SURIYAWUT SURIYA/SHUTTERSTOCK SURIYAWUT Common antidotes used in the ICU By Carrie L. Griffiths, PharmD, BCCCP, FCCM; Arzu Patel, BS; and Kristie A. Hertel, MSN, RN, CCRN, ACNP-BC Abstract: When ingested, some common household products can be poisonous, and, when taken improperly, both prescription and over- the-counter medications can result in overdoses. This article describes several common toxicities encountered in the ICU and their respec- tive antidotes. Keywords: acetaminophen, antidote, benzodiazepine, beta-blocker, calcium channel blocker, digoxin, digoxin immune fab, flumazenil, fomepizole, hyperinsulinemia-euglycemia therapy (HIET), naloxone, N-acetylcysteine, opioids, toxic alcohols www.nursingcriticalcare.com July l Nursing2020CriticalCare l 9 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. Common antidotes used in the ICU According to the 2018 National for overdose include advanced sites. That is, digoxin immune Poison Data System Annual age, metabolic disorders, and fab binds to digoxin, removing it Report, there were 2,099,751 drug interactions.4 Medications from its tissue binding sites, and human exposures to substances such as verapamil, atorvastatin, the bound drug is then pushed ranging from household cleaning omeprazole, potassium-depleting into the extracellular fluid. As products to prescription medica- diuretics, alprazolam, erythromy- a result, it is unable to exert its tions.1 In the critical care setting, cin, and tetracycline may lead to effect on its target tissues, revers- patients present with a variety of increased serum concentrations ing adverse events associated conditions, including intentional of digoxin.6,7 with overdose.7 or unintentional poisonings or Mechanism of toxicity. Adverse reactions. There have overdoses. Antidotes are used to Digoxin’s mechanism of action been reported allergic reactions counteract the toxicity of poisons. involves a blockade of sodium- to digoxin immune fab, includ- In the US, poison control centers potassium adenosine triphospha- ing urticaria, pruritus, erythema, are available 24/7 in every state tase, especially in myocardial tissue. angioedema, bronchospasm, and the District of Columbia to At therapeutic levels, this results in hypotension, and tachycardia. In assist with any type of poisoning. increased contractility, shortened addition, infusion-related reactions Poison control centers are avail- atrial contraction, and a prolonged have been observed, and are relat- able in several countries globally.2 atrioventricular (AV) refractory ed directly to the rate of admin- This article discusses several period. However, at supratherapeu- istration. The infusion should be common household substances tic levels, overexcitation of cardiac, stopped if either reaction type and over-the-counter (OTC) and gastrointestinal (GI), and central occurs. Digoxin immune fab may prescription medications along nervous tissues can lead to a variety also cause worsening of conges- with the proper use of their of toxicity symptoms.4,7 tive heart failure, atrial fibrillation, respective antidotes. Please note Clinical signs and symptoms. and phlebitis. Overcorrection of the that anticoagulant reversal agents Clinical signs of digitalis toxicity hyperkalemia caused by digoxin tox- are not discussed, as they were include confusion, loss of appe- icity may also lead to hypokalemia.7 covered in a previous issue of tite, and GI symptoms including Clinical pearls. Obtaining a this journal.3 nausea, vomiting, and diarrhea. serum digoxin level before treat- Patients may also experience ment is preferred, as this value Digoxin and digoxin immune vision disturbances, which are can be used to devise a dosing fab (Digibind, DigiFab) generally characterized by yellow- strategy for digoxin immune fab. Digoxin is a narrow therapeutic ing or blurry vision, light sensitiv- However, it is important to note index medication. Clinical ben- ity, or seeing “halos” or flashing that serum digoxin measurements efit is generally seen at serum lights.7 More severe symptoms of are nonessential for treatment concentrations ranging from overdose include cardiac arrhyth- monitoring. Serum concentrations 0.8 to 2 ng/mL; however, clini- mias, such as ventricular fibril- may appear to rise after digoxin cal benefit may be limited to a lation, ventricular tachycardia, immune fab administration, but lower range of 0.5–0.9 ng/mL asystole, AV block (first-, second-, this can be misleading as this in patients with heart failure.4 and third-degree), ventricular value can be attributed to drug Due to the narrow therapeutic extrasystoles, ventricular ectopic already bound to digoxin immune index of digoxin, unintentional activity, and bradycardia.4 fab and therefore unable to cause