2. THE APPROACH TO THE POISONED PATIENT Toxicology Skills Workshop Regions Hospital Emergency Medicine Program

3.  Develop a Systematic Approach  Look for Toxidromes (“Talkingdromes”)  Attention to ABCs and need for Antidote  Know the Indications for Decontamination Procedures  Enhance when possible and appropriate

4.  A – Antidote  B – Basics ; ABCs  C – Change catabolism  D – Distribute differently; Decontamination  E – Enhance elimination

5. AntidoteToxin/Drug OxygenCO, CN, H2S NaloxoneNarcotics/Opiates NACAPAP, Carbon tet Atropine, PralidoximeOrganophosphates CalciumHF, Fl, Oxalates DMSAAs, Lead, Hg Sodium BicarbonateTCA

6. AntidotesToxin/Drug Ethanol, 4MPEG, (methanol) Digoxin-specific FabDigoxin GlucoseInsulin Hydroxocobalamin*CN PhysostigmineAnticholinergics, central PyridoxineINH, hydrazines GlucagonBeta-blockers

7.  Airway  Breathing  Circulation  Do the DONT  Dextrose  Oxygen  Naloxone  Thiamine

8. Reduce Adsorption  Vomiting (Ipecac)  Generally not indicated or used in an ED setting  Contraindicated in patients < 6 mos old, caustic ingestions, actual or potential loss of airway reflexes, need to give oral antidote  Activated Charcoal  Most effective if given within one hour  Caution in the patient with altered mental status (need a protected airway)  Not effective for hydrocarbons, metals (Lead, Iron, Lithium)  Gastric Lavage  Rarely used  Consider in large, potentially life threatening ingestions not amenable to activated charcoal

9.  Hemodialysis  STUMBLE(D) - Dialysis  Salicylates  Theophylline  Uremia  Methanol  Barbiturates, Bromide  Lithium  Ethylene Glycol  Depakote (high levels)

10.  Focused History and Brief Tox Exam  History: what-when-how much  Reliability factor, relatives, paramedics  Exam  Vital signs  Mental status  Pupillary response  Skin changes, Odors/other prominent features. MATTERSMATTERS MATTERSMATTERS

11.  Exam  Vital signs Pulse up or down or normal BP up or down or normal Temp up or down or normal Resp up or down or normal

12.  Bradycardia (PACED)  Propranolol or other Beta blockers, Poppies (opiates)  Anticholinesterase drugs  Clonidine, CCBs, Ciguatera  Ethanol or other alcohols, Ergotamine  Digoxin

13.  Tachycardia (FAST)  Free base or other forms of cocaine  Anticholinergics, antihistamines, amphetamines  Sympathomimetics (ephedrine, amphetamines), Solvent abuse  Theophylline, Thyroid hormone

14.  Hypothermia (COOLS)  Carbon monoxide, Clonidine  Opiates  Oral hypoglycemics, Insulin  Liquor  Sedative-hypnotics

15.  Hyperthermia (NASA)  Nicotine, Neuroleptic malignant syndrome  Antihistamines  Salicylates, Sympathomimetics  Anticholinergics, Antidepressants

16.  Hypotension (CRASH)  Clonidine, CCBs (and B-blockers)  Reserpine or other antihypertensives  Antidepressants, Aminophylline, Alcohol  Sedative-hypnotics  Heroin or other opiates

17.  Hypertension (CT SCAN)  Cocaine  Thyroid supplements  Sympathomimetics  Caffeine  Anticholinergics, Amphetamines  Nicotine

18.  Rapid Respiration (PANT)  PCP, Paraquat, Pneumonitis (chemical)  ASA and other salicylates, Amphetamines  Non-cardiogenic pulmonary edema  Toxin-induced metabolic acidosis

19.  Slow Respirations (SLOW)  Sedative-hypnoptics, Strychnine, Snakes  Liquor  Opiates, OPs  Weed (marijuana)  Other causes: Nicotine, Clonidine, Chlorinated HC

20.  Seizures?  Hallucinations?  CNS depressed?

21.  WITH LA COPS  Withdrawals (alcohol, benzos)  INH, Insulin, Inderal  Tricyclics, theophylline  Hypoglycemics; Hemlock, water; Haldol  Lithium, Lidocaine, Lead, Lindane  Anticholinergics, Antiseizure

22.  WITH LA COPS  Cocaine, Camphor, CN, CO, Cholinergics  Organophosphates  PCP, PPA, propoxyphene  Sympathomimetics, Salicylates, Strychnine

23.  Miosis (COPS)  Cholinergics, Clonidine  Opiates, organophosphates  Phenothiazines, pilocarpine  Sedative-hypnotics, SAH  MydriASis (A3S)  Antihistamines, Antidepressants, Atropine  Sympathomimetics

