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Drug Overdose and Antidotes (FL INITIAL Autonomous Practice - Pharmacology)

2 Contact Hours including 2 Advanced Pharmacology Hours
Only FL APRNs will receive credit for this course.
This course is only applicable for Florida nurse practitioners who need to meet the autonomous practice initial licensure requirement.
This peer reviewed course is applicable for the following professions:
Advanced Registered Nurse Practitioner (ARNP)
This course will be updated or discontinued on or before Thursday, November 30, 2023

Nationally Accredited

CEUFast, Inc. is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. ANCC Provider number #P0274.


Outcomes

The purpose of this activity is to provide nurses with the knowledge needed to assess and treat a poisoned patient, specifically a patient with a known or possible drug overdose.

Objectives

After completing this course, the learner will be able to:

  1. Identify the first step in the treatment of a poisoned patient.
  2. Summarize vital sign changes caused by overdose with specific drugs.
  3. Identify two toxidromes.
  4. Outline the laboratory tests and diagnostic tests that should be done for all poisoned patients.
  5. Distinguish the drug level that should be measured in all poisoned patients.
  6. Summarize when gastric decontamination should be used.
  7. Categorize four antidotes and the indications for their use.
CEUFast Inc. and the course planners for this educational activity do not have any relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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To earn of certificate of completion you have one of two options:
  1. Take test and pass with a score of at least 80%
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    (NOTE: Some approval agencies and organizations require you to take a test and self reflection is NOT an option.)
Author:    Dana Bartlett (RN, BSN, MA, MA, CSPI)

Definition and Epidemiology

Poisoning is defined as the adverse effects caused by exposure to chemicals, drugs, or toxins. Poisonings can occur after ingestion, dermal exposure, inhalation, ocular exposure, and parenteral exposure, and they can occur after a suicide attempt, an adverse drug reaction, a therapeutic error, an environmental or occupational exposure, or an unintentional pediatric exposure.

Poisonings are a significant public health problem. Most poisonings do not cause death or lasting harm, but in 2019 in the United States, there were 1,923 deaths from poisonings and hundreds of thousands of poisoned patients who needed ER and/or ICU treatment, and antidotal therapy (Gummin et al., 2020).

Basics of Assessing and Treating a Poisoned Patient

The approach to managing a poisoned patient involves three steps. They are listed sequentially, but care providers can and often must do several steps simultaneously. Also, efficient use of resources is important. Nurses who are not providing direct patient care can speak with the patient’s family members to find out more information about the circumstances or call the poison control center for advice. 1-800-222-1222 will connect a caller to the closest poison control center in the United States.

  1. Assessment and Stabilization
  2. Clinical History
  3. Treatment: Dextrose, oxygen, naloxone, thiamine, gastric decontamination, antidotes

Clinical History

A comprehensive and complete clinical history is essential because:

  1. The patient’s age, co-morbidities, and current state of health are important determinants of her/his response to the ingestion.
  2. The treatment of a poisoned patient will largely depend on what the patient took or was exposed to, why the ingestion/exposure occurred, how much the patient took or was exposed to and when, and the patient’s signs and symptoms.
  3. Not knowing what the patient took is a common occurrence (Nelson et al., 2019a), especially if the ingestion was done with intent to cause self-harm (Levine, 2021).

Determine the time, route, and duration of the exposure, what was taken, why, and the amount.

Find out what prescription medications, over-the-counter medications, and supplements the patient takes. Obtain the patient’s medical records. If they are not available, family and friends of the patient may know about the patient’s medical and/or psychiatric conditions.

Assessment and Initial Stabilization

Airway, Breathing, Circulation

Begin treatment by evaluating and securing (if necessary) the patient’s airway, assessing breathing and circulation, and measuring body temperature (Nelson et al., 2019a; Olson & Vohra, 2018a). Obtain IV access, if needed, and start continuous cardiac monitoring.

If the patient’s oxygen saturation, respiratory, blood pressure, and heart rate, or temperature are abnormal, begin treatment with standard, supportive care (Nelson et al., 2019b; Olson & Vohra, 2018a): For example, if the patient’s oxygen saturation is abnormally low, administer supplemental oxygen, if the patient is hypotensive, give IV fluids and vasopressors, and if the patient is hyperthermic start cooling measures (Nelson et al., 2019b; Olson & Vohra, 2018a).

If the abnormal breathing and/or circulation are caused by a drug or toxin for which a specific antidote is available, the antidote can be used, but standard, supportive care measures are always at hand (an antidote may need to be ordered from the pharmacy), and nurses and physicians are familiar with their use.

Drugs and toxins can cause specific changes in vital signs and oxygen saturation, and abnormal vital signs are a helpful diagnostic tool if it is unknown what the patient was exposed to or ingested. Vital sign changes associated with an overdose or exposure are listed below (Nelson et al., 2019a; Olson & Vohra, 2018a).

