ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Approach to the child with occult toxic exposure

Approach to the child with occult toxic exposure
Literature review current through: Jan 2024.
This topic last updated: Apr 19, 2022.

INTRODUCTION — The general approach and initial management of the child who is suspected to have ingested or inhaled an unknown poison is reviewed here. Specific issues relating to management of common drug overdoses are discussed separately. (Refer to appropriate topic reviews.)

BACKGROUND — Toxic exposures occur frequently in children throughout the world. Common patterns of pediatric poisoning consist of exploratory ingestions in children younger than six years of age and intentional ingestions and recreational drug use in older children and adolescents [1]. Increase in mental illness in older children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic has also increased the incidence of substance use disorders (SUDs) and attempts at self-harm [2]. In many instances, the toxic agent is readily identified. However, in an important minority of exposures, a history of poisoning is not provided.

CLINICAL PRESENTATION — The clinical presentation of occult ingestion varies depending upon the ingested substance and can range from asymptomatic to critically ill. Occult toxic exposure should be considered in the differential diagnosis of children who present with acute onset of multiorgan system dysfunction, altered mental status, respiratory or cardiac compromise, unexplained metabolic acidosis, seizures, or a puzzling clinical picture [3,4]. The index of suspicion should be raised if the child is in the "at-risk" age group (one to four years of age) and/or has a previous history of ingestion or, in adolescents, a prior history of substance use disorder (SUD) [5].

Intentional etiologies for occult poisonings can also occur, including suicide attempts in older children and adolescents. In these cases, patients are often unwilling to provide a meaningful or accurate history of ingestion. Medical child abuse via forced ingestion in young children, particularly those who are younger than one year of age, must not be overlooked. (See "Suicidal behavior in children and adolescents: Epidemiology and risk factors" and "Medical child abuse (Munchausen syndrome by proxy)".)

Examples of medical child abuse by poisoning include:

Forced ingestion or intentional poisoning of children is a form of child abuse that overlaps with Munchausen syndrome by proxy (also known as medical child abuse). A variety of substances, including water, salt, pepper, and various drugs (prescription and illicit), may be used [6-10]. (See "Medical child abuse (Munchausen syndrome by proxy)".)

Water intoxication from forced water drinking presents with hyponatremic seizures, vomiting, coma, or death [11]. Excessive water ingestion may be a "punishment" for perceived wrongdoing by the child or may be a component of medical child abuse. Signs of physical abuse often coexist and should be sought (table 1). (See "Physical child abuse: Recognition".)

Salt poisoning typically presents in the first six months of life with unexplained hypernatremia, often recurrent. Salt is administered in milk or other liquids; there is one report of salt administered via nasogastric tube [12]. Salt poisoning may coexist with other unexplained recurrent illnesses if it is occurring in the context of medical child abuse (Munchausen syndrome by proxy). Serum sodium levels may be greater than 200 mmol/L, and urine sodium and chloride also are elevated. Renal and endocrinological evaluation is otherwise normal. (See "Etiology and evaluation of hypernatremia in adults", section on 'Sodium overload' and "Medical child abuse (Munchausen syndrome by proxy)".)

Intentional ipecac administration has been used to induce vomiting as a way to mimic illness. Ipecac poisoning should be considered in any child with unexplained recurrent episodes of vomiting. Chronic ipecac administration can cause electrolyte imbalances, dental erosion, and myopathies [13].

APPROACH — The approach to the poisoned child begins with initial evaluation and stabilization followed by a thorough evaluation to attempt to identify the agent(s) involved and assess the severity of exposure. The possibility of concomitant trauma or illness must be recognized and addressed before initiation of decontamination [14,15].

The tempo, sequence, methods, and priorities of management are dictated by the toxin(s) involved, the presenting and predicted severity of poisoning, and the presenting phase of poisoning. Management always begins with stabilization of the airway, breathing, and circulation, and treatment of life- and/or limb-threatening trauma. It is then directed to the provision of supportive care, prevention of poison absorption, and when appropriate, administration of antidotes and enhancement of elimination [16].

INITIAL EVALUATION AND STABILIZATION — Rapid evaluation of mental status, vital signs, and pupils enables classification of the patient into a state of physiologic excitation (eg, central nervous system stimulation [including seizures] and increased temperature, pulse, blood pressure, and respiration); depression (depressed mental status and decreased temperature, pulse, blood pressure, and respiration); or mixed physiologic state. This initial characterization helps to direct initial stabilization efforts and provides a clue to the etiologic agent (table 2) [16].

Airway — The airway of patients who have ingested an unknown substance must be monitored carefully and serially. The patency of the airway should be evaluated in patients with central nervous system depression. Even those who are awake and talking on arrival must be monitored closely, because their condition can rapidly deteriorate. When needed, the position of the head should be optimized to maintain airway patency. Endotracheal intubation should be performed in all patients in whom the airway is threatened or compromised. If intubation is necessary, cervical spine stabilization must be maintained whenever trauma is suspected. (See "Technique of emergency endotracheal intubation in children" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach" and "Pediatric cervical spinal motion restriction".)

Breathing — After the airway is assessed and adequately secured, as needed, the quality of breathing must be evaluated. Poisoned patients may develop respiratory failure for many reasons (table 3). External monitors (pulse oximetry, capnography) are useful in providing noninvasive, continuous assessment of oxygenation and ventilation. Some toxins decrease the respiratory drive, whereas others impair muscle contraction; still other toxins may directly damage the lung parenchyma or result in pulmonary edema and accompanying respiratory distress. Any of these mechanisms may result in hypoxia and/or hypercapnia.

In a symptomatic or rapidly deteriorating patient, measurement of arterial blood gas should be obtained. Supplemental oxygenation should be provided to maintain oxygen saturation >95 percent. Intubation and ventilation are required in patients who cannot sustain adequate oxygenation or ventilation or who have severe acid-base disturbances. Noninvasive ventilation or endotracheal intubation is sometimes necessary in patients with noncardiogenic pulmonary edema or acute respiratory distress syndrome from toxins. (See "Noninvasive ventilation for acute and impending respiratory failure in children" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach" and "Initiating mechanical ventilation in children".).

Circulation — Intoxication by various drugs may cause blood pressure and heart rate abnormalities (table 4) and/or cardiac conduction disturbances ranging from minor QT changes to a wide QRS complex form (table 5) [17-19]. Blood pressure measurement and a 12-lead electrocardiogram (ECG) should be obtained in all patients who present with occult toxic exposure. Continuous cardiac monitoring is useful and often necessary.

