eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Toxicology

Toxicity, Cough and Cold Preparation

Laleh Gharahbaghian, MD, Co-Director, Emergency Ultrasound Fellowship, Associate Director, Emergency Ultrasound, Clinical Instructor, Emergency Medicine, Stanford University Medical Center
Nicholas Lopez, MD, Resident Physician, Department of Emergency Medicine, Stanford University Medical Center, Kaiser Permanente Santa Clara Medical Center; Jennifer Oman, MD, Associate Clinical Professor, Department of Emergency Medicine, University of California at Irvine

Updated: Sep 24, 2009

Introduction

Background

Cough and cold suppressant medicines are widely used and favored by medical professionals and parents alike. However, minimal data support their effectiveness.  In 2006, the American College of Chest Physicians found that "literature regarding over-the-counter cough medications does not support the efficacy of such products in the pediatric age group."¹ In 2007, the US Food and Drug Administration (FDA) advisory committee recommended that the use of these medications be prohibited in children younger than 6 years.^2,3

Despite this, approximately 4 million children younger than 12 years are treated with nonprescription cough and cold products each week in the United States. Because these medications are available over-the-counter (OTC) and are found in most households, they are frequently implicated in pediatric toxic ingestions. Although most are unintentional, the number of intentional ingestions is growing, particularly for recreational use. The most common reported calls that involve OTC medications to poison control centers are for the ingestion of acetaminophen and cough and cold preparations.

The 3 main components of most cough and cold medicines are antihistamines, decongestants, and antitussives. First-generation antihistamines can be divided into 5 different categories. The most commonly used antihistamines in OTC preparations come from the alkylamine (eg, chlorpheniramine, brompheniramine) and ethanolamine (eg, diphenhydramine, clemastine) groups. Toxicity caused by these agents is not usually due to antihistamine properties but to anticholinergic properties. The 3 most commonly used oral decongestants are pseudoephedrine, phenylephrine, and phenylpropanolamine (withdrawn from US market). These agents stimulate alpha-adrenergic receptors and cause a sympathomimetic response at toxic doses. The most common antitussive in OTC preparations is dextromethorphan.

Most poisonings are asymptomatic or mildly symptomatic and do not require specific therapy. However, the clinician may encounter severe intoxications that require prompt recognition and appropriate disposition. Involvement of the regional poison control center, as well as a medical toxicology consultant, if available, may aid in the treatment and follow-up care of these patients, and they should be contacted for all significant ingestions.

Pathophysiology

Antihistamines

Antihistamines compete with histamine at H1 receptor sites on effector cells. Histamine is not a major mediator of the common cold, and the benefits of antihistamine in relieving congestion appear to be secondary to its anticholinergic properties. Toxicity is caused by anticholinergic properties. Atropine, the prototype of anticholinergics, and other substances with anticholinergic properties competitively inhibit the muscarinic effect of acetylcholine by blocking its action in the autonomic ganglia and at the neuromuscular junctions of the voluntary muscle system. They affect the peripheral and central autonomic nervous systems. Clinical toxicity is demonstrated by central nervous system depression or agitation, hyperactivity or psychosis, blurred vision, or abdominal discomfort.

Antihistamines are generally well absorbed after ingestion. Therapeutic effects begin within 15-30 minutes and are fully developed within 1 hour. They have varied peak plasma concentrations with a range of 1-5 hours. Diphenhydramine is toxic in acute doses of more than 5 mg/kg and potentially lethal in doses more than 10 mg/kg. In children, seizures have been observed with 150 mg of diphenhydramine, and fatalities have occurred with doses of less than 500 mg.

Decongestants

Pseudoephedrine, phenylephrine, and phenylpropanolamine cause direct presynaptic catecholamine release and may also block catecholamine reuptake and influence enzymes slowing catecholamine breakdown. Blood pressure elevation often is accompanied by a reflex bradycardia caused by the baroreceptors and results in postural hypotension. Clinical manifestations result from a direct effect on adrenergic receptors in muscles and glands and stimulation of the respiratory center and CNS. This causes bronchodilation, hyperexcitability, hallucinations, seizures, psychosis, intracranial bleeding or restlessness.

