Warfarin reversal guideline

Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. MJA 2004

Ethylene glycol poisoning

- commonly used as a coolant and preservative and is found in polishes and detergents

- ethylene glycol poisoning often exhibits three distinct clinical phases after ingestion due to toxic metabolites glycolate, glyoxalate and oxalate

- first 12 hours - CNS effect predominate, patient appears intoxicated

- 12-24 hours - cardiopulmonary effect predominate, tachycardia, tachypnea and raised BP are common

- 24-72 hours - renal effects predominate

- hypocalcemia may result from precipitation of calcium oxalate in tissues and may be severe enough to cause tetany and typical ECG changes

- high anion gap metabolic acidosis

- treatment: gastric lavage within 1 hour of ingestion

- inhibit metabolism with intravenous ethanol (competitive inhibitor of alcohol dehydrogenase). Ethanol requires treatment on the ITU because of risk of respiratory depression

- fomepizole is an alternative treatment, being more potent than ethanol but generally more expensive

Antidotes

Agent	Indication
Activated charcoal with sorbital	used for many oral toxins
Adenosine	Theophylline antidote for adenosine poisoning
Atropine	organophosphate and carbamate insecticides,nerve agents, some mushrooms
Beta blocker	theophylline
Calcium chloride	calcium channel blockers, black widow spider bites
Calcium gluconate	hydrofluoric acid
Chelators such as EDTA, dimercaprol (BAL), penicillamine, and 2,3-dimercaptosuccinic acid (DMSA, succimer)	heavy metal poisoning
Cyanide antidote (amyl nitrite, sodium nitrite, or thiosulfate)	cyanide poisoning
Cyproheptadine	serotonin syndrome
Deferoxamine mesylate	Iron poisoning
Digoxin Immune Fab antibody (Digibind and Digifab)	digoxin poisoning
Diphenhydramine hydrochloride and benztropine mesylate	Extrapyramidal reactions associated withantipsychotic
Ethanol or fomepizole	ethylene glycol poisoning and methanol poisoning
Flumazenil	benzodiazepine poisoning
Glucagon	beta blocker poisoning and calcium channel blockerpoisoning
100% oxygen or hyperbaric oxygen therapy (HBOT)	carbon monoxide poisoning and cyanide poisoning
Insulin	beta blocker poisoning and calcium channel blockerpoisoning
Leucovorin	methotrexate and trimethoprim
Methylene blue	treatment of conditions that cause methemoglobinemia
Naloxone hydrochloride	opioid poisoning
N-acetylcysteine	Paracetamol (acetaminophen) poisoning
Octreotide	oral hypoglycemic agents
Pralidoxime chloride (2-PAM)	organophosphate insecticides, followed after atropine
Protamine sulfate	Heparin poisoning
Prussian blue	Thallium poisoning
Physostigmine sulfate	anticholinergic poisoning
Pyridoxine	Isoniazid poisoning, ethylene glycol
Phytomenadione (vitamin K) and fresh frozen plasma	warfarin poisoning and indanedione
Sodium bicarbonate	ASA, TCAs with a wide QRS

Neuroleptic malignant syndrome

- rare but life threatening, idiosyncratic reaction to a neuroleptic medication
- characterised by fever, muscular rigidity, dysautonomia (sweating, tachypnea, tachycardia and labile blood pressure) and altered mental status
- thought to be secondary to decreased dopamine activity in CNS either from blockade of dopamine D2 receptor or decrease availability of dopamine itself
- blockade of dopamine neurotransmission in nigrostriatum and hypothalamus results in muscular rigidity and altered thermoregulation
- most common cause are haloperidol, fluphenazine depot preparation and chlorpromazine
- high creatinine kinase and high white cell counts are seen
- complications include rhabdomyolysis and subsequent renal failure
- stop all neuroleptic, correct volume depletion and hypotension with IV fluid
- bromocriptine 5mg tds is the treatment of choice (dantrolene was formerly recommended as initial treatment of choice although recent studies suggest that it is associated with increased mortality when used without bromocriptine)

Paracetamol poisoning

- 150mg/kg or 12gm in adult may be fatal
- PCM overdose causes hepatic injury through its reactive metabolit (NAPQI), which is normally rapidly detoxified by glutathione in liver cells. In PCM overdose, NAPQI production exceeds glutathione capacity and the metabolite reacts directly with the hepatic macromolecules causing liver injury
- treatment includes oral activated charcoal within 3-4 hours of ingestion
- antidote: N-acetylcysteine or methionine if allergic to NAC
- criteria for transfer to liver unit
 ~ encephalopathy or raised ICP
 ~ INR >2.0 at <48hours or INR>3.5 at <72hours (so measure INR every 12hours)
 ~ renal impairment (creainine > 200 μmol/L)
 ~ blood pH < 7.3 (lactic acidosis)
 ~ systolic BP < 80mmHg
- liver markers are poor indicator of hepatocyte death
- King's college criteria for liver transplantation
~ arterial pH < 7.3 or lactate >3.0 after adequate fluid resuscitation
~ or if all three of the following occurs in first 24 hours
   i) creatinine > 300
   ii) PT > 100 or INR > 6.5
   iii) grade III/IV encephalopathy

Organophosphate poisoning

- organophosphorus insecticides include malathion, parathion, dichlorvos and diazinon
- organophosphate irreversibly inhibit acetylcholinesterase and nicotinic synapses
- poisoning characterised by muscarinic and nicotinic effects
- muscarinic effect : nausea, vomiting, miosis, abdominal cramp, urinary and fecal incontinence, bronchorrhea, diaphoresis, salivation, lacrimation, bradycardia, conduction block, pulmonary edema
- nicotinic effect: twitching, fasciculation, weakness, cramp, hypoventilation with respiratory failure
- cholinesterase activity in plasma and red blood cells is reduced to less than 50% normal
- remove contaminated clothing and wash skin and mucous membrane with copious amount of water
- Atropine (muscarinic receptor antagonist) 0.5-2mg given IV every 5-10minutes until atropinization is adequate (drying of tracheobronchial secretion, dry mouth, flushing, dilated pupils, HR>120)
- Pralidoxime (oxime that reactivates phosphorylated cholinesterase) counteracts weakness (nicotinic effects)
- pralidoxime is contraindicated in carbamate poisoning.