Clinical Toxicology Antidotes Manual 2022 PDF

Ministry Of Health & Population ‫وزارة الصحة والسكان‬ Central Administration Of ‫االدارة المــركــزية‬ Critical & Urgent Care ‫للرعاية الحرجة والعاجلة‬ Clinic...

Ministry Of Health & Population ‫وزارة الصحة والسكان‬ Central Administration Of ‫االدارة المــركــزية‬ Critical & Urgent Care ‫للرعاية الحرجة والعاجلة‬ Clinical Toxicology Antidotes Manual Antidotes N Drug Name 1 N-acetylcysteine 2 Naloxone (Resicure) 3 Flumazenil (Anexate) 4 Obidoxime (Toxogonin) Digoxin-Specific FAB 5 (Digibind And Digifab) 6 Glucagon Hydroxocobalamin 7 (Cyanokit™) 8 Protamine Sulfate 9 Activated Charcoal Ministry Of Health & Population ‫وزارة الصحة والسكان‬ Central Administration Of ‫االدارة المــركــزية‬ Critical & Urgent Care ‫للرعاية الحرجة والعاجلة‬ What is antidote? ⮚ According to WHO: “Antidote was defined as a therapeutic substance used to counteract the toxic action(s) of a specified xenobiotic.” N-acetylcysteine Indications: ⮚ N-acetylcysteine (NAC) is a lifesaving therapy in the management of acetaminophen (paracetamol) poisoning ⮚ Mucolytic therapy: in respiratory condition with excessive and /or thick mucus production. ⮚ Cyclophosphamide-induced haemorragic cystitis. ⮚ Adjuvant in the treatment of obstructive lung diseases. Acetaminophen Toxicity Manifestations Toxic dose: > 12 gm ingestion 6-7 gm in an adult or 200 mg/kg in a child are the lowest threshold capable of toxicity. Initial symptoms of acetaminophen toxicity can take up to 12 hours to appear. Include: Phase 1 – 0-24 hours Nausea, vomiting, nothing Phase 2 – 24-72 hours elevated liver enzymes, prolonged PT Phase 3 – 72-96 hours Hepatic necrosis, encephalopathy, coagulopathy Phase 4 – 4 days- 2 weeks If damage is not irreversible, complete resolution of hepatic dysfunction will occur Ministry Of Health & Population ‫وزارة الصحة والسكان‬ Central Administration Of ‫االدارة المــركــزية‬ Critical & Urgent Care ‫للرعاية الحرجة والعاجلة‬ Investigations: Acetaminophen level (Nomogram) after 4 hours, if not detected after 8 hours, to predict hepatotoxicity, liver enzymes, Bilirubin, PT / INR, Electrolytes, Urea & Creatinine Dose: N-Acetylcysteine : Oral Loading dose: 140mg/kg diluted in juice or soda. Maintenance dose:70 mg/kg every 4hours for 17 doses over 72 hours. or N-Acetylcysteine : IV (5gm / 25ml) 3 doses. 150 mg /kg in 200 ml glucose 5% IV slowly over 15 min by infusion, then 50mg /kg in 500 ml 5 % dextrose 4 hour, then 100 mg/kg in 1 L. glucose 5% over 16 hour Special warnings and precautions for use: ⮚ It is most effective when administered within 8 to 10 hours of toxicity. Although the efficacy of N-acetylcysteine diminishes between 10 and 24 hours post-overdose, it should be administered up to 24 hours as it can still be of benefit. It may still be administered after 24 hours in patients at risk of severe liver damage. ⮚ 2- Anaphylactic reactions Particularly with the initial loading dose. The patient should be carefully observed during this period for signs of an anaphylactic reaction. Nausea, vomiting, flushing, skin rash, pruritus and urticaria are the most common features, but more serious anaphylactic reactions may develop angioedema, bronchospasm, respiratory distress, tachycardia and hypotension. Ministry Of Health & Population ‫وزارة الصحة والسكان‬ Central Administration Of ‫االدارة المــركــزية‬ Critical & Urgent Care ‫للرعاية الحرجة والعاجلة‬ Naloxone (Resicure): Indications: ⮚ Antidote for opoid overdose. ⮚ Preventing opoid abuse. ⮚ Shock (septic ,cardiogenic, spinal) by improving blood flow. Opoids Toxicity Clinical picture: Dosing: Adults: Start at 0.04-0.4 mg IV/ IM /SC. Repeat dose if initial response not adequate, up to 10mg total. Titrate to RR ≥ 12 and sufficient Tidal volume. if opoid naïve can start with 0.4 mg. Peds: 0.01 mg/kg IV /IM /SC can be used but not preferred) if opoid naïve (0.001mg/kg if opoid dependent). Titrate to 0.1mg/kg IV if no effect. Neonates: (Asphyxia neonatorum) 0.1 mg/kg via umbilical vein (IM, SC) q 2-3 min. For recurrent respiratory depression consider infusion: 2/3 of reversal dose infused hourly. Ministry Of Health & Population ‫وزارة الصحة والسكان‬ Central Administration Of ‫االدارة المــركــزية‬ Critical & Urgent Care ‫للرعاية