Table 1: Vital Sign Changes and Poisoning
Bradycardia:
  • Alpha-2 agonists (centrally-acting), e.g., clonidine, guanfacine
  • Beta-blockers
  • Calcium channel blockers
  • Digoxin
  • Opioids
  • Organophosphate pesticides
Tachycardia:
  • Anticholinergics, e.g., antihistamines
  • Antipsychotics
  • Beta-adrenergic agonists, e.g., albuterol
  • Cyclic antidepressants
  • Nicotine
  • Phencyclidine, aka PCP
  • Sympathomimetics, e.g., amphetamine, cocaine
  • Thyroid hormone
Hypotension:
  • Antihypertensives
  • Baclofen
  • Beta-blockers
  • Calcium channel blockers
  • Cyclic antidepressants
  • Ethanol
  • Opioids
  • Phenothiazines
  • Sedative-hypnotics, e.g., barbituates, benzodiazepines
Hypertension:
  • Alpha-1 adrenergic drugs
  • Drug withdrawal
  • Monoamine oxidase inhibitors
  • Nicotine
  • Phencyclidine
  • Sympathomimetics, e.g., amphetamine, cocaine
Bradypnea/Respiratory depression:
  • Alpha-2 agonists (centrally-acting), e.g., clonidine, guanfacine
  • Carbamate pesticides
  • Ethanol
  • Opioids
  • Organophosphate Pesticides
  • Sedative-hypnotics, e.g., barbituates, benzodiazepines
Tachypnea:
  • Methemoglobin inducers, e.g., local anesthetics
  • Salicylates
  • Sympathomimetics
  • Toxic Alcohols, e.g., ethylene glycol, methanol
Hypothermia:
  • Alpha-2 agonists (centrally-acting), e.g., clonidine, guanfacine
  • Carbon monoxide
  • Ethanol
  • Hypoglycemics
  • Opioids
  • Sedative-hypnotics, e.g., barbituates, benzodiazepines
Hyperthermia:
  • Anticholinergics, e.g., antihistamines
  • Monoamine oxidase inhibitors
  • Neuroleptic malignant syndrome from antipsychotics
  • Phencyclidine, aka PCP

Physical Examination

The physical examination can be done during or after the initial assessment. Physical signs that clinicians should look for in the context of an overdose or an exposure to a toxin include:

  • Neurologic: Level of consciousness. Focal neurologic symptoms rarely occur with poisoning. If the patient presents with focal neurologic symptoms, imaging studies should be done promptly imaged to evaluate for the presence of structural central nervous system abnormalities.
  • Cardiovascular: Peripheral perfusion.
  • Gastrointestinal: Presence/absence of bowel sounds.
  • Genitourinary: Urinary retention, incontinence.
  • Dermal: Skin color and temperature, skin turgor, mucous membranes (moist or dry), dry skin, or diaphoresis.
  • Ophthalmic: Pupil size, pupil reactivity.
  • Pulmonary: Bronchospasm, bronchorrhea (excess secretions)

Examine the patient for signs of trauma, and look for evidence of illicit drug use, e.g., needle marks.

Exposure to a toxin or an overdose with a specific drug, e.g., an opioid, will often cause specific physical findings: For example, an opioid overdose causes central nervous (CNS) system depression, respiratory depression, and miosis. The signs and symptoms that consistently occur after exposure to a toxin or an overdose with a drug, together with vital sign changes, are called a toxidrome, a combination of toxic and syndrome (Nelson et al., 2019a). Commonly occurring toxidromes are listed in Table 2 (Levine, 2021; Nelson et al., 2019a; Olson & Vohra, 2018a).

Table 2: Toxidromes


Anticholinergic: Antihistamines, atropine, cyclic antidepressants, antipsychotics
NeurologicAgitation, confusion, hallucinations
CardiovascularTachycardia, normal or slightly elevated blood pressure
DermalHot, flushed skin, dry mucous membranes
GastrointestinalAbsent or diminished bowel sounds
GenitourinaryUrinary retention
OphthalmicMydriasis
PulmonaryHyperventilation can occur in agitated patients
TemperatureElevated


Cholinergic: Organophosphate pesticides, cholinergic drugs used to treat Alzheimer's disease
NeurologicNormal or depressed sensorium
CardiovascularBradycardia can occur
DermalDiaphoresis
GastrointestinalDiarrhea and vomiting
GenitourinaryUrination
OphthalmicNormal or miotic
PulmonaryBronchospasm, bronchorrhea
TemperatureNormal
MiscellaneousLacrimation and salivation


Ethanol and sedative-hypnotics: Beverage alcohol, barbiturates, benzodiazepines
NeurologicCNS depression, ataxia, hyporeflexia
CardiovascularBradycardia and hypotension
GastrointestinalDecreased peristalsis, vomiting (ethanol)
OphthalmicPupil size, variable
PulmonaryRespiratory depression
TemperatureLow, hypothermia is possible


Opioid: Codeine, fentanyl, heroin, methadone
NeurologicCNS depression, hyporeflexia
CardiovascularBradycardia, hypotension
GastrointestinalDecreased peristalsis
OphthalmicMiosis
PulmonaryRespiratory depression
TemperatureLow, hypothermia is possible


Serotonin: SSRI antidepressants, fentanyl, MAOIs, MDMA, aka ecstasy, tramadol
NeurologicClonus, delirium, hyperreflexia, tremor, seizures
CardiovascularHypertension, tachycardia
DermalDiaphoresis
GastrointestinalIncreased peristalsis
Genitourinary 
OphthalmicNormal, mydriasis
PulmonaryNormal respiratory rate, tachypnea can occur
TemperatureNormal, elevated temperature can occur


