SECTION II. TOXICOLOGY
Maureen A. Madden
Poisoning represents one of the most common medical emergencies encountered worldwide and is especially problematic for children, who constitute the population that is most vulnerable and at risk for unintentional and preventable poisonings. The scope of toxic substances involved in poisoning is very broad, requiring healthcare providers to have an extensive knowledge of signs and symptoms of poisoning, as well as specific therapeutic interventions and antidotes. The vast majority of children who ingest poisons suffer no harm. However, healthcare providers must recognize, assess, and manage those exposures that are most likely to cause serious injury, illness, or death and initiate appropriate management to minimize the physical injury that may occur. Those patients identified as most at risk are likely to require management in an ICU setting.
A. Poisoning Versus Overdose
The term poison is often used to refer to nonpharmaceutical substances, and overdose is used for pharmaceuticals; however, any substance that enters the body and causes harm is a poison, and therefore the term poisoning is used in this section to describe the results of any exposure resulting in an adverse reaction such as injury, illness, or death.
B. Poison Exposure
Poison exposure means coming into some form of contact with a potentially harmful or toxic substance that can produce toxic effects. Such exposure can be through ingestion, inhalation, ocular or dermal contact, or parenteral injection.
C. Routes of Exposure
The manner in which a potentially toxic substance enters the body can influence the time of onset, intensity, and duration of toxic effects. Consistently, the most common route of exposure is ingestion. However, never overlook the importance of other routes of exposure, for example, inhalation and dermal routes for organophosphate insecticides; inhalation, nasal, ocular, and parenteral routes for drugs of abuse; ocular, dermal, oral, and inhalation for caustic chemicals; inhalation for gases, fumes, and vapors; and parenteral for envenomations. The effects of a poison exposure are determined by the degree of absorption of the substance into the bloodstream, the extent of metabolism to a less toxic or more toxic substance, distribution to target organs, and ultimate elimination from the body.
D. Acute Versus Chronic Exposure
Poisoning may be acute or chronic, but the overwhelming majority of human toxic exposures are acute with unintentional ingestions outnumbering intentional ingestions. Most poison exposures in children are the result of acute ingestion. Chronic overdoses, or an acute overdose of a drug also taken for a long period, are possible for children who require therapeutic drugs for medical conditions. Chronic exposures also occur for those abusing drugs, for victims of child abuse, and for victims of factitious disorder by proxy. Pharmacokinetics, toxic blood levels, and clinical manifestations of poisoning may differ between acute and chronic exposure to a drug. The cornerstone of treatment comprises a thorough evaluation of the poisoning exposure, careful assessment of the patient, and the application of supportive care as indicated. The most important aspect of managing a child with a potential poisoning exposure is meticulous attention to detail in both routine and intensive supportive care. When a toxic ingestion is suspected, initial management is always focused on stabilizing the patient’s condition utilizing the priorities of resuscitation: airway, breathing, and circulation (ABCs); and securing rapid intravenous (IV) access before instituting additional management and therapeutic interventions.
ROLE OF THE POISON CENTER
A. The poison center is a valuable source of expert clinical toxicology information. There are 56 poison control centers operating in the United States, providing 24 hr/day, and 7 day/week assistance. The poison control centers are staffed by physician, pharmacists, nurses, and experts in toxicology and are able to:
1. Provide expert advice about poisoning by drugs (legal, illegal, foreign, veterinary), household products, industrial chemicals, hazardous materials, environmental toxins, chemical warfare agents, drugs to treat exposure to biological warfare agents, snakes, spiders, plants, mushrooms, and pill identification.
7352. Determine whether a constellation of symptoms could be caused by poisoning.
3. Locate sources for unusual antidotes (e.g., botulinum antitoxin, exotic snake antivenins), treatments, and laboratory studies.
4. Conduct clinical and epidemiologic research, providing education and information on new drugs and the most up-to-date treatment recommendations.
B. Each patient referred to the poison control center becomes an anonymous part of a national database, which collectively identifies actual and, in some cases, previously unsuspected hazards. These data are uploaded by your local poison center in real time to the American Association of Poison Control Centers National Poison Data System (NPDS), as part of syndromic surveillance for public health threats. Data also are used to reformulate or repackage products or to require removal of products from the market.
C. The Joint Commission on Accreditation of Healthcare Organizations requires that the poison center phone number be posted in every healthcare facility. All U.S. poison control centers share the same phone number, 1-800-222-1222, and calls are automatically routed to the local poison control center according to the initiating telephone exchange and area code.
EPIDEMIOLOGY AND ETIOLOGY
1. The most comprehensive source of information about poison exposures in the United States is the “Annual Report of the American Association of Poison Control Centers’ NPDS,” published annually in the journal Clinical Toxicology and on the web at www.aapcc.org. It provides data for differentiation between common but relatively benign poison exposures and those with serious consequences.
2. In 2014, there were 2,165,142 human poison exposures reported to 56 poison centers in the United States. More than 91% of these exposures occurred in a residence. About 68% of the 2.2 million exposures reported to poison centers were treated at the exposure site, saving millions of dollars in medical expenses. A summary of the number of pediatric exposures and fatalities is found in Table 9.17 (Mowry, Spyker, Brooks, McMillan, & Schauben, 2015).
3. The most common poison exposures in children during 2014 are listed in Table 9.18. Table 9.19 lists those substances associated with the largest number of fatalities in all ages. This section focuses on the most dangerous poison exposures, rather than the most common.
B. Risk Factors
1. All ages are vulnerable to iatrogenic poisonings (e.g., incorrect drugs or routes of administration in a healthcare setting), environmental toxins (e.g., carbon monoxide, pesticides, contaminated water), inadvertent ingestion of substances improperly stored, and idiosyncratic reactions. Children of any age may be victims of child abuse or factitious disorder by proxy. The ingestion of a potentially poisonous substance typically represents a complex interaction of factors, including the child, substance, and environment. In addition, there are some age-related physiologic and behavioral factors that may predispose to, exacerbate, or mitigate poison exposures. Specifically, toddlers and adolescents demonstrate a bimodal high incidence of exposure to toxic substances.
Younger Than Age 6 Years
Cosmetics and personal care products
Household cleaning substances
Stimulants and street drugs
Source: Adapted from Mowry, J. B., Spyker, D. A., Brooks, D. E., McMillan, N., & Schauben, J. L. (2015). 2014 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 32nd Annual Report, Clinical Toxicology, 53, 962–1147. doi:10.3109/15563650.2015.1102927
Miscellaneous cardiovascular drugs
Miscellaneous stimulants and street drugs
SSRIs, selective serotonin reuptake inhibitors.
Source: Adapted from Mowry, J. B., Spyker, D. A., Brooks, D. E., McMillan, N., & Schauben, J. L. (2015). 2014 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 32nd annual report, Clinical Toxicology, 53, 962–1147. doi:10.3109/15563650.2015.1102927
2. The general concept of the “one-pill” rule states that a single adult therapeutic dose would not be expected to produce significant toxicity in a child. This is true for most agents but there are a small group of pharmaceutical agents and household products that can create life-threatening effects when ingested in very small quantities. A “sip or pill can kill,” is a category of products with the potential to cause life-threatening toxicity or death in a child younger than 2 years of age, despite the ingestion of only one or two tablets or sips (Michael & Sztajnkrycer, 2004). Approximately 24 agents have the potential to be fatal to individuals with small body mass. Nine of the most commonly ingested agents in this category are calcium channel antagonists, camphor, clonidine and the imidazolines, cyclic antidepressants, opioids and opiates, diphenoxylate/atropine (Lomotil), salicylates, sulfonylureas, and toxic alcohols (methanol, ethylene glycol and isopropanol; Michael & Sztajnkrycer, 2004).
a. Infants are poisoned when parents misread or disregard medication labels, when potentially harmful substances are left within an infant’s grasp, or when older siblings “feed” or “help with” infants. Immature GI tract flora 737predisposes infants to infant botulism from ingestion of honey and to methemoglobinemia from the ingestion of foods or well water high in nitrites. The infant’s immature nervous system exacerbates the risk of poisoning by any CNS toxin. Rapid respiratory and metabolic rates increase the risk of carbon monoxide poisoning. Immature hepatic and renal systems may or may not increase the risk of poison exposures, depending on the specific mechanisms for metabolism and excretion. An infant’s small body weight increases the potential for danger if an infant is envenomated by snakes or spiders.
b. Toddlers normal developmental characteristics increase the likelihood of ingestions in this age group. Toddlers are newly mobile, curious, and anxious to explore their environment through reaching, climbing, and tasting, yet too young to know what is dangerous and subsequently are poisoned when potentially poisonous substances are left within reach. There are three prominent reasons that typically put children at risk for toxic exposure: improper storage of substances in the home, children spending more time in other people’s homes, and caregiver distraction. Other factors that put children at risk are a chaotic or stressful home environment; an unemployed or single-parent household; parental illness or disability; accessibility to toxic agents; lack of proper supervision; grandparent visiting or caretaking; and desire to imitate adult behavior, including taking of medicines (Calello & Henretig, 2014). Children are unable to distinguish medicines and household products from benign look-alikes such as candy and soft drinks. Physiologically, toddlers face the same risks as infants in terms of the nervous, hepatic, and renal systems; respiratory and metabolic rate; and body weight.
c. School-age children may not be able to read or may misinterpret label instructions on products and medicines, succumb to “dares” of classmates, and may not be able to predict the consequences of their actions. Because of wide variability in normal growth and development, it is difficult generally to predict the physiologic effects of many poison exposures in children.
d. Preteens and adolescents may misinterpret label instructions on products and medicines, succumb to “dares” of classmates, explore more widely outside the home and school environment, abuse drugs, or attempt suicide. The majority of ingestions in this age group occur in the home and are intentional rather than accidental. Adolescent ingestions frequently involve multiple substances, are a result of either suicide attempts or substance abuse, and commonly a delay occurs between the ingestion and when medical attention is sought. Adolescents also have increased access to illicit and licit drugs and alcohol than younger children. Adolescents may be exposed to chemicals on the job. After about age 10, children metabolize acetaminophen as adults do (i.e., generate increased amounts of the hepatotoxic metabolite). As they near the upper end of the adolescent age range, physiologic responses approach, then equal, adult responses for all agents.
MANAGEMENT OF PATIENTS WITH POISON EXPOSURES
1. Most poisoning exposures in children younger than 6 years are unintentional and are not associated with malicious or suicidal intent. Poisonings in this age group usually involve one substance that is often nontoxic or minimally toxic. The amount ingested is usually small and children usually present for evaluation soon after ingestion. Usually the basic information is known: Children spill things, brag about taking medicine or “helping mommy,” or act guilty about having done something “forbidden.”
2. In the absence of history, a high index of suspicion is required to determine whether a poison exposure has occurred. Suspect a poison exposure when there is a sudden onset of illness; unexplained symptoms, findings, or laboratory values; an unusual complex of symptoms; exposure to a fire (carbon monoxide, cyanide); or psychiatric treatment in the child, a family member, or caretaker and therefore access to psychotropic drugs. In older children who are trauma victims, suspect drug or alcohol use as a precipitating factor. Also, previously undiagnosed medical conditions (e.g., glucose-6-phosphate dehydrogenase [G6PD] deficiency) may predispose to poisoning by some agents (naphthalene mothballs, dapsone), and the poison center can help identify such conditions.
3. To determine whether a poison exposure may have occurred, ask about medicines and products in the home; whether there have been visitors in the home or the child has visited elsewhere as an increasing number of exposures in children younger than 6 years of age involve ingestion of a grandparent’s 738or elderly caretaker’s medicine. These agents tend to be more toxic to children, often in sustained-release dosage forms. Ask whether herbal medicines, home remedies, or foreign preparations have been used or are available; or if the child has been breastfeeding. To assess environmental factors, ask whether anyone else is ill, for example, or whether there have been any home improvement projects or new appliances installed.
4. In addition to ascertaining the nature of any symptoms, history of an ingestion includes type and amount of ingestion if known; the possibility of multiple agents; the time of ingestion; time of presentation; any history of vomiting, choking, coughing, and/or alteration in mental status; and any interventions performed prior to presentation at the medical facility. This information can provide valuable clues in determining what the poison is or whether the available history is accurate.
As previously stated, this section focuses on the most dangerous poison exposures; therefore, assessment and management consist of a thorough evaluation of the poisoning exposure, careful assessment of the patient, and the application of basic supportive care as indicated. When a toxic ingestion is suspected, initial assessment and management are always focused on first stabilizing the patient’s condition utilizing the priorities of resuscitation, the ABCs, and securing rapid IV access. The poisoned patient often represents an acute-onset emergency with a broad range of multiorgan system pathophysiology. Any interventions related to the potentially urgent or emergent concerns of adequacy and stability of the respiratory system and circulatory system should supersede all other concerns and interventions.
In cases of poisoning, the letters D, E, and F can extend the initial stabilization mnemonic to include disability assessment, drugs, decontamination, ECG, and fever. These are important foci in the assessment and management of toxic exposures. The disability assessment includes a brief neurologic examination, including level of consciousness, pupillary size, and reactivity; drug therapy is the potential empiric use of items such as oxygen, dextrose, and naloxone. A point of care assessment of serum glucose is indicated for any patient who presents with altered mental status or lethargy as well as for any patient exposed to agents that might cause hypoglycemia. Hypoglycemia is one of the most easily detected and treatable effects secondary to toxic exposures.
