Toxidromes and a general approach to poisoning

Abstract

A toxicologic syndrome, or toxidrome, is a distinct pattern of effects of poisoning. Well-defined toxidromes are the opioid, anticholinergic, cholinergic and sympathomimetic, and an additional described toxidrome is GABAergic. These toxidromes are named for the receptor effects causing their specific clinical findings, and knowledge of toxidromes allows rapid pattern recognition of specific poisonings. In this review, toxidromes and the initial assessment and general approach to management of acute poisoning are discussed. This article details the receptor-level effects of the poisoning, key clinical signs and symptoms and the role antidotes play in treatment. Clinical resources such as Toxbase and others exist to provide detailed guidance on clinical management of poisoning.

Correspondence to Dr Robert J Hoffman; [email protected]

KEY POINTS

• Recognition of toxidromes is useful in evaluation and management of poisoning.

• History narrows the list of possible exposures.

• Vital signs and physical examination allow initial prognostication for many poisonings.

• Initial management should focus on stabilisation, decontamination and supportive care.

• Most poisonings require only basic laboratory investigations.

• A poison centre or a medical toxicologist can provide valuable management advice;www.ToxBase.org is a useful UK National Poison Information Service reference.

Background

The term toxidrome, a portmanteau of the words ‘toxicologic’ and ‘syndrome’, describes a distinct pattern of effects of poisoning. Well-defined toxidromes are the opioid, anticholinergic, cholinergic and sympathomimetic. An additionally described toxidrome is the GABAergic as noted in table 1. These are named for the receptor agonist or antagonist activity causing their specific pattern of clinical effects.

Table 1

Toxidromes

Toxidrome	Example agent	VS effects	Clinical findings	Antidote
Opioid	Fentanyl	T: – or ↓ BP: – or ↓ HR: – or ↓ RR: ↓	CNS: somnolence Pupils: miosis Skin: – Misc: pulmonary oedema	Naloxone
Sympathomimetic	Cocaine	T: ↑ BP: ↑ HR: ↑ RR: – to ↑	CNS: excitation Pupils: mydriasis Skin: diaphoretic, flushed Misc: tremor	None
Anticholinergic	Diphenhydramine	T: ↑ BP: ↑ HR: ↑ RR: – or ↑	CNS: delirium Pupils: mydriasis Skin: dry, flushed Misc: urinary retention, ↓ bowel sounds	Physostigmine
Cholinergic	Organophosphates	T: – BP: – HR: ↓ RR: ↑	CNS: delirium PNS: weakness Pupils: miosis Skin: diaphoretic Misc: DUMBELS	Atropine
				Pralidoxime
GABAergic	Diazepam	T: – BP: – HR: – RR: –	CNS: somnolence, coma Pupils: variable Skin: – Misc: –	Flumazenil

↑, increased; ↓, decreased; –, no change; BP, blood pressure; CNS, central nervous system; DUMBELS, diarrhoea, urination, miosis, bradycardia/bronchorrhoea/bronchospasm, emesis, lacrimation, salivation; HR, heart rate; Misc, miscellaneous; PNS, peripheral nervous system; RR, respiratory rate; T, temperature; VS, vital sign.

A review of toxidromes is typically included in the fundamental teaching of clinical toxicology.¹ Understanding toxidromes provides insight to toxicodynamics, which are the effects a toxin exerts on patients, typically at the receptor level. In this review, toxidromes and the initial assessment and general approach to management of acute poisoning are discussed. This article details the receptor-level effects of the poisoning, key clinical signs and symptoms and the role antidotes play in treatment. Most poisonings do not result in a toxidrome and most poisonings do not require any specific antidote. Understanding of toxidromes allows rapid pattern recognition of specific poisonings, elucidates appropriate use of antidotes and assists in the management of poisoned children.^{2 3} Resources such as Toxbase and others exist to provide clinicians detailed guidance on clinical management.⁴

Our aim in this review is to include information from an up-to-date evidence base with practice insights from specialists. Our literature review included search of the NCBI English-language databases using the term ‘toxidrome’, yielding 1358 results in six databases, and a PubMed search using the abstract/title words ‘poison, poisoning, toxin, toxic, intoxication, or toxicology’ from 2000 to 2024, limited to humans, clinical trials, meta-analyses, randomised clinical trial, review or systematic review, was yielding 48 666 results. These were evaluated for content deemed relevant to this topic.

