INTRODUCTION — The clinical features, evaluation, and management of clonidine and related imidazoline intoxication will be reviewed here. The clinical approach to the poisoned patient is discussed separately. (See "General approach to drug poisoning in adults" and "Approach to the child with occult toxic exposure".)
EPIDEMIOLOGY — Clonidine, an alpha-2 adrenergic agonist, is a biochemical derivative of imidazoline that was initially introduced as a topical nasal decongestant over 40 years ago [1]. Subsequently, clonidine has been primarily utilized for its potent antihypertensive effect, but is used on- and off-label for a wide variety of indications. Guanfacine, and the antispasticity agent tizanidine, are also oral central alpha-2 adrenergic agonist medications that are being more commonly prescribed. Related imidazolines are found in topical eye and nose decongestants. In the United States, more than 10,000 calls regarding clonidine exposure are made annually to regional poison control centers, and serious clinical findings often requiring hospitalization are common [2,3]. As an example, among about 28,000 unintentional clonidine exposures in United States children reported to poison control centers over 11 years, approximately 20 percent had moderate or major clinical effects [4].
Clonidine poisoning may occur from exploratory ingestion by young children, transdermal exposure from a clonidine patch, malicious drug administration, suicidal ingestion, or therapeutic error. Exploratory guanfacine exposures are also frequent, occurring in approximately 1500 children in the United States annually [4].
Clonidine exposure is frequently symptomatic in children and, in practice, pediatric poisoning often leads to endotracheal intubation; fortunately, deaths due to pediatric exploratory ingestion of clonidine are rare [4-8].
PHARMACOLOGY AND CELLULAR TOXICOLOGY
Imidazoline agents — Imidazolines and their common uses include:
●Clonidine – Clonidine is indicated for the treatment of hypertension in adults, but is also used for adjunctive anesthetic sedation and analgesia, spinal anesthesia, opioid detoxification, alcohol withdrawal, smoking cessation, and amelioration of postmenopausal hot flashes [9-14]. In children, it is used in the treatment of attention deficit disorder with hyperactivity, refractory conduct disorder, and Tourette syndrome [15-17]. In a mail survey of pediatricians, clonidine was also the second-most commonly prescribed (off-label) medication for treating sleep disturbances in children [18].
●Guanabenz and guanfacine – Guanabenz and guanfacine are related central alpha-2 adrenergic agonist medications used for hypertension. In addition, guanfacine is used for the treatment of behavioral disturbance in children [19].
●Topical decongestants (eg, tetrahydrozoline, oxymetazoline, and brimonidine) – Imidazoline derivatives, such as tetrahydrozoline, naphazoline, oxymetazoline, and xylometazoline, are found in commercial topical eye and nose decongestants. Brimonidine and apraclonidine are prescribed for treatment of glaucoma. Ingestion or systemic absorption of small amounts of these agents can produce toxicity syndromes strikingly similar to that produced by clonidine [20-22].
●Tizanidine – Tizanidine is a muscle relaxant used for the treatment of spasticity. In overdose, it has caused lethargy, coma, bradycardia, and hypotension [21].
●Lofexidine – Lofexidine is used as an alternative to clonidine for opioid detoxification. (See "Medically supervised opioid withdrawal during treatment for addiction", section on 'Alpha-2 adrenergic agonists'.)
●Dexmedetomidine – Dexmedetomidine is an alpha-2 agonist frequently used for sedation. (See "Pharmacologic agents for pediatric procedural sedation outside of the operating room", section on 'Dexmedetomidine' and "Sedative-analgesic medications in critically ill adults: Selection, initiation, maintenance, and withdrawal", section on 'Available agents'.)
●Xylazine – Xylazine is an alpha-2 agonist used in veterinary medicine for sedation and analgesia. Although it has no approved indications in humans, xylazine has become a drug of abuse and is also found as an adulterant in heroin and illicit fentanyl [23-30]. In humans, xylazine overdose has caused major toxicity consisting of coma, apnea, bradycardia, and hypotension as well as severe, necrotic skin ulcerations after repeated parenteral use [23-25,30]. The US Food and Drug Administration has issued an alert to health care professionals and a [27].
