eMedicine Specialties > Emergency Medicine > Toxicology
Toxicity, Anticholinergic: Treatment & Medication
Updated: Mar 26, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
- 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 IV access and frequently monitor vital signs. Administer naloxone and thiamine and assess for hypoglycemia in patients with altered mental status.
- Manage seizures with benzodiazepines.
- Physostigmine is not recommended in the prehospital setting.
- Avoid ipecac syrup and defer administration of activated charcoal unless a prolonged transport time is anticipated.
Emergency Department Care
Initial assessment and stabilization are required. Upon ED arrival, ensure an adequate airway and check that breathing is present and maintained. Provide oxygen and intubate if significant 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, if found. Obtain an ECG soon after ED arrival. Sinus tachycardia is common and does not require treatment in the stable patient. Administer sodium bicarbonate to patients with QRS prolongation (>100 milliseconds) or the presence of terminal right axis (R wave in aVR > 3 mm) on the ECG. Collect blood for laboratory analysis and quick glucose measurement while obtaining IV access. Closely examine patients for signs of trauma. Agitated patients may respond to reassurance. If chemical restraint is required, physostigmine or benzodiazepines may be used.
- Following initial stabilization, GI decontamination usually is necessary after anticholinergic poisoning by ingestion. Ipecac syrup is contraindicated because of the potential for AMS and seizures.
- For the vast majority of patients, single dose activated charcoal (1 g/kg with or without a cathartic) by mouth or nasogastric tube is sufficient for GI decontamination. Gastric lavage (followed by activated charcoal administration) is acceptable for patients presenting obtunded and within one hour of ingestion. GI decontamination with activated charcoal is recommended, even when patients present many hours postingestion, because of delayed gut emptying of anticholinergic agents and slowed peristalsis. Repeated doses of activated charcoal are not necessary for most patients.
- Most anticholinergic agents have large volumes of distribution and are highly protein-bound; therefore, hemodialysis and hemoperfusion are ineffective treatment methods.
- Following GI decontamination, patients often recover well with supportive care. Tachycardia often resolves with crystalloid infusions, control of agitation (eg, benzodiazepines), and fever control (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. Repeat ECG analysis 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 associated with significant psychomotor agitation. Agitation may be treated with the specific antidote, physostigmine, or nonspecifically with benzodiazepines. Although its use is controversial, physostigmine administration 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 signs or symptoms of urinary retention exist.
- 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; this complication has been reported 3 times in literature, and each occurred when physostigmine was administered to patients with severe tricyclic antidepressant poisoning. To avoid bradyasystole in patients, do not administer physostigmine in the presence of prolonged PR or QRS intervals on the ECG.
- Most patients can be treated safely without physostigmine, but it is recommended for use when at least one of the following aberrations are present: tachydysrhythmias with subsequent hemodynamic compromise, intractable seizures, or severe agitation or psychosis (in which the patient is considered a threat to self or others).
- Although some recommend the use of benzodiazepines as first-line agents for the control of agitation associated with the anticholinergic syndrome, a recent study suggests that physostigmine is significantly more effective and no less safe for use in this setting.
- Physostigmine is contraindicated in patients with cardiac conduction disturbances (prolonged PR and QRS intervals) on ECG analysis.
Consultations
- 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.
Medication
Medical therapy consists of anticonvulsants, antitachydysrhythmics, sodium bicarbonate, physostigmine, and sedatives.
GI decontaminant
Empirically used to minimize systemic absorption of the toxin.
Activated charcoal (Liqui-Char)
Most useful if administered within 4 h of ingestion. Repeat doses may be used, especially with ingestion of sustained release agents. Limited outcome studies exist, especially when administration is more than 1 h of ingestion.
Administration of charcoal by itself (in aqueous solution), as opposed to coadministration with a cathartic is becoming the current practice standard; this is because studies have not shown benefit from cathartics and, while most drugs and toxins are absorbed within 30-90 min, laxatives take hours to work. Also, dangerous fluid and electrolyte shifts have occurred when cathartics are used in small children.
When ingested dose is known, charcoal may be given at 10 times ingested dose of agent over 1 or 2 doses.
Adult
1g/kg PO/NG (50-75 g usual dose); may administer 0.5 g/kg PO/NG as repeat dose if desired
Cathartic: Not recommended
Pediatric
Administer as in adults (12.5-25 g usual dose); may administer 0.5 g/kg PO/NG as repeat dose if desired
<2 years: Cathartic administration not recommended
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; decreased levels occur when administered with sherbet, milk, or ice cream
Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies; unprotected airway with absent gag reflex
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Protect airway before administration in patients with absent gag reflex or a depressed level of consciousness; when considering repeat dosing, monitor for active bowel sounds to minimize risk of charcoal ileus
Benzodiazepines and other sedatives
For patients with agitation or psychosis, verbal reassurance and a quiet dimly lit room may be effective. When pharmacological intervention is required, control of agitation may be achieved with the administration of physostigmine or benzodiazepines (DOC). Treat seizures initially with benzodiazepines.
Diazepam (Valium)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.