Opioid toxidrome

The triad of miosis, central nervous system (CNS) depression and respiratory depression comprise the opioid toxidrome, with respiratory depression causing morbidity and mortality. Opioids have become a leading cause of poisoning death throughout the UK, European Union, Australasia, as well as the Americas. Opioids, such as morphine or fentanyl, bind opioid receptors causing specific, predictable effects. The mu opioid receptor mediates both central respiratory depression and euphoria. Other opioid receptor subtypes including kappa, delta and others exist, but details are these are beyond the scope of this review.

Naloxone reverses opioid-induced respiratory depression and CNS depression by antagonising opioid receptors. Naloxone may precipitate opioid withdrawal in patients with opioid tolerance, such as chronic opioid users. To avoid this, naloxone administration to opioid users should be dosed in small, titrated increments to reverse respiratory depression without inducing opioid withdrawal. As a result of the global opioid epidemic, naloxone distribution for bystander use has become a harm-reduction practice in the UK and many other countries.⁵

Sympathomimetic toxidrome

The sympathetic nervous system causes the ‘fight or flight’ physiological response to stressors.

Sympathomimetic or adrenergic agents include commonly misused substances such as amphetamines and cocaine; oral medications such as ephedrine and pseudoephedrine; and catecholamines such as epinephrine, norepinephrine and dopamine. The sympathomimetic toxidrome results from direct stimulation of adrenergic receptors and by way of increased release of excitatory CNS neurotransmitters. Adrenergic receptors involved are alpha (α-1 and α-2) and beta (β-1 and β-2). Their clinical effects include autonomic hyperactivity including tachycardia, hypertension, diaphoresis and pupillary dilation. Stimulatory neurotransmitters including norepinephrine, epinephrine and dopamine exert an excitatory CNS effect seen as psychomotor agitation, and sometimes psychosis. Treatment of the sympathomimetic toxidrome may include benzodiazepines for psychomotor agitation, and if needed antihypertensive medication to lower the heart rate and blood pressure.⁶

Anticholinergic toxidrome

The anticholinergic toxidrome mnemonic is ‘red as a beet, dry as a bone, blind as a bat, mad as a hatter, and full as a flask’. Causal medications include antihistamines such as diphenhydramine and chlorpheniramine, numerous psychiatric medications including antidepressants and antipsychotics, and Jimsonweed (Datura stramonium) exposures. This toxidrome results from antagonism of muscarinic parasympathetic receptors. The typical scope of clinical effects includes flushing, dry skin and mucous membranes; hyperthermia; blurred vision; altered mental status potentially including agitation, psychosis and distortion of perception of size and scale (Lilliputian hallucination); urinary retention with decreased bowel sounds; and tachycardia.⁷

Muscarinic receptor antagonism can be counterbalanced by increasing synaptic levels of acetylcholine. Physostigmine, an acetylcholinesterase inhibitor, is the antidote used to accomplish this. Physostigmine treatment can, however, overshoot the desired level of cholinergic tone needed, and cause cholinergic toxicity. Atropine, a potent and rapidly acting anticholinergic medication, should be available at the bedside when physostigmine is administered to correct any dangerous excess cholinergic effects.⁸ Physostigmine may cause cardiac dysrhythmia and death in patients with tricyclic antidepressant (TCA) toxicity. Therefore, physostigmine should only be administered after review of a 12-lead ECG is obtained and is confirmed to be absent of any TCA cardiac effects.⁹

Cholinergic toxidrome

Various mnemonics describe cholinergic toxicity, but DUMBELS (diarrhoea, urination, miosis, bradycardia/bronchorrhoea/bronchospasm, emesis, lacrimation, salivation) is the most used. These are toxic effects due to agonism of muscarinic receptors.

Toxicity may also include excess tone at nicotinic receptors, which is described by a less commonly used mnemonic MTWhF (Monday, Tuesday, Wednesday, Thursday, Friday), referring to mydriasis, tachycardia, weakness, hypertension and fasciculations/paralysis. The cholinergic toxidrome occurs secondary to excess acetylcholine at muscarinic and less commonly nicotinic receptors. This toxicity may result from medications such as pilocarpine or rivastigmine, nicotine, organophosphate or carbamate pesticides, or cholinergic mushrooms. It also may result from deadly military nerve agents such as sarin, soman or Novichok.¹⁰

The paralytic medication suxamethonium (succinylcholine) exemplifies the cholinergic effect on nicotinic receptors. A simplification of the differences between muscarinic and nicotinic toxicities is that muscarinic effects result in a ‘wet’ patient and nicotinic effects result in a ‘weak’ patient. Both muscarinic and nicotinic effects are typically present in severe or fatal poisoning. Severe morbidity or fatality from cholinergic poisons may result from the ‘killer B’s’—bradycardia, bronchospasm and bronchorrhea—or by paralysis and respiratory arrest.