Sympathomimetic: Amphetamine, cocaine, ADHD drugs like methylphenidate
NeurologicAgitation, tremor, seizures
CardiovascularHypertension, tachycardia
DermalDiaphoresis
GastrointestinalIncreased peristalsis can occur
GenitourinaryNormal
OphthalmicMydriasis
PulmonaryTachypnea
TemperatureElevated

Diagnostic Tests

If the ingestion was done to cause self-harm or if the patient’s intent is unknown, measure an acetaminophen level (Hendrickson & McKeown, 2019; Levine, 2021, Nelson, 2019b). Experience has shown that 1.4% to 8.4% of suicidal patients who have reportedly not taken acetaminophen will have a measurable acetaminophen level. Up to 2.2% will have a level that indicates the need for antidotal treatment, i.e., N-acetylcysteine (NAC) (Hendrickson & McKeown, 2019). Because of this and because toxicity caused by acetaminophen overdose has a delayed onset, an acetaminophen level should be measured in every patient who has taken a deliberate overdose or if the patient’s intent is not known/cannot be known.

Measure blood urea nitrogen (BUN), complete blood count (CBC), creatinine, electrolytes, glucose, a urinalysis, and a salicylate level, and get a 12-lead ECG (Levine, 2021; Nelson et al., 2019a). These tests and a 12-lead ECG should be the minimum diagnostic testing that is done (Levine, 2021).

Pulse oximetry measures oxygen saturation, but an arterial blood gas (ABG) or a venous blood gas (VBG) and serum lactate can help identify acid-base disturbances. Creatinine phosphokinase (CPK or CK), an ethanol level, and serum ketones are helpful diagnostic tests for poisoned patients, as well (Nelson et al., 2019b).

Blood levels of certain drugs can be quickly measured (Levine, 2021), and levels should be done if the history or clinical presentation confirms or suggests a poisoning with one of these drugs. Also, blood levels of some toxins can be measured. The list in Table 3 is not all-inclusive.

Table 3: Blood Levels of Drugs and Toxins
  • Acetaminophen
  • Aspirin
  • Carbamazepine
  • Carbon monoxide
  • Digoxin
  • Ethanol
  • Iron
  • Lead
  • Lithium
  • Methemoglobin
  • Phenytoin
  • Toxic alcohols
    • ethylene glycol
    • isopropyl alcohol
    • methanol
  • Valproic acid

Rapid urine drug screens measure the levels of drugs of abuse, e.g., amphetamine, barbiturates, benzodiazepines, cocaine, marijuana, opioids, and PCP (Levine, 2021; Olson & Vohra, 2018a). However, the commonly used urine drug screen is not clinically useful in the setting of an acute overdose because (Levine, 2021; Stellpflug et al., 2020):

  1. A positive test indicates recent use but not current use and/or intoxication with the drug.
  2. False negatives and false positives are possible.
  3. Some commonly abused drugs like clonazepam and fentanyl are not detected in standard urine drugs screens (Levine, 2021; Stellpflug et al., 2020).

Electrocardiogram (ECG)

Many drugs and toxins cause ECG changes (Khatib et al., 2021; Morgan, 2020; Clancy, 2019; Farkas et al., 2018; Olson & Vohra, 2018a; Tisdale, 2016), and a 12-lead ECG should be done for most poisoned patients. The list in Table 4 provides examples; it is not all-inclusive.

Table 4: ECG Changes and Poisoning
ECG ChangePoisoning
Heart BlocksBeta-blockers, calcium channel blockers, cocaine, cyclic antidepressants, digoxin
QRS prolongationAnticholinergics cyclic antidepressants, local anesthetics
QT prolongationAntiarrhythmics, antidepressants, antiemetics, antipsychotics, macrolide antibiotics, methadone

Imaging Studies

A simple x-ray of the stomach and the gut can detect the presence of radiopaque drugs or foreign materials (Levine, 2021; Schwartz, 2019; Olson & Vohra, 2018a).

Radiopaque drugs include chloral hydrate, enteric-coated tablets, iron, phenothiazines, and sustained-release tablets (Schwartz, 2019; Levine, 2021; Olson & Vohra, 2018a). However, an x-ray that does not detect a swallowed drug, even a drug that is radiopaque, cannot be considered as conclusive evidence that drug ingestion did not occur (Schwartz, 2019).

Metals like lead and mercury are radiopaque (Schwartz, 2019; Levine, 2021; Olson & Vohra, 2018a).

An x-ray can detect packages of illicit drugs that have been swallowed or inserted into the GI tract or a body cavity for smuggling, i.e., body packing (Schwartz, 2019). An x-ray is not likely to detect a package of an illicit drug that has been quickly swallowed to evade arrest, i.e., body stuffing (Schwartz, 2019).

Treatment of the Poisoned Patient

Dextrose, Oxygen, Naloxone, Thiamine: D.O.N.T

For many years, empiric administration of dextrose, oxygen, naloxone, and thiamine (D.O.N.T) was considered a standard treatment for all poisoned patients (Nelson et al., 2019b) but this is no longer the case.

