Toxicological Emergencies Zohair A. Al Aseri MD, FRCPC EM & CCM Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Objectives History and Physical Examination Urine Drug Screens Toxicology Screening Three gaps to look at Coma Cocktail ??????? Treatment Decontamination Enhanced Elimination ICU Admission Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM History and Physical Examination Difficulties No reliable history in patients with profoundly altered metal status Focused treatment decisions quite difficult. Multiple substances Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM History and Physical Examination Toxidromes Separating patients who have suspected poisoning into broad categories that are based on vital signs, eye findings, mental status, and muscle tone helps to determine drug or toxin class “toxidromes.” Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM History and Physical Examination Treat Toxidrome Yes No vital signs ocular findings mental status muscle tone determine drug or toxin class Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM History and Physical Examination Physical examination A rapid but careful physical examination of the patient is performed in stages. Initially, a rapid survey for CABs & life-threatening nature Then, a more focused examination for Signs of trauma Neurologic findings Skin changes Odors Eyes Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM History and Physical Examination Physical examination Patients may present with hypotension or hypertension bradyarrhythmias or tachyarrhythmias. The pathogenesis of hypotension varies and may include Hypovolemia Myocardial depression Cardiac arrhythmias Systemic vasodilation. Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM History and Physical Examination WITHDRAWAL Can be confused with acute intoxication, particularly when there is lack of historic data on the patient's prior substance use. The clinical signs and symptoms most often requiring treatment are agitation and seizures. Both treated most effectively with benzodiazepines. Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Odor Possible source Bitter Almonds Cyanide Carrots Cicutoxin (water hemlock) Fruity Diabetic ketoacidosis, isopropanol Garlic organophosphates, arsenic, dimethyl sulfoxide (DMSO), selenium Gasoline Petroleum distillates Mothballs Naphthalene, camphor Pears Chloral hydrate Pungent aromatic Ethchlorvynol Oil of wintergreen Methylsalicylate Rotten eggs Sulfur dioxide, hydrogen sulfide Freshly mowed hay Phosgene Odors that suggest the diagnosis Zohair AL Aseri FRCP EM & CCM

Agents causing an elevated anion gap (METAL ACID GAP) Methanol, metformin, massive overdoses Ethylene glycol Toluene Alcoholic ketoacidosis Lactic acidosis Acetaminophen (large overdoses) Cyanide, carbon monoxide, colchicine Isoniazid, iron, ibuprofen Diabetic ketoacidosis Generalized seizure-producing toxins Acetylsalicylic acid or other salicylates Paraldehyde, phenformin Zohair AL Aseri FRCP EM & CCM

Agents increasing the osmolar gap (ME DIE) Methanol Ethylene glycol Diuretics (mannitol), Diabetic ketoacidosis (acetone) Isopropyl alcohol Ethanol Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Common Toxidromes Cholinergic (Examples: organophosphates, carbamates, pilocarpine) (DUMBELLS) Diarrhea, diaphoresis Urination Miosis Bradycardia, bronchosecretions Emesis Lacrimation Lethargic Salivation Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Common Toxidromes Anticholinergic (Examples: antihistamines, cyclic antidepressants, atropine, benztropine, phenothiazines, scopolamine) Hyperthermia (HOT as a hare) Flushed (RED as a beet) Dry skin (DRY as a bone) Dilated pupils (BLIND as a bat) Delirium, hallucinations (MAD as a hatter) Tachycardia Urinary urgency and retention Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Common Toxidromes Sympathomimetic (Examples: cocaine, amphetamines, ephedrine, phencyclidine, pseudoephedrine) Mydriasis Tachycardia Hypertension Hyperthermia Seizures Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Common Toxidromes Opioid (Examples: heroin, morphine, codeine, methadone, fentanyl, oxycodone, hydrocodone) Miosis Bradycardia Hypotension Hypoventilation Coma Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Antidote Indication (agent) n-acetylcysteine Ethanol/fomepizole (4-MP) Oxygen/hyperbarics Naloxone/nalmefene Physostigmine Atropine/pralidoxime (2-PAM) Methylene blue Nitrites Deferoxamine Dimercaprol (BAL) Succimer (DMSA) Fab fragments Glucagon Sodium bicarbonate Calcium/insulin/dextrose Dextrose, glucagon, octreotide Acetaminophen Methanol/ethylene glycol Carbon monoxide Opioids Anticholinergics Organophosphates Methemoglobinemia Cyanide Iron Arsenic Lead, mercury Digoxin, colchicine, crotalids Beta-blockers Tricyclic antidepressants Calcium channel antagonists Oral hypoglycemics Antidotes and their indications Zohair AL Aseri FRCP EM & CCM