Antidotes for cholinergic poisoning include an antimuscarinic component, typically atropine, and an acetylcholinesterase-sparing component, typically pralidoxime or obidoxime. Antidote kits containing both medications were originally created for military use after nerve gas exposure, but are available and commonly stocked for use in the general population. Atropine is administered in a titrated manner to achieve the appropriate antimuscarinic effect, most importantly resolution of bronchorrhoea. Pralidoxime temporarily binds acetylcholinesterase to prevent an organophosphate toxin from permanently binding this enzyme. Pralidoxime binding is reversible and acetylcholinesterase is still functional once pralidoxime dissociates from the enzyme.

GABAergic toxidrome

The GABAergic toxidrome is described as ‘coma with normal vital signs’ in which patients are somnolent or even deeply comatose but typically have a normal resting heart rate, blood pressure and respiratory rate. This results from toxicity due to benzodiazepines and related non-benzodiazepine somnifacient ‘Z’ medications—zolpidem, zopeclone, eszopiclone and zalepon. Excess gamma-aminobutyric acid (GABA) tone is the common underlying mechanism causing this toxidrome. Significant CNS depression or coma also results from substances such as ethanol or barbiturates, but these substances commonly cause associated bradycardia, hypotension and respiratory depression distinct from the GABAergic toxidrome. The antidote flumazenil competitively antagonises benzodiazepine binding at the benzodiazepine receptor and may be judiciously used to reverse benzodiazepine-induced sedation.¹¹ Flumazenil does not always reverse benzodiazepine-induced respiratory depression, and it may precipitate benzodiazepine withdrawal in tolerant patients, or seizure in any patient. Its use should be limited to patients who are not tolerant to benzodiazepines and generally avoided in patients with seizure disorders.

Initial approach to poisoning

History

Frequently, poisoned paediatric patients must be managed with inadequate available history due to inability or unwillingness of the patient to provide details. Key components of a toxicologic history are shown in table 2.

Table 2

Key history after poison exposure

History component	Clinical significance
Substance	Bottles, containers or pictures of medications or substances can aid in identifying the toxin.
Time of exposure	Timing can help predict the expected trajectory of clinical symptoms or provide context for interpreting serum drug concentrations.
Dose of exposure	Approximation of an amount ingested allows for risk stratification that may guide levels of care or methods of decontamination.
Location of exposure	Environmental factors may give useful clues as to the possible poison involved when undifferentiated.
Intent of self-harm	Intentional poisonings carry greater risk of morbidity and self-harming behaviours require psychiatric evaluation.

Primary assessment and management

After acute exposure or poisoning, the initial focus should be rapid assessment of airway, breathing and circulation with immediate stabilisation if needed, followed by assessment of neurological status.¹² After exposure to hazardous chemicals such as military nerve agents or organophosphate pesticides, skin decontamination should be performed prior to the patient entering a hospital.¹³ For all patients, consultation with a poison information service or clinical toxicologist can provide valuable advice, improving the likelihood that appropriate care will occur.¹⁴

• Airway: Airway compromise may result directly from toxic effects, such as oedema secondary to caustic exposure or secondary to angioedema. In such cases, rapidly securing the airway by endotracheal intubation is indicated. Loss of airway patency from CNS depression and relaxation of airway tone is often resolved by simply repositioning the patient’s head and neck.

• Breathing: Many medications and abusable substances cause CNS depression and inadequate breathing. For opioid-induced respiratory depression, naloxone should be administered. In any case of respiratory depression, pulse oximetry and, if available, end tidal capnography, should be used for continuous monitoring. Supplemental oxygen should be administered to maintain normal oxygen saturation.