1. Clinical assessment in cases of poison exposure is no different from physical assessment for any other medical emergency. Clinical syndromes, called toxidromes, comprise a constellation of signs and symptoms that suggest a specific class of poisoning as seen in Table 9.20. Toxidromes integrate initial vital signs, mental status changes, symptoms, clinical findings, and laboratory results to help identify the toxin and allowing initiation of appropriate treatment in a timely manner. The clinical examination needs to be focused on the central and autonomic nervous system, eye findings, changes in skin, oral and GI mucosa, and odors. These are the areas most likely affected in toxic syndromes. In the poisoned child, after appropriate stabilization, there may be a role for laboratory testing.
2. The need for laboratory assessment depends on whether the poison is known; if so, what the poison is; whether knowledge of test results will affect medical care, prognosis, or disposition of the patient; and, in some cases, whether there are medicolegal considerations. In addition, serum and/or urine toxicology screens may be necessary to rule out the possibility of exposure to additional unknown agents.
a. For many poisonings with anticipated systemic effects, baseline serum electrolytes; renal and hepatic functions; respiratory, cardiovascular, and hematologic parameters; and ABG analyses are necessary.
b. For some poisons, quantitative measurement in urine or serum determines whether treatment is needed. Examples include acetaminophen, aspirin, lead, ethylene glycol, and methanol.
c. In other cases, laboratory studies may confirm the presence of particular substances but do not alter patient care (e.g., tricyclic antidepressants [TCAs]).
d. At other times, laboratory values cannot be returned in time to influence patient care (e.g., cyanide).
e. In some cases, the time between exposure and collection of the laboratory specimen influences the interpretation of laboratory results (e.g., acetaminophen, aspirin, carbon monoxide) as the screening assay only reflects the presence or absence of drugs or metabolites at or above a threshold concentration at the time the specimen is collected. It does not exclude the presence of drug or metabolite, only that the substance was not present at the minimal threshold quantity.
Excessive speech and motor activity
Altered mental status
Decreased bowel sounds
Decreased bowel sounds
Over-the-counter sleep preparations
GI distress (diarrhea)
Black widow spider bites
ADHD, attention deficit hyperactivity disorder; GI, gastrointestinal; PCP, phencyclidine.
aMnemonic: Hot as a hare, dry as a bone, red as a beet, mad as a hatter, blind as a bat.
740f. When a poisoning is suspected but not known, a comprehensive toxicology screen may be helpful in identifying the agent. How “comprehensive” such a screen is varies from facility to facility; it is essential to know what was tested for before declaring such a screening result to be negative.
g. It is usual, and desirable, to “treat the patient, not the laboratory.” When caring for a poisoned patient, the exact opposite is sometimes necessary to prevent devastating consequences. In some common, potentially fatal poisonings, metabolites are responsible for toxic effects, and ideally the patient would be treated before toxic metabolites are generated and while the patient is still asymptomatic. In cases of acetaminophen, ethylene glycol, and methanol poisoning, laboratory studies do guide therapy.
As previously discussed, after ensuring basic stabilization, the use of specific interventions or therapies, including antidotes and enhanced elimination techniques, is limited to cases for which there is expectation that a defined benefit will outweigh the risk of the procedure. There are limited data and information to distinguish lethal concentrations of certain drugs and toxic substances in children and the newer or limited-use therapies have limited pediatric experience. Therefore, indications for the use of interventions in children may be different from those in adults and need to be carefully considered before implementing them.
1. Prevention of Absorption. Decontamination is the initial step as it will limit further absorption of the toxin. This may refer to removal from contaminated air, irrigation of exposed eyes and skin, or GI tract decontamination via adsorption or enhanced elimination techniques.
a. Ocular exposure is treated by copious irrigation, at least 15 to 20 minutes for acidic substances and 30 minutes for alkaline substances, with subsequent reevaluation. One measure of the efficacy of irrigation is when a pH strip gently touched to the conjunctival cul-de-sac indicates a neutral pH. Ocular irrigation in children is difficult at best, and the optimal method to use is the one that can be initiated quickly and then maintained. Ocular irrigation in teens can be performed as in adults, with an irrigation device.
b. Dermal exposure is also treated by copious irrigation for the times specified previously. For older children, a shower is ideal. Ensure to protect staff from exposure to harmful substances with personal protective equipment, initiate irrigation, and remove and bag contaminated clothing.
c. GI tract decontamination refers to the practice of functionally removing an ingested toxin from the GI tract in order to decrease its absorption. Historically, many approaches have been adopted, including gastric evacuation (forced emesis or gastric lavage), intragastric binding (most commonly by single or multidose activated charcoal), or enhancing transit of toxins to decrease total absorption time (whole-bowel irrigation [WBI] or cathartics). As clinical practice has evolved and understanding of the efficacy, risks, and benefits of decontamination have grown, many practices have fallen out of favor. No controlled clinical studies have demonstrated that “routine” GI decontamination reduces morbidity and mortality in poisoned patients. However, evidence suggests that decontamination may reduce the absorption of toxins in the GI tract and may be helpful in very select circumstances. The decision to perform GI decontamination is based upon the specific poison(s) ingested, the time from ingestion to presentation, presenting symptoms, and the predicted severity of poisoning. GI decontamination is most likely to benefit patients who present within 1 hour of a known ingestion of a toxic agent and symptoms have not yet begun. Once symptoms have begun it is typically too late to initiate this intervention (Green, Harris, & Singer, 2008). As such, there is no single preferred strategy for the management of gastric decontamination in pediatric poisonings. The decision to implement a gastric emptying technique is largely dependent upon clinical status and specific situations. Use of an individualized approach based on the timing of ingestion, type of substance, and the amount of the ingested substance in conjunction with the clinical status will dictate treatment choices.
i. Ipecac syrup was once used to induce vomiting. The American Academy of Pediatrics no longer recommends the use of ipecac syrup to treat poisoning, even at home.
ii. Gastric lavage, a form of gastric emptying, also known as gastric irrigation, is the process of cleaning out the contents of the stomach artificially. It is no longer considered the standard of care in pediatric patients as the associated potential risks 741typically outweigh the benefit and therefore is limited in use (Benson et al., 2013). It is sometimes used in patients with known life-threatening overdoses and it is only performed when a benefit is anticipated and one of the following conditions exist: the substance does not bind to activated charcoal, the opportunity to use activated charcoal is significantly delayed or missed, or the child presents within 1 hour of ingestion without significant CNS symptoms already present. Gastric emptying will have limited benefit if attempted more than 1 hour after ingestion because most toxins will have been absorbed or passed through the pylorus already, except for agents that slow gastric motility. The efficacy of gastric lavage is limited by the respective sizes of the child, the tube, and the ingestion, commonly in tablet form.
1) If gastric lavage is to be implemented, the procedure should be only done by individuals with expertise and understanding of the risks associated with the procedure. The procedure consists of first ensuring that the airway is secure and then obtaining the materials necessary for the gastric lavage, including warm NS for instillation. The largest possible orogastric tube should be used, usually a 16- to 32-gauge French. Instill 50 to 100 mL of warm NS at a time, and then allow it to remain in the stomach for a few minutes and drain by gravity. Repeat until lavage fluid is clear. Activated charcoal and a cathartic can be administered before the lavage tube is withdrawn if indicated by the specific suspected or known agent ingested.
2) Gastric lavage is contraindicated for ingestion of caustic substances and hydrocarbons due to the risk of mucosal burns and risk of aspiration of substances into the airway and pulmonary system.
iii. WBI can facilitate removal of select toxins from the GI tract in some patients, but there is no convincing evidence from clinical studies that it improves the outcome of poisoned patients. It can be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs, particularly for those patients presenting greater than 2 hours after drug ingestion when activated charcoal is considered to be less effective. WBI can also be considered for patients who have ingested substantial amounts of iron, lithium, or potassium as the morbidity is high and there is a lack of other potentially effective options for GI decontamination. WBI can be considered for removal of ingested packets of illicit drugs in “body packers.” The concurrent administration of activated charcoal and WBI might decrease the effectiveness of the charcoal (Thanacoody et al., 2010).
1) The general procedure is the same as for bowel preparations. Secure the airway if necessary, and administer a polyethylene glycol–electrolyte solution until the rectal effluent is clear. The dose is 0.5 L/hr for young children and 1 to 2 L/hr for older children and adults. WBI is contraindicated in patients with bowel obstruction, perforation, or ileus, and in patients with hemodynamic instability or compromised unprotected airways.
iv. Activated charcoal is processed so that each molecule contains multiple binding sites. Activated charcoal adsorbs, or binds to, most clinically important drugs and poisons. This prevents absorption from the GI tract into the bloodstream. Activated charcoal does not adsorb metals (e.g., iron, lithium), caustic substances, ethanol, or many pesticides. When these substances are ingested, activated charcoal may still be indicated because of coingestants.
1) The usual dose of activated charcoal is 0.5 to 1 g/kg for young children, 25 to 50 g for older children, and 50 g per dose for adolescents and adults.
2) Activated charcoal should not be mixed with ice cream, syrups, or other items intended to improve palatability. The charcoal adsorbs many of these agents and would therefore be less effective.
3) Single doses of activated charcoal (SDAC) are indicated for the most serious poison exposures because it decreases the amount of toxic substance available for absorption into the bloodstream and should only be used for known serious poison exposures with early presentation, less than 1 hour 742after ingestion, and before onset of symptoms, especially CNS symptoms (Juurlink, 2016). This intervention is often used in the prehospital or emergency room environments.
4) Multiple doses of activated charcoal (MDAC; every 2–6 hours) are recommended in the setting of life-threatening ingestions such as carbamazepine, dapsone, phenobarbital, salicylates, phenytoin, quinine, and theophylline, as it is useful in lowering toxic blood levels and shortening the course of poisoning of substances that undergo enterohepatic or enterogastric recirculation. Some drugs are partially metabolized in the liver, and then active drug is secreted into bile and deposited in the small bowel. Subsequent doses of activated charcoal adsorb the drug as this occurs. This is true regardless of the route of exposure. Intestinal dialysis takes advantage of concentration gradients. As drug is adsorbed to charcoal in the GI tract, previously absorbed, unmetabolized drug moves from receptor sites and intracellular spaces into the GI tract. As this occurs, it, too, is adsorbed by subsequent doses of activated charcoal. Aspirin ingestion is sometimes considered another indication for MDAC, due to the propensity of aspirin tablets to form bezoars, though evidence is lacking.
5) Cautions. To prevent a charcoal impaction, always check for active bowel sounds before administering a dose of charcoal. When MDAC are given, cathartics are occasionally administered no more than once, or occasionally twice, per day to prevent electrolyte imbalance and dehydration. Errors have occurred when charcoal suspension in sorbitol has been mistakenly administered instead of charcoal in an aqueous suspension. Charcoal is contraindicated with absent bowel sounds because it may indicate ileus or obstruction. Always reassess for bowel sounds before administering the next dose of charcoal.
v. Cathartics. Cathartics are no longer routinely recommended. If cathartics are used at all to treat a poisoning, sorbitol, and magnesium citrate are the most common.
1) Sorbitol may be combined with charcoal or administered afterward. It should be administered no more than once per day. The dose is 1 to 2 g/kg.
2) Magnesium citrate may be combined with charcoal or administered afterward. It should be administered no more than once per day with a dose of 4 mL/kg.
2. Enhancement of Elimination. The ability and possibility of enhancing elimination depend on a substance’s volume of distribution and usual route of elimination.
a. Ion trapping is useful for some drugs that are more rapidly eliminated in an alkaline environment; examples include salicylates and phenobarbital. In these cases, administering sodium bicarbonate to alkalinize the urine enhances excretion. (Some drugs are more easily eliminated by acidifying the urine, but this is not recommended; precipitation of myoglobin and renal failure may occur.)
b. Extracorporeal measures to enhance elimination of toxins may be useful in certain dangerous poisonings by substances that can be retrieved from the vascular compartment. Depending on the child’s age, hemodialysis can be used for salicylates, lithium, methanol, and ethylene glycol, among others; hemoperfusion may be used for theophylline; and exchange transfusion is sometimes used to treat “gray baby syndrome” induced by chloramphenicol.
c. Lipid emulsion therapy (LET) is increasingly being considered as a rescue antidote to treat lipophilic drug toxicities such as anesthetics, calcium channel blockers (CCBs), and TCAs. LET has a number of known complications, including lipemia interfering with laboratory testing, pancreatitis and associated symptoms of abdominal pain, nausea and/or vomiting, and ARDS. The limited data associated with use and the known complications of LET reserves its use for hemodynamically unstable patients in whom supportive efforts are not successful (Gosselin et al., 2015).
D. Administration of Antidotes
Few pharmacologic antidotes are available as seen in Table 9.21. Most poisonings are treated by decontamination followed by symptomatic and supportive care. If a specific antidote is indicated, it is described as part of the treatment for poisonings considered in the following sections.
Vitamin K1, protamine
Supportive care, flumazenila
Botulinum antitoxin, BIG
Calcium channel blockers
Pralidoxime in organophosphate overdose
Oxygen, hyperbaric oxygen
Amyl nitrate, sodium nitrate, sodium thiosulfate
Digoxin Fab antibodies (Digibind)
British antilewisite, ethylenediaminetetraacetic acid, dimercaptosuccinic acid
Sulfonylureas (oral hypoglycemics)
Fomepizole, ethanol infusion, dialysis
BIG, botulism immune globulin; INH, isoniazid; NAC, N-acetylcysteine.
aFlumazenil may precipitate seizures when used with patients who are chronic benzodiazepine users or in situations, including tricyclic antidepressant overdose.