Measurements of blood glucose and oxygen saturation are immediately available. Dextrose should be given only if a patient has a depressed sensorium and bedside blood glucose measurement is not available (Olson & Vohra, 2018a).

Naloxone is the antidote for opioid poisoning. It is a very safe drug, but it can precipitate opioid withdrawal (Go, 2018), and its use has been associated with non-cardiogenic pulmonary edema and cardiac arrhythmias (Albertson, 2018; Lameijer et al., 2014; Yin, 2020).

Thiamine prevents/treats Wernicke encephalopathy, a disorder caused by thiamine deficiency in people who abuse alcohol (Olson & Vohra, 2018a). It is a very safe drug (Kearney, 2018a), but Wernicke encephalopathy is characterized by significant CNS changes.

Gastric Decontamination

Gastric decontamination is a group of techniques that can remove ingested drugs and toxins, prevent their absorption, or hasten their elimination. The techniques that are currently used include (Hoegberg, 2019; Olson & Vohra, 2018b):

  1. Activated charcoal
  2. Cathartics
  3. Multiple-dose activated charcoal
  4. Orogastric lavage
  5. Whole-bowel irrigation

Syrup of ipecac induces vomiting, but it is no longer available, and it is ineffective and potentially hazardous (Hojer et al., 2013).

Gastric decontamination has long been used to treat poisoned patients. Unfortunately, there is no conclusive evidence that it is effective (Hoegberg, 2019; Olson & Vohra, 2018b). There are no evidence-based guidelines that outline when and for whom gastric decontamination should be used (Hoegberg, 2019; Olson & Vohra, 2018b). In medical toxicology, gastrointestinal decontamination is highly controversial. There is insufficient evidence available to formulate an evidence-based decision on many of the scenarios that could occur; therefore, clinicians often make decisions based on a theoretical approach rather than evidence. (Hoegberg, 2019). Consult with a toxicologist or a poison control center before using gastric decontamination for a patient who has had bariatric surgery.

  • Activated charcoal: Activated charcoal (AC) adsorbs ingested xenobiotics and prevents them from being absorbed through the gut (Hoegberg, 2019; Kearney, 2018b; Smith & Howland, 2019a).
    • Charcoal is most effective when it is given ≤ one hour after ingestion (Hoegberg, 2019; Kearney, 2018b; Smith & Howland, 2019a). However, AC can be given > one hour after ingestion if the patient has ingested
      • a massive amount of drugs
      • a drug that slows peristalsis, e.g., an anticholinergic or an opioid
      • a sustained-release drug, or
      • a drug like aspirin that can form a bezoar (Olson & Vohra, 2018b)
    • Charcoal is contraindicated if the patient has CNS depression, does not have a normally functioning GI tract, has ingested an acid or an alkali, or if an endoscopy will be needed (Kearney, 2018b; Olson & Vohra, 2018b; Smith & Howland, 2019a).
    • Nausea and vomiting are common adverse effects of AC (Smith & Howland, 2019a), and pulmonary aspiration can occur (Hoegberg, 2019).
    • Charcoal will not adsorb alcohol, iron, hydrocarbons, lead, lithium, or magnesium, potassium, or sodium salts (Olson & Vohra, 2018b; Smith & Howland, 2019a).
    • The dose of AC is 1 g/kg, children < 5 years old 0.5 to 1 g/kg (Kearney, 2018b) or an AC to drug ratio of 10:1, up to an amount that can be tolerated (Smith & Howland, 2019a); this is typically 50 to 100 grams (Smith & Howland, 2019a).
  • Cathartics: Cathartics like magnesium citrate and sorbitol increase the transit time of ingested drugs (Olson & Vohra, 2018a), but there is no evidence that they are effective, and they should not be given (Hoegberg, 2019).
    • Pre-mixed AC often contains sorbitol. One-time use of AC with sorbitol is acceptable, but multiple doses of AC with sorbitol should not be given (Hoegberg, 2019).
  • Multiple-dose AC: Multiple-dose AC (MDAC) is the administration of serial doses of AC every two to four hours (Kearney, 2018b). The mechanism of action of MDAC is interruption of enterohepatic and/or enteroenteric recirculation of a drug or toxin (Olson & Vohra, 2018b).
    • MDAC is recommended if the patient has ingested a potentially life-threatening amount of certain drugs, e.g., amiodarone, carbamazepine, dapsone, phenobarbital, quinine, sotalol, theophylline, or verapamil (Hoegberg, 2019; Olson & Vohra, 2018a). Call the local poison control center for advice about when and for which drug ingestions MDAC is helpful.
    • The contradictions and adverse effects of MDAC are the same as for AC (Hoegberg, 2019).
    • There is not a universally accepted/used MDAC dose or duration of MDAC therapy, and Kearney (2018b) recommends 15 to 30 g/ 0.25 to 0.5 g, every two to four hours.
  • Orogastric lavage: Orogastric lavage is the insertion of a nasogastric tube into the stomach and the aspiration of ingested drugs.
    • There is little evidence that orogastric lavage is effective (Hoegberg, 2019; Olson & Vohra, 2018b). It is complicated, time-consuming, and invasive, and there are no universally accepted guidelines for the procedure (Hoegberg, 2019).
    • Orogastric lavage can be used if:
      • the patient has ingested a life-threatening drug
      • the patient has life-threatening signs and symptoms
      • the drug/toxin is not absorbed into AC
      • there is a high likelihood that there is a large amount of drug/toxin still in the gut; and
      • there is no antidote or alternative therapies like hemodialysis would be dangerous (Hoegberg, 2019)
    • Adverse effects of orogastric lavage include (but are not limited to) aspiration of gastric contents into the lungs, bleeding, electrolyte disturbances, esophageal injury, and vomiting (Hoegberg, 2019; Olson & Vohra, 2018b).

