George Sam Wang, MD
Barry H. Rumack, MD
Richard C. Dart, MD, PhD
Accidental and intentional exposures to toxic substances occur in children of all ages. Children younger than age 6 years are primarily involved in accidental exposures, with the peak incidence in 2-year-olds. Of the more than 2.5 million exposures reported by the American Association of Poison Control Centers’ National Poison Data System in 2011, a total of 62% of exposures occurred in those aged less than 20 years: 49% in children aged 5 years and younger, 6% aged 6–12 years, and 6% aged 13–19 years. Young children are occasionally exposed to intentional poisoning through the actions of parents or caregivers. Administration of agents such as diphenhydramine to induce sleep in a day-care setting, Munchausen syndrome by proxy to obtain parental secondary gain, or deliberate harm should be suspected when the history is not consistent. Involvement of child abuse specialists is very helpful in these cases (see Chapter 8). Substance abuse and intentional ingestions account for most exposures in the adolescent population. In some locales, small-scale industrial or manufacturing processes may be associated with homes and farms, and exposures to hazardous substances should be considered in the history.
Pediatric patients also have special considerations pertaining to nonpharmaceutical toxicologic exposures. Their shorter stature places them lower to the ground and some gas and vapor exposures will gather closer to the ground. They may have a greater inhalational exposure due to their higher minute ventilation. At their younger age, they may not be physically mature enough to remove themselves from exposures. They also have a large body surface area to weight ratio making them vulnerable to topical exposures and hypothermia.
Bronstein AC et al: 2011 Annual report of the America Association of Poison Control Centers’ National Poison Data System (NPDS): 29th Annual Report. Clin Toxicol (Phila) 2011;50:911–1164 [PMID: 23272763].
PHARMACOLOGIC PRINCIPLES OF TOXICOLOGY
In the evaluation of the poisoned patient, it is important to compare the anticipated pharmacologic or toxic effects with the patient’s clinical presentation. If the history is that the patient ingested a tranquilizer 30 minutes ago, but the clinical examination reveals dilated pupils, tachycardia, dry mouth, absent bowel sounds, and active hallucinations—clearly anticholinergic toxicity—diagnosis and therapy should proceed accordingly. In addition, standard pharmacokinetics (absorption, distribution, metabolism, and elimination) often cannot be applied in the setting of a supratherapeutic exposure, since these parameters are extrapolated from healthy volunteers receiving therapeutic doses.
Estimates of the LD50 (the amount per kilogram of body weight of a drug required to kill 50% of a group of experimental animals) or median lethal dose are of little clinical value in humans. It is usually impossible to determine with accuracy the amount swallowed or absorbed, the metabolic status of the patient, or in which patients the response to the agent will be atypical. Furthermore, these values are often not valid in humans even if the history is accurate.
Absorption is how the substance enters the body. Depending on the route, absorption times can vary in general, intravenous/intra-arterial > inhalation > sublingual > intramuscular > subcutaneous > intranasal > oral > rectal > dermal. Large overdoses, hypotension, decreased gut mobility are factors that can delay absorption.
The t1/2 of an agent must be interpreted carefully. Most published t1/2 values are for therapeutic dosages. The t1/2 may increase as the quantity of the ingested substance increases for many common intoxicants such as salicylates. One cannot rely on the published t1/2 for salicylate (2 hours) to assume rapid elimination of the drug. In an acute salicylate overdose (150 mg/kg), the apparent t1/2 is prolonged to 24–30 hours.
Volume of Distribution
The volume of distribution (Vd) of a drug is determined by dividing the amount of drug absorbed by the blood level. With theophylline, for example, the Vd is 0.46 L/kg body weight, or 32 L in an average adult. In contrast, digoxin distributes well beyond total body water. Because the calculation produces a volume above body weight, this figure is referred to as an “apparent volume of distribution.”
Using the pharmacokinetic principles permits a practical determination of the absorbed dose and permits an understanding of the patient’s status as to whether a therapeutic administration or an overdose has occurred. A 20-kg child with an acetaminophen blood level reported as 200 mcg/mL (equivalent to 200 mg/L) would have a body burden of 4000 mg of acetaminophen. This is ascertained by taking the volume of distribution of 1 L times the weight of the child times the blood level in milligram per liter. This would be consistent with an overdose history of having consumed eight extrastrength 500-mg tablets but would not be consistent with a history of therapeutic administration of 15 mg/kg for four doses. Such a therapeutic administration would have a maximum administered dose of 1200 mg (20 kg times 15 mg/kg times four doses), which is well under the calculated body burden. Given metabolism of the drug with a normal half-life of 2 hours, it is apparent that much of the first doses would have been metabolized further adding to an understanding that this must not have been a therapeutic dose. While patients who develop hepatic toxicity from acetaminophen might have a prolonged half-life later in the course, it would certainly not occur with early therapeutic doses.
Metabolism & Excretion
The route of excretion or detoxification is important for planning treatment. Methanol, for example, is metabolized to the toxic product, formic acid. This metabolic step may be blocked by the antidote fomepizole or ethanol and patients with renal failure may not eliminate methanol as readily.
Care of the poisoned patient should never be guided solely by laboratory measurements. Concentration results may not return in time to influence acute management. Initial treatment should be directed at symptomatic and supportive care, guided by the clinical presentation, followed by more specific therapy based on laboratory determinations. Clinical information may speed the identification of a toxic agent by the laboratory.
PREVENTING CHILDHOOD POISONINGS
Inclusion of poison prevention as part of routine well-child care should begin at the 6-month well-baby visit. The poison prevention handout included as Table 13–1 may be copied and distributed to parents. It contains poison prevention information as well as first-aid actions that should be taken in the event of an exposure. All poison control centers in the United States can be reached by dialing 1-800-222-1222; the call will be automatically routed to the correct regional center.
Table 13–1. Poison prevention and emergency treatment handout.
GENERAL TREATMENT OF POISONING
The telephone is often the first contact in pediatric poisoning. Some patients may contact their pediatrician’s office first. Proper telephone management can reduce morbidity and prevent unwarranted or excessive treatment. The decision to refer the patient is based on the identity and dose of the ingested agent, the age of the child, the time of day, the reliability of the parent, and whether child neglect or endangerment is suspected. Poison control centers are the source of expert telephone advice and have excellent follow-up programs to manage patients in the home as well as provide further poison prevention information.
INITIAL TELEPHONE CONTACT
Basic information obtained at the first telephone contact includes the patient’s name, age, weight, address, and telephone number; the agent and amount of agent ingested; the patient’s present condition; and the time elapsed since ingestion or other exposure. Use the history to evaluate the urgency of the situation and decide whether immediate emergency transportation to a health facility is indicated. An emergency exists if the ingestant is high risk (caustic solutions, hydrogen fluoride, drugs of abuse, or medications such as a calcium channel blocker, opioid, hypoglycemic agent, or antidepressant) or if the self-poisoning was intentional. If immediate danger does not exist, obtain more details about the suspected toxic agent. If the child requires transport to a health facility, instruct parents that everything in the vicinity of the child that may be a cause of poisoning should be brought to the healthcare facility.
It may be difficult to obtain an accurate history. Obtain names of drugs or ingredients, manufacturers, prescription numbers, names and phone numbers of prescribing physician and pharmacy, and any other pertinent information. Find out whether the substance was shared among several children, whether it had been recently purchased, who had last used it, how full the bottle was, and how much was spilled. Determine if this occurred in the home, school, or elsewhere. If unsure of the significance of an exposure, consult with a poison control center.
Each year, children are accidentally poisoned by medicines, polishes, insecticides, drain cleaners, bleaches, household chemicals, and materials commonly stored in the garage. It is the responsibility of adults to make sure that children are not exposed to potentially toxic substances.
Obtaining Information About Poisons
Current data on ingredients of commercial products and medications can be obtained from a certified regional poison center. It is important to have the actual container at hand when calling. Material safety data sheets (MSDS) are helpful in providing product ingredient and concentration information. Caution: Antidote information on labels of commercial products or in the Physicians’ Desk Reference may be incorrect or inappropriate.
In over 95% of cases of ingestion of potentially toxic substances by children, a trip to the hospital is not required. In these cases, it is important to call the parent at 1 and 4 hours after ingestion. If the child has ingested an additional unknown agent and develops symptoms, a change in management may be needed, including transportation to the hospital. An additional call should be made 24 hours after the ingestion to begin the process of poison prevention.
INITIAL EMERGENCY DEPARTMENT CONTACT
Make Certain the Patient Is Breathing
As in all emergencies, the principles of treatment are attention to Pediatric Advance Life Support algorithms in resuscitation: airway, breathing, and circulation. These are sometimes overlooked under the stressful conditions of a pediatric poisoning.
Initial therapy of the hypotensive patient should consist of laying the patient flat or head down and administering intravenous (IV) isotonic solutions. Vasopressors should be reserved for poisoned patients in shock who do not respond to these standard measures.
Treat Burns & Skin Exposures
Burns may occur following exposure to strongly acidic or strongly alkaline agents or petroleum distillates. Burned areas should be decontaminated by flooding with sterile saline solution or water. A burn unit should be consulted if more than minimal burn damage has been sustained. Skin decontamination should be performed in a patient with cutaneous exposure. Emergency department personnel in contact with a patient who has been contaminated (with an organophosphate insecticide, for example) should themselves be decontaminated if their skin or clothing becomes contaminated. Ocular exposures can initially be decontaminated at home by placing the child in the shower allowing the water to indirectly flow from the top of the head into the eyes. Otherwise, irrigation with assessment of pH should be performed in the emergency department.
Take a Pertinent History
The history should be taken from the parents and all individuals present at the scene. It may be crucial to determine all of the kinds of poisons in the home.
These may include drugs used by family members and their medical histories, dietary or herbal supplements, foreign medications, chemicals associated with the hobbies or occupations of family members, or the purity of the water supply.
DEFINITIVE THERAPY OF POISONING
Treatment of poisoning or potential poisoning has evolved over time, and general measures such as prevention of absorption and enhancement of excretion are only instituted when specifically indicated. Specific therapy is directed at each drug, chemical, or toxin as described in the management section that follows.
Prevention of Absorption
A. Emesis and Lavage
These measures are rarely used in pediatric patients and have their own associated risk. They should not be used routinely in the management of poisonings except in potential lethal exposures with poor treatment options, such as a large tricyclic antidepressant overdose. They should be performed only in consultation with a poison center.
The routine use of charcoal has decreased substantially in recent years, especially in unintentional pediatric ingestions where lick, sip, taste ingestions are rarely dangerous. Charcoal can be considered in patients who are awake, alert, and able to drink it voluntarily. It should never be given to patients with altered sensorium who are unable to protect their airway due to risk of aspiration. The dose of charcoal is 1–2 g/kg (maximum, 100 g) per dose. Repeating the dose of activated charcoal may be useful for those agents that slow passage through the gastrointestinal (GI) tract. When multiple doses of activated charcoal are given, repeated doses of sorbitol or saline cathartics must not be given. Repeated doses of cathartics may cause electrolyte imbalances and fluid loss. Charcoal dosing is repeated every 2–6 hours until charcoal is passed through the rectum. It is not useful in ingestions of heavy metals, and may be harmful in hydrocarbons, caustics, and solvent ingestions.
Cathartics do not improve outcome and should be avoided.
D. Whole Gut Lavage
Whole bowel lavage uses an orally administered, nonabsorbable hypertonic solution such as CoLyte or GoLYTELY. The use of this procedure in poisoned patients remains controversial. Preliminary recommendations for use of whole bowel irrigation include poisoning with sustained-release preparations, mechanical movement of items through the bowel (eg, cocaine packets, iron tablets), and poisoning with substances that are poorly absorbed by charcoal (eg, lithium, iron). Underlying bowel pathology and intestinal obstruction are relative contraindications to its use. Consultation with a certified regional poison center is recommended.
American Academy of Clinical Toxicology, European Association of Poisons Centers and Clinical Toxicologists: Position statement and practice guidelines on the use of multidose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol 1999;37:731 [PMID: 10584586].
Benson et al: Poison paper update: gastric lavage. Clin Toxicol 2013 Mar;51(3):140–6.
Chyka PA et al: Position paper: single-dose activated charcoal. American Academy of Clinical Toxicology; European Association of Poison Centres and Clinical Toxicologists. Clin Toxicol (Phila) 2005;43:61 [PMID: 15822758].
Gielen AC et al: Effects of improved access to safety counseling, products, and home visits on parents’ safety practices: results of a randomized trial. Arch Pediatr Adolesc Med 2002;156:33 [PMID: 11772188].
Hojer et al: Poisition paper update: ipecac syrup. Clin Toxicol 2013 Mar;15(3):134–9.
Thummel KE, Shen DD: Design and optimization of dosage regimens: pharmacokinetic data. In Goodman LS et al (eds): Goodman & Gilman’s The Pharmacological Basis of Therapeutics. McGraw-Hill; 2001;1917.
Enhancement of Excretion
Excretion of certain substances can be hastened by urinary alkalinization or dialysis and is reserved for very special circumstances. It is important to make certain that the patient is not volume depleted. Volume-depleted patients should receive a normal saline bolus of 10–20 mL/kg, followed by sufficient IV fluid administration to maintain urine output at 2–3 mL/kg/h.
A. Urinary Alkalinization
1. Alkaline diuresis—Urinary alkalinization should be chosen on the basis of the substance’s p Ka, so that ionized drug will be trapped in the tubular lumen and not reabsorbed (see Table 13–1). Thus, if the pKa is less than 7.5, urinary alkalinization is appropriate; if it is over 8.0, this technique is not usually beneficial. The pKa is sometimes included along with general drug information. Urinary alkalinization is achieved with sodium bicarbonate. It is important to observe for hypokalemia, caused by the shift of potassium intracellularly. Follow serum K+ and observe for electrocardiogram (ECG) evidence of hypokalemia. If complications such as renal failure or pulmonary edema are present, hemodialysis or hemoperfusion may be required. It is most commonly used for the treatment of salicylate toxicity and to prevent methotrexate toxicity.
