an 11-month-old infant presents to the ED for evaluation after that is found with an open bottle of diphenhydramine.

Gerretsen P, Pollock BG. Drugs v anticholinergic properties: a present perspective top top use and safety. Professional Opin drug Saf. 2011;10(5):751-765.Burns MJ, Linden CH, Graudins A, Brown RM, Fletcher KE. A to compare of physostigmine and also benzodiazepines because that the treatment of anticholinergic poisoning. Ann Emerg Med. 2000;35(4):374-381.Howland MA. Physostigmine salicylate. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. Goldfrank’s Toxicologic Emergencies. Ninth ed. Brand-new York, NY: McGraw Hill; 2011:759-762.Pentel P, Peterson CD. Asystole complicating physostigmine therapy of tricyclic antidepressant overdose. Ann Emerg Med. 1980;9(11):588-590.Boehnert MT, Lovejoy FH, Jr. Value of the QRS duration versus the serum drug level in predicting seizures and also ventricular arrhythmias ~ an acute overdose of tricyclic antidepressants. N Engl J Med. 1985;313(8):474-479.

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A previously healthy 11-month-old boy was brought to the ED after his parents uncovered him v an open up bottle of nonprescription diphenhydramine. On early presentation, the son was irritable with diffuse skin redness and also dry mucous membranes. He was tremulous and making nonpurposeful reaching motions with his arms. He had roving eye movements and also markedly dilated pupils the were minimally reactive. Initial critical signs were: blood pressure, 140/95 mm Hg; heart rate, 220 beats/minute; respiratory rate, 30 breaths/minute; temperature, 100.6ºF. Capillary glucose was 120 mg/dL, and oxygen saturation to be 100% top top room air. An electrocardiogram (ECG) revealed sinus tachycardia with normal QRS and QTc intervals.

What is the toxicological differential diagnosis?

Toxicity indigenous several various classes of drugs may reason an changed level the consciousness, tachycardia, and also hyperthermia. Serotonin agonists, such together selective serotonin reuptake inhibitors, may result in serotonin toxicity—a syndrome that includes altered cognition, autonomic changes (eg, tachycardia, hyperthermia), and also neuromuscular impacts (eg, rigidity, clonus), together with mydriasis and also diaphoresis. Neuroleptic malignant syndrome (NMS) occurs following exposure come dopamine antagonists, such together antipsychotic medications.

Neuroleptic malignant syndrome gift in a comparable manner to serotonin toxicity but tends to have actually a an ext indolent course compared with the abrupt onset and also resolution that serotonin toxicity. Sympathomimetic medicines (eg, methylphenidate) or medicine of abuse (eg, cocaine, methamphetamines) an outcome in catecholamine results including tachycardia, hypertension, diaphoresis, and mydriasis. Acetylsalicylic-acid (aspirin) toxicity (salicylism) often reasons tinnitus, hyperpnea, and gastrointestinal (GI) effects following exposure. Major toxicity may cause altered level the consciousness and hyperthermia; however, these are ominous and late findings. Mydriasis is no common.

What is the anticholinergic toxidrome?

Acetylcholine is a neurotransmitter current both in the main and peripheral worried systems. In the periphery, acetylcholine acts in ~ both the sympathetic and also parasympathetic contents of the autonomic worried system and also at somatic motor fibers. Acetylcholine action at 2 classes that receptors, namely, nicotinic and also muscarinic types. Muscarinic receptors are discovered in the central nervous mechanism (CNS) (specifically the brain) and peripherally on effector cells of the parasympathetic concerned system and also on sympathetically innervated sweat glands.1 Anticholinergic toxicity results from antagonism of muscarinic receptors and is much more appropriately described as antimuscarinic poisoning, though the state are offered interchangeably. Nicotinic receptor antagonists space used mostly for neuromuscular blockade and do not cause this syndrome.

“Hot as a hare” (anhidrosis with temperature elevation);“Red together a beet” (vasodilation with skin hyperemia);“Blind as a bat” (pupillary dilation through loss the accommodation);“Dry as a bone” (drying that mucosal surfaces and skin);“Full as a flask” (urinary retention); “Stuffed together a pepper” (constipation); and“Mad as a hatter” (describing the central anticholinergic impacts that are frequently present—eg, changed mental status manifested as agitation, delirium, hallucinations, abnormal picking movements, seldom seizures).

Elderly patients and also those v underlying medical disease or psychiatric disorders might be much more prone to the CNS manifestations the anticholinergic medications. Anticholinergic impacts can occur through ingestion, smoking, inhalation, and also topical absorption (including transdermal or ophthalmic routes). Delayed or lengthy effects may occur due to slow gastric emptying and lengthy GI absorption. The duration of effects is variable and main anticholinergic manifestations of confusion or agitation might be current for several days, even after peripheral manifestations have resolved (termed the main anticholinergic syndrome).

What space common reasons of anticholinergic toxicity?

Although anticholinergic results are often defined in terms of “toxicity,” these effects are regularly used because that therapeutic benefit. Such functions of anticholinergic agents incorporate the following:

Atropine to treat bradycardia; Ipratropium bromide to manage asthma; Antinauseants (eg, scopolamine, meclizine) for symptom relief; Tolterodine come treat advice incontinence and overactive bladder; andOphthalmologic medications (eg, scopolamine, homatropine) come inhibit ciliary spasm in patients v iritis.

Although the above medications are being supplied for a particular anticholinergic property, various other unintended and also troublesome anticholinergic results are regularly seen. Similarly, numerous other medications often have unintentional anticholinergic results (see Table). Anticholinergic “toxicity” is just an expansion of the impacts that take place with therapeutic use.

What is the therapy for patients through anticholinergic toxicity?

Most patients v anticholinergic toxicity execute well with supportive management. Benzodiazepines are the therapy of selection for agitation. Haloperidol and also other antipsychotics are reasonably contraindicated for therapy of agitation together they might impair temperature regulation and also lead come hyperthermia. Although likely of limited overall benefit, oral activated charcoal might reduce the quantity of drug absorbed.

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Antidotal therapy with physostigmine must be taken into consideration for pick patients presenting with transformed mental status as result of an anticholinergic. Physostigmine is an acetylcholinesterase inhibitor that avoids the breakdown of acetylcholine in the synaptic cleft, therefore antagonizing the results of anticholinergic drugs. A retreat study detailed a reduced incidence of complications and shorter time to recovery with the use of physostigmine contrasted with benzodiazepines in patients through anticholinergic toxicity.2 The usage of physostigmine in select patients may obviate the need for a more delirium workup, which often includes computed tomography or lumbar puncture.