max 22 g) NAC IV over 4 hours followed by 100 mg/kg (max 11 g) NAC IV over 16 hours High dose • 200 mg/kg (max 22 g) NAC IV over 4 hours followed by 200 mg/kg (max 11 g) NAC IV over 16 hours Who needs extended NAC therapy?

• Repeat paracetamol and ALT concentrations for ALL – 2 hours before the end of the 2nd infusion • Extended therapy for potential , until the patient is well & bloods are normalising Acetylcysteine for other poisonings

• Amanita phalloides • Arsenic • Paraquat • Some Hydrocarbons: benzene, carbon tetrachloride, chloroform • Some Essential oils: clove oil, pennyroyal oil What’s new in Acute digoxin poisoning?

• Titrated for acute poisoning (except cardiac arrest): • 2 vials IV initially and repeat 1 to 2 vials IV PRN guided by adequate perfusion and potassium <6 mmol/L • 5 vials IV for cardiac arrest • Life-threatening arrhythmia – calcium 30 mL IV • Hyperkalaemia – insulin, glucose, bicarb, salbutamol • Cross links to cardiac glycoside-containing plants (new) What’s new in chronic digoxin accumulation?

• Correct precipitating factors • Bradycardia alone – atropine, adrenaline, pacing • Bradycardia with – digoxin immune Fab • Hyperkalaemia – as per acute digoxin poisoning • Titrated digoxin immune Fab only in life-threatening arrhythmias or cardiac arrest • 1 vial IV initially and repeat 1 vial IV PRN guided by adequate perfusion and potassium <6 mmol/L • 2 vials IV for cardiac arrest What’s new in managing snake bite?

• No place for detection testing (VDK) • Resuscitation, supportive care, critical care facility, 24 hour lab & adequate antivenom • Updated antivenom recommendations Based on: Johnston CL et al. The Australian snake bite project 2005–2015 (ASP-20) MJA Aug 2017 Critical questions following a snake bite

Is there clinical or laboratory evidence of systemic envenoming? If so, which group or type of snake is most likely (based on clinical syndrome and local snake fauna)? Is antivenom indicated? • If so administer it as early as possible (within 2 hours if possible) Evidence of systemic envenoming Early administration of antivenom

• Antivenom may be required based on clinical symptoms only: • early clinical signs of envenoming especially headache and • systemically unwell appearance • signs of cardiovascular collapse (syncope, seizure, cardiac arrest) Snake antivenom recommendations

1 vial of tiger snake AV plus 1 vial of brown snake AV covers most cases of unidentified-snake envenoming

1 vial of polyvalent AV is indicated for: • likely mulga snake, death adder or taipan • any doubt about snake type Snake antivenom recommendations

• 1 vial of tiger snake AV is indicated for: • expert identification: definite tiger snake or red- bellied black snake • any snake bite in Tasmania • 1 vial of brown snake AV is indicated for: • expert identification: brown snake • any doubt about snake type • Discuss all suspected snake envenomings with a clinical toxicologist Other antivenom recommendations

• Funnel-web spider AV: for severe systemic envenoming • Red-back spider AV: • NOT recommended • analgesia is the mainstay • Box jellyfish AV: for cardiovascular collapse • Sea snake AV: polyvalent sea snake AV if systemic envenoming Button battery ingestion

• Potential for delayed presentation delayed diagnosis, severe complications: • caustic injury, viscus perforation, aorto-oesophageal fistula, catastrophic haemorrhage, death • Need a high index of suspicion is • Time critical neck-to-bottom X-ray • Referral ASAP for endoscopic removal NOAC antidotes

Dabigatran poisoning • : for life-threatening bleeding – may require higher doses after poisoning than for supra- therapeutic dosing

Apixaban & rivaroxaban poisoning • Andexanet alpha: (once available in Australia) for life- threatening bleeding Connolly S. Andexanet alpha for bleeding associated with factor Xa inhibitors NEJM April 2019 Novel psychoactive substances (NPS)

Management overview for NPSs Novel stimulants, eg cathinones Novel hallucinogens eg NBOMe Synthetic cannabinoid-receptor agonists (SCRAs) eg spice or K2 Fentanyl analogues Designer benzodiazepines So goodbye Toxicology & Wilderness…

…and welcome to the NEW bigger, better Toxicology & Toxinology in mid-2020