8/7/2018

Tintinalli’s Emergency : A Comprehensive Study Guide, 8e > Chapter 202:

Dan Quan; Frank Lovecchio

INTRODUCTION

Approximately 620 compounds have properties, including prescription , over-the- counter medications, and (Table 202-1). Many of these substances possess anticholinergic activity as either a direct therapeutic eect or an adverse eect, in addition to their primary or predominant pharmacologic eect. (d,l-), hyoscyamine, and (l-hyoscine) are natural that represent prototypical anticholinergic compounds.

1/16 8/7/2018 TABLE 202-1 Major Groups of Substances with Anticholinergic Activity

Class and Subclass Prototypical Agent(s)

Cyclic hydrochloride, hydrochloride, hydrochloride antidepressants

Antihistamines

Ethanolamines , Ethylenediamines Alkylamines Chlorpheniramine Piperazines Loratadine, , cetirizine Phenothiazines Prochlorperazine,

Antiparkinson drugs

Tropanes Benztropine mesylate Piperidines

Antipsychotics

Phenothiazines , , perphenazine , , molindone, , Nonphenothiazines

Antispasmodics

Cyclohexane Dicyclomine carboxylic acids bromide Quaternary ammonium

Belladonna alkaloids

Tropanes Atropine, , scopolamine hydrobromide Pyrrolidines Glycopyrrolate

Mydriatics

2/16 8/7/2018

Class and Subclass Prototypical Agent(s)

Phenylacetates hydrochloride Pyridines

Skeletal muscle relaxants

Tricyclics hydrochloride Ethylamines citrate

Plants

Datura species stramonium (Jimson ), Datura candida (angel's trumpet) species Mandragora oicinarum (mandrake) species (angel's tear, maikoa, or white angel's trumpet), Brugmansiaversicolor (angel's tear or angel's trumpet)

Mushrooms

Amanita species , Amanita pantherina

Antihistamine (particularly diphenhydramine) overdose is the most common overdose that produces anticholinergic toxicity.1 Toxicity in children may result from accidental ingestion of an anticholinergic medication, administration of hyoscyamine-containing agents to treat colic, the topical use of diphenhydramine-containing salves, and therapeutic application of a transdermal hyoscine patch.2,3,4,5 In the elderly, therapeutic doses of one or multiple medications with anticholinergic properties may produce anticholinergic symptoms or ileus without all the signs of the anticholinergic .6,7 Ophthalmologic instillation of anticholinergic mydriatic agents can cause toxicity, especially in the elderly or young children; thus patients are instructed to lie down and apply 5 minutes of gentle pressure on the nasolacrimal duct when instilling these agents.8

Atropine is the for a cholinergic syndrome produced from a nerve agent or an organophosphate insecticide.9 Use of high-dose atropine by someone without cholinesterase poisoning may result in anticholinergic toxicity within 1 hour. This occurred in Israel during the first Gulf War in 1991 when frightened civilians dosed themselves with atropine fearing an incoming Scud missile chemical weapon attack.

Plant poisonings may result in an anticholinergic toxidrome. In Taiwan, the anticholinergic toxidrome is most commonly associated with exposures.10 Belladonna -containing plants have potent anticholinergic eects producing toxicity 1 to 4 hours aer ingestion or sooner if smoked. Alkaloid plants are

3/16 8/7/2018

abused for their hallucinogenic eects.11,12 Group anticholinergic plant poisonings are common in adolescents seeking these psychoactive hallucinogenic eects.13,14 Inadvertent poisoning from the ingestion of belladonna-contaminated herbal teas and Chinese traditional has been reported.15,16 Ingestion of and berries, sometimes due to mistaken identity, can produce anticholinergic toxicity.17,18 Anticholinergics have been substituted for other abused psychoactive drugs and then sold to unwitting customers.19 Adulteration of commonly abused drugs, such as or , with scopolamine or atropine has been observed.20,21,22

PHARMACOLOGY

Anticholinergic absorption can occur aer ingestion, smoking, or ocular use. With oral ingestion, the onset of anticholinergic toxicity usually occurs within 1 to 2 hours. Because muscarinic blockade slows gastric emptying and decreases GI motility, absorption and peak clinical eects are oen delayed. An example is diphenoxylate-atropine (e.g., Lomotil®), an antidiarrheal agent that may present with toxicity up to 12 hours aer ingestion.

