Pediatric Toxicology: Part 1

     Although pediatric exposure to toxic substances has undergone a significant decline since the 1960s, it remains a common emergency in children in the United States. Ingestions account for a small but significant number of emergency department visits. This three-part series will discuss epidemiology and treatment principles, plus review common exposure medications and their ensuing effects.

     The most common unintentional ingestion that occurs in the home in children under the age of 6 is of toxic substances. Common contributors of accidental ingestions include improper storage of medications, poor supervision or distracted caretakers. Most episodes have a favorable outcome, as the ingestion is generally secondary to curiosity and does not involve large amounts of toxic substances. However, toxicological emergencies continue to be a significant, yet preventable, cause of morbidity and mortality. One particularly dangerous situation occurs with ingestion of sustained-release medications that can have prolonged and deleterious effects on children. EMS personnel must recognize and be prepared for those situations, which can cause rapid deterioration, serious illness or death.

EPIDEMIOLOGY
     In 2006, more than 2.4 million exposures to toxic agents in the general population were reported to poison control centers, although it is estimated there were many more unreported exposures. Fifty-one percent of total exposures—1.2 million—occurred in children under age 6 (see Table I). In this age group, the most common exposures were to cosmetics and personal products (see Table II).

     The peak incidence in all children occurs between ages 1–3, which accounts for 38% of the total exposures. This is due to developmental milestones, such as increased mobility, curiosity and oral exploration, as well as the attraction to brightly colored objects. There is a male predominance for ingestion in children younger than 13, and a female predominance in teenagers and adults.

     Most toxic exposures in 2006 were unintentional, accounting for just over 2 million (83%) episodes, while intentional ingestions accounted for just over 300,000 cases (13%). The majority of exposures in children under age 13 were unintentional; the majority of exposures in 13–19-year- olds were intentional.

     Of the reported exposures, there were 1,200 fatalities, of which 673 (55%) involved two or more toxic agents. Although children under 6 years accounted for most of the exposures, there were only 29 fatalities in this age group; there were no fatalities from intentional exposure in children under age 13 (see Table III). Toxic substances associated with the largest number of fatalities included sedatives, hypnotics, antipsychotics, opioids and cardiac medications.

GENERAL PRINCIPLES
     Most ingestions in the pediatric population require only supportive care. The clinical condition of the patient dictates care; the goal of treatment is to treat the patient, not the poison. Only a few toxic agents have specific antidotes, and many of these are not available in the prehospital setting. Specific antidotes should not be given blindly in an unknown overdose, as several of these can have toxic side effects if they are not indicated. For example, administering sodium bicarbonate, glucophage or calcium when not indicated can cause metabolic alkalosis, hyperglycemia and hypercalcemia, respectively. Supportive care and determining the ingested substance must always precede the administration of specific antidotes.

INITIAL CARE
     Immediately identify and correct any life threats. Because of their high metabolic demands and decreased respiratory reserves, pediatric patients are highly susceptible to hypoxia secondary to toxic exposures, especially those involving inhaled fumes. Correct existing hypoxia or respiratory disorders by providing ventilations and supplemental oxygen as needed. Provide cardiovascular support as needed by addressing existing issues such as hypovolemia and hypotension. Because of decreased glycogen stores, hypoglycemia is a common effect of many toxins in children. Many substances, such as ethanol, generally do not cause hypoglycemia in adults, but commonly do so in pediatric patients. Fortunately, hypoglycemia is easily recognized and treated. In the setting of altered mental status, the blood glucose should be evaluated and existing hypoglycemia must be corrected by administrating dextrose. Ingestions of substances that cause hypoglycemia, such as oral anti-hyperglycemic agents, mandate serial evaluations of the blood glucose.

HISTORY
     While providing initial patient care, assess the scene for accessible toxins and clues to what was ingested. Obtain all nonprescription and prescription medication bottles, and attempt to verify that they contain the medication on the label, as well as the appropriate amount of medication. When prescription medications are involved, the date the prescription was filled, dosage instructions and number of remaining pills can be utilized to determine if any pills are missing.

     Obtain a history of what might have been ingested, how much and when it might have been consumed, as well as any history of nausea and vomiting, altered mental status or treatments administered prior to EMS' arrival.