Formulation — Clonidine is supplied as 0.1, 0.2, and 0.3 mg tablets and in transdermal patch delivery systems containing 2.5, 5, or 7.5 mg of drug. Clonidine can also be compounded for patients who cannot take pills [31].
Guanfacine is supplied as 1, 2, 3, or 4 mg extended-release tablets.
Tizanidine is supplied in capsules or tablets containing 2, 4, or 6 mg of drug.
Toxic dose — No globally applicable minimum toxic dose of clonidine has been established. A review of low-dose clonidine poisonings among children details eight children who developed some combination of central nervous system, cardiovascular, or respiratory depression after alleged exposure to just one or two tablets [32]. An autistic child who was taking compounded clonidine developed sedation, bradycardia, and hypotension because of an eightfold compounding error by the pharmacy [31].
By contrast, survival has been documented after 1000-fold overdoses in both children and adults [33,34].
Topical imidazoles, though structurally similar to clonidine, are more polar than clonidine and less likely to cross the blood-brain barrier. Still, they have been implicated in pediatric poisoning after ingestion of small amounts of drug or after therapeutic use [20,35].
Mechanism of action — The pharmacological mechanisms through which clonidine lowers blood pressure and causes sedation are complex and still await full characterization [36-39].
●Clonidine and related imidazolines stimulate central alpha-2 adrenergic receptors and imidazoline receptors which are located primarily in the rostral ventrolateral medulla. This effect leads to decreased sympathetic outflow from the central nervous system and reduced plasma norepinephrine levels [37,39]. Imidazoline-1 receptors are involved in the hypotensive effects of clonidine [39].
●Endothelium-derived nitric oxide (NO) also plays a role in the antihypertensive effects of clonidine [36].
●Further sedative effects may occur from the stimulation of alpha-2 adrenergic receptors in the locus coeruleus, by augmented release of gamma-aminobutyric acid (GABA), and by interaction with opioid and serotonergic receptor systems [36].
●Stimulation of peripheral alpha-2 adrenergic receptors located in peripheral vascular smooth muscle causes vasoconstriction. This action explains the utility of imidazoline compounds as topically applied vasoconstrictors and the early and transient hypertension that is occasionally seen following clonidine overdose [38].
KINETICS — The absorption, distribution, and elimination of clonidine vary depending upon the formulation of clonidine and route of exposure.
Clonidine tablets — The pharmacokinetics for oral ingestion of clonidine tablets are as follows [40-42]:
●Bioavailability is 75 to 100 percent.
●Peak plasma clonidine concentrations occur at approximately 2 hours, and absorption is complete by 2.5 hours in hypertensive, fasting adults [40].
●Maximal blood pressure reduction occurs between three and eight hours after a routine daily dose [41].
●Clonidine in the bloodstream is 20 to 40 percent protein bound and has an apparent volume of distribution of 3.2 to 5.6 L/kg.
●Elimination half-life in therapeutic use ranges from 6 to 24 hours with more than half excreted unchanged in the urine [42].
Clonidine patch — Clonidine patch formulations are available in doses of 2.5, 5, and 7.5 mg contained in a timed matrix delivery system [43].
●Clonidine is delivered at a constant rate over seven days.
●The elimination half-life while the patch is adherent varies from 26 to 55 hours.
●Up to 75 percent of the total dose may remain in a clonidine patch after seven days of use.
Tetrahydrozoline — A child with central nervous system (CNS) depression, bradycardia, hypotension and hypothermia after tetrahydrozoline ingestion was found to have a plasma concentration of 24 ng/mL measured three hours after ingestion; in that case series the drug had an apparent elimination half-life of 4.4 hours [44].
CLINICAL FEATURES AND DIAGNOSIS — The diagnosis of clonidine or related imidazoline poisoning relies on a careful history and physical examination. A rapid overview summarizes the important clinical features and initial management (table 1).
History — Data obtained should include the specific agent, amount ingested, time of ingestion, and any co-ingestions. Any possible witnesses and emergency medical services (EMS) personnel who may have recovered pill bottles at the scene should be contacted. The patient's pharmacy may provide valuable information regarding prescribed medications, the date of the most recent refill, and the total number of pills dispensed.