One case report described a cardiomyopathy and left ventricular dysfunction as a result of persistent tachycardia from pseudoephedrine use with resolution upon its termination. Decongestants are absorbed readily from the GI tract (except for phenylephrine because of irregular absorption and first pass metabolism by the liver) and attain a high concentration in the CNS. Peak plasma concentrations are achieved within 1-2 hours after oral administration. Toxic levels of pseudoephedrine have not been identified.

Phenylpropanolamine has often been implicated in pediatric ingestion, with toxicity starting at 6-10 mg/kg. In November 2000, in an article in the New England Journal of Medicine, phenylpropanolamine was noted to increase the risk of stroke. Other effects of phenylpropanolamine are seizure, cerebral vasculitis and kidney failure.⁴ Although this study did not include children, phenylpropanolamine was removed from the OTC market in the United States. However, preparations containing this substance may still be in homes and in medications from foreign countries. All household medications should be checked for phenylpropanolamine, which should be discarded.

Antitussives

Dextromethorphan is the methylated dextro-isomer of levorphanol, a codeine analog.

Dextromethorphan.

In addition, dextromethorphan and its primary active metabolite, dextrorphan, which shows similar effects to other N-methyl-D-aspartate (NMDA) antagonists such as phencyclidine (PCP), demonstrate anticonvulsant activity in animals by antagonizing the action of glutamate and are classified as a dissociative medication. The usefulness of quantitative determination for dextromethorphan is unclear because no correlation exists between blood levels and clinical effects. However, qualitative determination in blood or urine can demonstrate the presence or absence of dextromethorphan. The pharmacokinetics of dextromethorphan are such that a peak serum concentration of 0.1-0.2 mg/mL was reached after a single 20-mg oral dose in healthy volunteers. Five percent of persons of European ethnicity lack the ability to metabolize the drug normally, leading to toxic levels with smaller doses.

Note that adolescents have become increasingly interested in dextromethorphan for intentional intoxications. According to the Substance Abuse and Mental Health Services Administration (SAMHSA), the rate of emergency department visits resulting from nonmedical use of dextromethorphan for those aged 12-20 years was 7.1 visits per 100,000 population, compared with 2.6 visits or fewer per 100,000 for other age groups. Effects of megadosing (5-10 times the recommended dose) are similar to that of PCP by causing ataxia, abnormal muscle movements, respiratory depression, and dissociative hallucinations at high doses. Dextromethorphan can cause false positive test-results for PCP in urine toxicologic screening tests.

The half-life of dextromethorphan is short (typical intoxication lasting 6-8 h); the mainstay of treatment is supportive care. Narcan has been used with intermittent success to reverse ataxia and respiratory depression.

Chlorpheniramine is an OTC antihistamine that is usually used in adults. However, the abuse potential of this medication by adolescents has been recently reported. Its effects in deliberate megadosing for intoxication are similar to that of dextromethorphan.

Codeine is also thought to have antitussive effects and may be prescribed in combination with promethazine (Phenergan) for cough in the pediatric population. This medication is not recommended for use in the pediatric population. Codeine is an opioid analgesic and is the most commonly ingested opioid, in toxic doses, by children younger than 6 years, as reported by the American Association of Poison Control Centers (AAPCC). Doses greater than 5 mg/kg are reported to produce respiratory and CNS depression.

Frequency

United States

The AAPCC reports that cough and cold preparations account for 111,222 total exposures, 4.5% of total human exposures (65,044 annual exposures for children younger than 6 years and 15,539 annual exposure in children aged 6-17 years) based on cumulative data reported in 2008.⁵   Although cough and cold preparations represent a large majority of exposures in the pediatric population, they are not responsible for a significant proportion of pediatric morbidity and mortality.

Mortality/Morbidity

Morbidity and mortality differ based on the 2 categories of pediatric toxic ingestion: unintentional (children <6 y) and intentional (adolescents aged 13-19 y). Of 19 pharmaceutical-associated fatalities in the category of children younger than 6 years, 4 involved cough and cold preparations. Of 46 pharmaceutical-associated fatalities in adolescents aged 13-19 years, 2 involved cough and cold preparations.