The evaluation and management of circulatory compromise in patients with intoxication of unknown or multiple agents should occur according to Advanced Cardiac Life Support (ACLS) or Pediatric Advanced Life Support (PALS) guidelines. (See "Assessment of systemic perfusion in children" and "Pediatric basic life support (BLS) for health care providers" and "Primary drugs in pediatric resuscitation".)

In certain toxidromes, (eg, monomorphic, wide complex tachycardias) it is important to recognize that deviations from ACLS protocols are necessary, because ACLS and PALS guidelines often are not toxicology-specific [20]. (See "Initial management of the critically ill adult with an unknown overdose", section on 'Monomorphic, wide-complex tachycardia'.)

The child should be evaluated for signs of shock because of the potential for rapid decompensation. At least one intravenous (IV) line should be established in the stable patient and two large bore intravenous lines in the unstable or deteriorating patient. Intraosseous access must be obtained in those unstable patients for whom a peripheral line cannot be rapidly established. (See "Vascular (venous) access for pediatric resuscitation and other pediatric emergencies".)

Altered mental status — Various drugs can cause mental status changes ranging from agitation to coma (table 6).

Hypoxemia and hypoglycemia are two common causes of altered mental status in the poisoned patient that should be promptly evaluated and addressed during the initial stabilization. In addition, administration of naloxone or thiamine should be considered in poisoned children and adolescents who are thought to have opiate intoxication or thiamine deficiency, respectively. In contrast, the use of flumazenil to reverse benzodiazepine ingestion is not routinely recommended as part of a "coma cocktail" because of potential serious adverse effects (eg, precipitation of seizures). (See "Benzodiazepine poisoning", section on 'Role of antidote (flumazenil)'.)

Hypoxemia – Rapid evaluation of oxygenation should be performed in all patients with altered mental status. This can be performed with a bedside pulse oximeter and/or arterial blood gas measurement, which provides additional information about the patient's ventilation and acid-base status and may, in turn, affect diagnosis and management (see 'Ancillary studies' below).

Pulse oximetry does not accurately reflect oxyhemoglobin saturation (falsely normal reading) in patients with carbon monoxide poisoning. If carbon monoxide toxicity is a diagnostic consideration, the carboxyhemoglobin level should be measured by co-oximetry using a blood gas sample. (See "Carbon monoxide poisoning".)

Pulse oximetry is also inaccurate (falsely low reading) in patients with methemoglobinemia and sulfhemoglobinemia (table 7). (See "Pulse oximetry", section on 'Troubleshooting sources of error'.)

Humidified oxygen should be administered to symptomatic poisoned children with altered mental status in whom hypoxemia is suspected or documented. Endotracheal intubation is required in patients who cannot sustain adequate ventilation or oxygenation (while on supplemental oxygen). (See "Technique of emergency endotracheal intubation in children" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

Hypoglycemia – Several drugs cause hypoglycemia, which can be both profound and protracted (table 8). Rapid assessment of blood glucose can be performed at the bedside with a glucose strip using either capillary or venous blood [21]. An age-appropriate, concentrated dextrose solution must be administered if blood glucose is low, if the accuracy of the result is questioned, or in cases where rapid assessment of blood glucose is not available [3,21]. The dose for dextrose is 0.25 g/kg administered intravenously or intraosseously. This is usually achieved with 2.5 mL/kg of 10 percent dextrose solution since extravasation of higher concentrations of glucose will lead to severe tissue damage. Higher concentrations can be used in older children and adolescents. (See "Approach to hypoglycemia in infants and children", section on 'Treatment'.)

Opiate intoxication – Administration of naloxone is indicated in patients who have depressed mental status, diminished respirations, miotic pupils, or other circumstantial evidence of opiate/opioid intoxication [22-24]. The dose of naloxone varies depending upon the age of the child, the type of opioid suspected to be involved, and the clinical scenario. High doses of naloxone are sometimes required, and repeated doses might be needed for long-acting agents. (See "Opioid intoxication in children and adolescents", section on 'Naloxone'.)

Thiamine deficiency – The administration of thiamine should be considered in children and adolescents who may be thiamine-deficient because of chronic disease, malnutrition, eating disorders, or alcoholism [3,21]. (See "Wernicke encephalopathy".)

The notion that thiamine must be given before dextrose to avoid precipitating Wernicke's encephalopathy is largely unsupported [21]. Uptake of thiamine into cells is slower than that of dextrose [25], and withholding dextrose until the administration of thiamine is complete is detrimental to those with actual hypoglycemia [26].

Other considerations — Additional considerations in the initial stabilization of the child with an unknown toxic exposure include:

Occult trauma – The patient should be completely undressed and examined to look for signs of occult trauma.

Decontamination – Gastrointestinal decontamination may be indicated as part of the initial stabilization in children who have ingested a potentially life-threatening amount of poison (eg, iron) [4]. Ocular and/or dermal decontamination may be necessary if coincident external exposure has occurred. (See "Gastrointestinal decontamination of the poisoned patient".)

DIAGNOSIS OF POISONING — After the initial evaluation and stabilization, efforts should be focused on identification of agent(s) involved, assessment of severity, and prediction of toxicity.

It is essential to identify potentially fatal agents and those with delayed clinical toxicity (table 9) as soon as possible so that appropriate intervention can be undertaken. The most common fatal drug ingestions in children younger than six years of age include prenatal iron supplements, antidepressants, cardiotoxic agents, illicit drugs, analgesics, and salicylates (table 10) [27]. In addition, a number of drugs can be fatal if ingested by a toddler, even in small amounts (table 11) [28-34]. The most common fatal nondrug ingestions in children younger than six years of age include hydrocarbons, alcohols, cosmetics, cleaning products (including laundry detergent pods), and pesticides [1,3,35]. (See "Acute hydrocarbon exposure: Clinical toxicity, evaluation, and diagnosis".)

History — Obtaining an accurate history in an intoxicated pediatric patient is challenging, but crucial. The patient and relatives may be unwilling or unable to provide the details of the history [36], and the personnel accompanying the patient to medical care may not know the details of exposure (eg, agent, time, volume, immediate clinical effects). The patient's history should be confirmed and correlated whenever possible with the signs, symptoms, and laboratory data expected from poisoning with the agent(s) implicated by history.

In the young child, the circumstances surrounding the ingestion can provide useful information (eg, location, activity just before ingestion) [5,37]. Potential agents ingested in the kitchen, for example, may be different than those in the bathroom or garage [5].

It is important to ask about exposure to the most commonly ingested agents in children younger than six years, which include cosmetics and personal care products, cleaning products, analgesics, cough and cold preparations, topical agents, plants, pesticides, and vitamins [1,35].