• Circulation: Poisoning commonly results in cardiovascular effects, the most concerning and dangerous being bradycardia and hypotension. It is important to detect tachycardia and hypertension, but these less commonly necessitate immediate intervention. Continuous cardiac monitoring and repeated blood pressure measurements are indicated after exposures causing or capable of causing cardiovascular effects. Intravenous access should be established, and hypotension treated by 20 mL/kg of crystalloid fluid bolus. For hypotension persisting despite multiple intravenous fluid boluses, vasopressor support may be necessary. In unstable patients, if peripheral intravenous access cannot be rapidly established, intraosseous access is a reliable and recommended alternative for administration of fluid or medications until definitive vascular access can be obtained.¹⁵

• Disability/dextrose: Altered sensorium or seizure activity necessitates bedside assessment of blood glucose. Hypoglycaemia is treated with oral glucose or dextrose containing intravenous fluids.

• ECG: A 12-lead ECG should be obtained after intentional ingestions or exposure to poisons capable of causing cardiac dysrhythmia. ECG analysis should include evaluation of conduction intervals, in particular prolonged QRS interval, which results from sodium channel blocking toxins, and may be associated with dysrhythmia, seizures and fatality.¹⁶ Ischaemic changes are important to note but rare in paediatric poisoning.

Vital signs

Due to the dynamic effects of poisoning, serial examinations and frequent reassessment of vital signs are necessary. Continuous or repeated assessments of heart rate, blood pressure, respiratory rate and oxygen saturation should be conducted. Temperature measurement is important to detect hyperthermia associated with certain poisons, particularly stimulants or serotonergic poisoning.

Physical examination

Examination of poisoned patients includes a complete physical examination with detailed evaluation of pupils, skin, lung sounds, bowel and bladder findings. When history is limited, examination findings may be the only clues in diagnosing poisoning.

• Neurological: Neurological states may range from coma to agitated delirium or seizure. The presence of tremor, weakness, impaired coordination, clonus, dystonia or hyper-reflexia may help differentiate between toxidromes.

• Ocular: Pupil size and reactivity assist in toxidrome diagnosis. Nystagmus can result from ethanol, benzodiazepines, anticonvulsants, ketamine, dextromethorphan, phencyclidine or serotonin syndrome.

• Oropharynx: Lesions, burns or oedema can result from caustic ingestion.

• Cardiovascular: Bradycardia and hypotension result from cardiovascular medications and other substances decreasing adrenergic tone; tachycardia and hypertension can result from adrenergic or sympathomimetic agents.

• Pulmonary: Bronchorrhoea and bronchospasm may result from cholinergic substances, pulmonary irritant gases or toxin-induced cardiac failure.

• Gastrointestinal: Vomiting is the most common adverse effect after poisoning, and it is typically non-specific. Presence or absence of bowel sounds can help differentiate toxidromes.

• Dermatological: Both diaphoresis and dry skin are associated with toxidromes and colouration or rashes may be associated with specific poisonings such as heavy metal or anticonvulsant exposures.

• Psychiatric: Many toxins, particularly drugs of abuse, can cause psychosis or hallucinations, as may withdrawal from benzodiazepines.¹⁷

Diagnostic testing

Laboratory investigations are selected based on the history and examination findings and commonly may include¹⁸:

• Blood glucose measurement to detect hypoglycaemia.

• ECG to evaluate for cardiotoxicity, with serial ECGs after exposure to cardiotoxins such as beta blockers, calcium channel blockers, TCAs or antipsychotics.

• Serum electrolytes and renal function assessment.

• Quantitative serum drug levels for paracetamol (acetaminophen) and salicylates after ingestion with intent of self-harm or potentially toxic exposure to these medications.¹⁹

• Urine or serum pregnancy testing when appropriate.

In specific cases, the following may be useful:

• Haemoglobin co-oximetry to detect carboxyhaemoglobin from carbon monoxide exposure, or methemoglobinaemia.

• Quantitative serum drug or toxin concentrations.

• Serum osmolarity in suspected toxic alcohol exposure.

• Blood gas for pH and serum lactate.

• Drug of abuse testing for use in forensics or child protection.

Management

Decontamination

Decontamination, either external or gastrointestinal, may be required. External decontamination is used to cleanse the skin or eyes after a chemical or caustic exposure. Skin decontamination: After chemical exposure, patients should have affected areas copiously irrigated with water or normal saline. Ocular irrigation: After ocular exposure to caustic liquids or gases, removal of any contact lens and irrigation with water or normal saline using a dedicated eye rinse sink or eye irrigation lenses is needed. Assessment of visual acuity and pH testing of tears should be done quickly at bedside without delaying irrigation with repeat assessment after irrigation.