Hemodialysis is useful in the treatment of some poisons and in the general management of a critically ill patient. Although peritoneal dialysis can enhance elimination of a few medications, it is typically too slow to be clinically useful. Continuous hemofiltration techniques may be used when hypotensive patients may not tolerate traditional hemodialysis; however, clearance rates may also be slower. Dialysis should be considered part of supportive care if the patient satisfies any of the following criteria:
1. Clinical criteria
A. Potentially life-threatening toxicity that is caused by a dialyzable drug and cannot be treated by conservative means.
B. Hypotension threatening renal or hepatic function that cannot be corrected by adjusting circulating volume.
C. Marked hyperosmolality or severe acid-base or electrolyte disturbances not responding to therapy.
D. Marked hypothermia or hyperthermia not responding to therapy.
2. Immediate dialysis—Immediate dialysis should be considered in ethylene glycol and methanol poisoning only if acidosis is refractory, the patient does not respond to fomepizole treatment, or blood levels of ethanol of 100 mg/dL are consistently maintained. Refractory salicylate intoxication may benefit from dialysis.
MANAGEMENT OF SPECIFIC COMMON POISONINGS
Overdosage of acetaminophen is the most common pediatric poisoning and can produce severe hepatotoxicity. The incidence of hepatotoxicity in adults and adolescents has been reported to be 10 times higher than in children younger than age 5 years. In the latter group, fewer than 0.1% develop hepatotoxicity after acetaminophen overdose. In children, toxicity most commonly results from repeated overdosage arising from confusion about the age-appropriate dose, use of multiple products that contain acetaminophen, or use of adult suppositories.
Acetaminophen is normally metabolized in the liver. A small percentage of the drug goes through a pathway leading to a toxic metabolite. Normally, this electrophilic reactant is removed harmlessly by conjugation with glutathione. In overdosage, the supply of glutathione becomes exhausted, and the metabolite may bind covalently to components of liver cells to produce necrosis. Some authors have proposed that therapeutic doses of acetaminophen may be toxic to children with depleted glutathione stores. However, there is no evidence that administration of therapeutic doses can cause toxicity, and only a few inadequate case reports have been made in this regard.
Treatment is to administer acetylcysteine. It may be administered either orally or intravenously. Consultation on difficult cases may be obtained from your regional poison control center or the Rocky Mountain Poison and Drug Center (1-800-525-6115). Blood levels should be obtained 4 hours after ingestion or as soon as possible thereafter and plotted on Figure 13–1. The nomogram is used only for acute ingestion, not repeated supratherapeutic ingestions. If the patient has ingested acetaminophen in a liquid preparation, blood levels obtained 2 hours after ingestion will accurately reflect the toxicity to be expected relative to the standard nomogram (see Figure 13–1). Acetylcysteine is administered to patients whose acetaminophen levels plot in the toxic range on the nomogram. Acetylcysteine is effective even when given more than 24 hours after ingestion, although it is most effective when given within 8 hours postingestion.
Figure 13–1. Semi-logarithmic plot of plasma acetaminophen levels versus time. (Modified and reproduced, with permission, from Rumack BH, Matthew H: Acetaminophen poisoning and toxicity. Pediatrics 1975;55:871.)
For children weighing 40 kg or more, IV acetylcysteine (Acetadote) should be administered as a loading dose of 150 mg/kg administered over 15–60 min; followed by a second infusion of 50 mg/kg over 4 hours, and then a third infusion of 100 mg/kg over 16 hours.
For patients weighing less than 40 kg, IV acetylcysteine must have less dilution to avoid hyponatremia (a dosage calculator is available at http://www.acetadote.com) (Table 13–2). Patient-tailored therapy is critical when utilizing the IV “20-hour” protocol and those patients who still have acetaminophen measurable and/or elevated aspartate transaminase/alanine transaminase (AST/ALT) may need treatment beyond the 20 hours called for in the product insert.
Table 13–2. Intravenous acetylcysteine administration dosing.
The oral (PO) dose of acetylcysteine is 140 mg/kg, diluted to a 5% solution in sweet fruit juice or carbonated soft drink. The primary problems associated with administration are nausea and vomiting. After this loading dose, 70 mg/kg should be administered orally every 4 hours for 72 hours. AST–serum glutamic oxaloacetic transaminase (AST–SGOT), ALT–serum glutamic pyruvic transaminase (ALT–SGPT), serum bilirubin, and plasma prothrombin time should be followed daily. Significant abnormalities of liver function may not peak until 72–96 hours after ingestion.
Repeated miscalculated overdoses given by parents to treat fever are the major source of toxicity in children younger than age 10 years, and parents are often unaware of the significance of symptoms of toxicity, thus delaying its prompt recognition and therapy.
Dart RC, Rumack BH: Patient-tailored acetylcysteine administration. Ann Emerg Med 2007;50:280–281 [PMID: 17418449].
Rumack BH: Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol 2002;40:3 [PMID: 11990202].
Yarema MC et al: Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning. Ann Emerg Med 2009;54(4):606–614 [PMID: 19556028].
ALCOHOL, ETHYL (ETHANOL)
Alcoholic beverages, tinctures, cosmetics, mouthwashes, rubbing alcohol, and hand sanitizers are common sources of poisoning in children. Concomitant exposure to other depressant drugs increases the seriousness of the intoxication. In most states, alcohol levels of 50–80 mg/dL are considered compatible with impaired faculties, and levels of 80–100 mg/dL are considered evidence of intoxication. (Blood levels cited here are for adults; comparable figures for children are not available.)
Recent erroneous information regarding hand sanitizers has indicated that a “lick” following application on the hand could cause toxicity in children. In fact, this is not the case, but because these hand sanitizers contain 62% ethanol, toxicity following ingestion is very possible. Potential blood ethanol concentration following consumption of a 62% solution in a 10-kg child is calculated as follows:
1 oz = 30 mL × 62% = 18.6 mL of pure ethanol
18.6 mL × 0.79 (the specific gravity) = 14.7 g of ethanol, or 14,700 mg
In a patient weighing 10 kg, the distribution into total body water (Vd) will be 6 L—this is the amount of the body water into which the ethanol will be distributed.
14,700 mg ÷ 6 L = 2450 mg/L
2450 mg/L ÷ 10 = 245 mg/dL
Based on these calculations, a 10-kg child consuming 0.5 oz would have a concentration of 122.5 mg/dL; a 20-kg child consuming 1 oz would have a concentration of 122.5 mg/dL; a 30-kg child consuming 1 oz would have a concentration of 81.7 mg/dL; and a 70-kg adult consuming 1 oz would have a concentration of 35 mg/dL.
One “pump” from a hand sanitizer bottle dispenses approximately 2.5 mL of the product. If ingested, this amount (containing 62% ethanol) would create a blood ethanol concentration as follows:
1. In a 10-kg child: 23.1 mg/dL.
2. In a 20-kg child: 11.6 mg/dL.
3. In a 30-kg child: 7.7 mg/dL.
Children show a change in sensorium with blood levels as low as 10–20 mg/dL and any child displaying such changes should be seen immediately. Although a “lick” or a “drop” is unlikely to produce toxicity, the accuracy of the history should be considered when determining whether or not to see a child.
Complete absorption of alcohol requires 30 minutes to 6 hours, depending on the volume, the presence of food, and the time spent in consuming the alcohol. The rate of metabolic degradation is constant (about 20 mg/h in an adult). Absolute ethanol, 1 mL/kg, results in a peak blood level of about 100 mg/dL in 1 hour after ingestion. Acute intoxication and chronic alcoholism increase the risk of subarachnoid hemorrhage.
Management of hypoglycemia and acidosis is usually the only measure required. Start an IV drip of D5W or D10W if blood glucose is less than 60 mg/dL. Fructose and glucagon have been suggested but are no longer used. Death is usually caused by respiratory failure. In severe cases, cerebral edema may occur and should be appropriately treated.
AMPHETAMINES & RELATED DRUGS (METHAMPHETAMINE, MDMA)
A. Acute Poisoning
Amphetamine, 3,4-methylenedioxy-N-methylamphetamine (MDMA), and methamphetamine poisoning is common because of the widespread availability of “diet pills” and the use of “ecstasy,” “speed,” “crank,” “crystal,” and “ice” by adolescents. (Care must be taken in the interpretation of slang terms because they have multiple meanings.) A new cause of amphetamine poisoning is drugs for treating attention-deficit/hyperactivity disorder, such as methylphenidate. There are also newer designer drugs, synthetic cannabinoids (“spice, K2”) and MPDV or mephedrone (“bath salts, plant food”), which cause effects similar to stimulants.
Symptoms include central nervous system (CNS) stimulation, anxiety, hyperactivity, hyperpyrexia, diaphoresis, hypertension, abdominal cramps, nausea and vomiting, and inability to void urine. MDMA has been associated with hyponatremia and seizures. Severe cases often include rhabdomyolysis. A toxic psychosis indistinguishable from paranoid schizophrenia may occur. Methamphetamine laboratories in homes are a potential cause of childhood exposure to a variety of hazardous and toxic substances. Maternal use and the effect on the fetus as well as exposures of young children are a continuing problem.
B. Chronic Poisoning
Chronic amphetamine users develop tolerance; more than 1500 mg of IV methamphetamine can be used daily. Hyperactivity, disorganization, and euphoria are followed by exhaustion, depression, and coma lasting 2–3 days. Heavy users, taking more than 100 mg/d, have restlessness, incoordination of thought, insomnia, nervousness, irritability, and visual hallucinations. Psychosis may be precipitated by the chronic administration of high doses. Chronic MDMA use can lead to serotonin depletion, which can manifest as depression, weakness, tremors, GI complaints, and suicidal thoughts.
The treatment of choice is diazepam, titrated in small increments to effect. Very large total doses may be needed. In cases of extreme agitation or hallucinations, droperidol (0.1 mg/kg per dose) or haloperidol (up to 0.1 mg/kg) parenterally has been used. Hyperthermia should be aggressively controlled. Chronic users may be withdrawn rapidly from amphetamines. If amphetamine–barbiturate combination tablets have been used, the barbiturates must be withdrawn gradually to prevent withdrawal seizures. Psychiatric treatment should be provided.
Carvalho M et al: Toxicity of amphetamines: an update. Arch Toxicol 2012;86(8):1167–1231 [PMID: 22392347].
Intoxication from local anesthetics may be associated with CNS stimulation, acidosis, delirium, ataxia, shock, convulsions, and death. Methemoglobinemia has been reported following local mouth or dental analgesia, typically with benzocaine or prilocaine. It has also been reported with use of topical preparations in infants. The maximum recommended dose for subcutaneous (SQ) infiltration of lidocaine is 4.5 mg/kg (Table 13–3). The temptation to exceed this dose in procedures lasting a long time is great and may result in inadvertent overdosage. PO application of viscous lidocaine may produce toxicity. Hypercapnia may lower the seizure threshold to locally injected anesthetics.
Table 13–3. Pharmacologic properties of local anesthetics.
Local anesthetics used in obstetrics cross the placental barrier and are not efficiently metabolized by the fetal liver. Mepivacaine, lidocaine, and bupivacaine can cause fetal bradycardia, neonatal depression, and death. Accidental injection of mepivacaine into the head of the fetus during paracervical anesthesia has caused neonatal asphyxia, cyanosis, acidosis, bradycardia, convulsions, and death.
If the anesthetic has been ingested, mucous membranes should be cleansed carefully and activated charcoal may be administered. If it is a topical application, the area should be cleaned and irrigated. Oxygen administration is indicated, with assisted ventilation if necessary. Symptomatic methemoglobinemia is treated with methylene blue, 1%, 0.2 mL/kg (1–2 mg/kg per dose, IV) over 5–10 minutes; this should promptly relieve the cyanosis. Acidosis may be treated with sodium bicarbonate, seizures with diazepam, and bradycardia with atropine. In the event of cardiac arrest, 20% fat emulsion therapy should be initiated. Initial 1.5 mL/kg bolus over 1 minute, followed by 0.25 mL/kg/min for up to 20–30 minutes until spontaneous circulation returns. Repeat bolus can be considered. Therapeutic levels of mepivacaine, lidocaine, and procaine are less than 5 mg/mL.
Ozcan MS, Weinberg G: Update on the use of lipid emulsions in local anesthetic systemic toxicity: a focus on differential efficacy and lipid emulsion as part of advanced cardiac life support. Int Anesthesiol Clin 2011;29(4):91–103 [PMID: 21956080].
Spiller HA et al: Multi-center retrospective evaluation of oral benzocaine exposure in children. Vet Hum Toxicol 2000;42:228 [PMID: 10928690].
ANTIHISTAMINES & COUGH & COLD PREPARATIONS
The use of cough and cold preparations in young children has recently been called into question due to potential toxicity. In 2007, manufacturers voluntarily removed preparations intended for use in children younger than the age of 4 from the market. Considerable controversy remains as to the toxicity of these medications if they are used according to labeled directions and an evaluation of the cases on file at FDA stated, “In the cases judged to be therapeutic intent or unknown intent, several factors appeared to contribute to the administration of an overdosage: administration of two medicines containing the same ingredients, failure to use a measuring device, use of an adult product, use of the wrong product because of product misidentification, and two or more caregivers administering the same medication. In the cases of non-therapeutic intent, circumstances involved attempts at sedation and several included apparent attempts of overt child abuse and were under investigation by law enforcement authorities.”
Medications included in this area are: antihistamine (brompheniramine, chlorpheniramine, diphenhydramine, doxylamine), antitussive (dextromethorphan), expectorant (guaifenesin), and decongestant (pseudoephedrine, phenylephrine). Although antihistamines typically cause CNS depression, children often react paradoxically with excitement, hallucinations, delirium, ataxia, tremors, and convulsions followed by CNS depression, respiratory failure, or cardiovascular collapse. Anticholinergic effects such as dry mouth, fixed dilated pupils, flushed face, fever, and hallucinations may be prominent.
They are absorbed rapidly and metabolized by the liver, lungs, and kidneys. A potentially toxic dose is 10–50 mg/kg of the most commonly used antihistamines, but toxic reactions have occurred at much lower doses.