It is important to ask about recent illnesses and regular therapy with common medications. The overdosing of common medications (eg, acetaminophen, ibuprofen) may result in chronic poisoning [3]. Among the 26 fatal toxic exposures in children younger than six years of age in the United States in 2001, eight were caused by therapeutic errors (acetaminophen, aspirin, methadone, morphine, oxycodone) [38]. (See "Salicylate (aspirin) poisoning: Clinical manifestations and evaluation" and "Acetaminophen (paracetamol) poisoning: Management in adults and children".)

Information that is provided by an adolescent patient, particularly one with an intentional ingestion, may not be reliable [36,39,40]. Adolescents commonly present with ethanol or illicit drug intoxications. It is important to ask other household members about all medications (prescription and over-the-counter), vitamin and mineral supplements (particularly prenatal vitamins), herbal remedies, and folk remedies that are present in the home, as well as those that are used by recent visitors [22]. Adolescents may also be exposed to occult toxins in the work or school environment (eg, alkaline corrosives, gases and fumes, cleaning agents, bleaches, various drugs, acids, pesticides, and hydrocarbons) [41].

Paramedics can provide important information about open containers, empty bottles, spilled contents, drug paraphernalia, or suicide notes at the scene. If such items exist, the paramedics (or someone at the scene) should bring them to the hospital [22]. Unknown pills or chemicals may be identified by consultation with a regional poison control center (1-800-222-1222), computerized poison identification system, or product manufacturer (eg, material data safety sheet). However, it is important to recognize that there are many counterfeit pills that are almost undistinguishable from the real ones [42].

It is also important to know about interventions in the prehospital setting (eg, administration of oxygen, intravenous fluid, sedatives, dextrose, or naloxone) since these may alter the patient's condition at the time of presentation.

Information about the quantity and timing of ingestion is helpful in making decisions about decontamination or the use of antidotes (see below). Younger children tend to ingest small quantities of single agents. In one study of 66 children (age 1.5 to 4.5 years), the volume of a "mouthful" was calculated by subtracting the volume of apple juice remaining in a cup after the child had taken one sip from the original volume [43]. The mean volume of a mouthful was 9.3 mL (95% CI, 8 to 11 mL), with a range of 3.5 to 29 mL. In contrast to younger children, older children and adolescents, in whom the ingestion is more likely intentional, ingest larger quantities of a single agent or ingest multiple agents. In some cases, the only information that is available about the time of ingestion is the last time that the patient was observed to be doing well.

Information from the past medical history is useful in the identification of available medications, possible co-ingestants, baseline health status, and potential complicating factors (eg, G6PD deficiency). If the patient or family member cannot provide this information, it may be obtained from medical records, pharmacy profiles, or Medic-Alert bracelets.

Information from the social history may be useful in determining the circumstances, intent, and/or agent of exposure. For example, unwitnessed, unintentional ingestions in young children tend to occur at times of decreased parental supervision (eg, when there are household visitors or holiday parties) [3,4]. Vaping in the household can give access to concentrated nicotine solutions to pediatric patients. (See "Nicotine poisoning (e-cigarettes, tobacco products, plants, and pesticides)".)

A history of illicit drug use in the patient or family members may provide a clue to the agent. Drug use in close family members has been associated with unintentional (unsupervised) ingestion of illicit substances [44,45]. Drug use in older siblings may encourage similar behavior in younger ones (eg, inhalant abuse). (See "Inhalant misuse in children and adolescents".)

Physical examination — The physical examination, particularly the evaluation of mental status and vital signs, should be repeated frequently to determine the course of poisoning and the need for further intervention.

After the initial diagnostic evaluation and stabilization, other physical findings should be sought to further define a particular toxic syndrome (toxidrome), to narrow the potential etiologies of poisoning (table 2), and to evaluate the possibility of child abuse (table 1). (See "Physical child abuse: Recognition".)

The diagnosis may be assisted by [28]:

Temperature alterations (table 12)

Blood pressure and heart rate alterations (table 4)

Respiratory disturbances (table 13)

Pupillary findings (table 14)

Skin findings (table 15)

Neuromuscular abnormalities (table 16)

Mental status alterations (table 6)

Characteristic odors (table 17); these odors may not be detectable by all examiners

Other aspects of the physical examination may suggest particular agents or routes of exposure:

Nosebleeds may occur in individuals who inhale cocaine or use volatile substances. The latter may also cause facial rash, flushing, blisters, or a ring of paint around the mouth and nose (the "huffer rash").

Fingertip burns can be seen in patients who smoke crack cocaine.

Decayed teeth are often seen in methamphetamine users ("meth mouth").

Wood's light (ultraviolet) examination of the patient's mouth or clothes may reveal fluorescence if the patient has ingested antifreeze solution (eg, ethylene glycol), which commonly contains fluorescein dye (added to help in the identification of radiator leaks) [46].

Needle tracks suggest intravenous drug use.

Discrepancies between the physical examination and the history may reflect an inaccurate ingestion history, a brief or prolonged time interval between exposure and physical examination, or intentional poisoning.

Ancillary studies — The laboratory evaluation of the child with an unknown ingestion is performed to detect metabolic effects of the poison that have both diagnostic and therapeutic implications. The laboratory evaluation should include the following (table 8 and table 18 and table 19 and table 20):

Rapid determination of blood glucose

Acid base status (using venous or arterial blood gas)

Electrolytes

Blood urea nitrogen and creatinine

Serum osmolality (in suspected ingestion of toxic alcohols or with the presence of a high anion gap acidosis)

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) if acetaminophen ingestion suspected

Quantitative acetaminophen serum concentration (if suicidal intent or if suspected based on history)

Quantitative salicylate serum concentration (in patients with respiratory alkalosis and/or metabolic acidosis)

Urine dipstick test

Urine pregnancy test (in postmenarchal females)

Electrocardiogram

Chocolate-colored blood that fails to turn red after 10 minutes of exposure to air suggests methemoglobinemia, which may be caused by a number of agents, including aniline dyes, benzocaine-containing teething products, dapsone, naphthalene, nitrites, and pyridium (table 18) [5,36]. Co-oximetry measuring methemoglobin will confirm the diagnosis. (See "Methemoglobinemia".).

Occasionally, it may be helpful to save samples of blood (10 mL, heparinized), urine (100 mL, first voided), vomitus, and gastric contents (first lavage aspiration) for subsequent analysis [5]. Such samples should be appropriately labeled; they should be processed and stored according to specific instructions supplied by the laboratory. Care should be taken to establish a chain of evidence for law enforcement purposes if intentional poisoning or Munchausen by proxy are suspected (this includes proper sealing, labeling, and storing of specimens to ensure that they cannot be tampered with). (See "Medical child abuse (Munchausen syndrome by proxy)".)

Rapid blood glucose — Several drugs cause hypoglycemia (table 8); rapid assessment of blood glucose can be performed at the bedside with a glucose strip and is indicated for any patient with altered mental status. (See 'Altered mental status' above.)