If the ingestant is unknown, a history of glaucoma or hypertension in an adult patient or household member suggests a possible clonidine exposure as does a patch medication prescribed for behavioral disturbance in a pediatric patient or sibling. (See "Approach to the child with occult toxic exposure".)
The circumstances that led to the poisoning should be considered, as suicidal or malicious overdoses may warrant involvement of social services. It is also important to review the medical history for conditions which may predispose patients to the toxic effects of clonidine, such as airway compromise or preexisting cardiac conduction abnormalities.
A detailed knowledge of the patient's coingestants and chronic medications is important, as clonidine exacerbates the hypotension of coingested antihypertensive medications (eg, beta blockers, calcium channel blockers) and the lethargy or coma following ingestion of ethanol, barbiturates, and other sedative hypnotics (eg, benzodiazepines, zolpidem, chloral hydrate). The clinical approach to the poisoned patient is discussed separately. (See "General approach to drug poisoning in adults" and "Approach to the child with occult toxic exposure".)
Physical examination — The classic toxic syndrome, or "toxidrome," associated with clonidine consists of central nervous system depression, bradycardia, and small pupil size [45-47]. Overdose of guanfacine tends to be less severe than with clonidine; common clinical effects consist of drowsiness, bradycardia, and hypotension [4,48]. However, prolonged orthostatic hypotension may occur with extended-release forms of guanfacine [49].
Up to 60 percent of clonidine exposures that are reported to regional poison control centers result in symptoms [5]. However, clinical presentations can vary [4,5,46,47]. The relative frequency of findings in children poisoned with clonidine are shown in the table (table 2).
Signs of toxicity are usually seen within one hour of clonidine tablet ingestion and new findings rarely appear more than four hours after exposure [46,47].
Clonidine patch exposure through ingestion or self-application to the skin may result in signs of toxicity beyond four hours [50,51]. A full body search for adherent transdermal patches is an important aspect of the physical examination.
Depressed mental status, ranging from lethargy to coma, is the most common finding after clonidine poisoning [4,5,46,47]. Miosis, hyporeflexia, and hypotonia often accompany the alteration in mental status and making the differentiation of clonidine poisoning from opioid toxicity difficult (table 3). Transient responsiveness to painful stimuli is more frequently seen in patients poisoned with clonidine than with opioids.
Respiratory depression and apnea may accompany clonidine poisoning, especially among children, and may require immediate airway support [4,5,46,47]. Children will often resume breathing upon tactile stimulation. Approximately 2 percent of children (age ≤12 years) poisoned by clonidine, guanfacine, or tizanidine, reported to United States poison control centers, were treated with endotracheal intubation; respiratory depression is a more common feature of clonidine poisoning than of guanfacine poisoning [4,48].
Bradycardia and hypotension are prominent signs of clonidine and related imidazoline toxicity among children [4]. In a cohort of 108 hospitalized adolescent and adult clonidine overdoses, 76 percent developed bradycardia, which persisted for a median duration of 20 hours; hypotension was noted in 24 percent [52]. Sinus bradycardia is the usual rhythm, although atrioventricular (AV) block and sinus arrest have been described [53,54]. Second-degree AV block or complete AV dissociation are uncommon and should prompt consideration of toxicity from other cardioactive agents, such as digoxin, beta blockers, or calcium channel blockers (waveform 1 and waveform 2).
Tizanidine is unusual for the class as it has myocardial potassium-channel blocking activity and may prolong the electrocardiographic QT interval [55].
Hypertension occurs transiently in many patients with clonidine overdose, particularly after a large ingestion [36,46]. In addition, hypertension has been reported in patients with clonidine poisoning who receive naloxone. Hypertension progressing to hypotension has also been reported after guanfacine overdose [56]. Hypertensive emergency requiring treatment is very rare [57].
Pallor, hypothermia, and dry mouth may also be seen following clonidine poisoning [46,58].
DIFFERENTIAL DIAGNOSIS — There are many causes of coma that deserve consideration when evaluating the patient with suspected clonidine poisoning (table 4). In the poisoned patient, it is especially important to consider hypoglycemia and potential traumatic brain injury. (See "Evaluation of stupor and coma in children" and "Stupor and coma in adults".)
