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General Approach to the Poisoned Patient. Presented by Dr. Levy Prepared by Dr. Trey Woods D.O. PGY1 Emergency Medicine Residency St. JosepH Health Center Warren Ohio. Why do we discuss toxicology?. In practice, toxicology makes up 5-30% of your cases
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General Approach to the Poisoned Patient • Presented by Dr. Levy • Prepared by • Dr. Trey Woods D.O. PGY1 • Emergency Medicine Residency • St. JosepH Health Center • Warren Ohio
Why do we discuss toxicology? • In practice, toxicology makes up 5-30% of your cases • Inservice and written boards, about 8% • Oral boards, about 15%
Poison facts • >2 million toxic exposures per year • More than half of exposures, <6 yoa • Toxin-related deaths on the rise
Objectives • Supportive care is main means to decrease morbidity and mortality • Learn about gastric decontamination • Learn and know all antidotes • Know toxidromes and treatment
General ApproachABC’s of Toxicology • A-Antidotes and alter absorption (in some instances prior to airway-decontamination with organophosphates to protect others, cyanide toxicity where antidotes are lifesaving) • B-Basics; ABC’s • C-Change metabolism (NAC, ethanol) • D-Distribute differently (calcium gluconate, O2) • E-Elimination (diuresis, dialysis, hemoperfusion)
TOXIDROMES • A. Introduction • 1. “Physiologic fingerprints” that occur in the form of syndromes or groups of symptoms which are observed to occur together in response to exposure to one of a pharmacologically similar group of agents • 2. Useful in determining the class of agents involved in an unknown poisoning • 3. Result of receptor interaction or neurotransmitter release leading to stimulation or inhibition of the different divisions of the autonomic nervous system
Sympathetic or sympathomimetic • Agents: cocaine, phencyclidine, ephedrine/pseudoephedrine, theophylline, amphetamines, LSD, phenylpropanolamine, caffeine • 2. Presentation: mydriasis, tachycardia, hypertension, hyperthermia, diaphoresis, seizure, central nervous system (CNS) excitation • Similar to withdrawal toxidrome • Similar to anticholinergic toxidrome except: • Diaphoresis and normal bowel sounds with sympathomimetic toxidrome • Dry skin and absent bowel sounds with anticholinergic toxidrome
Cholinergic-Toxidrome (Muscarinic) • Agents: organophosphates and carbamate insecticides, pilocarpine, some species of mushroom, carbachol, acetylcholine, betel nut • 2. Presentation: DUMBBELS • D-Diarrhea U-Urination M-Miosis B-Bronchorrhea B-Bradycardia E-Emesis L-Lacrimation S-Salivation
Cholinergic Toxidrome (Nicotinic) • Agents: organophosphate/carbamate insecticides, tobacco, Indian tobacco, Black widow spider venom • 2. Presentation: tachycardia, hypertension, muscle fasciculations, muscle weakness
Anticholinergic Toxidrome • Agents: belladonna alkaloids (atropine), Jimson weed, tricyclic antidepressants, antihistamines, phenothiazines, scopolamine, some species of mushroom, anti-motility agents, over-the-counter sleeping aids • 2. Presentation: “red as a beet (flushing), dry as a bone (dry skin), mad as a hatter (delirium, hallucinations), hot as Hades (hyperthermia), blind as a bat (mydriasis).” Also see hypertension, tachycardia, urinary retention, absent bowel sounds, seizures
Narcotic Toxidrome • Agents: codeine, lomotil, heroin, propoxyphene, pentazocine, meperidine, hydrocodone, methadone, fentanyl, “China White” • 2. Presentation: coma, hypotension, miosis, hypoventilation
Withdrawal Toxidrome • Cause: abrupt termination of various agents, including: ethanol, narcotics, benzodiazepines, barbiturates, chloral hydrate, other sedative-hypnotics • 2. Presentation: diarrhea, piloerection, lacrimation, crampy abdominal pain, hallucinations, mydriasis, tachycardia, hypertension, yawning, seizure (ethanol, benzodiazepine, barbiturate). Similar to sympathetic toxidrome
Decontamination • Eye: irrigate with normal saline for 15 - 20 minutes • Don’t forget skin! Remove clothes, wash skin with soap and water (Organophosphates, HFl acid) • HAZMAT may be necessary
Eyes • Should be treated IMMEDIATELY, copious irrigation • Usually 2L with NS • Can take up to 2 hours for alkali exposure to get the tears to neutralize to ph <8
To lavage or not? • Controversial • Indicated for recent ingestions<1hr or particularly toxic substances like TCA’s • Do not use in a sleepy patient unless intubated
Gastrointestinal decontamination: perform if within 1 hour of ingestion • 1. Consider the following when making decision to empty • Toxin and the amount • Is the ingestion toxic? • Clinical course since ingestion? • Time since ingestion (In general, little affect after 1 hour) • History of vomiting • Presence of agent in stomach (Iron) • Benefit vs risk • Is the agent bound by activated charcoal?