Blood gas — Arterial or venous blood gas measurement offers a rapid evaluation of acid-base status (table 19), as well as assessment of oxygenation (arterial blood gas only) and ventilation [47,48]. In a symptomatic or rapidly deteriorating patient, the results of the arterial blood gas can be used to direct stabilization and supportive care while awaiting other laboratory results. Cooximetry can be used to rapidly establish the diagnosis of carbon monoxide toxicity or methemoglobinemia.

Electrolytes — Measurement of serum electrolytes provides information about renal function, which is essential for the elimination of some toxins, and further information about acid-base status (table 8). The electrolyte results can be used to calculate the anion gap (Na – [Cl + HCO3]) [49-51], which helps to differentiate among the forms of metabolic acidosis (table 20) [52]. (See "Approach to the child with metabolic acidosis".)

Serum osmolality — The serum osmolality (which must be calculated by freezing point depression) is essential for the calculation of the osmolal gap. The osmolal gap is elevated in the presence of unmeasured osmotically active substances (table 21). The most important substances in the group are the toxic alcohols [53,54]. Calculation of the osmolal gap requires simultaneous measurement of plasma osmolality, electrolytes, blood urea nitrogen (BUN), and creatinine [55,56]. (See "Serum osmolal gap".)

Because ethanol is so frequently consumed, a concomitantly performed serum ethanol concentration is to be added to the osmolar gap calculation for more accuracy.

Urinalysis — A urinalysis is necessary for the evaluation of rhabdomyolysis with myoglobinuria, the prompt treatment of which may prevent renal failure. (See "Rhabdomyolysis: Clinical manifestations and diagnosis" and "Clinical features and diagnosis of heme pigment-induced acute kidney injury" and "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)".)

Examination of the urine can also be helpful in the diagnosis of ethylene glycol ingestion:

Microscopic examination of the urine may reveal calcium oxalate crystals (picture 1A-B), although the absence of crystalluria does not preclude the presence of ethylene glycol ingestion. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis".)

Urine examination by Wood's light (ultraviolet) may reveal fluorescence if the patient has ingested antifreeze solution, which commonly contains fluorescein dye (added to help in the identification of radiator leaks) [46]. However, this finding is neither sensitive nor specific for the diagnosis of ethylene glycol poisoning [57,58]. A negative control urine sample should be tested simultaneously.

Electrocardiogram — Changes on electrocardiogram suggest poisoning by certain agents (table 5) and may indicate the need for specific intervention (eg, sodium bicarbonate infusion [1 mEq/kg]) for a widened QRS interval or ventricular arrhythmia. Many drugs cause QT prolongation. Patients with this finding should be placed in cardiac monitoring, and the use of any other QT-prolonging drugs (eg, ondansetron) must be avoided (table 22).

Toxicology screens — The need for toxicology screening in patients with occult toxic exposure depends upon the clinical scenario. Toxicology screening is rarely necessary in children who have an unintentional ingestion and are asymptomatic or have clinical findings that are consistent with the history. It is indicated in children in whom the diagnosis of poisoning is uncertain, who have coma of unknown etiology, where there is suspicion of child abuse or Munchausen syndrome by proxy, and in whom the administration of an antidote depends upon the rapid identification of the toxic agent. Care should be taken to establish a chain of evidence for law enforcement purposes if intentional poisoning or Munchausen by proxy are suspected (this includes proper sealing, labeling, and storing of specimens to ensure that they cannot be tampered with). (See "Medical child abuse (Munchausen syndrome by proxy)".)

Urine toxicology screens provide qualitative data about the recent use of substances included in the screen. Urine screens usually test for a limited number of substances (typically drugs of abuse). Positive and negative immunoassay screens for drugs do not absolutely confirm or refute poisoning diagnoses and may need confirmation by gas chromatography-mass spectrophotometry (GC-MS). False positives may occur if structurally similar substances cross-react with the assay (table 23). On the other hand, a negative screen may reflect a drug concentration below the threshold limit of detection because the specimen was obtained before or after peak concentration. Furthermore, the newer synthetic illicit drugs (such as cannabinoids, cathinones, synthetic opioids, and many others) will not be detected by routine drug of abuse screens. (See "Testing for drugs of abuse (DOAs)", section on 'False-negative results'.)

Qualitative screens are inexpensive and provide rapid results (usually within one hour). However, they provide no information about timing or quantity of ingestion. The information obtained rarely affects clinical management, but may at times be useful in anticipating the potential for withdrawal and in determining psychiatric disposition [19,59]. The spectrum of drugs included in the urine screen varies by institution; therefore, clinicians should be familiar with the spectrum of drugs tested at their institution [60]. (See "Testing for drugs of abuse (DOAs)".)

Serum testing provides quantitative data and is important in the diagnosis and management of ingestion of several drugs and medications (table 24). As a general rule, drug concentrations should be ordered selectively depending upon the history, physical examination findings, and clinical condition [19,61]. However, screening for acetaminophen and salicylates is strongly recommended for patients with an uncertain history or intentional poisoning; few early signs may be present following lethal doses of these agents, and specific treatments are available and highly effective if implemented early [62,63]. Quantitative testing may also be considered for agents that have delayed clinical effects (table 9). Serial testing might be necessary for agents with delayed absorption.

The interpretation of a single drug concentration for any drug must be made with caution because poisoning is a dynamic and rapidly changing process. Intervention may be required despite serum concentrations in the therapeutic range. Results of these tests should always be considered in conjunction with the time of exposure. Levels that are obtained early in the course, while the drug is still distributing throughout the body, are difficult to interpret properly. On the other hand, samples drawn very late after an exposure may be deceivingly low because the drug has already moved into the tissues or has been partially metabolized.

Comprehensive qualitative toxic screening of urine, blood, or other body fluids is expensive and usually requires six hours or longer for results. Such testing rarely leads to changes in patient management and disposition, and is unlikely to affect patient outcome [64-66]. In one retrospective study of comprehensive toxicology screens in 463 children younger than 19 years of age, 51 percent were positive for exogenous toxins [64]. Among the positive screens, 97 percent were either suspected by history or physical examination, present in the limited portion of the toxicology screen, or clinically insignificant; in the remaining 3 percent, patient management was not altered as a result of the positive screen [64].

Nonetheless, such a comprehensive panel may be useful in patients who are critically ill or in whom the clinical picture does not fit the stated history [3,36]. The results of a comprehensive toxicology screen may affect the social evaluation and disposition when child abuse is suspected. The spectrum of drugs included in the comprehensive drug screen varies by institution; clinicians should be familiar with the spectrum of drugs tested at their institution [60].

