#34444: Caring for the Poisoned Patient

Nursing care of the poisoned patient should follow this process:

These steps are discussed individually but they can be, and many times are, essentially done at the same time. Also, aside from evaluating the ABCs, which is always the first step, the steps do not need to be performed in a specific order; the circumstances of each case will dictate what needs to be done and when. Simplified, the process is: assess and stabilize the ABCs, provide symptomatic and supportive care, administer an antidote if there is a need, and increase the elimination of or remove the poison.

Begin the care of a poisoned patient by assessing the ABCs. In some cases of poisoning or overdose, there will not be significant and/or characteristic changes in the ABCs or the ABCs may be normal. However, there are drugs and toxins that can cause distinctive and serious derangements in the ABCs (Table 1) [2,3].

These changes in pulse, blood pressure, body temperature, and breathing can help confirm an ingestion or help identify what the patient has taken if the ingestion was not witnessed or if the patient is unconscious or incoherent. Many drugs and toxins can cause changes in the ABCs, but it is vital to remember no single change in one of the ABCs can be considered diagnostic. A 12-lead electrocardiogram (ECG) should also be obtained while the ABCs are being assessed. ECG changes and poisoning will be discussed in detail later in this course.

In most poisonings, the British Thoracic Society recommends aiming at an oxygen saturation of 94% to 98%, unless the patient is at risk of hypercapnic respiratory failure.

(https://thorax.bmj.com/content/72/Suppl_1/ii1 Last Accessed: March 15, 2024)

Level of Evidence: D (Randomized controlled trials)

If the poisoned patient has a significant derangement in her or his ABCs, the first step is to provide supportive care. In addition, treatment measures that are considered standard for any patient should be instituted. Secure the patient's airway if it is compromised or may become so, and administer supplemental oxygen if the patient is hypoxic or ventilation is inadequate. If the patient is hypotensive and her or his lungs are clear, an IV infusion of 0.9% sodium chloride or lactated Ringer's solution should be used. Hyperthermia or hypothermia can be treated with cooling or warming measures.

Some poisoned patients will require specific treatments or an antidote. For example, the patient who has taken an overdose of metoprolol and is hypotensive should be given an IV infusion of glucagon. The patient who has taken an overdose of heroin and has respiratory depression and inadequate ventilation requires naloxone along with oxygen. However, with very few exceptions, standard, supportive care is always the appropriate first choice for treatment.

Drug levels or levels of toxins can be measured in blood or urine, and these levels can be used to predict the possibility of toxic effects of an overdose, to assess the level of damage done by an overdose, and to determine the need for specific therapies. Drug/toxin levels should be obtained if a patient has ingested or been exposed to [13]:

The levels of these drugs and toxins are (usually) quickly available and can be used to assess damage, predict toxicity, or help clinicians determine the need for treatment. However, in many cases, drug levels or toxin levels are not useful because they are not reliable as indicators or predictors of toxicity and/or the levels cannot be quickly processed and reported, so they are not useful for the management of an acutely ill patient. In addition, there is a risk of false positive and/or false negative results for certain drugs; this will be discussed in more detail later in this course.

If there is no reliable information about what the poisoned patient ingested, the following laboratory and screening tests can be useful diagnostic tools [2,3,4]:

The urine drug screen is often used as part of a diagnostic workup in cases of poisoning, and most urine drug screens measure levels of several common drugs of abuse, such as amphetamine, cocaine, cannabis, and opioids. Using and interpreting the urine drug screen is complicated. Each screen has different sensitivity, specificity, time limit for detection, and amount of drug metabolite that can be detected, and they confirm prior use but not necessarily current intoxication. They may not detect other commonly abused drugs, including oxycodone and methadone, and false-positive and false-negative results are common [5,13,14]. For example, many of the commonly used urine drug screens will not detect alprazolam, clonazepam, or lorazepam, even if there has been a recent ingestion of one of these drugs, and antihistamines can cause a false positive for TCAs [14]. Perhaps most importantly, there is little convincing evidence that urine drug screens used during the acute care phase of a poisoned patient have any significant impact on management or outcomes [15,16].

The laboratory tests needed to assess and evaluate a poisoned patient will depend on what the patient has ingested or been exposed to and the patient's clinical condition. If the drug or toxin responsible for the poisoning is unknown, one or several of the following tests may help determine what the exposure might have been. A single laboratory test is rarely sufficient to identify an unknown drug or toxin.

Please note that the drugs and toxins associated with the laboratory abnormalities discussed in the following section are not the only ones that may cause changes. Rather, they are drugs and toxins that are commonly encountered and cause significant laboratory changes that would be a prominent part of the clinical presentation of a patient who has been poisoned.

An arterial blood gas test can be used to detect and diagnose acid-base disturbances and hypoxemia. Acetaminophen (in severe cases), aspirin, carbon monoxide, cyanide, ethanol (in alcoholic ketoacidosis), ethylene glycol, ibuprofen (in severe cases), iron, isoniazid, metformin, and methanol can all cause acidosis [2,3]. Barbiturates, carbon monoxide, cyanide, opioids, and simple asphyxiants (e.g., methane) can cause hypoxemia [2,3].

Acetaminophen is one of the most commonly ingested drugs in cases of self-poisoning. The early signs and symptoms of acetaminophen poisoning are nonspecific and often mild in intensity. There may not be any signs or symptoms early in the course (or symptoms may be nonspecific), and the longer the time between toxic ingestion of acetaminophen and antidotal therapy, the less effective the treatment will be. An acetaminophen level should always be obtained in cases of self-poisoning.

BUN and serum creatinine levels are used to evaluate renal function and detect renal damage. Acetaminophen poisoning can on occasion cause elevations in BUN and creatinine, as can a massive ingestion of ibuprofen. Ethylene glycol and methanol poisoning produce metabolites that are directly toxic to the kidney.

A complete blood count (CBC) can detect hemolysis and other blood abnormalities. Benzocaine, dapsone, naphthalene mothballs, and nitrites can cause hemolysis. Benzocaine, dapsone, lidocaine, nitrites, phenazopyridine, and prilocaine can cause methemoglobinemia [2]. Anticoagulant rodenticides (e.g., d-CON) and warfarin can cause abnormal coagulation studies [2].

Measurement of blood glucose levels should be considered. Hypoglycemia can be caused by aspirin, sulfonylurea, and ethanol poisoning. Hyperglycemia can be caused by iron poisoning, beta blockers, and calcium channel blockers [3].

Poisoning from many drugs and toxins can result in specific electrolyte imbalances. For example, an elevated anion gap can be caused by acetaminophen (in very serious cases), aspirin, carbon monoxide, cyanide, ethanol (in alcoholic ketoacidosis), ethylene glycol, iron, isoniazid, metformin, and methanol. Changes in specific electrolytes associated with poisoning are too numerous to discuss. As examples, MDMA (Ecstasy) can cause hyponatremia, digoxin and hydrofluoric acid can cause hyperkalemia, and hydrofluoric acid poisoning can cause hypocalcemia and hypomagnesemia [2].

Ethanol (in alcoholic ketoacidosis), ethylene glycol, isopropyl alcohol, and methanol can increase serum osmolality and cause an elevated osmolar gap. Acetaminophen, Amanita phalloides mushroom, and valproic acid poisoning can cause liver damage and elevation of hepatic transaminases. Urinalysis can be useful in assessing imbalances. In cases of isopropyl alcohol poisoning, ketonuria may be seen. One of the metabolites of ethylene glycol, oxalic acid, forms a complex with calcium, and the calcium oxalate crystals may be seen in the urine of patients who have ingested this toxin.