Activated charcoal should be used to reduce drug absorption. Whole bowel irrigation may be useful for sustained-release preparations. Physostigmine (0.5–2.0 mg IV, slowly administered) dramatically reverses the central and peripheral anticholinergic effects of antihistamines, but it should be used only for diagnostic purposes in patients without cardiotoxicity or seizures. Benzodiazepines, such as lorazepam (0.1 mg/kg IV) can be used to control seizures or agitation. Cardiac dysrhythmias and hypotension should be treated with normal saline at a dose of 10–20 mg/kg and a vasopressor if necessary. Sodium bicarbonate may be useful if there is QRS widening at a dose of 1–2 mEq/kg, making certain that the arterial pH does not exceed 7.55. Forced diuresis is not helpful. Exchange transfusion was reported to be effective in one case.
Dart RC et al: Pediatric fatalities associated with over the counter (nonprescription) cough and cold medications. Ann Emerg Med 2009;53:411–417 [PMID: 19101060].
Yin S. Malicious use of pharmaceuticals in children. J Pediatr 2010;157(5):832–836 [PMID: 20650468].
Arsenic is used in some insecticides (fruit tree or tobacco sprays), rodenticides, weed killers, and wood preservatives. It can also be found in some fireworks. It is well absorbed primarily through the GI and respiratory tracts, but skin absorption may occur. Arsenic can be found in the urine, hair, and nails by laboratory testing.
Highly toxic soluble derivatives of this compound, such as sodium arsenite, are frequently found in liquid preparations and can cause death in as many as 65% of victims. The organic arsenates found in persistent or preemergence weed killers are relatively less soluble and less toxic. Poisonings with a liquid arsenical preparation that does not contain alkyl methanearsonate compounds should be considered potentially lethal. Patients exhibiting clinical signs other than gastroenteritis should receive treatment until laboratory tests indicate that treatment is no longer necessary.
A. Acute Poisoning
Abdominal pain, vomiting, watery and bloody diarrhea, cardiovascular collapse, paresthesias, neck pain, and garlic odor on the breath occur as the first signs of acute poisoning. Convulsions, coma, anuria, and exfoliative dermatitis are later signs. Inhalation may cause pulmonary edema. Death is the result of cardiovascular collapse.
B. Chronic Poisoning
Anorexia, generalized weakness, giddiness, colic, abdominal pain, polyneuritis, dermatitis, nail changes, alopecia, and anemia often develop.
In acute poisoning, administer activated charcoal. Then immediately give dimercaprol (commonly known as BAL), 3–5 mg/kg intramuscularly (IM), and follow with 2 mg/kg IM every 4 hours. The dimercaprol–arsenic complex is dialyzable. A second choice is succimer. The initial dose is 10 mg/kg every 8 hours for 5 days. A third choice is penicillamine, 100 mg/kg PO to a maximum of 1 g/d in four divided doses.
Chronic arsenic intoxication should be treated with succimer or penicillamine. Collect a 24-hour baseline urine specimen, greater than 50 mcg/L is elevated. Elevated levels must be correlated with history, as seafood can contain high levels of organic arsenic and cause a transient increase in urinary arsenic. With elevated levels, speciation of the sample is recommended, or a seafood holiday for 1 week and repeat lab work. If treatment is initiated, continue chelation for 5 days. After 10 days, repeat the 5-day cycle once or twice, depending on how soon the urine arsenic level falls below 50 mcg/L/24 hrs.
Abernathy CO et al: Arsenic: health effects, mechanisms of actions, and research issues. Environ Health Perspect 1999;107:593 [PMID: 10379007].
Stephanopoulus DE et al: Treatment and toxicokinetics of acute pediatric arsenic ingestion: danger of arsenic insecticides in children. Pediatr Crit Care Med 2002;3(1):74–80.
BARBITURATES & BENZODIAZEPINES
Barbiturates are rarely used today, and have mostly been replaced with benzodiazepines for their use in seizures or for sedation. The toxic effects of barbiturates include confusion, poor coordination, coma, miotic or fixed dilated pupils, and respiratory depression. Respiratory acidosis is commonly associated with pulmonary atelectasis, and hypotension occurs frequently in severely poisoned patients. Ingestion of more than 6 mg/kg of long-acting or 3 mg/kg of short-acting barbiturates is usually toxic. Benzodiazepines typically cause CNS depression and lethargy in unintentional oral ingestions. Large oral overdoses or iatrogenic IV overdose can cause cardiovascular or respiratory depression.
Careful, conservative management with emphasis on maintaining a clear airway, adequate ventilation, and control of hypotension is critical. Urinary alkalinization and the use of multiple-dose charcoal may decrease the elimination half-life of phenobarbital but have not been shown to alter the clinical course. Hemodialysis is not useful in the treatment of poisoning with short-acting barbiturates or benzodiazepines. Analeptics are contraindicated. Flumazenil can be considered if severe CNS depression or respiratory depression develops after benzodiazepine overdose using a dose of 0.01 mg/kg IV (maximum dose of 0.2 mg).
Gaudreault P et al: Benzodiazepine poisoning: clinical and pharmacological considerations and treatment. Drug Saf 1991;6(4):247 [PMID: 1888441].
Kreshak AA et al: Flumazenil administration in poisoned pediatric patients. Pediatr Emerg Care 2012;28(5):488 [PMID: 22531190].
BELLADONNA ALKALOIDS (ATROPINE, JIMSONWEED, POTATO LEAVES, SCOPOLAMINE, STRAMONIUM)
The effects of anticholinergic compounds include dry mouth; thirst; decreased sweating with hot, dry, red skin; high fever; and tachycardia that may be preceded by bradycardia. The pupils are dilated, and vision is blurred. Speech and swallowing may be impaired. Hallucinations, delirium, and coma are common. Leukocytosis may occur, confusing the diagnosis.
Atropinism has been caused by normal doses of atropine or homatropine eye drops, especially in children with Down syndrome. Many common plants and over-the-counter medications contain belladonna alkaloids.
If the patient is awake and showing no signs or symptoms, administration of activated charcoal can be considered. Gastric emptying is slowed by anticholinergics, so that gastric decontamination may be useful even if delayed. Benzodiazepines should be administered to control agitation. Bolus dosing should be given in escalating doses, and high doses may be required. Physostigmine (0.5–2.0 mg IV, administered slowly) dramatically reverses the central and peripheral signs of atropinism but should be used only as a diagnostic agent. It should not be given in patients with cardiotoxicity or seizures. Hyperthermia should be aggressively controlled. Catheterization may be needed if the patient cannot void.
Burns MJ et al: A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med 2000;35:374 [PMID: 10736125].
Vearrier D, Greenberg MI: Anticholinergic delirium following Datura stramonium ingestion: implications for the internet age. J Emerg Trauma Shock 2010;3(3):303 [PMID: 20930988].
β-BLOCKERS & CALCIUM CHANNEL BLOCKERS
β-Blockers and calcium channel blockers primarily cause cardiovascular toxicity; bradycardia, hypotension, and various degrees of heart block; a cardiac dysrhythmias may develop. Severe toxicity can cause CNS depression. The β-blocker propranolol is associated with seizures. Hyperglycemia can be seen with calcium channel blocker toxicity.
Initial stabilization with IV fluid resuscitation with isotonic fluids should be initiated. Atropine can be given for symptomatic bradycardia. Calcium at doses of 20 mg/kg and repeated as needed should be administered. Infusions of calcium chloride 10%, 0.2–0.5 mL/kg/h, can be started after initial bolus dosing. Glucagon can be administered; 50–100 mcg/kg (5–10 mg) IV bolus followed by 2–5 mg/h infusion if patient improves. Vasopressors such as dopamine or norepinephrine should be started if patient continues to be hypotensive and bradycardic. In patients who are severely poisoned and refractory to these initial measures, hyperinsulinemia euglycemic therapy should be started. Your regional poison control center should be contacted for further details on dosing of this therapy.
Dewitt CR, Waksman JC: Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. Toxicol Rev 2004;23(4):223–238 [PMID: 15898828].
Engebretsen KM, Kaczmarek KM, Morgan J, Holger JS: High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Clin Toxicol (Phila) 2011;49(4):277–283 [PMID: 21563902].
The degree of toxicity correlates well with the carboxyhemoglobin level taken soon after acute exposure but not after oxygen has been given or when there has been some time since exposure. Onset of symptoms may be more rapid and more severe if the patient lives at a high altitude, has a high respiratory rate (ie, infants), is pregnant, or has myocardial insufficiency or lung disease. Normal blood may contain up to 5% carboxyhemoglobin (10% in smokers). Neonates may have elevated carboxyhemoglobin levels due to breakdown of bilirubin.
Presenting symptoms can include nonspecific symptoms such as headache or flu-like illness. Other effects include confusion, unsteadiness, and coma. Proteinuria, glycosuria, elevated serum aminotransferase levels, or ECG changes may be present in the acute phase. Permanent cardiac, liver, renal, or CNS damage occurs occasionally. The outcome of severe poisoning may be complete recovery, vegetative state, or any degree of mental injury between these extremes. The primary mental deficits are neuropsychiatric.
The biologic half-life of carbon monoxide on room air is approximately 200–300 minutes; on 100% oxygen, it is 60–90 minutes. Thus, 100% oxygen should be administered immediately. Hyperbaric oxygen therapy at 2.0–2.5 atm of oxygen shortens the half-life to 30 minutes. The use of hyperbaric oxygen therapy for delayed neurologic sequelae can be considered, but remains controversial. After the level has been reduced to near zero, therapy is aimed at the nonspecific sequelae of anoxia. Evaluation of the source should be performed before the patient returns to the home.
Buckley NA, et al: Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev 2011;13(4):CD002041 [PMID: 21491385].
Chou KJ: Characteristics and outcome of children with carbon monoxide poisoning with and without smoke exposure referred for hyperbaric oxygen therapy. Pediatr Emerg Care 2000;3:151 [PMID: 10888449].
1. Acids (Hydrochloric, Hydrofluoric, Nitric, & Sulfuric Acids; Sodium Bisulfate)
Strong acids are commonly found in metal and toilet bowl cleaners, batteries, and other products. Hydrofluoric acid is the most toxic and hydrochloric acid the least toxic of these household substances. However, even a few drops can be fatal if aspirated into the trachea.
Painful swallowing, mucous membrane burns, bloody emesis, abdominal pain, respiratory distress due to edema of the epiglottis, thirst, shock, and renal failure can occur. Coma and convulsions sometimes are seen terminally. Residual lesions include esophageal, gastric, and pyloric strictures as well as scars of the cornea, skin, and oropharynx.
Hydrofluoric acid is a particularly dangerous poison. Dermal exposure creates a penetrating burn that can progress for hours or days. Large dermal exposure or ingestion may produce life-threatening hypocalcemia abruptly as well as burn reactions.
Emetics and lavage are contraindicated. Water or milk (< 15 mL/kg) is used to dilute the acid, because a heat-producing chemical reaction does not occur. Take care not to induce emesis by excessive fluid administration. Alkalis should not be used. Burned areas of the skin, mucous membranes, or eyes should be washed with copious amounts of warm water. Opioids for pain may be needed. An endotracheal tube may be required to alleviate laryngeal edema. Esophagoscopy should be performed if the patient has significant burns or difficulty in swallowing, drooling, vomiting or stridor. Acids are likely to produce gastric burns or esophageal burns. Evidence is not conclusive, but corticosteroids have not proved to be of use.
Hydrofluoric acid burns on skin are treated with 10% calcium gluconate gel or calcium gluconate infusion. Severe exposure may require large doses of IV calcium. Therapy should be guided by calcium levels, the ECG, and clinical signs.
2. Bases (Clinitest Tablets, Clorox, Drano, Liquid-Plumr, Purex, Sani-Clor—Examine the Label or Call a Poison Center to Determine Contents)
Alkalis produce more severe injuries than acids. Some substances, such as Clinitest tablets or Drano, are quite toxic, whereas the chlorinated bleaches (3%–6% solutions of sodium hypochlorite) are usually not toxic. When sodium hypochlorite comes in contact with acid in the stomach, hypochlorous acid, which is very irritating to the mucous membranes and skin, is formed. Rapid inactivation of this substance prevents systemic toxicity. Chlorinated bleaches, when mixed with a strong acid (toilet bowl cleaners) or ammonia, may produce irritating chlorine or chloramine gas, which can cause serious lung injury if inhaled in a closed space (eg, bathroom).
Alkalis can burn the skin, mucous membranes, and eyes. Respiratory distress may be due to edema of the epiglottis, pulmonary edema resulting from inhalation of fumes, or pneumonia. Mediastinitis or other intercurrent infections or shock can occur. Perforation of the esophagus or stomach is rare.
The skin and mucous membranes should be cleansed with copious amounts of water. A local anesthetic can be instilled in the eye if necessary to alleviate blepharospasm. The eye should be irrigated for at least 20–30 minutes. Ophthalmologic consultation should be obtained for all alkaline eye burns.
Ingestions should be treated with water as a diluent. Routine esophagoscopy is no longer indicated to rule out burns of the esophagus due to chlorinated bleaches unless an unusually large amount has been ingested or the patient is symptomatic. Symptoms that are concerning for significant injury esophageal injury include drooling, persistent vomiting, and stridor. The absence of oral lesions does not rule out the possibility of laryngeal or esophageal burns following granular alkali ingestion. The use of corticosteroids is controversial, but has not been shown to improve long-term outcome except possibly in partial-thickness esophageal burns. Antibiotics may be needed if mediastinitis is likely, but they should not be used prophylactically. (See Caustic Burns of the Esophagus section in Chapter 21.)
Crain EF, Gershel JC, Mezey AP: Caustic ingestions-symptoms as predictors of esophageal injury. Am J Dis Child 1984;138:863–865 [PMID: 6475876].
Hamza AF et al: Caustic esophageal strictures in children: 30 years’ experience. J Pediatr Surg 2003;338:828 [PMID: 12778375].