Drugs and toxins that can cause coma or hypotension and are not detected by most drug screens include bromides, carbon monoxide, chloral hydrate, clonidine, cyanide, organophosphates, tetrahydrozoline (in over-the-counter eye drops), beta blockers, calcium-channel blockers, colchicine, digitalis, and iron [3,60].

Radiologic evaluation — Plain radiographs of the chest should be obtained in children and adolescents with inhalation exposures and in those with respiratory symptoms and signs (table 13 and table 25). Radiographs also may be obtained to search for concomitant injury and to confirm the placement of endotracheal tubes, nasogastric tubes, and central lines [67]. In addition, certain radiopaque toxins, including packets of illicit drugs smuggled internally by body packers, may be visualized by plain film radiographs (table 26 and image 1 and image 2) [68] (see "Internal concealment of drugs of abuse (body packing)"). Finally, radiographs are useful in locating dangerous foreign body ingestions, such as magnets and button batteries. (See "Button and cylindrical battery ingestion: Clinical features, diagnosis, and initial management" and "Foreign bodies of the esophagus and gastrointestinal tract in children".)

Computed tomography (CT) has little utility in the diagnosis of poisoning. However, CT of the head can be useful in identifying injuries from or complications of poisoning such as intracranial hemorrhage (eg, in cocaine intoxication) or cerebral edema as a complication of hypoxemia or salicylate ingestion. Abdominal CT has also been described for the evaluation of body packers (internal concealment of illicit drugs). (See "Internal concealment of drugs of abuse (body packing)", section on 'Advanced abdominal imaging'.)

MANAGEMENT — Optimal management of the poisoned child depends upon the specific poison(s) involved, the presenting and predicted severity of illness, and elapsed time between exposure and presentation. Supportive care is the mainstay of therapy, which variably involves decontamination, antidotal therapy, and enhanced elimination techniques [22].

Supportive care — Supportive care is the most important aspect of treatment and, when coupled with decontamination, is usually sufficient for complete recovery. Supportive care for toxic exposures is similar to that provided for other medical problems, but certain issues are managed slightly differently:

Airway protection by endotracheal intubation should be performed early in the poisoned patient with depressed mental status because of the high risk for aspiration and its associated complications, particularly when gastric decontamination is necessary [69]. Endotracheal intubation with mechanical ventilation is also indicated for severe acid-base disturbances or acute respiratory failure. In addition, mechanical ventilation may be necessary in patients who require sedation and/or paralysis to limit the extent of complications such as hyperthermia, acidosis, and rhabdomyolysis.

Hypotension should be managed initially with intravenous fluids. Vasopressors are required when hypotension does not resolve with volume expansion. Direct-acting vasopressors, such as norepinephrine, have been shown to be more effective than indirect-acting agents, such as dopamine, when tricyclic antidepressants have been ingested (see "Tricyclic antidepressant poisoning"). In some cases, intra-aortic balloon pump (IABP) or cardiopulmonary bypass has been used [70].

Hypertension in agitated patients is best treated initially with nonspecific sedatives such as a benzodiazepine [71]. When hypertension necessitates specific therapy because of associated end-organ dysfunction, preferred treatments are nitroprusside, esmolol, or phentolamine. The use of beta-blockers alone for patients with sympathetic hyperactivity (eg, cocaine intoxication) is not recommended because it may result in unopposed alpha-adrenergic stimulation and intensified vasoconstriction [71,72]. Short acting agents are generally preferred because they are easily titrated.

Ventricular tachycardias are usually treated with standard Advanced Cardiac Life Support (ACLS) or Pediatric Advanced Life Support (PALS) recommendations: lidocaine, procainamide, amiodarone, and cardioversion or defibrillation. However, when ventricular tachycardias occur in the context of intoxication with tricyclic antidepressants or other membrane-active agents, sodium bicarbonate is the first-line therapy. Treatment with magnesium sulfate, overdrive pacing with isoproterenol, or a temporary pacemaker may be effective in patients with drug-induced torsades de pointes and prolonged QT intervals on electrocardiogram (ECG). Digoxin-poisoned patients with life-threatening tachyarrhythmias or bradyarrhythmias should be treated with specific Fab fragments (Digibind). (See "Digitalis (cardiac glycoside) poisoning".)

Bradyarrhythmias associated with hypotension should be treated in the standard fashion with atropine or temporary pacing. However, in patients with calcium channel blocker or beta blocker intoxication, the administration of calcium and glucagon may obviate the need for further measures. In the more severe cases, and in consultation with the poison center or clinical toxicologist, high-dose insulin and dextrose (also known as hyperinsulinemia/euglycemia therapy) or lipid infusions can be used. (See "Calcium channel blocker poisoning" and "Major side effects of beta blockers".)

Seizures are typically treated with benzodiazepines followed by barbiturates if necessary. Phenytoin may be effective in controlling seizures caused by agents that stabilize neuronal membranes (eg, propranolol), but is not indicated in most poisonings and is potentially harmful in seizures resulting from theophylline [73]. Seizures caused by certain agents may require specific antidotes for their successful termination (eg, pyridoxine for isoniazid toxicity, glucose for hypoglycemic agents). (See "Management of convulsive status epilepticus in children".)

Drug-associated agitation is usually treated with benzodiazepines, carefully supplemented with high potency neuroleptics (eg, haloperidol, olanzapine, or risperidone) as needed [74]. Agitation associated with certain toxidromes may be best treated with specific agents (eg, physostigmine for the anticholinergic syndrome) [75]. (See appropriate topic reviews).

Decontamination — Following initial patient stabilization, patient decontamination is a priority, as long as there are no contraindications. The sooner decontamination is performed, the more effective it is at preventing poison absorption. Decontamination of poisoned children is discussed in detail separately. (See "Gastrointestinal decontamination of the poisoned patient".)

Activated charcoal is generally the preferred method of GI decontamination in children but is not routinely recommended. The use of activated charcoal is controversial in the asymptomatic patient and probably unnecessary in most cases. If activated charcoal is to be administered, voluntary ingestion in the alert and cooperative patient is always preferred to nasogastric administration. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Activated charcoal'.)

The clinical benefit of gastric lavage has not been confirmed in controlled studies, and its routine use in the management of poisoned patients is no longer recommended by the American Academy of Clinical Toxicology or the European Association of Poisons Centres and Clinical Toxicologists. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Gastric lavage'.)

Whole bowel irrigation is another technique that may be used for patients who have ingested large amounts of substances that are not well bound to activated charcoal  (table 27), for those who have ingested sustained-release preparations, and for those with illicit drug packets (body packers) [22]. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Whole bowel irrigation'.)