     If intentional ingestion is suspected, inquire about recent behavior or past occurrences of ingestion or personal harm. In these situations, the patient should be transported regardless of his presentation, or the amount and type of substance ingested.

CONTINUED MONITORING AND ASSESSMENT
     Obtain the patient's temperature, as many toxic substances can cause hypothermia or hyperthermia. Monitor vital signs, including cardiac rhythm, oxygen saturation and capnography, if available. Many cardiac medications and antidepressants affect cardiac conduction. Changes in the electrical conduction of the heart, along with clinical findings and the scene assessment, can provide important clues about the substance ingested. Changes in oxygen saturation and capnography can provide early detection of disorders in oxygenation and ventilation.

     Toxidromes, which are patterns of clinical findings associated with specific types of toxins, are manifested through the central and autonomic nervous systems (see Table IV). Seizures may result from several toxic agents, including oral hypoglycemics and calcium channel blockers, and can be caused by substances that would not cause seizures in adults. When a seizure occurs, standard anticonvulsant therapy should be provided. Recognizing a specific toxidrome might provide further clues to the substance ingested and guide further treatment.

     Examination of the pupils can often provide clues to the type of substance ingested; however, this also has the potential to be misleading. Certain narcotics or narcotic combinations, such as propoxyphene (Darvon), diphenoxylate/atropine (Lomotil) and pentazocine (Talwin) may not cause the pupils to constrict. In the setting of mixed overdoses, pupil reaction is varied and is based on the types and amounts of substances ingested.

ADDITIONAL TREATMENT
     In addition to specific antidotes, the general treatment of toxic exposures may include gastric emptying, as well as blocking absorption and enhancing elimination of the agent.

Gastric Emptying
     Gastric emptying is a long-standing treatment for toxic exposures that has fallen out of favor in recent years. Several studies have shown no improvement in the outcome of asymptomatic patients, and subsequently, this method of management has declined in use. Gastric emptying can be considered if the patient is symptomatic, or if there is a risk of developing significant signs and symptoms based on the amount and type of toxic agents ingested. Unless medications that slow gastric motility, like anticholingerics, have been ingested, gastric emptying is of no benefit more than one hour after the ingestion. There are two primary methods of gastric emptying available in the prehospital setting: syrup of ipecac and gastric lavage. Although gastric lavage in its pure sense (instilling and removing fluid from the stomach) is not typical in the prehospital setting, many EMS agencies place nasogastric tubes in overdose patients and perform gastric emptying by suctioning the stomach contents.

Syrup of Ipecac
     Syrup of ipecac was first made available as a nonprescription medication in 1965 at the request of several medical associations, including the American Academy of Pediatrics (AAP). In the 1980s, the AAP recommended that a one-ounce bottle of ipecac be kept in all homes to induce vomiting in the event of a toxic ingestion. This led to its widespread use as a standard treatment in both the home and emergency medical setting.

     However, studies have shown no improvement in outcome after the administration of ipecac, and it has only a minimal effect in the expulsion of gastric contents. Because it induces prolonged vomiting, the patient may not be able to receive additional therapies, such as activated charcoal or acetylcysteine (Mucomyst). Another potentially detrimental effect is the increased risk of aspiration after its administration. Because of lack of evidence of efficacy, associated complications such as gastric rupture and Mallory—Weiss syndrome, and abuse issues, the role of ipecac in the treatment of toxic ingestions is no longer recommended and its use has diminished significantly. In 1985, ipecac was administered in 15% of reported exposures; in 2006, only 0.1% of toxic exposures received the treatment.

     In 1997, and again in 2004, the American Academy of Clinical Toxicology and the European Association of Poison Centers and Clinical Toxicologists issued a joint position paper against using ipecac in the treatment of toxic ingestions. In 2003, the AAP published a policy statement recommending that ipecac be removed from residences and not be used in home treatment. Finally, in 2003, the Nonprescription Drugs Advisory Committee, a subcommittee of the FDA, voted to remove over-the- counter approval of ipecac. Despite this recommendation, at the time of this writing, ipecac remains an OTC medication. Although prehospital providers should never administer ipecac to a patient, it must be determined if it was administered prior to their arrival.