Source: Adapted from Madden, M. A. (2015). Pediatric toxicology: Emerging trends. Journal of Pediatric Intensive Care, 4, 103–110.
E. Provision of Supportive Care
For all the substances discussed throughout this section, the premise is that initial stabilization techniques have been addressed and instituted when indicated. Provision of supportive care and symptom management from poisoning encompasses monitoring to ensure airway protection especially in the obtunded child, maintaining adequate oxygenation and ventilation, correction of any hypotension or hypertension, correction of acid–base or electrolyte disturbances, monitoring for dysrhythmias, rhabdomyolysis, and awareness of current medical problems and medications.
Incomplete gastrointestinal decontamination: Virtually any solid dosage form
Drug concretion or bezoar. Examples: Aspirin, iron, meprobamate
Enterohepatic recirculation. Examples: Amitriptyline, digoxin, phencyclidine
Ingestion of anticholinergic drug, or drug with anticholinergic properties. Examples: Antihistamines, atropine, tricyclic antidepressants, glutethimide
Exposure to especially lipid-soluble substances. Examples: Some organophosphate insecticides, anesthetic agents, ethchlorvynol
Incorrect or incomplete history
Incorrect laboratory values
Reexposure in the hospital
Descriptions of individual toxins indicate whether one particular drug (e.g., antiarrhythmic, anticonvulsant, vasopressor) is preferred. Increasing or recurrent symptoms may be expected with some poisonings and occur unexpectedly in others. See Table 9.22 for possible reasons.
F. Prevention of Future Episodes
Circumstances contributing to iatrogenic poisonings must be considered. For young children, age- and development-specific poison-prevention teaching may be required. Suspicions of abuse require legal and social service involvement. Drug abuse prevention and treatment programs and psychiatric intervention may be required for older children and adolescents.
POISONINGS BY PHARMACEUTICAL AGENTS
Acetaminophen is contained within hundreds of prescription and nonprescription analgesics, both alone and in combination with other analgesics, including opioids; in combination with antihistamines in over-the-counter sleeping preparations; and in combination with decongestants, antihistamines, antitussives, expectorants, and analgesics in products to treat coughs, colds, and allergies. Most preparations are oral, but the drug also is available as rectal suppositories and an IV formulation.
1. Acetaminophen is rapidly absorbed from the GI tract, but food or coingestants may delay peak absorption until about 4 hours after ingestion.
2. Acetaminophen is metabolized in the liver. After about the age of 10 years, approximately 5% to 10% of the drug is metabolized by a hepatotoxic metabolite that is normally detoxified by the enzyme glutathione. In overdose, the body’s glutathione stores are depleted, causing liver damage characteristic of acetaminophen overdose. In children younger than 10 years, a different metabolic pathway may be followed, presumably providing some degree of hepatic protection. This relative protection is not entirely reliable, and infants and young children can also die of hepatic injury after acute or chronic acetaminophen overdose. There is some renal metabolism of acetaminophen; therefore renal injury, although not as common as hepatic injury, is possible.
3. The toxic dose of acetaminophen is related to body weight (or ideal body weight in the case of markedly obese individuals); ingestions of unknown amounts or greater than 150 mg/kg require laboratory assessment of absorbed acetaminophen to predict toxicity.
4. Because the toxic effects of acetaminophen overdose are due to metabolites, symptoms of toxicity are delayed. Only rarely, after massive overdose, does a patient develop mental status changes, significant GI tract symptoms, and acidosis within hours after ingestion. Often there are no symptoms of overdose for 6 to 14 hours after ingestion. The earliest symptoms are nausea and vomiting. Within 24 to 48 hours after ingestion, hepatic enzymes elevate. The patient may experience increasing GI 745tract symptoms and right upper quadrant pain, or the patient may feel relatively well. Within 72 to 96 hours after an untreated, severe overdose, hepatic encephalopathy with coagulopathies and hyperglycemia may ensue, followed rapidly by hepatic failure and death.
a. History should include the specific name of the drug as there may be many formulations; the amount ingested; the time of ingestion; and whether ingestion was acute, chronic, or both; the type, onset, duration, or absence of symptoms; and whether there were coingestants.
b. Serum acetaminophen level should be obtained at least 4 hours after ingestion. Also baseline hepatic, renal, and hematologic studies, including prothrombin time (PT)/international normalized ratio (INR) as a measure of synthetic function of the liver, should be obtained if the level is toxic, if ingestion was large or chronic by history, or occurred more than 8 to 12 hours earlier.
6. Treatment of acetaminophen poisoning is straightforward and typically successful if the antidote administration of N-acetylcysteine (NAC), is initiated within 8 to 12 hours after ingestion, if indicated. A determination of need for intervention is made using the Rumack–Matthew nomogram. The nomogram is a sensitive risk-prediction tool and identifies patients at very low risk or very high risk of developing hepatotoxicity after acetaminophen overdose and stratify those who do or do not require administration of NAC. Patients with acetaminophen concentrations below the “possible” line for hepatotoxicity on the Rumack–Matthew nomogram may be discharged home after they are medically cleared. If the ingestion occurred with intent to do self-harm, a thorough psychosocial, psychological, and/or psychiatric evaluation is indicated before the patient can be discharged safely from the medical care facility. All patients above the nomogram line for possible hepatotoxicity should be treated with the specific antidote NAC, which serves as a glutathione precursor and substitute to prevent N-acetyl-p-benzoquinoneimine-induced (NAPQI) hepatocellular injury and decrease the risk of developing hepatotoxicity. The nomogram may be used most effectively after acute, single ingestions (where entire ingestion occurs within an 8-hour period), a known time of ingestion, immediate-release formulation, and in the absence of formulations or coingestants that alter absorption and bowel motility (e.g., anticholinergics, opioids). Delayed treatment still has some utility. Indications for NAC include a toxic acetaminophen level in blood obtained 4 or more hours after ingestion and/or toxic ingestion by history or suspicion when laboratory results cannot be returned by 8 hours after ingestion. The entire course of therapy must be administered to every patient with an acute ingestion and a toxic acetaminophen level, even if the plasma acetaminophen level becomes negative. NAC is being used to treat effects of the toxic metabolite, not the parent compound.
a. Oral NAC
i. The loading dose is NAC 140 mg/kg administered orally (PO), followed by 70 mg/kg every 4 hours for 17 doses, for a total of 18 doses over 72 hours. Make a 3-to-1 dilution of the drug in juice or a beverage palatable to the patient. In an alert patient, offer the diluted drug over ice in a covered container.
ii. Administration of PO NAC is often complicated by vomiting induced by the poisoning and NAC itself. If a dose of NAC is vomited within 1 hour of administration, the dose must be repeated. If an antiemetic is required, use ondansetron or another antiemetic that does not require hepatic metabolism. If necessary for successful NAC administration, a duodenal tube may be placed with radiographic confirmation of placement.
b. IV NAC was approved by the U.S. Food and Drug Administration (FDA) in January 2004 under the brand name Acetadote and is now the recommended route for treatment by poison control. It is a 21-hour IV regimen consisting of three doses with a total dose of 300 mg/kg administered.
i. The loading dose is 150 mg/kg, administered over 60 minutes; second dose of 50 mg/kg (max dose 5 g) is infused over 4 hours. Finally, 100 mg/kg is infused over 16 hours (Taketomo, Hodding, & Kraus, 2015). Fluid and electrolyte imbalance is a concern for small children; call the poison center for additional dosing information. Poison control typically recommends the utilization of the IV formulation for increased tolerance and compliance.
c. Other treatment includes daily monitoring of hepatic enzymes and symptomatic and supportive care.
7467. Special considerations include the need for a high index of suspicion. Acetaminophen poisoning is perfectly treatable if recognized early but potentially fatal if untreated. Those who recover and have no clinical or laboratory evidence of hepatic injury are not expected to experience sequelae. Those who develop liver failure from this poisoning may undergo successful liver transplantation.
B. Anesthetics for Topical Use
Anesthetics for topical use contain benzocaine, dibucaine, prilocaine, and lidocaine. They are found in prescription and nonprescription remedies, including teething lotions, first-aid creams, and drugs infiltrated into wounds before suturing. Children have died rapidly after the ingestion of dibucaine.
1. Children experience the rapid onset of dysrhythmias, seizures, and methemoglobinemia after ingestion or absorption of these drugs. As little as several milligrams is sufficient for toxic effects to occur.
2. Suspect methemoglobinemia in patients who are cyanotic and do not respond to oxygen. Methemoglobinemia is a disorder characterized by the presence of a higher than normal level of methemoglobin (metHb, i.e., ferric [Fe3+] rather than ferrous [Fe2+] hemoglobin) in the blood. Methemoglobin has a decreased ability to bind oxygen and results in an increased affinity of bound oxygen to the three other ferrous heme sites within the same hemoglobin unit. This leads to an overall reduced ability of the RBC to release oxygen to tissues, with the associated oxygen–hemoglobin dissociation curve shifted to the left. When methemoglobin concentration is elevated in RBCs, tissue hypoxia can occur due to the overall reduced ability of the RBC to release oxygen to tissues. Bedside pulse oximetry in the presence of methemoglobinemia may be misleading. The pulse oximeter only measures the relative absorbance of two wavelengths of light to differentiate oxyhemoglobin from deoxyhemoglobin. Methemoglobin increases absorption of light at both wavelengths and therefore offers optical interference to pulse oximetry by falsely absorbing light and generating false readings, plateauing at approximately 85%. Pulse oximetry measurements are often falsely high in those with high-level methemoglobinemia. The severity of the cyanosis does not correspond to the pulse oximetry reading: A patient may appear extremely cyanotic but still have a pulse oximetry reading in the high 80s. Newer pulse oximetry models have improved technology to differentiate methemoglobin.
3. Tentative diagnosis can be made by inspection of the blood. A drop of the patient’s blood on a piece of filter paper appears brown next to a drop of “normal” blood. Laboratory confirmation reports a percentage of methemoglobin, the amount of normal hemoglobin that has been converted to methemoglobin and therefore cannot transport oxygen.
4. Specific treatment for methemoglobinemia is the IV administration of methylene blue. Treatment for other toxic manifestations is symptomatic and supportive.
SSRIs have become more widely prescribed than TCAs and other cyclic antidepressants because there are fewer dangerous effects in overdose and fewer unpleasant side effects for patients. Poison center data support the widespread availability and lower toxicity of SSRIs compared with TCAs. In 2014, TCAs alone or formulated with other drugs accounted for 10,349 calls to poison centers and were associated with 46 fatalities and major life-threatening effects in 341 cases. The corresponding numbers for SSRIs were 31,169 exposures, with 99 fatalities and life-threatening effects in 118 cases.
1. TCAs include amitriptyline (Elavil), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor), and others, both singly and in combination with other psychotropic agents. There are no approved therapeutic indications and no safe doses for these drugs in very young children, who may have access to drugs belonging to an older sibling or other family member. Imipramine is used in the treatment of nocturnal enuresis in older children. The TCAs may be used to treat depression in preteens and adolescents, although treatment with SSRIs is now more common. Evidence-based management guidelines for TCA poisoning are available from the American Association of Poison Control Centers (AAPCC).
a. In general, these drugs are rapidly absorbed in the GI tract and undergo first-pass metabolism in the liver. Conjugates are then renally eliminated. Cyclic antidepressants are very lipophilic and highly protein bound, leading to large volumes of distribution. They have long elimination half-lives that often exceed 24 hours 747(>31–46 hours for amitriptyline). In an overdose, altered pharmacokinetics may prolong elimination and increase toxic effects. Cyclic antidepressants have significant anticholinergic effects that can delay gastric emptying, particularly in large ingestions, with significant amounts of unabsorbed drug remaining in the GI tract. In addition, the acidosis that results from respiratory depression and hypotension reduces protein binding, resulting in higher serum levels of active free drug. Although the exact therapeutic mechanism of cyclic antidepressants is not known, it is most likely related to decreased central norepinephrine and serotonin reuptake, resulting in increased levels of these amines in the brain.
b. TCA’s toxic effects are related to the following four pharmacologic effects: anticholinergic, direct alpha-adrenergic blockade, inhibition of norepinephrine and serotonin reuptake, and blockade of fast sodium channels in myocardial cells. The most serious adverse effects of cyclic antidepressant toxicity are due to CNS effects and cardiovascular instability. Depressed mental status is generally caused by the antihistamine and anticholinergic properties of cyclic antidepressants, whereas seizures are thought to be due to increased CNS levels of biogenic amines. Life-threatening cardiovascular complications are due to impaired conduction from fast sodium channel blockade. This alters depolarization, widens the QRS complex, and prolongs the PR and QT intervals. Impaired cardiac conduction may lead to heart block and unstable ventricular dysrhythmias or asystole. Cyclic antidepressants have also been shown to directly depress myocardial contractility. However, the profound hypotension seen in serious cyclic antidepressant poisoning is primarily due to vasodilatation from direct alpha-adrenergic blockade. Early hypertension may precede the significant hypotension characteristic of this poisoning.
c. The toxic dose cannot be predicted with certainty. Any amount is potentially dangerous for infants, toddlers, and young children. For adolescents and adults, the toxic amount is variable, with 10 to 20 mg/kg generally noted to cause significant toxicity. EMS transport, GI tract decontamination, and at least 6 hours of ED evaluation are required for all ingestions in young children and ingestions larger than a therapeutic dose in older children. A patient who develops any clinical signs of toxicity within the 6-hour observation period requires admission to a monitored bed until the patient has been asymptomatic for 24 hours.