Antidotes

Commonly used antidotes and antidotes that are used to treat overdose of or exposure to a specific drug or toxin are discussed in this section.

Antivenom: Crotalinae Envenomation

A serious envenomation by a rattlesnake, water moccasin, and a copperhead can be treated with one of two antivenoms:

  1. Crotalidae polyvalent immune Fab (Fab antivenom), brand name CroFab® or
  2. Crotalidae immune F(ab')2 (equine), brand name Anavip.® (Pizon & Ruha, 2019)

Deciding when, for whom, and how to give antivenom for venomous snakebite is very complex; consult with a toxicologist or a local poison control center.

Deferoxamine

Deferoxamine binds to free iron, and it is the antidote for iron poisoning (Cantrell, 2018). Deferoxamine is used if the serum iron level is > 400-500 mcg/dL or when a patient has signs/symptoms of severe iron poisoning. Deferoxamine is given IV; the dose is weight-based (Cantrell, 2019).

Deferoxamine's adverse effects are pain at the injection site, hypotension, bacterial growth with Yersinia enterocolitica and subsequent sepsis, and ARDS after prolonged infusions (Cantrell, 2019).

Deferoxamine should be used cautiously if the patient is sensitive to the drug or if the patient has renal failure or anuria and is not receiving hemodialysis (Cantrell, 2018).

Digoxin-Specific Antibodies

Digoxin-specific antibodies, aka FAB fragments, bind free digoxin and are used to treat patients who have signs of serious digoxin poisoning, e.g., hyperkalemia, life-threatening arrhythmias, or an elevated digoxin level, or children who have ingested > 4 mg and adults who have ingested > 10 mg (Kearney, 2018c; Smith & Howland, 2019bst).

Digoxin-specific antibodies are given IV. Calculate the dose by using the steady-state digoxin level or by the amount of digoxin ingested (Kearney, 2018c).

If the amount ingested or the steady-state level is unknown, empiric dosing can be done (Kearney, 2018c).

Adverse effects include hypersensitivity reactions, exacerbation of heart failure, and hypokalemia. There are no contraindications; use with caution in patients who have a sensitivity to sheep (ovine) products or the food enzymes bromelain (pineapple) and papain (papaya) (Kearney, 2018c).

Flumazenil

Flumazenil is a competitive antagonist at benzodiazepine receptors in the CNS (Howland, 2019a; Ho, 2018), and IV flumazenil reverses the CNS depression and respiratory depression caused by benzodiazepines (Ho, 2018).

Flumazenil should only be used if:

  1. it is certain that the patient took only a benzodiazepine
  2. the patient is not benzodiazepine tolerant
  3. the patient has CNS depression, and
  4. the vital signs, the ECG, and other aspects of the neurologic examination are normal (Howland, 2019a)

Flumazenil has been associated with significant adverse effects (Howland, 2019a), and “the use of flumazenil in patients with coma of unknown etiology or with possible mixed drug overdose is not recommended” (Ho, 2018).

Fomepizole (4-methylpyrazole)

The toxic metabolites of ethylene glycol and methanol (primary ingredients of antifreeze and windshield washer fluid, respectively) are produced by alcohol dehydrogenase (Howland, 2019b; Kearney, 2018d). Fomepizole inhibits alcohol dehydrogenase activity, and it is the antidote for ethylene glycol and methanol poisoning (Howland, 2019b; Kearney, 2018d).

Fomepizole is given IV: A loading dose of 15 mg/kg, then 10 mg/kg, four doses, every 12 hours (Kearney, 2018d). Increase the subsequent doses to 15 mg/kg, and continue until the ethylene glycol level or the methanol level is < 20 mg/dL.

Fomepizole is contraindicated if the patient is sensitive to the drug or other pyrazole drugs (Kearney, 2018d).

Adverse effects include dizziness, headache, nausea, and injection site irritation (Kearney, 2018d).

Glucagon

Glucagon is used to treat beta-blocker and calcium channel blocker overdose. Glucagon bypasses beta receptors in the heart and increases heart rate, cardiac contractility, and cardiac conduction (Howland & Smith, 2019; Kearney, 2018e).

This is an off-label use of the drug, and the dose of glucagon used to treat beta-blocker or calcium channel blocker overdose is empirical.

Howland and Smith (2019) recommend an IV bolus of 3-5 mg, infused in over 3 to 10 minutes, then repeat the bolus dose as needed or give a continuous infusion of 2-5 mg/hour in 5% dextrose.

Glucagon is contraindicated in patients with a pheochromocytoma or a hypersensitivity to the drug (Kearney, 2018e).

Adverse effects of glucagon include transient hyperglycemia, hypokalemia, nausea, and vomiting (Kearney, 2018e).