Gastric lavage • Large bore orogastric tube (36 - 40 F) Place patient in left lateral decubitus position • Infuse 250 cc aliquots of saline, drain, repeat until clear (at least 2 liters) • Remember airway protection • Complications: aspiration, esophageal rupture, epistaxis, hypothermia
GI contamination • Charcoal-now procedure of choice if appropriate substance. Major risk is aspiration. • May use NG/OG tube or give orally. If giving orally, assure patient is awake and airway protected.
Multi-dose Charcoal • Used with some select drugs • Used to interrupt enterohepatic recirculation. • Do not use sorbitol with MDAC • Useful for: carbamazapine, theophylline, barbituates, salicylates, dapsone, depakote, digoxin, quinine, phenytoin
GI contamination-when charcoal doesn’t work • C-Caustics • H-Hydrocarbons • A-Alcohols • I-Iron • L-Lithium • L-Lead(and other heavy metals)
whole bowel irrigation • Polyethylene glycol electrolyte solution is instilled at a rate of 2 L/hr until the rectal effluent is clear. Often requires nasogastric (NG) placement for administration
Consider whole bowel irrigation for: • Drugs where charcoal can not be used • Sustained release preparations • Heavy Metals • Body packers (stuffers) • Iron • Lithium • Large quantities of toxic substances
Are any lab values helpful? • ECG • Chem 7 • Acetaminophen level, ASA, ETOH • Serum osmolality • VBG (determine pH)
Useful lab values • Calculate the anion gap • AG=Na-(HCO3+Cl) • Causes anion gap: • AT MUDPILES (alcohols, toluene, methanol, paraldehyde/phen phen, iron/INH, lactic acidosis, ethylene glycol, salicylates/strychnine)
Useful lab values • Osmolar gap=measure serum osmolality-calculated serum osmolality • Calculated=2Na+glucose/18+BUN/2+ethanol/6 • Causes Osmolar Gap: • ME DIE (methanol, ethanol, diuretic, isopropyl, ethylene glycol)
Drugs to Dialyze-ISTUMBLE • I-Isopropanol • S-Salicylates • T-Theophylline • U-Urea • M-Methanol • B-Barbituates • L-Lithium • E-Ethylene glycol
Elimination enhancement • Alkalinization of the urine • Mechanism: promotes excretion of weak acids by “ion trapping” in the renal tubules • Administer intravenous sodium bicarbonate to increase urinary pH to 7.5 - 8 • Uses • 1 - 2 mEq/kg bolus followed by infusion of 3 amps of NaHCO3 in 1 L of D5W at 1.5 - 2 times maintenance • Keep serum pH < 7.55 • Useful: Phenobarbital, salicylates
Antidotes • Iron-deferoximine • Nitrites-methylene blueOrganophosphates-atropine,pralidoxime (2-PAM)Opioids-naloxonePhenothiazines-diphenhydramine,BenzotropineIsoniazid (INH)-pyridoxineDigoxin/Oleander-Digitalis Fab fragments • Acetaminophen-NAC • Arsenic-BAL • Mercury-BAL • Lead-Dimercaprol, EDTA • Carbon monoxide-O2, hyperbaric in severe/pregnant • Cyanide-amyl nitrite OR sodium nitrite, sodium thiosulfate • Ethylene glycol/methanol-ethanol, fomepizole
Tricyclic Antidepressants • 25 MILION ANNUAL PRESCRIPTIONS • 75% OF FATALITIES AWAKE/ALERT AT SCENE! • 23% OF SEIZURES OCCUR IN THE INITIAL AWAKE AND ALERT PATIENT.
