Treatment of anticholinergic toxicity primarily includes observation, monitoring, and good supportive care (Table 202-4). Temperature monitoring and treatment of hyperthermia are essential. GI decontamination with activated charcoal may be warranted to decrease absorption if the ingestion occurred within 1 hour. Although the benefit of activated charcoal is equivocal after 1 hour from ingestion, the decreased gut motility associated with anticholinergic ingestions may warrant charcoal administration beyond this 1-hour window.34,35,36 Multidose activated charcoal is not recommended in patients with impaired GI motility, such as with anticholinergic toxicity.37 Ipecac syrup is contraindicated in an anticholinergic overdose, and its use in any overdose patient should be abandoned.31,38
TABLE 202-4Treatment of Anticholinergic Toxicity ||Download (.pdf) TABLE 202-4 Treatment of Anticholinergic Toxicity
|Action ||Agent ||Comments |
|GI decontamination ||Activated charcoal ||May be more effective due to the decreased GI motility. |
|Sedation ||Benzodiazepines ||Decreases the risk of hyperthermia, rhabdomyolysis, and traumatic injuries. |
|Wide-complex tachyarrhythmias ||Sodium bicarbonate ||Arrhythmia due to sodium-channel blockade; avoid class IA antiarrhythmics (procainamide). |
|Cholinesterase inhibition ||Physostigmine ||Use for cases of severe agitation or delirium; avoid when cardiac conduction abnormalities are present (see "Treatment" section). |
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, because prolonged use of physical restraints in the struggling and agitated patient may lead to further complications.
Pharmacologic sedation should begin with IV administration of a benzodiazepine, such as lorazepam or diazepam. Benzodiazepines are not a specific antidote, and some patients may be refractory to large doses. Phenothiazines should be avoided because of their own anticholinergic effects. In severe cases of agitation when adequate sedation cannot be achieved without impairing respiration, mechanical ventilation and deep sedation may be necessary.
Intravenous sodium bicarbonate should be used to treat wide-complex tachydysrhythmias.24,25 Class IA antiarrhythmic agents should be avoided because of their own sodium-channel blockade properties.
Physostigmine is a reversible acetylcholinesterase inhibitor (mechanistically related to the carbamate insecticides) that crosses the blood–brain barrier because of its lipophilic tertiary ammonium properties. Acetylcholinesterase inhibition results in acetylcholine accumulation that reverses both central and peripheral anticholinergic effects. Using physostigmine to reverse anticholinergic toxicity is controversial.39,40
The major adverse effects of physostigmine—profound bradycardia and seizures—were historically touted as common, but evidence for this belief is lacking.41 Importantly, the risk of these adverse effects appears greater in patients without anticholinergic toxicity, so accurate diagnosis of anticholinergic toxicity is important before administering physostigmine.40,41
Evidence for benefits of physostigmine in anticholinergic toxicity is mixed. Retrospective analysis of 52 patients42 and case reports43,44,45 found that physostigmine was significantly better in controlling agitation and reversing delirium compared with benzodiazepines and was associated with fewer complications and a shorter recovery time. There was no difference in adverse effects between the two groups. Conversely, a different case series did not find that physostigmine use reduced complications or shortened length of stay in 17 patients with severe agitation and delirium after Jimson weed ingestion.46 However, no adverse effects or complications were observed from physostigmine use.
Physostigmine can be used in cases of severe agitation and delirium from pure anticholinergic toxicity, especially in cases necessitating physical restraints and resistant to benzodiazepines. The adult dose of physostigmine is 0.5 to 2 milligrams (pediatric dose is 0.02 milligram/kg with a maximum dose of 2 milligrams) by slow IV administration over 5 minutes. When effective, a significant decrease in agitation may be apparent within 15 to 20 minutes. Provide continuous cardiac monitoring before and during administration of physostigmine to assess for potential bradycardia. Monitor the patient for signs of cholinergic excess, such as diarrhea, urination, miosis, bradycardia, bronchospasm, bronchorrhea, emesis, lacrimation, and salivation. In cases of uncertain anticholinergic poisoning, a diagnostic challenge with physostigmine is not recommended because of the small but increased risk of adverse effects in patients without anticholinergic toxicity.40,41
Physostigmine may be repeated in the same dose if required. Patients who remain asymptomatic for more than 6 hours after the first dose of physostigmine will not require repeat physostigmine dosing.47 Contraindications to physostigmine use include asthma, nonpharmacologically mediated intestinal or bladder obstruction, cardiac conduction disturbances, and suspected concomitant sodium-channel antagonist poisoning.