see also: [[organophosphates]] Murray tox: [Cholinergic Syndrome](x-devonthink-item://C8AE745C-C96E-4AEF-9010-D441840C6DF4?page=87) > [!Key Points] > - Causes:: [[organophosphates]], nerve agents > - Antidote:: [[atropine]], [[Pralidoxime]] > - mnemonic:: SLUDGEMS, DUMBELLS, "killer Bs" -- Bronchorrhoea and *bronchospasm*, *bradycardia*, BP (low), seizures needing Benzos # Overview Syndrome is caused by **increased acetylcholine** at central and peripheral muscarinic receptors and peripheral nicotnic receptors. ![[Pasted image 20230626221320.png]] # Causes **Anticholinesterases** - neostigmine (doesn't cross BBB) and physostigmine (does cross BBB) -- reversible binding to cholinesterases **Irreversible binding to cholinesterases** - [[organophosphates]] - [Nerve agents](bear://x-callback-url/open-note?id=A0D93844-3A41-4A3A-A57B-41BE4624DC2A-6644-000006E267A5E5AA) - Sarin - Soman - Tabun - VX **Others** - [[Nicotine poisoning]] - Some muscarine-containing mushrooms - Too much [neostigmine](craftdocs://open?blockId=E228009F-F999-4929-84F8-77B6A5EBC75F&spaceId=4ae8a7a1-b5e9-bd42-51eb-38086e5b5899) reversal after anaesthesia - Donepezil # Clinical Features 1. altered consciousness 2. bradyarrhythmias (usually) 3. muscular weakness 4. wetness (lacrimation, salvation, bronchorea, sweating) **CNS** - agitation --> coma/seizures - seizures - resp depression **CVS** - bradyarrhythmias more common than tachyarrhythmias - HTN (or with severe toxidrome, hypotension) **muscular** - fasciulations and cramaping (early) - weakness and paralysis (later) **autonomic cholinergic effects** - flushing - [[miosis]] (pupil constriction) - salivation - sweating **metabolic effects** - hypokalemia - hyperglycemia - metabolic acidois s 1. CNS: agitation, resp depression, coma, confusion, seizures 2. NM: fasciculation, weakness 3. Parasympathetic muscarinic: lacrimation, salivation, defaecation, urination, bronchorrhoea, bronchospasm, miosis, bradycardia 4. Parasympathetic nicotinic effects: Hypertension, tachycardia, sweating, mydriasis **Cholinergic CNS effects** - agitation - confusion - seizures - coma - respiritory depression **Muscarinic effects** - salivation - lacrimation - urination - diarrhoea - abdominal cramps - nausea/vomiting - miosis - **bradycardia** - bronchospasm/bronchorrhea **Nicotnic effects** - muscle spasms/fasciculations -- initially - muscle weakenss/paralysis -- later - tachycardia and HTN -- due to stimulation of nicotinic receptors at sympathetic ganglion , usually overshaddowed by muscarinic bradycardia > Note that although bradycardia secondary to increased vagal tone is typical, tachycardia may also occur secondary to **hypoxia**, **peripheral vasodilation** and the effects of **nicotinic** stimulation. # Treatment ## Atropine - to treat the muscarinic effects - **bradycardia** - **pulmonary secretions** Endpoints: - resolution of wheeze - HR > 80 BPM - Systolic BP > 80 **Dose** (sometimes very large) - 1200mcg (50mcg/kg in paeds) - double dose Q 5 minute until endpoints achieved - infusion at 10-20% of the cumulative dose required to achieve adequate atropinization > over atropinization can lead to [[Anticholinergic toxicity|anticholinergic syndrome]] (confusion, pyrexia, absent bowel sounds) ## Pralidoxime (2-PAM) - prevents the irreversible binding of agent - need to be given early, eg VX can become irreversible in minutes # Risk assessment # Toxic Mechanism # Clinical features # Treatment # Mnemonic SLUDGEMS Siallorhoea Lacrimation Urination Diarrhoea Gastrointestinal distress: abdominal pain due to hypermotility Emesis Miosis - constricted pupils Seizures Also... tachycardia bronchorrhoea hypothermia diaphoresis muscle fasciculations paralysis