d. The presentation of a tricyclic overdose is variable with cardiovascular and CNS symptoms predominating. A classic presentation of TCA overdose poisoning includes hypotension; metabolic acidosis; and numerous dysrhythmias, especially ventricular dysrhythmias and conduction delays and potentially the rapid onset of grand mal seizures and coma, perhaps within 30 minutes of ingestion. Common ECG findings are numerous, with sinus tachycardia being the most common, followed by prolonged PR and widening of QRS intervals with resultant ventricular arrhythmias.
e. When assessing the patient, strict attention to managing the ABCs is imperative. It is necessary to anticipate the potential need to secure the airway with intubation, if the patient is still conscious, as there may be a rapid change in mental status secondary to the CNS effects of the poisoning. The most useful laboratory study is ABG analysis. Symptomatic patients are likely to develop acidosis that is resistant to correction. Laboratory measurements of drug and metabolite levels correlate loosely with expected toxicity but are not necessary for patient care because they are not used to determine treatment.
f. Treatment includes implementing GI tract decontamination if the patient presents within 1 hour of ingestion and prior to onset of symptoms; maintaining serum pH between 7.45 and 7.55; cardiac monitoring; and treatment of hypotension, seizures, and dysrhythmias.
i. Administer activated charcoal every 4 hours until the patient is asymptomatic; check for the presence of bowel sounds before each charcoal dose.
ii. Sodium bicarbonate is the drug of choice to treat TCA poisoning. Life-threatening cardiovascular complications are due to impaired conduction from fast sodium channel blockade and the administration of sodium bicarbonate overcomes this blockade by the induction of alkalosis and resultant correction in acidosis, leading to decreased drug binding to sodium channels. This correction results in stabilization of the cardiac rhythm. Although hyperventilation is sometimes used to correct acidosis, sodium 748bicarbonate is preferred as it is much more effective.
iii. Lidocaine, magnesium sulfate, or overdrive pacing may be indicated for dysrhythmias unresponsive to a normalized pH. Recently, LET has been proposed as an effective antidote to treat cardiotoxicity from overdose of myocardium-poisoning lipophilic drugs, including CCBs, beta-blockers, digoxin, local anesthetics, cyclic antidepressants, antipsychotics, and atypical antidepressants. Although there are not enough data to support the routine use of IV LET as a rescue agent in all settings, treatment protocols have been developed regarding its use in specific clinical scenarios. Because the potential risks of administering high doses of LET should be considered only after advanced cardiac life support measures have been unsuccessful.
iv. Hypotension must be treated aggressively and may require invasive support if fluids, positioning, and norepinephrine are ineffective. The administration of hypertonic sodium chloride has been shown to be as effective as sodium bicarbonate in reversing QRS prolongation and hypotension.
v. Benzodiazepines, such as diazepam or lorazepam, may be used for the management of agitation or seizures. The pharmacologic effects of phenytoin may be elevated, increasing the pharmacologic effects and risk of toxicity so the use of phenytoin or fosphenytoin is to be avoided.
vi. Physostigmine is a short-acting cholinesterase inhibitor that has been described as causing asystole and seizures. There is no role for its use in the management of tricyclic toxicity.
g. Amoxapine is a cyclic antidepressant that causes few cardiovascular effects after overdose, but it is often associated with status epilepticus. An overdose of amoxapine requires aggressive seizure control, often including intubation and neuromuscular blockade.
2. Serotonin uptake inhibitors include citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil, Seroxat), sertraline (Zoloft, Lustral) and escitalopram (Lexapro, Cipralex).
a. Effects of single-drug overdoses tend to be mild, including drowsiness and GI effects. Citalopram especially is associated with a greater incidence of seizures and cardiac effects, including QTc prolongation. Early recognition is necessary to ensure appropriate resuscitative interventions and to limit exposure to other medications that may potentially exacerbate the serotonin syndrome and associated symptoms. Although most clinical symptoms are mild to moderate, patients have the potential to deteriorate quickly. In the syndrome’s mildest stage, symptoms are often attributed to other causes, and in its most severe form, it can easily be mistaken for neuroleptic malignant syndrome. Severe serotonin toxicity is characterized by muscle rigidity, which can cause the body temperature to elevate rapidly to over 40°C. This hypertonicity can mask the classic and diagnostic signs of hyperreflexia and clonus. Patients may have unstable and labile vital signs with confusion or delirium and can experience tonic–clonic seizures. If the muscle rigidity and hyperthermia are not treated properly, patients can develop cellular damage and enzyme dysfunction leading to rhabdomyolysis, myoglobinuria, renal failure, metabolic acidosis, ARDS, and/or disseminated intravascular coagulation (Wang, Vashistha, Kaur, & Houchens, 2016).
b. Serotonin syndrome is a potentially life-threatening condition that can lead to multiorgan failure within hours if not recognized. It may occur idiosyncratically, after large overdoses, or especially with an overdose of more than one drug. It is caused by elevated serotonin levels in the central and peripheral nervous systems. The classic presentation is a triad of autonomic dysfunction, neuromuscular excitation, and altered mental status. Ascending neuromuscular effects may lead to respiratory compromise. Potential physical exam findings of autonomic dysfunction include diaphoresis, tachycardia, nausea and vomiting, and mydriasis. Other signs are hyperactive bowel sounds, diarrhea, and flushing. Clinical findings associated with neuromuscular excitation are myoclonus, hyperreflexia, hyperthermia, hypertonicity, and rigidity. Other signs are spontaneous or inducible clonus, ocular clonus, and tremor. Patients often present with confusion and agitation as well as anxiety, lethargy, and coma. The symptoms vary based on the severity of the serotonergic toxicity and may not present simultaneously (Wang et al., 2016).
c. There are several conditions that can alter the regulation of serotonin, including therapeutic doses, drug interactions, intentional 749or unintentional overdoses, and overlapping transitions between medications. The only drugs that have been reliably confirmed to precipitate serotonin syndrome are monoamine oxidase inhibitors (MAOIs), SSRIs, serotonin–norepinephrine reuptake inhibitors (SNRIs), and serotonin releasers. But there are other drugs that have been implicated with serotonin syndrome and are categorized into five different classes:
i. Drugs that decrease serotonin breakdown (e.g., MAOIs, linezolid, methylene blue, procarbazine)
ii. Drugs that decrease serotonin reuptake (e.g., SSRIs, SNRIs, TCA, opioids [meperidine, buprenorphine, tramadol, tapentadol], dextromethorphan, antiepileptics [carbamazepine, valproate], and antiemetics [ondansetron, granisetron, metoclopramide], and the herbal preparation St. John’s wort)
iii. Drugs that increase serotonin precursors or agonists (e.g., tryptophan, lithium, fentanyl, and lysergic acid diethylamide [LSD])
iv. Drugs that increase serotonin release (e.g., fenfluramine, amphetamines, and methylenedioxymethamphetamine [MDMA; ecstasy])
v. Drugs that prevent breakdown of the agents listed earlier (e.g., erythromycin, ciprofloxacin, fluconazole, ritonavir, and grapefruit juice)
d. Treatment consists of two primary interventions: to discontinue the serotonergic agent and to provide supportive care. Treatment may include GI decontamination when appropriate. For severe serotonin toxicity, treatment should focus on management of the ABCs. The two primary life-threatening concerns are hyperthermia (temperature >40°C or 104°F) and muscle rigidity, which can lead to hypoventilation. Controlling hyperthermia and rigidity can prevent other severe complications such as rhabdomyolysis. Patients with severe serotonin toxicity should be sedated using benzodiazepines, neuromuscularly relaxed with a nondepolarizing medication, intubated, and supported with mechanical ventilation. This will reverse ventilatory hypertonia. Neuromuscular relaxation will also prevent the exacerbation of hyperthermia, which is due to muscle rigidity. Standard cooling measures should be used to manage hyperthermia. Antipyretics have no role in the treatment of serotonin syndrome since the hyperthermia is not caused by a change in the hypothalamic temperature set point. Most patients demonstrate improvement within 24 hours of stopping the precipitating drug and implementing therapy.
i. Cyproheptadine is a serotonin and histamine antagonist with anticholinergic and sedative effects. Antiserotonin and antihistamine drugs appear to compete with serotonin and histamine, respectively, for receptor sites. The recommended initial dose of cyproheptadine is 12 mg, followed by 2 mg every 2 hours if symptoms continue. Maintenance dosing with 8 mg every 6 hours should be prescribed once stabilization is achieved. The total daily dose for adults should not exceed 0.5 mg/kg/d. Cyproheptadine is available only in oral form but can be crushed and administered via a nasogastric tube (Taketomo, Hodding, & Kraus, 2015).
e. Because patients are often prescribed more than one drug, those with a history of having overdosed on an SRI should be evaluated for coingestion of other drugs, especially other antidepressants.
Benzodiazepines are used as adjuncts to anesthesia, as anticonvulsants, for muscle spasms, and for anxiety relief. Young children may have access to these drugs if they are being taken therapeutically by family members. They may also be abused or self-administered in suicide attempts. The combination of a benzodiazepine with ethanol or another CNS depressant significantly increases toxicity. In general, overdoses of these drugs can be successfully treated with respiratory support and sometimes the antidote flumazenil.
1. Commonly used benzodiazepines include alprazolam, clonazepam, oxazepam, lorazepam, diazepam, and chlordiazepoxide. Midazolam is used as an adjunct to anesthesia.
2. Benzodiazepines act by enhancing the effects of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain. The many types of drugs within the class make it impossible to generalize about absorption and elimination. Some of those prescribed for therapeutic use in the outpatient 750setting (e.g., diazepam) have a long half-life; therefore, significant and prolonged respiratory depression should be anticipated in someone who abused the drug or took a large quantity.
3. Effects of overdose include respiratory and CNS depression, which may necessitate intubation and mechanical ventilatory support. In an uncomplicated overdose, there are no specific drug-related laboratory values of use. In a potential mixed overdose, determination of coingestants is important.
4. Flumazenil is the specific antidote. Flumazenil effectively reverses respiratory depression associated with benzodiazepine overdose, but there are contraindications. A test dose may be used to help determine whether respiratory depression is caused by a benzodiazepine overdose, although it should not be used to maintain wakefulness. Caution must be used to avoid precipitating withdrawal in a patient who is dependent on a benzodiazepine. Flumazenil should never be used if the patient has also overdosed on a TCA because an increased risk of seizures has been associated with this use. Likewise, flumazenil should not be used if the patient is known to have a seizure disorder.
5. Treatment includes primarily symptomatic and supportive care, including potential intubation. If the patient is habituated to the drug, withdrawal symptoms may occur. A protocol to prevent acute withdrawal and accomplish gradual withdrawal must be implemented.
E. Calcium-Channel Blockers
CCBs include amlodopine, diltiazem, nicardipine, nifedipine, verapamil, and others, in regular and sustained-release preparations. As indications for their use in cardiovascular disease and other conditions have increased, poison exposures and fatalities in children have also increased. No antidote or universally effective treatment exists. Aggressive GI tract decontamination may be necessary depending upon the clinical circumstances and vigorous supportive care are required.
1. CCBs are easily absorbed from the GI tract. Elimination rates vary but can be prolonged for days after an overdose.
2. Calcium is required for cellular contraction. These drugs, therapeutically and in overdose, slow the influx of calcium through calcium channels into the intracellular space of cardiac nodal tissue, myocardial tissue, and vascular (especially arteriolar) tissue. The result is conduction delays, diminished cardiac output, and hypotension.
3. The toxic dose is variable but small. The ingestion of any amount (concept of “one sip or pill can kill”) of any of these CCB agents should be considered potentially fatal in a child.
4. Physical assessment must be comprehensive. There are multiple mechanisms for hypotension (decreased cardiac output, diminished peripheral vascular resistance), hypoxia and apnea (bradydysrhythmias, heart block, decreased cardiac output), and metabolic acidosis (hypoperfusion, hypoxia). Also common are CNS depression, seizures, possibly hypoxic seizures, headache, flushing, and hyperglycemia (CCBs inhibit insulin release). Electrolyte monitoring, ABG analysis, ECG, and continuous assessment of respiratory and cardiovascular status are needed. Recognize that the patient may exhibit hypotension with relative preservation of mental status until cerebral perfusion is affected.
5. Treatment with GI decontamination may be considered because CCBs slow gastric motility and delay gastric emptying. Options include activated charcoal, gastric lavage, and consideration of WBI for ingestion of multiple tablets or sustained-release preparations. High-dose IV calcium chloride or calcium gluconate is indicated as theoretically it creates a concentration gradient large enough to partially overcome the channel blockade, driving calcium into the cells, although it is not usually effective. In a patient with stable electrolyte and acid–base status, calcium chloride is preferred because it contains a higher concentration of calcium. (Extravasation of calcium chloride can cause tissue necrosis, so placement and patency of peripheral IV lines must be checked before each administration by this route.) Insulin plus dextrose has been used to stabilize blood pressure in patients refractory to other treatments. The disruption of calcium homeostasis causes a negative chronotropic and inotropic effect and vasodilatation as well as impaired glucose metabolism. Glucagon may be used to increase the heart rate and conduction velocity, although it, too, is not always effective. Otherwise, treatment is symptomatic and supportive, including fluid resuscitation with crystalloid solutions. If volume expansion does not raise the blood pressure to the desired level, vasopressors (e.g., dopamine, epinephrine) can stimulate myocardial contractility and cause vasoconstriction supporting blood pressure and cardiac output. If 751refractory hypotension exists, various combinations of vasoactive infusions may be necessary. In the hypotensive and bradycardic patient, administer atropine.