Gastric Lavage
     Like syrup of ipecac, the use of gastric lavage as a standard therapy has come under scrutiny and has been shown to have no impact on outcome in non-life-threatening conditions. Its use is therefore discouraged in the asymptomatic patient or in patients where mild or moderate toxicity is expected. Limitations of this procedure include the relatively large-sized pill fragments as compared to the small diameter gastric tubes used in pediatric patients. The inability to retrieve pill fragments does not guarantee they are not present, nor does the retrieval of fragments ensure that absorption did not take place before the procedure was initiated.

     Similar to their position on ipecac, the American Academy of Clinical Toxicology and the European Association of Poison Centers and Clinical Toxicologists issued a joint position statement in 1997 against the use of gastric lavage in the routine treatment of toxic ingestions. Lavage can be considered if a potentially life-threatening amount of certain toxic agents has been ingested, if there are life-threatening signs and symptoms present, or there is a suspected risk of significant toxicity. Ingestions that may necessitate lavage include calcium channel blockers, cyclic antidepressants, chloroquine and substances that cannot be absorbed by activated charcoal, such as alcohols, heavy metals and glycols. Gastric lavage is absolutely contraindicated after the ingestion of hydrocarbons and caustic agents, or if the airway is not protected by an intact gag reflex or endotracheal intubation.

Blocking Absorption
     With binding surface area of 1000–3000 m² per gram, activated charcoal is an effective agent in binding with toxins, thereby blocking their absorption from the gastrointestinal system. This is the recommended treatment in children. It is suggested that charcoal be administered within one hour of the ingestion; however, there are no data to recommend or discourage administration after one hour has passed.

     Activated charcoal is a thick solution with a coarse, grainy consistency that many patients find displeasing. Adding it to non-caffeinated soda, juice or flavored milk makes it more palatable. Having the patient drink the solution through a straw bypasses many of the unpleasant sensations associated with activated charcoal.

     If the amount of toxin ingested is known, the dose of charcoal is 10:1. However, since this is often unknown, a standard dose of 1 g/kg, with a maximum dose of 100 g, is acceptable (Table V). Activated charcoal is ineffective in binding with heavy metals, minerals, glycols and alcohols. It is contraindicated in ingestions of hydrocarbons and caustic agents. Bowel sounds must be assessed and determined to be present prior to administration of charcoal, as it is contraindicated in the setting of a bowel obstruction.

     Although charcoal does not induce vomiting, the psychological effects of drinking the solution, as well as the ingested toxin, causes vomiting in approximately 15% of patients to whom activated charcoal is administered. As a result, charcoal is contraindicated when airway reflexes are absent, unless administered by gastric tube. In this situation, the provider must be absolutely certain of the tube's placement. Administration of charcoal through a gastric tube mistakenly placed in the trachea has led to disastrous outcomes, including death.

     The administration of activated charcoal after gastric lavage is a procedure that should be used with caution, as it has been shown to cause an increased incidence in the need for intubation, aspiration and ICU admission. It has been suggested that this combination of therapy should not be performed in the routine treatment of toxic ingestions, and that administering activated charcoal alone is more effective than when preceded by gastric lavage.

Enhanced Elimination
     The final general treatment of ingested toxins is to enhance elimination of the substance. Many charcoals contain sorbitol, which is a cathartic. Once bound with the toxin, it moves quickly through the GI system and is expelled through the feces. Sorbitol should be used with caution in children due to the potential for diarrhea, as well as fluid and electrolyte imbalances. Hypernatremic dehydration and cardiovascular collapse have occurred in infants; therefore, it is not recommended in children younger than 1 year. It has been found that there is no known benefit or improved clinical outcome in administering a combination of activated charcoal and cathartics. Additionally, there is an increased incidence of vomiting when the charcoal/sorbitol mixture is administered. This has led to the recommendation that such combinations not be used in the routine management of toxic exposures, but rather activated charcoal should be administered alone. Sorbitol is a medication in and of itself; therefore, prehospital providers should ensure it is permitted within their local or state scope of practice.

