Toxicology Presentation

I Toxicology Catherine Van, PharmD, BCPS Assistant Professor Department of Pharmacy Practice West Coast University School of Pharmacy EMMA Approach to Treating a Poisoned Patient a Stabilize the patient 2 Clinical evaluation 3 Preventing of further toxin absorption and enhancing toxin elimination U Antidote (if available) g Supportive care and follow up SCPAS Eben First Aid for Poison Exposures Inhaled Poison Immediately get the person to fresh air. Avoid breathing fumes. Open doors and windows. Poison on the Skin Remove contaminated clothing and flood skin with water for 10 minutes. Wash gently with soap and water and rinse. Avoid further contamination of victim or first aid providers. Poison in the Eye Flood the open eye with lukewarm or cool water poured from a glass 2 or 3 in. (~5-8 cm) before flushing the eye. Repeat for 10 to 15 continuous minutes. Remove contact lenses. Avoid ocular vasoconstrictor drops. Swallowed Poison 2 Unless the patient is unconscious, having convulsions, or cannot swallow, give 2 to 4 ounces (~60-120 mL) of water immediately and then seek further help. Dipiro 11th ed. Chapter 7. Clinical Evaluation: Overview  CABs  Circulation, airway, breathing  Dextrose  EKG  QRS  QTc  Check for patches  Vital signs  Pupil size  Temperature  Drug screen  Labs (BMP, ABG, osmolality) Clinical Evaluation: Drug Testing  Qualitative (urine screen)  Rarely guides therapy  Misleading due to false positives depending on assays used  Examples:  Amphetamines: pseudoephedrine, phentermine  false positive  Phencyclidine (PCP): tramadol, venlafaxine, dextromethorphan  false positive Dipiro 11th ed. Chapter 7.  Quantitative  Determination of serum concentrations  Pre-hospital care history  Examples? Digoxintylenol ind APAPethanol tonsal tohold phenytoin vouporicadd carbamazepine Clinical Evaluation: History  Obtain pertinent information  What is the name of chemical/medication ingested?  When was it ingested?  How much was ingested?  Any other medications that were co-ingested?  Ask about OTC products  Dosage form of the medication?  IR vs. ER vs. DR  Helps you determine the peak of onset and duration  Oftentimes if ER or EC is ingested, duration is prolonged along with theone peak so Approach to Treating a Poisoned Patient Stabilize the patient Clinical evaluation Preventing of further toxin absorption and enhancing toxin elimination Antidote (if available) Supportive care and follow up 86 Gta Gastrointestinal Decontamination  Ipecac syrup  Previously used to induce vomiting for treatment of ingested poisons  2003 - AAP: ipecac syrup should not be used to treat poisonings at home and parents should discard the medication  2010: no longer manufactured for use in the United States  2014: annual poison control report 132 individuals es received ipecac syrup, with or without poison center direction NO LONGER RECOMMENDED! AAP: American Academy of Pediatrics Dipiro 11th ed. Chapter 7. Gastrointestinal Decontamination 2 Ob signs  Gastric lavage  Involves placement of an orogastric tube and removing the gastric contents  Not for routine use; may be considered for lifethreatening ingestion that occurred within 1Is hour or when the substance is not absorbed by activated charcoal 8D as sulfuricacid  Not for ingestion of a corrosive agent Nitricacid  Complications: aspiration pneumonitis, laryngospasm, esophageal and gastric perforation, and fluid and electrolyte imbalance Dipiro 11th ed. Chapter 7. Gastrointestinal Decontamination 3 Activated charcoal: most effective when given within the first hour  Adsorbs toxins in the GIT  NOT effective for iron, lead, lithium, alcohols, and corrosives  Dosing (PO, NG) Es s  Children younger than 1 year: 1 g/kg  1-12 years old: 25 to 50 g  For an adolescent or adult: 25 to 100 g  Shake container thoroughly before administration  Following administration, rinse container with a small quantity of water and administer any residue to ensure patient has received the entire dose Dipiro 11th ed. Chapter 7; Lexicomp: Activated Charcoal Gastrointestinal Decontamination  Activated charcoal (cont.):  Contraindications a  When the airway is not protected  2GIT is not intact; perforation A m  Risks: emesis following administration, pulmonary i