Anticholinergic poisoning

INTRODUCTION — Anticholinergic toxicity is frequently encountered in the emergency department, and thus, it is essential that emergency clinicians be familiar with this toxidrome. There are approximately 8000 to 10,000 exposures to anticholinergic substances (including plants, drugs, and antispasmodics) reported to United States Poison Centers annually [1-5]. Despite the large number of recorded cases, there are typically two or fewer annual fatalities.

The basic mechanisms, presentation, and management of anticholinergic poisoning are reviewed here. Discussions of specific agents that can cause an anticholinergic toxidrome and the general approach to the poisoned patient are found separately. (See "General approach to drug poisoning in adults".)

A summary table to facilitate emergency management of anticholinergic overdose is provided (table 1).

ANTICHOLINERGIC MEDICATIONS AND POISONS — Over 600 compounds have anticholinergic properties, including prescription drugs, over-the-counter medications, and plants (table 2).

Examples of classes of medications with anticholinergic properties include antihistamines (eg, diphenhydramine), tricyclic antidepressants (TCAs; eg, amitriptyline), sleep aids (eg, doxylamine), cold preparations, scopolamine (hyoscine), and tainted illicit street drugs (eg, heroin "cut" with scopolamine). Atropine, a belladonna alkaloid, is a commonly used anticholinergic medication for the treatment of bradyarrhythmias.

Many plants, such as jimson weed (Datura stramonium) and deadly nightshade (Atropa belladonna), may produce anticholinergic toxicity. These may be marketed as "natural" remedies [6]. Jimson weed contains significant concentrations of belladonna alkaloids (hyoscyamine, hyoscine, atropine, and scopolamine). Parts of jimson weed may be ingested (or, less commonly, smoked), usually by adolescents, for their hallucinatory effects [7].

Significant anticholinergic toxicity has also been observed after the topical application of eye drops. Cyclopentolate, commonly used as a mydriatic and cycloplegic, can induce peripheral and systemic symptoms [8]. Toxicity is dose related, and neonates and children appear to be more susceptible. While systemic effects generally improve spontaneously within several hours, treatment with physostigmine may be needed for severe toxicity [9]. (See 'Antidotal therapy with physostigmine for severe toxicity' below.)

PHARMACOLOGY AND CELLULAR TOXICOLOGY — Anticholinergic drugs competitively inhibit binding of the neurotransmitter acetylcholine to muscarinic acetylcholine receptors and are commonly called "antimuscarinic agents." Muscarinic receptors are found in the central nervous system (CNS); in the heart; and on peripheral postganglionic cholinergic nerves in smooth muscle (intestinal and bronchial), the secretory glands (salivary and sweat), and the ciliary body of the eye. Anticholinergic agents do not antagonize the effects at nicotinic acetylcholine receptors, such as at the neuromuscular junction.

KINETICS — The onset of anticholinergic toxicity varies depending on the particular toxin but usually occurs within one to two hours of oral ingestion. Atropine is rapidly absorbed from the gastrointestinal tract and achieves peak plasma concentrations within two hours. Diphenoxylate-atropine (eg, Lomotil) is an antidiarrheal agent that may present with toxicity up to 12 hours after ingestion [10]. Toxicity from scopolamine (hyoscine) may persist for over a day.

CLINICAL FEATURES OF OVERDOSE

Signs of severe toxicity — Effects on the central nervous system (CNS) are associated with more severe anticholinergic toxicity. These CNS effects may include anxiety, agitation, dysarthria, confusion, disorientation, visual hallucinations, bizarre behavior, delirium, psychosis (usually paranoia), coma, and seizures. Central effects often develop concomitantly with peripheral effects (described below) but may persist or manifest after peripheral effects resolve. Patients with CNS toxicity require closer observation and more aggressive care. (See 'Management' below.)

Range of peripheral and central signs of toxicity — The classic description of anticholinergic intoxication is well known but does not distinguish between peripheral and central signs of toxicity. Anticholinergic toxicity should be characterized as peripheral, central, or both peripheral and central. Peripheral findings alone are less concerning; central findings, alone or in combination with peripheral signs, are consistent with more severe toxicity.