As in all poisonings, careful consideration should be given to the potential for coingested toxic agents. Clonidine exacerbates the lethargy or coma following ingestion of opioids, ethanol, barbiturates, and other sedative hypnotics (eg, benzodiazepines, zolpidem, chloral hydrate). (See "Approach to the child with occult toxic exposure".)
Among toxic agents that may cause coma, other centrally acting, though chemically distinct, antihypertensive medications, including methyldopa, guanfacine, and guanabenz, also decrease sympathetic outflow and mimic clonidine's toxic effects. In patients with a history of heroin or fentanyl use, xylazine may be an adulterant and may contribute to the toxicity of these illicit drugs.
The combination of central nervous system depression and pupillary miosis closely resembles the toxic syndrome seen with opioid intoxication, which may be further confused by the variable response of clonidine poisoning to naloxone (table 3). Many other sedative-hypnotic and psychoactive agents may also produce somnolence and bradycardia. (See "Acute opioid intoxication in adults" and "Opioid intoxication in children and adolescents".)
LABORATORY EVALUATION — Quantitative and qualitative testing for clonidine is available from dedicated toxicology reference laboratories with methodology, such as gas chromatography or mass spectroscopy. However, the results usually cannot be obtained in time to be useful for patient management. Thus, specific measurement of clonidine in the urine or other fluids is typically performed for forensic or other nonclinical purposes.
Further laboratory evaluation of clonidine poisoning varies depending on the circumstances of exposure. A witnessed exploratory ingestion in a toddler or a known therapeutic error in a hospitalized patient may merit little laboratory investigation whereas an unwitnessed suicidal overdose may lead to more extensive testing, especially if clonidine is not the definite cause of symptoms. Other ancillary studies may be indicated in selected patients in whom trauma, infection, or other etiologies besides poisoning are suspected. (See "Evaluation of stupor and coma in children" and "Stupor and coma in adults" and "Approach to the child with occult toxic exposure" and "General approach to drug poisoning in adults".)
We suggest the following tests in adolescent and adult patients with altered mental function and suspected clonidine overdose:
●Bedside glucose determination, to exclude hypoglycemia as the cause of reduced consciousness.
●Arterial blood gas evaluation or venous blood gas measurement combined with pulse oximetry to assess adequacy of ventilation in patients with serious and persistent respiratory depression.
●Serum acetaminophen level in patients who ingest clonidine with suicidal intent.
●Serum ethanol level, to identify patients at a higher risk for coma and respiratory depression due to coingestion of clonidine and ethanol.
●Electrocardiogram (ECG), to evaluate for drug-induced cardiac electrical dysfunction.
●Chest radiography, if the history or exam suggests the possibility of pulmonary aspiration.
Other studies that may be helpful in selected patients include:
●Serum electrolyte determination, in the setting of likely coingestants, to assess for electrolyte disturbance or metabolic acidosis and to calculate the anion gap.
●Serum blood urea nitrogen and creatinine to identify patients with renal insufficiency who may have delayed elimination of clonidine after overdose.
●Rapid urine pregnancy test in postmenarchal women.
MANAGEMENT — Consultation with a clinical toxicologist is available to provide guidance in managing individual patients. To obtain emergency consultation with a medical toxicologist, in the United States, call 1-800-222-1222, or the nearest international regional poison center. Contact information for poison centers around the world is provided separately. (See 'Additional resources' below.)
The management for clonidine and related imidazoline intoxications is the same. (See 'Formulation' above and 'Imidazoline agents' above.) Almost all clonidine poisoned patients will have good outcomes with attentive supportive care alone. A rapid overview summarizes the important clinical features and initial management of clonidine poisoning (table 1).
No randomized controlled trials exist to guide specific care. The recommendations for gastrointestinal decontamination and potential antidotal therapy given below are based upon individual reports and case series.
Basic measures — Management begins with assessment and stabilization of the airway, breathing, and circulation.
●Respiratory depression often responds transiently to tactile stimulation of the patient. However, clinicians should proceed with endotracheal intubation and mechanical ventilation if there is any doubt about the patient's ability to breathe adequately on their own or if pulmonary aspiration poses a significant risk.