Both commonly prescribed and illicitly used drugs can cause ECG abnormalities [5,17]. Antiarrhythmic drugs, digoxin, diphenhydramine, phenothiazines, propoxyphene, and TCAs can cause prolonged QRS. Amiodarone, chlorpromazine, droperidol, erythromycin, haloperidol, methadone, sotalol, and thioridazine are drugs that can cause a prolonged QT and possibly torsades de pointes [18,19]. In addition, amphetamine, anticholinergic drugs, beta blockers, calcium channel blockers, cocaine, digoxin, and phenothiazines are associated with other conduction defects and arrhythmias.

There are two common situations for which imaging studies should be used in the assessment of a poisoned patient: visualizing a potentially dangerous foreign object (e.g., a button battery, lead-containing paint chips), or visualizing intact illicit drugs or medications in the gastrointestinal tract.

Button batteries, also known as disk batteries, are used in calculators, hearing aids, watches, and other electronic devices. These objects are small, easily swallowed, and clearly visible on a plain x-ray. A disc battery that is lodged in the esophagus and is not promptly removed can cause significant tissue damage and, rarely, death, and an x-ray should be done as soon as possible in these cases [20]. The dangers of pediatric exposure to lead are well known, and unfortunately, ingestion of lead-containing paint chips is still a relatively common occurrence. Lead paint chips are radiopaque, and their presence in the gut confirms an ingestion and helps guide management.

Imaging studies can also detect packets of illicit drugs that have been deliberately swallowed or inserted into body cavities (commonly called packing or stuffing). Intact drug packets are easily seen with a plain x-ray, but the presence of small and loosely secured drug packets that were swallowed may not be clearly visible [21,22,23,24]. There is some evidence that low-dose computed tomography (CT) is the best technique to reliably detect swallowed drug packets [22].

Some prescription and over-the counter medications are radiopaque and may appear on x-ray, including chloral hydrate, iron, phenothiazines, and enteric-coated and sustained-release preparations [21]. However, the reliability of x-ray to detect these agents in the gut is not established.

Imaging studies can also be useful in assessing for the presence of an ingestion of a simple hydrocarbon (e.g., gasoline, kerosene). Simple hydrocarbons are generally not dangerous, unless they are aspirated into the lungs. If aspiration occurs, pneumonitis is possible.

Activated charcoal is produced from carbonaceous substances such as peat or wood that have been pulverized and specially treated. This charcoal powder is added to a liquid (most often water and sorbitol) and delivered orally. Activated charcoal adsorbs (not absorbs) drugs or toxins in the gut, and it can also interrupt their enterohepatic and enteroenteric recirculation [25]. Most drugs and toxins are well adsorbed by activated charcoal, but acids, alkalis, alcohols, iron, and lithium are not. The adsorption bond is very strong. The charcoal-drug complex is excreted in the stool, absorbed by macrophages, or dissociated slowly enough so the drug does not cause harm. Although it is clear that activated charcoal can adsorb toxins and drugs, it is unknown if this action improves clinical outcomes [25,26,28,29,30]. However, the capacity of activated charcoal to significantly decrease drug absorption, the simplicity of the technique, and its relative lack of adverse effects have resulted in activated charcoal still being recommended for the treatment of poisoned patients.

Activated charcoal should be given if the drug/toxin is susceptible, if a toxic dose of a drug/toxin was ingested, and if the ingestion occurred within one hour of arrival [31]. This timeframe should not be considered inviolable, and if there are no contraindications and a substantial amount of drug/toxin may still be in the gut, late administration of activated charcoal may be done.

Contraindications to the use of activated charcoal include:

The most common adverse effect of activated charcoal is vomiting. Vomiting is a risk factor for aspiration, and patients who vomit after being given activated charcoal may develop adult respiratory distress syndrome (ARDS) and pneumonitis [25,32]. Fortunately, serious respiratory complications caused by activated charcoal are uncommon, and aspiration of gastric contents and charcoal may be no worse than aspiration of gastric contents alone [25,26,33]. Other possible adverse effects of activated charcoal are abdominal pain, constipation, diarrhea, and nausea [26].

The prescribed dose of activated charcoal is usually a 10:1 ratio of activated charcoal to drug, but other dosing recommendations have been published (e.g., 25–100 g of activated charcoal for an adult, 0.5–2.0 g/kg for a child) and the optimal dose is not known [25,26,30]. Dosing activated charcoal will always be an uncertain process, given that it is unusual to know exactly how much of a drug was ingested, how much drug is still in the gut, and how the adsorptive ability of activated charcoal will be affected by food and co-ingestants. In general, 50–100 g of activated charcoal is likely more than enough for most poisoned patients, and the risk of vomiting may increase as the amount of activated charcoal is increased [25].

Activated charcoal has a gritty texture and an unappetizing appearance, so it is not unusual for patients to refuse to drink it. The powder can be mixed with anything tasteful that masks its appearance (e.g., chocolate syrup, ice cream, juice). This will decrease its adsorptive strength, but this effect is not considered clinically important.

In the past, cathartics were used to increase gastrointestinal transit time and decrease the absorption of ingested drugs. The osmotic cathartics magnesium citrate and sorbitol were once commonly used to treat poisoned patients; however, cathartics, either alone or used with activated charcoal, are no longer generally recommended as a treatment for the poisoned patient [25,34]. Some brands of activated charcoal are pre-mixed with a sorbitol cathartic, and a one-time dose can be given safely. Excessive use of cathartics can cause abdominal cramping, electrolyte imbalances, and fluid loss.

Gastric lavage involves the insertion of an orogastric tube into the stomach to manually suction out the contents. It is the most intuitively logical gastrointestinal decontamination technique, but it is considered a therapy with very limited (if any) benefits [25,26,27]. There is no conclusive evidence that it improves clinical outcomes, and its routine use is not recommended [27]. The amount of drug that is removed varies considerably, and gastric lavage may push drugs that are in the stomach past the pylorus and into the small intestine. Activated charcoal is less invasive and probably more effective.

Gastric lavage should be done if:

Gastric lavage is contraindicated if the criteria for use are not met; spontaneous emesis has occurred; it has been more than one hour since the ingestion occurred; the patient ingested an acid or alkali; the patient has a bleeding disorder; or if the patient is a body packer or stuffer. Possible adverse effects of gastric lavage include (but are not limited to) aspiration, bleeding, hypoxia, and injury to the airway, esophagus, or stomach.

If done, gastric lavage should be administered with the patient in the left lateral decubitus position with his or her head and neck supported. This position may help prevent ingested drug from being pushed through the pylorus. A 36–40F orogastric tube is used for adults; for children, a 22–28F tube is recommended.

After the tube is confirmed to be in the stomach, suction is initiated. After this, activated charcoal can be instilled if the patient has ingested a large amount of drug. Then, 250 mL of saline lavage solution is instilled. (For pediatric patients, use 10–15 mL/kg, to a maximum of 250 mL.) The instilled solution is then aspirated and the process repeated until several liters have been given (0.5–1.0 liter for children) or until the aspirate is clear. If indicated, one may finish with a dose of activated charcoal.