aspiration so hot suggal mom  Two formulations (plain and with sorbitol)  Avoid formulation with sorbitol due to electrolyte disturbances Dipiro 11th ed. Chapter 7. Gastrointestinal Decontamination Ngtroutinlygiven U as(magnesium  Cathartics citrate, sorbitol)  Thought to decrease rate of absorption by increasing     GI elimination of the poison and poison-activated charcoal complex Unproven value Poisoned patients do not routinely require a cathartic Rarely given without concurrent activated charcoal administration If used, a cathartic should be administered only once and only if bowel sounds are present Dipiro 11th ed. Chapter 7. Gastric Decontamination 5  Whole-Bowel Irrigation  Polyethylene glycol administered continuously through NG tube for 4-12 hours or more  May be useful in following situations  DR or EC drug formulations  Substances that are not adsorbed by activated charcoal  Emesis, abdominal cramps, and intestinal bloating have been reported  Contraindications its É  Ileus, bowel perforation or obstruction, GI bleed, gopenly Dipiro 11th ed. Chapter 7. intractable emesis y Is GI Enhancing Elimination 1  Multiple dose activated charcoal (MDAC): “charcoal intestinal dialysis”  Enhance passage of drugs from the bloodstream into e the gastrointestinal tract and subsequent adsorption  May be useful for life-threatening ingestions of carbamazepine, dapsone, phenobarbital, quinine, theophylline it path  Dose: Fyn  Adult: 50-100 g followed by 25-50 g every 4 hours  Until serious symptoms abate, or the serum concentration of the toxin is below the toxic range Dipiro 11th ed. Chapter 7.; Lexicomp: Activated Charcoal Enhancing Elimination 2  Urine alkalinization (to achieve a urine pH of 7.5 or greater)  Toxic ingestion of weak acids (salicylates/phenobarbital)  “Trapping” ionized drug in renal tubule and minimizing reabsorption  Achieved by IV administration of sodium bicarbonate  1-2 mEq/kg (mmol/kg) bolus followed by Fs  Infusion of 100-150 mEq (mmol) in 1 L of D5W at 1.5- 2 times the rate of maintenance fluid administration 3  Hemodialysis  Considered when patient is critically ill, duration of symptoms is a expected to be prolonged, and the drug is dialyzable  Low molecular weight (< 1,000 daltons)  Low protein binding (< 80%)  Small volume of distribution (< 1 L/kg) Dipiro 11th ed. Chapter 7. Common Toxidromes Toxidrome pg ornamingof miosis I constriction Clinical presentation pypist EMMA Treatment Opioid Miosis, CNS depression, ↓ RR Naloxone Sedative-hypnotic, benzodiazepines CNS depression, ↓ RR (that can lead to respiratory depression) Flumazenil (use with caution) Sympathomimetic (cocaine, amphetamines, etc.) Mydriasis, agitation, hallucination, Benzodiazepine seizures, ↑ RR, hyperthermia, tachycardia, hypertension Anticholinergic Mydriasis, agitation, hallucination, ↑ RR, hyperthermia, tachycardia, skin flushed and dry, anhidrosis tosweatnomaly Benzodiazepine Physostigmine (use with caution) Abdominal pain, N/V/D, generalized weakness, altered mental status, bronchorrhea SLUDGE symptoms  muscarinic stimulation Muscle fasciculations, muscle cramps/weakness  nicotinic stimulation Atropine Pralidoxime Bending Cholinergic I inability Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; Lexi-Tox Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. Goldfrank's Toxicologic Emergencies, 10e; 2015 Available at: http://accesspharmacy.mhmedical. com/content.aspx?bookid=1163&se ctionid=65090540 Anticholinergic Symptoms - Tip Hot as a hare (fever), dry as a bone (dry skin and mucous membranes), red as a beet (flushing), blind as a bat (mydriasis), mad as a hatter (altered mental status) Cholinergic Symptoms – Tip D: diarrhea S: salivation U: urination L: lacrimation M: miosis U: urination B: bradycardia/bronchospasm/bron -chorrhea D: diarrhea E: emesis E: emesis L: lacrimation + the Killer Bs (bradycardia/bronchospasm/bron -chorrhea) S: salivation G: GI symptoms Case  24-year-old woman presents to emergency department at night. Her father drops her off stating he was unable to wake her up. He also reported there was opened Norco bottle in the medicine cabinet. RN informs you that patient is lethargic with slow respirations. dos  Vitals: P 70; BP 110/70; RR 8; O2 sat 87% Normal 12 