Adult
5-10 mg IV q10min; titrate to effect; significant doses may be required to control agitation
Pediatric
30 days to 5 years: 0.2-0.5 mg IV (slowly) q2-5min; titrate to effect
>5 years: 1 mg IV (slowly) q2-5min
Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor for respiratory depression with high or repeated doses; caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)
Lorazepam (Ativan)
Sedative hypnotic with short onset of effects and relatively long half-life.
By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.
Monitoring patient's blood pressure after administering dose is important. Adjust prn.
Adult
2 mg IV/IM; titrate to effect; some patients may require much larger doses
Pediatric
0.05 mg/kg IV/IM
Effects are potentiated by phenothiazines, narcotics, barbiturates, MAOIs, and other antidepressants
Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor for respiratory depression with high or repeated doses; caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease
Phenobarbital (Luminal)
Used for patients refractory to diazepam or lorazepam.
Adult
70-100 mg slow IV initial to control agitation; small increments may be given not to exceed 500 mg
10-20 mg/kg IV no faster than 100 mg/min to control seizures
Pediatric
50 mg IV initial (2-6 mg/kg); small increments may be given at 1-min intervals not to exceed 10-20 mg/kg; children will likely need intubation with larger doses
May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); coadministration with alcohol may produce additive CNS effects and fatality; chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy); menstrual irregularities also may occur
Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritic patients
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor for respiratory depression with high or repeated doses; in prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema
Midazolam (Versed)
Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain vascular access.
Adult
0.01-0.05 mg/kg (usually 0.5-4 mg, up to 10 mg) IV given slowly over several min; may repeat q10-15min until adequate response achieved
Pediatric
<32 weeks: 0.5 mcg/kg/min IV infusion
>32 weeks: 1 mcg/kg/min IV infusion
Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min continuous infusion
Status epilepticus (refractory to standard therapy), >2 months and children: 0.15 mg/kg followed by continuous infusion of 1 mcg/kg/min, titrating dose upward q5min until seizures controlled
Sedative effects may be antagonized by theophyllines; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects because of decreased clearance; reduce dose of thiopental by 15% when using together
Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (diluent)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lower dosages in patients with organic brain syndrome, and patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
Cardiovascular agents
Used only when patient is diagnosed with tricyclic antidepressant overdose or when evidence of sodium channel blockade is present. Routine use is not recommended.
Sodium bicarbonate
Anecdotally, has been effective in treating antihistamine induced QRS prolongation (>100 ms) with a quinidinelike ECG pattern.
Adult
1 mEq/kg IV push; may repeat once; if effective, (narrowing of QRS), begin sodium bicarbonate gtt, 3 amps (44 mEq/amp) in 1 L D5 W; infuse at twice maintenance; not to exceed 50-100 mEq; monitor serum pH frequently and keep in a range of 7.50-7.55; discontinue drip when anticholinergic manifestations resolve and monitor for recurrence
Pediatric
Administer as in adults
Urinary alkalinization, induced by increased sodium bicarbonate concentrations, may cause decreased levels of lithium, tetracyclines, chlorpropamide, methotrexate, and salicylates; Increases levels of amphetamines pseudoephedrine, flecainide, anorexiants, mecamylamine, ephedrine, quinidine, and quinine
Alkalosis; hypernatremia; hypocalcemia; severe pulmonary edema; unknown abdominal pain
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Can cause alkalosis (monitor serum pH; not to exceed 7.55), decreased plasma potassium, hypocalcemia and hypernatremia; caution in electrolyte imbalances such as patients with CHF, cirrhosis, edema, corticosteroid use, or renal failure; when administering, avoid extravasation because can cause tissue necrosis
Cholinergic agents
Reversible anticholinesterase inhibitor that increases the concentration of ACh at the sites of cholinergic neurotransmission. Readily crosses the blood-brain barrier to produce desired CNS effects.
Physostigmine (Antilirium)
Inhibits destruction of acetylcholine by acetylcholinesterase, which facilitates transmission of impulses across myoneural junction.
Clinical effects last 20-60 min. Repeat prn.
Adult
2 mg IV at a slow, controlled rate (no faster than 4 min)
Pediatric
0.02-0.06 mg IV at a slow, controlled rate, not to exceed 0.5 mg/min or 2 mg as a single dose
Atropine antagonizes muscarinic effects; effects of neuromuscular agents are increased
Documented hypersensitivity; GI or GU obstruction
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor heart rate and rhythm during use.
IV injection contains benzyl alcohol; should not be used in neonates; caution in epilepsy, asthma, bradycardia, hyperthyroidism, cardiac arrhythmias, gangrene, peptic ulcer, diabetes, and patients receiving choline esters of depolarizing neuromuscular blockers; anticholinesterase insensitivity can develop for brief or prolonged periods
More on Toxicity, Anticholinergic |
| Overview: Toxicity, Anticholinergic |
| Differential Diagnoses & Workup: Toxicity, Anticholinergic |
 Treatment & Medication: Toxicity, Anticholinergic |
| Follow-up: Toxicity, Anticholinergic |
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References
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McFarland KA. Anticholinergic poisoning. In: Emergency Medicine. 1998.
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Further Reading
Keywords
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