الحرجة والعاجلة‬ Flumazenil (Anexate): Indications: o Benzodiazepine antagonist in Benzodiazepine over dose/ poisoning. o Treatment of non- benzodiazepine hypnotics (Z-drugs : Zolpidem, Zaleplon). o Hepatic encephalopathy: Beneficial short- term effects in people with cirrhosis. Benzodiazepine overdose Clinical picture: - Drowsiness, weakness, ataxia, respiratory depression, hypotension , hypothermia and coma. - Nystagmus - Slurred speech – Hallucinations - Hypotonia - Amnesia. Dosing: Initial dose: 0.2 mg IV @ 0.1 mg/min. May repeat with 0.3mg , then 0.5mg. Infusion: 0.1-1 mg/hr IV (in NS or D5W) Flumazenil should be used with caution in patients with head injury as it may be capable of precipitating convulsions or altering cerebral blood flow in patients receiving benzodiazepines. Obidoxime (Toxogonin): Indication: For organophosphorus compounds toxicity specially used by farmers in agriculture or house holding either by inhalation, dermal or ingestion. Initial Management: Atropine infusion 2-5 mg IV every 15 min until relief of bronchospasm and dryness of chest secretions, as this is the greatest life threat. Do not rely on heart rate and pupillary size. Obidoxime Dosing: Adult dose: (4-8 mg/kg) in 100 ml saline IV over 15-30 min or 2 amp. (500mg) loading dose then 1 amp. every 8 h. Maintenance: not more than 750 mg IV daily. Peds: 4-8 mg/kg in 100 ml saline IV over 30-60min Maintenance: 10 mg/kg/h IV.daily Ministry Of Health & Population ‫وزارة الصحة والسكان‬ Central Administration Of ‫االدارة المــركــزية‬ Critical & Urgent Care ‫للرعاية الحرجة والعاجلة‬ DIGOXIN-SPECIFIC FAB (DIGIBIND AND DIGIFAB): Indication: Digoxin and Cardiotoxic Steroidtoxicity/overdose. Digoxin Toxicity Manifestations With severe toxicity, ventricular tachycardia may be (bidirectional) and ventricular fibrillation can occur. ‘Reverse tick’ T-wave inversion is not a sign of toxicity. Characteristic arrhythmias are those in which a tachyarrhythmia occurs simultaneously with sinus or atrioventricular node suppression, such as atrial and junctional tachycardia with atrioventricular block. However, sinus bradycardia, atrioventricular block and ventricular ectopy are more common. Dosing: Reconstitute with 4 ml sterile H2O IV over 30 min (IVP if critical) Storage Refrigerate at 2° to 8°C (36° to 46°F). Unreconstituted vials can be stored at up to 30°C (86°F) for a total of 30 days. GLUCAGON: Indication: Calcium Channel Blocker or Beta Blocker Poisoning Adult dose : 50u/kg (max 10 mg) IV over 1-2 min, repeat q 10-15min 1-2 times PRN Then: 1-5 mg/h (max 10 mg/h) IV in D5W Peds: 50ug/kgIV load then 70 ug/kg/hr CYANIDE ANTIDOTE KIT [HOPE NITHIODOTE KIT] Indications: 1- Cyanide Poisoning. 2- Consider in Smoke Inhalation with Hypotension and Lactic Acidosis Sodium Nitrite (NaNO2) 3% (30 mg/ml) Adult: 10 mL (300 mg) IV over 2-4 min Peds: ~0.2 ml/kg IV over 2-4 min. Sodium Thiosulfate 25% (250 mg/ml) Adult: 50 mL (12.5 g) IV over 10-30 min Peds: 0.5 g/kg (2 mL/kg) IV as adult Warning: no nitrite if smoke/fire victim/CO exposure. Ministry Of Health & Population ‫وزارة الصحة والسكان‬ Central Administration Of ‫االدارة المــركــزية‬ Critical & Urgent Care ‫للرعاية الحرجة والعاجلة‬ HYDROXOCOBALAMIN (CYANOKIT™) Indication: Cyanide Poisoning Dose: 70 mg/kg (max 5 g) IV over 30 min Repeat prn (max total 15 g) IV over 6-8 h. PROTAMINE SULFATE: Indication: Heparin Poisoning 1 mg (max 50 mg) neutralizes 100 U heparin, or 100 anti-XaU of dalteparin/tinzaparin, or 1 mg of enoxaparin Load: 1% solution IV over > 10 min Then: 0.5 mg/100 anti-Xa U if still bleeding. Activated Charcoal A. Single dose Activated Charcoal: Uses: For gastrointestinal decontamination (decrease absorption) Dosage recommendation: - Beneficial if administered within 1hour of drug ingestion. - The dose is roughly based on 10:1 ratio of AC to the drug for adsorption. Children up to 1 year of age: 10-25 g or 0.5 – 1 g/kg. Children up to 1 to 12 years of age: 25 to 50 g or 0.5 to 1 g/kg. Adolescents and adults: 25 to 100 g. Use of activated charcoal with other forms of gastric emptying Activated charcoal may be used with other forms of gastric emptying in the following clinical situations: 1- Symptomatic patients presenting in the first hour after ingestion of substances that may result in life-threatening and/or severe, difficult to treat cardiovascular consequences: calcium-channel blockers, beta-blockers, tricyclic antidepressants. 