●Bradycardia is typically mild, but may respond to atropine [46,59]. Bradycardia is often persistent, and response to atropine short-lived, so the value of this therapy is undetermined [52]. Isolated hypotension may initially be treated with Trendelenburg positioning and rapid administration of intravenous isotonic crystalloid fluids (normal saline or Ringer's lactate solution).
Dopamine, or similar pressor agents, may be useful in the minority of patients whose bradycardia or hypotension that does not respond to stimulation, intravenous atropine administration and rapid intravenous infusion of isotonic fluids.
●Hypertension may be noted early after clonidine overdose. As hypertension is typically of short duration and is often followed by hypotension, use of antihypertensive therapy is only warranted when there are signs of hypertensive emergency, a rare event after clonidine poisoning. (See "Moderate to severe hypertensive retinopathy and hypertensive encephalopathy in adults".)
In the unlikely event that hypertension must be treated, a short-acting, easily titratable agent, such as nitroprusside is advised. Beta adrenergic antagonist agents should be avoided as they may lead to unopposed alpha adrenergic action with worsening of hypertension.
●Hypothermic patients merit external warming. (See "Accidental hypothermia in adults" and "Hypothermia in children: Management".)
External decontamination — Any adherent transdermal patches found on diligent search of the patient's skin during exposure should be removed.
Gastrointestinal decontamination — Clonidine and related imidazolines bind well to activated charcoal (AC), the primary means of decontamination after drug overdose. The recommendation of AC administration following clonidine overdose derives from indirect evidence of benefit in volunteers, animal studies, and evidence of benefit following ingestions of other medications [60,61]. Because of adverse effects, such as vomiting and dehydration, the combination of a cathartic (eg, sorbitol) and AC should be used sparingly, if at all, and only a single dose of a cathartic should be given to any patient. The greatest benefit occurs if AC is given within one hour. The efficacy of AC as a function of time from ingestion is discussed in detail separately. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Evidence of efficacy and adverse effects'.)
We do not recommend gastric emptying by gastric lavage or by syrup of ipecac induced emesis in patients who ingest clonidine or related imidazolines based on randomized controlled trials showing minimal benefit and possible risk to patients who undergo gastric emptying after poisoning. (See "Gastrointestinal decontamination of the poisoned patient".)
Tablet or liquid preparation — We suggest that patients who present within one hour of a known or suspected ingestion of a potentially toxic dose of clonidine tablets or related imidazoline tablets, or within 30 minutes of ingestion of an imidazoline liquid preparation, receive AC (1 g/kg, maximum dose 50 g) by mouth or nasogastric tube. Great care must be taken to ensure that the airway is not compromised prior to administration and that pulmonary aspiration risk be minimized. Patients with respiratory depression or coma should first have their airway secured, as needed based on clinical evaluation, prior to AC administration.
In patients who present for care more than two hours after ingestion of clonidine tablet, related imidazoline tablet, or imidazoline liquid preparation, we suggest that AC not be given because the likelihood of preventing medication absorption is low and is outweighed by the risk of pulmonary aspiration.
Clonidine patch — We suggest the nasogastric administration of whole bowel irrigation (WBI) (500 mL to 1 L of polyethylene glycol per hour) after oral administration of AC (1 g/kg, maximum dose 50 g) in patients who have ingested clonidine transdermal patches. In this setting, AC may also prevent delayed absorption of clonidine when administered more than one hour after ingestion. Safe administration of WBI requires attention to the following provisions [62]:
●The patient should have bowel sounds present and no evidence of gastrointestinal obstruction.
●Airway adequacy must be assessed and secured, if necessary, prior to the procedure.
●Nasogastric tube placement must be radiographically confirmed prior to initiation of whole bowel irrigation.
●The patient should be maintained in an upright position (minimum 45 degree elevation of the head) throughout the procedure.
Gastrointestinal decontamination is discussed in detail separately. (See "Gastrointestinal decontamination of the poisoned patient".)
Specific treatment measures and antidotal therapy — No true antidote for clonidine or related imidazoline intoxication exists. Naloxone and alpha adrenergic antagonists have been utilized to treat seriously poisoned patients with inconsistent results.