Toxins accessible to hemodialysis (UNSTABLE) Uremia No response to conventional therapy Salicylates Theophylline Alcohols (isopropanol, methanol) Boric acid, barbiturates Lithium Ethylene glycol Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Urine Drug Screens Detect only natural opiates Do not detect synthetic or semisynthetic products morphine codeine heroin Oxycodone Hydrocodone Fentanyl Propoxyphene Meperidine methadone. Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Urine Drug Screens Ferric Chloride Test Installation of several drops of 10% ferric chloride into 1 to 2 mL of the patient's urine. A purple color indicates the possibility of salicylate use. A negative test in a previously healthy adolescent with normal kidneys is strong evidence of no recent salicylate use. Positive tests indicate the possible presence of salicylate and do not correlate with toxicity Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Urine Drug Screens Routine use of rapidly (meaning a few hours) available drug or coma urine screens have little use in the acute management of the overdose patient. Zohair AL Aseri FRCP EM & CCM

Urine Drug Screens, issues…….. Most assays rely on the antibody identification of drug metabolites some drugs remain positive days after use and may not be related to the patient's current clinical picture. The positive identification of drug metabolites likewise is influenced by chronicity of ingestion fat solubility Coingestions. Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM URINE FLUORESCENCE Fluorescence was reliably identified 100% of the time in the samples collected in the first 2 hours after ingestion of ethylene glycol. Reliability decreased with time to 60% by 2 to 4 hours and 20% by 4 to 6 hours. not detected after 6 hours limited diagnostic utility. Winter M.L., Ellis M.D., Snodgrass W.R.,  Urine fluorescence using a Wood's lamp to detect the antifreeze additive sodium fluorescein: a qualitative adjunctive test in suspected ethylene glycol ingestions.   Ann Emerg Med (1990) 19 : pp 663-667. Zohair AL Aseri FRCP EM & CCM

Supportive serum toxicology assays Acetaminophen Lithium Salicylate Valproic acid Carbamazepine Co-oximetry (carboxyhemoglobin, methemoglobin) Digoxin Phenobarbital Iron Ethanol Methanol Ethylene glycol Theophylline Data from Wu AH, McKay C, Broussard LA, et al. National Academy of Clinical Biochemistry Laboratory Medicine practice guidelines: recommendations for the use of laboratory tests to support poisoned patients who present to the emergency department. Clin Chem 2003;49:357–79. Skelton H., Dann L.M.,  et al.   Drug screening of patients who deliberately harm themselves admitted to the emergency department.   Ther Drug Monit (1998) 20 : pp 98-103.   Zohair AL Aseri FRCP EM & CCM

Three gaps are important in toxicology: Anion gap Osmolal gap Oxygen saturation gap Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Anion Gap An increase in the anion gap to greater than 20 mEq/L strongly suggests an organic acidosis. Zohair AL Aseri FRCP EM & CCM