Sex

According to the AAPCC, females represent 41% of reported pediatric toxic exposures in children aged 6-12 years and 53% of the reported exposures in teenagers.

Age

Unintentional exposures tend to occur in children younger than 6 years because they are eager to explore their environment and place objects into their mouths. Unfortunately, as many as 30% of children who experience one ingestion experience a repeat ingestion.

The peak age for childhood poisoning ranges from 1-3 years. Based on cumulative data from 1991-95, the AAPCC reported that 43% of toxic ingestions are in children younger than 6 years, the vast majority of which are unintentional. In the 2008 report, only 47% of reported adolescent ingestions were unintentional; others cases were motivated by suicidal intention or recreational abuse.⁵ Both suicidal and recreational ingestion occur with increased frequency in the teenage population and may involve multiple substances at higher doses. Studies have shown that when adolescents are surveyed their knowledge of the lethal potential of OTC medications is poor. In fact, 50% believed some, like acetaminophen, were benign.

Clinical

History

• Unintentional ingestion of cough and cold preparation
  • Unintentional exposures tend to occur in children younger than 6 years because they are eager to explore their environment and place objects into their mouths.
  • Unintentional ingestion typically represents a smaller dose of the toxic substance, and the child presents to the emergency department soon after ingestion.
  • Unfortunately, as many as 30% of children who experience one ingestion experience a repeat ingestion. In this age group, the possibility of child abuse or neglect should be explored.
• Intentional ingestion
  • Only 47% of reported adolescent ingestions are accidental, others are motivated by suicidal intention or recreational abuse. Both suicidal and recreational ingestion occur with increased frequency in the teenage population, and it may involve multiple substances at higher doses.
  • Dextromethorphan has been used as a recreational drug by adolescents. A 2006 study showed a 10-fold increase in California Poison Control System dextromethorphan abuse cases from 1999 (0.23 cases per 1000 calls) to 2004 (2.15 cases per 1000 calls).⁶ Coricidin HBP Cough & Cold Tablets were the most commonly reported dextromethorphan-containing products abused, followed by dextromethorphan-containing Robitussin formulations.
  • Eliciting the specific OTC medication ingested is important because dextromethorphan is often present in combination with pseudoephedrine, antihistamines/anticholinergics, and acetaminophen.

Physical

• General findings
  • Physical findings widely vary, depending on the agent or combination of agents ingested.
  • If a single antihistamine agent has been ingested, a predominance of anticholinergic effects are demonstrated. The anticholinergic toxidrome consists of agitation; fever; urinary retention; dry, hot, flushed skin; and dilated pupils.
  • Although most cough and cold preparations are a combination of medications, a single toxidrome may not be present. The history is helpful to guide the expected physical examination findings; however, the history is often inaccurate.
• The following physical examination findings are examples of what is possible, in addition to the common findings; however, the presentation of a patient with a toxic ingestion is not always straightforward. In general, the combined effects of the various classes of drugs in OTC preparations have been broken down into the following systems based on the approach in POISINDEX.
  • Vital signs
    • Findings include hyperthermia, tachypnea, tachycardia, and hypertension.
    • Hyperthermia has been reported with ingestion of both diphenhydramine and OTC antihistamine/decongestant combinations. Case reports secondary to combination products are ascribed to the sympathomimetic component.
  • Head, ears, eyes, nose, and throat (HEENT)
    • Anticholinergic effects include mydriasis, nasal dryness and stuffiness, eye dryness, and mouth and throat dryness secondary to antihistamines.
    • Dilated and minimally reactive pupils have been seen with antihistamine toxicity related to anticholinergic effects.
    • Mydriasis and nystagmus may be observed with dextromethorphan ingestion.
• Cardiovascular
  • Abnormalities include arrhythmia (eg, atrioventricular [AV] block) and cardiac arrest.
  • ECG changes occur secondary to the antihistamine and the sympathomimetic components. Antihistamines commonly cause tachycardia.
• Respiratory: Findings include respiratory depression and adult respiratory distress syndrome.
• Neurologic: Abnormal findings include dizziness, ataxia, hyperexcitability, somnolence, seizures, dystonia, dyskinesia, toxic psychosis (anxiety, agitation, hallucination), intracranial hemorrhage, and coma.
• GI: Gastroenteritis (diarrhea, nausea, vomiting) can occur with the ethanolamine class of antihistamines.
• Genitourinary
  • Urinary retention is a common anticholinergic adverse effect of the antihistamines.
  • Rhabdomyolysis (ie, decreased urinary output and increased creatinine phosphokinase) has been associated with doxylamine overdose and may require treatment with intravenous (IV) hydration, furosemide, and urine alkalization.
• Hematologic
  • Most hematologic effects are secondary to long-term use.
  • Findings include hemolytic anemia, thrombocytopenia, and agranulocytosis
• Psychiatric: Children may experience visual hallucinations following therapeutic doses of triprolidine (antihistamine/pseudoephedrine) combinations.
• Dermatologic: Urticaria and hot, dry skin may be noted.
• Effects during breastfeeding: Potential changes in behavior of the infant include irritability, disturbed sleep patterns, and excessive crying.
• Other: Drug interactions between monoamine oxidase inhibitors (MAOIs) or serotonin reuptake inhibitors with dextromethorphan may result in a serotonin syndrome. Serotonin syndrome consists of mental status changes, such as agitation, myoclonus, hyperreflexia, diaphoresis, shivering, tremor, diarrhea, headache, fever, or incoordination.