Antidotes — Antidote administration is appropriate when there is a poisoning for which an antidote exists, the actual or predicted severity of poisoning warrants its use, expected benefits of therapy outweigh its associated risk, and there are no contraindications. Antidotes reduce or reverse poison effects by a variety of means. They may prevent absorption, bind and neutralize poisons directly, antagonize end-organ effects, or inhibit drug conversion to more toxic metabolites. The pediatric doses for antidotes recommended for stocking in hospitals that accept emergency admissions are provided in the tables (table 28A-B) [22,76].

The pharmacokinetics of the intoxicant and the antidote must be considered because the toxidrome may recur if the antidote is eliminated more rapidly than the ingested substance, particularly if the antidote acts by antagonizing end-organ effects or inhibiting conversion to toxic metabolites. As an example, somnolence and respiratory depression due to ingested opiates acutely reverse with the administration of naloxone but recur in approximately one-third of cases because the elimination half-life of naloxone is only 60 to 90 minutes (see "Opioid intoxication in children and adolescents"). Thus, in certain situations, antidotes may require repeated administration or continuous infusion.

The risks and benefits of antidote administration also must be carefully weighed in the setting of multiple drug ingestion. Many antidotes (eg, antivenom, chelating agents, N-acetylcysteine) may be used concurrently without adverse effects. However, notable exceptions exist. When drugs that have opposite effects are taken at the same time, the reversal of one agent may unmask the toxicity of another. As an example, in a patient who ingested diazepam and cocaine, the administration of flumazenil, the benzodiazepine antidote, could lower the seizure threshold and increase the risk of serious complications. (See "Cocaine: Acute intoxication".)

In addition, when drugs that have similar effects are co-ingested, the antidote may not seem to have any effect. This is a common problem when opioids are ingested with large amounts of ethanol. In such circumstances, naloxone may be administered in such large amounts that it results in opioid withdrawal. For this reason, naloxone should be administered at lower doses in patients in whom there is a suspicion of opioid dependence. (See "Opioid withdrawal in adolescents".)

Diagnostic trial — In some cases, the clinical response to an antidote may suggest the etiology of poisoning [36]. Antidotes should be used in selected clinical scenarios by clinicians who are experienced in their use, or after consultation with available experts such as those at regional Poison Control Centers (1-800-222-1222). Examples include:

Improved alertness in response to flumazenil for benzodiazepine ingestion; flumazenil is contraindicated in drug ingestions that may precipitate seizures and in patients with a known seizure disorder. It also may precipitate withdrawal in patients with benzodiazepine dependence.

Improved alertness in response to glucose for insulin or oral hypoglycemic agent ingestion.

Improved alertness in response to physostigmine for anticholinergic agent ingestion; physostigmine is contraindicated in tricyclic antidepressant overdoses. Physostigmine should not be administered to patients who have a widened QRS interval on electrocardiogram.

Improved alertness in response to naloxone for opiate/opioid ingestion.

Improved clotting in response to protamine for heparin overdoses.

Abatement of dystonia in response to diphenhydramine for phenothiazine ingestion.

Enhanced elimination — Once detected, enhanced elimination techniques can be used for several drugs and toxins (table 29). Enhanced elimination techniques, which include multidose activated charcoal, urinary alkalinization, hemodialysis, and hemoperfusion, are discussed in detail separately. (See "Enhanced elimination of poisons".)

Disposition — Following initial evaluation, treatment, and a short period of observation, disposition of the patient is based upon the observed and predicted severity of toxicity. Patients who develop only mild toxicity and who have only a low predicted severity can be observed in the emergency department until they are asymptomatic. An observation period of six hours is usually adequate for this purpose. All patients with intentional overdose require psychiatric assessment prior to discharge.

Other factors to consider in the disposition include whether the child's caregivers understand the potential for delayed consequences of poisoning, have a means of transportation to return if necessary, and are able to provide adequate observation at home [4]. In addition, if a suboptimal home environment contributed to the ingestion, consultation with a social worker or case manager may be indicated, particularly if child neglect is being considered. (See "Child neglect: Evaluation and management".)

Longer observation (or hospital admission) may be necessary for patients who are thought to have ingested substances with delayed effects (table 9), sustained release preparations, or multiple agents. The duration of observation varies depending upon the expected time of onset and duration of symptoms. The half-lives of drugs are calculated based upon therapeutic dosing; in the overdose setting, the calculated half-life may be inaccurate and the duration of symptoms prolonged

The toxicity of agents varies depending upon whether the ingestion is acute or chronic, whether other substances have been ingested, the time between ingestion and presentation, and the child's baseline health status. Thus, decisions regarding admission should be based both on drug levels (when available) and the clinical scenario.

Patients with moderate observed toxicity or those who are at risk for such on the basis of history or initial laboratory data should be admitted to an intermediate care floor or an appropriate observation unit for continued monitoring and treatment. Patients with significant toxicity should be admitted to an intensive care unit (ICU) (table 30).

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Another helpful resource is the Cornell University Poisonous Plants Informational Database (www.ansci.cornell.edu/plants/index.html).

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

Occult toxic exposure should be considered in the differential diagnosis of children who present with acute onset of multiorgan system dysfunction, altered mental status, respiratory or cardiac compromise, unexplained metabolic acidosis, seizures, or a puzzling clinical picture. The index of suspicion should be raised if the child is in the "at-risk" age group (one to four years of age), has history of substance use disorder (SUD), and/or has a previous history of poisoning. (See 'Clinical presentation' above.)

In older children and adolescents with occult poisoning, suspect suicide attempts or recreational abuse of illicit or prescription drugs. Child abuse via forced ingestion in young children also occurs, particularly in those who are younger than one year of age. (See 'Clinical presentation' above.)

The approach to the poisoned child begins with initial evaluation and stabilization of airway, breathing, circulation, and evaluation and treatment of any neurologic issues, while fully exposing the patient. (See 'Approach' above and 'Initial evaluation and stabilization' above.)

Hypoxemia and hypoglycemia are two common causes of altered mental status in the poisoned patient that should be promptly evaluated and addressed during initial stabilization. (See 'Initial evaluation and stabilization' above.)

Administration of naloxone is indicated in patients who have depressed mental status, diminished respirations, miotic pupils, or other circumstantial evidence of opioid intoxication. (See 'Altered mental status' above.)

History and physical examination are helpful in determining the type of poisoning in a significant number of children. (See 'Diagnosis of poisoning' above.)

Evaluation of mental status, vital signs, and pupils, along with assessment of skin and other findings (toxidrome recognition) may provide clues to the type of poisoning and help guide empiric and directed treatment (table 2). (See 'Physical examination' above.)

