Continuing Education Activity

Atropine or atropine sulfate carries FDA indications for anti-sialagogue/anti-vagal effect, organophosphate/muscarinic poisoning, and bradycardia. Atropine acts as a competitive, reversible antagonist of muscarinic receptors: an anticholinergic drug. This activity outlines the indications, mechanism of action, safe administration, adverse effects, contraindications, toxicology, and monitoring of atropine.

Objectives:

• Identify the mechanism of action of atropine.
• Describe the potential adverse effects of atropine.
• Summarize the indications for atropine use.
• Review interprofessional team strategies for improving care coordination and communication to enhance patient outcomes and minimize adverse events with atropine.

Indications

Atropine or atropine sulfate carries FDA indications for anti-sialagogue/anti-vagal effect, organophosphate/muscarinic poisoning, and bradycardia.[1][2] It was originally synthesized from the plant Atropa belladonna, which is where the drug derives its name.

Antisialagogue

While atropine can be used independently for anti-salivation effects, it is not formally recommended for routine use in controlled airways, though it can be used off-label for minimizing secretions in the intubated patient. Glycopyrrolate is at least five times more potent than atropine in its antisialagogue effect 

Anticholinergic Poisoning

Acetylcholine works on three different receptors that merit attention in nerve agent poisonings. Atropine is only useful to counter muscarinic effects (pralidoxime and benzodiazepines act on the others). If there are local symptoms in the eyes or respiratory tract, atropine is not indicated. Intravenous (IV) atropine indications include patients with hypersalivation, bronchial secretions, or bradycardia. Large doses and repeat doses may be required. Ingestions especially require higher doses (up to 20 mg). Titrate to effect by monitoring the patient’s ability to clear excess secretions. Pupils and heart rate are poor indications of appropriate dosing in these patients.

Bradycardia

Atropine is the first-line therapy (Class IIa) for symptomatic bradycardia in the absence of reversible causes. Treatments for bradydysrhythmias are indicated when there is a structural disease of the infra-nodal system or if the heart rate is less than 50 beats/min with unstable vital signs. Approximately 20% of bradydysrhythmias are due to endogenous cardiac electrical systems. The structural disease may or may not require resuscitation and should be closely monitored with medication and pacing readily available. If there is no improvement in the clinical state after repeat doses of atropine, additional treatments with atropine are unlikely to be effective. However, transient improvements with repeat dosing are an indication to continue treatment with atropine (which may exceed standard cumulative dosing maximums). Pediatric bradycardia is rarely cardiac and often secondary to hypoxia and hypoventilation. If bradycardia persists despite adequate respiratory support, atropine is indicated.

Rapid Sequence Intubation (RSI) Pretreatment

Although not recommended as a routine agent, atropine may be used 3 to 5 minutes before initiation of RSI to prevent bradycardia. In the setting of post-intubation-related bradycardia, atropine is indicated. Post-induction bradycardia is seen more commonly in the pediatric population due to the predominance of vagal response, even without the use of succinylcholine.

Atropine/diphenoxylate is an antimotility agent that can be useful in the treatment of diarrhea as second-line therapy by allowing the central-acting opioid effect of diphenoxylate and capitalization on its anticholinergic side effect of constipation to slow motility. Subtherapeutic amounts of atropine are included in the dosage form to discourage diphenoxylate abuse. It may potentiate barbiturates, alcohol, or tranquilizers, and therefore, its use requires caution.

Under current ACLS protocols, atropine is indicated for symptomatic bradycardia and not in a pulseless patient. The AHA has removed all indications for atropine in the pulseless patient.

Atropine is not indicated in beta-blocker-induced bradycardias or hypotension, though its use is unlikely to be harmful. Glucagon is the first line to treat beta-blockade-induced symptoms.

Pregnancy Class B: It does cross the placenta and may lead to fetal tachycardia; however, it does not cause fetal abnormalities.[3]

Mechanism of Action

Atropine is an antimuscarinic that works through competitive inhibition of postganglionic acetylcholine receptors and direct vagolytic action, which leads to parasympathetic inhibition of the acetylcholine receptors in smooth muscle. The end effect of increased parasympathetic inhibition allows for preexisting sympathetic stimulation to predominate, creating increased cardiac output and other associated antimuscarinic adverse effects, as described herein.[4]

Administration

Atropine can be administered by intravenous (IV), subcutaneous, intramuscular, or endotracheal (ET) methods; IV is preferred. For ET administration, dilute 1 mg to 2 mg in 10 mL of sterile water or normal saline before administration. For pediatric ET, double the usual IV dose and dilute in 3 to 5 mL.