20perminute  PE mm no  Eyes: nonreactive, 1 mm Nomad Il  Neuro: alert but slow to respond, lethargic Case Presentation stabilize  What is your approach to this patient? supportiveare evaluate prevent Antidote  What toxic syndrome does this patient present with? opcode  Signs/symptoms that supports your clinical judgment? miosis RB asdepression lethargic  What medication(s) can cause this? NOV CO  What is the treatment for this toxic syndrome? Naloxone Nayan maintainairwayoxygen Activatedcharcoal so opiodsoverdose NOIgenerallyadministedtoadultptwesuspected Naloxone  Competitive opioid receptor antagonist  Goal of therapy: reverse respiratory depression  Potential to precipitate withdrawal in addicted patient  give lower initial naloxone dose  Starting dose: 0.04 mg-2 mg IV x 1 and titrate to effect  If no response is observed after 10 mg total, consider other causes 2 of respiratory depression  Duration of naloxone’s effect is generally shorter than many opioids, such as methadone and extended-release formulations, and requires close monitoring and repeated administration  May need to consider continuous infusion: two-thirds (2/3) of the initial effective naloxone bolus given on an hourly basis Dipiro 11th ed. Chapter 7.; Lexicomp: Naloxone Case  22-year-old male is brought to ED by the campus police. Patient was found intoxicated along with empty bottle of lorazepam by his side. He recently broke up with his girlfriend and wanted to commit suicide. He has slurred speech and ataxic gait. Currently he is able to protect his instability and airway. Yid  Vitals P 80; BP 120/78; RR 12; O2 sat 94% (room air) Case Presentation  What is your approach to this patient? stabilizePt UABI oxygen ifneeded  What toxic syndrome does this patient present with? sedative hypnotic i B2d Benzodiazepines  Signs/symptoms that supports your clinical judgment? ReducedRB Isdepression ataxiaslurredspeech  What medication(s) can cause this? Long pomBED  What is the treatment for this toxic syndrome? maintainairway oxygen ifneeded Gideiontoiration Faerie Flumazenil  Flumazenil  MOA: competitive antagonist at benzodiazepine receptor (GABA)  Dose: 0.2 mg over 2 minutes; if the desired level of consciousness not obtained 30 seconds after dose, 0.3 mg can be administered over 3 minutes; if desired level of consciousness still not obtained, 0.5 mg can be administered over 5 minutes and repeated at 1minute intervals (usual max cumulative dose: 3 mg)  Patients with partial response at 3 mg may require additional titration up to a total dose of 5 mg (although doses >3 mg do not reliably produce additional effects)  If no response 5 minutes after a cumulative dose of 5 mg, major cause of sedation not likely due to benzodiazepines or may be due to exposure to additional CNS depressants  Onset of action: 1-2 minutes  May precipitate BZD withdrawal and seizuresMS Lexicomp; Lexi-Tox w Fiumarail havetobe contos Flumazenil  Flumazenil (cont.)  Indication  Pure BZD overdose in a non-tolerant individual who has  CNS depression, normal vital signs, normal EKG findings  Contraindications  Hypersensitivity to flumazenil, benzodiazepines, or any component of the formulation  Patients administered benzodiazepines for control of potentially life-threatening conditions (eg, control of morseizaresthatdondstopon intracranial pressure or status epilepticus) a A terown  Patients who may have ingested or are showing signs of cyclic-antidepressant overdosage Lexicomp; Lexi-Tox; Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019 Case  48-year-old male with history of poly-substance abuse presents to ED with chest pain. He presents to ED s/p cocaine abuse.  Vitals: P 140; BP 186/98; RR 22; O2 sat 100% (RA); T 40.1 C  PE subsist  Neuro: agitated  Eyes: 8 mm, reactive  CV: tachycardia  Skin: diaphoretic sweating Case Presentation stabilizetheptKABI  What is your approach to this patient? oxygenHeneeded  What toxic syndrome does this patient present with? sympathomimetic  Signs/symptoms that supports your clinical judgment? Agitation tachycardia diaphoresis HINmydaisis ingportend  What medication(s) can cause this? cocaine  What is the treatment for this toxic syndrome? maintainairway oxygen ifneeded1 supporting Treatment – Sympathomimetic Toxicity  Supportive care  Manage agitation and seizures  BENZODIAZEPINES  Hyperthermia  Cooling measures  Additional medications for seizures  Barbiturates, propofol  Chest pain  Nitroglycerin High remainsonentrolled my  Refractory HTN BP  Phentolamine (alpha 1 blocker) no Colo Atenolol BBlockers unopposed alphastimulation What blood pressure lowering agent would you avoid in this patient? Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; Lexi-Tox Case  37-year-old female presents to ED after taking 2 full bottles of Benadryl 25mg (#100 tablets in each bottle). On arrival, she is hallucinating and uncooperative with the nursing staff.  Vitals: P 130; BP 140/80; RR 18; T 38.6 C  PE  Neuro: hallucinating, not following commands Nona 29nonreactive  Eyes: 8mm,  Skin: flushed and dry  CV: tachycardic Case Presentation stabliePI CRAB  What is your approach to this patient? oxygenHeneeded  What toxic syndrome does this patient present with? Anticholinergic  Signs/symptoms that supports your clinical judgment? mydrasis flusheddry skintachycardiahallucination hypersthene  What medication(s) can cause this? Antihistamine Benadryl  What is the treatment for this toxic syndrome? maintainairwayto a ifneeded decontonation photigine 161 Physostigmine  MOA: reversible acetylcholinesterase inhibitor  Tertiary amine structure of physostigmine permits CNS penetration and differentiates it from neostigmine and pyridostigmine  Dose: 0.5-2 mg IV infused over at least 5 minutes  Rapid administration  bradycardia, seizure, hypersalivation leading to respiratory difficulty  Onset of action within minutes  Repeat a dose in 15 minutes if no effect is seen Pental P, Peterson CD: Asystole complicating physostigmine treatment of tricyclic antidepressant overdose. Ann Emerg Med. 1980;9:588-590. Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; LexiTox Physostigmine  Indication for use  Presence of antimuscarinic manifestations WITHOUT evidence of widened QRS interval  Normal QRS interval < 0.12 seconds  Physostigmine should not be administered in patients with bradycardia or widening of the QRS complex, tricyclic antidepressant intoxication, asthma, or gastrointestinal or genitourinary Eggobstruction Bus As  Continuous cardiac monitoring recommended Pental P, Peterson CD: Asystole complicating physostigmine treatment of tricyclic antidepressant overdose. Ann Emerg Med. 1980;9:588-590. Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; LexiTox Treatment  Agitation/Delirium  Benzodiazepines are appropriate initial intervention  BZDs are ineffective for reversal of delirium— therefore physostigmine is preferred over BZDs  Controlled agitation (96% vs 24%)  Reversed delirium (87% vs 0%)  Hyperthermia deteriamtagitation Gophysostigmeifproffered  Control agitation/delirium is primary Kon control Both Burns MJ, Linden CH, Graudins A, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med. 2000;35:374-81. Case  60-year-old man, who is a farmer, is brought to ED via ambulance. He was found down. Witness states he was spraying insecticides. 6855  Vitals: P 70; BP 130/80; RR 20; T 37.1 C  PE  Neuro: lethargic 4 8  Head: excessive secretions, lacrimation  Lungs: rhonchi God in  Skin: diaphoretic  GU: diarrhea t carbamates atropine supportive Cholinergic Treatment  Atropine  Muscarinic receptor antagonist  Dose: Fyi  1 to 2 mg IV bolus for mild to moderate poisoning and 3 to 5 mg IV bolus for severe poisoning with unconsciousness  Double the dose every 3 to 5 minutes until improvement is observed  Side effects: tachycardia Lexicomp; Dipiro 11th ed. Chapter 7. Cholinergic Treatment  Organophosphate-cholinesterase binding is reversible initially then becomes irreversible Pralidoxime – breaks that bond and reactivates acetylcholinesterase  Dose: 1-2 grams IV over 15-30 minutes; repeat dose in 1 hr and then every 10-12 hours as needed or 30 mg/kg IV x 1 then 8 mg/kg/hr  Caution: elevation in SBP, sudden cardiac and respiratory arrest 2/2 laryngospasm and muscle rigidity (with rapid IV administration)  Initiate ASAP for organophosphate insecticide (preferably within 36 to 72 hours of exposure) in conjunction with atropine  NOT needed for carbamate insecticide poisoning Dipiro 11th ed. Chapter 7.; Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; Lexi-Tox