Gastrointestinal decontamination: Rarely, gastric lavage or nasogastric aspiration of liquid poisons is indicated. Gastric lavage: Nasogastric aspiration of ingested liquid formulations may be performed in patients with ingestions deemed to be a high risk of morbidity such as organophosphates. Orogastric lavage was previously a widely practised procedure but is recognised to be a high risk, with weak and limited evidence of benefit.²⁰ Activated charcoal (AC) can be considered after ingestion of a potentially toxic amount of a substance within the previous hour, or in cases of anticholinergic or opioid ingestions as late as 2–4 hours.²¹ Due to risk of aspiration, AC is contraindicated in patients with compromised airways or CNS depression.

Numerous antidotes exist, but a small number are frequently used including AC, naloxone, N-acetylcysteine and benzodiazepines.²² Table 3 shows a list of commonly used antidotes. Many antidotes and treatments, such as fomepizole, high-dose insulin therapy and most antidote infusions, are used infrequently and may be stocked in limited quantities, so early involvement of a pharmacist or contact with a poison centre is beneficial and recommended for such cases. Additionally, there are institutional variations in antidote administration dosing protocols, with N-acetylcysteine being an example: many institutions are preferentially transitioning to less complex protocols, such as the shortened N-acetylcysteine dosing schedule (SNAP).²³

Table 3

Antidotes

Xenobiotic	Antidote	Indication	Initial dose
Acetaminophen	N-acetylcysteine	Risk of hepatotoxicity	150* mg/kg intravenous infused over 60 min or 100* mg/kg intravenous infused over 120 min
Anticholinergics	Physostigmine	Altered mental status	0.02 mg/kg intravenous, maximum 0.5 mg initial dose (repeat every 5–10 min as needed) *Keep atropine available for use if excess cholinergic tone occurs from physostigmine.
Beta blockers/calcium channel blockers	High-dose insulin euglycaemic therapy	Hypotension, bradycardia	1 unit/kg intravenous bolus *Coadminister glucose 0.25 mg/kg up to 25 g intravenous if initial blood glucose is <11.1 mmol/L (200 mg/dL).
Carbon monoxide	Oxygen, hyperbaric oxygen	Toxicity with elevated carboxyhaemoglobin	100% FiO2
Cholinergics	Atropine	Bronchorrhoea, bradycardia	Atropine 0.02 mg/kg intravenous (0.02 mg/kg intravenous, maximum initial dose 1 mg) Repeat every 5 min as needed; if multiple doses are required, double the dose with each administration (eg, 1 mg intravenous, then 2 mg intravenous, then 4 mg intravenous, then 8 mg intravenous).
	Pralidoxime	Fasciculations, weakness	Pralidoxime (20–50 mg/kg up to 2 g intravenous; infused over 15 min) (600 mg intramuscular in adolescents or adults with no vascular access)
Cyanide	Hydroxocobalamin	Toxicity	70 mg/kg intravenous up to maximum dose of 5 g, infused over 15 min
	Sodium thiosulfate	Toxicity	500 mg/kg intravenous, maximum dose 12.5 g infused over 10 min. May be repeated once if symptoms recur. *Use sodium thiosulfate if hydroxocobalamin is unavailable; use both antidotes if they are both available.
Digoxin	Digoxin-specific antibody	Life-threatening dysrhythmia, 6-hour digoxin blood concentration >12.8 nmol/L (10 μg/L)	Acute toxicity: 10–20 vials intravenous Chronic toxicity: 1–2 vials (<20 kg), 3–6 vials (>20 kg), 1 vial (40 mg)
Iron	Deferoxamine	Systemic toxicity, serum iron concentration >89.5 μmol/L (500 μg/dL)	Infuse 5 mg/kg/hour intravenous to maximum initial dose of 5 g.
Isoniazid	Pyridoxine	Seizures, CNS depression, coma	70 mg/kg intravenous, maximum dose 5 g intravenous
Sulfonylureas	Octreotide	Rebound hypoglycaemia	1 μg/kg subcutaneous, maximum dose 50 μg
Super warfarin rodenticides	Vitamin K1	Coagulopathy, bleeding	0.4 mg/kg once per day Major bleeding: once per day and 0.3 mg/kg up to 10 mg intravenous
Toxic alcohols (ethylene glycol, methanol)	Fomepizole	Exposure	15 mg/kg intravenous
Opioids	Naloxone	Respiratory depression	Opioid-naïve patient (0.4 mg intravenous, repeat every 2–5 min as needed) Opioid-tolerant patient (0.04 mg intravenous, repeat every 2–5 min as needed) 1 spray intranasal in one nostril (4 mg/0.1mL, repeat every 2–3 min as needed)

*May vary by institution.