Key ancillary studies include rapid blood glucose, electrolytes with calculation of an anion gap, venous or arterial blood gas, serum acetaminophen concentration, and electrocardiogram. Patients with respiratory alkalosis or metabolic acidosis and/or an elevated anion gap also warrant measurement of a salicylate level and serum osmolality. (See 'Ancillary studies' above.)

Supportive care is the most important aspect of treatment and, when coupled with decontamination (when indicated), is usually sufficient for complete recovery. (See 'Supportive care' above and 'Decontamination' above.)

Antidotes should be used in selected clinical scenarios by clinicians who are experienced in their use, or after consultation with available experts such as those at regional Poison Control Centers. (See 'Regional poison control centers' above and 'Antidotes' above.)

  1. Gummin DD, Mowry JB, Beuhler MC, et al. 2019 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 37th Annual Report. Clin Toxicol (Phila) 2020; 58:1360.
  2. Yard E, Radhakrishnan L, Ballesteros MF, et al. Emergency Department Visits for Suspected Suicide Attempts Among Persons Aged 12-25 Years Before and During the COVID-19 Pandemic - United States, January 2019-May 2021. MMWR Morb Mortal Wkly Rep 2021; 70:888.
  3. O'Donnell KA, Osterhoudt KC, Burns MM, et al. Toxicologic emergencies. In: Fleisher and Ludwig's Textbook of Pediatric Emergency Medicine, 7th ed, Shaw KN, Bachur RG (Eds), Wolters Kluwer, Philadelphia 2016. p.1061.
  4. Bryant S, Singer J. Management of toxic exposure in children. Emerg Med Clin North Am 2003; 21:101.
  5. Mofenson HC, Greensher J. The unknown poison. Pediatrics 1974; 54:336.
  6. Friedman EM. Caustic ingestions and foreign body aspirations: an overlooked form of child abuse. Ann Otol Rhinol Laryngol 1987; 96:709.
  7. Dine MS, McGovern ME. Intentional poisoning of children--an overlooked category of child abuse: report of seven cases and review of the literature. Pediatrics 1982; 70:32.
  8. Cohle SD, Trestrail JD 3rd, Graham MA, et al. Fatal pepper aspiration. Am J Dis Child 1988; 142:633.
  9. Henretig FM, Paschall R, Donaruma-Kwoh MM. Child abuse by poisoning. In: Child Abuse Medical Diagnosis & Management, 3rd ed, Reece R, Christian C (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2009. p.549.
  10. Siew LT, Auerbach M, Baum CR, et al. Respiratory failure caused by a suspicious white powder: a case report of intentional methadone poisoning in an infant. Pediatr Emerg Care 2012; 28:918.
  11. Arieff AI, Kronlund BA. Fatal child abuse by forced water intoxication. Pediatrics 1999; 103:1292.
  12. Meadow R. Non-accidental salt poisoning. Arch Dis Child 1993; 68:448.
  13. McClung HJ, Murray R, Braden NJ, et al. Intentional ipecac poisoning in children. Am J Dis Child 1988; 142:637.
  14. Goldfrank LR, Flomenbaum NE, Lewin NA, et al. Principles of managing the poisoned or overdosed patient: An overview. In: Goldfrank's Toxicologic Emergencies, 6th ed, Goldfrank L (Ed), Appleton and Lange, Stamford 1998. p.31.
  15. Clinical policy for the initial approach to patients presenting with acute toxic ingestion or dermal or inhalation exposure. American College of Emergency Physicians. Ann Emerg Med 1995; 25:570.
  16. Linden CH. General considerations in the evaluation and treatment of poisoning. In: Intensive Care Medicine, Rippe JM, Irwin RS, Fink MP, Cerra FB (Eds), Little Brown and Company, Boston 1996. p.1455.
  17. Clancy C. Electrophysiologic and electrocardiographic principles. In: Goldfrank's Toxicologic Emergencies, 9th ed, Nelson L et al (Ed), McGraw Hill, Stamford 2011. p.314.
  18. Boehnert MT, Lovejoy FH Jr. Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. N Engl J Med 1985; 313:474.
  19. Kirk M, Pace S. Pearls, pitfalls, and updates in toxicology. Emerg Med Clin North Am 1997; 15:427.
  20. Albertson TE, Dawson A, de Latorre F, et al. TOX-ACLS: toxicologic-oriented advanced cardiac life support. Ann Emerg Med 2001; 37:S78.
  21. Hoffman RS, Goldfrank LR. The poisoned patient with altered consciousness. Controversies in the use of a 'coma cocktail'. JAMA 1995; 274:562.
  22. Clinical policy for the initial approach to patients presenting with acute toxic ingestion or dermal or inhalation exposure. Ann Emerg Med 1999; 33:735.
  23. Goldfrank L, Weisman RS, Errick JK, Lo MW. A dosing nomogram for continuous infusion intravenous naloxone. Ann Emerg Med 1986; 15:566.
  24. Hoffman JR, Schriger DL, Luo JS. The empiric use of naloxone in patients with altered mental status: a reappraisal. Ann Emerg Med 1991; 20:246.
  25. Tate JR, Nixon PF. Measurement of Michaelis constant for human erythrocyte transketolase and thiamin diphosphate. Anal Biochem 1987; 160:78.
  26. Schabelman E, Kuo D. Glucose before thiamine for Wernicke encephalopathy: a literature review. J Emerg Med 2012; 42:488.
  27. Finkelstein Y, Hutson JR, Wax PM, et al. Toxico-surveillance of infant and toddler poisonings in the United States. J Med Toxicol 2012; 8:263.
  28. Emery, D, Singer J. Highly toxic ingestions for toddlers: when a pill can kill. Pediatr Emerg Med Rep 1998; 3:111.
  29. Osterhoudt, KC . The toxic toddler: drugs that can kill in small doses. Contemp Pediatr 2000; 17:73.
  30. Bar-Oz B, Levichek Z, Koren G. Medications that can be fatal for a toddler with one tablet or teaspoonful: a 2004 update. Paediatr Drugs 2004; 6:123.
  31. Matteucci MJ. One pill can kill: assessing the potential for fatal poisonings in children. Pediatr Ann 2005; 34:964.
  32. Chomchai C, Sirisamut T, Silpasupagornwong U. Pediatric fatality from gun bluing solution: the need for a chemical equivalent of the one-pill-can-kill list. J Med Assoc Thai 2012; 95:821.
  33. Sutter ME, Gerona RR, Davis MT, et al. Fatal Fentanyl: One Pill Can Kill. Acad Emerg Med 2017; 24:106.
  34. Michael JB, Sztajnkrycer MD. Deadly pediatric poisons: nine common agents that kill at low doses. Emerg Med Clin North Am 2004; 22:1019.