24.  Diaphoretic (SOAP)  Sympathomimetics  Organophosphates  ASA or salicylates  Phencyclidine (PCP)

25.  Dry Skin  Antihistamines, Anticholinergics  Bullous Lesions  Barbiturates and other sedative- hypnotics  Carbon monoxide  Tricyclics (personal case series) www.acponline.org/graphics/bioterro/bullous.jpg

26.  Flushed  CO (rare)  Anticholinergics  Boric acid  CN (rare)

27.  Cyanosis  Phenazopyridine  Aniline dyes  Nitrates  Nitrites  Ergotamine  Dapsone  Any agent hypoxia, hypotension  MetHb

28.  Bitter Almonds  Carrots  Fruity  Garlic  Gasoline -Cyanide -Cicutoxin (water hemlock) -DKA, Isopropanol -OP, As, DMSO, selenium, thallium, phosphorus -Petroleum distillates

29.  Mothballs  Pears  Pungent aromatic  Oil of wintergreen  Rotten eggs -Naphthlene, camphor -Chloral hydrate -Ethchlorvynol -Methylsalicylate -Sulfur dioxide, hydrogen sulfide

30.  Toxicology Screens  Urine Stat  Urine vs Serum  Acetaminophen level  Routine Tests  CBC  SMA-7  Anion Gap  ABGs

31. *Clinical Symptoms may dictate treatment, not level.

32.  A MUD PILE CAT ASA Methanol Uremia DKA Paraldehyde, Phenformin INH, Iron, Ibuprofen Lactic acidosis Ethylene Glycol

33.  A MUD PILE CAT CO, CN, Caffeine AKA Theophylline, Toluene  Others Benzyl alcohol Metaldehyde Formaldehyde H 2 S

34.  Decreased Anion Gap  Bromide  Lithium  Hypermagnesemia  Hypercalcemia

35.  Calculated  2(Na)+[Glu/18] + [BUN/2.8] + EtOH(mg/dL)/4.6 Osm Gap = measured - calculated  Significant if >10  Really significant if >19

36.  Increased Osmolar Gap  MAD GAS Mannitol Alcohols (met, EG, Iso, eth) Dyes, Diuretics, DMSO Glycerol Acetone Sorbitol

37.  A 40 year old man collapsed at work while moving his car. He has a hx of depression. He had recently attended his mother’s funeral the day before.  He was found slumped over the steering wheel of his car, lethargic and incoherent. A co- worker left the patient and went to call medics. He was intubated and transferred to Regions Hospital.

38.  Examination BP 130/88, P90, R-vent, T 101 2 Pupils 6mm unreactive but equal. Skin warm, red, dry Absent bowel sounds  Labs were unremarkable ABG:pH 7.50, 32, 140 EKG - QRS 102, occasional PVC

39. Is there a Toxidrome?  A. Opioid  B. Anticholinergic  C. Delayed Exercise Syndrome  D. Cholinergic poisoning Is there an antidote?

40.  Anticholinergic (antihistamines, cyclic antidepressants, Jimson weed) Hot as a hare (hyperthermia) Red as a beet (flushed) Dry as a bone (dry skin, urinary retention) Blind as a bat (mydriasis) Mad as a hatter (hallucinations, delirium, myoclonic jerking)

41.  Also with anticholinergic Mydriasis Tachycardia Hypertension Hyperthermia Seizures  How do you treat it? Supportive care TCAs – Sodium Bicarb for widened QRS Benzodiazepenes for agitation, seizures Consider physostigmine for pure anticholinergic overdoses (contraindicated in TCA overdose or with dysrhythmias)

42. Toxidromes: Case #2  A 19 year old male presents after from a party after his friends noted he was “acting funny.” He was “out of control” and not making sense, so they decided to bring him into the Emergency Room.  The patient is agitated on arrival

43.  Examination BP 180/114, P120, R20, T 101 The patient is agitated and appears to be hallucinating Pupils 6mm sluggish but equal. Skin warm, red, very diaphoretic  Labs were unremarkable EKG – sinus tachycardia

44. Toxidromes: Case #2 Is there a Toxidrome? A. Opioid B. Anticholinergic C. Sympathomimetic D. Cholinergic

45. SSympathomimetics (cocaine, amphetamines, ephedrine) Mydriasis Tachycardia Hypertension Hyperthermia Seizures Diaphoresis TTreatment Supportive care Benzodiazepines as needed

46. Toxidromes: Case #3  A 40 y/o female is brought by medics. A family member called after a suicide note was found and the patient was found unresponsive.  On medic arrival the patient was noted to be very somnolent. She was transported to Regions Hospital.