2- Symptomatic patients who have ingested agents that slow gastrointestinal motility. 3- Patients taking sustained-release medications. 4- Patients taking massive or life-threatening amounts of medication (especially paracetamol, theophylline, aspirin, ibuprofen) where the grams ingested will likely supersede the activated charcoal: Drug ratio of 10:1. Ministry Of Health & Population ‫وزارة الصحة والسكان‬ Central Administration Of ‫االدارة المــركــزية‬ Critical & Urgent Care ‫للرعاية الحرجة والعاجلة‬ Contraindication Patients with an unprotected airway (depressed state of consciousness without endotracheal intubation). Patients at risk of aspiration (e.g. hydrocarbon with high aspiration potential). Patients at risk of haemorrhage or GI perforation due to pathology, recent surgery or medical conditions. Where activated charcoal in the GIT may obscure endoscopic visualization, though corrosives by themselves are not a contraindication and activated charcoal can be used if there are co-ingestants that are systemic toxins. Struggling child and uncooperative adults. Complications Inappropriate use of activated charcoal can lead to more serious morbidities: Aspiration leading to pulmonary problems. Emesis – especially when activated charcoal is administered with sorbitol. Theoretical risk GI obstruction, constipation, or haemorrhagic rectal ulceration (none reported with single dose activated charcoal). Corneal abrasions on direct ocular contact. Substances where Activated Charcoal is contraindicated and poorly adsorbed Alkali Ethanol & other alcohols Ethylene glycol Fluoride Inorganic salts Iron Lithium Mineral acids Potassium Hydrocarbons. Caustics B. Multiple Dose Activated Charcoal (MDAC): Considered only if a patient has ingested a life-threatening amount of Carbamazepine, dapsone, digoxin, phenobarbital, salicylates, quinine or theophylline. Uses: To increasing systemic clearance of various drugs (Enhanced Elimination). Dose: A loading dose of 1 g/ kg of aqueous slurry orally or via nasogastric or orogastric tube followed by other dose after 4hours, preferred with lactulose. Ministry Of Health & Population ‫وزارة الصحة والسكان‬ Central Administration Of ‫االدارة المــركــزية‬ Critical & Urgent Care ‫للرعاية الحرجة والعاجلة‬ References: Casarett and Doull’s Toxicology: The Basic Science of Poisons, 6th ed. ISBN-10 0-07-134721-6. Erickson TB, Thompson TM, and Lu JJ. (2007):The approach to the patient with an unknown overdose. Emerg Med Clin North Am. 25(2):249-281. ERKEKOGLU, Pınar; OGAWA, Tomohisa (2021): Medical Toxicology. BoD–Books on Demand. Hamad E, Babu K and Bebarta VS. (2016): Case Files of the University of - Massachusetts Toxicology Fellowship: Does This Smoke Inhalation Victim Require Treatment with Cyanide Antidote? Journal of medical toxicology : official journal of the American College of Medical Toxicology, 12(2):192- 198. Marraffa JM, Cohen V and Howland MA. (2012):Antidotes for toxicological emergencies: a practical review. American journal of health- system pharmacy : AJHP : official journal of the American Society of Health- System Pharmacists, 1;69(3):199-212. Oxford Desk Reference Toxicology. Edited by Nick Bateman, Robert Jefferson, Simon Thomas, John Paul Thompson, and Allister Vale. ISBN: 9780199594740. second chapter. Pillay VV. (2008):Current views on antidotal therapy in managing cases of poisoning and overdose. The Journal of the Association of Physicians of India, 56:881-892. The pill book. The illustrated guide to the most prescribed drugs 14th edition. Harold M Silverman. ISBN. 978-0-553-90763-6 Smith TW, Haber E, Yeatman L, Butler VP Jr. Reversal of advanced digoxin intoxication with Fab fragments of digoxin-specific antibodies. N Engl J Med. 1976; 294:797-800. Wenger TL, Butler VP Jr, Haber E, Smith TW. Treatment of 63 severely digitalis-toxic patients with digoxin-specific antibody fragments. J Am Coll Cardiol. 1985; 5:118A-123A. Gibb I, Adams PC, Parnham AJ, Jennings K. Plasma digoxin: Assay anomalies in Fab-treated patients. Br J Clin Pharmacol. 1983; 16:445-447.