Hydroxocobalamin

Hydroxocobalamin combines with cyanide, and it is the preferred antidote for acute cyanide poisoning and for cyanide poisoning that occurs during smoke inhalation (Howland, 2019c; Meier, 2018).

The dose is 5 mg, IV, given over 15 minutes (Meier, 2018), children should be given 70 mg/kg (Meier, 2018). A second 5 mg dose can be delivered in severe cases, infused in over 15 minutes to 2 hours as needed (Howland, 2019c; Meier, 2018).

Hydroxocobalamin is reconstituted with 200 mL of 0.9% sodium chloride. Lactated Ringers or dextrose 5% in water can be used if 0.9% sodium chloride is not available (Howland, 2019c).

Hydroxocobalamin is contraindicated in known sensitivity to the drug (Meier, 2018).

Adverse effects include erythema, headache, hypertension, injection site reaction, nausea, rash, and interference with the accuracy of laboratory tests (Howland, 2019c; Meier, 2018).

High-dose Insulin and Dextrose

High-dose insulin and dextrose therapy are used to treat beta-blocker and calcium channel blocker overdose (Brubacher, 2019; Jang, 2019). High-dose insulin and glucose increase cardiac contractility and provide an energy source for the myocardium (dextrose) and a way for the energy source to be utilized (insulin) (Jang, 2019).

An IV bolus of 1 unit/kg of regular insulin is given, and this is followed by a continuous infusion of 1 unit/kg/hour, titrated up as needed. Dextrose 50% boluses and a continuous infusion of 10% dextrose are used to maintain euglycemia (Birnbaum, 2018). Increased blood pressure and improved peripheral perfusion will occur in 15 to 40 minutes (Jang, 2019).

Adverse effects are hypoglycemia and hypokalemia (Jang, 2019).

Insulin levels may remain elevated for 24 hours after the insulin-dextrose infusion has been stopped, so glucose levels should be closely monitored during this time (Bartlett, 2016).

Lipid Emulsion

Lipid emulsion therapy, aka lipid rescue, is used to treat cardiotoxicity caused by local anesthetics (Benowitz, 2018; Kearney, 2018f), and occasionally it has been successful for treating poisoning caused by antidepressants, beta-blockers, calcium channel blockers, cocaine, and other drugs (Gosselin & Bania, 2019; Kearney, 2018f). In the latter situation, lipid emulsion can be used if the patient is severely ill and has not responded to maximal therapy with standard resuscitation and/or antidotal treatment (Gosselin & Bania, 2019). The mechanism of action of lipid therapy is not known with certainty (Kearney, 2018f)

There is no standard dose (Gosselin & Bania, 2019). The typical recommendation is 1.5 mL/kg of 20% solution given IV over 2 to 3 minutes, then give 0.25 mL/kg to 0.5 mL/kg (or 15 mL/kg/hour) IV over 30 to 60 minutes (Gosselin & Bania, 2019; Kearney, 2018f).

Contraindications include allergy to eggs or soy, abnormal metabolism, hyperlipidemia, and lipid nephrosis (Kearney, 2018f)

Adverse effects include pancreatitis or exacerbation of pancreatic disease and interference with the accuracy of laboratory tests (Kearney, 2018f).

Methylene Blue

Methylene blue is the antidote for methemoglobinemia (Howland, 2019d; Garza & Kearney, 2018). Methemoglobin is a form of oxidized hemoglobin that cannot bind with oxygen. Local anesthetics, nitrites, and other chemicals and drugs cause methemoglobin formation, and methemoglobinemia can cause cyanosis, hypoxia and, if the methemoglobin level is very high, coma, and seizures (Price, 2019).

The dose of methylene blue is 1-2 mg/kg of 1% solution (0.1-0.2 mL/kg) IV, given over 5 minutes. If needed, repeat the dose 30-60 minutes later (Garza & Kearney, 2018).

Contraindications include (but not) sensitivity to the drug, G6PD deficiency, and severe renal failure (Garza & Kearney, 2018).

High doses can cause hemolysis, and the concomitant use of methylene blue and serotonergic drugs can cause serotonin syndrome (Garza & Kearney, 2018).

N-acetylcysteine

N-acetylcysteine (NAC) is the antidote for acetaminophen poisoning (Kearney, 2018g), and it prevents liver damage caused by acetaminophen overdose.

The dose of NAC is (Kearney, 2018g):

  1. 150 mg/kg, IV, infused over 60 minutes, followed immediately by
  2. 50 mg/kg, IV, infused over 4 hours, followed immediately by
  3. 100 mg/kg, IV, infused in over 16 hours

If after the 3rd dose has finished there is clinical or laboratory evidence of liver damage or if there is a measurable acetaminophen level, continue infusing NAC at 100 mg/kg over 16 hours/62.5 mL hour of a 1-liter bag) until there is no detectable serum acetaminophen and there is no clinical or laboratory evidence of liver damage (Kearney, 2018g).

N-acetylcysteine can be given PO if needed and is contraindicated if the patient is hypersensitive to the drug (Kearney, 2018g).

N-acetylcysteine IV can cause an anaphylactoid reaction (Kearney, 2018g); this occurs in approximately 8.2% of all patients (Yarema et al., 2018).