Acetaminophen Overdose  4 stages  Stage 1: hepatic injury not occurred yet  Nonspecific clinical findings: N/V, diaphoresis  Stage II: onset of liver injury (AST is most sensitive)  Most common within 24-36 hours  In severe overdose-AST concentration may increase in 12 hours  Stage III: maximal hepatotoxicity-most common between 72 pt most tie and 96 hours after ingestion  Fulminant hepatic failure with encephalopathy and coma  AST/ALT >10,000 is common  Stage IV: recovery phase  Most cases: AST, pH, PT and INR, and lactate are normal by 7 days Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Acetaminophen Toxicity  Toxic dose: 10 grams or 200 mg/kg  N-acetylcysteine (NAC) is an antidote for acetaminophen toxicity  Prevents toxicity by limiting the formation of NAPQI (toxic metabolite to liver)  Increases the capacity to detoxify NAPQI that is formed  In fulminant hepatic failure, NAC treats toxicity through nonspecific mechanisms that preserve multiorgan function  Should be initiated as soon as possible after 4 hours and o o not delayed past 8 hours of an acute overdose a Dipiro 11th ed. Chapter 7.; Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. if posted TO Dontnotto wait thatlong treatwi acetystine Nghaat Revised Rumack-Matthew nomogram • When acetaminophen plasma concentrations are below the nomogram treatment line, there is little risk of toxicity  acetylcysteine NOT necessary • Acetaminophen blood sample should be drawn no sooner than 4 hours after the ingestion to ensure peak concentrations have been reached I Do If Dart RC, Mullins ME, Matoushek T, et al. JAMA Netw Open. 2023;6(8):e2327739.; Dipiro 11th ed. Chapter 7 2hr0 need toretrofitI IV or PO NAC  IV NAC is recommended  Pregnant women  APAP-induced liver failure  Intractable vomiting preventing PO treatment  IV and PO routes are equally efficacious in preventing or treating acetaminophen toxicity  PO NAC is associated with greater than 20% risk of vomiting Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Duration of NAC  Treatment should be continued beyond the prescribed protocol length  If there is evidence of significant liver injury ([AST] > 1,000 IU/L, PT/INR greater than twice normal, or encephalopathy is present) or APAP metabolism is incomplete ([APAP] detectable)  21 hours IV infusion dosing (consists of 3 doses)  150 mg/kg (max 15 g) in 200 mL infused over 60 minutes  50 mg/kg (max 5 g) in 500 mL infused over 4 hours  100 mg/kg (max 10 g) in 1000mL infused over 16 hours  72 hours PO regimen (consists of 18 doses)  140 mg/kg PO x 1 then 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration Dipiro 11th ed. Chapter 7.; Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Stopping Criteria - NAC  Serum acetaminophen concentration <10 mcg/mL  INR <2  Serum transaminases are normal for the patient or, if elevated, have decreased from the peak by 25% to 50%  Patient is clinically well Lexicomp Acute Salicylate Toxicity  Clinical presentation theears ringingin  Vomiting, tachypnea, tinnitus  development of anion gap metabolic acidosis  As acidosis worsens, severe CNS symptoms develop (confusion, agitation, seizures, and coma)  Dextrose administration may reverse delirium and coma even with normal glucose levels  Laboratory evaluation  Recommended therapeutic salicylate level: 10-30 mg/dL  Tinnitus is NOT specific sign for toxicity Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Management of Acute Salicylate Toxicity  Multi-dose activated charcoal 2  Fluid replacement 3  Serum and urine alkalinization  IV sodium bicarbonate UGoal of urine pH ≥ 7.5  Systemic pH not to exceed 7.55 s  Should correct hypokalemia Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Management of Acute Salicylate Toxicity 6Dextrose administration: for all patients with altered mental status in salicylate toxicity regardless of serum glucose concentration  Administer 0.5-1 g/kg of dextrose due to altered glucose transportation and metabolism in the CNS  Dialysis  Severe salicylate poisoning, altered mental status, ARDS requiring supplemental oxygen, standard therapy deemed to be failing regardless of the salicylate concentration, salicylate concentrations above 100 mg/dL, and salicylate