CNS, central nervous system.

Supportive care

• Supportive care includes monitoring for adverse effects, such as respiratory compromise, hypotension, hyperthermia, agitation, or end-organ dysfunction, and addressing such issues if they arise. This is recommended for most poison exposures. Vital signs should be maintained within safe, acceptable limits. Hypotension is the most common vital sign abnormality requiring treatment, typically by intravenous fluid bolus, or using a vasopressor such as norepinephrine if fluid-resistant hypotension is present. Nausea and vomiting are common and should be treated with antiemetics such as ondansetron.

• Extracorporeal toxin removal (ECTR) by haemodialysis or continuous renal replacement therapy (CRRT) may be indicated. This is most typical when poisoning is severe or anticipated to progress to severe or fatal toxicity, there is an absence of life-saving alternatives, effects are refractory to supportive measures or when there is renal insufficiency impairing xenobiotic elimination.^{24 25} In such circumstances, the ECTR must be capable of removing the poison from the blood compartment and significantly contribute to total body clearance of the toxin. Specific indications vary by xenobiotic, but can be considered in substances with small volume of distribution and minimal protein binding. The Extracorporeal Treatments in Poisoning work group has published recommendations for specific xenobiotics which can be referenced online at http://extrip-workgroup.org. Table 4 shows a list of toxins for which CRRT may be indicated.

Table 4

Toxins amenable to continuous renal replacement therapy (CRRT)

Toxins amenable to CRRT
Atenolol	Lithium
Bromide	Metformin
Caffeine	Methanol
Carbamazepine	Salicylates
Diethylene glycol	Theophylline
Ethylene glycol	Valproic acid

Disposition

A risk assessment, which factors in the poison, dose, patient characteristics, and clinical and laboratory findings, guides management and disposition. Patients with mild toxicity and a low predicted severity can be observed in the emergency department. Observation periods vary depending on the toxin, but 4–6 hours is adequate for many exposures. Longer observation periods and admission are needed if there is potential for delayed complications (eg, calcium channel blocker ingestion, sustained release formulations). Patients requiring prolonged monitoring or treatment can be admitted to a general paediatric ward or paediatric intensive care unit depending on staff capabilities and the severity of poisoning. All patients with intentional overdose require psychiatric assessment prior to discharge.

Ethics statements

Patient consent for publication

Not applicable.

Ethics approval

Not applicable.

Footnote

Contributors RJH contributed substantially to the conception, drafting, revision and approval of the final content of this manuscript. AN contributed substantially to the drafting, revision and approval of the final content of this manuscript. RJH and AN conceived the content of the article. RJH wrote the outline and AN wrote the first full draft. Both authors reviewed the final version of the manuscript and approved it for submission. RJH is the guarantor of the manuscript content.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Provenance and peer review Commissioned; externally peer reviewed.

References

¹ Hendrickson RG, Bania TC, Baum CR, et al. The 2021 Core Content of Medical Toxicology. J Med Toxicol 2021; 17: 425–36. doi:10.1007/s13181-021-00844-5

² Calello DP, Henretig FM. Pediatric toxicology: specialized approach to the poisoned child. Emerg Med Clin North Am 2014; 32: 29–52. doi:10.1016/j.emc.2013.09.008

³ Toce MS, Burns MM. The Poisoned Pediatric Patient. Pediatr Rev 2017; 38: 207–20. doi:10.1542/pir.2016-0130

⁴ Pyper K, Robertson C, Eddleston M, et al. Use of the online poisons information database TOXBASE and admissions rates for poisoned patients from emergency departments in England and Wales during 2008 to 2015. J Am Coll Emerg Physicians Open 2020; 1: 1078–89. doi:10.1002/emp2.12116

⁵ Strang J, McDonald R, Campbell G, et al. Take-Home Naloxone for the Emergency Interim Management of Opioid Overdose: The Public Health Application of an Emergency Medicine. Drugs (Abingdon Engl) 2019; 79: 1395–418. doi:10.1007/s40265-019-01154-5