Naloxone

Naloxone prevents opioids from binding to opioid receptors and displaces opioids from opioid receptors (Nelson & Howland, 2019; Go, 2018). Naloxone has been reported to reverse the toxic effects of clonidine overdose and overdose effects of other drugs (Go, 2018).

Naloxone can be given IV, IM, intra-nasally, continuous infusion, and other routes (Go, 2018).

Naloxone is intended to reverse respiratory depression and restore adequate ventilation, not to restore full consciousness. Use the lowest dose that will safely do this (Nelson & Olsen, 2019).

The dose is 0.4 mg to 2 mg IV (Go, 2018), but a lower starting dose like 0.04 mg is advisable if the patient is opioid-dependent (Nelson & Howland, 2019; Go, 2018).

Doses can be given at 2-to-3-minute intervals as needed (Go, 2018); if a total of 10 mg has been given without a response, likely, the patient is not opioid toxic (Nelson & Olsen, 2019).

If the patient requires multiple naloxone doses, a continuous naloxone infusion is helpful. Use two-thirds of the amount that restored ventilation and give this amount every hour (Nelson & Olsen, 2019; Go, 2018).

Naloxone is contraindicated in patients who have a hypersensitivity to the drug (Go, 2018).

Adverse effects include precipitation of opioid withdrawal, unmasking the toxic effects of co-ingestants, pulmonary edema, and ventricular fibrillation (Elkattaway et al., 2021; Go, 2018). Pulmonary edema and ventricular fibrillation are rare adverse effects (Elkattaway et al., 2021).

Precipitation of opioid withdrawal can cause a catecholamine surge. This catecholamine surge and hypercapnia from the opioid can cause serious signs and symptoms, and these can be avoided by ventilating the patient before giving naloxone (Nelson & Howland, 2019).

Physostigmine

Physostigmine is an acetylcholinesterase inhibitor, and it is used to diagnose and treat severe anticholinergic poisoning (Howland, 2019e; Kearney, 2018h).

The dose for adults is 1 – 2 mg, IV, given slowly over at least 5 minutes. The pediatric dose is 0.02 mg kg to a maximum of 0.5 mg (Howland, 2019e). Continuous IV infusions have also been used (Wang et al., 2021).
Before giving physostigmine, have atropine at the bedside and place the patient on continuous cardiac monitoring (Howland, 2019e). Do a 12-lead ECG and check for conduction defects and prolonged intervals. If needed, repeated doses of 0.5 mg at 10-to-15-minute intervals can be given (Kearney, 2018h).

Physostigmine is contraindicated if the patient has taken an overdose of a tricyclic antidepressant (TCA), and for patients who have cardiac conduction defects, bladder or intestinal obstruction, parkinsonian syndrome, peripheral vascular disease, reactive airway disease, or known hypersensitivity to the drug, and it should not be used concurrently with depolarizing neuromuscular blockers, e.g., succinylcholine (Howland, 2019e; Kearney, 2018h).

Adverse effects include (but are not limited to) asystole, bradycardia, seizures, heart blocks, bronchorrhea, bronchospasm, fasciculations, muscle weakness, diarrhea, seizures, and vomiting (Howland, 2019e; Kearney, 2018h).

Pralidoxime (2-PAM)

Pralidoxime (2-PAM) reverses acetylcholinesterase inhibition caused by organophosphate pesticide poisoning (Howland, 2019f; Geller, 2018). Pralidoxime and atropine are the recommended antidotes for organophosphate poisoning (Howland, 2019f).

The optimal dose of 2-PAM and the optimum duration of treatment with 2-Pam are not known. Pralidoxime should be given as soon as possible (Howland, 2019f; Geller, 2018). If not, the acetylcholinesterase inhibition is irreversible (Geller, 2018).

Give a loading dose of 1 to 2 grams, diluted in 100 mL of 0.9% sodium chloride, infused in over 15 to 30 minutes. Follow this by a continuous infusion of 1% 2-PAM in 0.9% sodium chloride at 400 to 600 mg/hour; doses as high as 8 to 10 mg/kg/hour can be used (Geller, 2018).

The pediatric dose is a loading dose of 30 mg/kg (maximum dose of 2 grams), 1% solution mixed with 0.9% sodium chloride, infused in over 15 to 30 minutes. The continuous infusion rate is 10 to 20 mg/kg/hour (Geller, 2018).

Pralidoxime is contraindicated in patients who have a hypersensitivity to the drug, and it should be used cautiously in patients who have myasthenia gravis or renal impairment (Geller, 2018).

Adverse effects include (but are not limited to) blurred vision, dizziness, and diastolic blood pressure elevation (Howland, 2019f; Geller, 2018). Hypertension, laryngospasm, muscle rigidity, tachycardia, and transient neuromuscular blockade can occur with rapid IV infusion (Geller, 2018).

Sodium Bicarbonate

For poisoned patients, sodium bicarbonate IV is most often used to treat salicylate (aspirin) overdose and TCA overdose (Howland, 2019g; Kearney, 2018i).

Sodium bicarbonate therapy alkalinizes the serum and the urine, decreasing the movement of aspirin in the CNS and increasing renal excretion of aspirin. Sodium bicarbonate therapy is used for symptomatic patients with an aspirin level above the therapeutic range (Lugassy, 2019; Wax & Haynes, 2019).