concentrations above 90 mg/dL with impaired renal function Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Beta Blocker Toxicity  Properties of beta blockers  Membrane stabilizing activity—inhibit fast sodium most this channels—results in widened QRS interval g Propranolol, acebutolol   Lipophilicity  Rapidly cross BBB; may cause seizures and delirium  Propranolol  Intrinsic sympathomimetic activity (ISA)  Both agonist and antagonist at the beta blocker site  Pindolol, acebutolol Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Beta Blocker Toxicity  Presentation  Symptomatic within 2 hours (all symptoms develop within 6 hours)  Does not apply to sustained release or sotalol (delayed toxicity up to 24 hours) 90166  Bradycardia and hypotension  Bronchospasm  Hypoglycemia  Altered mental status (lipophilic beta blockers) Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. atknewthisslide Beta Blocker Toxicity  Treatment  Supportive  Hypotension - IV fluid boluses  Bradycardia - atropine 0.5-1 mg IV 3-5 minutes up to 3 mg good83 p Hypoglycemia - dextrose  Seizures - lorazepam  Reverse cardiotoxic effects  IV glucagon  IV calcium  High dose insulin and glucose infusions  Lipid emulsion therapy Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. A Fyi Glucagon  Activates receptors at the site independent from beta- adrenergic agents resulting in calcium release and contraction of the heart  Dosing: ISD  2 to 10 mg bolus; if no clinical response, may repeat bolus dose after 10 to 15 minutes  Then start continuous infusion at 2-5 mg/hr (range: 1-15 mg/hr) and titrate to achieve adequate hemodynamic response  Infusion is only started if there is an increase in pulse or blood pressure after the bolus Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; Lexicomp Fyi Calcium Salts  Reversing hypotension in beta blocker and calcium channel blocker toxicity  Dose: Fyi  Various different dosages  Calcium chloride 1-2 grams over 10 minutes then 20-40 mg/kg/hr titrated to improved BP and contractility  Calcium gluconate 60 mg/kg/dose over 10 minutes then initiate 60-120 mg/kg/hr titrated to improve BP and contractility  Monitor  Hypercalcemia, irritation when infusing Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; Lexicomp Fyi High Dose Insulin and Dextrose  Theoretical mechanism  Beta blockers inhibit pancreatic insulin release which decreases available glucose for cardiac metabolism  decreased CO  Insulin appears to improve inotropic effects by being a substrate for cardiac metabolism  Dosing  Regular insulin: 1 unit/kg bolus dose, followed by an infusion of 0.51 units/kg/hr titrated to clinical response  Some studies show there is no max dose  Dextrose: 0.5 gm/kg bolus then infusion started at 0.5 gm/kg/hr  Monitor  Glucose, potassium, vital signs Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; Lexicomp Fyi Lipid Emulsion Therapy  Lipid emulsion therapy  Improving cardiac metabolism  Dosage for lipid emulsion 20%  Bolus: 1.5 mL/kg IV over one minute  Infusion: 0.25 mL/kg/minute over 1 hour  Adverse effects  Elevated triglycerides, pancreatitis  Pulmonary toxicity  Fat overload syndrome Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; Lexicomp Calcium Channel Blocker Toxicity  Two types of calcium channel blocker  Dihydropyridines  Potent vasodilators with very little effect on contractility  Amlodipine, nifedipine, felodipine  Non-dihydropyridines  Decrease contractility and cardiac conduction  Diltiazem and verapamil Dipiro 12th ed. Chapter 8.; Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Supper awol Calcium Channel Blocker Toxicity 3has yinsulinidot slipid  Presentation  General: Life-threatening cardiac toxicity (bradycardia, depressed contractility, and dysrhythmias) within 1 to 3 hours of ingestion, delayed by 12 to 18 hours if a sustained-release product is involved  Symptoms:  Nausea and vomiting within 1 hour  Dizziness, lethargy, and coma within 1 to 3 hours (mental status may be preserved in absence of significant hypotension) Dipiro 12th ed. Chapter 8.; Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Calcium Channel Blocker Toxicity  Presentation (cont.)  