Cholinergic receptors exist as two major subtypes: muscarinic receptors and nicotinic receptors. Muscarinic receptors are found predominantly on autonomic eector cells that are innervated by postganglionic parasympathetic nerves, on some ganglia, and in the brain, particularly the hippocampus, cortex, and thalamus. Nicotinic receptors are found at peripheral autonomic ganglia, neuromuscular junctions, and also the brain. is the neurotransmitter that modulates both receptor types. Five genes encode for muscarinic receptors through G protein receptor activation; four seem to be physiologically active (Table 202- 2).

4/16 8/7/2018 TABLE 202-2 Muscarinic Receptors

Receptor Target Organ Receptor Action When Stimulated

M1 Autonomic ganglia Decreases activity in autonomic ganglia Brain Increases salivary and gastric acid secretion Salivary glands Stomach

M2 Heart Decreases sinus node rate and slows conduction through the atrioventricular node Decreases the force of atrial contraction and possibly ventricular contraction

M3 Smooth muscle Bronchospasm Endocrine/exocrine Mild vasodilation glands Increases saliva and gastric acid production Iris Constricts the pupil

M4 CNS Multiple actions

M5 Has not been elucidated

The structure of nicotinic receptors is complex, composed of several subunits that are encoded by multiple genes. The subunits are combined into four main families of nicotinic receptors: the muscle type, found at the neuromuscular junction; the ganglion type, found in autonomic ganglia; and two brain types, found in the CNS.

Anticholinergic drugs and plant toxins competitively inhibit or antagonize the binding of the neurotransmitter acetylcholine to muscarinic acetylcholine receptors. The term anticholinergic is technically a misnomer; a more accurate term is antimuscarinic agents, because anticholinergic agents do not antagonize the eects at nicotinic acetylcholine receptors, such as at the neuromuscular junction. Clinical manifestations from these drugs are modulated through disturbances in the CNS (central eects) and the parasympathetic nervous system (peripheral eects) (Table 202-3).

5/16 8/7/2018 TABLE 202-3 Muscarinic and Antimuscarinic Eects

Organ Stimulation or Muscarinic Eect Antagonism or Antimuscarinic Eect

Brain Complex interactions Complex interactions Possible improvement in memory Impairs memory Produces agitation, , and

Eye ↓ pupil size (miosis) ↑ pupil size () ↓ intraocular pressure ↑ intraocular pressure ↑ tear production Loss of accommodation (blurred vision)

Mouth ↑ saliva production ↓ saliva production Dry mucous membranes

Lungs Bronchospasm Bronchodilation ↑ bronchial secretions

Heart ↓ heart rate ↑ heart rate Slows atrioventricular conduction Enhances atrioventricular conduction

Peripheral Vasodilation (modest) Vasoconstriction (very modest) vasculature

GI ↑ motility ↓ motility ↑ gastric acid production ↓ gastric acid production Produces emesis

Urinary Stimulates bladder contraction and ↓ bladder activity expulsion of urine Promotes

Skin ↑ sweat production ↓ sweat production (dry skin) Cutaneous vasodilation (flushed appearance)

The signs and symptoms of anticholinergic toxicity are a result of both central and peripheral cholinergic blockade. The central anticholinergic syndrome refers to the clinical state when the central eects of

6/16 8/7/2018 muscarinic receptor antagonism predominate, with fever, agitation, delirium, and coma. The peripheral anticholinergic syndrome refers to the syndrome seen with peripheral muscarinic antagonism, such as , flushed dry skin, dry mouth, ileus, and urinary retention.

The full range of clinical manifestations associated with anticholinergic overdose may only be partly explained by muscarinic receptor blockade. Many of these anticholinergic agents possess activity at other cell membrane receptors, and toxicity aer overdose can be a mixture of multiple pharmacologic mechanisms. For example, the clinical findings associated with cyclic antidepressant overdose are only partly characterized by the anticholinergic eects that vary considerably among dierent cyclic antidepressants. The most life-threatening complications of cyclic antidepressant overdose are a result of the sodium-channel blocking eects on the heart, producing wide-complex tachydysrhythmias, not the anticholinergic eects.