Causes

• Drug abuse has been reported with dextromethorphan. Easy accessibility and a false sense of safety have contributed to its increase in recreational use.
• Deliberate ingestion can lead to intoxication with symptoms of euphoria, bizarre behavior, hyperactivity, auditory hallucinations, visual hallucinations, and association of sounds with colors.
• Slang names for dextromethorphan include CCC, triple C, DXM, dex, poor man's PCP, skittles, and robo.

Differential Diagnoses

Other Problems to Be Considered

• Altered mental status - Trauma, tumor, intussusception, shock, alcohol or drug abuse, epilepsy, encephalopathy, inborn errors, opiates, uremia
• Neurologic conditions - Subdural or arachnoid hemorrhage
• Psychosis - Psychiatric (schizophrenia, mania), drug-induced (amphetamines, hallucinogens), withdrawal states (alcohol, barbiturates), cerebrovascular, endocrine (hyperthyroid, steroid), hypoxia (carbon monoxide, anemia), metabolic (encephalopathy, uremia), neoplastic (glioblastoma), pyogenic infections (CNS abscess, sepsis), seizure disorder (postictal psychosis, temporal lobe seizures), trauma, viral infections (encephalitis)
• Seizures - Febrile, new-onset, drug-induced

Workup

Laboratory Studies

The following studies are indicated in suspected cough and cold preparation toxicity:

• Emergency drug screens
  • Emergency drug screens rarely aid clinical decisions because turn-around time often is very long; furthermore, screens are not sensitive or specific for many drugs, leading to either a missed diagnosis or a false diagnosis of systemic drug presence.
  • In addition, a positive screen result is difficult to use as the explanation for a patient's presentation because cause and effect can be ascertained only from patient history.
  • In the setting of an intentional overdose, the patient's history may be unreliable and unverifiable.
  • In general, drug screens are ordered when poisoning is suspected as the cause of an altered level of consciousness, unexplained seizures, or new onset of unusual behavior.
  • Drugs can be screened in blood or urine. Serum concentrations of over-the-counter (OTC) cough and cold preparations are not helpful.
  • Which drug screens to order should be decided in coordination with a regional toxicology center because most of these tests are costly and add little to a complete history with a known ingestion.
• Blood and urine analysis
  • An electrolyte panel and a CBC count are recommended for all cases of possible toxicity.
  • A plasma creatinine kinase level test may be helpful if rhabdomyolysis is suspected secondary to a antihistamine/decongestant combination that contains phenylpropanolamine, pseudoephedrine, or phenylephrine. The test result for myoglobin should be positive if rhabdomyolysis is present.
  • Several antihistamine/decongestant combinations are also combined with salicylates or acetaminophen. Blood levels should be measured for potential concurrent acetaminophen or salicylate ingestion.

Imaging Studies

• Imaging studies are not useful in identifying ingestion of cold and cough preparations.
• Chest radiography is useful if the patient has severe respiratory or CNS depression. This rules out pulmonary edema and adult respiratory distress syndrome.