TCA Pathophys • MUSCARINIC ANTICHOLINERGIC SYNDROME • TACHYCARDIA, MYOSIS, AGITATION,HOT/DRY SKIN, ETC... • NA+ CHANNEL BLOCKADE • WIDE QRS, PR PROLONGATION – NEGATIVE INOTROPY – INCREASED AUTOMATICITY • K+ CHANNEL BLOCKADE • PROLONGED QT TACHYCARDIA PROTECTIVE • TORSADES DE POINTES
TCA Pathophys • AMINE RE-UPTAKE INHIBITION • – NE>SEROTONIN>DOPAMINE • – REASON FOR POOR RESPONSE TO DOPAMINE • GABA BLOCKADE • CONTRIBUTES TO SZ’S • ALPHA 1&2 BLOCKADE • HYPOTENSION • REFLEX TACHYCARDIA – MIOSIS
TCA clinical Features • CNS • AGITATION <---------------->COMATOSE • GCS<8 POOR PROGNOSIS, SZ’S (10 %), PUPILS USUALY DILATED* • CNS FINDINGS PRIMARILY • SECONDARY TO ANTICHOLINERGIC EFFECTS
TCA clinical Features • CARDIOVASCULAR • TACHY----------------->BRADY • HYPOTENSION • QRS WIDENING • ARRYTHMIAS • QT PROLONGATION->TORSADES OTHER • OTHER • SKIN, GI, GU
TCA Management • ABC’S • (AGGRESSIVE AIRWAY MGMT) • DECONTAMINATION & AC • HYPERVENTILATION • SODIUM BICARBONATE (1-2 mEq/kg) • ALTERED LOC – WIDE QRS, AV BLOCKS • PRESSORS • EPINEPHRINE DRIP IS BEST DOPAMINE (PARADOXICAL HYPOTENSION
Serotonin Syndrome • Pathophysiology • Excessive stimulation of serotonin 5HT1A receptors • Idiosyncratic reaction • Causes • SSRIs alone or in combination with other serotoninergic agents • First described with MAO inhibitors • Beware of meperidine
Serotonin Syndrome • Diagnosis • Altered mental status, autonomic instability (fever), neuromuscular abnormalities (rigidity), Ping-pong gaze? • GI –NAUSEA, SALIVATION,DIARRHEA, ABD CRAMPS • SKIN – DIAPHORESIS, PILOERECTION – FLUSHED SKIN, HYPERPYREXIA • Complications RHABDOMYOLYSIS, SEIZURES, ASPIRATION • Treatment • Supportive with aggressive treatment of hyperthermia • Usually resolves in 24 hours
MAOI’s • MAO is a mitochondrial enzyme that deaminates the aromatic amines of NE, Serotonin, and Dopamine. • There are two types of MAO, MAO-A, and MAO-B. A type preferentially deaminates NE and Serotonin, whereas B primarily DOP • Non-selective MAO • Isocarboxazid, phenelzine, and tranylcypromine, • Selective MAO-B • Selegiline
MAOI’s • Clinical Pres • Acute Overdose may occur 12-24 hrs after ingestion. • A continuum from 1st sympathomimetic state followed by cardio collapse and death. • Hyperpyrexia, tachy, tachypnea, HTN (early), Hypoten (late), Muscle rigidity, flushing, diaphoresis, oliguria, AMS, Sz’s, and coma. • Tyramine Rxn (promote NE release and get sympathomimetic response) • With foods aged cheese/meat, red wines, sauerkraut • Serotonin Syndrome
MAOI’s • Dx • EKG, BGL, CPK, CBC, Lytes, HCG, Urine myoblobin, lactate, renal, liver panels • Management • Supportive, Airway, Cardiac monitor, pulse ox, freq neuro checks. Consider GI Decontam with Charcoal, Sz’s tx with benzos, cooling measures, HTN managed with nitroprusside (avoid long half-life), Hypoten managed with phenylepherine. Muscle rigidity consider dantrolene. • Serotonin agonsits ie cyproheptadine 4-8mg po q 4-6, or chlorpromazine (after fluid resus) 12.5-25mg IV, and repeat in 6hrs.