Signs:  Hypotension and bradycardia within 1 to 6 hours  Unresponsiveness and depressed reflexes within 1 to 6 hours  Atrioventricular block, intraventricular conduction defects, and ventricular dysrhythmias on ECG Dipiro 12th ed. Chapter 8.; Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Calcium Channel Blocker Toxicity  Treatment I  Supportive care similar to beta blockers toxicity  One difference: patient are usually hyperglycemic  IV calcium 2  Usually given first (or concomitant with early fluid resuscitation)  IV glucagon  No longer recommended for calcium channel blocker overdose 3  Vasopressors (norepinephrine  others) a High dose insulin and dextrose infusion g Lipid emulsion therapy  Can be considered in refractory cases Dipiro 12th ed. Chapter 8.; Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Iron Overdose  Children are usually attracted to sweet taste of the chewable gummies  Chewable gummies contain less iron than prenatal vitamins (10-15 vs. 65 mg elemental)  Toxic ingestion dose: greater than 20 mg/kg  Clinical presentation: nonspecific GI symptoms to tachycardia, metabolic acidosis, lethargy, hypovolemia, shock, seizures, hepatic failure  Iron levels > 500 ng/mL Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; Lexicomp Deferoxaminegantigforgeose  Deferoxamine binds with the excess iron and forms ferrioxamine, which is excreted by the kidney—resulting in urine color change  Dose (IV): 5 mg/kg/hr titrate every 15 min up to 15 mg/kg/hr (different dosing than manufacturer) O  Side effects  Rate-related hypotension  Pulmonary toxicity  Tachycardia Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; Lexicomp Digoxin Toxicity  Pharmacology  Cardiac glycosides inhibit the sodium-potassium-ATPase, causing an increase in intracellular sodium and a decrease in intracellular potassium  Intracellular increase of sodium leads to intracellular increase of calcium  assists with contractility  Presentation  Bradycardia, abdominal pain (GI side effects), neurological defects (confusion, visual disturbances)  Labs: digoxin level, basic metabolic panel  EKG: arrhythmias Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019. Digoxin Toxicity  Treatment  DigiFab- binds to digoxin and excreted by the kidneys and removed from the body  Dosage: each vial of DigiFab containing 40mg binds to 0.5mg of digoxin  Based on number of tablets ingested:  Total body load (mg) = 0.8 x (amount (mg) digoxin tablets ingested)  DigiFab dose (vials) = total body load (mg)/0.5  Based on level:  Dose (vials)=[(serum digoxin level (ng/mL) X weight (kg)]/ 100  Empiric (unknown amount ingested): 10-20 vials Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank's Toxicologic Emergencies, 11e. McGraw Hill; 2019.; Lexicomp DigiFab Indication  Treatment of life-threatening or potentially life- threatening digoxin intoxication, including:  Acute digoxin ingestion (≥10 mg in adults; 4 mg [>0.1 mg/kg] in children); resulting in serum concentration ≥10 ng/mL)  Chronic ingestion leading to steady state digoxin concentrations >6 ng/mL in adults or >4 ng/mL in children  Manifestations of life-threatening digoxin toxicity due to overdose (severe ventricular arrhythmias, progressive bradycardia, second- or third-degree heart block not responsive to atropine, serum potassium concentration >5.5 mEq/L in adults or >6 mEq/L in children) Lexi-Tox Let’s Practice  Patient (72 kg) presents to ED with N/V, abdominal pain, and confusion. EMT states they found a bottle of digoxin that was filled yesterday with 3 tablets left (label reads “digoxin 125mcg PO daily #90”) T omg tooomg he IS 125 X 1000  PMH: heart failure, atrial fibrillation 1257  Labs: digoxin 16 ng/mL, SCr 4 (baseline 1.1) Total bodyloadangle o.nl mglldigoItgbingested 0.8 or12SmgXEtab 87 Vial TotalBody 0 e f in X 90 3 if vial o isms 81tab Let’s Practice  How many DigiFab vials are needed (based on amount ingested and based on level)? Exod Additional Antidotes Antidote Indication Levocarnitine Valproic acid- or topiramateinduced hyperammonemia Fomepizole (preferred), ethanol (second line) Toxic alcohols (ethylene glycol, methanol) Sodium nitrite + sodium thiosulfate Hydroxocobalamin Cyanide toxicity Leucovorin Methotrexate 3 Methylene blue Methemoglobinemia Octreotide Sulfonylurea-induced hypoglycemia Pyridoxine (vitamin B6) Isoniazid toxicity 4 0 Pet