●"Red as a beet" (peripheral) – Cutaneous vasodilation occurs as a means to dissipate heat by shunting blood to the skin in order to compensate for the loss of sweat production.

●"Dry as a bone" (anhidrosis; peripheral) – Sweat glands are innervated by muscarinic receptors, so anticholinergic medications produce dry skin.

●"Hot as a hare" (anhidrotic hyperthermia; peripheral) – Interference with normal heat-dissipation mechanisms (ie, sweating) frequently leads to hyperthermia.

●"Blind as a bat" (nonreactive mydriasis; peripheral) – Muscarinic input contributes to both pupillary constriction and effective accommodation. Anticholinergic medications generally produce pupillary dilation and ineffective accommodation that frequently manifests as blurry vision.

●"Mad as a hatter" (delirium, hallucinations; central) – Blockade of muscarinic receptors in the CNS accounts for these findings. These CNS signs and symptoms (ie, central anticholinergic toxicity) are the most worrisome and, if present, the patient can be considered to have "severe" anticholinergic toxicity.

Specific manifestations of CNS anticholinergic toxicity include anxiety, agitation, dysarthria, confusion, disorientation, visual hallucinations, bizarre behavior, delirium, psychosis (usually paranoia), coma, and seizures. Hallucinations are often described as "Alice in Wonderland-like" or "Lilliputian type," where people appear to become larger and smaller. Patients with altered mental status often present with agitation and may appear to grab invisible objects from the air [11]. Although central and peripheral anticholinergic effects are commonly seen together, in some cases, central effects may persist after resolution of peripheral symptoms. Central effects do not occur in all patients with mild anticholinergic toxicity; however, patients who initially manifest only peripheral anticholinergic effects should be observed for the appearance of central anticholinergic effects.

●"Full as a flask" (peripheral) – The detrusor muscle of the bladder and the urethral sphincter are both under muscarinic control; anticholinergic substances reduce detrusor contraction (thereby reducing or eliminating the desire to urinate) and prevent normal opening of the urethral sphincter (contributing to urinary retention).

Other clinical features not mentioned in the description above include other peripheral anticholinergic manifestations such as tachycardia, which is the earliest and most reliable sign of anticholinergic toxicity, and decreased or absent bowel sounds.

Chronic toxicity — Clinicians should be aware of the risk for chronic anticholinergic toxicity. Patients treated chronically with multiple psychiatric medications that possess anticholinergic effects may present with more subtle findings (eg, confusion, alteration in mental status) consistent with anticholinergic toxicity [12]. Such patients may not manifest all aspects of anticholinergic toxicity, and their symptoms may be wrongly attributed to other diagnoses. Clinicians should be aware of psychotropic agents and other classes of medications with anticholinergic properties (table 2).

LABORATORY EVALUATION — Serum drug levels of anticholinergic agents are neither helpful nor readily available in the clinical setting; the diagnosis of anticholinergic toxicity is based on clinical findings and occasionally the results of a diagnostic/therapeutic trial of physostigmine. (See 'Antidotal therapy with physostigmine for severe toxicity' below.)

The following basic screening tests should be obtained in any patient with suspected overdose:

●Fingerstick glucose to rule out hypoglycemia as the cause of any alteration in mental status

●Acetaminophen and salicylate levels to rule out these common coingestions

●Electrocardiogram (ECG) to rule out conduction system poisoning that affects the QRS or the QTc intervals

●Pregnancy test in all women of childbearing age

It is crucial that clinicians obtain an ECG in patients with anticholinergic toxicity. The ECG enables detection of prolonged QRS interval duration and arrhythmias from possible overdose of tricyclic antidepressants (TCAs), certain phenothiazines (eg, mesoridazine and thioridazine), diphenhydramine, and other agents. It also allows detection of QTc interval prolongation. Astemizole, an antihistamine with anticholinergic properties, was removed from the market in the United States because of QT prolongation and its association with torsades de pointes [13,14].