6. Serum calcium levels must be monitored closely while treatment continues. In addition, other electrolytes must be serially monitored, including potassium, magnesium, and serum glucose levels. No absolute change in the quantity of the patient’s calcium stores occurs, but there is a change in the distribution of calcium stores.
Chloroquine is used to treat malaria and rarely for other medical conditions, such as rheumatoid arthritis. It is rapidly absorbed and has a narrow therapeutic margin. Exposures are unintentional in children, suicidal in adults, and a result of therapeutic error in all ages (i.e., taking the drug daily rather than weekly, as indicated). There is no antidote and no therapy has been proved to be effective for patients with severe chloroquine poisoning, which is usually fatal. Overdoses are infrequent, but apnea, hypotension, seizures, cardiorespiratory collapse, and death can occur within 30 to 60 minutes after ingestion.
1. The toxic dose of chloroquine overlaps the therapeutic dose. Chloroquine poisoning in children, although infrequent, is extremely dangerous because of the narrow margin between therapeutic and toxic doses. Children have died after ingestion of less than 300 mg.
2. If a patient survives to reach the ICU, treatment includes activated charcoal (and possibly a cathartic) if not already administered, and vigorous symptomatic and supportive respiratory, cardiac, and neurologic care. Epinephrine and diazepam are the drugs of choice for cardiac effects and seizures. Close monitoring of electrolytes is necessary. Patients are often hypokalemic.
Digoxin is a purified cardiac glycoside similar to digitoxin extracted from the foxglove plant. Digoxin overdoses in the pediatric population are usually acute, although chronic intoxication may occur. Children may have access to their own drugs or those of family members. Pediatric therapeutic doses must be carefully calculated and measured, and blood levels must be carefully monitored. Some plants contain cardiac glycosides with digitalis-like effects if ingested, including purple foxglove (Digitalis purpurea) and oleander (Nerium oleander). Poisoning by these plants is treated the same as digitalis poisoning.
1. Digitalis usually is absorbed rapidly and excreted renally.
2. The toxic effects of digitalis are exacerbations of therapeutic effects. Digitalis interferes with the Na+–K+–ATPase pump, found in smooth muscle and abundantly in cardiac tissue. Therapeutically, this maintains the correct proportions of intracellular and interstitial sodium, potassium, and calcium necessary for cellular contraction and nodal conduction. When the Na+–K+–ATPase pump is poisoned by toxic concentrations of digitalis, intracellular calcium levels rise, intracellular potassium is depleted, and serum potassium levels become markedly elevated. However, patients may present with hypokalemia when digitalis is administered chronically in conjunction with diuretics. Any and every dysrhythmia can result. Atrial dysrhythmias, bradycardia, and heart block are most common, along with ventricular irritability and hypotension.
3. A toxic dose can be estimated by history, but there is no substitute for laboratory evaluation of serum levels and careful evaluation of the patient. The therapeutic trough range is 0.5 to 2 ng/mL, but toxicity can occur within this range.
4. Clinical effects of acute overdose occur in the GI and cardiovascular systems: nausea, vomiting, hypotension, bradycardia, and dysrhythmias. In chronic overdose, visual changes are also described, especially yellow or green “halos” or “hazes.” Laboratory evaluation of electrolytes, especially potassium, and renal function is needed, along with the serum digitalis level. Continuous ECG monitoring is essential.
5. Treatment of digitalis overdose includes prevention of absorption, intensive monitoring, administration of the antidote, and symptomatic and supportive care.
a. GI tract decontamination may be indicated, particularly if there is a delay in obtaining the antidote digoxin immune Fab, with administration of MDAC to enhance clearance of digitoxin.
b. Usual measures are indicated to treat bradycardia and other dysrhythmias, hypotension, and hyperkalemia.
c. Administration of the antidote, digoxin immune Fab, quickly reverses severe hyperkalemia and life-threatening dysrhythmias. Care must be taken when administering the antidote in patients who are chronically treated with digoxin, as the reversal can lead to the occurrence of the underlying cardiac condition or arrhythmia. IV administration of 40 mg of digoxin 752immune Fab fragments (one vial) binds approximately 0.5 mg of digitalis. The poison center can help to make other dose determinations if the amount of ingested digitalis is not available. Patients with renal failure may need dialysis to remove the digoxin immune Fab complex.
d. If the antidote is not available, standard but aggressive treatment is needed to treat hyperkalemia (insulin, glucose, and sodium bicarbonate), support blood pressure, and treat dysrhythmias. Patients in renal failure require dialysis to remove digitalis.
e. Monitoring serum digoxin levels can be confusing after antidote administration, as some laboratory methods measure and report a concentration that includes both free digitalis and that bound to Fab. It is necessary to know whether reported digitalis levels are of free digitalis only. This is especially important for patients treated therapeutically with digitalis who must remain digitalized. Consultation with a cardiologist should occur for these patients.
H. Diphenoxylate and Atropine
Diphenoxylate–atropine combinations (e.g., Lomotil) are used to treat diarrhea in adults. There is no safe amount of this drug for young children. This is a category of products with the potential to cause life-threatening toxicity or death in a child younger than 2 years of age, despite the ingestion of only one or two tablets or sips. The combination of powerful opioid and anticholinergic effects is the reason for both its therapeutic usefulness in adults and its danger in young children.
1. The anticholinergic effects of atropine cause this drug to be retained in the GI tract for prolonged periods. The onset of opioid effects can be delayed for as long as 24 hours after ingestion.
2. Every child who ingests any amount of this drug must be monitored for 24 hours, ideally in an ICU setting, especially when symptomatic.
3. Treatment includes GI tract decontamination, symptomatic and supportive care, and careful monitoring for the onset of CNS and respiratory depression induced by diphenoxylate, the opioid component of this drug. Naloxone is effective for symptoms of opioid overdose.
I. Oral Hypoglycemic Agents
The mechanism of action of sulfonylureas or oral hypoglycemic agents, including glyburide and glipizide, results in increased insulin production, and can cause the delayed onset of significant hypoglycemia in children, even in single-tablet ingestions. Every young child who swallows even one of these pills requires GI tract decontamination when presenting early after ingestion and admission, with hourly serum glucose determinations, for 24 hours. If hypoglycemia occurs, treat with IV dextrose. Glucagon may be ineffective because small children have little stored glycogen. Octreotide, whose mechanism of action is theorized to suppress insulin release, may be administered to stabilize serum glucose in conjunction with dextrose infusion to prevent hypoglycemia.
J. Imidazoline Derivatives
Clonidine, like many other imidazoline derivatives, is usually thought of as a selective α2-adrenergic agonist and is approved for use as a centrally acting antihypertensive, in addition to ocular and nasal vasoconstrictors as tetrahydrozoline, naphazoline, and oxymetazoline. All are α2-agonists with mixed central and peripheral effects. A single tablet of clonidine, inadvertent application of even a used clonidine patch, or just several drops of the other drugs can cause the onset of coma, respiratory depression, and hypotension within 30 minutes of ingestion (or topical application for liquid vasoconstrictors and decongestants). GI tract decontamination is indicated for solid dosage forms with activated charcoal if the patient presents within 1 hour of ingestion and prior to symptoms. Symptomatic and supportive care is required for 24 to 36 hours, and a full recovery is expected.
Iron in the form of adult-strength supplements and prenatal vitamins with iron cause dangerous overdose in children younger than 6 years of age. Prescription-strength preparations may contain 60 to 65 mg of elemental iron per tablet, although some contain more than 100 mg of elemental iron. Fatalities in children from iron poisoning have declined because over-the-counter preparations now usually contain less than 30 mg of elemental iron per tablet. Overdoses of children’s chewable multiple vitamins with iron may cause iron toxicity, but they have not been associated with iron-related fatalities in children. Iron supplements are sometimes used in suicide attempts by others, especially pregnant teenagers. The use of deferoxamine, a specific antidote, is important but may be limited in serious iron poisoning because of side effects, especially hypotension.
1. In overdose, iron causes significant corrosive injury to the GI tract. Absorption of iron is thus enhanced. Circulating free iron injures blood vessels and damages hepatocytes. As iron is metabolized, free hydrogen is released; in concert with other events, this produces metabolic acidosis.
7532. Mild symptoms may occur with ingestion of more than 20 mg/kg of essential iron. Significant toxicity or death is possible with ingestions of more than 60 mg/kg; this amount of iron can be ingested by a 10-kg child who swallows just 10 typical prescription-strength adult preparations. The amount of essential iron in each iron salt varies; the potential risk is calculated by determining the iron salt and the amount of essential iron in each preparation, the number of pills missing, and the child’s body weight. Actual risk is determined by serum iron levels and the presence or absence of symptoms.
3. The course of severe iron poisoning is typically described in five sequential phases, although individual patients may not always demonstrate each of the phases. There is no universal agreement as to number of phases or times assigned to those phases.
a. Phase I usually occurs within the first 6 hours after ingestion, includes GI tract symptoms, possibly severe, consisting of hemorrhagic gastritis, vomiting, hematemesis, diarrhea, lethargy, and pallor. A patient is unlikely to develop significant systemic toxicity without first having GI symptoms. In severe cases, the GI losses of blood and fluid may be massive and lead to shock and coma.
b. Phase II is a latent phase occurring about 6 to 12 hours after ingestion, during which the patient is asymptomatic or demonstrates an improvement in symptoms, especially when supportive care was initiated during phase I. The systemic insults described in phase I continue during this asymptomatic phase, and the patient abruptly enters phase III in serious ingestions. The only findings on examination may be lethargy, mild tachycardia, or tachypnea.
c. Phase III occurs about 12 to about 24 hours after ingestion, involves a rapid onset of cardiovascular collapse and multisystem damage. Hypotension, marked metabolic acidosis, increasing lethargy and coma, seizures, pulmonary edema, hepatorenal failure with coagulopathies, shock, and hypoglycemia occur due to mitochondrial damage and hepatocellular injury.
d. Phase IV occurs 2 to 3 days postingestion and is characterized by hepatic injury. Death may occur rapidly or after days or weeks of complications, including intestinal necrosis.
e. Phase V occurs 2 to 6 weeks postingestion and is characterized by late scarring of the GI tract, which causes pyloric obstruction or hepatic cirrhosis. However, these complications are rare, even in severe cases.
4. Assessment of these patients includes careful evaluation of physical findings and laboratory results. Determine the nature of any symptoms and the time of onset compared with the time of ingestion.
a. Initial laboratory studies include an ideal serum iron level, which is a peak level at 2 to 6 hours after ingestion, complete blood count (CBC), and electrolytes. Patients with more than mild GI tract symptoms also require ABG analysis and baseline hepatic and renal function studies. Typing and crossmatch are indicated if there is frank bleeding or guaiac-positive stools.
b. Iron tablets (not pediatric chewable vitamins with iron) are radiopaque. An abdominal radiograph may permit counting of tablets in the child’s GI tract, but a negative image cannot be used to rule out iron ingestion.
5. Treatment of the iron-poisoned child includes GI tract decontamination, chelation with deferoxamine, and symptomatic and supportive care.
a. GI tract decontamination may include WBI. If an abdominal radiograph demonstrates iron pills in the intestinal tract, WBI is used until the appropriate number of pills is counted in the rectal effluent or until a repeat radiographic examination documents that the pills have been removed. Iron is not adsorbed to activated charcoal.
b. Chelation is indicated if the serum iron level is greater than 350 mcg/dL in the presence of symptoms, or if the serum iron is greater than 500 mcg/dL. Deferoxamine is administered IV. The intramuscular route may be used only when severe symptoms are not present. The usual dose of deferoxamine is 15 mg/kg/hr. Higher doses are sometimes used but may be associated with hypotension. “Vin rosé-”colored urine, is a marker for elimination of deferoxamine-iron chelate, but this does not always appear and is not always reliable. Serum iron levels are more accurate.
c. Serum iron levels must be repeated until it is certain that levels are dropping and that there is not a concretion, or clump, of iron tablets being slowly absorbed from the GI tract.
d. Symptomatic and supportive care is required with aggressive measures to stop GI tract bleeding, correct hypovolemia and hypotension, and treat coagulopathies and other consequences of hepatic failure. After the acute phase passes, the patient will require follow-up with gastroenterology to monitor for GI obstruction secondary to strictures and scarring.
e. Iron poisoning is associated with two special dangers. Parents and healthcare providers often 754think of iron as “just” a vitamin and are ignorant of the fact that quite small amounts of this essential element can cause fatalities in children. Second, the asymptomatic latent phase of iron poisoning fools parents and healthcare providers who misinterpret the absence of symptoms as absence of risk.
Isoniazid (INH) is used to treat tuberculosis. Young children may have access to the drug, and it is used in suicide attempts by teenagers.
1. INH, given therapeutically or taken in overdose, depletes the body of pyridoxine (vitamin B6). Pyridoxine is a cofactor in numerous enzymatic reactions, including those responsible for the generation of GABA. GABA is an inhibitory neurotransmitter in the CNS and the depletion leads to seizures.
2. An overdose of INH can precipitate depressed mental status or the onset of generalized tonic–clonic seizures, potentially within 30 minutes of ingestion as it is rapidly absorbed, and the subsequent development of severe acidosis.