CENTRAL ALPHA-2 ADRENERGIC AGONIST
Central alpha-2 adrenergic agonists are common over-the-counter and prescribed medication. The imidazolines are found in nasal decongestants and eye drops to relieve redness. Clonidine and guanfacine are used most commonly to treat attention deficit hyperactivity disorder or hypertension. Dexmedetomidine is an IV central alpha-2 adrenergic agonist used for sedation. These medications exert their effects by stimulating presynaptic alpha-2 adrenergic receptors in the brain, resulting in decreased norepinephrine release and decreased sympathetic outflow.
Most common effects are related to CNS sedation. They can present similar to an opioid toxidrome with miosis, CNS depression, and respiratory depression. Other common effects include bradycardia and hypotension.
If the patient becomes obtunded, or has inability to protect their airway, intubation may be indicated. Naloxone has been tried to reverse signs of toxicity with varying success. Symptomatic bradycardia can be treated with IV fluid resuscitation or atropine. Hypotension should be treated initially with IV fluid resuscitation, followed by vasopressors if needed
Shinha Y, Cranswick NE: Clonidine poisoning in children: a recent experience. J Paediatr Child Health 2004;40:678–680 [PMID: 15569283].
Cocaine is absorbed intranasally or via inhalation or ingestion. Effects are noted almost immediately when the drug is taken intravenously or smoked. Peak effects are delayed for about an hour when the drug is taken orally or nasally. Cocaine prevents the reuptake of endogenous catecholamines, thereby causing an initial sympathetic discharge, followed by catechol depletion after chronic abuse.
A local anesthetic and vasoconstrictor, cocaine is also a potent stimulant to both the CNS and the cardiovascular system. The initial tachycardia, hyperpnea, hypertension, and stimulation of the CNS are often followed by coma, seizures, hypotension, and respiratory depression. In severe cases of overdose, various dysrhythmias may be seen, including sinus tachycardia, atrial arrhythmias, premature ventricular contractions, bigeminy, and ventricular fibrillation. If large doses are taken intravenously, cardiac failure, dysrhythmias, rhabdomyolysis, or hyperthermia may result in death.
In addition to those poisoned through recreational use of cocaine, others are at risk of overdose. A “body stuffer” is one who quickly ingests the drug, usually poorly wrapped, to avoid discovery. A “body packer” wraps the drug carefully for prolonged transport. A stuffer typically manifests toxicity within hours of ingestion; a packer is asymptomatic unless the package ruptures, usually days later. Newborns of cocaine using mothers may continue to have seizures for months after birth.
Except in cases of body stuffers or body packers, decontamination is seldom possible. Activated charcoal should be administered, and whole bowel irrigation may be useful in cases of body packers. Testing for cocaine in blood or plasma is generally not clinically useful, but a qualitative analysis of the urine may aid in confirming the diagnosis. For severe cases, an ECG is indicated. In suspected cases of body packing, radiographs of the GI tract may show multiple packets. Radiographic films are usually not helpful for identifying stuffers. Seizures are treated with IV benzodiazepines such as lorazepam, titrated to response. Hypotension is treated with standard agents. Because cocaine abuse may deplete norepinephrine, an indirect agent such as dopamine may be less effective than a direct agent such as norepinephrine. Agitation is best treated with a benzodiazepine.
Delaney-Black V: Prenatal cocaine exposure as a risk factor for later developmental outcomes. JAMA 2001;286:46 [PMID: 11434823].
Flach PM et al: “Drug mules” as a radiological challenge: sensitivity and specificity in identifying internal cocaine in body packers, body pushers, and body stuffers by computer tomography, plain radiography and Lodox. Eur J Radiol 2012;81(10):2518–2526 [PMID: 22178312].
Qureshi AI et al: Cocaine use and the likelihood of nonfatal myocardial infarction and stroke: data from the Third National Health and Nutrition Examination Survey. Circulation 2001;103:502 [PMID: 11157713].
The only known toxic effects following acute ingestion of oral contraceptive agents are nausea, vomiting, and vaginal bleeding in girls.
COSMETICS & RELATED PRODUCTS
Cosmetics and personal care products are the most frequently involved substance in pediatric patients less than 5 years of age. Luckily, most of them do not cause significant toxicity. The relative toxicities of commonly ingested products in this group are listed in Table 13–4. Permanent wave neutralizers may contain bromates, peroxides, or perborates. Bromates have been removed from most products because they can cause nausea, vomiting, abdominal pain, shock, hemolysis, renal failure, and convulsions.
Table 13–4. Relative toxicities of cosmetics and similar products.
Poisoning is treated by gastric lavage with 1% sodium thiosulfate. Sodium bicarbonate, 2%, in the lavage fluid may reduce hydrobromic acid formation. Sodium thiosulfate, 25%, 1.65 mL/kg, can be given intravenously, but methylene blue should not be used to treat methemoglobinemia in this situation because it increases the toxicity of bromates. Dialysis is indicated in renal failure but does not enhance excretion of bromate.
Perborates can cause boric acid poisoning. Single acute ingestions of boric acid are generally benign. However, significant toxicity can result from massive acute ingestions.
Fingernail polish removers used to contain toluene but now usually have an acetone base, which does not require specific treatment other than monitoring CNS status.
Cobalt, copper, cadmium, iron, lead, nickel, silver, bismuth, and tin are sometimes found in metallic hair dyes. In large amounts, they can cause skin sensitization, urticaria, dermatitis, eye damage, vertigo, hypertension, asthma, methemoglobinemia, tremors, convulsions, and coma. Treatment for ingestions is to administer demulcents and, only with large amounts, the appropriate antidote for the heavy metal involved.
Home permanent wave lotions, hair straighteners, and hair removers usually contain thioglycolic acid salts, which cause alkaline irritation and perhaps CNS depression.
Shaving lotion, hair tonic, hair straighteners, cologne, and toilet water contain denatured alcohol, which can cause CNS depression and hypoglycemia.
Deodorants usually consist of an antibacterial agent in a cream base. Antiperspirants are aluminum salts, which frequently cause skin sensitization. Zirconium oxide can cause granulomas in the axilla with chronic use.
Cyclic antidepressants (eg, amitriptyline, imipramine) have a very low ratio of toxic to therapeutic doses, and even a moderate overdose can have serious effects.
Cyclic antidepressant overdosage can cause a progression of illness beginning with sudden onset coma within 1–2 hours of ingestion, followed by convulsions, hypotension, and dysrhythmias. These effects may be life-threatening and require rapid intervention. One agent, amoxapine, differs in that it causes fewer cardiovascular complications, but it is associated with a higher incidence of seizures.
Decontamination should include administration of activated charcoal unless the patient is symptomatic.
An ECG should be obtained in all patients. A QRS interval greater than 100 ms specifically identifies patients at risk to develop dysrhythmias. If dysrhythmias are demonstrated, the patient should be admitted and monitored until free of irregularity for 24 hours. Another indication for monitoring is persistent tachycardia of more than 110 beats/min. The onset of dysrhythmias is rare beyond 24 hours after ingestion.
Alkalinization with sodium bicarbonate (0.5–1.0 mEq/kg IV) may dramatically reverse ventricular dysrhythmias and narrow the QRS interval. If intubated, hyperventilation may be helpful. Lidocaine may be added for treatment of arrhythmias. Bolus administration of sodium bicarbonate is recommended for all patients with QRS widening to above 120 ms and for those with significant dysrhythmias, to achieve a pH of 7.5–7.6. Forced diuresis is contraindicated. A benzodiazepine should be given for convulsions.
Cyclic antidepressants block the reuptake of catecholamines, thereby producing initial hypertension followed by hypotension. Vasopressors are generally effective. Dopamine is the agent of choice because it is readily available. If dopamine is ineffective, norepinephrine (0.1–1 mcg/kg/min, titrated to response) should be added. Diuresis and hemodialysis are not effective. Treatment with physostigmine is contraindicated.
Kerr GW et al: Tricyclic antidepressant overdose: a review. Emerg Med J 2001;18:236 [PMID: 11435353].
DIGITALIS & OTHER CARDIAC GLYCOSIDES
Acute toxicity is typically the result of incorrect dosing, and chronic toxicity is due to unrecognized renal insufficiency. Clinical features include nausea, vomiting, diarrhea, headache, delirium, confusion, and, occasionally, coma. Cardiac dysrhythmias typically involve bradydysrhythmias, but every type of dysrhythmia has been reported in digitalis intoxication, including atrial fibrillation, paroxysmal atrial tachycardia, and atrial flutter. Death usually is the result of ventricular fibrillation. Transplacental intoxication by digitalis has been reported. Cardiac glycosides, such as yellow oleander and foxglove, can cause digitalis toxicity in large ingestions as well.
If patient is awake and alert, consider administering activated charcoal. Potassium is contraindicated in acute overdosage unless there is laboratory evidence of hypokalemia. In acute overdosage, hyperkalemia is more common. Hypokalemia is common in chronic toxicity.
The patient must be monitored carefully for ECG changes. The correction of acidosis better demonstrates the degree of potassium deficiency present. Bradycardias have been treated with atropine. Phenytoin, lidocaine, magnesium salts (not in renal failure), amiodarone, and bretylium have been used to correct arrhythmias.
Definitive treatment is with digoxin immune Fab (ovine) (Digibind). Indications for its use include hypotension or any dysrhythmia, typically ventricular dysrhythmias and progressive bradydysrhythmias that produce clinical concern, or hyperkalemia in an acute overdose. Elevated T waves indicate high potassium and may be an indication for digoxin immune Fab (Digibind, DigiFab) use. Techniques of determining dosage and indications related to levels, when available are described in product literature. High doses of digoxin immune Fab may be needed in cardiac glycoside overdose.
Rajapakse S: Management of yellow oleander poisoning. Clin Toxicol (Phila) 2009;47(3):206–212 [PMID: 19306191].
Woolf AD et al: The use of digoxin-specific Fab fragments for severe digitalis intoxication in children. N Engl J Med 1992;326:1739 [PMID: 1997016].
DIPHENOXYLATE WITH ATROPINE (LOMOTIL) & LOPERAMIDE (IMODIUM)
Loperamide (Imodium) has largely replaced Lomotil and does not produce significant toxicity. Ingestions of up to 0.4 mg/kg can safely be managed at home.
Lomotil is still widely available and contains diphenoxylate hydrochloride, a synthetic narcotic, and atropine sulfate. Small amounts are potentially lethal in children; it is contraindicated in children younger than age 2 years. Early signs of intoxication with this preparation result from its anticholinergic effect and consist of fever, facial flushing, tachypnea, and lethargy. However, the miotic effect of the narcotic predominates. Later, hypothermia, increasing CNS depression, and loss of the facial flush occur. Seizures are probably secondary to hypoxia.
Prolonged monitoring (24 hours) with pulse oximetry and careful attention to airway is sufficient in most cases.
Naloxone hydrochloride (0.4–2.0 mg IV in children and adults) should be given for signs of respiratory depression. Repeated doses may be required because the duration of action of diphenoxylate is considerably longer than that of naloxone.
McCarron MM et al: Diphenoxylate-atropine (Lomotil) overdose in children: an update. Pediatrics 1991;87:694 [PMID: 2020516].
DISINFECTANTS & DEODORIZERS
Naphthalene is commonly found in mothballs, disinfectants, and deodorizers. Naphthalene’s toxicity is often not fully appreciated. It is absorbed not only when ingested but also through the skin and lungs. It is potentially hazardous to store baby clothes in naphthalene, because baby oil is an excellent solvent that may increase dermal absorption. Note: Most mothballs contain para-dichlorobenzene and not naphthalene (see next section). Metabolic products of naphthalene may cause severe hemolytic anemia, similar to that due to primaquine toxicity, 2–7 days after ingestion. Other physical findings include vomiting, diarrhea, jaundice, oliguria, anuria, coma, and convulsions.
If the patient is awake and alert, consideration can be given for administering activated charcoal. Methemoglobinemia and hemolysis may occur 24–48 hours after ingestion. Life-threatening hemolysis and anemia may require blood transfusions.
Siegel E, Wason S: Mothball toxicity. Pediatr Clin North Am 1986;33:369 [PMID: 3515301].
2. P-Dichlorobenzene, Phenolic Acids, & Others
Disinfectants and deodorizers containing p-dichlorobenzene or sodium sulfate are much less toxic than those containing naphthalene. They typically cause mucous membrane irritation and GI upset. Camphor can cause seizures after ingestion. Disinfectants containing phenolic acids are highly toxic, especially if they contain a borate ion. Phenol precipitates tissue proteins and causes respiratory alkalosis followed by metabolic acidosis. Some phenols cause methemoglobinemia.
Local gangrene occurs after prolonged contact with tissue. Phenol is readily absorbed from the GI tract, causing diffuse capillary damage and, in some cases, methemoglobinemia. Phenol can also be absorbed dermally. Pentachlorophenol, which has been used in terminal rinsing of diapers, has caused infant fatalities.
The toxicity of alkalis, quaternary ammonium compounds, pine oil, and halogenated disinfectants varies with the concentration of active ingredients. Wick deodorizers are usually of moderate toxicity. Iodophor disinfectants are the safest. Spray deodorizers are not usually toxic, because a child is not likely to swallow a very large dose.
Signs and symptoms of acute quaternary ammonium compound ingestion include diaphoresis, strong irritation, thirst, vomiting, diarrhea, cyanosis, hyperactivity, coma, convulsions, hypotension, abdominal pain, and pulmonary edema. Acute liver or renal failure may develop later.
Mainstay to phenol toxicity is symptomatic and supportive care. The metabolic acidosis must be managed carefully. Anticonvulsants or measures to treat shock may be needed.
Because phenols are absorbed through the skin, exposed areas should be irrigated copiously with water. Undiluted polyethylene glycol may be a useful solvent as well.
Van Berkel M, de Wolff FA: Survival after acute benzalkonium chloride poisoning. Hum Toxicol 1988;7:191 [PMID: 3378808].
DISK-SHAPED “BUTTON” BATTERIES
Small, flat, smooth disk-shaped batteries measure between 10 and 25 mm in diameter. About 69% of them pass through the GI tract in 48 hours and 85% in 72 hours. Some may become entrapped. These batteries contain caustic materials and heavy metals.