Intravenous injection of antihistamines, particularly those aecting the H1 histamine receptor antagonists (diphenhydramine), seems to cause in some patients. This eect may be attributed to the drug increasing dopamine levels in the nucleus accumbens area of the brain that stimulates the reward and motivation system.23

CLINICAL FEATURES

The classic features of the anticholinergic toxidrome can be stated as:

Dry as a bone

Red as a beet

Hot as a hare

Blind as a bat

Mad as a hatter

Stued as a pipe

Dry skin (especially dry axillae) and dry mucous membranes (e.g., dry mouth) are the typical peripheral clinical manifestations, the result of impaired sweat gland and salivary gland secretions, respectively. The skin may be warm and flushed (red) from cutaneous vasodilatation. Other typical peripheral features of muscarinic blockade include hypoactive or absent bowel sounds secondary to decreased peristalsis and GI motility. A palpable bladder or enlargement on bedside US secondary to urinary retention may be seen.

Sinus tachycardia is usually present. More malignant dysrhythmias are less common. Ingestions of large amounts of diphenhydramine have been associated with wide-complex tachydysrhythmias from a sodium- channel blocking eect and not from an anticholinergic eect.24,25 Diphenhydramine overdose has been

7/16 8/7/2018

reported to cause QT-interval prolongation.26,27 Dilated pupils are oen a delayed clinical finding (12 to 24 hours) that may not be observed despite the presence of other anticholinergic signs.

The delirium of the central anticholinergic syndrome is characterized by restlessness, irritability, disorientation, , agitation, auditory and visual hallucinations, and incoherent speech. The anticholinergic toxic patient has great diiculty interacting appropriately with environmental stimuli. Lilliputian ("little people") hallucinations have been described in this setting. Repetitive picking at the bed clothes or imaginary objects is also characteristic. A characteristic feature of anticholinergic delirium is dysarthria, manifested by a staccato speech pattern and diicult-to-comprehend speech. This may be exacerbated by severe dysphasia from decreased mucous secretion. High-pitched cries may sometimes be heard. Patients may also exhibit jerking movements of the extremities and seizures.

Although this delirium is usually accompanied by the peripheral manifestations discussed above, clinical presentations vary, and tachycardia without delirium or delirium without tachycardia may occur. "Agitated depression" can occur from both central excitation and depression. Depression is usually associated with higher doses, and features include lethargy, somnolence, and coma. Overdose with olanzapine, an with significant anticholinergic properties, produces unpredicTable fluctuations in mental status, from somnolence to agitation lasting hours.28

Agitation-induced is a worrisome complication of anticholinergic toxicity, and its development may be significantly potentiated by decreased sweating and the inability to dissipate heat. A markedly elevated body temperature may lead to multisystem organ dysfunction and rhabdomyolysis, resulting in liver, kidney, and brain injury and coagulopathy. Fatalities associated with anticholinergic overdose are characterized by severe agitation, status epilepticus, hyperthermia, wide-complex tachydysrhythmias (usually from sodium channel–blocker eect), and cardiovascular collapse.29

The risk of toxicity for most anticholinergic agents is dose related. For example, severity of diphenhydramine overdose correlates with the amount ingested, with moderate symptoms occurring aer ingestion of 300 milligrams30 and 7.5 milligrams/kg in children,31 and severe symptoms seen only aer ingestions of 1000 milligrams or more in adults.30

DIAGNOSIS

DRUG SCREENING

In patients with altered mental status, obtain routine laboratory evaluation, including measurement of electrolytes, glucose, creatine kinase, and pulse oximetry. In most cases of isolated anticholinergic toxicity, these tests should be normal. Limited urine drugs-of-abuse screening generally does not detect anticholinergic agents, although some rapid screens may produce positive results for cyclic antidepressants due to the structural similarities of some anticholinergic compounds, particularly diphenhydramine and hydroxyzine. Comprehensive urine drug screens, usually performed by thin layer chromatography or mass

8/16 8/7/2018 spectrometry, may detect most antihistamines and phenothiazines, although such testing does not usually detect plant alkaloids, scopolamine, or atropine. A positive drug screen for an anticholinergic agent only indicates exposure, such as a therapeutic dose, and does not necessarily imply an overdose or supratherapeutic ingestion.