⁶ Gosselin S, Hoffman RS. The Management of Agitated Toxidromes. Emerg Med Clin North Am 2022; 40: 223–35. doi:10.1016/j.emc.2022.01.009

⁷ McCoy CE, Honda R. Anticholinergic Toxicity in the Emergency Department. J Educ Teach Emerg Med 2023; 8: S25–47. doi:10.21980/J8D07Z

⁸ Watkins JW, Schwarz ES, Arroyo-Plasencia AM, et al. The Use of Physostigmine by Toxicologists in Anticholinergic Toxicity. J Med Toxicol 2015; 11: 179–84. doi:10.1007/s13181-014-0452-x

⁹ Arens AM, Kearney T. Adverse Effects of Physostigmine. J Med Toxicol 2019; 15: 184–91. doi:10.1007/s13181-019-00697-z

¹⁰ Weir AGA, Makin S, Breeze J. Nerve agents: emergency preparedness. BMJ Mil Health 2020; 166: 42–6. doi:10.1136/jramc-2019-001380

¹¹ Veiraiah A, Dyas J, Cooper G, et al. Flumazenil use in benzodiazepine overdose in the UK: a retrospective survey of NPIS data. Emerg Med J 2012; 29: 565–9. doi:10.1136/emj.2010.095075

¹² Parris MA, Calello DP. Found Down: Approach to the Patient with an Unknown Poisoning. Emerg Med Clin North Am 2022; 40: 193–222. doi:10.1016/j.emc.2022.01.011

¹³ Haslam JD, Russell P, Hill S, et al. Chemical, biological, radiological, and nuclear mass casualty medicine: a review of lessons from the Salisbury and Amesbury Novichok nerve agent incidents. Br J Anaesth 2022; 128: e200–5. doi:10.1016/j.bja.2021.10.008

¹⁴ Farkas A, Kostic M, Huang C-C, et al. Poison center consultation reduces hospital length of stay. Clin Toxicol (Phila) 2022; 60: 863–8. doi:10.1080/15563650.2022.2039686

¹⁵ Elliott A, Dubé P-A, Cossette-Côté A, et al. Intraosseous administration of antidotes - a systematic review. Clin Toxicol (Phila) 2017; 55: 1025–54. doi:10.1080/15563650.2017.1337122

¹⁶ Yates C, Manini AF. Utility of the electrocardiogram in drug overdose and poisoning: theoretical considerations and clinical implications. Curr Cardiol Rev 2012; 8: 137–51. doi:10.2174/157340312801784961

¹⁷ Beckmann D, Lowman KL, Nargiso J, et al. Substance-induced Psychosis in Youth. Child Adolesc Psychiatr Clin N Am 2020; 29: 131–43. doi:10.1016/j.chc.2019.08.006

¹⁸ Bechtel L, Holstege CP. Utilizing the Toxicology Laboratory in the Poisoned Patient. Emerg Med Clin North Am 2022; 40: 431–41. doi:10.1016/j.emc.2022.01.003

¹⁹ Hoffman RJ, Nelson L. Rational use of toxicology testing in children. Curr Opin Pediatr 2001; 13: 183–8. doi:10.1097/00008480-200104000-00017

²⁰ Benson BE, Hoppu K, Troutman WG, et al. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila) 2013; 51: 140–6. doi:10.3109/15563650.2013.770154

²¹ Chyka PA, Seger D, Krenzelok EP, et al. Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43: 61–87. doi:10.1081/clt-200051867

²² Marraffa JM, Cohen V, Howland MA. Antidotes for toxicological emergencies: a practical review. Am J Health Syst Pharm 2012; 69: 199–212. doi:10.2146/ajhp110014

²³ Humphries C, Roberts G, Taheem A, et al. SNAPTIMED study: does the Scottish and Newcastle Antiemetic Protocol achieve timely intervention and management from the emergency department to discharge for paracetamol poisoning? Emerg Med J 2023; 40: 221–3. doi:10.1136/emermed-2021-212180

²⁴ Ghannoum M, Nolin TD, Lavergne V, et al. Blood purification in toxicology: nephrology’s ugly duckling. Adv Chronic Kidney Dis 2011; 18: 160–6. doi:10.1053/j.ackd.2011.01.008

²⁵ Ghannoum M, Lavergne V, Gosselin S, et al. Practice Trends in the Use of Extracorporeal Treatments for Poisoning in Four Countries. Semin Dial 2016; 29: 71–80. doi:10.1111/sdi.12448