     Alkalinization of the urine by administering 1–2 mEq/kg of sodium bicarbonate is effective in the setting of toxins that are excreted through the renal system as weak acids or weak bases. Sodium bicarbonate ionizes the toxin so it is unable to be reabsorbed in the kidneys. Forced diuresis by administration of isotonic intravenous fluids will further enhance renal elimination. Ion trapping is beneficial in exposures to salicylates, chlorpropamide and phenobarbital.

     Part two of this three-part series will appear in the May issue.

Bibliograhy
Abbruzzi G, Stork C. Pediatric toxicologic concerns. Emerg Med Clin North Am 20(1): 223–247, 2002.
American Academy of Pediatrics. AAP Publications Retired and Reaffirmed. Pediatrics 116:796, 2005.
American Academy of Pediatrics Committee on Drugs. Camphor: Who needs it? Pediatrics 62:404–406, 1978.
American Academy of Pediatrics Policy Statement. Camphor Revisited: Focus on Toxicity. Pediatrics 94: 127–128, 1994.
American Academy of Pediatrics Policy Statement Committee on Injury, Violence, and Poison Prevention. Poison treatment in the home. Pediatrics 112(5):1182–1185, 2003.
Artman M, Boerth RC. Clonidine poisoning. Am J Dis Child 137:171–174, 1983.
Banner W, Lund ME, Clawson L. Failure of naloxone to reverse clonidine toxic effect. Am J Dis Child 137: 1170–1171, 1983.
Belson MG, Gorman SE, et al. Calcium channel blocker ingestions in children. Am J Emerg Med 18(5):581–586, 2000.
Botma M, Colquhoun-Flannery W, Leighton S. Laryngeal oedema caused by accidental ingestion of oil of wintergreen. Int J Pediatr Otorhinolaryngol 58:229–232, 2001.
Bronstein AC, Spyker DA, et al. 2006 annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clin Toxicol 45:8, 815–917, 2007.
Bryant S, Singer J. Management of toxic exposure in children. Emerg Med Clin No Amer 21(1):101–119, 2003.
Calello DP, Kelly A, Osterhoudt KC. Case files of the Medical Toxicology Fellowship Training Program at the Children's Hospital of Philadelphia: A pediatric exploratory sulfonylurea ingestion. J Med Toxicol 2(1):19–24, 2006.
Calkins T, Chan TC, et al. Review of prehospital sodium bicarbonate use for cyclic antidepressant overdose. Emerg Med J 20(5):483–486, 2003.
Chyka PA, Erdman AR, et al. Salicylate poisoning: An evidence-based consensus guideline for out-of-hospital management. Clin Toxicol 45(2):95–131, 2007.
Clarke SFJ, Dargan PI, Jones AL. Naloxone in opioid poisoning: Walking the tightrope. Emerg Med J 22(9):612–616, 2005.
Code of Federal Regulations, Title 21, Volume 4, 21CFR201.308. Revised as of April 1, 2007. Davis JE. Are one or two dangerous? Methyl salicylate exposure in toddlers. J Emerg Med 32(1):63–69, 2007.
Fisher DH, Moss M, et al. Critical care for clonidine poisoning in toddlers. Crit Care Med 18(10):1124–1128, 1990.
Frommer DA, Kulig KW, et al. Tricyclic antidepressant overdose: A review. JAMA 257(4):521–526, 1987.
Geib AJ, Babu K, et al. Adverse Effects in children after unintentional buprenorphine exposure. Pediatrics 118(4): 1746–1751, 2006.
Goel A, Aggarwal P. Camphor: A lesser-known killer. South Med J 100(2):135, 2007.
Gremse DA, Artman M, Boerth RC. Hypertension associated with naloxone treatment of clonidine poisoning. J Pediatr 8(5:1):776–778, 1986.
Heidemann SM, Sarnaik AP. Clonidine poisoning in children. Crit Care Med 18(6):618–620, 1990.
Henry PD. Comparative pharmacology of calcium antagonists: Nifedipine, verapamil and diltiazem. Am J Cardiol 46:1047–1058, 1980.
Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes. JAMA 287(3):360–372, 2002.
Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: A review. Emerg Med J 18(4):236-241, 2001.