Give the patient a bolus of 1-2 mEq/kg and then start a continuous infusion with three ampules (132 mEq) in 1 liter of 5% dextrose in water. Titrate the infusion to achieve and maintain a urine pH of 7.5 to 8.0 (Lugassy, 2019).

Sodium bicarbonate is used to treat arrhythmias and hypotension caused by TCA overdose (Sahalnick, 2020), and it should be given before these occur if the QRS is prolonged (Howland, 2019g, Kearney, 2018i).

The dose is 1-2 mEq/kg of 8.4% sodium bicarbonate, IV push (Sahalnick, 2020; Kearney, 2018i); this can be repeated several times (Kearney, 2018i).

If the QRS duration decreases or if arrhythmias and/or hypotension resolve, a continuous infusion of sodium bicarbonate should be started (Sahalnick, 2020). There is no standard dosing. Typical recommendations are 150 mL of 8.4% sodium bicarbonate in 1 L of 5% dextrose in water, infused at 250 mL/hour or twice the maintenance fluid rate for the patient (Howland, 2019g; Sahalnick, 2020).

The infusion should be adjusted to maintain a serum pH of 7.50 to 7.55 (Sahalnick, 2020); increasing the serum pH and maintaining alkalosis is thought to decrease the cardiotoxic effects of TCA overdose.

Case Study

A 21-year-old female is brought to an ER by ambulance; the patient had called 911 and said that she had taken 30 acetaminophen tablets, 500 mg.

The patient is awake, alert, and oriented, and her vital signs are within normal limits. The physical examination is unremarkable; there are no abnormal findings.

According to the patient’s parents, the ingestion happened five hours ago, and they are sure that the patient did not ingest anything else. They are not sure of the amount the patient consumed.

The patient has a PMH of depression, and she has been prescribed fluoxetine, 20 mg QD. The parents brought the fluoxetine to the ER, and there are no missing tablets.

The use of AC is not indicated; the ingestion happened > 1 hour ago. This is not a sustained-release or extended-release drug, and acetaminophen does not slow gut peristalsis or cause delayed absorption. There are no indications for the use of orogastric lavage, i.e., the patient is clinically stable, and death from acetaminophen poisoning is unusual, and it is delayed.

There is no need for empiric administration of dextrose, oxygen, naloxone, or thiamine.

The toxic dose of acetaminophen is > 12 grams; the patient ingested 15 grams. Acetaminophen poisoning causes delayed liver damage and occasionally kidney damage, and the need for treatment is determined on the acetaminophen level, clinical evidence of liver damage, and the amount ingested (Olson, 2018). The laboratory test results are:

  • Acetaminophen level: 199 mcg/mL
  • Salicylate level: < 0.1 mg/dL
  • AST: 11 IU/L
  • ALT: 14 IU/L
  • BUN: 12 mg/dL
  • Creatinine: 0.5 mg/dL
  • INR: 0.9

There is no clinical or laboratory evidence of liver or kidney damage. Still, the patient (reportedly) took a toxic dose of acetaminophen, and the acetaminophen level of 182, done six hours after the ingestion, indicates the need for antidotal therapy with NAC.

Select one of the following methods to complete this course.

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References

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  • Nelson, L.S. & Howland. M.A. (2019). Chapter A4: Opioid Antagonists. In L.S. Nelson, M. A. Howland, N.A. Lewin, S. W. Smith, L. R. Goldfrank & R. S. Hoffman (Eds). Goldfrank's Toxicologic Emergencies, 11th ed. New York, NY: McGraw-Hill Education. Online edition. Accessed October 5, 2021. Visit Source.
  • Nelson, L.S. & Olsen, D. (2019). Chapter 36: Opioids. In L.S. Nelson, M. A. Howland, N.A. Lewin, S. W. Smith, L. R. Goldfrank & R. S. Hoffman (Eds). Goldfrank's Toxicologic Emergencies, 11th ed. New York, NY: McGraw-Hill Education. Online edition. Accessed October 5, 2021. Visit Source.
  • Olson, K.R. (2018). Acetaminophen. In K.R. Olson, I.B. Anderson, N.L. Benowitz, P.D. Blanc, R.F. Clark, T.E. Kearney, S.Y. Kim-Katz & A.H.B. Wu (Eds). Poisoning & Drug Overdose, 7th ed. New York, NY: McGraw-Hill Education. 73-76.
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  • Price, N.L. (2019). Chapter 124: Methemoglobin Inducers. In L.S. Nelson, M. A. Howland, N.A. Lewin, S. W. Smith, L. R. Goldfrank & R. S. Hoffman (Eds). Goldfrank's Toxicologic Emergencies, 11th ed. New York, NY: McGraw-Hill Education. Online edition. Accessed October 4, 2021. Visit Source.
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  • Schwartz, D.T. (2019). Chapter 8: Principles of Diagnostic Imaging. In L.S. Nelson, M. A. Howland, N.A. Lewin, S. W. Smith, L. R. Goldfrank & R. S. Hoffman (Eds). Goldfrank's Toxicologic Emergencies, 11th ed. New York, NY: McGraw-Hill Education. Online edition. Accessed September 30, 2021. Visit Source.
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