Syrup of ipecac is an over-the-counter preparation that contains several alkaloids that act centrally and locally to induce vomiting. There is no doubt that syrup of ipecac consistently induces emesis; however, the amount of drug removed by ipecac-induced emesis is variable and unpredictable. There is no evidence of its clinical benefit for poisoned patients, and its use can interfere with other, more effective gastrointestinal decontamination techniques. Syrup of ipecac is associated with potential adverse effects (e.g., drowsiness, occasionally prolonged vomiting) that are hazardous for the patient. Situations in which syrup of ipecac may be an appropriate treatment are rare, and this approach is not recommended by the American Academy of Toxicology, the European Association of Poisons Centres and Clinical Toxicologists, or the American Academy of Pediatrics [35,36,37].

Whole bowel irrigation is performed by instilling a non-absorbable, osmotically balanced polyethylene glycol (PEG) solution into the patient's gut orally or through a nasogastric tube. For infants and children 9 months to 5 years of age, the goal rate is 500 mL per hour; for children 6 to 12 years of age, the rate is 1,000 mL per hour. For adults and children 13 years of age and older, the goal rate is 1,500–2,000 mL per hour. The flow and volume of the PEG solution acts as a continuous irrigation and mechanically removes ingested drugs/toxins.

As with all gastrointestinal decontamination techniques, there is a logical basis for the use of whole bowel irrigation, but there has been little research on it and no conclusive evidence for its effectiveness [25,26,38]. Despite these limitations, whole bowel irrigation may be prescribed.

Indications for whole bowel irrigation include ingestion of drug packets, a foreign body, or a toxic amount of an enteric-coated medication, an extended-release medication, or iron, lithium, or potassium. Contraindications are bowel obstruction, ileus, or any condition that affects normal bowel functioning; a clinically significant gastrointestinal hemorrhage; continued vomiting; inability of the patient to protect his/her airway; and hemodynamic instability.

Possible adverse effects of whole bowel irrigation are those that would be expected from instillation of large volumes of liquid into the gut: bloating, cramping, diarrhea, nausea, and vomiting. Whole bowel irrigation is unpleasant for the patient, and it is a time-consuming procedure for the staff.

Bites from pit vipers, such as rattlesnakes, can cause significant tissue damage and serious systemic effects, with the exception of copperhead snake envenomations, which are generally mild and do not typically require antidotal treatment. Envenomation from poisonous spiders can on occasion cause serious systemic effects, but these situations are relatively rare. Antivenom is seldom needed for spider bites, and this situation will not be discussed in this course.

Crotalidae polyvalent immune FAB (CroFab) antivenom has replaced crotalinae polyvalent antivenom as the antidote for pit viper envenomation [39]. The older antivenom was derived from horse serum and the risk of anaphylactic reaction was much higher than the risk associated with CroFab, which is derived from sheep serum.

Antivenom binds to the snake venom and inactivates it. Prompt use of antivenom can prevent tissue damage and systemic effects when supportive care alone cannot. Antivenom should be given to patients who have significant signs and symptoms of envenomation by a pit viper, including pain, swelling, coagulopathies, hypotension, and neurologic signs/symptoms (e.g., fasciculations, paresthesias). CroFab is contraindicated in persons with sensitivity to sheep or sheep products or to papayas or papain. Anaphylaxis is a potential adverse effect, and drugs and equipment to treat anaphylaxis should be immediately available. Crofab is administered via IV, and the initial dose is usually 4 to 6 vials (range: 4 to 12 vials) [40]. Each vial should be reconstituted with 18 mL of 0.9% sodium chloride. Gently rotate/swirl the vials; do not shake. The reconstituted CroFab should be instilled into an IV bag of 0.9% sodium chloride to a total volume of 250 mL. The infusion should be started at 20–50 mL per hour for the first 10 minutes [40]. If the patient has no signs or symptoms of anaphylaxis, increase the rate so the full dose is delivered within one hour. One hour after the infusion is complete, assess the patient for a clinical response. If there is no response or the response is unsatisfactory, give four to six vials and repeat as needed. When a good response has been achieved, give two vials every six hours for three doses [40].

Atropine is a competitive antagonist of acetylcholine at parasympathetic and sympathetic synapses and at the neuromuscular junction. Atropine is used as an antidotal therapy to treat cases of organophosphate or carbamate insecticide poisoning [41]. Exposure to these chemicals can cause potentially dangerous bronchorrhea and bronchoconstriction; atropine can be very effective in reversing these effects.

Atropine also increases heart rate and cardiac conduction, and as such, it can be used to treat symptomatic, drug-induced bradycardia caused by beta blockers, calcium channel blockers, clonidine, and digoxin.

Atropine is indicated for patients with symptomatic organophosphate or carbamate insecticide poisoning or drug-induced bradycardia [41,42]. However, it is typically considered a second-line therapy for drug-induced bradycardia, and it is unlikely to have a lasting effect [43,44]. Atropine is contraindicated for patients who cannot tolerate tachycardia or with angle-closure glaucoma, bowel obstruction, myasthenia gravis, or urinary tract obstruction.

Potential adverse effects of atropine include blurred vision, dry mouth, palpitations, tachycardia, and urinary retention. Agitation and delirium can occur if large doses are used.

For organophosphate/carbamate poisoning, the initial adult dose is 2–5 mg IV; the initial pediatric dose is 0.05 mg/kg IV [42]. Subsequent doses should be based on the patient's clinical and pulmonary status. In severe cases, a continuous infusion may be administered for several days, and a seriously poisoned patient may require hundreds of milligrams of atropine [42].

As treatment for symptomatic drug-induced bradycardia, the dose of atropine is 0.5 mg IV, given rapidly. This dose is repeated every three to five minutes up to 3 mg. Doses less than 0.5 mg and slow administration may cause a paradoxical bradycardia.

Calcium channel blockers (e.g., amlodipine, diltiazem, verapamil) inhibit the movement of calcium through voltage-gated calcium channels, while high doses of calcium increase calcium flow across cell membranes and increase the release of calcium from intracellular stores. Patients who have been poisoned with a calcium channel blocker are unlikely to respond to atropine and the commonly used vasopressors. Intravenous boluses of calcium chloride or calcium gluconate are first-line treatments for calcium channel blocker overdose, but this is often ineffective or the improvements in cardiovascular status are short-lived [44,45,46]. Nonetheless, calcium salts are often given in these clinical situations.

Calcium replacement is also indicated for symptomatic cases of beta-blocker poisoning and symptomatic cases of hydrofluoric acid burns and poisoning [47]. Hydrofluoric acid is used in the home as a rust remover and aluminum cleaner, and it has many industrial uses as well. Hydrofluoric acid poisoning causes pain, burns, and possibly profound hypocalcemia.

The dose for treating a beta blocker or calcium channel blocker overdose is 1 gram of calcium chloride or calcium gluconate given IV over 10 minutes. The dose can be repeated every 20 minutes up to four doses. If a continuous infusion is given, the dose is 0.02–0.04 g/kg per hour. It is important to closely monitor serum calcium levels and heart rate and rhythm during calcium therapy. If calcium chloride is used, infusing through a central venous catheter may minimize irritating side effects.