Batteries impacted in the esophagus may cause symptoms of refusal to take food, increased salivation, vomiting with or without blood, and pain or discomfort. Aspiration into the trachea may also occur. Fatalities have been reported in association with esophageal perforation.
When a history of disk battery ingestion is obtained, radiographs of the entire respiratory tract and GI tract should be taken so that the battery can be located and the proper therapy determined.
Any disk battery ingestion should be referred for evaluation and radiographs. If the disk battery is located in the esophagus, it must be removed immediately. Any prolonged time in the esophagus can cause injury. Consultation with GI or surgical subspecialty is recommended.
Location of the disk battery below the esophagus has been associated with tissue damage, but the course is benign in most cases. Perforated Meckel diverticulum has been the major complication. It may take as long as 7 days for spontaneous passage to occur, and lack of movement in the GI tract may not require removal in an asymptomatic patient.
Some researchers have suggested repeated radiographs and surgical intervention if passage of the battery pauses, but this approach may be excessive. Batteries that have opened in the GI tract have been associated with some toxicity due to mercury, but the patients have recovered.
Emesis is ineffective. Asymptomatic patients may simply be observed and stools examined for passage of the battery. If the battery has not passed within 7 days or if the patient becomes symptomatic, radiographs should be repeated. If the battery has come apart or appears not to be moving, a purgative, enema, or nonabsorbable intestinal lavage solution should be administered. If these methods are unsuccessful, surgical intervention may be required. Levels of heavy metals (mainly mercury) should be measured in patients in whom the battery has opened or symptoms have developed.
Brumbaugh D et al: Hemorrhagic complications following esophageal button battery ingestion. Arch Otolaryngol Head Neck Surg 2011;137(4):416–417.
Centers for Disease Control and Prevention (CDC): Injuries from batteries among children aged < 13 years-United States, 1995–2010. MMWR Morb Mortal Wkly Rep 2012;61(34):661–666.
Sharpe SJ et al: Pediatric battery-related emergency department visits in the United States, 1990–2009. Pediatrics 2012;129(6):1111 [PMID: 22585763].
ETHYLENE GLYCOL & METHANOL
Ethylene glycol and methanol are the toxic alcohols. The primary source of ethylene glycol is antifreeze, whereas methanol is present in windshield wiper fluid and also as an ethanol denaturant. Ethylene glycol causes severe metabolic acidosis and renal failure. Methanol causes metabolic acidosis and blindness. Onset of symptoms with both agents occurs within several hours after ingestion, longer if ethanol was ingested simultaneously.
The primary treatment is to block the enzyme alcohol dehydrogenase, which converts both agents to their toxic metabolites. This is accomplished with fomepizole (loading dose of 15 mg/kg) or ethanol. Fomepizole is preferred for children, due to its reduced side effects in this age group. Hemodialysis is indicated with high concentrations, persistent metabolic acidosis, or end organ toxicity.
Brent J: Fomepizole for the treatment of pediatric ethylene and diethylene glycol, butoxyethanol, and methanol poisonings. Clin Toxicol (Phila) 2010;48(5):401–406 [PMID: 20586570].
γ-HYDROXYBUTYRATE, γ-BUTYROLACTONE, & BUTANEDIOL
γ-Hydroxybutyrate (GHB), γ-butyrolactone (GBL), and butanediol have become popular drugs of abuse in adolescents and adults. GHB is a CNS depressant that is structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid. GBL and butanediol are converted in the body to GHB. These drugs cause deep but short-lived coma; the coma often lasts only 1–4 hours. Treatment consists of supportive care with close attention to airway and endotracheal intubation if respiratory depression or decreased gag reflex complicates the poisoning. Atropine has been used successfully for symptomatic bradycardia.
Withdrawal from GHB, GBL, or butanediol can cause several days of extreme agitation, hallucination, or tachycardia. Treatment with high doses of benzodiazepines or with butyrophenones (eg, haloperidol or droperidol) or secobarbital may be needed for several days.
Dyer JE et al: Gamma-hydroxybutyrate withdrawal syndrome. Ann Emerg Med 2001;37:147 [PMID: 11174231].
Sporer KA et al: Gamma-hydroxybutyrate serum levels and clinical syndrome after severe overdose. Ann Emerg Med 2003;42:3 [PMID: 12827115].
HYDROCARBONS (BENZENE, CHARCOAL LIGHTER FLUID, GASOLINE, KEROSENE, PETROLEUM DISTILLATES, TURPENTINE)
Ingestion of hydrocarbons may cause irritation of mucous membranes, CNS depression, or aspiration pneumonitis. Although a small amount (10 mL) of certain hydrocarbons is potentially fatal, patients have survived ingestion of several ounces of other petroleum distillates. Hydrocarbons with high volatility, low viscosity, and low surface tension have more risk or aspiration pneumonitis. Benzene, kerosene, red seal oil furniture polish, and some of the essential oils are very dangerous. A dose exceeding 1 mL/kg is likely to cause CNS depression. A history of coughing or choking, as well as vomiting, suggests aspiration with resulting hydrocarbon pneumonia. This is an acute hemorrhagic necrotizing disease that usually develops within 24 hours of the ingestion and resolves without sequelae in 3–5 days. However, several weeks may be required for full resolution of hydrocarbon pneumonia. Pulmonary edema and hemorrhage, cardiac dilation and dysrhythmias, hepatosplenomegaly, proteinuria, and hematuria can occur following large overdoses. Hypoglycemia is occasionally present. A chest radiograph may reveal pneumonia within hours after the ingestion. An abnormal urinalysis in a child with a previously normal urinary tract suggests a large overdose.
Both emetics and lavage should be avoided. Initial supportive care, observing for CNS depression or respiratory distress.
Epinephrine should be avoided with halogenated hydrocarbons because it may affect an already sensitized myocardium. The usefulness of corticosteroids is debated, and antibiotics should be reserved for patients with infections (pneumonitis can cause fevers and infiltrates). Oxygen and mist are helpful. Surfactant therapy for severe hydrocarbon-induced lung injury has been used successfully. Extracorporeal membrane oxygenation has been successful in at least two cases of failure with standard therapy.
Marsolek MR et al: Inhalant abuse: monitoring trends by using poison control data, 1993–2008. Pediatrics 2010;125(5):906–913 [PMID: 20403928].
Mastropietro SW et al: Early administration of intratracheal surfactant (calfactant) after hydrocarbon aspiration. Pediatrics 2011;127(6):e1600– e1604 [PMID: 21624800].
Most exposures in children do not produce symptoms. In one study, for example, children ingesting up to 2.4 g remained asymptomatic. When symptoms occur, the most common are abdominal pain, vomiting, drowsiness, and lethargy. In rare cases, apnea (especially in young children), seizures, metabolic acidosis, and CNS depression leading to coma have occurred.
If a child has ingested less than 100 mg/kg, dilution with water or milk may be all that is necessary to minimize the GI upset. In children, the volume of liquid used for dilution should be less than 4 oz. When the ingested amount is more than 400 mg/kg, seizures or CNS depression may occur. There is no specific antidote. Neither alkalinization of the urine nor hemodialysis is helpful in elimination of ibuprofen. However, hemodialysis may be needed to correct acid base abnormalities.
Cuzzolin L et al: NSAID-induced nephrotoxicity from the fetus to the child. Drug Safety 2001;242:9 [PMID: 11219488].
Marciniak KE et al: Massive ibuprofen overdose requiring extracorporeal membrane oxygenation for cardiovascular support. Pediatr Crit Care Med 2007;8:180–182 [PMID: 17273120].
INSECT STINGS (BEE, WASP, & HORNET)
Insect stings are painful but not usually dangerous; however, death from anaphylaxis may occur. Bee venom has hemolytic, neurotoxic, and histamine-like activities that can on rare occasion cause hemoglobinuria and severe anaphylactoid reactions. Massive envenomation from numerous stings may cause hemolysis, rhabdomyolysis, and shock leading to multiple-organ failure.
The physician should remove the stinger, taking care not to squeeze the attached venom sac. For allergic reactions, epinephrine 1:1000 solution, 0.01 mL/kg, should be administered IV or SQ above the site of the sting. Three to four whiffs from an isoproterenol aerosol inhaler may be given at 3- to 4-minute intervals as needed. Corticosteroids (hydrocortisone; 100 mg IV) and diphenhydramine (1.5 mg/kg IV) are useful ancillary drugs but have no immediate effect.
Ephedrine or antihistamines may be used for 2 or 3 days to prevent recurrence of symptoms.
A patient who has had a potentially life-threatening insect sting should be desensitized against the Hymenoptera group, because the honey bee, wasp, hornet, and yellow jacket have common antigens in their venom. For the more usual stings, cold compresses, aspirin, and diphenhydramine (1 mg/kg PO) are sufficient.
Ross RN et al: Effectiveness of specific immunotherapy in the treatment of hymenoptera venom hypersensitivity: a meta-analysis. Clin Ther 2000;22:351 [PMID: 10963289].
Vetter RS et al: Mass envenomations by honey bees and wasps. West J Med 1999;170:223 [PMID: 10344177].
The petroleum distillates or other organic solvents used in these products are often as toxic as the insecticide itself.
1. Chlorinated Hydrocarbons (eg, Aldrin, Carbinol, Chlordane, DDT, Dieldrin, Endrin, Heptachlor, Lindane, Toxaphene)
Signs of intoxication include salivation, GI irritability, abdominal pain, vomiting, diarrhea, CNS depression, and convulsions. Inhalation exposure causes irritation of the eyes, nose, and throat; blurred vision; cough; and pulmonary edema.
Chlorinated hydrocarbons are absorbed through the skin, respiratory tract, and GI tract. Decontamination of skin with soap and evacuation of the stomach contents are critical. All contaminated clothing should be removed. Castor oil, milk, and other substances containing fats or oils should not be left in the stomach because they increase absorption of the chlorinated hydrocarbons. Convulsions should be treated with diazepam (0.1–0.3 mg/kg IV). Epinephrine should not be used because it may cause cardiac arrhythmias.
2. Organophosphate (Cholinesterase-Inhibiting) Insecticides (eg, Chlorothion, Co-Ral, DFP, Diazinon, Malathion, Paraoxon, Parathion, Phosdrin, TEPP, Thio-TEPP)
Dizziness, headache, blurred vision, miosis, tearing, salivation, nausea, vomiting, diarrhea, hyperglycemia, cyanosis, sense of constriction of the chest, dyspnea, sweating, weakness, muscular twitching, convulsions, loss of reflexes and sphincter control, and coma can occur.
The clinical findings are the result of cholinesterase inhibition, which causes an accumulation of acetylcholine. The onset of symptoms occurs within 12 hours of the exposure. Red cell cholinesterase levels should be measured as soon as possible. (Some normal individuals have a low serum cholinesterase level.) Normal values vary in different laboratories. In general, a decrease of red cell cholinesterase to below 25% of normal indicates significant exposure.
Repeated low-grade exposure may result in sudden, acute toxic reactions. This syndrome usually occurs after repeated household spraying rather than agricultural exposure.
Although all organophosphates act by inhibiting cholinesterase activity, they vary greatly in their toxicity. Parathion, for example, is 100 times more toxic than malathion. Toxicity is influenced by the specific compound, type of formulation (liquid or solid), vehicle, and route of absorption (lungs, skin, or GI tract).
Decontamination of skin, nails, hair, and clothing with soapy water is extremely important. Atropine plus a cholinesterase reactivator, pralidoxime, is an antidote for organophosphate insecticide poisoning. After assessment and management of the ABCs, atropine should be given and repeated every few minutes until airway secretions diminish. An appropriate starting dose of atropine is 2–4 mg IV in an adult and 0.05 mg/kg in a child. The patient should receive enough atropine to stop secretions (mydriasis in not an appropriate stopping point). Severe poisoning may require gram quantities of atropine administered over 24 hours.
Because atropine antagonizes the muscarinic parasympathetic effects of the organophosphates but does not affect the nicotinic receptor, it does not improve muscular weakness. Pralidoxime should also be given immediately in more severe cases and repeated every 6–12 hours as needed (25–50 mg/kg diluted to 5% and infused over 5–30 minutes at a rate of no more than 500 mg/min). Pralidoxime should be used in addition to—not in place of—atropine if red cell cholinesterase is less than 25% of normal. Pralidoxime is most useful within 48 hours after the exposure but has shown some effects 2–6 days later. Morphine, theophylline, aminophylline, succinylcholine, and tranquilizers of the reserpine and phenothiazine types are contraindicated. Hyperglycemia is common in severe poisonings.
3. Carbamates (eg, Carbaryl, Sevin, Zectran)
Carbamate insecticides are reversible inhibitors of cholinesterase. The signs and symptoms of intoxication are similar to those associated with organophosphate poisoning but are generally less severe. Atropine titrated to effect is sufficient treatment. Pralidoxime should not be used with carbaryl poisoning but is of value with other carbamates. In combined exposures to organophosphates, give atropine but reserve pralidoxime for cases in which the red cell cholinesterase is depressed below 25% of normal or marked effects of nicotinic receptor stimulation are present.
4. Botanical Insecticides (eg, Black Flag Bug Killer, Black Leaf CPR Insect Killer, Flit Aerosol House & Garden Insect Killer, French’s Flea Powder, Raid)
Allergic reactions, asthma-like symptoms, coma, and convulsions have been reported. Pyrethrins, allethrin, and rotenone do not commonly cause signs of toxicity. Antihistamines, short-acting barbiturates, and atropine are helpful as symptomatic treatment.
Eisenstein EM, Amitai Y: Index of suspicion: case 1. Organophosphate intoxication. Pediatr Rev 2000;21:205 [PMID: 10854316].
Roberts JR et al: Pesticide exposure in children. Pediatrics 2012;130(6):e1765– e1788 [PMID: 23184105].