Patients with severe psychomotor agitation and seizures should have a serum creatine kinase level checked to rule out rhabdomyolysis. Doxylamine, an antihistamine found in an over-the-counter sleep aid, is unique in that it has been associated with nontraumatic rhabdomyolysis [15-18].

Additional tests may be necessary depending on clinical circumstances (eg, cardiac enzymes for patients with chest pain, coagulation studies for suspected disseminated intravascular coagulation, assessment of renal function testing in patients with rhabdomyolysis).

DIFFERENTIAL DIAGNOSIS — Any substance or condition that produces an alteration in mental status, tachycardia, urinary retention, or seizure should be included in the differential diagnosis. A wide range of medical conditions and drugs can cause delirium (table 3). (See "Diagnosis of delirium and confusional states" and "General approach to drug poisoning in adults".)

Organic processes, such as meningitis and sepsis, should also be considered. The timing of onset of delirium may help differentiate toxin-induced causes from organic ones, as delirium from anticholinergic poisoning usually begins more abruptly than that from organic causes, such as sepsis or uremia.

Because so many classes of drugs and toxins have anticholinergic effects, clinicians must differentiate pure anticholinergic poisoning from poisonings in which anticholinergic toxicity is but one aspect. Tricyclic antidepressants (TCAs) can produce anticholinergic effects, but these generally occur soon after overdose, and effects from quinidine-like sodium channel blockade (resulting in a prolonged QRS interval) and alpha blockade (resulting in hypotension) are usually more prominent (see "Tricyclic antidepressant poisoning"). Phenothiazines have modest anticholinergic effects, but their sedating and alpha-blocking properties tend to predominate.

Sympathomimetic overdose and serotonin toxicity may cause agitation, tachycardia, and hyperthermia but can usually be differentiated from anticholinergic toxicity. Sympathomimetic overdose and serotonin toxicity generally cause diaphoresis, in contradistinction to anticholinergic overdose. (See "Serotonin syndrome (serotonin toxicity)".)

In a patient with altered mental status, agitation, and hyperthermia, salicylate overdose should also be considered. (See "Salicylate (aspirin) poisoning: Clinical manifestations and evaluation".)

DIAGNOSIS — The diagnosis of anticholinergic poisoning is based on the clinical signs and symptoms of antimuscarinic toxicity. These include tachycardia, flushing, anhidrosis, hyperthermia, blurry vision (mydriasis), delirium with agitation, and diminished bowel sounds. (See 'Clinical features of overdose' above.)

Anticholinergic poisoning is most easily diagnosed when a history of exposure to an anticholinergic substance is obtained and the patient presents with confusion, delirium, or hallucinations. However, in patients where no history is available or when the exposure is unknown, anticholinergic poisoning should be considered in patients with altered mental status and physical examination findings consistent with anticholinergic poisoning. In cases where the diagnosis is unclear and there is no contraindication, the patient's response to the administration of physostigmine may be helpful with diagnosis. If a patient is administered an appropriate dose and rate of physostigmine and develops signs and symptoms of cholinergic excess (eg, bradycardia, sweating), the patient does not have anticholinergic poisoning. (See 'Antidotal therapy with physostigmine for severe toxicity' below.)

MANAGEMENT

Airway, breathing, circulation, monitoring — Management of the poisoned patient must always begin with stabilization of the airway, breathing, and circulation. Patients should have intravenous (IV) access, supplemental oxygen, cardiac monitoring, and continuous pulse oximetry. A summary table to facilitate emergency management of anticholinergic overdose is provided (table 1).

Many medications have anticholinergic properties, and they manifest toxicities, including cardiotoxicity, at different times and to different degrees. Therefore, we suggest continuing cardiac monitoring and pulse oximetry until cardiac symptoms (eg, tachycardia) and central nervous system (CNS) toxicity resolve and an appropriate period of observation is completed. Further guidance can be provided by a medical toxicologist. (See 'Regional poison control centers' below.)