Depending on the route and the severity of a hydrofluoric acid exposure, calcium may be given topically, as an intradermal injection, intra-arterially, IV, as an ocular wash, or as a nebulized solution. Dosing recommendations for these applications are complex and beyond the scope of this course.

Calcium therapy is contraindicated in cases of known or suspected digoxin toxicity. Potential adverse effects include local tissue irritation, hypercalcemia, bradycardia, dysrhythmias, hypotension, syncope, and neuromuscular weakness.

Iron toxicity can cause CNS depression, hypotension, metabolic acidosis, and shock. Deferoxamine is the antidote for significant iron poisoning; it binds to the ferric form of iron, forming a water-soluble compound that is excreted in the urine, which will often cause the urine to turn pink or light red.

Deferoxamine is indicated if the serum iron level is greater than 500 mcg/L or if a patient with iron poisoning has severe symptoms (e.g., CNS depression or coma, hypotension, prolonged diarrhea and/or vomiting, shock) or anion gap metabolic acidosis. It may also be used for patients with many undissolved iron tablets in the gut [48].

Deferoxamine should be used cautiously in patients who are anuric and/or who have severe renal disease. The most significant possible adverse effects of deferoxamine are ARDS and hypotension. ARDS has been reported after deferoxamine infusions of 32 to 72 hours [48]. Acute lung injury and Yersinia enterocolitica sepsis are possible complications if therapy continues for more than 24 hours.

Deferoxamine is given as an IV infusion, and the standard dose is 15 mg/kg per hour, but higher doses can be used, if needed, up to a maximum 6 grams per day. Most patients require the drug for about 24 hours, but there are no agreed-upon endpoint criteria. If a patient requires deferoxamine therapy for more than 24 hours, use the lowest dose possible.

The myocardium normally uses free fatty acids for energy, but when the myocardium is stressed, as with calcium channel blocker poisoning, it switches to glucose metabolism for fuel. However, calcium channel blocker toxicity also impairs insulin release and glucose uptake. The resultant lack of energy compounds the toxic effects of calcium channel blockers on the myocardium. Dextrose and insulin give the poisoned myocardium a source of energy and the means to use it. In addition, insulin has a positive inotropic effect [43,44,49]. Although dextrose and insulin are primarily used for calcium channel blocker poisoning, there is also evidence that this therapy may be helpful for treating beta blocker poisoning. Both uses are off-label, and guidelines recommend that dextrose be used only as an adjuvant component of high-dose insulin therapy [50,51]. Dextrose-insulin therapy appears to be effective for correcting hypotension and less effective for correcting bradycardia and conduction defects.

There is no standard, universal regimen for high-dose insulin/dextrose therapy, but the goals are the same: provide the heart with an energy source and the means to use it while maintaining euglycemia. The following dosing regimen should be considered a guideline [52]:

There are no contraindications for high-dose insulin/glucose use. Common adverse effects include hypoglycemia and hypokalemia, but these can be managed and have not been reported to cause serious harm. Hypophosphatemia and hypomagnesemia are possible, and vein irritation from the dextrose infusion is common [49,52,53].

Digoxin-specific antibodies, also called Fab fragments, irreversibly bind to free digoxin to resolve symptoms of digoxin toxicity. The Fab-digoxin complex is then renally excreted. As the Fab-drug complex is excreted, an imbalance in the concentrations of digoxin between the tissues and the serum develops. As a result, more digoxin travels from the tissues into the serum and is bound to the Fab fragments and excreted. The effectiveness of digoxin-specific antibodies has been reported to be 50% to 90% [54].

Fab fragments are recommended to treat patients with digoxin poisoning who have life-threatening arrhythmias or cardiac arrest, acute ingestions causing serum digoxin levels ≥10 ng/mL at six hours or more after ingestion (or chronic ingestions causing steady-state serum digoxin concentrations exceeding 6 ng/mL in adults or 4 ng/mL in children), serum potassium levels ≥5.0 mEq/L, or have ingested ≥10 mg [55]. It is important to note that abnormally high serum potassium is a better predictor of potentially serious harm from digoxin poisoning than the serum digoxin level or ECG changes.

It should be noted that there is no universal agreement on these indications, and Fab fragment guidelines differ slightly. There are no contraindications to the use of Fab fragments, but if a patient is allergic to sheep or papaya/papain, the risks versus benefits should be carefully considered. Patients with atrial fibrillation or heart failure may experience an exacerbation. Hypokalemia is possible [51].

Fab fragments are dosed according to the number of vials. There are two methods for dosing: by the serum digoxin level or by the amount of digoxin ingested (Table 2). If the amount ingested is not known and a serum digoxin level cannot be quickly obtained, 10 to 20 vials can be given empirically [2,51]. Fab fragments can be given as an IV bolus, but they are usually administered IV over 30 minutes. The response to Fab fragments should be seen within 30 minutes.

Cyanide disrupts mitochondrial production of adenosine triphosphate (ATP) and causes body-wide cellular asphyxia, often causing cardiac arrest and death. Hydroxocobalamin is the preferred antidote for cyanide poisoning [56,57]. Hydroxocobalamin competitively binds to cyanide and forms cyanocobalamin (vitamin B12), which is then excreted in the urine.

The dose is 5 grams IV diluted with 0.9% sodium chloride and infused over 15 minutes. A second 5-gram dose can be administered, if needed, as an infusion over 15 minutes to 2 hours. More severe symptoms call for a faster infusion rate. Pediatric dosing is not in the prescribing information, but some recommend 70 mg/kg (maximum: 5 grams). Renal function should be monitored for seven days after administration of hydroxocobalamin [51].

There are no contraindications to its use. Adverse effects include acute renal failure, erythema, headache, increased blood pressure, injection reactions, and transient chromaturia.

Flumazenil is a benzodiazepine antagonist that prevents benzodiazepines from binding to receptors. It will reverse the CNS and respiratory depression caused by these drugs, avoiding the need for endotracheal intubation. The indications for flumazenil are accidental, symptomatic pediatric ingestion of a benzodiazepine; oversedation caused by therapeutic use; and reversal of paradoxical reactions to a benzodiazepine [58]. Flumazenil should not be routinely used for known or suspected benzodiazepine overdoses, as these overdoses are rarely fatal and can be successfully treated with symptomatic/supportive care. In addition, flumazenil should not be used as a routine treatment for an overdose patient when the ingested drug has not been identified.

Flumazenil is given in gradually increasing doses until the patient responds, starting with a dose of 0.2 mg IV [24]. If there is no response, increase to 0.3 mg; in the presence of continued non-response, doses of 0.5 mg may be given every 30 seconds up to a maximum of 3 mg.

Flumazenil is contraindicated if a patient has a seizure disorder, if he/she has ingested a medication that is likely to cause seizures, or if the patient is habituated to benzodiazepines [51]. In the latter situation, administering flumazenil can precipitate benzodiazepine withdrawal. Potential adverse effects include anxiety, headache, nausea, and vomiting.

Ethylene glycol and methanol are commonly called the toxic alcohols. These alcohols are metabolized by alcohol dehydrogenase to acids and other compounds that can cause profound acidosis, coma, permanent ocular damage, and renal failure. Fomepizole blocks the metabolism of ethylene glycol and methanol by inhibiting the activity of alcohol dehydrogenase [59]. Fomepizole is much easier and less risky to use than hemodialysis or the traditional antidote for toxic alcohol poisoning, ethanol. Thus, it is indicated in cases of confirmed or suspected ethylene glycol or methanol poisoning [51].