3. The only effective treatment for INH-induced seizures is IV pyridoxine. If the dose of INH is known, the dose of pyridoxine is a milligram-per-milligram equivalent (70 mg/kg up to 5 g). If the dose is unknown, pyridoxine 5 g IV, should be administered (Taketomo et al., 2015). Benzodiazepine (lorazepam or diazepam) is an effective adjunct as it enhances the action of GABA, but it cannot assist with synthesis of GABA and is not a substitute for pyridoxine.
4. Once seizures are controlled, GI tract decontamination utilizing activated charcoal can be considered, but is likely to be ineffective due to time elapsed. Acidosis often corrects itself once seizures are controlled, but it is amenable to the usual therapies. Treatment otherwise is symptomatic and supportive.
Opioids are found in a variety of prescription preparations and illicit or street drugs. Because the ICU nurse is familiar with the administration of opioid analgesics and antitussives, this section simply emphasizes a few points related to overdose.
1. The classic triad of symptoms (miosis, respiratory depression, and coma) may be masked by concomitant administration of other drugs. Abusers of stimulant drugs, such as cocaine and amphetamines, frequently use an opioid or other depressant simultaneously. Opioids may be abused inadvertently when drug dealers substitute them for or combine them with other drugs.
2. Young children can be markedly sensitive to some opioids. Dangerous situations may occur when parents each inadvertently administer a codeine-containing antitussive.
3. Some opioids are associated with clinically significant differences:
a. Meperidine (Demerol) use or abuse is not necessarily associated with pinpoint pupils. Also, normeperidine, the first metabolite of meperidine, is a CNS stimulant; chronic use or abuse is therefore associated with seizures.
b. Propoxyphene (Darvon) and pentazocine (Talwin) may require up to 10 mg of naloxone to reverse the respiratory depression they induce, much higher than the standard naloxone dose.
c. Methadone has a half-life of about 24 hours, much longer than other opioids, and requires sustained doses of naloxone by IV infusion to prevent respiratory depression until the methadone is eliminated.
4. Dermal patches and oral lozenges containing fentanyl, even if they were used and discarded, are a significant risk to children who access them, for example, by retrieving them from a trash can. Discarded fentanyl patches contain sufficient residual drug to seriously poison a child who chews, swallows, or applies one to the skin.
N. Salicylate Poisoning
Salicylate poisoning is most often due to aspirin. However, most fatal salicylate poisonings in children occur from ingestion of methyl salicylate (oil of wintergreen), a rapidly absorbed liquid, and from GI tract preparations containing bismuth subsalicylate. Older children and teenagers may take aspirin in suicide attempts. Although chronic salicylate poisoning may occur on therapeutic doses, such doses are rarely used in children.
1. Aspirin is rapidly absorbed. In therapeutic doses, it has a small volume of distribution and is bound to serum proteins. It undergoes hepatic metabolism and renal excretion. With chronic administration, receptors are saturated and free salicylate accumulates rapidly.
2. The actions of salicylate in overdose are complex and interdependent. Salicylates impair cellular respiration by uncoupling oxidative phosphorylation. Stimulation of the central respiratory drive causes primary respiratory alkalosis. A primary metabolic acidosis is independently caused by salicylates, 755eventually becoming the primary acid–base abnormality as mitochondria are affected. Interference with carbohydrate and lipid metabolism generates organic acids and ketone formation. Increased metabolic demands result in hypoglycemia, both in the serum and the CNS. Uncoupling of oxidative phosphorylation leads to hyperthermia. Direct CNS toxicity can cause tremor, agitation, seizures, and coma. Sequence and exact clinical effects depend on size, timing, and acuity of ingestion and the age and health of the patient. A careful evaluation of each patient’s status and history is essential.
3. Acute toxicity generally correlates with ingested dose. Ingestions of greater than 150 mg/kg by history may be associated with mild toxicity, moderate toxicity ingestions up to 300 mg/kg, severe toxicity with doses of 300 to 500 mg/kg and greater than 500 mg/kg with fatality. Severe poisoning include high salicylate blood levels: 7.25 mmol/L (100 mg/dL) in acute ingestions or 40 mg/dL in chronic ingestions, significant neurotoxicity (agitation, coma, convulsions), kidney failure, pulmonary edema, or cardiovascular instability. Death is often a result of pulmonary edema leading to cardiovascular collapse. Optimally, plasma levels should be assessed 4 hours after ingestion and then every 2 hours after that to allow calculation of the maximum level, which can then be used as a guide to the degree of toxicity expected.
4. In the absence of history, suspect salicylate poisoning in a patient who presents with tachypnea, tachycardia, hyperthermia, diaphoresis, mental status changes, respiratory alkalosis, metabolic acidosis, or mixed acid–base abnormalities. If present, tinnitus is an important clue, as is frank or occult GI tract bleeding.
5. Treatment objectives include cardiopulmonary stabilization, prevention of absorption, correction of fluid deficits, correction of acid–base abnormalities, and enhancement of excretion and elimination. As with all significant overdoses, ABCs should be evaluated and stabilized as necessary. Dehydration and concomitant electrolyte abnormalities must be immediately corrected. Initial treatment includes GI decontamination, followed by MDAC administered every 4 hours with a cathartic once in 24 hours if salicylate levels continue to rise. Activated charcoal can limit further gut absorption by binding to the available salicylates. MDAC may enhance salicylate elimination and may shorten the serum half-life as well as assist in treating bezoars with ongoing absorption of salicylates, which should be suspected when salicylate levels continue to rise or fail to decrease despite appropriate treatment. Hydration is essential but must be controlled to avoid precipitating pulmonary edema. Potassium supplementation is often needed. Renal excretion of salicylic acid depends on urinary pH. Alkalinization of blood and urine enhances urinary excretion. Ion trapping may occur, as aspirin is a weak acid and ionizes when exposed to a basic environment, such as alkaline urine, and is excreted more readily. The administration of sufficient amounts of sodium bicarbonate to correct acidosis and achieve a urine pH between 7.5 and 8 enhances renal excretion of salicylate. Hemodialysis can be used to enhance the removal of salicylate from the blood and is usually used in those who are severely poisoned. Otherwise, treatment must be aggressive, but primarily is symptomatic and supportive.
6. Special Considerations
a. Aspirin tablets may clump together in the stomach, forming concretions, or bezoars, that may be slowly absorbed over an extended period. If a large ingestion is suspected, it is essential to measure serial salicylate levels to avert the delayed onset of fatal effects as well as with ingestion of sustained-release forms of aspirin, which can result in the delayed onset of symptoms.
b. The time between ingestion and death from salicylate poisoning can often be measured in just hours, so a high index of suspicion and aggressive management are essential to prevent serious CNS effects and fatalities.
Sympathomimetic drugs are represented by both legal and illegal agents in the pediatric age group: Cocaine is a legal, useful topical vasoconstrictor and a widely abused street drug; amphetamines are used as weight-control agents, to treat hyperactivity disorders, and as the street drug “speed”; legal decongestants and appetite suppressants are sold as “street speed” or amphetamine look-alikes. Ephedra, even if it is not available legally, can be obtained via the Internet. The use of designer and over-the-counter drugs has exploded, due to Internet and social media descriptions. Over-the-counter medications, particularly those containing dextromethorphan (known as dex), have become popular recreational drugs among adolescents in addition to the numerous emerging synthetic compounds and herbal agents. Children are poisoned by ingesting appetite suppressants or taking an overdose of cough, cold, or allergy preparations containing decongestants and by swallowing available street drugs. Adolescents are 756poisoned by taking overdoses of appetite suppressants, by abusing street drugs, or by attempting to avoid arrest by swallowing illicit drugs. Hallucinogenic amphetamines (MDMA, methylenedioxyamphetamine [MDA], Ecstasy, “Adam,” “Eve”) are abused as “party drugs” or “rave drugs.” The intended use, route of administration, and duration of action of these drugs may differ, but the acute clinical effects are indistinguishable, and treatment of acute effects is essentially the same.
1. The toxic dose is variable and may be idiosyncratic. In street drugs, the actual amount of drug, as opposed to adulterants, is unknown.
2. Clinical effects are as expected for any sympathomimetic agent: tachycardia; hypertension; diaphoresis; mydriasis; agitation and tremulousness; and central vasoconstriction, including cardiac, cerebral, and visceral effects. In significant poisoning, ventricular dysrhythmias, seizures, hyperthermia, and coma may develop. The hallucinations sought by users of “party” or “rave” drugs are accompanied by other sympathomimetic effects, especially extreme hyperthermia.
3. Clinical assessment and laboratory evaluation are straightforward. As with all significant overdoses, ABCs should be evaluated and stabilized as necessary. When unknown agents are suspected, acetaminophen and salicylate levels should be obtained as they are common coingestants. ECG should be obtained to evaluate for conduction disorders, which are common with these category of agents. Dehydration and relative hypovolemia is common so fluid hydration status needs to be assessed and corrected. If the patient has severe agitation, serum electrolytes, renal function, and CK should be evaluated as rhabdomyolysis is a potential consequence. When possible, identification of the drug involved helps to predict the duration of effects: a few hours for cocaine unless complicated by cardiac, cerebral, or other events caused by vasoconstriction, hyperthermia, or seizures; 18 to 24 hours for amphetamines, with the same caveat; variable times are needed for the other drugs and are dependent to some extent on whether they are sustained-release preparations. Although radiographic examinations are not generally indicated in poisoning by sympathomimetic drugs, in the case of swallowed illegal drugs, they may help to visualize the number and location of the packets.
4. Treatment of these poisonings includes GI tract decontamination when indicated plus symptomatic and supportive care. A single dose of activated charcoal with a cathartic is indicated unless drug packets (e.g., vials, condoms, balloons, foil) have been swallowed. In these cases, WBI may be indicated until the packets pass. If agitation is present, it can be treated with the administration of benzodiazepines. Severe hyperthermia may result secondary to muscle rigidity and needs to be treated by minimizing muscle activity. If benzodiazepines do not adequately treat agitation and muscle rigidity, intubation with a nondepolarizing neuromuscular agent, to minimize hyperkalemia and rhabdomyolysis, may be required.
P. Synthetic and Herbal Products
The emergence of numerous synthetic compounds and herbal agents has led to significant rise in use of such agents among adolescents. These emerging substances are being used for recreational purposes without any knowledge of their potential harmful effects. These new substances have resulted in significant poisoning morbidity and mortality in the pediatric population, producing acute and chronic toxicity as well as numerous deaths. Spice, a synthetic cannabinoid, first marketed as an “herbal” product, and bath salts, synthetic cathinone stimulants that mimic cocaine-type effects, are the most well-known drug trends. Both types of products were marketed and sold in gas stations and over the Internet without any age restrictions in the United States before the Drug Enforcement Agency banned possession and sale of the chemicals that were utilized in the production of these agents. Yet a whole new line of synthetic and herbal products continues to emerge, marketed along the same pathways as spice and bath salts. The constantly changing names and product chemical contents create a challenging environment for healthcare professionals to understand the products being utilized. There are limited studies to track potency or side effects because of the nature of the constantly changing chemicals and ingredients. Many individuals are utilizing alternative or synthetic drugs under the false belief that they are legal substitutes for popular street drugs and are therefore safe. The manufacturers of these synthetic drugs change the chemical content, change the names, and mark the packaging as “not intended for human consumption” or “research chemical,” which does not deter individuals from using them. These emerging drugs are also more readily available through legitimate sources such as convenience stores, gas station markets, gardening/plant stores, and via the Internet.
1. The toxic dose is variable and may be idiosyncratic. In street drugs, the actual amount of drug, as opposed to adulterants, is unknown.
2. Clinical effects are wide ranging as described in Table 9.23.
3. Clinical assessment and laboratory evaluation are straightforward. When possible, identification of the drug involved helps to predict the duration of effects.
4. Treatment of these poisonings includes GI tract decontamination when indicated and then aggressive symptomatic and supportive care.
POISONING BY NONPHARMACEUTICAL AGENTS
A. Carbon Monoxide
Carbon monoxide is a colorless, odorless, tasteless, nonirritating, and highly toxic gas. It is a major product of the incomplete combustion of carbon and carbon-containing compounds. The most common residential sources are house fires, exhaust from automobiles and gas-powered equipment, furnaces, space heaters, wood- and coal-burning stoves and fireplaces, gas ovens, and hot water heaters. Methylene chloride, found in paint strippers, is metabolized to carbon monoxide after ingestion, inhalation, or dermal absorption.
1. Carbon monoxide has an affinity for hemoglobin 200 times greater than that of oxygen. Besides displacing oxygen at hemoglobin receptor sites, it inhibits the release of oxygen from hemoglobin. Therefore inadequate amounts of oxygen are circulating, and that which is circulating is less available to tissues.
2. The effects of carbon monoxide poisoning are related to hypoxemia and the resultant direct tissue hypoxia; the greater the amount of carboxyhemoglobin, which is a stable complex of carbon monoxide that forms in RBCs when carbon monoxide is inhaled, the more severe the symptoms. Direct cellular toxicity also occurs. A carboxyhemoglobin level of about 10% may be associated with headache, nausea, and lethargy. As the carboxyhemoglobin level increases, GI tract and CNS symptoms increase. At a level of 50% the patient is unconscious, and victims of carbon monoxide exposure die at levels of about 70% or greater. Symptoms of chronic carbon monoxide exposure (e.g., due to malfunctioning furnaces or clogged chimneys) are often mistaken for a viral or flulike illness.