Agents causing an elevated anion gap (METAL ACID GAP) Methanol, metformin, massive overdoses Ethylene glycol Toluene Alcoholic ketoacidosis Lactic acidosis Acetaminophen (large overdoses) Cyanide, carbon monoxide, colchicine Isoniazid, iron, ibuprofen Diabetic ketoacidosis Generalized seizure-producing toxins Acetylsalicylic acid or other salicylates Paraldehyde, phenformin Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Osmolal Gap Low-molecular-weight drugs and toxins increase the discrepancy between measured and calculated plasma osmolality. Normal plasma osmolality is 285 to 295 mOsm. Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Osmolal Gap Pitfalls Measurement of osmolality by vapor pressure osmometry does not detect volatile alcohols such as ethanol and methanol Freezing point depression osmometry, measures all of these solutes Osmolal gap of 10 mOsm in a patient who started at − 9 mOsm may be significantly elevated With time the osmotically active parent compound will be metabolized to the acidic metabolites. Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Oxygen Saturation Gap Three ways to measure the oxygen saturation Co-oximetry Arterial blood gas Pulse oximetry Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Oxygen Saturation Gap 5% difference between the saturation calculated from an arterial blood gas and the saturation measured by co-oximetry. Toxins that are associated with an elevated oxygen saturation gap include Co-oximetry determines oxygen saturation by detecting the absorption of four different wavelengths, enabling it to directly measure levels of four types of hemoglobin species: oxyhemoglobin, reduced hemoglobin, carboxyhemoglobin, and methemoglobin. arterial blood gas analysis calculates oxygen saturation from the measured oxygen tension using an assumed standard oxygen-hemoglobin dissociation curve. Pulse oximetry estimates oxygen saturation by emitting a red light (wavelength of 660 nm) absorbed mainly by reduced hemoglobin and a near-infrared light (wavelength of 940 nm) absorbed by oxyhemoglobin Carbon monoxide Methemoglobinemia Cyanide Hydrogen sulfide Zohair AL Aseri FRCP EM & CCM 30

Zohair AL Aseri FRCP EM & CCM Oxygen Saturation Gap CO has a wavelength absorption coefficient similar to that of oxyhemoglobin; therefore, it is registered as oxyhemoglobin by pulse oximetry leading to overestimation of oxygen saturation when compared to co-oximetry. Abnormally high venous oxygen content (arteriolization of venous blood) is characteristic of cyanide and hydrogen sulfide poisoning. Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM GENERAL TREATMENT CABs. Protection of the cervical spine (unless trauma has been excluded). A rapid assessment of the need of endotracheal intubation Attention to any abnormalities of the vital signs. Discontinuing the offending Any life-threatening abnormalities A 12-lead EKG is obtained along with continuous cardiac monitoring. ABG Zohair AL Aseri FRCP EM & CCM

Initial supportive measures Endotracheal intubation is indicated when there is concern regarding airway protection and clinical deterioration acute respiratory failure. the need for high levels of supplemental oxygen It decreases (but does not eliminate) the risk of aspiration (which is approximately 11% in the comatose patient with drug overdose). Zohair AL Aseri FRCP EM & CCM

Initial supportive measures Rapid IV normal saline solution infusion is indicated in most instances. Vasopressors may be required for refractory hypotension. The vasopressor of choice depends on the type of intoxication Hypertension-induced (reflex) bradycardia generally should not be treated. Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Hemodialysis Toxins Characteristics low molecular weight (< 500 d) water soluble low protein binding (< 70 to 80%) small volume of distribution (< 1 L/kg). It can especially be effective in correcting concomitant electrolyte abnormality and metabolic acidosis. I,e: methanol, ethylene glycol, boric acid, Salicylates lithium. Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM SUMMARY It is important to recognize that there is a paucity of evidence-based information on the management of poisoned patient. Vital sign in toxicology add: abg, ecg, anion. osmolar and o saturation gap Supportive treatment and ABCs management Decontamination Limit the use of screening tesating The results of the tests should be reviewed in the context of the clinical scenario. Zohair AL Aseri FRCP EM & CCM

Zohair AL Aseri FRCP EM & CCM Thank You ??????? Zohair AL Aseri FRCP EM & CCM