Indications for the use of fomepizole include serum ethylene glycol level >20 mg/dL; a documented history of ingestion of a toxic amount of ethylene glycol or methanol; or a known or suspected ingestion of ethylene glycol or methanol and a serum pH <7.3, an osmolal gap >10 mOsm/L, a serum bicarbonate level <20 mEq/L, or oxalate crystals in the urine.

It is administered in a loading dose of 15 mg/kg (maximum: 1 g). The drug is diluted in 100 mL of normal saline or 5% dextrose and infused slowly over 30 minutes [24]. The loading dose is followed by four doses of 10 mg/kg, each dose separated by 12 hours. After the fourth dose, the patient should receive doses of 15 mg/kg every 12 hours until the ethylene glycol or methanol level is <20 mg/dL [51].

There are no contraindications to the use of fomepizole. Adverse effects are usually mild and include dizziness, headache, nausea, and irritation at the infusion site.

Beta blocker poisoning causes bradycardia, cardiac conduction delays, and hypotension. Treatment with sympathomimetics and/or vasopressors (e.g., epinephrine, norepinephrine) may not be effective because these drugs work by stimulating adrenergic receptors. In these cases, glucagon is the treatment of choice [50]. Glucagon binds to specific cell membrane receptors, bypasses the adrenergic receptors, and increases the intracellular concentration of cyclic adenosine monophosphate (cAMP). cAMP is a second messenger, and it activates intracellular enzymes that affect myocardial activity. In cases of beta blocker poisoning, glucagon increases heart rate, improves cardiac conduction, and increases contractile force. It has also been used as a second-line option for treating calcium channel blocker poisoning [43,46,50,51].

The dose of glucagon is 5 mg for adults or 50 mcg/kg for children, delivered as a bolus over one minute. If blood pressure and pulse do not improve one to three minutes after the bolus, a second dose is given; if two doses do not provide a response, it is unlikely further doses will. If blood pressure and pulse do improve, a continuous infusion of 2–5 mg per hour is started (70 mcg/kg per hour for children). There are no criteria for an endpoint for glucagon therapy.

The presence of insulinoma or pheochromocytoma is a contraindication to glucagon use. Hyperglycemia, hypokalemia, nausea, and vomiting are common adverse effects.

Levocarnitine (L-carnitine) is a naturally occurring amino acid derivative that is used by the mitochondria for fatty acid metabolism. Valproic acid poisoning prevents the synthesis of levocarnitine. This in turn disrupts fatty acid metabolism, and acute valproic acid poisoning is often characterized by hyperammonemic CNS depression, coma, and hepatic damage. Exogenous levocarnitine decreases serum ammonia levels and may be effective at improving the clinical course of acute valproic acid poisoning [60,61].

Levocarnitine should be considered in the treatment of acute valproic acid overdose if there is severe hepatotoxicity, coma, a serum valproic acid level >450 mcg/mL, or hyperammonemic encephalopathy. The initial dose of levocarnitine is 100 mg/kg IV (maximum: 6 g) given over 30 minutes. This is followed by 50 mg/kg IV (maximum: 3 g) given every eight hours [51]. The endpoint of therapy has not been well-defined, but should be based on the patient's neurologic status, serum ammonia level, and serum valproic acid level.

There are no known contraindications to the use of levocarnitine. Adverse effects are primarily gastrointestinal (e.g., diarrhea, nausea, vomiting).

Intravenous lipid emulsion involves the use of an emulsion of egg phospholipids and soybean oil as an accepted antidote for treating toxicity caused by local anesthetics [62]. Its use in the treatment of symptomatic overdoses of antiepileptics, cardiovascular medications (e.g., beta blockers, calcium channel blockers), and antidepressants (e.g., bupropion, tricyclic antidepressants) has produced mixed results [62]. The antidotal/therapeutic mechanism of action is not known, but animal studies suggest that lipid emulsion forms a tight bond with certain lipid-soluble drugs, preventing them from reaching tissues and receptor sites, or that the lipid emulsion may actively remove drugs that have already reached these areas [63].

Lipid emulsion is considered a second-line therapy for treating symptomatic overdose of drugs and toxins. The initial bolus dose for IV lipid emulsion is 20% solution, 1.5 mL/kg, infused in over five minutes. Following the bolus dose, a continuous infusion of 20% solution 0.25 mL/kg should be given over 30 to 60 minutes [51,63]. The dose can be repeated several times, or the infusion rate can be increased, if needed. Intravenous lipid emulsion has been used for children, but there is no specific pediatric dosing [51].

There are no specific contraindications for the use of IV lipid emulsion. Adverse effects include (but are not limited to) acute kidney injury, acute lung injury, cardiac arrest, interference with laboratory tests, pancreatitis, and recurrent or delayed toxic effects from the ingested drug [63,64].

Excessive oxidative stress can change hemoglobin to methemoglobin, a form of hemoglobin that cannot carry oxygen. Chemicals such as nitrates and some drugs—particularly dapsone, local anesthetics like benzocaine, and phenazopyridine—can cause the formation of methemoglobin and overwhelm the body's normal methemoglobin reducing mechanisms. Methemoglobinemia produces very distressing signs and symptoms, and for some patients, the hypoxemia can be dangerous. Waiting for methemoglobinemia to spontaneously resolve is not reasonable or safe.

Methylene blue increases the activity of the nicotinamide adenine dinucleotide phosphate-reducing system (normally a minor pathway) and changes methemoglobin back to hemoglobin [65]. Methylene blue should be used for patients who have a methemoglobin level greater than 30% or who have a higher than normal methemoglobin level and signs and symptoms of hypoxemia [65]. However, methylene blue should be avoided in the presence of severe renal failure, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or methemoglobin reductase deficiency. It should not be used to reverse methemoglobinemia that was induced during treatment for cyanide poisoning [51].

The recommended dose is 1–2 mg/kg IV of a 1% solution given over five minutes; this dose may be repeated after 60 minutes. The IV line should be flushed with normal saline, as methylene blue irritates the veins. Methylene blue produces maximal effects within 30 minutes of administration, with a rapid reduction in methemoglobin and improvement in signs of methemoglobinemia. Nonresponse after two doses could be a sign that the patient has G6PD deficiency or methemoglobin reductase deficiency, the doses have been too low, or the drug is still present in the gut.

Dizziness, headache, and nausea may develop. High doses (greater than 7 mg/kg) may cause methemoglobinemia or hemolysis [65].

When a toxic dose of acetaminophen greater than 7.5 grams or 150 mg/kg is ingested, the normal metabolic pathways for the drug are overwhelmed and a large amount of a toxic metabolite is produced. This metabolite binds to the liver and can cause significant hepatic damage; acetaminophen poisoning (intentional and unintentional) is a leading cause of acute liver injury and failure and the need for liver transplant. By several complex mechanisms, N-acetylcysteine (NAC) counteracts the effects of acetaminophen poisoning.

NAC is indicated for patients who are known to or suspected to have acutely ingested a toxic amount of acetaminophen and who have a serum acetaminophen level that is at or above the probable toxicity line on the Rumack-Matthew nomogram (Figure 1). NAC may also be used for patients who have a chronic ingestion of toxic doses of acetaminophen and evidence of liver damage.