overdose or toxicity is possible. Treatment and monitoring. toxicity. Until the bound drug For example, in cases of severe Digoxin immune fab is an immu- is excreted in the urine, serum renal insufficiency, the half-life noglobulin fragment that possesses levels will not be truly indicative of digoxin can be increased from a highly specific affinity for digox- of unbound digoxin.6 In patients 36 to 48 hours up to 100 hours; in. It has been available for use with renal impairment, excre- as a result, these patients have in digoxin toxicity since 1986.4 tion can be delayed by a week an increased risk of accidental This affinity is greater than that or longer. Monitoring measures overdose.5 Other risk factors of digoxin for its tissue binding recommended are ECG changes, 10 l Nursing2020CriticalCare l Volume 15, Number 4 www.nursingcriticalcare.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. temperature, BP, and electrolytes cemia, lactic acidosis, metabolic glucose should be checked every (in particular, potassium levels).7 acidosis, altered mental status, 20 minutes, then hourly for the dysrhythmias, and seizures.8 duration of the infusion. The Beta-blockers/calcium Treatment and monitoring. onset of action of insulin is gener- channel blockers and Hyperinsulinemia-euglycemia ally 15 to 45 minutes; however, it hyperinsulinemia- therapy (HIET) can be used as can be delayed, even by several euglycemia therapy an antidote for beta-blocker and hours. HIET should be continued Two classes of widely used anti- calcium channel blocker over- until the patient’s heart rate is hypertensive medications, beta- dose, in addition to supportive greater than 50 beats/minute, and blockers and calcium channel care. Advantages of HIET include systolic BP remains greater than blockers, are associated with high its wide availability, relatively 100 mm Hg. A dextrose infusion mortality due to overdose and lower cost, and minimal adverse may be required for up to 24 resulting poison-induced cardiogenic events.9 There are no irreversible hours after discontinuation of the shock. In the US, beta-blockers adverse reactions associated with insulin infusion.8 are the fifth most-commonly HIET; it may cause hypoglycemia prescribed class of medication.8 and hypokalemia, both of which Acetaminophen and Mortality associated with calcium can be resolved with relative N-acetylcysteine channel blockers is the highest ease.8 Insulin works to reverse Acetaminophen is one of the most among cardiovascular medications.9 the effects of beta-blockers and commonly used OTC medica- Mechanism of toxicity. calcium channel blockers via tions; its analgesic and antipyretic Overdose occurs either intention- several mechanisms; it increases properties lend itself to being ally or unintentionally due to low inotropy and intracellular glucose used in many combination prod- health literacy.9 Beta-blockers transport, and enhances micro- ucts. Because of its ubiquity, it is work by competitively inhibiting vascular perfusion. Overall, this often viewed as benign, and at beta-receptors, indirectly decreas- leads to increased cardiac output therapeutic concentrations, the ing the amount of cyclic adenos- and elevated BP.9 safety profile of acetaminophen ine monophosphate produced. Although there are no estab- is very good. In addition, acet- This reduces the amount of cal- lished guidelines for the use of aminophen is often included in cium entering calcium channels. insulin as an antidote, typical dos- OTC combination cough, cold, As a result, heart rate and con- ing includes an I.V. bolus dose, and pain medications, increas- tractility are decreased.10 followed by a continuous infu- ing the likelihood of accidental Calcium channel blockers also sion. It is recommended to titrate overdose. Accidental overdose is affect the entry of calcium by the dose based on the patient’s exceedingly prevalent and can directly blocking calcium chan- glycemic status. In addition, an lead to significant hepatotoxicity nels.11 This leads to relaxation of I.V. dextrose bolus, followed by that progresses rapidly.12,13 In the vascular smooth muscle and a continuous dextrose infusion, US, acetaminophen toxicity is the vasodilation. Non-dihydropyridine may be given with the insulin most common cause of acute liver calcium channel blockers such bolus based on the patient’s blood failure and the primary reason for as diltiazem and verapamil also glucose. However, it is likely, emergent liver transplants.13 inhibit the sinoatrial and AV especially in cases of calcium Mechanism of toxicity. nodes. channel blocker overdose, that Acetaminophen is metabolized by Clinical signs and symp- the patient will be hyperglycemic, a variety of pathways in the liver, toms. Overdose can lead to