ANTICHOLINERGIC SYNDROME

A 21 year-old male with a history of depression, bipolar and substance abuse presents in police custody after being petitioned by family for bizarre behavior and suspected overdose.  He was found in his tree fort writhing on floor beside empty bottles of Flexeril,  Seroquel and Tylenol

 PM.   He had told a friend that he would be smoking some "devil's trumpet" later on.  The patient appears confused and agitated.  He is not following commands.  He is tachycardic, warm, agitated, with large pupils.  The patient was staring around the room telling you he is seeing "little people."  Nursing helps you to briefly restrain the patient as IV fluids are started and you order 4mg of Ativan stat IV push.      

ANTICHOLINERGIC TOXICITY

    Background/Pathophysiology

• Acetylcholine is a neurotransmitter that binds to receptors in the peripheral nervous system and central nervous system
• The central anticholinergic syndrome refers to the clinical presentation when the central effects of muscarinic receptor antagonism predominate, with fever, agitation, delirium, and coma.
• Also includes restlessness, irritability, disorientation, confusion, agitation, auditory and visual hallucinations, and incoherent speech.  
• The peripheral anticholinergic syndrome refers to the syndrome seen with peripheral muscarinic antagonism, such as tachycardia, flushed dry skin, dry mouth, ileus, and urinary retention.
• 
  
• Anticholinergic agents competitively inhibit acetylcholine receptors 
• (generally refers to drugs that act at muscarinic, not nicotinic receptors). 
• (An anticholinergic is a substance that antagonizes the action of the neurotransmitter acetylcholine.) 
• A large number of pharmaceuticals and substances found in plants possess anticholinergic activity 
•  The effects often seen within hours of ingestion, and can last from hours to weeks.
• Acetylcholine has many functions including:
•  innervating the ciliary body of the eye, sweat glands,
•  and involuntary smooth muscle cells of the gastrointestinal, pulmonary, and urinary tracts ( inducing muscle contraction)

Drugs with Anticholinergic Properties

• Medications with anticholinergic properties are ubiquitous
• Antihistamines (benadryl overdose) are the most common drug causing anticholinergic toxicity
•  These include antihistamines, tricyclic antidepressants, insomnia drugs, antispasmodics, antidiarrheals, over-the-counter cold medications, herbals, bronchodilators, scopolamine, deadly nightshade, and atropine. 
• Recreational drugs with anticholinergic properties include jimson weed, nicotine (at high doses), and heroin with scopolamine (“pole,” “DXM”). (Am J Emerg Med 1998;16[5]:517.) 

Symptoms/Mnemonic

•   Patients with toxicity are classically described as: 
•  “dry as a bone”  --  skin, mucous membranes, axillae  (lost ability to sweat)
• “hot as a hare” (hyperthermia secondary to impaired sweat production), 
• “red as a beet” (vasodilatory response that attempts to compensate for loss of sweat production), 
• “full as a flask” (urine retention, decreased bowel sounds and ileus), 
• “mad as a hatter” (agitation, confusion, hallucinations, coma, seizures, and rarely death),
•  and “blind as a bat”    ----->>>>  DILATED PUPILS  (MYDRIASIS...stems from impaired papillary constriction and accommodation causing diplopia and increased intraocular pressure)
•   ✭ Tachycardia, however, is the earliest and most common symptom.  (but it's absence does not exclude anticholinergic syndrome)
• due to decreased vagal tone on the AV Node
• The differential diagnosis of patients with anticholinergic medication toxicity is extensive, and includes conditions that cause tachycardia, hyperthermia, confusion, and coma.

Diagnosis

• No routine laboratory tests confirm anticholinergic poisoning
•  based on clinical exam/suspicion
• However, Routine laboratory evaluation, including measurement of electrolytes, glucose, and pulse oximetry, should be checked in the presence of abnormal mental status. In most cases of isolated anticholinergic toxicity, these tests should be normal.
• Should include an ECG to evaluate the QTc interval
• Must rule out co-ingestants
•  Limited urine drugs-of-abuse screening generally does not detect anticholinergic agents, although some rapid screens may pick up cyclic antidepressants.