Naloxone — We suggest that clonidine-poisoned patients with marked central nervous system (CNS) depression and apnea receive a trial of intravenous naloxone (0.1 mg/kg, maximum single dose: 2 mg; may be repeated every one to two minutes up to 10 mg total dose). Clinicians particularly knowledgeable of naloxone pharmacology, and of clonidine poisoning physiology, might consider, higher maximum single doses, especially in children [7]. However, other authors disagree [63]. Regardless of dose used, patients not responding to naloxone treatment should receive timely provision of aggressive supportive care. Patients who improve after naloxone administration still warrant hospital admission and intensive monitoring for recurrence of symptoms.
Many patients who respond to the initial dose of naloxone do not require additional doses [46]. However, if altered mental status and respiratory depression recur, we suggest the administration of additional intermittent doses as needed rather than a continuous infusion.
Naloxone therapy for clonidine overdose has been rarely associated with the onset of acute hypertension [7,64].
Evidence regarding the benefit of naloxone for reversal of clonidine toxicity is limited. In case reports and case series, intravenous (IV) naloxone administration at a dose of 0.05 to 0.1 mg/kg (maximum single dose, 10 mg) has reversed signs of clonidine, guanfacine, tetrahydrozoline, and tizanidine poisoning in some pediatric patients [7,45-47,65-68]. In one of the largest studies (51 children), naloxone reversed depressed mental status in approximately 80 percent of patients; a single dose of 10 mg did not appear to increase the rate of response compared to 6 mg or less. [7]. By contrast, in a cohort of 108 adolescent and adult patients with clonidine poisoning, naloxone (dose range 0.1 to 14 mg) was not found to result in improvement of Glasgow Coma Scale (GCS) unless concomitant opioid poisoning was suspected [52]. Experience with naloxone administration for related imidazolines is limited [47].
Alpha adrenergic antagonists — The nonselective alpha adrenergic antagonist, tolazoline, and the specific alpha-2 adrenergic antagonist, yohimbine, have been proposed as potential antidotes to clonidine poisoning [69,70], but the risk associated with these agents exceeds any expected benefit [46,69,71,72]. Thus, the use of these agents for treatment of clonidine or xylazine poisoning is strongly discouraged. Selective alpha-1 adrenergic antagonists would be expected to promote hypotension and should also be avoided.
Indications for extracorporeal removal — Clonidine is not amenable to extracorporeal removal (eg, multiple dose AC, hemodialysis, hemoperfusion).
Disposition — Further management depends on presence of symptoms and reason for ingestion.
Symptomatic patients — All patients displaying clonidine or related imidazoline toxicity warrant hospital admission and intensive medical care regardless of their response to naloxone. These patients typically fully recover within 24 to 48 hours. Bradycardia and hypotension associated with extended-release guanfacine poisoning may be prolonged [73].
Asymptomatic patients — Disposition of asymptomatic patients depends on the clonidine formulation ingested:
●Oral imidazoline preparations - Patients who remain asymptomatic at six hours after exploratory or inadvertent ingestion of clonidine tablets, imidazoline tablets, or imidazoline liquids may be discharged home as long as close observation and ability to rapidly return for medical care, if needed, is assured. Extended-release guanfacine formulations may warrant longer observation periods.
●Clonidine patch preparations - Asymptomatic patients who ingest a clonidine transdermal patch should be admitted and closely monitored because signs of poisoning may be delayed for up to 24 hours in this setting [50].
Suicidal overdose — Patients who ingest clonidine or related imidazolines with intent of self-harm warrant mental health consultation, measurement of serum acetaminophen levels, and careful evaluation for other coingestants. (See 'Laboratory evaluation' above.)
Patients should be evaluated by the mental health provider before discharge from medical care. Psychiatric evaluation should be deferred in symptomatic patients until after they have recovered. (See "Approach to the child with occult toxic exposure" and "General approach to drug poisoning in adults".)
ADDITIONAL PEDIATRIC CONSIDERATIONS — Clonidine is frequently prescribed for behavior problems in children. Clonidine exposure often involves young children who ingest their own medication or that of another child in the household [46,74]. Ingestion of as little as one clonidine tablet or one swallow of imidazoline containing eye drops has been associated with life-threatening toxicity in children; but fortunately pediatric deaths are rare and typically associated with large-dose exposures [4].