Iron has many different formulations with varying amounts of elemental iron. Three common formulations include ferrous fumarate (33%), ferrous sulfate (20%), and ferrous gluconate (12%). Typically, doses of more than 20 mg/kg of elemental iron will cause symptoms. Five stages of intoxication may occur in iron poisoning: (1) Hemorrhagic gastroenteritis, which occurs 30–60 minutes after ingestion and may be associated with shock, acidosis, coagulation defects, and coma. This phase usually lasts 4–6 hours. (2) Phase of improvement, lasting 2–12 hours, during which patient looks better. (3) Delayed shock, which may occur 12–48 hours after ingestion. Metabolic acidosis, fever, leukocytosis, and coma may also be present. (4) Liver damage with hepatic failure. (5) Residual pyloric stenosis, which may develop about 4 weeks after the ingestion.
Once iron is absorbed from the GI tract, it is not normally eliminated in feces but may be partially excreted in the urine, giving it a red color prior to chelation. A reddish discoloration of the urine suggests a serum iron level greater than 350 mg/dL.
GI decontamination is based on clinical assessment. The patient should be referred to a healthcare facility if symptomatic or if the history indicates toxic amounts. Gastric lavage and whole bowel irrigation should be considered in potentially life-threatening overdoses.
Shock is treated in the usual manner. Sodium bicarbonate and Fleet Phospho-Soda left in the stomach to form the insoluble phosphate or carbonate have not shown clinical benefit and have caused lethal hypernatremia or hyperphosphatemia. Deferoxamine, a specific chelating agent for iron, is a useful adjunct in the treatment of severe iron poisoning. It forms a soluble complex that is excreted in the urine. It is contraindicated in patients with renal failure unless dialysis can be used. IV deferoxamine chelation therapy should be instituted if the patient has a metabolic acidosis, persistent symptoms and a serum iron determination cannot be obtained readily, or if the peak serum iron exceeds 400 mcg/dL (62.6 μmol/L) at 4–5 hours after ingestion.
Deferoxamine should not be delayed until serum iron levels are available in serious cases of poisoning. IV administration is indicated if the patient is in shock, in which case it should be given at a dosage of 15 mg/kg/h. Infusion rates up to 35 mg/kg/h have been used in life-threatening poisonings. Rapid IV administration can cause hypotension, facial flushing, urticaria, tachycardia, and shock. Deferoxamine, 90 mg/kg IM every 8 hours (maximum, 1 g), may be given if IV access cannot be established, but the procedure is painful. The indications for discontinuation of deferoxamine have not been clearly delineated. Generally, it can be stopped after 12–24 hours if the acidosis has resolved and the patient is improving. Use of deferoxamine for greater than 24 hours has been associated with ARDS.
Hemodialysis, peritoneal dialysis, or exchange transfusion can be used to increase the excretion of the dialyzable complex. Urine output should be monitored and urine sediment examined for evidence of renal tubular damage. Initial laboratory studies should include blood typing and cross-matching; total protein; serum iron, sodium, potassium, and chloride; Pco2; pH; and liver function tests. Serum iron levels fall rapidly even if deferoxamine is not given.
After the acute episode, liver function studies and an upper GI series are indicated to rule out residual damage.
Black J et al: Child abuse by intentional iron poisoning presenting as shock and persistent acidosis. Pediatrics 2003;111:197 [PMID: 12509576].
Juurlink DN et al: Iron poisoning in young children: association with the birth of a sibling. CMAJ 2003;165:1539 [PMID: 12796332].
Lead poisoning (plumbism) causes vague symptoms, including weakness, irritability, weight loss, vomiting, personality changes, ataxia, constipation, headache, and colicky abdominal pain. Late manifestations consist of retarded development, convulsions, and coma associated with increased intracranial pressure, which is a medical emergency.
Plumbism usually occurs insidiously in children younger than age 5 years. The most likely sources of lead include flaking leaded paint, artist’s paints, fruit tree sprays, solder, brass alloys, home-glazed pottery, and fumes from burning batteries. Only paint containing less than 1% lead is safe for interior use (eg, furniture, toys). Repetitive ingestions of small amounts of lead are far more serious than a single massive exposure. Toxic effects are likely to occur if more than 0.5 mg of lead per day is absorbed. In the US, lead levels continue to decline. Lead poisoning is more common abroad, so particular attention should be paid to immigrant and refugee populations or use of foreign remedies.
Blood lead levels are used to assess the severity of exposure. A complete blood count and serum ferritin concentration should be obtained; iron deficiency increases absorption of lead. Glycosuria, proteinuria, hematuria, and aminoaciduria occur frequently. Blood lead levels usually exceed 80 mcg/dL in symptomatic patients. Abnormal blood lead levels should be repeated in asymptomatic patients to rule out laboratory error. Specimens must be meticulously obtained in acid-washed containers. A normocytic, slightly hypochromic anemia with basophilic stippling of the red cells and reticulocytosis may be present in plumbism. Stippling of red blood cells is absent in cases involving only recent ingestion.
The cerebrospinal fluid (CSF) protein is elevated, and the white cell count usually is less than 100 cells/mL. CSF pressure may be elevated in patients with encephalopathy; lumbar punctures must be performed cautiously to prevent herniation.
Refer to the CDC guidelines for the most up to date recommendations on lead treatment. Succimer is an orally administered chelator approved for use in children and reported to be as efficacious as calcium edetate. Treatment for blood lead levels of 20–45 mcg/dL in children has not been determined. Succimer should be initiated at blood lead levels over 45 mcg/dL. The initial dose is 10 mg/kg (350 mg/m2) every 8 hours for 5 days. The same dose is then given every 12 hours for 14 days. At least 2 weeks should elapse between courses. Blood lead levels increase somewhat (ie, rebound) after discontinuation of therapy. Courses of dimercaprol (4 mg/kg per dose) and calcium edetate may still be used but are no longer the preferred method, except in cases of lead encephalopathy.
Encephalopathy associated with cerebral edema needs to be treated with standard measures. Anticonvulsants may be needed. A high-calcium, high-phosphorus diet and large doses of vitamin D may remove lead from the blood by depositing it in the bones. A public health team should evaluate the source of the lead. Necessary corrections should be completed before the child is returned home.
Jones RL et al: Trends in blood lead levels and blood lead testing among US children aged 1 to 5 years, 1988–2004. Pediatrics 2009;123(3):e376–e385 [PMID: 19254973].
Rogan WJ et al: Treatment of lead-exposed children trial group: the effect of chelation therapy with succimer on neuropsychological development in children exposed to lead. N Engl J Med 2001;344:1421 [PMID: 11346806].
Although not strictly toxic, small magnets have been found to cause bowel obstructions in children. Recent cases have resulted in warnings and a recall by the Consumer Product Safety Commission following intestinal perforation and death in a 20-month-old child. Obstruction may occur following ingestion of as few as two magnets. Radiographs should be obtained and surgical consultation may be indicated.
Alzahem AM et al: Ingested magnets and gastrointestinal complications. J Paediatr Child Health 2007:43:497 [PMID: 17535185].
Consumer Product Safety Commission: http://www.cpsc.gov/CPSCPUB/PREREL/prhtml07/07163.html 2007.
Toxic mushrooms are often difficult to distinguish from edible varieties. Contact a poison control center to obtain identification assistance. Symptoms vary with the species ingested, time of year, stage of maturity, quantity eaten, method of preparation, and interval since ingestion. The most common symptom is GI upset within a few hours of ingestion. A mushroom that is toxic to one individual may not be toxic to another. Drinking alcohol and eating certain mushrooms may cause a reaction similar to that seen with disulfiram and alcohol. Cooking destroys some toxins but not the deadly one produced by Amanita phalloides, which is responsible for 90% of deaths due to mushroom poisoning. Mushroom toxins are absorbed relatively slowly. Onset of symptoms within 2 hours of ingestion suggests muscarinic toxin, whereas a delay of symptoms for 6–48 hours after ingestion strongly suggests Amanita (amanitin) poisoning. Patients who have ingested A phalloides may relapse and die of hepatic or renal failure following initial improvement.
Mushroom poisoning may produce muscarinic symptoms (salivation, vomiting, diarrhea, cramping abdominal pain, tenesmus, miosis, and dyspnea), coma, convulsions, hallucinations, hemolysis, and delayed hepatic and renal failure.
Consideration should be given to administering activated charcoal. However, many mushrooms cause emesis and this may not be feasible. Supportive care with IV fluid resuscitation may be needed due to emesis and diarrhea. If the patient has muscarinic signs, give atropine, 0.05 mg/kg IM (0.02 mg/kg in toddlers), and repeat as needed (usually every 30 minutes) to keep the patient atropinized. Atropine, however, is used only when cholinergic effects are present and not for all mushrooms. Hypoglycemia is most likely to occur in patients with delayed onset of symptoms. Try to identify the mushroom if the patient is symptomatic. Consultation with a certified poison center is recommended. Local botanical gardens, university departments of botany, and societies of mycologists may be able to help. Supportive care is usually all that is needed; however, in the case of A phalloides, penicillin, silibinin, or hemodialysis may be indicated.
Lampe KF, McCann MA: Differential diagnosis of poisoning by North American mushrooms, with particular emphasis on Amanita phalloides-like intoxication. Ann Emerg Med 1987;16:956 [PMID: 3631682].
Pawlowska J et al: Liver transplantation in three family members after Amanita phalloides mushroom poisoning. Transplant Proc 2002;34:3313 [PMID: 12493457].
NITRITES, NITRATES, ANILINE, PENTACHLOROPHENOL, & DINITROPHENOL
Nausea, vertigo, vomiting, cyanosis (methemoglobinemia), cramping, abdominal pain, tachycardia, cardiovascular collapse, tachypnea, coma, shock, convulsions, and death are possible manifestations of nitrite or nitrate poisoning.
Nitrite and nitrate compounds found in the home include amyl nitrite, butyl nitrates, isobutyl nitrates, nitroglycerin, pentaerythritol tetranitrate, sodium nitrite, nitrobenzene, and phenazopyridine. Pentachlorophenol and dinitrophenol, which are found in wood preservatives, produce methemoglobinemia and high fever because of uncoupling of oxidative phosphorylation. Headache, dizziness, and bradycardia have been reported. High concentrations of nitrites in well water or spinach have been the most common cause of nitrite-induced methemoglobinemia. Symptoms do not usually occur until 15%–50% of the hemoglobin has been converted to methemoglobin. A rapid test is to compare a drop of normal blood with the patient’s blood on a dry filter paper. Brown discoloration of the patient’s blood indicates a methemoglobin level of more than 15%.
In the setting of a recent ingestion, consider administering activated charcoal if the patient is awake and alert. Decontaminate affected skin with soap and water. Oxygen and artificial respiration may be needed. If the blood methemoglobin level exceeds 30%, or if levels cannot be obtained and the patient is symptomatic, give a 1% solution of methylene blue (0.2 mL/kg IV) over 5–10 minutes. Avoid perivascular infiltration, because it causes necrosis of the skin and subcutaneous tissues. A dramatic change in the degree of cyanosis should occur. Transfusion is occasionally necessary. Epinephrine and other vasoconstrictors are contraindicated. If reflex bradycardia occurs, atropine should be used.
Kennedy N et al: Faulty sausage production causing methaemoglobinaemia. Arch Dis Child 1997;76:367 [PMID: 9166036].
OPIOIDS & OPIATES
Opioid and opiate-related medical problems may include drug addiction, withdrawal in a newborn infant, and accidental overdoses. They can vary in onset of action and duration of action. Opioids, including heroin, methadone, morphine, and codeine are routinely detected on most urine drug assays. However, many of the more commonly used oral opiates, such as oxycodone, hydrocodone, buprenorphine are not detected on standard urine drug assays. Care should be directed on clinical suspicion of ingestion.
Narcotic-addicted adolescents often have other medical problems, including cellulitis, abscesses, thrombophlebitis, tetanus, infective endocarditis, human immunodeficiency virus (HIV) infection, tuberculosis, hepatitis, malaria, foreign body emboli, thrombosis of pulmonary arterioles, diabetes mellitus, obstetric complications, nephropathy, and peptic ulcer.
Opioids and opiates can cause respiratory depression, stridor, coma, increased oropharyngeal secretions, sinus bradycardia, and urinary retention. Pulmonary edema rarely occurs in children but has been reported; deaths usually result from aspiration of gastric contents, respiratory arrest, and cerebral edema. Convulsions may occur with propoxyphene overdosage.
The indication for the administration of naloxone is respiratory depression. Although suggested doses for naloxone hydrochloride range from 0.01 to 0.1 mg/kg, it is generally unnecessary to calculate the dosage on this basis. This extremely safe antidote should be given in sufficient quantity to reverse opioid-binding sites. Doses as low as 0.04 mg have been affective for reversal. For children younger than age 1 year, one ampoule (0.4 mg) should be given initially; if there is no response, five more ampoules (2 mg) should be given rapidly. Older children should be given 0.4–0.8 mg, followed by 2–4 mg if there is no response. An improvement in respiratory status may be followed by respiratory depression, because the antagonist’s duration of action is less than 1 hour. Neonates poisoned in utero may require 10–30 mg/kg to reverse the effect. Naloxone infusion can be used for persistent symptoms. Depending on the formulation, some exposures may need to be observed for 24 hours due to the duration of effect.
B. Withdrawal in the Addict
Diazepam (10 mg every 6 hours PO), and antiemetics has been recommended for the treatment of mild narcotic withdrawal in ambulatory adolescents. Management of withdrawal in the confirmed addict may be accomplished with the administration of clonidine, by substitution with methadone or buprenorphine, or with reintroduction of the original addicting agent, if available through a supervised drug withdrawal program. A tapered course over 3 weeks will accomplish this goal. Death rarely, if ever, occurs. The abrupt discontinuation of narcotics (cold turkey method) is not recommended and may cause severe physical withdrawal signs.
C. Withdrawal in the Newborn
A newborn infant in opioid withdrawal is usually small for gestational age and demonstrates yawning, sneezing, decreased Moro reflex, hunger but uncoordinated sucking action, jitteriness, tremor, constant movement, a shrill protracted cry, increased tendon reflexes, convulsions, vomiting, fever, watery diarrhea, cyanosis, dehydration, vasomotor instability, seizure, and collapse.