DIFFERENTIAL DIAGNOSIS

The dierential diagnosis of anticholinergic toxicity includes life-threatening presentations such as viral encephalitis, Reye's syndrome, head trauma, and sedative-hypnotic withdrawal, postictal state, other intoxications, neuroleptic malignant syndrome, and an acute psychotic disorder. The dierence between anticholinergic toxicity and sympathomimetic toxicity (e.g., cocaine toxicity or delirium tremens) can be subtle, because patients with either may develop tachycardia, mydriasis, and delirium. The presence of red dry skin and the absence of bowel sounds suggest anticholinergic poisoning.32 At times, patients presenting with acute psychotic disorders may have an abnormal mental status, suggesting anticholinergic toxicity, but true delirium and attention deficits are much more characteristic of the latter condition. Other CNS disorders, such as viral encephalitis, may also aect cholinergic outflow and produce similar anticholinergic clinical signs not related to a toxic exposure.33

TREATMENT

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 aer 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

9/16 8/7/2018 TABLE 202-4 Treatment of Anticholinergic Toxicity

Action Agent Comments

GI Activated May be more eective due to the decreased GI motility. decontamination charcoal

Sedation Decreases the risk of hyperthermia, rhabdomyolysis, and traumatic injuries.

Wide-complex Sodium Arrhythmia due to sodium-channel blockade; avoid class IA tachyarrhythmias bicarbonate antiarrhythmics (procainamide).

Cholinesterase Use for cases of severe agitation or delirium; avoid when cardiac inhibition 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 , 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 eects. 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 eects. Using physostigmine to reverse anticholinergic toxicity is controversial.39,40

The major adverse eects 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 eects appears

10/16 8/7/2018 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 dierence in adverse eects between the two groups. Conversely, a dierent case series did not find that physostigmine use reduced complications or shortened length of stay in 17 patients with severe agitation and delirium aer Jimson weed ingestion.46 However, no adverse eects 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 eective, 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 eects 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 aer the first dose of physostigmine will not require repeat physostigmine dosing.47 Contraindications to physostigmine use include , nonpharmacologically mediated intestinal or bladder obstruction, cardiac conduction disturbances, and suspected concomitant sodium-channel antagonist poisoning.

DISPOSITION AND FOLLOW-UP

Patients with mild symptoms of anticholinergic toxicity that resolve aer 6 hours of ED observation may be considered for disposition. Because the duration of action of physostigmine is generally shorter than the duration of action of many anticholinergic agents, the reversal eect may dissipate, resulting in recurrent toxicity. Most symptomatic patients, including those patients who have received physostigmine, require hospital observation for at least 24 hours.

REFERENCES

1. Mory JB, Spyker DA, Cantelina LR et al.: 2013 Annual Report of the American Association of Control Centers’ National Poison Data System (NPDS): 31st Annual Report. Clin Toxicol (Phila) 52: 1032, 2014.

11/16 8/7/2018 [PubMed: 25559822]

2. Myers JH, Moro-Sutherland D, Shook JE: Anticholinergic poisoning in colicky infants treated with hyoscyamine sulfate. Am J Emerg Med 15: 532, 1997. [PubMed: 9270398]

3. Lee AC, So KT: Acute anticholinergic poisoning in children. Hong Kong Med J 11: 520, 2005. [PubMed: 16340032]

4. Reilly JF Jr, Weisse ME: Topically induced diphenhydramine toxicity. J Emerg Med 8: 59, 1990. [PubMed: 2351800]

5. Frampton A, Spinks J: Hyperthermia associated with central anticholinergic syndrome caused by a transdermal hyoscine patch in a child with cerebral palsy. Emerg Med J 22: 678, 2005. [PubMed: 16113205]

6. Feinberg M: The problems of anticholinergic adverse eects in older patients. Drugs Aging 3: 335, 1993. [PubMed: 8369593]

7. Tune LE: Anticholinergic eects of medication in elderly patients. J Clin Psychiatr 62: 11, 2001. [PubMed: 11584981]

8. Barker DB, Solomon DA: The potential for mental status changes associated with systemic absorption of anticholinergic ophthalmic medications: concerns in the elderly. DICP 24: 847, 1990. [PubMed: 2260344]