RUMACK-MATTHEW NOMOGRAM

Figure 1

Source: [48]

NAC can be given IV or orally. The two forms are equally effective, but the oral formulation requires three days of treatment (compared to 21 hours for the IV formulation) and is more difficult for the patient to tolerate and the staff to manage. Regardless of delivery method, guidelines recommend the chosen regimen should deliver at least 300 mg/kg IV or orally during the first 20 to 24 hours of treatment [51,76].

The dose for the oral preparation is 140 mg/kg, followed in four hours by 70 mg/kg given every four hours to a total of 17 doses; if emesis occurs within one hour of administration, the dose should be readministered [51]. Oral NAC is available as a liquid or an effervescent tablet.

The current, FDA-approved IV protocol involves an initial dose of 150 mg/kg IV, infused over 60 minutes, followed by 50 mg/kg IV infused in over four hours. Finally, 100 mg/kg IV is infused over 16 hours. These infusions should be given consecutively, with no gap [51,66]. Several hours before the third infusion will be completed, a serum acetaminophen level, liver function, and international normalized ratio (INR) should be assessed. If there is measurable serum acetaminophen or if the liver function tests and/or INR are abnormally elevated, NAC therapy should be continued. In situations of a massive acetaminophen overdose, the IV NAC protocol may be altered, with higher doses of NAC administered [67]. In addition, research has shown that a two-infusion protocol—200 mg/kg over four hours followed by 100 mg/kg over 16 hours—may decrease the number of hypersensitivity reactions [51,68].

There are no contraindications to the use of NAC. However, the oral form cannot be used if the patient has a malfunctioning gut, and the IV form should be used cautiously if the patient has asthma or bronchospasm.

The most common adverse effect of IV NAC is a hypersensitivity reaction; these usually happen in the first hour of treatment. Most of the hypersensitivity reactions are mild, self-limited, and easily treated; anaphylaxis occurs very infrequently. The coagulation tests may be falsely elevated by NAC. Nausea and vomiting are common adverse effects of the oral formulation.

According to the Department of Veterans Affairs, providers should consider prescribing naloxone for patients at risk for opioid overdose.

(https://www.healthquality.va.gov/guidelines/mh/srb Last Accessed: March 15, 2024)

Level of Evidence: Expert Opinion/Consensus Statement

Opioids bind to specific mu and kappa receptors in the brain and spinal cord. When these receptors are stimulated, CNS activity in certain parts of the brain is decreased and the clinical effects of opioids (e.g., analgesia, respiratory depression, sedation) are produced. Naloxone is a competitive opioid antagonist that displaces and prevents binding of opioids to receptors. As such, it can reverse respiratory depression and help avoid endotracheal intubation and prolonged hospital stays.

Naloxone is used to reverse respiratory depression caused by opioid poisoning. Although naloxone will reverse sedation, this should not be the primary goal of its use. There is some evidence that naloxone will reverse CNS and respiratory depression caused by clonidine, ethanol, guanfacine, and valproic acid poisoning and the toxic effects of other drugs, but the evidence for this is anecdotal and inconsistent [23].

The adult dose of naloxone is 0.4–2 mg given IV, intramuscular, or subcutaneously. The intranasal dose is 4 mg or 8 mg in each nostril. Naloxone can also be given intra-lingually, intra-osseously, via an endotracheal tube, or as nebulized solution. The pediatric dose (for children older than 5 years of age) is 0.1 mg/kg (maximum: 2 mg) [51].

For both children and adults, repeat doses of naloxone can be given until the desired effect has been attained. However, if there is no response after 5–10 mg, it is unlikely the patient has opioid poisoning. Reversing the effects of some opioids (e.g., buprenorphine) may require higher-than-normal doses of naloxone.

Because the half-life of some opioids is long and the effects of naloxone diminish and are gone in one to two hours, some patients with opioid poisoning will require a continuous IV infusion. In these cases, give the patient two-thirds of the dose that was successful in reversing respiratory depression every hour, or 0.4–0.8 mg/hour. In addition, patients who are opioid-poisoned and have been given naloxone should be observed for reoccurrence of respiratory and CNS depression; in some cases, six hours of observation after a dose of naloxone is required.

There are essentially no contraindications for the use of naloxone. However, it should be used cautiously in patients who are opioid-dependent, as in some clinical situations, precipitation of opioid withdrawal can result in arrhythmias and pulmonary edema. Naloxone should not be used to treat infants who have been exposed to opioids in utero.

Octreotide is a synthetic analog of somatostatin, a naturally occurring hormone that helps regulate the endocrine system. It decreases the release of insulin by the pancreas. Patients with sulfonylurea poisoning often have profound hypoglycemia that lasts for days and is not easily treated with IV dextrose or food, and octreotide has been successfully used for adults and children as an antidotal therapy for these cases [69].

To reverse sulfonylurea poisoning, the adult dose is 50–100 mcg administered subcutaneously every 6 to 12 hours; the pediatric dose is 1–2 mcg/kg every 6 to 12 hours. The IV dosing for adults is a 50-mcg bolus, followed by a continuous infusion of 25 mcg/hour; the pediatric dose is 1 mcg/kg/hour. In either case, octreotide should be administered for at least 12 hours. After therapy is stopped, serum glucose should be monitored for 24 hours, as hypoglycemia can recur [51].

There are no contraindications to the use of octreotide. Potential adverse effects are generally minor and include (but are not limited to) abdominal pain, bradycardia, chest pain, diarrhea, flatulence, hyperglycemia, hypertension, injection site pain, and nausea.

Physostigmine is a reversible inhibitor of acetylcholinesterase, increasing the activity and concentration of acetylcholine at cholinergic synapses. It has been used to identify and/or treat patients who have severe anticholinergic poisoning that cannot be managed with supportive care [70]. Anticholinergic poisoning can be caused by atropine, antihistamines, antipsychotics, TCAs, and some plants and mushrooms.

Physostigmine should never be used to treat the anticholinergic effects of TCAs, and it should never be used concurrently with depolarizing neuromuscular blockers such as succinylcholine [51]. Because physostigmine increases acetylcholine concentration at synapses, it should be used cautiously or avoided if the patient has a bladder or intestinal obstruction, asthma, diabetes, gangrene, Parkinson disease, cardiac conduction defects, peripheral vascular disease, or reactive airway disease.

Prior to administering physostigmine, a 12-lead ECG and cardiac monitoring should be done to assess for cardiac conduction defects. To initiate treatment, administer 0.5–2 mg IV slowly at a rate of ≤1 mg/minute. (The pediatric dose is 0.02 mg/kg at a rate of ≤0.5 mg/kg.) The dose can be repeated as needed every 10 to 30 minutes, up to a maximum 4 mg for adults and 2 mg for children [51].

Adverse effects of physostigmine include (but are not limited to) asystole, bradycardia, heart block, bronchospasm, gastrointestinal effects (e.g., nausea, vomiting), and seizures [70].

Organophosphate and carbamate insecticides bond to acetylcholinesterase. If the bonding is not interrupted, it becomes irreversible and the enzyme is permanently damaged [71]. This results in excess cholinergic stimulation. Pralidoxime, also known as 2-PAM, can break this bond, and when it is used with atropine, the two are synergistic [71].

2-PAM is approved for the treatment of symptomatic organophosphate or carbamate insecticide poisoning. It may also be used for persons exposed to certain chemical warfare agents, such as sarin and tabun, which are essentially organophosphates.