  35. Shannon M. Ingestion of toxic substances by children. N Engl J Med 2000; 342:186.
  36. Woolf AD. Poisoning by unknown agents. Pediatr Rev 1999; 20:166.
  37. Brayden RM, MacLean WE Jr, Bonfiglio JF, Altemeier W. Behavioral antecedents of pediatric poisonings. Clin Pediatr (Phila) 1993; 32:30.
  38. Litovitz TL, Klein-Schwartz W, Rodgers GC Jr, et al. 2001 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2002; 20:391.
  39. Soslow AR. Acute drug overdose: one hospital's experience. Ann Emerg Med 1981; 10:18.
  40. Wright N. An assessment of the unreliability of the history given by self-poisoned patients. Clin Toxicol 1980; 16:381.
  41. Woolf A, Alpert HR, Garg A, Lesko S. Adolescent occupational toxic exposures: a national study. Arch Pediatr Adolesc Med 2001; 155:704.
  42. United States Department of Justice/Drug Enforcement Administration. Drug Fact Sheet: Counterfeit Pills. https://www.dea.gov/sites/default/files/2021-05/Counterfeit%20Pills%20fact%20SHEET-5-13-21-FINAL.pdf.
  43. Ratnapalan S, Potylitsina Y, Tan LH, et al. Measuring a toddler's mouthful: toxicologic considerations. J Pediatr 2003; 142:729.
  44. Havlik DM, Nolte KB. Fatal "crack" cocaine ingestion in an infant. Am J Forensic Med Pathol 2000; 21:245.
  45. Boros CA, Parsons DW, Zoanetti GD, et al. Cannabis cookies: a cause of coma. J Paediatr Child Health 1996; 32:194.
  46. Winter ML, Ellis MD, Snodgrass WR. Urine fluorescence using a Wood's lamp to detect the antifreeze additive sodium fluorescein: a qualitative adjunctive test in suspected ethylene glycol ingestions. Ann Emerg Med 1990; 19:663.
  47. Fulop M. Flow diagrams for the diagnosis of acid-base disorders. J Emerg Med 1998; 16:97.
  48. Rutecki GW, Whittier FC. An approach to clinical acid-base problem solving. Compr Ther 1998; 24:553.
  49. Gabow PA. Disorders associated with an altered anion gap. Kidney Int 1985; 27:472.
  50. Emmett M, Narins RG. Clinical use of the anion gap. Medicine (Baltimore) 1977; 56:38.
  51. Hoffman RS. Fluid, electrolyte, and acid-base principles. In: Goldfrank's Toxicologic Emergencies, 6th ed, Goldfrank L, et al (Eds), Appleton and Lange, Stamford 1998. p.243.
  52. Jurado RL, del Rio C, Nassar G, et al. Low anion gap. South Med J 1998; 91:624.
  53. Steinhart B. Case report: severe ethylene glycol intoxication with normal osmolal gap--"a chilling thought". J Emerg Med 1990; 8:583.
  54. Glaser DS. Utility of the serum osmol gap in the diagnosis of methanol or ethylene glycol ingestion. Ann Emerg Med 1996; 27:343.
  55. Eisen TF, Lacouture PG, Woolf A. Serum osmolality in alcohol ingestions: differences in availability among laboratories of teaching hospital, nonteaching hospital, and commercial facilities. Am J Emerg Med 1989; 7:256.
  56. Hoffman RS, Smilkstein MJ, Howland MA, Goldfrank LR. Osmol gaps revisited: normal values and limitations. J Toxicol Clin Toxicol 1993; 31:81.
  57. Wallace KL, Suchard JR, Curry SC, Reagan C. Diagnostic use of physicians' detection of urine fluorescence in a simulated ingestion of sodium fluorescein-containing antifreeze. Ann Emerg Med 2001; 38:49.
  58. Casavant MJ, Shah MN, Battels R. Does fluorescent urine indicate antifreeze ingestion by children? Pediatrics 2001; 107:113.
  59. Osterloh JD, Snyder JW. Laboratory principles and techniques to evaluate the poisoned or overdosed patient. In: Goldfrank's Toxicologic Emergencies, 6th ed, Goldfrank L, et al (Eds), Appleton and Lange, Stamford 1998. p.64.
  60. Wiley JF 2nd. Difficult diagnoses in toxicology. Poisons not detected by the comprehensive drug screen. Pediatr Clin North Am 1991; 38:725.
  61. Osterloh JD. Utility and reliability of emergency toxicologic testing. Emerg Med Clin North Am 1990; 8:693.
  62. Ashbourne JF, Olson KR, Khayam-Bashi H. Value of rapid screening for acetaminophen in all patients with intentional drug overdose. Ann Emerg Med 1989; 18:1035.
  63. Sporer KA, Khayam-Bashi H. Acetaminophen and salicylate serum levels in patients with suicidal ingestion or altered mental status. Am J Emerg Med 1996; 14:443.
  64. Belson MG, Simon HK. Utility of comprehensive toxicologic screens in children. Am J Emerg Med 1999; 17:221.
  65. Brett AS. Implications of discordance between clinical impression and toxicology analysis in drug overdose. Arch Intern Med 1988; 148:437.
  66. Kellermann AL, Fihn SD, LoGerfo JP, Copass MK. Impact of drug screening in suspected overdose. Ann Emerg Med 1987; 16:1206.
  67. Schwartz DT. Diagnostic imaging. In: Goldfrank's Toxicologic Emergencies, 9th ed, Nelson L et al (Ed), McGraw Hill, Stamford 2011. p.45.
  68. Florez MV, Evans JM, Daly TR. The radiodensity of medications seen on x-ray films. Mayo Clin Proc 1998; 73:516.
  69. Roy TM, Ossorio MA, Cipolla LM, et al. Pulmonary complications after tricyclic antidepressant overdose. Chest 1989; 96:852.
  70. Johnson NJ, Gaieski DF, Allen SR, et al. A review of emergency cardiopulmonary bypass for severe poisoning by cardiotoxic drugs. J Med Toxicol 2013; 9:54.
  71. Hollander JE. The management of cocaine-associated myocardial ischemia. N Engl J Med 1995; 333:1267.
  72. Lange RA, Cigarroa RG, Flores ED, et al. Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade. Ann Intern Med 1990; 112:897.
  73. Blake KV, Massey KL, Hendeles L, et al. Relative efficacy of phenytoin and phenobarbital for the prevention of theophylline-induced seizures in mice. Ann Emerg Med 1988; 17:1024.
  74. Battaglia J, Moss S, Rush J, et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Am J Emerg Med 1997; 15:335.
  75. Burns MJ, Linden CH, Graudins A, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med 2000; 35:374.
  76. Dart RC, Borron SW, Caravati EM, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med 2009; 54:386.
Topic 6496 Version 25.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