General discussions of the basic facets of the management of poisonings are found separately. (See "General approach to drug poisoning in adults" and "Initial management of the critically ill adult with an unknown overdose" and "Gastrointestinal decontamination of the poisoned patient".)

Cardiotoxicity — Sinus tachycardia is a common finding in patients with anticholinergic toxicity. Although the heart rate can occasionally exceed 150 beats/minute, specific therapy to slow the heart rate is rarely necessary; tachycardia usually resolves with time.

Prolonged QRS intervals and wide complex tachyarrhythmias related to anticholinergic poisoning are treated with sodium bicarbonate [19,20]. The use of sodium bicarbonate, including dosing, in the treatment of poison-related cardiotoxicity is discussed in detail separately. (See "Tricyclic antidepressant poisoning", section on 'Sodium bicarbonate for cardiac toxicity'.)

Agitation, seizures, hyperthermia — Agitation and seizures are worrisome signs of central anticholinergic toxicity. They should initially be treated with benzodiazepines (eg, lorazepam 1 to 2 mg IV [pediatric dose 0.1 mg/kg up to 2 mg maximum single dose]). Benzodiazepines are effective, safe, and can be used in high doses to control symptoms. Treatment with physostigmine may also be needed. (See 'Antidotal therapy with physostigmine for severe toxicity' below.)

Evidence supporting the use of benzodiazepines to treat agitation and seizures is discussed separately. (See "Convulsive status epilepticus in adults: Management", section on 'First therapy: Benzodiazepines'.)

Phenothiazines and butyrophenones should not be used to sedate patients with anticholinergic toxicity; they are themselves anticholinergic and may exacerbate rather than improve symptoms. Likewise, ziprasidone may prolong the QT interval, and olanzapine, another injectable second-generation antipsychotic, possesses anticholinergic properties; and these medications too should be avoided.

Hyperthermia should be treated with standard interventions, including evaporative cooling for moderate to severe cases. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults".)

Rhabdomyolysis management is discussed in detail separately. (See "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)" and "Rhabdomyolysis: Clinical manifestations and diagnosis".)

Decontamination — Although systemic anticholinergic toxicity has been reported from cutaneous and ocular absorption, most anticholinergic toxicity results from ingestion [21-23].

Depending on the poison and the route and timing of exposure, gastrointestinal (GI) decontamination should be performed; in the vast majority of cases, this consists only of administration of activated charcoal (AC). If the patient's mental status is intact and ingestion of an anticholinergic agent is likely, we suggest AC (1 g/kg; maximum 50 g) be given. AC should be withheld in patients with a depressed mental status who may not be able to protect their airway, unless tracheal intubation is performed first. However, tracheal intubation should not be performed for the sole purpose of giving AC. (See "Gastrointestinal decontamination of the poisoned patient".)

Gastric lavage is seldom needed, and induced emesis should be avoided. External decontamination may be necessary for topical agents (eg, removal of a scopolamine (hyoscine) patch).

Antidotal therapy with physostigmine for severe toxicity

Indications, contraindications, and cautions — Most patients with anticholinergic toxicity do well with supportive care alone, but some may benefit from antidotal therapy with physostigmine [24,25]. We believe that physostigmine is indicated when patients manifest significant central anticholinergic toxicity (eg, moderate to severe agitation or delirium). Typically, central anticholinergic toxicity often occurs concurrently with peripheral toxicity, but this is not always the case. Physostigmine should not be given if a condition other than a purely anticholinergic poisoning is suspected (eg, tricyclic antidepressant [TCA] overdose). Other relative contraindications to physostigmine include reactive airway disease, intestinal obstruction, epilepsy, and cardiac conduction abnormalities.