3. Evaluating victims of carbon monoxide poisoning requires close attention to symptoms experienced at any time since exposure, not just at the time of evaluation. Standard pulse oximetry, as with methemoblobin, cannot distinguish between carboxyhemoglobin and oxyhemoglobin. The carboxyhemoglobin level at the time of presentation may have declined markedly since the patient was exposed. Carboxyhemoglobin is measured via either arterial or venous blood, to assess lactate and acid–base status as measures of tissue hypoxia. Arterial blood is preferred for the diagnosis of carbon monoxide poisoning due to its precision in assessment of acidosis, especially lactic acidosis, which affects the assessment of the severity and management of carbon monoxide poisoning An ECG should 759be obtained to evaluate for myocardial ischemia. Cherry-red skin is a hallmark finding associated with carbon monoxide poisoning. After an acute exposure to carbon monoxide, those who have lost consciousness, even if they are now awake, and fetuses are at greatest risk.
4. The initial treatment for carbon monoxide poisoning is administration of 100% oxygen. Carbon monoxide elimination occurs primarily via the pulmonary circulation by competitive binding of hemoglobin to oxygen. The rate of elimination is related proportionally to the degree of oxygenation, atmospheric conditions, and minute ventilation. The half-life of carbon monoxide is approximately 300 minutes in an individual breathing room air. The application of high-flow oxygen via a nonrebreather mask can reduce the half-life to approximately 80 minutes. Hyperbaric oxygen, which has a pressure three times atmospheric pressure, reduces the half-life even further to approximately 20 to 30 minutes and is indicated for those who were or are unconscious, pregnant women, those who remain symptomatic after oxygen administration, those who have severe metabolic acidosis, concern for end-organ ischemia, and those with recurrent symptoms. Hyperbaric oxygen may improve tissue oxygenation by bypassing the normal transfer of oxygen via hemoglobin (Weaver, 2009).
5. Other treatment is primarily symptomatic and supportive.
6. Special Considerations
a. Children and household pets are at greatest risk for carbon monoxide poisoning because of their rapid respiratory and metabolic rates. When a family is poisoned by carbon monoxide, children are generally more seriously ill.
b. Aggressive treatment is required because long-term neuropsychiatric sequelae have been documented in adults with carbon monoxide exposure. Because of the difficulty or impossibility of conducting and interpreting such tests in children, long-term sequelae are postulated but not documented.
c. Consider carbon monoxide poisoning in any family or gathering in which a number of people become ill with GI and CNS complaints.
d. Unless the source of carbon monoxide is known (e.g., a suicide attempt with automobile exhaust, house fire) or remedied (e.g., repair of a faulty furnace), patients and their families must not return to a possibly contaminated environment.
e. Encourage the installation of carbon monoxide alarms in dwellings intended for human occupancy. Some individual states have mandated placement of carbon monoxide alarms in certain types of dwellings.
B. Caustic Substances
Caustic substances are strong acids or alkalis that cause chemical burns on the tissues that come in contact with the substance. Young children are injured by unintentional contact with household substances, especially with improper storage, whereas older children may ingest these substances in suicide attempts. Occasionally children are exposed when they attempt unsupervised experiments. Although the sources and mechanisms of injury are different, treatment and nursing care for both are essentially the same for both acids and alkalis. The single exception is hydrofluoric acid, which is considered separately.
Over the past 10 years, there has been an increase in ingestion incidence of a specific caustic substance, the button battery cell. There are four main types of button cell: mercury, silver, alkaline manganese, and lithium. Although these cells are sealed, they contain corrosive and toxic chemicals. The most serious injuries are usually associated with 20-mm-diameter batteries, about the size of a nickel, as they are likely to get lodged in a small child’s esophagus. Lodgment in the esophagus can lead to tissue injury, with mucosal damage and necrosis within hours and with exposure to gastric acid there is a remote risk of leakage of the cell contents leading to perforation or death (Litovitz, Whitaker, Clark, White, & Marsolek, 2010).
a. Acids, such as sulfuric acid, hydrochloric acid, and muriatic acid (dilute hydrochloric acid), are found in toilet bowl cleaners, swimming pool chemicals, metal cleaners, and concrete and masonry cleaners. These products tend to be liquids and after ingestion are usually associated with greater injury to the stomach than to the esophagus.
b. Alkaline substances are liquids or solids found in wet cement, drain openers, oven cleaners, laundry detergent packets/pods, and automatic dishwasher detergent. Examples include sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, and some phosphates. Children who bite into ammonia 760capsules are likely to develop an alkaline burn on the tip of the tongue.
2. Mechanism of Injury
a. Acids precipitate proteins and dehydrate tissues; exposure causes vascular thrombosis and the rapid formation of eschar. This hard crust helps to limit further penetration of acid into tissue. In general, serious injury is associated with exposure to products with a pH less than 2.
b. Alkaline substances cause vascular thrombosis and liquefaction necrosis. They disrupt cell walls and combine with lipids, which accounts for the soapy appearance of tissue and provides no protection whatsoever from further penetration of the chemical into tissue. In general, serious injury is associated with products with a pH higher than 12.
3. The degree of injury is determined by several factors. In addition to pH, the physical form of the substance may influence toxicity: liquid products transit the oropharynx and esophagus quickly and may cause the greatest injury to the stomach. However, a very viscous liquid may cause significantly greater injury. Solids and crystals are associated with injury to the lips, mouth, oropharynx, and esophagus. Duration of contact with tissue also influences the extent of injury. The presence of food and liquid in the stomach minimizes the amount and duration of contact between the caustic substance and the gastric mucosa.
4. Ocular and dermal exposure to caustic substances requires copious irrigation with saline or water. If there are any symptoms after irrigation, ocular exposures to caustic substances require ophthalmologic consultation. After initial irrigation, dermal exposures to caustic substances are treated as thermal burns.
5. After ingestion of a caustic product, there is no strict correlation between the presence or absence of symptoms (including pain) and presence, location, or degree of injury.
a. Mild effects of inflammation and irritation without blistering require only symptomatic and supportive care.
b. Partial- or full-thickness injuries occur when the substance burns through the epidermis with partial thickness and down through the dermis with full thickness. With ingestion of an acid (typically a liquid), there is risk of gastric perforation within about 3 days of ingestion. Otherwise, the risk of perforation is greatest during the granulation phase, perhaps up to 2 weeks. Then the development of scar tissue and esophageal stricture commences.
c. Initial pain may be oral, substernal, or epigastric.
6. Assessment of the patient during the initial exposure includes visual inspection of exposed tissue, evaluation of acid–base and fluid and electrolyte status, determination of hemoglobin and hematocrit, and perhaps radiographic examinations to determine the presence or absence of free air.
a. Dilution is not recommended due to the risk of aspiration as well as lack of efficacy. Neutralizing or buffering agents are contraindicated due to the risk of vomiting, causing esophageal reinjury, and the possibility of aspiration. In addition, the risk of heat injury associated with the neutralization process prohibits the use of these agents.
b. Observe for respiratory distress. Soft-tissue swelling and aspiration of caustic material can contribute to respiratory difficulty. If significant edema is present, oral or nasotracheal intubation is dangerous, and a tracheotomy or cricothyrotomy is needed.
c. Observe for signs of fluid and electrolyte imbalance to evaluate loss of fluids or third-spacing of fluids.
d. Observe for acidosis if the patient has ingested a large quantity of an acid, as may occur in a suicide attempt. Although direct injury is generally confined to points of contact with the chemical, acidosis is one possible systemic manifestation associated with acid ingestion.
e. Esophagoscopy and endoscopy may be indicated. If the initial injury is thought to be severe or if circumferential burns are found on esophagoscopy, additional surgical procedures may be indicated. The surgical procedures that may be indicated include gastrectomy to remove necrotic tissue, insertion of a string or stent in the esophogus, or insertion of a gastric feeding tube. Esophagectomy and colonic interposition (removing the esophagus and replacing it with a length of the patient’s own colon) may also be performed.
f. The use of steroids is controversial and depends upon the severity of injury and may 761be utilized based on the preference and experience of individual treating physicians. Steroids may decrease the formation of restrictive scar tissue after circumferential burns but may also weaken tissue and predispose the patient to infection.
g. Antibiotics are prescribed for patients taking steroids and for patients with specific indications.
h. Observe the patient for signs of perforation and sepsis. Perforation may be accompanied by abdominal distention and a change in the amount or character of the patient’s pain.
i. Analgesics are indicated.
j. Patients must remain NPO (taking nothing by mouth) until esophagoscopy is performed.
8. Special Considerations
a. Until the patient is decontaminated, healthcare providers must protect themselves with appropriate personal protective equipment to avoid contact with caustic materials.
b. If the patient has sustained a serious injury, psychosocial considerations for the patient and the family come to the forefront. Ocular and dermal exposures may cause significant disfigurement, and ocular exposures may result in permanent blindness. Poisoning with significant injury means that the patient may require permanent tracheostomy or gastrostomy or both, major surgery and follow-up for esophagectomy and colonic interposition, or regular esophageal dilation, for many years to come. Also, the risk of developing cancer at the site of the injury, although delayed for decades, is greater than in the general population.
9. Hydrofluoric acid is different from other caustic agents in that it is absorbed dermally, even through intact skin, and can cause both local and systemic effects. It is used industrially to etch glass and computer chips, as a cleaning agent for metals and air-conditioning units, and as a rust remover. Products with low, but potentially dangerous concentrations of hydrofluoric acid, are sold for home use as rust removers and metal brighteners. Hydrofluoric acid is toxic by all routes of exposure, but dermal exposure is the most common.
a. In concentrations above 50%, hydrofluoric acid causes immediate local tissue injury along with significant pain. In concentrations between 20% and 50%, the onset of local injury and pain can be delayed for 8 hours or longer. In concentrations lower than 20%, the effects of exposure may not be evident for 24 hours.
b. Hydrofluoric acid is absorbed through the skin and precipitates both calcium and magnesium with resulting intense pain at the exposure site. With significant exposure, systemic hypocalcemia, hypomagnesemia, hyperkalemia, and possibly fatal ventricular dysrhythmias are present.
c. Initial treatment is copious irrigation with running water, even in the absence of local effects. With exposure to the hands, subungual concentrations of hydrofluoric acid may be difficult to remove and often necessitate removal or splitting of the nails or injection of calcium.
d. Local pain is treated with a calcium gluconate gel, prepared by mixing 3.5 g of calcium gluconate powder in 5 oz of water-soluble gel (Taketomo et al., 2015), and is applied to painful areas until the pain subsides. When pain recurs, additional gel is applied. The patient should apply the gel liberally at home if pain recurs and return for further care if the gel ceases to be effective.
e. More serious exposures may be treated with subcutaneous, IV, or intra-arterial infusions of calcium gluconate. Even minimal dermal exposure to high concentrations of hydrofluoric acid may cause systemic hypocalcemia. These patients must be admitted to monitored beds, and serial calcium levels must be closely monitored until adverse effects are corrected.
Cyanide is thought of as a fast-acting lethal poison, but in some circumstances a slower onset of symptoms is possible. Treatment involves aggressive supportive care and the rapid administration of amyl nitrite, sodium nitrite, and sodium thiosulfate, packaged as a cyanide antidote kit or hydroxocobalamin.
1. There are many potential sources of cyanide poisoning. Victims of fires may develop cyanide poisoning along with carbon monoxide poisoning. A number of plant seeds (apples, peaches, plums, pears, nectarines, and cherries) contain amygdalin, which generates hydrogen cyanide after ingestion. Laetrile, an ineffective treatment for cancer, is derived from apricot kernels and has caused death from cyanide poisoning. Cyanide is a metabolite of nitroprusside; rapid or prolonged treatment can cause symptoms of cyanide poisoning. Nonoccupational 762cyanide poisoning in adults and teenagers is likely to result from suicidal ingestion of laboratory or photographic chemicals. Children have died rapidly after swallowing professional jewelry-cleaning solutions containing cyanide. Acetonitrile, which is metabolized to cyanide, is found in liquids used to dissolve artificial fingernail glue; delayed onset of symptoms and death have occurred when this was swallowed.
2. Cyanide binds with ferric iron contained within cytochrome oxidase, impairing adenosine triphosphate (ATP) production and thereby aerobic metabolism and cellular utilization of oxygen results in anoxic tissue injury. Other metalloenzyme systems are affected as well.
3. The toxic dose depends on the form of the chemical and route of administration, but toxic effects are usually severe. Small amounts of cyanide salts can cause rapid loss of consciousness and death. Toxicity develops more slowly with cyanide ingestion than inhalation because absorption takes longer. Substances that are metabolized to cyanide (e.g., amygdalin glycosides, acetonitrile, nitroprusside) have a delayed onset of action, and the toxic dose is variable.
4. Clinical effects are related to hypoxia and typically progress within minutes from dizziness and headache to coma and death. Severe lactic acidosis from tissue hypoxia and hypotension are prominent. The high anion gap metabolic acidosis, high lactate, and elevated mixed venous saturation suggest cyanide toxicity in patients who are at risk. Patients with lesser exposures and those exposed to substances that must be metabolized have a less precipitous onset of symptoms.
5. ABGs must be followed closely in addition to serum electrolytes and lactate. If possible, measuring mixed venous saturation may be helpful. Depending upon the exposure route, co-oximetry to measure carboxyhemoglobin and methemoglobin may be beneficial to determine whether there is a concomitant exposure. Cyanide can be measured in serum, but levels cannot be returned in time to be useful for acutely poisoned patients.