The onset of symptoms commonly begins in the first 48 hours but may be delayed as long as 8 days, depending on the timing of the mother’s last fix and her predelivery medication. The diagnosis can be confirmed easily by identifying the narcotic in the urine of the mother and the newborn.
Several treatment methods have been suggested for narcotic withdrawal in the newborn. Phenobarbital (8 mg/kg/d IM or PO in four doses for 4 days and then reduced by one-third every 2 days as signs decrease) may be continued for as long as 3 weeks. Methadone may be necessary in those infants with congenital methadone addiction who are not controlled in their withdrawal by large doses of phenobarbital. Dosage should be 0.5 mg/kg/d in two divided doses but can be increased gradually as needed. After control of the symptoms is achieved, the dose may be tapered over 4 weeks.
It is unclear whether prophylactic treatment with these drugs decreases the complication rate. The mortality rate of untreated narcotic withdrawal in the newborn may be as high as 45%.
Bailey JE, Campagna E, Dart RC: The underrecognized toll of prescription opioid abuse on young children. Ann Emerg Med 2009;53:419–424 [PMID: 18774623].
Geib AJ et al: Adverse effects in children after unintentional buprenorphine exposure. Pediatrics 2006;118(4):1746–1751 [PMID: 17015570].
ORAL HYPOGLYCEMICS (SULFONYLUREAS, METFORMIN)
Noninsulin hypoglycemic and antidiabetic medications include α-glucosidase inhibitors biguanides, gliptins, meglitinides, sulfonylureas, and thiazolidinediones. They are all used to treat hyperglycemia in diabetics. Sulfonylureas (acetohexamide, glipizide, glyburide) are the only oral hypoglycemic that actively secretes endogenous insulin and can cause hypoglycemia. The meglitinides (nateglinide, repaglinide) have scarce reports of hypoglycemia. Biguanides can rarely cause lactic acidosis in acute large overdose or in renal failure. Hypoglycemic symptoms are variable but can include altered mental status, diaphoresis, seizures, or coma.
Children with possible exposures to sulfonylureas should be admitted for 24 hours. Mainstay of treatment is treating hypoglycemia. If patient is awake and alert, with minimal symptoms, PO glucose can be given. With more severe hypoglycemia or symptomatic, immediate treatment with 0.5–1 g/kg IV dextrose bolus should be administered. With repeated episodes of hypoglycemia, once euglycemia is achieved, octreotide should be considered at 1 mcg/kg SC/IV every 6 hours as needed for hypoglycemia. Metformin toxicity should be treated supportively, hemodialysis may be needed for severe acid-base abnormalities or patients with renal failure.
Glatstein M, Scolnik D, Betur Y: Octreotide for the treatment of sulfonylurea poisoning. Clin Toxicol (Phila) 2012;50(9):795–804 [PMID: 23046209].
Lung DD, Olson KR: Hypoglycemia in pediatric sulfonylurea poisoning: an 8-year poison center retrospective study. Pediatrics 2011;127(6):e1558–e1564 [PMID: 21606145].
ANTIPSYCHOTICS (TYPICAL & ATYPICAL)
Typical antipsychotics include butyrophenones (droperidol, haloperidol), and the phenothiazines (promethazine, chlorpromazine, thioridazine). Atypical antipsychotics include benzapines (clozapine, olanzapine, quetiapine) and indoles (risperidone, ziprasidone).
A. Extrapyramidal Crisis
Episodes characterized by torticollis, stiffening of the body, spasticity, poor speech, catatonia, and inability to communicate although conscious are typical manifestations. These episodes usually last a few seconds to a few minutes but have rarely caused death. Extrapyramidal crises may represent idiosyncratic reactions and are aggravated by dehydration. The signs and symptoms occur most often in children who have received prochlorperazine. They are commonly mistaken for psychotic episodes. These extrapyramidal symptoms are more common with typical antipsychotics (butyrophenones, phenothiazines).
Lethargy and deep prolonged coma are the most common symptoms seen in toxicity. Of the typical antipsychotics, promazine, chlorpromazine, and prochlorperazine are the drugs most likely to cause respiratory depression and precipitous drops in blood pressure. Risperidone and quetiapine are atypical antipsychotics that can cause CNS depression. Clozapine, olanzapine, and quetiapine most commonly cause hypotension and also antimuscarinic symptoms. QTc prolongation can occur, most commonly with thioridazine and ziprasidone. Occasionally, paradoxic hyperactivity and extrapyramidal signs as well as hyperglycemia and acetonemia are present. Seizures are uncommon.
C. Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome is a rare idiosyncratic complication that may be lethal. It is a syndrome involving mental status change (confusion, coma), motor abnormalities (lead pipe rigidity, clonus), and autonomic dysfunction (tachycardia, hyperpyrexia). Typically it occurs 1–2 weeks after starting therapy, and can occur at therapeutic doses.
Extrapyramidal signs are alleviated within minutes by the slow IV administration of diphenhydramine, 1–2 mg/kg (maximum, 50 mg), or benztropine mesylate, 1–2 mg IV (1 mg/min). No other treatment is usually indicated.
Patients with overdoses should receive conservative supportive care. Hypotension may be treated with standard agents, starting with isotonic saline administration. Agitation is best treated with benzodiazepines. Neuroleptic malignant syndrome is treated by discontinuing the drug, and treating hyperthermia and agitation aggressively with benzodiazepines and sedation. In refractory cases, bromocriptine can be considered, although the evidence for its use is not clear
Levine M, Ruha AM: Overdose of atypical antipsychotics: clinical presentation, mechanisms of toxicity and management. CNS Drugs 2012;26(7):601–611 [PMID: 22668123].
Minns AB, Clark RG: Toxicology and overdose of atypical antipsychotics. J Emerg Med 2012;43(5):906–913 [PMID: 22555052].
Many common ornamental, garden, and wild plants are potentially toxic. Only in a few cases will small amounts of a plant cause severe illness or death. Table 13–5 lists the most toxic plants, symptoms and signs of poisoning, and treatment. Contact your poison control center for assistance with identification.
Table 13–5. Poisoning due to plants.a
Psychotropic drugs consist of four general classes: stimulants (amphetamines, cocaine), depressants (eg, narcotics, barbiturates), antidepressants and tranquilizers, and hallucinogens (eg, lysergic acid diethylamide [LSD], phencyclidine [PCP]).
The following clinical findings are commonly seen in patients abusing drugs. See also other entries discussed in alphabetic order in this chapter.
Agitation, euphoria, grandiose feelings, tachycardia, fever, abdominal cramps, visual and auditory hallucinations, mydriasis, coma, convulsions, and respiratory depression.
Emotional lability, ataxia, diplopia, nystagmus, vertigo, poor accommodation, respiratory depression, coma, apnea, and convulsions. Dilation of conjunctival blood vessels suggests marijuana ingestion. Narcotics cause miotic pupils and, occasionally, pulmonary edema.
C. Antidepressants and Tranquilizers
Hypotension, lethargy, respiratory depression, coma, and extrapyramidal reactions.
D. Hallucinogens and Psychoactive Drugs
Belladonna alkaloids cause mydriasis, dry mouth, nausea, vomiting, urinary retention, confusion, disorientation, paranoiddelusions, hallucinations, fever, hypotension, aggressive behavior, convulsions, and coma. Psychoactive drugs such as LSD cause mydriasis, unexplained bizarre behavior, hallucinations, and generalized undifferentiated psychotic behavior.
Only a small percentage of the persons using drugs come to the attention of physicians; those who do are usually experiencing adverse reactions such as panic states, drug psychoses, homicidal or suicidal thoughts, or respiratory depression.
Even with cooperative patients, an accurate history is difficult to obtain. A drug history is most easily obtained in a quiet spot by a gentle, nonthreatening, honest examiner, and without the parents present. The user often does not really know what drug has been taken or how much. Street drugs are almost always adulterated with one or more other compounds. Multiple drugs are often taken together. Friends may be a useful source of information.
The patient’s general appearance, skin, lymphatics, cardiorespiratory status, GI tract, and CNS should be focused on during the physical examination, because they often provide clues suggesting drug abuse.
Hallucinogens are not life-threatening unless the patient is frankly homicidal or suicidal. A specific diagnosis is usually not necessary for management; instead, the presenting signs and symptoms are treated. Does the patient appear intoxicated? In withdrawal? “Flashing back?” Is some illness or injury (eg, head trauma) being masked by a drug effect? (Remember that a known drug user may still have hallucinations from meningoencephalitis.)
The signs and symptoms in a given patient are a function not only of the drug and the dose but also of the level of acquired tolerance, the “setting,” the patient’s physical condition and personality traits, the potentiating effects of other drugs, and many other factors.
A common drug problem is the “bad trip,” which is usually a panic reaction. This is best managed by “talking the patient down” and minimizing auditory and visual stimuli. Allowing the patient to sit with a friend while the drug effect dissipates may be the best treatment. This may take several hours. The physician’s job is not to terminate the drug effect but to help the patient through the bad experience.
Drug therapy is often unnecessary and may complicate the clinical course of a drug-related panic reaction.
Although phenothiazines have been commonly used to treat bad trips, they should be avoided if the specific drug is unknown, because they may enhance toxicity or produce unwanted side effects. Benzodiazepines are the drug of choice if a sedative effect is required. Physical restraints are rarely indicated and usually increase the patient’s panic reaction.
For treatment of life-threatening drug abuse, consult the section on the specific drug elsewhere in this chapter and the section on general management at the beginning of the chapter.
After the acute episode, the physician must decide whether psychiatric referral is indicated; in general, patients who have made suicidal gestures or attempts and adolescents who are not communicating with their families should be referred.
Rosenbaum CD et al. J Med Toxicol 2012 Mar;8(1):15–32 [PMID 22271566].
The use of childproof containers and publicity regarding accidental poisoning have reduced the incidence of acute salicylate poisoning. Nevertheless, serious intoxication still occurs and must be regarded as an emergency. In recent years, the frequency of poisoning has begun to rise again.
Salicylates uncouple oxidative phosphorylation, leading to increased heat production, excessive sweating, and dehydration. They also interfere with glucose metabolism and may cause hypo- or hyperglycemia. Respiratory center stimulation occurs early.
Patients usually have signs of hyperventilation, sweating, dehydration, and fever. Vomiting and diarrhea sometimes occur. In severe cases, disorientation, convulsions, and coma may develop.
The severity of acute intoxication can, in some measure, be judged by serum salicylate levels. High levels are always dangerous irrespective of clinical signs, and low levels may be misleading in chronic cases. Other laboratory values usually indicate metabolic acidosis despite hyperventilation, low serum K+ values, and often abnormal serum glucose levels.
In mild and moderate poisoning, stimulation of the respiratory center produces respiratory alkalosis and may complain of tinnitus or hearing loss. In severe intoxication (occurring in severe acute ingestion with high salicylate levels and in chronic toxicity with lower levels), respiratory response is unable to overcome the metabolic overdose.
Once the urine becomes acidic, progressively smaller amounts of salicylate are excreted. Until this process is reversed, the half-life will remain prolonged, because metabolism contributes little to the removal of salicylate.
Chronic severe poisoning may occur as early as 3 days after a regimen of salicylate is begun. Findings usually include vomiting, diarrhea, and dehydration.
Charcoal binds salicylates well and should be given for acute ingestions. Mild poisoning may require only the administration of oral fluids and confirmation that the salicylate level is falling. Moderate poisoning involves moderate dehydration and depletion of potassium. Fluids must be administered at a rate of 2–3 mL/kg/h to correct dehydration and produce urine with a pH of greater than 7.0. Initial IV solutions should be isotonic, with sodium bicarbonate constituting half the electrolyte content. Once the patient is rehydrated, the solution can contain more free water and approximately 40 mEq/L of K+.
Severe toxicity is marked by major dehydration. Symptoms may be confused with those of Reye syndrome, encephalopathy, and metabolic acidosis. Salicylate levels may even be in the therapeutic range. Major fluid correction of dehydration is required. Once this has been accomplished, hypokalemia must be corrected and sodium bicarbonate given. Usual requirements are sodium bicarbonate, 1–2 mEq/kg/h over the first 6–8 hours, and K+, 20–40 mEq/L. A urine flow of 2–3 mL/kg/h should be established. Despite this treatment, some patients will develop the paradoxical aciduria of salicylism. This is due to hypokalemia and the saving of K+ and excretion of H+ in the renal tubule. Correction of K+ will allow the urine to become alkaline and ionize the salicylate, resulting in excretion rather than reabsorption of nonionized salicylate in acid urine.
Renal failure or pulmonary edema is an indication for dialysis. Hemodialysis is most effective and peritoneal dialysis is relatively ineffective. Hemodialysis should be used in all patients with altered mental status or deteriorating clinical status. Acetazolamide should not be used.
Yip L et al: Concepts and controversies in salicylate toxicity. Emerg Med Clin North Am 1994;12:351 [PMID: 8187688].
Scorpion stings are common in arid areas of the southwestern United States. Scorpion venom is more toxic than most snake venoms, but only minute amounts are injected. Although neurologic manifestations may last a week, most clinical signs subside within 24–48 hours.
The most common scorpions in the United States are Vejovis, Hadrurus, Androctonus, and Centruroides species. Stings by the first three produce edema and pain. Stings by Centruroides (the Bark scorpion) cause tingling or burning paresthesias that begin at the site of the sting; other findings include hypersalivation, restlessness, muscular fasciculation, abdominal cramps, opisthotonos, convulsions, urinary incontinence, and respiratory failure.
Sedation with benzodiazepines is the primary therapy. Antivenom is reserved for severe poisoning. In severe cases, the airway may become compromised by secretions and weakness of respiratory muscles. Endotracheal intubation may be required. Patients may require treatment for seizures, hypertension, or tachycardia.
The prognosis is good as long as the patient’s airway is managed appropriately and sedation is achieved.
Boyer LV et al: Antivenom for critically ill children with neurotoxicity from scorpion stings. N Engl J Med 2009;360:2090–2098 [PMID: 19439743].