Treatment

Treatment of anticholinergic toxicity is generally supportive but can be complex   those with obtundation or at risk for aspiration may require intubation Primarily includes observation, monitoring, and good supportive care  Temperature monitoring and treatment of hyperthermia is essential  (see below) What about activated charcoal?? Tintinalli states that GI decontamination with activated charcoal may be warranted to decrease absorption.  Although the American Academy of Clinical Toxicology position statement on the administration of activated charcoal is equivocal regarding the potential benefits of charcoal administration after 1 hour from ingestion, the decreased gut motility associated with anticholinergic ingestions may warrant charcoal administration beyond this 1-hour window... evidence that suggests activated charcoal is more effective in the presence of anticholinergic activity. In patients with impaired GI motility, such as with anticholinergic toxicity, multidose activated charcoal should be used only with careful monitoring to prevent vomiting and pulmonary aspiration. can cause chemical pneumonitis if aspirated  Ipecac syrup is contraindicated in an anticholinergic overdose. Hyperthermia - what about antipyretics? Hyperthermia should be treated aggressively with external cooling, including intravenous crystalloid administration, ice packs on the body, cooling blankets, fans, and mist.   ✭  Because hyperthermia is the result of a hypermetabolic state, there is no role for antipyretics (e.g., acetaminophen). Cardiac monitoring is essential to detect induced arrhythmias.  Sinus tachycardia, although very common, does not require any specific treatment  (other than supportive)  Prolonged QTc is a known occurrence with anticholinergic poisonings and should be treated with sodium bicarbonate to prevent arrhythmias, which include Torsades de pointes.  Benzo's, Benzo's, Benzo's Agitated patients can be treated with benzodiazepines,  Note phenothiazines such as Thorazine and butyrophenones such as Haldol should not be used because they have anticholinergic properties, and can exacerbate poisoning symptoms. (Am J Emerg Med 1989;7[3]:313.) Other/Misc.  What is the role for Physostigmine??  Physostigmine is a peripheral and central-acting reversible carbamate acetylcholinesterase inhibitor (that's a mouthful) and antidote to anticholinergic medications.    Acetylcholinesterase inhibition results in acetylcholine accumulation that reverses both central and peripheral anticholinergic effects. The major adverse effects from physostigmine are dysrhythmias, profound bradycardia, and seizures. The risk of these adverse effects appears greater in patients without anticholinergic toxicity. can be considered in cases of severe agitation not responding to benzodiazepines  Its use is controversial because it lowers the seizure threshold It can also induce a cholinergic crisis (DUMBELS: Diarrhea, Urination, Miosis,Bronchospasm/Bronchorrhea, Emesis, Lacrimation, and Sweating), can induce arrhythmias (most notably in patients with a prolonged QTc), and has been reported to cause asystole in patients with tricyclic antidepressant depressant ingestions . Most recommend consulting a medical toxicologist or regional poison control center before administering this medication. (Ann Emerg Med 1980;9[11]:588; Suchard JR. Med2003;42[1]:14.)  Disposition Asymptomatic patients or those with mild symptoms that resolve within six hours can be safely discharged. All other patients should be admitted for monitoring. Patients with significant symptoms require monitoring in intensive care.

Pearls   -- (Excerpts From Tintinalli)  

-The differential diagnosis of anticholinergic toxicity includes life-threatening presentations such as viral encephalitis, Reye syndrome, head trauma, alcohol and sedative-hypnotic withdrawal, postictal state, other intoxications, neuroleptic malignant syndrome, and an acute psychotic disorder.

 -The difference between anticholinergic toxicity and sympathomimetic toxicity (e.g., cocaine toxicity or delirium tremens) can be subtle, as patients with either may develop tachycardia, mydriasis, and delirium. The presence of red dry skin and the absence of bowel sounds suggest anticholinergic poisoning.

-The major therapeutic challenge in the treatment of moderate to severe anticholinergic poisoning involves obtaining adequate control of the agitated individual. Inadequate sedation may lead to worsening hyperthermia, rhabdomyolysis, and traumatic injuries. Although physical restraints may be required to gain initial control, pharmacologic sedation is strongly recommended. Prolonged use of physical restraints in the struggling and agitated patient may lead to further complications.

-Dilated pupils are often a delayed clinical finding (12 to 24 hours) that may not be observed despite the presence of other anticholinergic signs.

-The anticholinergic toxic patient has great difficulty interacting appropriately with environmental stimuli. Lilliputian (little people) hallucinations have been described in this setting. Repetitive picking at the bed clothes or imaginary objects is also characteristic. Another characteristic feature of anticholinergic delirium is dysarthria, manifested by a staccato speech pattern and difficult-to-comprehend speech. This may be exacerbated by severe dysphasia from decreased mucous secretion. High-pitched cries may sometimes be heard. Patients may also exhibit jerking movements of the extremities and seizures.