In addition to routine anticipatory guidance regarding poisoning prevention, clinicians should counsel caretakers about measures to prevent clonidine or imidazoline poisonings as follows:
●Used transdermal clonidine patch preparations contain a significant amount of clonidine. These patches should be carefully discarded so that young children cannot find them in the trash. Caretakers should be alerted to the serious toxicity these patches pose if ingested or reapplied to the skin.
●Topical imidazoline preparations, which are tasteless and highly potent after ingestion, often do not have child-resistant closures and need to be maintained out of reach of children. (See "Prevention of poisoning in children", section on 'Anticipatory guidance'.)
ADDITIONAL RESOURCES
Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)
Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment".)
SUMMARY AND RECOMMENDATIONS
●A rapid overview summarizes the important clinical features and initial management of clonidine poisoning (table 1).
●Clonidine, an alpha-2 agonist, is a biochemical derivative of imidazoline that causes lethargy, coma, small pupils (miosis), bradycardia, hypotension, transient hypertension, and respiratory depression in overdose. (See 'Clinical features and diagnosis' above.)
●Ingestion of as little as one clonidine tablet or one swallow of imidazoline containing eye drops is a serious exposure in children. (See 'Additional pediatric considerations' above.)
●The diagnosis of clonidine poisoning relies on a careful history and physical examination. Most signs of toxicity are seen within one hour of ingestion of clonidine tablets and new findings rarely appear more than four hours after exposure. Clonidine patch exposure through ingestion or self-application to the skin may develop signs of toxicity beyond four hours. (See 'Clinical features and diagnosis' above.)
●Almost all clonidine poisoned patients will have good outcomes with attentive supportive care of airway, breathing, and circulation. (See 'Basic measures' above.)
●The patient should be fully exposed and any adherent transdermal patches should be removed. (See 'External decontamination' above.)
●We suggest that patients who ingest clonidine tablets or related imidazoline preparations and who present within the one hour of known or suspected clonidine ingestion receive activated charcoal (AC) (1 g/kg, maximum dose 50 g) by mouth or nasogastric tube (Grade 2C). Charcoal should be withheld in patients who are sedated and may not be able to protect their airway, unless endotracheal intubation is performed first. However, endotracheal intubation should not be performed solely for the purpose of giving charcoal. (See 'Gastrointestinal decontamination' above.)
●Because the likelihood of preventing medication absorption is low and is outweighed by the risk of pulmonary aspiration, we suggest that patients who seek care more than two hours after known or suspected clonidine tablet or related imidazoline preparation ingestion not receive AC. (See 'Gastrointestinal decontamination' above.)
●We suggest that patients who ingest clonidine transdermal patches and who present within the first hour receive a single oral dose of AC (Grade 2C). In this setting, AC may also prevent delayed absorption of clonidine when administered more than one hour after ingestion. We suggest that AC be followed by nasogastric whole bowel irrigation with polyethylene glycol (Grade 2C). Endotracheal intubation may be necessary in symptomatic patients to avoid aspiration. In addition, gastrointestinal integrity must be assured before initiation of whole bowel irrigation. (See 'Gastrointestinal decontamination' above.)
●We recommend not emptying the stomach by gastric lavage or syrup of ipecac induced emesis (Grade 1B). (See 'Gastrointestinal decontamination' above.)
●We suggest that patients poisoned with clonidine or related imidazolines with marked central nervous system (CNS) depression and apnea receive intravenous naloxone (Grade 2C). This treatment should not delay the timely provision of aggressive supportive care in patients who do not respond. (See 'Specific treatment measures and antidotal therapy' above.)
●We admit the following patients with clonidine or related imidazoline ingestion:
•All symptomatic patients
•All patients who ingest transdermal patches
●Patients who are suicidal warrant psychiatric evaluation prior to discharge and should also be carefully evaluated for coingestions, including the measurement of an acetaminophen level
●Patients who are asymptomatic for six hours after ingestion of clonidine or related imidazoline tablets or liquid, and who are not suicidal, may be discharged home as long as close observation and the ability to return rapidly if care is needed are assured. (See 'Disposition' above.)