Other Tests

• Electrocardiogram
  • An ECG is indicated especially if tachycardia or bradycardia is present.
  • Antihistamines may cause a prolonged QTc or QRS complex and ST-T segment abnormalities. Several cases of prolonged QTc and QRS intervals, with nonspecific ST and T wave changes, have been reported secondary to antihistamine ingestions.

Procedures

• A lumbar puncture is helpful in excluding other causes (eg, infectious, autoimmune) of altered mental status or new-onset seizures in the setting of an unknown toxic exposure.

Treatment

Medical Care

• General guidelines for treatment of cough and cold preparation poisoning
  • Ensure the patient has adequate airway, breathing, and circulation. Place the child on a cardiorespiratory monitor and/or obtain intravenous (IV) access if the child appears ill or is symptomatic. Administer oxygen, naloxone, and glucose to the patient if an unexplained decreased level of consciousness is observed.
  • Obtain the patient's history through a relative or Emergency Medical Technician (EMT). Examine the patient, looking for an anticholinergic toxidrome.
  • Obtain appropriate lab tests and an ECG.
  • Consider decontamination with activated charcoal.
  • Provide other supportive measures. Consider admission to a hospital if ingestion is significant or if the patient continues to be symptomatic.
  • Contact the regional poison control center.
• GI decontamination
  • Activated charcoal is the first-line defense in GI decontamination and should be given to the patient if a significant ingestion has occurred within recent hours before presentation.
  • Optimal dose of charcoal is not well established. The usual dose is 25-100 g in adults and adolescents, 25-50 g in children aged 1-12 years, and 1 g/kg in infants younger than 1 year. It is most effective if administered within 1 hour of ingestion.
  • Complications include emesis and aspiration.
• Other methods of decontamination
  • Controversial methods of decontamination include gastric lavage and ipecac syrup. Use of these agents should be on the advice of a poison center or toxicologist.
  • Ipecac and gastric lavage have fallen into disfavor, and cathartic therapy is not recommended, especially in children. Emesis is not usually recommended and is specifically contraindicated if a depressed gag reflex, CNS depression, ingestion of a corrosive substance, or situation with high aspiration potential is noted.
• Treatment of dystonic reactions
  • Dystonic reactions are treated with diphenhydramine in doses of 1 mg/kg IV every 2 minutes, with a maximum of 5 mg/kg/d, unless the dystonic reaction is thought to be caused by or involve antihistamine intoxication.
  • Acute dystonic reactions to antihistamines may be treated with oral (PO) or IV diazepam in children. The dose is 0.1-0.3 mg/kg (slowly if IV) and as much as 10 mg in adults.
• Treatment of seizures
  • Seizures can be treated with lorazepam. The pediatric dose is 0.05-0.1 mg/kg every 5 minutes as needed.
  • Monitor for hypotension, respiratory depression, and the need for endotracheal intubation.
• Treatment of serotonin syndrome
  • Serotonin syndrome must be managed by addressing each symptom individually.
  • Hyperthermia should be managed by undressing the patient and enhancing evaporative heat loss by keeping the skin damp and using cooling fans.
  • Muscle activity and agitation may be diminished with the use of diazepam.
  • Cyproheptadine is a nonspecific 5-hydroxytryptamine (5HT, serotonin) antagonist that has been shown to block development of serotonin syndrome in animals and is suggested as an antidote for serotonin syndrome in humans. It is available only as an oral preparation.
  • Propranolol also has been used to some benefit as a 5HT1A receptor antagonist.
• Treatment of other conditions
  • Cardiac arrhythmia can be managed with the appropriate cardiac medicine per pediatric advanced life support (PALS) guidelines.⁷ In diphenhydramine overdoses, bicarbonate may be helpful in treating QRS complex abnormalities and cardiac dysrhythmias. Treatment with bicarbonate in this overdose should be used in concert with poison center or medical toxicology consultation.
  • Rhabdomyolysis needs to be managed by ensuring adequate hydration and renal function, followed by a solution of sodium bicarbonate and potassium chloride to produce adequate urine flow and a urine pH of at least 7.5. Monitor sodium pH to avoid inducing severe alkalemia. Furosemide or mannitol may be needed to maintain diuresis. Chart strict intake and outputs.
  • Muscle rigidity and hyperactivity are secondary to sympathomimetic toxicity and can be controlled with neuromuscular paralysis.
  • Hyperthermia associated with sympathomimetics can be controlled with external evaporative cooling, removing the patient's clothes, and spraying with tepid water and fanning.
• Use of physostigmine
  • Use of physostigmine in antihistamine poisoning is extremely controversial, and it should not be given unless directed by a regional poison control center or in direct consultation with a medical toxicologist. Physostigmine, an anticholinesterase, may be indicated in the suspected anticholinergic poisoning for its therapeutic value.
  • It is a tertiary amine that crosses the blood brain barrier and reverses both the central and the peripheral effects of anticholinergics. Long-lasting reversal of anticholinergic signs and symptoms is not achieved because of the relatively short duration of action from physostigmine (20-60 min). Indications are severe life-threatening complications, such as coma, hypotension with dysrhythmias unresponsive to other attempts at treatment, and intractable seizures.
  • Adolescent and adult trial dosages are 2 mg IV slowly every 5 minutes. To administer, dilute the dose of physostigmine in 10 mL of dextrose 5% in water (D5W) or in 10 mL of isotonic sodium chloride solution.