9. Geller RJ, Lopez GP, Cutler S et al.: Atropine availability as an antidote for nerve agent casualties: validated rapid reformulation of high-concentration atropine from bulk powder. Ann Emerg Med 41: 453, 2003. [PubM ed: 12658242]

10. Lin TJ, Nelson LS, Tsai JL et al.: Common in plant poisonings in Taiwan. J Toxicol Clin Toxicol 47: 161, 2009. [PubMed: 18788001]

11. Francis PD, Clarke CF: Angel trumpet lily poisoning in five adolescents: clinical findings and management. J Paediatr Child Health 35: 93, 1999. [PubMed: 10234644]

12. Isbister GK, Oakley P, Dawson AH, Whyte IM: Presumed Angel’s trumpet (Brugmansia) poisoning: clinical eects and epidemiology. Emerg Med (Fremantle) 15: 376, 2003. [PubMed: 14631706]

12/16 8/7/2018

13. Tiongson J, Salen P: Mass ingestion of jimsonweed by eleven teenagers. Del Med J 70: 471, 1998. [PubMed: 9846457]

14. Wiebe TH, Sigurdson ES, Katz LY: Angel’s trumpet () poisoning and delirium in adolescents in Winnipeg, Manitoba: Summer 2006. Paediatr Child Health 13: 193, 2008. [PubMed: 19252697]

15. Chan TY: Anticholinergic poisoning due to Chinese herbal medicines. Vet Hum Toxicol 37: 156, 1995. [PubMed: 7631497]

16. Hsu CK, Leo P, Shastry D et al.: Anticholinergic poisoning associated with herbal tea. Arch Intern Med 155: 2245, 1995. [PubMed: 748724 7]

17. Di Grande A, Paradiso R, Amico S et al.: Anticholinergic toxicity associated with lupin ingestion: case report. Eur J Emerg Med 11: 119, 2004. [PubMed: 15028905]

18. Mateo Montoya A, Mavrakanas N, Schutz JS: Acute anticholinergic syndrome from mistaken for blueberries. Eur J Ophthalmol 19: 170, 2009. [PubMed: 19123171]

19. Vallersnes OM, Lund C, Duns AK et al.: Epidemic of poisoning caused by scopolamine disguised as Rohypnol tablets. Clin Toxicol (Phila) 47: 889, 2009. [PubMed: 19821638]

20. Weiner AL, Bayer MJ, McKay CA Jr et al.: Anticholinergic poisoning with adulterated intranasal cocaine. Am J Emerg Med 16: 517, 1998. [PubMed: 10802423]

21. Hamilton RJ, Perrone J, Homan R et al.: A descriptive study of an epidemic of poisoning caused by heroin adulterated with scopolamine. J Toxicol Clin Toxicol 38: 597, 2000. [PubMed: 11185966]

22. Ridder WP, Klimek M, Rupreht J: [Physostigmine for the immediate treatment of a patient with the central anticholinergic syndrome induced by cocaine cut with atropine.] Ned Tijdschr Geneeskd 149: 1701, 2005. [PubM ed: 16104118]

23. Oleson EB, Ferris MJ, España RA, Harp J, Jones SR: Eects of the histamine H1 and benztropine analog diphenylpyraline on dopamine uptake, locomotion and reward. Eur J Pharmacol 683:

13/16 8/7/2018 161, 2012. [PubMed: 2 2445882]

24. Holger JS, Harris CR, Engebretsen KM: Physostigmine, sodium bicarbonate, or hypertonic saline to treat diphenhydramine toxicity. Vet Hum Toxicol 44: 1, 2002. [PubMed: 11824763]

25. Sharma AN, Hexdall AH, Chang EK et al.: Diphenhydramine-induced wide complex dysrhythmia responds to treatment with sodium bicarbonate. Am J Emerg Med 21: 212, 2003. [PubMed: 12811715]

26. Thakur AC, Aslam AK, Aslam AF et al.: QT interval prolongation in diphenhydramine toxicity. Int J Cardiol 98: 341, 2005. [PubMed: 15686790]

27. Sype JW, Khan IA: Prolonged QT interval with markedly abnormal ventricular repolarization in diphenhydramine overdose. Int J Cardiol 99: 333, 2005. [PubMed: 15749198]