Based on evidence from observational studies, the management of known or suspected isolated anticholinergic poisoning with physostigmine appears to be safe and associated with few complications when given appropriately [26-28]. Physostigmine appears to be superior to benzodiazepines in the management of agitation and delirium due to isolated anticholinergic toxicity. Although patients with minor anticholinergic toxicity may respond well to small doses of benzodiazepines, those with moderate to severe agitation will likely respond better to physostigmine. Studies and trials supporting the use of physostigmine include the following:

●In a trial of 19 children (ages 10 to 18 years) presenting for anticholinergic toxicity (both central and peripheral symptoms), a physostigmine bolus and four-hour infusion, compared with a lorazepam bolus, decreased the rate of delirium and the agitation scores [29]. No patients experienced a serious adverse event.

●In a retrospective study of 52 consecutive patients treated for anticholinergic poisoning, physostigmine was significantly more effective than benzodiazepines in controlling agitation and delirium [30]. Patients treated with physostigmine experienced fewer complications and had shorter recovery times.

●In a retrospective study of bedside consultations performed by medical toxicologists for anticholinergic toxicity, the use of physostigmine was associated with a significantly lower rate of intubation compared with benzodiazepines [31].

●The results of a small randomized trial in children comparing physostigmine with lorazepam suggest that physostigmine is superior to lorazepam for the treatment of anticholinergic delirium [29]. However, this study involved only 19 children and involved a continuous physostigmine infusion. Physostigmine can cause harm, and an infusion may increase that risk without appreciable benefit compared with intermittent IV dosing.

The use of physostigmine is controversial [30]. If the patient is not poisoned with an anticholinergic substance, or if physostigmine is given injudiciously, cholinergic toxicity may result. Symptoms of cholinergic excess include diarrhea, urination, miosis, bronchospasm/bronchorrhea, emesis, lacrimation, and sweating (the mnemonic often used is DUMBELS). Seizures and bradyarrhythmias may also ensue. In patients who develop cholinergic toxicity, atropine may be administered. A reasonable starting dose of atropine is half the dose of the physostigmine that was administered, titrated to clinical effect. The clinical findings of cholinergic toxicity are described in greater detail separately. (See "Organophosphate and carbamate poisoning", section on 'Acute toxicity'.)

There are case reports of TCA-poisoned patients with a wide QRS interval (greater than 0.10 seconds) by electrocardiogram (ECG) who developed asystole following physostigmine administration [32]. Although it is commonly taught that physostigmine should not be given in the setting of known or suspected TCA overdose, some have questioned the basis for this proscription [33]. On a practical level, it is uncommon for patients with significant TCA poisoning to develop the delirium suggestive of severe central anticholinergic toxicity. While TCAs are weak anticholinergics, they are strong antihistamines, and TCA-poisoned patients are usually sedated, not delirious or agitated. Physostigmine would therefore not be considered in these patients based on their mental status. As a general rule, we do not use physostigmine when TCA poisoning is known or suspected, or when the duration of the QRS interval is at or above 100 msec.

Administration and pharmacology — Because physostigmine is used infrequently and unfamiliar to many clinicians, we recommend it be given after consultation with a medical toxicologist or regional poison center. (See 'Regional poison control centers' below.)

Before physostigmine is given, the patient should be placed on a cardiac monitor, and atropine and resuscitative equipment should be available at the bedside.

In adults, the recommended dose of physostigmine is 0.5 to 2 mg (0.02 mg/kg IV up to a maximum of 0.5 mg per dose in pediatric patients). The drug should be given by slow IV push generally over five minutes. Overly rapid administration may result in cholinergic symptoms or seizures.

The half-life of physostigmine is approximately 15 minutes, but its effects often last significantly longer. Additional, smaller doses may be repeated after 20 to 30 minutes if delirium recurs. Although patient symptoms and signs should guide the duration of physostigmine therapy, it is worth noting that in one retrospective study, none of the 14 patients with anticholinergic toxicity required additional physostigmine more than 6.5 hours after their initial dose [34].

Physostigmine is a carbamate acetylcholinesterase inhibitor that binds reversibly to inhibit acetylcholinesterase in both the peripheral nervous system and CNS. Once physostigmine blocks acetylcholinesterase, the concentration of acetylcholine at muscarinic receptors increases and usually overcomes any anticholinergic blockade. Physostigmine is a tertiary amine and crosses the blood-brain barrier; other medicinal carbamates (eg, neostigmine, pyridostigmine) are unable to traverse this barrier. Physostigmine is thus extremely useful in reversing the peripheral and central effects of anticholinergic toxicity.