Anti-psychotics • Block dopamine receptors, may also inhibit alpha adrenergic receptors, myocardial potassium efflux, and muscarinic receptors. • Used to treat pyschosis, depression, and agitation • Acute OD--present with CNS and Card effects • Sedation, Pinpoint pupils, sz’s, coma. • Hypotension, tachy, resp arrest, QT prolongation, and torsades • Urinary Retention, Dry mouth, absence of sweat, ileus and akathesia • Extrapyramidal can occur at therapeutic levels and OD. • Torticollis, rigidity, oculogyric crisis, bradykinesia, and tremor
Anti-psychotics • Neuroleptic malignant syndrome NMS • AMS, Fever, and rigidity (rhabdo) • Clozapine is unique and can cause agranulocytosis at therapeutic levels • DX Testing: • Lytes, BGL, CPK, CBC, coag’s, Renal/liver panel, Urine Tox, and HCG, EKG • Mostly supportive care: may require ET, tx hypotension with fluids if persistent PRESSORS including phenylephrine or NE, Consider GI decontam. Tx dystonic rxn with diphenhydramine or benztropine. • QT- tx with Mag, torsades despite mag consider over-ride pacing
Lithium • Preparations/use • Used in treatment of bipolar and other psychiatric disorders • Available in regular and sustained release preparations • Toxic dose • Variable, depends on acute vs chronic ingestion • Narrow therapeutic index • Remember, patients with chronic toxicity are at higher risk than acute toxicity
LI Pathophys • Lithium is a cation that enters the cells and substitutes for sodium or potassium • Stabilizes cell membranes • Toxic levels depress neural excitation and synaptic transmission • Entry into the brain is slow, and elimination is by renal excretion (identical to the excretion of sodium) • Any state that causes dehydration, sodium depletion, or increased sodium reabsorption may result in lithium toxicity. Therefore, gastroenteritis, diuretic use, and lithium - induced diabetes insipidus all increase the risk of chronic toxicity • Interactions • Use of any diuretic that affects sodium excretion predisposes to toxicity
LI Presentation • Central nervous system (CNS) (Most commonly affected) • Mild to moderate intoxication: lethargy, weakness, slurred speech, ataxia, tremor, myoclonic jerks, hyper-reflexia • Severe intoxication: agitated delirium, coma, seizure • Persistent CNS effects are common • Gastrointestinal (GI) • Nausea, vomiting, diarrhea are more common with acute toxicity • Cardiovascular • T wave inversion,bradycardia or sinus node arrest, Rarely life-threatening
LI Presentation • Renal • Nephrogenic diabetes insipidus • Hematologic • WBC may be elevated in therapeutic or toxic doses (15 - 20 K) • Has been used to treat leukopenia • Acute vs chronic toxicity • Acute: more GI symptoms, serum levels may be higher • Chronic: fewer GI effects, more serious presentation, even if levels lower than acute
LI DX • Be suspicious in any patient with neurologic and/or GI symptoms • Lithium is usually not on the emergency drug screen! • Levels • Therapeutic: 0.6 - 1.2 mEq/L • Peak levels up to 9.3 mEq/L have been reported in acute ingestion without significant toxicity • Serial levels useful • Elevated levels confirm toxicity, but treatment primarily based on clinical presentation
LI TX • GI decontamination • Lavage • Charcoal ineffective, but should be given if suspect co-ingestion • Whole bowel irrigation for increasing levels, sustained- release preparations • Supportive care • IV fluids (NS) to replace fluids and sodium, Avoid diuretics • Indications for hemodialysis a. Severe alteration in mental status, Seizure, Renal failure, Ventricular dysrhythmias, Inability to tolerate fluids - congestive heart failure (CHF)