Consultations

• Contact a regional poison control center.
• Consult a toxicologist or pediatric toxicologist.
• Psychiatric and neurologic complications require consultation.

Medication

Antidotes

These agents are used in the management of poisoning and overdose, prevention of toxic effects, and metabolic disorders in which toxic substances accrue. Mechanisms of action vary (eg, antagonists, toxin transformation, altered metabolism, chelation, directed antibodies).

Physostigmine (Antilirium)

Use of physostigmine in antihistamine poisoning is extremely controversial, and it should not be given unless directed by a regional poison control center or in direct consultation with a toxicologist. Physostigmine, an anticholinesterase, may be indicated in the suspected anticholinergic poisoning for its therapeutic and diagnostic value.

Dosing

Adult

Adolescent and adult trial dosages are 2 mg IV slowly q5min
To administer, dilute the dose of physostigmine in 10 mL of D5W or NS

Pediatric

Trial doses of 0.02 mg/kg or 0.5 mg IV given slowly q5min initially
To administer physostigmine, dilute the dose of physostigmine in 10 mL of D5W or NS
The therapeutic dose is the lowest effective trial dose of physostigmine, which should be repeated if life-threatening symptoms recur

Interactions

If tricyclic antidepressants were ingested, the use of physostigmine is contraindicated and may precipitate intractable seizures and cardiac arrest; prolonged respiratory depression may occur with bethanechol, methacholine, or succinylcholine

Contraindications

Documented hypersensitivity; cardiovascular disease; heart block; bronchospasm; vagotonic symptoms (especially bradycardia); intestinal and/or bladder obstruction; severe peripheral vascular disease (gangrene); diabetes; recent administration of succinylcholine; tricyclic antidepressants

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Physostigmine, even when used appropriately, may precipitate seizures, cholinergic crisis, arrhythmias, or cardiac arrest; potential adverse effects include asystole in the setting of conduction disturbance or cyclic antidepressant toxicity, seizures, muscle weakness, cholinergic crisis (eg, bradycardia, salivation, lacrimation, bronchospasm, bronchorrhea, diarrhea); before use, confirm presence of normal ECG (no conduction disturbance), absence of exposure to other cardiotoxic substances, and presence of peripheral and central signs of antimuscarinic toxicity; as added precaution, have atropine at bedside for use if cholinergic symptoms develop

Diphenhydramine (Benadryl)

DOC for initial treatment of acute dystonia or akathisia not caused by antihistamines. Use diazepam for treatment of acute dystonia secondary to antihistamines.

