AntiDos and Donts Craig Smollin MD Associate Medical Director, - PDF document

Anti’Dos and Don’ts Craig Smollin MD Associate Medical Director, California Poison Control Center, San Francisco Assistant Professor of Emergency Medicine, University of California, San Francisco I. Background: The most common interventions in acute poisoning are (1):  Decontamination  Intravenous Fluids  Supplemental oxygen First and foremost the acutely poisoned patient needs GOOD SUPPORTIVE CARE. However, the emergency physician will be called upon to use a number of different antidotes. Which specific antidotes should the emergency physician be most familiar with? A paper published by Dart et. al. (2) provides some guidance on this issue. Based on a review of the current literature, this group of experts considered 24 different antidotes of which they recommended that 12 be available for immediate use. These antidotes are listed in Table 1 . The following 4 cases illustrate the use of several of these antidotes: I. A problem of persistent hypoglycemia A 57 year-old male with a h/o benzodiazepine use presents after found by EMS with altered mental status. Initial GCS in the field was reported as 11. Upon arrival in the ED he is confused and ataxic with slurred speech. He is noted to be mildly hypertensive, tachycardic and he has diaphoresis. Initial vital signs = BP 159/96, P 105, RR 20, 97% on RA Initial finger stick glucose = 41 mg/dL The patient receives 1 amp of D50 with improvement in his GCS to 14. He confirms that he has no h/o diabetes and did not overdose on any medications. We will consider and answer the following questions: (see below for answers and references) What are the signs and symptoms of hypoglycemia? What drugs and toxins are commonly associated with hypoglycemia? Why do you think this patient developed hypoglycemia?

What are the treatment options and is there a specific antidote that you would use to treat this patient? II. An overdose of an unusual Rat Poison A 29 year-old male presented to the ED after a suicide attempt by ingesting a large amount of rat poison. In the ED the patient was diaphoretic and in respiratory distress. Initial vital signs were BP 113/99, P 100, RR 28, and O2 sat 88% on RA. Physical exam is significant for profound diaphoresis, diffuse rhonchi throughout both lung fields, tachycardia, urinary incontinence and muscle fasciculations. We will consider and answer the following questions: What toxins have been used as rodenticides? Which ones are more commonly used? What “toxidrome” does this patient exhibit? Do you need to know the specific drug ingested in order to treat this patient? Which antidotes are used in the treatment of this poisoning? What is the endpoint of therapy? III. An overdose of an antihypertensive medication A 45 year-old female with a history of depression presents 1 hour after a large ingestion of her antihypertensive medications. On arrival she is somnolent but arousable and has a GCS of 14. Initial vital signs are BP 83/50, HR 65, RR 18, O2 sat 98% RA. Initial finger stick glucose = 235 (there is no history of diabetes). We will consider and answer the following questions: What is the toxicology differential diagnosis of a patient with hypotension and bradycardia or relative bradycardia? What is the significance of hyperglycemia in this setting? Which antidotes would you consider giving to this patient? What is high dose insulin euglycemia therapy (HIET)? IV. A blue patient A 34 year-old HIV positive woman presents with a complaint of feeling light headed, nauseated and short of breath. Vital signs were BP 124/88, P 116, RR 18, and O2 sat 82% on NRB mask. She was in no respiratory distress, but appeared to have a blue discoloration of the lips, gums, face and peripherally in the digits and nail beds. The rest of the exam was unremarkable. ABG = pH 7.44, pCO2 31, pO2 307, Sat 98%, Lactate 1.0 We will consider and answer the following questions:

What is the differential diagnosis of the blue patient? What does “cyanosis” with a normal pO2 suggest? A diagnostic test was performed….what was it? Which drugs and toxins are associated with this condition? What is the antidote, and what are the potential complications of its administration?

ANSWERS AND REFERENCES Case I. What are the signs and symptoms of hypoglycemia? Autonomic Neuroglycopenic • Tremor • Dizzy/lightheaded • Tachycardia • Confusion • Sweating • Ataxia • Pallor • Blurred vision • Weakness • Paresthesias • Nausea • Focal neuro deficit • Hunger • Seizures • Palpitations • Coma Drugs and toxins commonly associated with hypoglycemia: Insulin, sulfonylureas, pentamidine, aspirin, beta blockers, alcohol, ackee fruit, valporic acid, quinine, and vacor. Why do you think this patient developed hypoglycemia? This patient was exposed to a sulfonylurea. What are the treatment options and is there a specific antidote that you would use to treat this patient? Both oral and IV have both been used to treat hypoglycemia. Octreotide has been shown to be effective in the management of patient with persistent hypoglycemia secondary to sulfonylurea overdoses (See the following reference for an excellent review of the use of this antidote - 3). Key pearls in sulfonylurea overdose (1) Duration of hypoglycemia of some sulfonylureas may be up to 72 hours. (2) A single tablet of glipizide or glyburide can cause symptomatic hypoglycemia in infants or toddlers. (3) Risk factors include young age, malnutrition, alcohol use and kidney disease.

Case II. What toxins have been used as rodenticides? Which ones are more commonly used? Currently in the united states, the superwarfarins are used in rat poison. Patients will typically present asymptomatically with a dramatically elevated INR, or they may present with acute bleeding. However there are numerous different toxins that have been used in the past or that are currently used in other countries, many of which have serious poisoning potential. List of selected toxins used in rat poison:  “super” warfarin  Phosphides  Strychnine  Vacor  Arsenic  Bromethalin  Sodium fluoroacetate  Tetramine What “toxidrome” does this patient exhibit? Cholinergic or “SLUDGE” syndrome Do you need to know the specific drug ingested in order to treat this patient? No. Once the cholinergic toxidrome is identified, treatment with atropine and pralidoxime should be initiated immediately. Which antidotes are used in the treatment of this poisoning? What is the endpoint of therapy? Mainstays of therapy in the treatment of organophosphate and carbamate toxicity:  Special attention to airway and breathing o Intubation o Administration of atropine (2 mg q 5 min in adults) o Pralidoxime  Rigorous intravenous hydration  Decontamination

Case III. What is the toxicologic ddx of patients with hypotension and bradycardia or relative bradycardia? Calcium channel blockers, beta blockers, digoxin toxicity, clonidine, organophosphates or carbamate poisoning, hyperkalemia. What is the significance of hyperglycemia in this setting? Because inhibition of calcium channels in the pancreas results in decreased release of insulin, hyperglycemia is suggestive of acute calcium channel blocker toxicity. In addition, hyperglycemia in acute CCB overdose may be predictive of a severe toxicity (4). Which antidotes would you consider giving to this patient? Intravenous fluids, boluses of calcium, glucagon, vasopressors and pacing have all been used and would all be appropriate to consider in this situation. However, high dose insulin, euglycemic therapy (HIET) has been demonstrated in animals to be more effective (5). There are many case reports in the literature as well suggesting its improved efficacy in humans. What is high dose insulin euglycemia therapy (HIET)? How does it work? HIET regimen: Bolus of Regular Insulin 1U/kg followed by infusion at 0.5-1.0 U/kg/h. Give 25 grams (50cc of D50W) initially and monitor glucose frequently to prevent hypoglycemia. Monitor serum K and replace as needed Proposed Mechanism: CCB overdose induces insulin deficient state. Inhibition of glucose uptake by heart may be cause of toxicity. HIET may reverse these metabolic derangements (5). Note that there are no randomized controlled trials in humans.