47.  Examination BP 100/65, P50, R6, T 98.6 The patient is arousable only to sternal rub. Pupils 2mm sluggish but equal. Skin cool, dry  Labs were unremarkable EKG – sinus bradycardia

48. Toxidromes: Case #3 Is there a Toxidrome? A. Opioid B. Anticholinergic C. Sympathomimetic D. Cholinergic Is there an antidote?

49.  Narcotic (heroin, methadone, other opioids) Miosis Bradycardia Hypotension Hypoventilation Coma/CNS depression  Treatment Naloxone

50.  Clonidine  Hypotension usually more profound  May require HIGH dose naloxone to see any effect  Tetrahydrozaline  Periodic apnea in kids  Kids should be admitted if symptomatic in ED

51. Toxidromes: Case #4  A 50 y/o male is brought in after being found in his garage. According to paramedics, there were several containers of liquids in glass jars near the patient. They also noted a large amount of emesis. He was noted to have altered mental status and some respiratory distress prior to arrival. He was intubated prior to arrival and transported to Regions Hospital.

52.  Examination BP 110/65, P50, R - intubated, T 98.6 The patient is obtunded, intubated Pupils 2mm sluggish but equal. There are copious secretions in the patient’s mouth and in the endotracheal tube Incontinent of both urine and stool Skin is cool, diaphretic  Labs were unremarkable EKG – sinus bradycardia

53. Toxidromes: Case #4 Is there a Toxidrome? A. Serotonin Syndrome B. Anticholinergic C. Sympathomimetic D. Cholinergic Is there an antidote?

54.  Cholinergic (DUMBELS or SLUG BAM)  Salivation  Lacrimation  Urination  GI complaints (nausea, vomiting, diarrhea)  Bradycardia, Bronchoconstriction  Abdominal cramping  Miosis, Muscle fasciculations  Treatments: Pralidoxime (2PAM), Atropine

55. MORE TALKINGDROMES

56.  Salicylates (ASPIRIN) Harris  Altered MS (lethargy to coma)  Sweating  Pulmonary edema  Increased ventilation, temp, heart rate  Ringing in ears  Irritable  Nausea and vomiting

57.  Serotonin Syndrome  VS: T, HR, BP (unstable)  MS: Agitation, coma  Pupils: Mydriasis  Skin: Diaphoresis  Other: LE rigidity, myoclonus, hyperreflexia, seizure

58.  MAOI and other drug  Idiosyncratic reaction  Alteration in MS  Autonomic instability  Neuromuscular abnormality  Treatment is supportive  Symptoms resolve 24-72 hrs  Lactic acidosis, rhabdo, hyperthermia

59.  Specific drugs  SSRIs (i.e., Prozac)  Dextromethorphan  Demerol  Ecstasy (MDMA): hallucinogenic amphetamine  Cocaine  L-tryptophan

60. Acetaminophen Toxicity - Metabolism  Metabolized in the liver primarily to nontoxic glucoronide and sulfide conjugates, however small amount is converted via cytochrome P450 to potentially toxic NAPQI  Normally, NAPQI is conjugated with glutathione to nontoxic metabolites  In significant overdose, glutathione stores are depleted  NAPQI destroys hepatocytes leading to liver failure

61. Acetaminophen Toxicity – Clinical Presentation  First few hours  Non-specific signs and symptoms  Nausea, vomiting, pallor, diaphoresis  Even severely poisoned patients may remain symptomatic  18 – 24 hours  Asymptomatic phase  No laboratory evidence of hepatotoxicity  After 24 – 36 hours  Aminotransferases begin to rise  Signs and symptoms of hepatotoxicity N, V, RUQ pain, hepatic enlargement, jaundice  72 – 96 hours  Peak hepatotoxicity  Although massive liver necrosis can occur, recovery is the rule and usually complete if the patient survives

62. Acetaminophen Level - Levels are important - Check levels in all cases of suspected overdose or polydrug overdose - Antidotal therapy is most effective if started within 8 – 10 hours - Signs and symptoms are delayed for 18 – 36 hours - Rumack-Matthew nomogram - Used to predict the severity of toicity and need for antidotal therapy - 4 hour level - Levels above the line require antidotal therapy

63. Acetaminophen Toxicity - Antidote  N-acetylcysteine (NAC)  Glutathione precursor and glutathione substitute  Increases substrate supply for the non-toxic sulfate conjugation pathway  Available as oral and IV form  Extremely effective if initiated within 8 hours  Standard of care to treat patients up to 24 hours

64.  ABCs - Antidotes  Decontaminate - Special Treatments?  Toxidromes?  Investigate - look closely  REASSESS, MONITOR, SUPPORT