During shortages of physostigmine in the United States, alternative agents such as oral and/or transdermal rivastigmine have been successfully used as treatment options for anticholinergic delirium [35,36]. In a study of 22 patients with anticholinergic delirium, all were treated with a rivastigmine patch (median dose 13.3 mg, patch removed after 24 hours), and 15 received oral rivastigmine (median dose 6 mg); all patients except for one with a co-ingestion improved, and no patient suffered an adverse event attributed to rivastigmine [35]. Other case reports also describe successful use of rivastigmine [37-39]. However, while rivastigmine is a tertiary amine that crosses the blood-brain barrier similar to physostigmine, it is unclear whether rivastigmine administration caused the observed improvement or whether these patients would have had similar outcomes without it. Further experience is necessary to determine the efficacy and safety of rivastigmine before it can be routinely recommended to treat anticholinergic delirium.

PEDIATRIC CONSIDERATIONS — Unintentional ingestions are the leading cause of anticholinergic poisoning among children. The clinical presentation and management are similar to that in adults. Management consists of close observation, supportive care, activated charcoal (AC) administration, and physostigmine, if indicated. The pediatric dose of physostigmine is 0.02 mg/kg (maximum 0.5 mg).

Adolescents may ingest a variety of substances for their hallucinogenic properties or with suicidal intent, including drugs with anticholinergic properties [40-42]. Plants such as jimson weed are easily found in the environment and a popular item for consumption [7]. Management is the same as that for adults.

DISPOSITION — The following disposition suggestions are based on our clinical experience. Asymptomatic patients who have ingested an anticholinergic substance should receive gastrointestinal (GI) decontamination with activated charcoal (AC) and be observed in the emergency department for a minimum of six hours. If they remain asymptomatic during this observation period, they may be discharged.

Patients with mild anticholinergic toxicity should receive GI decontamination with AC (if possible) and may be treated with benzodiazepines (if necessary) and observed for resolution of symptoms. If symptoms resolve within a reasonable timeframe (six hours), they may be discharged; if not, they should be admitted for observation, including pulse oximetry and cardiac monitoring.

Patients who have severe anticholinergic toxicity, and patients treated with physostigmine, should be admitted to an intensive care unit for observation.

Certain anticholinergic agents (eg, scopolamine [hyoscine]) can have effects for 24 to 48 hours following exposure. In rare instances, effects have lasted up to two weeks. Such patients require a longer period of observation.

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

●Anticholinergic medications ─ Over 600 compounds have anticholinergic properties, including prescription drugs, over-the-counter medications, and plants (table 2). Anticholinergic medication overdose is common, especially antihistamines such as diphenhydramine, and occurs most often through oral ingestion. (See 'Anticholinergic medications and poisons' above.)

●Pharmacology – Anticholinergic drugs competitively inhibit binding of acetylcholine to muscarinic acetylcholine receptors in the central nervous system (CNS), heart, peripheral postganglionic cholinergic nerves in smooth muscle, secretory glands, and the ciliary body of the eye. (See 'Pharmacology and cellular toxicology' above.)

●Clinical features of toxicity ─ The classic signs of anticholinergic intoxication are summarized in the following mnemonic (see 'Clinical features of overdose' above):

•"Red as a beet" (cutaneous vasodilation)

•"Dry as a bone" (anhidrosis)

•"Hot as a hare" (anhidrotic hyperthermia)

•"Blind as a bat" (nonreactive mydriasis)

•"Mad as a hatter" (delirium, hallucinations)

•"Full as a flask" (urinary retention)

Effects on the CNS are associated with more severe toxicity and may include anxiety, agitation, dysarthria, confusion, disorientation, visual hallucinations, bizarre behavior, delirium, psychosis (usually paranoia), coma, and seizures. (See 'Signs of severe toxicity' above.)