SEROTONIN REUPTAKE INHIBITORS
Fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and many other agents comprise this class of drugs. Adverse effects in therapeutic dosing include suicidal thoughts, aggressive behavior, extrapyramidal effects, and cardiac dysrhythmias, and in overdose may include vomiting, lethargy, seizures, hypertension, tachycardia, hyperthermia, and abdominal pain. The findings in overdose are included in the serotonin syndrome due to the action of these drugs, which results in an increase of serotonin (5-hydroxytryptamine [5-HT]). Despite the degree of toxicity these agents generally are not life-threatening and intervention usually is not necessary.
Emptying the stomach is not helpful, but activated charcoal may be useful. Laboratory measurements of the drugs are not of benefit other than to establish their presence.
Treatment with benzodiazepines is most beneficial. Hypotension may be treated with fluids or norepinephrine. Cyproheptadine is an antagonist of serotonin, but its use has been limited. A dose of 0.25 mg/kg/d divided every 6 hours to a maximum of 12 mg/d may be useful in treating the serotonin syndrome. Adults and older adolescents have been treated with 12 mg initially followed by 2 mg every 2 hours to a maximum of 32 mg/d.
Boyer EW, Shannon M: The serotonin syndrome. N Engl J Med 2005;352:1112 [PMID: 15784664].
Despite the lethal potential of venomous snakes, human morbidity and mortality rates are surprisingly low. The outcome depends on the size of the child, the site of the bite, the degree of envenomation, the type of snake, and the effectiveness of treatment.
Nearly all poisonous snakebites in the United States are caused by pit vipers (rattlesnakes, water moccasins, and copperheads). A few are caused by elapids (coral snakes), and occasional bites occur from cobras and other nonindigenous exotic snakes kept as pets. Snake venom is a complex mixture of enzymes, peptides, and proteins that may have predominantly cytotoxic, neurotoxic, hemotoxic, or cardiotoxic effects but other effects as well. Up to 25% of bites by pit vipers do not result in venom injection. Pit viper venom causes predominantly local injury with pain, discoloration, edema, and hemorrhage.
Swelling and pain occur soon after rattlesnake bite and are a certain indication that envenomation has occurred. During the first few hours, swelling and ecchymosis extend proximally from the bite. The bite is often obvious as a double puncture mark surrounded by ecchymosis. Hematemesis, melena, hemoptysis, and other manifestations of coagulopathy develop in severe cases. Respiratory difficulty and shock are the ultimate causes of death. Even in fatal rattlesnake bites, a period of 6–8 hours usually elapses between the bite and death; as a result, there is usually enough time to start effective treatment.
Coral snake envenomation causes little local pain, swelling, or necrosis, and systemic reactions are often delayed. The signs of coral snake envenomation include bulbar paralysis, dysphagia, and dysphoria; these signs may appear in 5–10 hours and may be followed by total peripheral paralysis and death in 24 hours.
Children in snake-infested areas should wear boots and long trousers, should not walk barefoot, and should be cautioned not to explore under ledges or in holes.
A. Emergency (First-Aid) Treatment
The most important first-aid measure is transportation to a medical facility. Splint the affected extremity and minimize the patient’s motion. Tourniquets and ice packs are contraindicated. Incision and suction are not useful for either crotalid or elapid snake bite.
B. Definitive Medical Management
Blood should be drawn for hematocrit, clotting time and platelet function, and serum electrolyte determinations. Establish two secure IV sites for the administration of antivenom and other medications.
Specific antivenom is indicated when signs of progressive envenomation are present. Two antivenoms are available for treating pit viper envenomation: polyvalent pit viper antivenom and polyvalent Crotalidae Fab (CroFab). Both are effective, but their indications differ. For coral snake bites, an eastern coral snake antivenom (Wyeth Laboratories) is available. Patients with pit viper bites should receive antivenom if progressive local injury, coagulopathy, or systemic signs (eg, hypotension, confusion) are present. (Antivenom should not be given IM or SQ.) See package labeling or call your certified poison center for details of use. Hemorrhage, pain, and shock diminish rapidly with adequate amounts of antivenom. For coral snake bites, give three to five vials of antivenom in 250–500 mL of isotonic saline solution. An additional three to five vials may be required. While generally considered best if administered within the first 6 hours, recent evidence demonstrates that delayed use may be therapeutic.
Administer an opioid or opiate to control pain. Cryotherapy is contraindicated because it commonly causes additional tissue damage. Early physiotherapy minimizes contractures. In rare cases, fasciotomy to relieve pressure within muscular compartments is required. The evaluation of function and of pulses will better predict the need for fasciotomy. Antihistamines and corticosteroids (hydrocortisone, 1 mg/kg, given PO for a week) are useful in the treatment of serum sickness or anaphylactic shock. Antibiotics are not needed unless clinical signs of infection occur. Tetanus status should be evaluated and the patient immunized, if needed.
Bebarta V, Dart RC: Effectiveness of delayed use of crotalidae polyvalent immune FAB (ovine) antivenoms. J Toxicol Clin Toxicol 2004;42:321–324 [PMID: 15362603].
Dart RC, McNally J: Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med 2001;37:181 [PMID: 11174237].
Offerman SR et al: Crotaline Fab antivenom for the treatment of children with rattle snake envenomation. Pediatrics 2002;110:968 [PMID: 12415038].
SOAPS & DETERGENTS
Soap is made from salts of fatty acids. Some toilet soap bars contain both soap and detergent. Ingestion of soap bars may cause vomiting and diarrhea, but they have a low toxicity. Induced emesis is unnecessary.
Detergents are nonsoap synthetic products used for cleaning purposes because of their surfactant properties. Commercial products include granules, powders, and liquids. Dishwasher detergents are very alkaline and can cause caustic burns. Low concentrations of bleaching and antibacterial agents as well as enzymes are found in many preparations. The pure compounds are moderately toxic, but the concentration used is too small to alter the product’s toxicity significantly, although occasional primary or allergic irritative phenomena have been noted in persons who frequently use such products and in employees manufacturing these products. Unit dose detergents, or packets, have become popular and have packaging attractive to young children. They are usually a mix of glycol ethers, ethyl alcohol and surfactant. They can cause CNS depression and respiratory distress if ingested.
A. Cationic Detergents (Ceepryn, Diaparene Cream, Phemerol, Zephiran)
Cationic detergents in dilute solutions (0.5%) cause mucosal irritation, but higher concentrations (10%–15%) may cause caustic burns to mucosa. Clinical effects include nausea, vomiting, collapse, coma, and convulsions. As little as 2.25 g of some cationic agents have caused death in an adult. In four cases, 100–400 mg/kg of benzalkonium chloride caused death. Cationic detergents are rapidly inactivated by tissues and ordinary soap.
Because of the caustic potential and rapid onset of seizures, emesis is not recommended. Activated charcoal should be administered. Anticonvulsants may be needed.
B. Anionic Detergents
Most common household detergents are anionic. Laundry compounds have water softener (sodium phosphate) added, which is a strong irritant and may reduce ionized calcium. Anionic detergents irritate the skin by removing natural oils. Although ingestion causes diarrhea, intestinal distention, and vomiting, no fatalities have been reported.
The only treatment usually required is to discontinue use if skin irritation occurs and replace fluids and electrolytes. Induced vomiting is not indicated following ingestion of automatic dishwasher detergent, because of its alkalinity. Dilute with water or milk.
C. Nonionic Detergents (Brij Products; Tritons X-45, X-100, X-102, and X-144)
These compounds include lauryl, stearyl, and oleyl alcohols and octyl phenol. They have a minimal irritating effect on the skin and are almost always nontoxic when swallowed.
Centers for Disease Control and Prevention (CDC): Health hazards associated with laundry detergent pods—United States. May–June 2012. MMWR Morb Mortal Wkly Rep. 2012;61(41):825–829 [PMID: 23076090].
Perry HE. Pediatric poisonings from household products: hydrofluoric acid and methacrylic acid. Curr Opin Pediatr 2011;13(2):157–161 [PMID: 11317059].
Most medically important bites in the United States are caused by the black widow spider (Latrodectus mactans) and the North American brown recluse (violin) spider (Loxosceles reclusa). Positive identification of the spider is helpful, because many spider bites may mimic those of the brown recluse spider.
1. Black Widow Spider
The black widow spider is endemic to nearly all areas of the United States. The initial bite causes sharp fleeting pain that spreads centripetally. Local and systemic muscular cramping, abdominal pain, nausea and vomiting, and shock can occur. Convulsions occur more commonly in small children than in older children. Systemic signs of black widow spider bite may be confused with other causes of acute abdomen. Although paresthesias, nervousness, and transient muscle spasms may persist for weeks in survivors, recovery from the acute phase is generally complete within 3 days. In contrast to popular opinion, death is extremely rare.
Initial pain control should be achieved with use of benzodiazepines and opioids or opiates. Antivenom is effective, but supplies are limited, and should be reserved for severe cases in which the previously mentioned therapies have failed. Local treatment of the bite is not helpful
2. Brown Recluse Spider (Violin Spider)
The North American brown recluse spider is most commonly seen in the central and Midwestern areas of the United States. Its bite characteristically produces a localized reaction with progressively severe pain within 24 hours. The initial bleb on an erythematous ischemic base is replaced by a black eschar within 1 week. This eschar separates in 2–5 weeks, leaving an ulcer that heals slowly. Systemic signs include cyanosis, morbilliform rash, fever, chills, malaise, weakness, nausea and vomiting, joint pains, hemolytic reactions with hemoglobinuria, jaundice, and delirium. Fatalities are rare. Fatal disseminated intravascular coagulation has been reported.
Although of unproved efficacy, the following therapies have been used: dexamethasone, 4 mg IV four times a day, during the acute phase; polymorphonuclear leukocyte inhibitors, such as dapsone or colchicine. Supportive wound care is recommended, with possible reconstruction/debridement.
Clark RF et al: Clinical presentation and treatment of black widow spider envenomation: a review of 163 cases. Ann Emerg Med 1992;21:782 [PMID: 1351707].
Sams HH et al: Nineteen documented cases of Loxosceles reclusa envenomation. J Am Acad Dermatol 2001;44:603 [PMID: 11260528].
THYROID PREPARATIONS (THYROID DESICCATED, SODIUM LEVOTHYROXINE)
Ingestion of the equivalent of 50–150 g of desiccated thyroid can cause signs of hyperthyroidism, including irritability, mydriasis, hyperpyrexia, tachycardia, and diarrhea. Maximal clinical effect occurs about 9 days after ingestion—several days after the protein-bound iodine level has fallen dramatically.
Administer activated charcoal. If the patient develops clinical signs of toxicity, propranolol, 0.01–0.1 mg/kg (maximum, 1 mg), is useful because of its antiadrenergic activity.
Brown RS et al: Successful treatment of massive acute thyroid hormone poisoning with iopanoic acid. J Pediatr 1998;132:903 [PMID: 9602214].
Accidental ingestion of excessive amounts of vitamins rarely causes significant problems. Vary rare cases of hypervitaminosis A do occur, however, particularly in patients with poor hepatic or renal function. Hypervitaminosis A can result in increased intracranial pressure, ocular toxicity, and hepatotoxicity. However, chronic doses more than 50,000–100,000 IU are required for toxicity. The fluoride contained in many multivitamin preparations is not a realistic hazard, because a 2- or 3-year-old child could eat 100 tablets, containing 1 mg of sodium fluoride per tablet, without experiencing serious symptoms. Iron poisoning has been reported with multivitamin tablets containing iron. Pyridoxine abuse has caused neuropathies; nicotinic acid can result in flushing, and rarely hypotension and hepatotoxicity. Most gummy vitamins do not contain iron.
Dean BS, Krenzelok EP: Multiple vitamins and vitamins with iron: accidental poisoning in children. Vet Hum Toxicol 1988;30:23 [PMID: 3354178].
Lab HS et al: Risk of vitamin A toxicity from candy-like chewable vitamin supplements for children. Pediatrics 2006;118(2):820–824 [PMID: 16882846].
WARFARIN (COUMADIN) AND OTHER ORAL ANTICOAGULANTS
Warfarin is used as a rodenticide. It causes hypoprothrombinemia and capillary injury. It is absorbed readily from the GI tract but is absorbed poorly through the skin. A dose of 0.5 mg/kg of warfarin may be toxic in a child. A prothrombin time is helpful in establishing the severity of the poisoning. Newer oral anticoagulants have been developed that have direct inhibition to specific clotting factors. Examples include dabigatran and rivaroxaban. Toxic dose has not been established, but bleeding complications can occur at therapeutic doses. Thrombin clotting time and activated partial thromboplastin time can provide information on anticoagulant activity.
If bleeding occurs or the prothrombin time is prolonged, give 1–5 mg of vitamin K1 (phytonadione) IM or SQ. For large ingestions with established toxicity, 0.6 mg/kg may be given. No clear therapy is available for the newer direct factor inhibitors. Therapy has been focused on using fresh frozen plasma, prothrombin complex concentrate, and activated factor.
Another group of long-acting anticoagulant rodenticides (brodifacoum, difenacoum, bromadiolone, diphacinone, pinene, valone, and coumatetralyl) has been a more serious toxicologic problem than warfarin. They also cause hypoprothrombinemia and a bleeding diathesis that responds to phytonadione, although the anticoagulant activity may persist for periods ranging from 6 weeks to several months. However, most unintentional ingestions can be watched at home without further evaluation. If there are concerns for large ingestions, a prothrombin time at 48 hours can determine extent of toxicity. Treatment with vitamin K1 may be needed for weeks, at high doses.
Eerenberg ES et al: Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2012;125(16):1573–1579 [PMID: 21900088].
Gunja N, Coggins A, Bidny S: Management of intentional superwarfarin poisoning with long-term vitamin K and brodifacoum levels. Clin Toxicol (Phila) 2011;49(5):385–390 [PMID: 21740137].
Shepherd G, Klein-Schwartz W, Anderson BD: Acute, unintentional pediatric brodifacoum ingestions. Pediatr Emerg Care 2002;19(3):174–178 [PMID: 12066002].