Koren G. Medications which can kill a toddler with one tablet or teaspoonful. Clin Toxicol 31(3):407–413, 1993.
Liebelt EL, Shannon MW. Small doses, big problems: A selected review of highly toxic common medications. Pediatr Emer Care 9(5): 292–297, 1993.
Lewis JM, Klein-Schwartz W, et al. Continuous naloxone infusion in pediatric narcotic overdose. Amer J Dis Child 138(10):944–946, 1984.
Little GL, Boniface KS. Are one or two dangerous? Sulfonylurea exposure in toddlers. J Emerg Med 28(3): 305–310, 2005.
Manoguerra AS, Erdman AR, et al. Camphor poisoning: An evidence-based practice guideline for out-of-hospital management. Clin Toxicol 44(4):357–370, 2006.
Meyer D, Tobias JD. Adverse effects following the inadvertent administration of opioids to infants and children. Clin Pediatr 44(6):499–503, 2005.
Michael JB, Sztajnkrycer MD. Deadly pediatric poisons: Nine common agents that kill at low doses. Emerg Med Clin No Am 22:1019–1050, 2004.
Newton EH, Shih RD, Hoffman RS. Cyclic antidepressant overdose: A review of current management strategies. Amer J Emerg Med 12(3):376–379, 1994.
Olson KR, Erdman AR, et al. Calcium channel blocker ingestion: An evidence-based consensus guideline for out-of-hospital management. Clin Toxicol 43(7):797–822, 2005.
Olsson JM, Pruitt AW. Management of clonidine ingestion in children. J Pediatr 103(4):646–50, 1983.
Passal DB, Crespin FH. Verapamil poisoning in an infant. Pediatr 73:543–545, 1984.
Ragucci KR, Trangmar PR, et al. Camphor ingestion in a 10-year-old male. South Med J 100(2):204–207, 2007.
Ramoska EA, Spiller HA, Myers A. Calcium channel blocker toxicity. Ann Emerg Med 19(6):649–653, 1990.
Ramoska EA, Spiller HA, et al. A one year evaluation of calcium channel blocker overdoses: Toxicity and treatment. Ann Emerg Med 22(2):196–200, 1993.
Ranniger C, Roche C. Are one or two dangerous? Calcium channel blocker exposure in toddlers. J Emerg Med 33(2): 145–154, 2007.
Rosenbaum TG, Kou M. Are one or two dangerous? Tricyclic antidepressant exposure in toddlers. J Emerg Med 28(2): 169–174, 2005.
Rowden AK, Fasano CJ. Emergency management of oral hypoglycemic drug toxicity. Emerg Med Clin No Amer 25(2): 347–356, 2007.
Sachdeva D, Stadnyk JM. Are one or two dangerous? Opioid exposure in toddlers. J Emerg Med 29(1):77–84, 2005.
Salhanick SD, Shannon MW. Management of calcium channel antagonist overdose. Practical Drug Safety 26(2):65–79, 2003.
Shannon M. Ingestion of toxic substances by children. N Engl J Med 342(3):186–191, 2000.
Shannon M. The demise of ipecac. Pediatr 112(5):1180–1181, 2003.
Szlatenyi CS, Capes KF, Wang RY. Delayed hypoglycemia in a child after ingestion of a single glipizide tablet. Ann Emerg Med 31(6):773–776, 1998.
Thomas TJ, Pauze D, Love JN. Are one or two dangerous? Diphenoxylate-atropine exposure in toddlers. J Emerg Med, 34(1):71–75, 2008.
Transcript of the June 12, 2003, meeting of the Food and Drug Administration Center for Drug Evaluation and Research, Nonprescription Drugs Advisory Committee.
Tucker JR. Indications for, techniques of, complications of, and efficacy of gastric lavage in the treatment of the poisoned child. Curr Opin Pediatr 12(2):163–165, 2000.
Wiley JF, Wiley CC, et al. Clonidine poisoning in young children. J Pediatr 16(4):654–658, 1990.

Robert Vroman, BS, NREMT-P, has been involved in all levels of EMS for 17 years, working with both rural and urban services as a provider and educator. He has a degree in Emergency Medical Care from Western Carolina University and is currently a member of the Paramedic Education Program faculty at HealthONE EMS in Englewood, CO.