Pralidoxime must be given with atropine, as 2-PAM alone is not effective to treat the neuromuscular signs and symptoms of organophosphate poisoning. The adult dose is 1–2 g, diluted in 100 mL of 0.9% normal saline and infused in over 15 to 30 minutes. The pediatric dose is 25–50 mg/kg (maximum: 1 g). After the bolus dose, most patients will require a continuous IV infusion, but repeat bolus dosing can be used as well. For an adult, the continuous infusion should be 8 mg/kg per hour; the pediatric dose is 10–20 mg/kg per hour [51].

It is important to give 2-PAM as soon as possible. The longer the period of time from exposure to treatment with 2-PAM, the less likely it is the drug will break the bond between acetylcholinesterase and the insecticide.

There are no contraindications for 2-PAM, but the drug should be used cautiously in patients with myasthenia gravis. Diplopia, dizziness, drowsiness, headache, and nausea may occur. If 2-PAM is given too rapidly, laryngospasm and serious cardiac and neurologic effects are possible [71].

An overdose of the anti-tubercular drug isoniazid interferes with pyridoxine (vitamin B6) availability in the brain. Pyridoxine is essential in the production of GABA, a major inhibitory neurotransmitter. Patients who have taken an overdose of isoniazid are at risk for seizures due to the decrease in GABA production. These seizures often do not respond to conventional therapy but can be ameliorated with pyridoxine supplementation [72].

The chemical monomethyl hydrazine has similar effects to those seen with isoniazid, and pyridoxine is used for patients with toxic exposures to this substance [73]. Also referred to as MMH, monomethyl hydrazine is found in some mushrooms, most notably false morels, and is part of the formulation for some types of rocket propellants. Because MMH is believed to have the same action as isoniazid, treatment is similar for both types of poisonings [73].

One gram of pyridoxine should be given for every gram of isoniazid or MMH ingested; the dose should be diluted in either 5% or 0.9% normal saline and infused at a rate of 1 g per minute. If the isoniazid dose ingested is not known, give 5 g and repeat this dose every 5 to 10 minutes as needed. (The pediatric dose is 70 mg/kg up to a 5 g maximum.) [51] Seizures caused by isoniazid overdose will usually stop within minutes of giving pyridoxine, but if seizures continue, benzodiazepines should be added to the treatment regimen. Massive doses of pyridoxine cause sensory neuropathy, but when used for isoniazid poisoning, pyridoxine does do not produce adverse effects.

Using sodium bicarbonate as an antidote is referred to as alkalinization, and sodium bicarbonate has three primary uses in toxicology: treatment of aspirin poisoning, symptomatic TCA poisoning, and ethylene glycol and methanol poisoning [74].

Sodium thiosulfate is the antidote for cyanide poisoning. It binds to cyanide to form a thiocyanate, and this compound, which is minimally toxic, is excreted renally. The result is a rapid reversal of the toxic effects of cyanide poisoning.

Sodium thiosulfate is administered at a dose of 1.65 mL/kg IV of a 25% solution (maximum: 12.5 g) [75]. It should be administered in conjunction with sodium nitrite, with sodium nitrite started first [51]. The rate of infusion depends on the clinical condition of the patient; it can be given as a rapid IV bolus or infused over 10 to 30 minutes. Minor adverse effects are possible and include injection site irritation, muscle cramping, nausea, and vomiting.

Patient A, a girl 14 years of age, is brought to a local emergency department by her parents at 9 p.m. The parents state that 45 minutes prior to arriving they found the patient in her room. She was very upset and stated that she had just taken "a whole bottle of pills." The parents are able to account for their daughter's actions and location since she returned from school at 3 p.m., and they state that during that time she had been awake, alert, and acting normally. She had been alone for only 5 to 10 minutes. The father found an empty bottle of acetaminophen 500-mg tablets in the patient's room. The bottle contained 60 tablets when it was purchased, but neither parent can remember how many tablets were in the bottle before the exposure. They estimate that it might have been half full.

Patient A is awake, alert, and oriented to time, place, and person. Her speech is clear. Her vital signs are: temperature 98.3°F; pulse 80 beats per minute and regular; respiratory rate 16 breaths per minute; and blood pressure 112/60 mm Hg. Her skin is warm and dry, and no cyanosis is noted. Her pupils are 5 mm in diameter, and they are equal in size and normally reactive to light. Her chest is clear to auscultation, and her heart tones are normal. She has a normal gag reflex and bowel signs, and her bladder is not distended. She weighs 55 kg. Patient A has a past medical history of bipolar disorder, for which she takes lithium carbonate 300 mg, once in the morning and once in the evening; her last dose was at 9 a.m. today. The medication is given to the patient by the parents, and they are sure that she did not and could not have access to it. The patient has no other medical problems and takes no other medications. Neither parent takes any prescription medications. They state that the only other medication in the house is antacid tablets.

Patient A's ABCs are normal, and this is to be expected. Acetaminophen causes delayed onset liver and (occasionally) kidney damage, typically about 24 hours after ingestion. If a patient had taken a massive overdose of acetaminophen, other organ systems could be affected and there would be changes in the ABCs. However, these cases are rare, and even then, it takes time for toxicity to develop. A dose of acetaminophen greater than 7.5 g or 150 mg/kg is considered potentially toxic. It is estimated that Patient A may have taken 15 g or 272 mg/kg. This is a large dose and potentially toxic, but she has presented to the emergency department soon after the ingestion. As such, the dose does not put her at risk for serious derangements of the ABCs. If the ABCs were abnormal, an exposure to another drug or toxin would be strongly considered. There is no indication that dextrose, oxygen, naloxone, or thiamine is needed.

It appears that the patient ingested only acetaminophen, had no access to any other medications, and the history seems accurate and reliable. The patient takes lithium carbonate, and it is very unlikely that an overdose of this medication was ingested. However, the possibility should be kept in mind. The patient does not have any signs or symptoms of a toxidrome, and the physical exam is normal.

As a part of the treatment plan, gastric decontamination is considered. The patient is awake and alert, has a normal gag reflex, and has a normally functioning gastrointestinal tract. It is very unlikely that Patient A's mental status or ability to maintain her airway will deteriorate. There are no contraindications to the use of activated charcoal and it binds very well to acetaminophen, so activated charcoal would be the gastric decontamination technique to use. Syrup of ipecac should never be used, lavage is reserved for patients who have ingested a life-threatening amount of a dangerous drug and/or drug for which there is no effective antidote, and whole bowel irrigation is reserved for drugs that are not adsorbed by activated charcoal or sustained-release preparations. One dose of plain charcoal should be given. Most activated charcoal is available in 50-g doses.

NAC is a highly effective antidote for acetaminophen poisoning. It is commonly available, easy to administer, and relatively safe. It can be given any time within eight hours of an acetaminophen overdose and be equally effective; after eight hours, the effectiveness begins to decrease. Patient A may need NAC depending on the amount of drug she took. However, the time of ingestion in this case is known and within eight hours of arrival, so there is no need to give NAC immediately. NAC should be used for acetaminophen poisoning if the patient has ingested a toxic dose, there is evidence of liver damage, or the serum acetaminophen level is toxic. In this case, the dose is unknown, and it is too early to see signs, symptoms, or laboratory evidence of liver damage, so the decision of whether or not to use NAC will depend on the serum acetaminophen level. Hospital laboratories can usually perform and report the results of serum acetaminophen level test within one hour of receiving the blood sample.