6. Antidote treatment is initiated for patients with known cyanide poisoning and serious clinical effects. In the United States, there are now several types of cyanide antidotes available. The Cyanide Antidote Kit, a three-part cyanide antidote kit, contains amyl nitrite, sodium nitrite, and sodium thiosulfate. This combination of agents is now available as the branded Cyanide Antidote Package or as the generic cyanide antidote kit. Nithiodote, recently approved by FDA, contains sodium nitrite and sodium thiosulfate and is only used in situations deemed life-threatening. In 2006, FDA approved hydroxocobalamin, a novel cyanide antidote, available as the branded Cyanokit.
a. Hydroxocobalamin or vitamin B12a, detoxifies cyanide and forms cyanocobalamin, which is renally excreted. Hydroxocobalamin is an appealing cyanide antidote because it is relatively safe, does not compromise the blood’s oxygen-carrying capacity, and, unlike the nitrites or sodium thiosulfate, does not produce hypotension. The empiric adult dose of hydroxocobalamin is 5 g, which can be infused over a period of 15 minutes, with the infusion repeated if necessary; the pediatric dose is 70 mg/kg, up to a maximum of the adult dose, administered at the same infusion rate (Taketomo et al., 2015). Hydroxocobalamin is known to cause a reddish discoloration of the urine that typically resolves within 48 hours.
The mechanism of action of amyl nitrite and sodium nitrite as antidotes for cyanide poisoning is to produce methemoglobinemia and vasodilation. Vasodilation may contribute to their therapeutic and adverse effects. If the Cyanide Antidote Kit is used: methemoglobin is first induced with nitrites; cyanmethemoglobin is formed as cyanide and is thus removed from cytochrome oxidase. Rhodanese, an endogenous enzyme, then facilitates the formation of thiocyanate, a much less toxic metabolite, which is renally excreted. Administration of sodium thiosulfate results in the formation of relatively nontoxic thiocyanate.
b. Amyl nitrite ampules are broken, placed in a cloth, and held in front of the patient’s mouth for 15 of 30 seconds, then repeated until vascular access is obtained. This permits the formation of about 5% methemoglobin. This step may be skipped in favor of immediate administration of IV sodium nitrite.
c. Sodium nitrite induces the formation of additional methemoglobin. Clinical response to sodium nitrate administration has been seen with methemoglobin levels of less than 10%. Methemoglobin concentrations should be closely monitored and maintained less than 30% and generally discontinued when levels exceed 30%. In children, the amount of sodium nitrite is calculated according to body weight and titrated 763to actual hemoglobin levels. Doses must be carefully calculated because inducing too high a level of methemoglobinemia worsens hypoxia. High levels cannot be treated with methylene blue because to do so would liberate free cyanide.
d. Administration of sodium thiosulfate results in the formation of thiocyanate, which is eliminated renally.
e. Treatment also includes respiratory support and symptomatic and supportive care.
f. Patients with a known cyanide exposure but without clinical effects are treated with sodium thiosulfate component alone if not using hydroxocobalamin.
7. Special Considerations
a. Too high a level of methemoglobin can itself be fatal. Neither carboxyhemoglobin nor methemoglobin is capable of carrying oxygen, so such patients can develop functional hypoxia. Pediatric doses of nitrites must be carefully calculated, and methemoglobin levels must be monitored.
b. If neurologic criteria for death is met by a patient with cyanide poisoning he or she may be considered a potential organ donor.
Envenomations by snakes and spiders will not be considered in depth. Always consult the poison center when treating a patient with a snake or spider bite. All venoms are extremely complex mixtures; any bite resulting in symptoms indicates a poisoning with the potential for serious multisystem effects. Children are at greater risk than adults because of their small body size in relationship to the amount of venom injected.
1. The venom of the Crotalinae (rattlesnakes, copperheads, and cottonmouths [water moccasins]) can cause the rapid onset of life-threatening effects, although this is not expected with bites of copperheads and cottonmouths. Action at numerous venom receptors results in hypotension, increased capillary permeability resulting in local ecchymosis and edema, pulmonary edema, local tissue injury, myocardial injury, and bleeding and clotting disorders. Local wound care and intensive supportive care are both essential. Definitive antidotal treatment is the administration of antivenin; Crotalidae Polyvalent Immune Fab (Ovine [CroFab]) is an antigen-binding fragment antivenin derived from sheep and has superseded equine polyvalent crotalid antivenin as the treatment for crotalid envenomations. Patients are eligible for therapy with Crotalidae Polyvalent Immune Fab (Ovine) if they have moderate envenomation, severe envenomation, or any degree of envenomation with progression of the envenomation syndrome. As the antivenin dose reflects venom size, not patient size, the FDA recommends the same initial and subsequent doses for pediatric patients. There is no substitute for administration of sufficient quantities of antivenin in a patient poisoned by a rattlesnake. With the reduced side effect profile of antigen-binding fragment antivenin and the improvement in tissue injury with antivenin administration, the threshold for dosing is lower. Common treatment errors include withholding antivenin in a patient with a life- or limb-threatening envenomation for fear of allergic reactions and performing fasciotomy in lieu of administering sufficient antivenin in patients with peripheral edema. The patient should be monitored for signs of an allergic reaction (hives, urticaria, erythema; wheezing, respiratory distress; edema of face, lips, tongue, or throat) to the antivenin during administration. Late coagulopathy has been reported after using Crotalidae Polyvalent Immune Fab (Ovine).
2. The venom of the Elapidae (the coral snakes) tends to have significant neurotoxicity, inducing neuromuscular dysfunction and can cause fatal poisoning specifically by respiratory muscle paralysis. Onset of symptoms may be delayed for 10 to 12 hours after envenomation. Fortunately, such fatalities are extremely rare. Treatment is directed at stabilization and respiratory support. In the United States, production of coral snake antivenin has ceased. The FDA had extended the expiration date for North American Coral Snake Antivenin through April 30, 2017. After this time, unless stock remains and the expiration date is further extended, there will be no commercially available coral snake antivenin.
3. The venom of the black widow spider (Latrodectus mactans) produces protein venom that affects the victim’s nervous system. This neurotoxic protein is one of the most potent venoms secreted by an animal. Some people are slightly affected by the venom, but others may have a severe response. The first symptom is acute pain at the site of the bite, although there may only be a minimal local reaction. Symptoms usually start within 20 minutes to 1 hour after the bite and can cause paralysis of respiratory muscles, although this is not usual. The most common symptoms are immediate, intense local pain at the site of the bite (which can 764be identified by two tiny fang marks, about 0.5 cm [¼ in] apart); muscle weakness, ataxia, and ptosis, especially in children; and intensely painful muscle contractions and diaphoresis in the affected limb, across the abdomen for lower-extremity bites and across the back and shoulders for upper-extremity bites. Treatment includes administration of narcotic analgesics and a benzodiazepine. Antivenin is available, but its use is usually required only for severe systemic effects.
Ethanol is found in alcoholic beverages, mouthwash, and cosmetics such as perfumes, tonics, and hair spray. It is used therapeutically as the antidote for ethylene glycol and methanol poisoning when fomepizole is not available. Isopropyl alcohol is a low-molecular-weight hydrocarbon commonly found as both a solvent as well as a disinfectant and is commonly used as an ethanol substitute and ingested by individuals. It can be found in many mouthwashes, skin lotions, rubbing alcohol, and hand sanitizers. Young children are poisoned unintentionally or by adults who give them alcoholic beverages. Preteens and adolescents may indulge in binge drinking and may be alcohol dependent. Young adults are devising ways to use ethanol without actually drinking it. They are still becoming intoxicated, since the delicate tissues of the vagina, anus, and eyeball absorb alcohol readily, but without the knowledge that these routes may result in injury or overdose. The addition of energy drinks, typically containing caffeine and other energy-producing supplements, either ingested alone or in combination with alcohol, has created another circumstance in which people do not comprehend the risks. In these cases, they are as vulnerable as adults to atrial dysrhythmias following binges and to medical and behavioral consequences of alcoholism.
1. Ethanol is rapidly absorbed and widely distributed. The primary route of absorption is oral, although it can be absorbed by inhalation and other routes. It is well known as a CNS depressant. The concomitant use of ethanol and other drugs is common, and combinations of ethanol with other sedative-hypnotics or opioids may potentiate the sedative effects. In children, ethanol’s hypoglycemic effects are significant; the immature liver does not maintain sufficient glycogen stores to counteract ethanol-induced hypoglycemia.
2. Symptoms related to ethanol-induced CNS depression are lethargy, ataxia, respiratory depression, hypothermia, and coma. These effects may begin within an hour of ingestion, followed within a few hours by hypoglycemic seizures, coma, and death. These signs usually occur when the ethanol level in the blood exceeds 50 to 100 mg/dL. However, hypoglycemia can be seen with serum ethanol levels as low as 50 mg/dL. Metabolic acidosis may be present in large ingestions. Following isopropanol ingestion, the patient may simply appear intoxicated, as with ethanol intoxication and may have a history of abdominal pain, nausea, and sometimes hematemesis.
3. Toxicity may occur with an ethanol ingestion of 1 g/kg. Using the formula: amount of alcoholic product ingested (mL/kg) multiplied by the percentage of ethanol in the product (%) divided by the body weight of the patient (in kilograms), will provide a rough estimate of blood ethanol concentration. A 4 mL/kg ingestion of 100% ethanol is life threatening. A fatal dose in children is approximately 3 g/kg; the fatal dose in adolescents and adults is widely variable, from 5 to 8 g/kg.
4. Physical assessment is straightforward. Laboratory studies required include serum ethanol and methanol levels, electrolytes, glucose, and ABG analysis. It is necessary to evaluate for salicylate and acetaminophen since coingestion is highly probable with ethanol ingestion.
5. Treatment. Gastric emptying is not useful greater than 1 hour after ingestion. Activated charcoal does not adsorb ethanol. Careful monitoring and correction of serum glucose are essential. Other treatment is symptomatic and supportive. Ethanol is removed by hemodialysis, which may be indicated for serious or potentially fatal ingestions.
6. Special Consideration. Even preteens and young adolescents may be alcohol dependent. Be alert for signs of impending withdrawal: tremors, agitation, hallucinations, and seizures. Benzodiazepines are usually indicated for initial management of alcohol withdrawal.
F. Ethylene Glycol
Ethylene glycol is an ingredient in antifreeze, deicing products, detergents, paints, and cosmetics. The most common source of ethylene glycol poisoning in the pediatric population is from antifreeze. Unintentional ingestions are the norm in young children, whereas adolescents drink antifreeze in suicide attempts or as an ethanol surrogate. This is a dangerous poisoning because ethylene glycol is sweet but extremely toxic in small amounts. Effects are due to metabolites and are therefore delayed. Parents or victims mistakenly may believe that absence of early symptoms indicates absence of toxicity.
7651. Ethylene glycol is rapidly absorbed from the GI tract and is widely distributed. During the several steps in its metabolism, glycolic acid, lactic acid, and a number of other organic acids are generated, leading to the metabolic acidosis characteristic of this poisoning. Oxalic acid precipitates with calcium, leading to the deposition of calcium oxalate crystals in soft tissue (including the kidney) and renal failure.
2. The toxic dose is variable but small; a dose requiring medical treatment varies but is considered more than 0.1 mL/kg body weight of pure substance. Poison control centers often use more than a lick or taste in a child or more than a mouthful in an adult as a dose requiring hospital assessment (Caravati et al., 2005). The orally lethal dose in humans is approximately 1.4 mL/kg of pure ethylene glycol (Brent, 2001).
3. Toxic effects are delayed for as long as 12 to 24 hours; early effects resemble alcoholic intoxication. As the poisoning progresses, nonspecific symptoms of lethargy and GI tract complaints, such as nausea and vomiting, evolve into ataxia, seizures, stupor, coma, and renal failure. In the absence of specific history, ethylene glycol poisoning should be suspected in any patient who presents with or develops both coma and metabolic acidosis.
4. A serum ethylene glycol level is most useful but is not always easily obtained. The presence of an anion gap metabolic acidosis is more readily ascertained and is extremely useful. ABG analysis is required. Other laboratory tests that should be performed include screening for coingestions such as acetaminophen and salicylates; CBC, blood glucose, serum electrolytes, magnesium, calcium, BUN, creatinine, lactate, osmolar and anion gap, and urinalysis. A few hours after ingestion, the urine can be examined for the presence of calcium oxalate crystals. A serum ethanol level should be drawn in anticipation of antidotal therapy with ethanol if fomepizole is not available.
5. Treatment includes prevention of absorption (if possible), prevention of metabolism to toxic metabolites, and enhanced elimination.
a. Gastric emptying is useful only within 1 hour of ingestion.
b. Specific antidotes to ethylene glycol poisoning are the alcohol dehydrogenase inhibitors fomepizole and ethanol. The goal of antidotal treatment with fomepizole or ethanol is to prevent metabolism of ethylene glycol into toxic components until ethylene glycol can be eliminated renally or by hemodialysis. Either antidote is administered until the serum ethylene glycol level is less than 20 mg/dL. Dosing of both is altered by concurrent hemodialysis.
i. Fomepizole is administered IV every 12 hours. The loading dose is 15 mg/kg; maintenance dose is 10 mg/kg for four doses, followed by 15 mg/kg until therapy is no longer needed.
ii. The initial dose of ethanol is calculated according to age, whether ethanol is already present, and whether the patient is habituated to ethanol. Subsequent doses are titrated to the serum ethanol level, which should be maintained at 100 mg/dL. To prevent ethanol-induced hypoglycemia, serum glucose must be carefully monitored and corrected if necessary.
c. Hemodialysis is indicated if the ethylene glycol level is greater than 50 mg/dL or with severe acidosis or evidence of end-organ damage irrespective of level.