Dosing

Adult

25-50 mg PO q6-8h prn; not to exceed 400 mg/d
10-50 mg IV/IM q6-8hprn; not to exceed 400 mg/d

Pediatric

1 mg/kg IV q2min, not to exceed 5 mg/kg/d or 300 mg/d

Interactions

Potentiates effect of CNS depressants; because of alcohol content, do not give syrup dosage form to patient taking medications that can cause disulfiramlike reactions

Contraindications

Documented hypersensitivity; MAOIs

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur

Diazepam (Valium)

For treatment of acute dystonic reactions caused by antihistamines. Also indicated for muscle activity and agitation associated with serotonin syndrome. Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.

Dosing

Adult

5-15 mg IV q5min, repeat prn; not to exceed 30 mg in 8 h

Pediatric

0.1-0.3 mg/kg/dose PO or IV (infused over 2-3 min) q15-30min; repeat in 2-4 h prn; not to exceed 10 mg for cumulative dose

Interactions

Phenothiazines, barbiturates, alcohols, and MAOIs increase CNS toxicity when administered concurrently

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)

Lorazepam (Ativan)

Used to treat seizures. Sedative hypnotic with short onset of effects and relatively long half-life. By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. Important to monitor patient's blood pressure after administering dose. Adjust prn.

Dosing

Adult

4 mg/dose IV slowly over 2-5 min and repeat in 10-15 min prn; not to exceed 8/mg dose
1-10 mg/d PO/IV/IM divided bid/tid

Pediatric

Infants and children: 0.1 mg/kg IV slowly over 2-5 min; repeat prn in 10-15 min at 0.05 mg/kg; not to exceed 4 mg/dose
Adolescents: 0.07 mg/kg IV slowly over 2-5 min and repeat in 10-15 min prn; not to exceed 4 mg/dose

Interactions

Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs

Contraindications

Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease; monitor for hypotension and respiratory depression

Naloxone (Narcan)

Used to treat opioid overdose. Prevents or reverses opioid effects (hypotension, respiratory depression, sedation), possibly by displacing opiates from their receptors. Possesses short onset of action (2 min), duration of action is 30-60 min, and half-life is 1 h. May also be administered via endotracheal tube at 2-2.5 times the IV dose.

Dosing

Adult

0.4-2 mg IV/IM; may be repeated in 1-2 min intervals following IV use and 10 min intervals following IM use; not to exceed cumulative dose of 10 mg

Pediatric

0.01 mg/kg/dose IV/IM
<20 kg or <5 years: 0.1 mg/kg/dose IV/IM not to exceed 2 mg/dose
>20 kg or >5 years: 0.1-2 mg/dose IV/IM; may repeat dose prn; not to exceed cumulative dose of 10 mg

Interactions

Compatible with bisulfite and alkaline IV solutions; decreases the analgesic effects of narcotics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in cardiovascular disease (may cause tachycardia, hypertension, or dysrhythmias); also know to cause nausea, vomiting, diaphoresis, blurred vision, or seizures; may precipitate withdrawal symptoms in patients addicted to opiates

Decontamination agents

Consider activated charcoal decontamination in any patient who presents within 4 hours of ingestion.

Activated charcoal (Actidose-Aqua, Liqui-Char)

Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.

Dosing

Adult

25-100 g PO as a single dose

Pediatric

<1 year: 1 g/kg PO as a single dose
1-12 years: 25-50 g PO as a single dose
Adolescents: Administer as in adults

Interactions

May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix charcoal with sherbet, milk, or ice cream (decreases adsorptive properties)

Contraindications

Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adverse effects include nausea, vomiting, and possible aspiration in an unprotected airway; stools turn back from the charcoal; monitor for bowel sounds

Follow-up

Further Inpatient Care

• Patients with suspected cough and cold preparation poisoning with persistent or significant hypertension, dysrhythmia, or CNS stimulation require admission for monitoring.
• The decision to admit the patient to the ICU should be based on the initial presentation, any comorbid diseases, nature and number of the involved agents, and the potential for delayed toxicity.
• For all intentional overdoses, a psychiatric evaluation is necessary.