28. Palenzona S, Meier PJ, Kupferschmidt H, Rauber-Luethy C: The clinical picture of olanzapine poisoning with special reference to fluctuating mental status. J Toxicol Clin Toxicol 42: 27, 2004. [PubMed: 15083933]

29. Pragst F, Herre S, Bakdash A: Poisonings with diphenhydramine—a survey of 68 clinical and 55 death cases. Forensic Sci Int 161: 189, 2006. [PubMed: 16857332]

30. Radovanovic D, Meier PJ, Guirguis M et al.: Dose-dependent toxicity of diphenhydramine overdose. Hum Exp Toxicol 19: 489, 2000. [PubMed: 11204550]

31. Scharman EJ, Erdman AR, Wax PM et al.: Diphenhydramine and dimenhydrinate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 44: 205, 2006. [PubMed: 16749537]

32. Ramjan KA, Williams AJ, Isbister GK, Elliott EJ: Red as a beet and blind as a bat: anticholinergic delirium in adolescents: lessons for the paediatrician. J Paediatr Child Health 43: 779, 2007. [PubMed: 17924941]

33. Perrone J, Chu J, Stecker MM: Viral encephalitis masquerading as a fulminant anticholinergic toxidrome. J Toxicol Clin Toxicol 35: 627, 1997. [PubMed: 9365431] 14/16 8/7/2018

34. Isbister GK, Kumar VV: Indications for single-dose activated charcoal administration in acute overdose. Curr Opin Crit Care 17: 351, 2011. [PubMed: 21716104]

35. Green R, Sitar DS, Tenenbein M: Eect of anticholinergic drugs on the eicacy of activated charcoal. J Toxicol Clin Toxicol 42: 267, 2004. [PubMed: 15362593]

36. Adams BK, Mann MD, Aboo A et al.: Prolonged gastric emptying half-time and gastric hypomotility aer . Am J Emerg Med 22: 548, 2004. [PubMed: 15666259]

37. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 37: 731, 1999. [PubMed: 10584586]

38. Hojer J, Troutman WG, Hoppi K et al.: Position paper update: ipecac syrup for gastrointestinal decontamination. Clin Toxicol (Phila) 51: 134, 2013. [PubMed: 23406298]

39. Shannon M: Toxicology reviews: physostigmine. Pediatr Emerg Care 14: 224, 1998. [PubMed: 9655671]

40. Frascogna N: Physostigmine: is there a role for this antidote in pediatric poisonings? Curr Opin Pediatr 19: 201, 2007. [PubMed: 1749 6766]

41. Schneir AB, Oerman SR, Ly BT et al.: Complications of diagnostic physostigmine administration to emergency department patients. Ann Emerg Med 42: 14, 2003. [PubMed: 12827117]

42. Burns MJ, Linden CH, Graudins A et al.: A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med 35: 374, 2000. [PubMed: 10736125]

43. Beaver KM, Gavin TJ: Treatment of acute anticholinergic poisoning with physostigmine. Am J Emerg Med 16: 505, 1998. [PubMed: 9725 967]

15/16 8/7/2018

44. Teoh R, Page AV, Hardern R: Physostigmine as treatment for severe CNS anticholinergic toxicity. Emerg Med J 18: 412, 2001. [PubMed: 11559630]

45. Weizberg M, Su M, Mazzola JL et al.: Altered mental status from olanzapine overdose treated with physostigmine. Clin Toxicol (Phila) 44: 319, 2006. [PubMed: 16749552]

46. Salen P, Shih R, Sierzenski P, Reed J: Eect of physostigmine and gastric lavage in a Datura stramonium- induced anticholinergic poisoning epidemic. Am J Emerg Med 21: 316, 2003. [PubMed: 12898490]

47. Rosenbaum C, Bird SB: Timing and frequency of physostigmine redosing for antimuscarinic toxicity. J Med Toxicol 6: 386, 2010. [PubMed: 20405266]

McGraw Hill Copyright © McGraw-Hill Global Education Holdings, LLC. All rights reserved. Your IP address is 5 0.26.48.115 Terms of Use • Privacy Policy • Notice • Accessibility

Access Provided by: Brookdale University Medical Center Silverchair

16/16