Atropine


Article Author:
Kevin McLendon


Article Editor:
Charles Preuss


Editors In Chief:
Dustin Constant
Donald Kushner


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
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Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
11/23/2018 10:42:32 AM

Indications

Atropine or atropine sulfate carries FDA indications for anti-sialagogue/anti-vagal effect, organophosphate/muscarinic poisoning, and bradycardia.[1][2]

Antisialagogue

While atropine can be used independently for anti-salivation effects, it most commonly is secondary to anticholinergic or antimuscarinic poisoning which is discussed below. It is not formally recommended for routine use in controlled airways, though can be used off-label for minimizing secretions in the intubated patient.

Anticholinergic Poisoning

Acetylcholine works on three different receptors that must be addressed in nerve agent poisonings. Atropine is only useful to counter muscarinic effects (pralidoxime and benzodiazepines address the others). If there are local symptoms to the eyes or respiratory tract, atropine is not indicated. Intravenous (IV) atropine is indicated for 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 infranodal 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 3-5min prior to 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 (Lomotil) is an antimotility agent that can be used in the treatment of diarrhea as a second-line therapy. This allows 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 must be used with caution.

Under current ACLS protocols, atropine is indicated for symptomatic bradycardia and not in a pulseless patient. All indications for atropine in the pulseless patient have been removed by the AHA.

Atropine is not indicated in beta-blocker-induced bradycardias or hypotension, though its use is unlikely to be harmful. Glucagon is 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. This 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 side effects as described herein.[4]

Administration

Administration

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

  • Antisialagogue/antivagal: 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 dosing up to 20 mg, titrate to effect of secretion control, not VS)
  • Bradycardia: 1 mg every 3 to 5 minutes (3 mg max), repeat until desired heart rate is obtained, most effective for sinus and AV nodal disease.
  • Pediatric: 0.01 mg/kg to 0.03 mg/kg every 3 to 5 minutes. Pediatric minimum dose 0.1 mg, maximum dose 0.5 mg (child) and 1.0 mg (adolescent); maximum cumulative dose 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 routine. 

In general, dosing of atropine can be repeated every 5 minutes until a maximum of 0.04 mg/kg is reached.

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

Adverse Effects

The most common adverse effects are related to the 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 that can be prevented by combined IV delivery of metoclopramide with atropine before anesthesia. 

Contraindications

Atropine does not carry a FDA Boxed Warning nor any absolute indications. There are multiple conditions that carry a cautionary status, however, relative contraindications are overridden by the clinical need, especially in the unstable or poisoning patient.

Use with 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 advised in 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.

By understanding the adverse reactions, the above cautionary situations are easily understood 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 presenting with 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 fatal dose. 

All Datura plant species have endogenous atropine and other assorted anticholinergic alkaloids. This includes Jimson weed and angel’s trumpet, which is 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. Avoid 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

Atropine is only used to treat a few conditions, but this alkaloid is life-saving. All healthcare workers should be aware of how to use atropine, the dose, and method of administration. In patients with bradycardia and poisoning from cholinergic agents, atropine can immediately reverse the slow heart rate and reduce the mortality. Nurses should always make sure that atropine is available in the cardiac arrest cart. More importantly, there should be a syringe and needle also 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 required, and hence it should be readily available. The pharmacist is the person responsible for ensuring that stock supplies of atropine are available in each department.[8][9]  (Level V) 

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 V)


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Atropine - Questions

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Which of the following is used to reduce excessive secretions during anesthesia?



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What is the most dangerous side effect of atropine in infants?



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Which of the following about atropine is false?



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A 55-year-old man receives general anesthesia during heart surgery. Which of the following would be the most effective in reducing excessive secretions during the general anesthesia?



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When atropine is administered, the patient should monitored for which of the following?



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Which of the following increases the activity of the sinoatrial node?



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Which of the following effects of atropine is helpful for patients before anesthesia?



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A 71-year-old woman receives treatment with atropine. Which of the following is the most likely therapeutic use of atropine in this patient?



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Which of the following medications is contraindicated in glaucoma?



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Which of the following is correct in describing the effect of local application of atropine on the eye?



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A 61-year-old man presents with sinus bradycardia and he receives treatment with atropine. Which of the following is least likely an effect of atropine on this patient?



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Why is atropine administered to patients intraoperatively?



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A 5-year-old boy was found to have eaten an unknown amount of jimson weed and rushed to the emergency room. The patient is bradycardic, his pupils are dilated and he is confused and terrified in the ED. Which of the following agents would be an antidote for this toxicity?



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Which of the following is an anticholinergic agent?



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A nurse is administering atropine sulfate intramuscularly in the preoperative period. What are potential adverse effects of atropine use before surgery? Select all that apply.



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A 67-year-old male is brought in to the emergency department by his wife after she found him in their shed behaving strangely. There were no signs of trauma, but he was sitting next to several bottles of pesticides. She reports he has a history of depression, and she believes he may have tried to harm himself. On physical exam, he is drowsy, sweating profusely and has an episode of emesis. He develops respiratory failure requiring intubation soon after arrival to the emergency department. The antidote used to treat his condition has which of the following mechanism of action?



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Atropine - References

References

Avetisov SE,Fisenko VP,Zhuravlev AS,Avetisov KS, [Atropine use for the prevention of myopia progression]. Vestnik oftalmologii. 2018     [PubMed]
Smulyan H, The Beat Goes On: The Story of 5 Ageless Cardiac Drugs. The American journal of the medical sciences. 2018 Apr 25     [PubMed]
Atropine null. 2006     [PubMed]
Belladonna null. 2006     [PubMed]
Wu PC,Chuang MN,Choi J,Chen H,Wu G,Ohno-Matsui K,Jonas JB,Cheung CMG, Update in myopia and treatment strategy of atropine use in myopia control. Eye (London, England). 2018 Jun 11     [PubMed]
Menezes RG,Usman MS,Hussain SA,Madadin M,Siddiqi TJ,Fatima H,Ram P,Pasha SB,Senthilkumaran S,Fatima TQ,Luis SA, Cerbera odollam toxicity: A review. Journal of forensic and legal medicine. 2018 Aug     [PubMed]
Krzyzak M,Regina A,Jesin RC,Deeb L,Steinberg E,Majlesi N, Anticholinergic Toxicity Secondary to Overuse of Topricin Cream, a Homeopathic Medication. Cureus. 2018 Mar 5     [PubMed]
Hansen M,Eriksson C,Skarica B,Meckler G,Guise JM, Safety events in pediatric out-of-hospital cardiac arrest. The American journal of emergency medicine. 2018 Mar     [PubMed]
Squires N,Wills A,Rowson J, The management of drooling in adults with neurological conditions. Current opinion in otolaryngology     [PubMed]
Ho ML,Gatien M,Vaillancourt C,Whitham V,Stiell IG, Utility of prehospital electrocardiogram characteristics as prognostic markers in out-of-hospital pulseless electrical activity arrests. Emergency medicine journal : EMJ. 2018 Feb     [PubMed]
More SR,Dabhade SS,Ghongane BB, Drug Audit of Intravenous Anaesthetic Agents in Tertiary Care Hospital. Journal of clinical and diagnostic research : JCDR. 2015 Nov     [PubMed]

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