Further Outpatient Care

• Most regional poison control centers have their own protocols on who may be observed at home; contact them if ingestion has occurred.
• As a general rule, patients who ingest less than 3 times the maximum daily dose can be observed at home.
• If symptoms are present (other than mild somnolence) or ingestion is more than 4 times the maximum daily dose, the patient should be referred to a health care facility. The patient should be observed for 4-6 hours following ingestion of liquid and immediate-release solid preparations. Ingestion of sustained-release products may result in delayed onset of symptoms and may require longer periods of observation.
• If the patient has ingested less than 10 mg/kg of dextromethorphan, the patient can be treated at home. If the patient has ingested a long-acting dextromethorphan, refer the patient to a health care facility for evaluation.
• If the ingestion was intentional, prompt psychiatric evaluation and admission is warranted.
• Additional counseling and social work involvement may be required for patients engaging in recreational abuse.
• Further outpatient treatment should include teaching the patient's caretaker about medication storage and safety. 

Deterrence/Prevention

• Medications should be labeled and stored safety.
• Child-resistant closures should be applied to all medications and substances that can cause significant toxicity, such as cough and cold medications.

Patient Education

• Patient education is an important part of pediatric toxicology. Half of children who ingested a poison do it again within a year. Review poison prevention techniques with parents. Encourage poison proofing of the home and posting local poison control center telephone numbers by telephones throughout the home.
• One study showed that only 30% of caregivers who administered acetaminophen were able to demonstrate both accurate measuring and correct dosage for their child.
• Parents should be taught the following 4 guidelines to prevent future ingestions:
  1. Keep household cleaning products in high locked cabinets rather than under the sink. Safety latches should be place on all kitchen and bathroom cabinets and drawers that contain potentially hazardous substances.
  2. Parents should lock all reachable medicine cabinets, always keep medications in their original (childproof) containers and dispose of unused prescriptions by flushing them down the toilet.
  3. Medication should be considered "medicine," not a toy or candy. Medicine should never be referred to as candy and, if possible, not administered in front of other children. Parents, relatives, and friends also should childproof their homes.
  4. Although ipecac syrup has fallen into disfavor within some medical circles, it is still recommended that parents have it readily available in the home for use with medical direction from a physician or poison control center.
• In instances of recreational abuse, adolescents and their parents should be counseled on the dangers of addiction, as well as the health risks from dextromethorphan, especially in combination with pseudoephedrine, acetaminophen, and antihistamines.
• For excellent patient education resources, visit eMedicine's Drug Overdose Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

Miscellaneous

Medicolegal Pitfalls

• Some states have laws mandating the reporting of child abuse, suspicion of child abuse, and neglect. If the history of ingestion is suspicious, reporting may be necessary.

Multimedia

Media file 1: Dextromethorphan.

References

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Keywords

cough and cold preparation toxicity, antihistamine toxicity, antitussive toxicity, decongestant toxicity, cough medicine ingestion, cold medicine ingestion, cough and cold medicine poisoning, incidental ingestion, unintentional ingestion, cough & cold medicine, stroke, PCP, dissociative hallucinations, dextromethorphan codeine, respiratory depression, pharmaceutical-associated fatalities, Robitussin, respiratory depression, adult respiratory distress syndrome, gastroenteritis, urinary retention, rhabdomyolysis, treatment, diagnosis

Contributor Information and Disclosures

Author

Laleh Gharahbaghian, MD, Co-Director, Emergency Ultrasound Fellowship, Associate Director, Emergency Ultrasound, Clinical Instructor, Emergency Medicine, Stanford University Medical Center
Laleh Gharahbaghian, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine
Disclosure: Sonosite Honoraria Speaking and teaching

Coauthor(s)

Nicholas Lopez, MD, Resident Physician, Department of Emergency Medicine, Stanford University Medical Center, Kaiser Permanente Santa Clara Medical Center
Nicholas Lopez, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Emergency Medicine Residents Association
Disclosure: Nothing to disclose.

Jennifer Oman, MD, Associate Clinical Professor, Department of Emergency Medicine, University of California at Irvine
Disclosure: Nothing to disclose.

Medical Editor

William T Zempsky, MD, Associate Director, Assistant Professor, Department of Pediatrics, Division of Pediatric Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center
William T Zempsky, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Jeffrey R Tucker, MD, Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center
Jeffrey R Tucker, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Pediatrics, and Massachusetts Medical Society
Disclosure: Merck Salary Employment

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Timothy E Corden, MD, Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin
Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society
Disclosure: Nothing to disclose.

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