It is clear a serum acetaminophen level should be obtained, but it must be done four hours or later after the ingestion. If the level is measured sooner, it cannot be reliably interpreted. Interpreting the level as toxic or nontoxic on the basis of the numerical value alone could lead to treatment errors. The level and associated risk for hepatotoxicity should be interpreted using the Rumack-Matthew nomogram. Serum hepatic transaminases, BUN, and serum creatinine should also be obtained. Although it is unlikely the patient had access to her lithium, it would be prudent to check a lithium level as well. There is no need for other laboratory tests, an ECG, or imaging studies.

In some cases, a serum aspirin level should be checked. It is not unusual for patients to use the terms acetaminophen and aspirin interchangeably. However, because of the particulars of this case study, an aspirin level would not be needed.

When an overdose of acetaminophen is taken, the two primary metabolic pathways for the drug become saturated and a third pathway is used. This metabolic pathway produces large amounts of a toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI), and it is this metabolite that causes liver and kidney damage. Manipulating the pH of the urine or serum would not affect acetaminophen metabolism or the production of NAPQI, so these techniques are not used. Acetaminophen can be quickly and easily removed with hemodialysis, but hemodialysis has risks. Because there is a highly effective antidote available, hemodialysis or any other type of extracorporeal removal would not be needed.

At this point, care of Patient A focuses on monitoring vital signs, arranging a consultation with a mental health professional, maintaining patient safety, and treating with NAC if her acetaminophen level is greater than 150 mcg/mL.

Patient B, a man 56 years of age, is brought to the emergency department at 4:30 p.m. His wife called EMS because the patient had reportedly taken an overdose of his prescription medications. According to the EMS personnel, the ingestion was unwitnessed; Patient B had told the wife that he wanted to die and that some time that morning he had "taken all of his pills." The exact time of ingestion is not known, but a reasonable estimate is 10 a.m. The EMS personnel report that they found empty bottles of bupropion, metoprolol, and verapamil (all three sustained-release formulations), and the patient's name was on the bottles. The patient told EMS that he had been drinking vodka and when that ran out, he drank some antifreeze. The EMS personnel did not find any bottles of antifreeze. He has a past history of chronic alcohol abuse, depression, and hypertension.

Patient B is awake and alert, but drowsy. His vital signs are: temperature 97.8°F; pulse 44 beats per minute; respiratory rate 16 breaths per minute; and blood pressure 82/38 mm Hg. The cardiac monitor shows sinus bradycardia. His oxygen saturation is 93%, and his bedside serum glucose level is 148 mg/dL. His nail beds are cyanotic, there is no peripheral edema, and his skin is cool and clammy. His pupils are 5 mm and reactive, his lungs are clear, and his heart tones are normal. His abdomen is soft and nontender, and there is no bladder distention.

The most immediate need in this situation is to stabilize the ABCs. Supplemental oxygen is applied, and IV access is obtained. It is reasonable to assume that the bradycardia and hypotension are being caused by the metoprolol and verapamil. Atropine, fluids, and vasopressors are seldom effective for the cardiovascular toxicity caused by beta blockers and calcium channel blockers. Those drugs can be tried, but if they do not quickly reverse the bradycardia and hypotension, additional treatment should not be delayed. For Patient B, antidotal care is a top priority. Antidotal care may also be needed to treat ethylene glycol poisoning.

The physician administers 10% calcium chloride 10 mL IV over 5 minutes. The dose can be repeated every 10 to 20 minutes, or a continuous infusion can be used. Concurrently, an IV bolus dose of glucagon is given, 5 mg over five minutes. This can be followed (if needed) with a continuous IV infusion at 1–5 mg/hour. If these are unsuccessful, a dextrose-insulin infusion and cardiac pacing are the next steps. Give a bolus dose of regular insulin, 1 Unit/kg, followed by a continuous infusion of regular insulin at 1–10 Units/kg/hour. As the insulin is being given, the patient should receive an IV bolus of 25 g of 50% dextrose. Additional glucose should be given to maintain the serum glucose level of 100–200 mg/dL. Consider giving fomepizole. Antifreeze almost always contains ethylene glycol, but many hospital laboratories are not prepared to measure ethylene glycol levels. If a level cannot be obtained, the decision to use fomepizole will depend on how likely it is the patient ingested ethylene glycol, the patient's arterial blood gases, and if the patient has a large anion gap and/or a large osmolar gap. The risks of fomepizole are slight, and the benefit can be enormous.

Patient B's serum glucose is normal, so he does not require dextrose. Supplemental oxygen is started immediately. He does not have signs or symptoms of an opioid poisoning, so naloxone is not appropriate. Although he chronically abuses alcohol, the patient has no signs of Wernicke-Korsakoff syndrome, so thiamine should not be given.

The circumstances of the overdose are not very clear, but if Patient B did take the medications and the antifreeze, there is a substantial risk for serious morbidity and death. The time of ingestion is not known with certainty, but it appears that it happened approximately 6.5 hours prior to arrival. Given the patient's clinical condition and the empty bottles of metoprolol and verapamil, it seems reasonable to assume that he took an overdose of these medications and took an intoxicant that can cause CNS depression—in this case, ethanol and/or ethylene glycol.

Upon physical examination there is no evidence of a toxidrome, as would be expected. Because the patient has ingested a beta blocker, a calcium channel blocker, ethanol, and a toxic alcohol, the patient should be assessed for signs and symptoms of circulatory compromise, respiratory depression, intoxication, and metabolic acidosis. Circulatory compromise is evident. The patient is drowsy, and this may be due to the bupropion, the ethanol, the ethylene glycol, or a combination of the three. There is no respiratory depression, so Patient B may not have ingested sufficient quantities of the alcohols for this to develop. There are no signs of metabolic acidosis, but this could develop in the next few hours. Laboratory confirmation is needed to detect and confirm an acid-base disturbance. If acidosis is present, it could, in part, explain the CNS depression.

Gastric decontamination should not be performed for Patient B. Although the patient has ingested medications and a toxin that can be very dangerous, it has been more than one hour since the ingestion. Also, it could cause the patient's CNS depression to worsen. Any method of gastric decontamination would put the patient at risk for aspiration and/or worsening of his cardiac status and would probably not be useful.

Measurement of Patient B's serum acetaminophen level, serum ethanol level, and serum ethylene glycol level should be attempted. Blood levels of bupropion, metoprolol, and verapamil can be done, but they cannot be obtained immediately and would not be useful in caring for the patient. Obtain electrolytes to look for an anion gap, assess arterial blood gases to check for an acid-base disturbance, and request a serum osmolarity to look for an osmolar gap. A 12-lead ECG should be done, and the patient should be on continuous cardiac monitoring. Urinalysis should also be ordered. Ethylene glycol metabolism produces oxalate crystals in the urine, which could help confirm the diagnosis.

Bupropion, metoprolol, and verapamil cannot be removed by dialysis or hemoperfusion nor can their elimination be enhanced by manipulating the pH of the urine. However, hemodialysis is very effective at removing ethylene glycol and the toxic aids produced by ethylene glycol metabolism. A nephrologist should be notified of the possible need for hemodialysis.