Other clinical features not included in the mnemonic are tachycardia, the earliest and most reliable sign of anticholinergic toxicity, and decreased or absent bowel sounds. Although central and peripheral anticholinergic effects are commonly seen together, sometimes central effects may persist or manifest after resolution of peripheral symptoms.

●Differential diagnosis ─ Any substance or condition that produces an alteration in mental status, tachycardia, urinary retention, or seizure may be included in the differential diagnosis (table 3). Organic processes, such as meningitis and sepsis, should also be considered. Delirium from anticholinergic poisoning usually begins more abruptly than that from organic causes, such as sepsis or uremia. (See 'Differential diagnosis' above.)

●Laboratory and other testing ─ Serum concentrations of anticholinergic agents are neither helpful nor readily available in the clinical setting. Obtain fingerstick blood glucose, acetaminophen and salicylate serum concentrations, and an electrocardiogram (ECG) to evaluate for hypoglycemia, co-ingestions, and conduction system poisoning that affects the QRS or the QTc intervals. (See 'Laboratory evaluation' above.)

●Diagnosis ─ The diagnosis of anticholinergic toxicity is based on clinical findings and occasionally the results of a diagnostic/therapeutic trial of physostigmine. (See 'Diagnosis' above.)

●Overview of management ─ A summary table to facilitate emergency management of anticholinergic overdose is provided (table 1). Management includes supportive care, assessment and stabilization of the airway, breathing, and circulation, treatment of agitation and seizures, gastrointestinal decontamination if appropriate, and potential antidotal physostigmine therapy.

•Agitation and seizure treatment ─ We recommend that agitation and seizures be treated initially with benzodiazepines (Grade 1A). Benzodiazepines are effective and safe, and they can be used in high doses to control symptoms. (See 'Airway, breathing, circulation, monitoring' above and 'Agitation, seizures, hyperthermia' above.)

Phenothiazines and butyrophenones should not be used to sedate patients with anticholinergic toxicity; they are themselves anticholinergic and may exacerbate rather than improve symptoms. Hyperthermia can be a dangerous complication and should be treated with standard interventions. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults".)

•Gastrointestinal (GI) decontamination ─ If the patient's mental status is intact and ingestion of an anticholinergic agent is likely, we suggest decontamination with activated charcoal (AC; 1 g/kg, maximum 50 g) (Grade 2C). AC is withheld from somnolent and sedated patients and those who cannot protect their airway, unless tracheal intubation is performed. Intubation should not be performed solely for the purpose of giving AC. (See 'Decontamination' above.)

•Antidotal physostigmine therapy ─ We suggest administering physostigmine to patients with an isolated anticholinergic poisoning and signs of significant central anticholinergic toxicity (eg, moderate to severe agitation or delirium) (Grade 2C). The use of physostigmine is controversial, and it should not be given if a condition other than a purely anticholinergic poisoning is suspected. (See 'Antidotal therapy with physostigmine for severe toxicity' above.)

-Before physostigmine is administered, the patient should be on a cardiac monitor, and atropine and resuscitative equipment should be at the bedside.

-In adults, the dose of physostigmine is 0.5 to 2 mg (0.02 mg/kg intravenously [IV], up to a maximum of 0.5 mg per dose in pediatric patients). The drug is given by slow IV push.

-Relative contraindications include reactive airway disease, intestinal obstruction, seizure, and cardiac conduction abnormalities. (See 'Indications, contraindications, and cautions' above.)

-If clinicians are uncomfortable with its use, they should obtain consultation with a medical toxicologist or regional poison center before physostigmine is given.

●Disposition ─ Asymptomatic patients should be observed in the emergency department for a minimum of six hours. If they remain asymptomatic, they may be discharged. Patients with mild anticholinergic toxicity should be treated and observed for resolution of symptoms. Patients who have severe anticholinergic toxicity and patients treated with physostigmine should be observed for at least 24 hours. (See 'Disposition' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Stephen J Traub, MD, former section editor of the toxicology program, for 20 years of dedicated service.