Anticholinergic Toxicity Treatment & Management

Prehospital care includes the following:

• Rapidly transport the patient to the nearest emergency facility with advanced life support (ALS) capabilities.
• Focus primary assessment on circulatory, respiratory, and neurologic systems.
• Obtain intravenous access and frequently monitor vital signs.
• Administer naloxone if respiratory depression due to opioid intoxication is suspected.
• Assess for hypoglycemia in patients with altered mental status.
• Manage seizures with benzodiazepines.
• Physostigmine is not recommended in the prehospital setting.

Initial assessment and stabilization are required in the emergency department (ED). Upon arrival, ensure that the airway is adequate and that breathing is present and maintained. ^[3] Provide oxygen and intubate if significant central nervous system (CNS) or respiratory depression exists. Assess circulation and initiate cardiac and pulse oximetry monitoring. Examine the patient's body for transdermal drug delivery patches (eg, scopolamine) and remove any if found.

Obtain an electrocardiogram (ECG) soon after ED arrival. Sinus tachycardia is common and does not require treatment in the stable patient. Consider administration of sodium bicarbonate to patients with signs of sodium channel blockade such as QRS prolongation (> 100 milliseconds) or a terminal R wave in aVR > 3 mm on the ECG.

Collect blood for laboratory analysis and quick glucose measurement while obtaining intravenous access. Closely examine patients for signs of trauma.

Agitated patients may respond to reassurance. If pharmacological intervention is required, physostigmine or benzodiazepines may be used.

Following initial stabilization, gastrointestinal (GI) decontamination may be undertaken in patients with recent (typically < 1 hour), clinically significant ingestions that are anticipated to result in moderate-to-severe anticholinergic toxicity. For the vast majority of patients, a single dose of activated charcoal (1 g/kg) by mouth is sufficient for GI decontamination. Administration of activated charcoal may be considered in patients with more remote ingestions (> 1 hr) if it is suspected that a significant amount of drug remains in the GI tract (eg, bezoar formation or delayed absoption due to anticholinergic ileus).

Patients with altered mental status or impaired airway protective reflexes are at risk for charcoal aspiration and pneumonitis. These patients should be intubated with a cuffed endotracheal tube to prevent aspiration prior to administration of activated charcoal via orogastric tube. Gastric lavage is typically not indicated following anticholinergic medication overdose. 

Most anticholinergic agents have large volumes of distribution and are highly protein bound. Therefore, hemodialysis and hemoperfusion are ineffective treatment methods.

Patients often recover well with supportive care. Tachycardia may be responsive to crystalloid infusions, control of agitation (eg, benzodiazepines), and control of hyperthermia (eg, fluids, antipyretics, active cooling measures). Administer a trial dose of physostigmine over 2-5 minutes for patients with narrow QRS supraventricular tachydysrhythmias resulting in hemodynamic deterioration or ischemic pain. Ventricular arrhythmias can be treated with lidocaine.

Manage seizures with benzodiazepines, preferably diazepam or lorazepam. Use phenobarbital and other barbiturates for intractable seizures. Phenytoin has no proven role for toxin-induced seizures and should not be used. Perform a repeat ECG immediately following seizure activity because acidosis can potentiate conduction aberrancies with certain agents.

Patients with hallucinations often respond to reassurance and do not require specific treatment unless they also have significant psychomotor agitation. Agitation may be treated with the specific antidote, physostigmine, or nonspecifically with benzodiazepines. Although its use is controversial, physostigmine is safe and effective for controlling agitated delirium if the ECG indicates the absence of prolonged PR and QRS intervals. Phenothiazines are contraindicated because of their anticholinergic properties. Perform bladder catheterization if the patient shows signs or symptoms of urinary retention.

The antidote for anticholinergic toxicity is physostigmine salicylate. Physostigmine is the only reversible acetylcholinesterase inhibitor capable of directly antagonizing the CNS manifestations of anticholinergic toxicity; it is an uncharged tertiary amine that efficiently crosses the blood-brain barrier.

By inhibiting acetylcholinesterase, the enzyme responsible for the hydrolysis of acetylcholine, an increased concentration of acetylcholine augments stimulation at muscarinic and nicotinic receptors. Physostigmine can reverse the central effects of coma, seizures, severe dyskinesias, hallucinations, agitation, and respiratory depression. The most common indication for physostigmine is to control agitated delirium.

The most common adverse effects from physostigmine are peripheral cholinergic manifestations (eg, vomiting, diarrhea, abdominal cramps, diaphoresis). Physostigmine also may produce seizures, a complication frequently reported when administered to individuals with tricyclic antidepressant poisoning. Rarely, physostigmine may produce bradyasystole; three cases of this complication have been reported in literature, and all occurred in patients given physostigmine for severe tricyclic antidepressant poisoning. To avoid bradyasystole, do not administer physostigmine to patients whose ECG shows a prolonged PR or QRS interval.

Most patients can be treated safely without physostigmine, but its use is recommended when at least one of the following aberrations is present:

• Tachydysrhythmias with subsequent hemodynamic compromise
• Intractable seizures
• Severe agitation or psychosis (in which the patient is considered a threat to self or others)

Although some authors recommend the use of benzodiazepines as first-line agents for the control of agitation associated with the anticholinergic syndrome, one study suggests that physostigmine is significantly more effective and no less safe for use in this setting. ^[13]

Physostigmine is contraindicated in patients with cardiac conduction disturbances (prolonged PR and QRS intervals) on ECG. It should not be used in patients with asthma or diabetes mellitus.

Admission decisions are based on patient symptomatology. Patients without anticholinergic signs or symptoms can be discharged after a 4-6 hour observation period. Individuals with initial mild toxicity that resolves during initial observation also may be discharged.

Admit and monitor symptomatic patients, usually in an ICU setting, until a symptom-free period of 4 hours without the aid of antidotes or supportive therapy is documented.

Consult with a regional poison center and/or toxicologist in all toxic exposures for assistance with decontamination and therapeutic intervention decisions, particularly regarding the use of physostigmine. Psychiatric consultation is mandatory in all intentional ingestions. In chronic intoxication or overmedication, contact the prescribing physician to prevent recurrence.