• Antisialagogue/anti-vagal: 0.5 mg to 1 mg every 1 to 2 hours
• Organophosphate or muscarinic poisoning: 2 mg to 3 mg every 20 to 30 minutes (may require doses up to 20 mg, titrate to effect for secretion control)
• Bradycardia: 1 mg every 3 to 5 minutes (3 mg max), repeat until obtaining desired heart rate, most effective for sinus and AV nodal disease.
• Pediatric: 0.01 mg/kg to 0.03 mg/kg every 3 to 5 minutes. The pediatric minimum dose is 0.1 mg, the maximum dose is 0.5 mg (child) and 1.0 mg (adolescent), and the maximum cumulative dose is 1 mg (child) and 2 mg (adolescent).
• Rapid sequence intubation pretreatment: 0.01 mg/kg IV for adults with bradycardia secondary to repeat dosing of succinylcholine. Pediatric 0.02 mg/kg IV, minimum dose 0.1 mg. Not recommended as a routine treatment. 

In general, the dosing of atropine is repeatable every 5 minutes until reaching a maximum of 0.04 mg/kg.

Dosing in adults to greater than 0.5 mg and slow IV pushes correlate with paradoxical bradycardia (though likely transient) and ventricular fibrillation (VF). 

Adverse Effects

The most common adverse effects are related to the drug's antimuscarinic properties, including xerostomia, blurred vision, photophobia, tachycardia, flushing, and hot skin. Constipation, difficulty with urination, and anhidrosis can occur, especially in at-risk populations (most notably, the elderly). In rare cases, delirium or coma may occur. Hypersensitivity reactions may occur and are usually limited to a skin rash that could progress to exfoliation.[5]

Atropine decreases the rate of mexiletine absorption, which can be prevented by combined IV delivery of metoclopramide with atropine before anesthesia. 

Contraindications

Atropine does not carry an FDA Boxed Warning nor any absolute indications. Multiple conditions carry a cautionary status. However, relative contraindications are overridden by the clinical need, especially in unstable or poisoned patients.

Clinicians need to exercise caution in patients with coronary heart disease, acute myocardial ischemia, congestive heart failure, tachycardia, or hypertension, as the increased cardiac demand and possible further worsening of tachycardia and hypertension can prove detrimental to patient outcomes.

Furthermore, caution is necessary for use with elderly patients, chronic lung disease patients, acute angle glaucoma, obstructive diseases (uropathy, toxic megacolon, paralytic ileus, pyloric stenosis, prostatic hypertrophy), myasthenia gravis, or in situations with environmental heat exposure.

Clinician's understanding of the adverse reactions makes the above cautionary situations easily recognizable by compounding effects on preexisting conditions.

Monitoring

Tachycardia is the most common side effect; titrate dose to effect when treating bradydysrhythmia in patients with coronary artery disease. Atropine may precipitate acute angle glaucoma, pyloric obstruction, urinary retention due to benign prostatic hyperplasia, or viscid plugs in patients with chronic lung diseases.

Toxicity

Overdose can lead to increased antimuscarinic side effects of dilated pupils, warm, dry skin, tachycardia, tremor, ataxia, delirium, and coma. In extreme toxicity, circulatory collapse secondary to respiratory failure may occur after paralysis and coma. Ten milligrams or less may be fatal to a child, while there is no known adult lethal dose. 

All Datura plant species have endogenous atropine and other assorted anticholinergic alkaloids. These include Jimson weed and angel’s trumpet, typically seen in warm or temperate climate areas. It may be accidental ingestion or intentionally smoked or ingested for the goal effect of hallucinations. While treatment for ingestions is similar to other toxic overdoses of anticholinergics, whole-bowel irrigation is recommended after a large quantity of seed ingestion. Clinicians need to avoid using phenothiazines in these patients. Physostigmine is the basis of reversal.

Treatment of overdose includes a short-acting barbiturate or diazepam as needed for convulsions or excitement. Avoid dosing for sedation as it can cause respiratory collapse. Physostigmine is useful as an antidote to treat delirium and coma. Repeat doses may be required as physostigmine has a shorter half-life. Monitor respiratory effort and supplement, if necessary.[6][7]

Enhancing Healthcare Team Outcomes

Indications for atropine only include a few conditions, but this alkaloid is life-saving. All interprofessional healthcare team members should be aware of how to use atropine, the dose, and the method of administration. Clinicians can use this drug in patients with bradycardia and poisoning from cholinergic agents; atropine can immediately reverse the slow heart rate and reduce mortality. Nursing staff should always make sure that atropine is available in the cardiac arrest cart. More importantly, a syringe and needle should also be available as the drug can only be administered intravenously. Similarly, the anesthesia nurse should ensure that atropine is available in the operating room at all times. On almost every cardiology and cardiac surgery floor, atropine may be necessary, so it should be readily available. The pharmacist is the team member responsible for ensuring that stock supplies of atropine are available in each department, verifying dosing, and performing medication reconciliation for drug-drug interactions.[8][9] [Level 5] 

Outcomes

Atropine is a very useful drug to reverse bradycardia from many causes. It works immediately and is relatively safe when used at therapeutic doses. There are countless reports on the number of lives saved through the use of atropine in patients with bradycardia or organophosphate poisoning.[10][11] [Level 5]