Atropine

Atropine is a naturally occurring tertiary amine alkaloid and competitive muscarinic antagonist. It is a core emergency drug for symptomatic bradycardia and organophosphate or carbamate poisoning, and is also used as an antisialagogue, with cholinesterase inhibitors at reversal, and as a cycloplegic in the eye.

Classification. Antimuscarinic (anticholinergic); non-selective M1 to M5 antagonist; tertiary amine.

Mechanism. Competitively blocks acetylcholine at muscarinic receptors in the heart, glands, smooth muscle, eye and brain. No effect at nicotinic receptors, so it does not reverse muscle weakness or fasciculation from cholinesterase inhibitors.

Pharmacodynamics. Raises sinus rate and speeds atrioventricular nodal conduction; dries secretions; relaxes bronchial, gut and bladder smooth muscle; causes mydriasis and cycloplegia. Small doses (under 0.5 mg in adults) can cause paradoxical bradycardia through a central vagal effect.

Pharmacokinetics. IV onset within 1 minute, peak at 2 to 4 minutes. Hepatic metabolism with about half excreted unchanged in urine. Half life 2 to 4 hours in adults, longer in older adults and young children. Crosses the blood brain barrier and placenta.

Symptomatic bradycardia, adult.

• Atropine 1 mg IV, repeated every 3 to 5 minutes to a maximum total of 3 mg. Some resuscitation practice uses 500 micrograms as each dose, with the same 3 mg maximum.

• If no response, move to transcutaneous pacing or an adrenaline or dopamine infusion.

• Often ineffective in Mobitz type II block, complete heart block with broad QRS, and after heart transplant (denervated heart, risk of paradoxical high grade block).

• No longer used in asystole or pulseless electrical activity.

Symptomatic bradycardia, children. 0.02 mg/kg IV or intraosseous, maximum single dose 0.5 mg; may repeat once after 5 minutes. Treat hypoxia first.

Organophosphate and carbamate poisoning, adult. Common in East Africa from agricultural pesticides; atropine is life saving and stock should be generous.

• Loading: 1 to 3 mg IV bolus, then double the dose every 5 minutes until atropinisation.

• Atropinisation targets: clear chest on auscultation, heart rate over 80/min, systolic blood pressure over 80 mmHg, dry axillae, pupils no longer pinpoint.

• Maintenance: infusion giving 10 to 20% of the total loading dose each hour.

• Reassess every 15 minutes at first. If atropine toxicity appears (confusion, hyperthermia, absent bowel sounds, urinary retention), stop the infusion for 30 to 60 minutes and restart at 70 to 80% of the previous rate.

• Do not use tachycardia or pupil size alone as end points.

• Duration: taper over 24 to 72 hours or longer for lipid soluble organophosphates; total doses of tens to hundreds of milligrams are sometimes needed.

• Oxime where available: pralidoxime 30 mg/kg IV over 20 minutes, then 8 mg/kg/hour infusion; benefit is debated and supply in the region is limited.

Organophosphate poisoning, children. 0.02 to 0.05 mg/kg IV, doubled every 5 minutes to atropinisation, then 10 to 20% of the loading total each hour.

Antisialagogue and vagolytic before anaesthesia, adult. 0.3 to 0.6 mg IV immediately before induction, or IM 30 to 60 minutes before. Children: 0.02 mg/kg IV or IM (maximum 0.6 mg).

With neostigmine for reversal. Atropine 15 to 20 micrograms/kg IV given before or with neostigmine.

Ophthalmic cycloplegia and uveitis. Atropine 1% eye drops, one drop once or twice daily, up to four times daily in severe anterior uveitis. Cycloplegic refraction in children: one drop of 0.5% or 1% twice daily for 1 to 3 days before examination. Low concentration atropine (0.01% to 0.05% once nightly) for myopia control in children is specialist use.

Contraindications. In life threatening bradycardia or poisoning there are no absolute contraindications. Otherwise: angle closure glaucoma, obstructive uropathy, paralytic ileus, pyloric stenosis, toxic megacolon, myasthenia gravis (unless reversing cholinesterase inhibitor effects), tachyarrhythmia.

Warnings. Tachycardia can worsen myocardial ischaemia. Hyperthermia in children and hot environments from loss of sweating. Central toxicity (agitation, delirium, hallucinations) at high doses and in older adults. Ocular use in infants can cause systemic toxicity.

Adverse effects. Dry mouth, flushing, hot dry skin, tachycardia, palpitations, blurred vision, photophobia, raised intraocular pressure, urinary retention, constipation, confusion, delirium, hyperthermia.

Interactions. Additive anticholinergic burden with tricyclic antidepressants, antihistamines, antipsychotics, antiparkinsonian antimuscarinics and hyoscine. Slows gut transit and alters absorption of oral drugs. Opposes cholinesterase inhibitors and metoclopramide.

Special groups.

• Pregnancy: crosses the placenta and can cause foetal tachycardia; use without hesitation in emergencies.

• Breastfeeding: single doses compatible; repeated doses may reduce milk supply and cause infant anticholinergic effects.

• Children: weight based dosing; higher risk of hyperthermia.

• Older adults: higher risk of delirium and urinary retention; avoid routine use as an antisialagogue.

• Kidney impairment: longer half life; no change in emergency doses; reduce repeated ophthalmic and maintenance use where toxicity appears.

• Liver impairment: no adjustment.

Overdose. Antimuscarinic toxidrome; supportive care, benzodiazepines for agitation, external cooling; physostigmine for severe delirium where QRS is normal.

Formulations. Injection as atropine sulphate 0.6 mg/mL, 1 mg/mL and prefilled syringes 1 mg in 10 mL and 3 mg in 10 mL; eye drops 0.5% and 1%; autoinjectors for nerve agent exposure.

Administration. IV bolus as a rapid push followed by a flush. For organophosphate maintenance, prepare an infusion in 0.9% sodium chloride at a concentration that allows easy hourly rate changes. Endotracheal administration is no longer advised. Eye drops: apply pressure over the lacrimal sac for 1 minute.

Baseline. Heart rate, rhythm, blood pressure, 12 lead ECG, temperature. Poisoning: chest auscultation, secretions, pupil size, oxygen saturation, plasma or red cell cholinesterase where available.

Monitoring.

• Bradycardia: continuous ECG and blood pressure; readiness to pace.

• Organophosphate poisoning: atropinisation targets every 5 to 15 minutes during loading, then hourly; signs of atropine toxicity; neck flexion strength and respiratory function for intermediate syndrome over the first 1 to 4 days.

• Temperature and bladder in all repeated dosing.

Referral and escalation. Organophosphate poisoning with respiratory failure, need for ventilation, or rising atropine requirement needs intensive care. Bradycardia not responding to 3 mg needs pacing.

Common prescribing errors. Under dosing in organophosphate poisoning; adult doses under 0.5 mg; relying on pupils or heart rate rather than chest signs; using atropine in a transplanted heart.