Toxicology

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Toxicology

  1. 1. Toxicology Dalhousie Critical Care Lecture Series
  2. 2. Objectives <ul><li>Discuss findings of sympathomimetic, anti-cholinergic, cholinergic and narcotic toxidromes </li></ul><ul><li>Discuss the essential investigations of a potential drug overdose. </li></ul><ul><li>Demonstrate the ability to calculate an anion gap, serum osmolality and osmolar gap. What is the significance of an elevated AG or osmolar gap? </li></ul><ul><li>Discuss the presentation and management of common overdoses including: </li></ul><ul><ul><li>Toxic Alcohols </li></ul></ul><ul><ul><li>ASA </li></ul></ul><ul><ul><li>Tylenol </li></ul></ul><ul><ul><li>TCAs </li></ul></ul><ul><ul><li>Neuroleptic Malignant Syndrome and Serotonin syndrome </li></ul></ul><ul><li>Which overdoses require nephrology consults for consideration of dialysis? </li></ul>
  3. 3. Overdose <ul><li>Requires high index of suspicion </li></ul><ul><ul><li>Non-specific symptoms </li></ul></ul><ul><ul><ul><li>Tylenol O/D </li></ul></ul></ul><ul><ul><li>Presents as other issues </li></ul></ul><ul><ul><ul><li>AMI in setting of CO overdose </li></ul></ul></ul>
  4. 4. Overdose <ul><li>Suspect in the setting of: </li></ul><ul><ul><li>Altered LOC/coma </li></ul></ul><ul><ul><li>Trauma </li></ul></ul><ul><ul><li>Life threatening arrythmia </li></ul></ul><ul><ul><li>Unexpected clinical findings </li></ul></ul>
  5. 5. Diagnosis - History <ul><li>May be unreliable or incomplete </li></ul><ul><li>Things to consider </li></ul><ul><ul><li>History of depression/prior overdose </li></ul></ul><ul><ul><li>Time of ingestion/last seen well </li></ul></ul><ul><ul><li>Pill bottles present at scene </li></ul></ul><ul><ul><li>Time of last refill </li></ul></ul><ul><ul><li>Medications of family memebers </li></ul></ul>
  6. 6. Diagnosis - PE <ul><li>Vitals </li></ul><ul><ul><li>HR, BP, RR, Temp, O2 sat </li></ul></ul><ul><li>Neuro </li></ul><ul><ul><li>LOC, pupils </li></ul></ul><ul><li>CVS </li></ul><ul><ul><li>Arrythmias </li></ul></ul><ul><li>Skin </li></ul>
  7. 7. Increased Osmolal Gap <ul><li>Osmolarity = 2x[Na] + glc + urea </li></ul><ul><li>Osmolar gap = measured – calculated </li></ul><ul><li>normal = between 270 -290 </li></ul><ul><li>Normal osmolar gap <10 </li></ul>
  8. 8. Toxicology Critical Care Lecture Series
  9. 9. What is a toxidrome? <ul><li>A collection of symptoms and signs that consistently occur after ingestion of a particular toxin or drug class or agent </li></ul><ul><li>Often identified with a basic history & physical examination </li></ul><ul><li>Rapid identification of the toxidrome saves time in evaluating and managing a poisoned patient </li></ul>
  10. 10. Anticholinergic <ul><li>Mydriasis </li></ul><ul><li>Blurred vision </li></ul><ul><li>Fever </li></ul><ul><li>Flushed dry skin </li></ul><ul><li>Psycosis, coma </li></ul><ul><li>Seizures </li></ul><ul><li>Ileus </li></ul><ul><li>Urinary retention </li></ul><ul><li>Hypertension </li></ul><ul><li>Tachycardia </li></ul><ul><li>Eg. TCA, antihistamines, atropine, benztropine </li></ul><ul><li>Blind as a bat, hot as a hare, dry as a bone, red as a beet, mad as a hatter </li></ul>
  11. 11. Anticholinergic Toxidrome - Management <ul><li>ABC, supportive care, consider GI decontamination </li></ul><ul><li>Benzodiazepines </li></ul><ul><li>Physostigmine – specific antidote. </li></ul><ul><li>May be used if </li></ul><ul><ul><li>Severe agitation or psychosis unresponsive to other therapy </li></ul></ul><ul><ul><li>Sever peripheral and central anticholinergic features </li></ul></ul><ul><ul><li>NO history of seizures </li></ul></ul><ul><ul><li>Normal ECG especially QRS duration </li></ul></ul><ul><ul><li>NO co-ingestion of drugs altering intraventricular conduction </li></ul></ul><ul><ul><ul><li>E.g. TCA’s </li></ul></ul></ul><ul><ul><li>Cardio-respiratory monitoring and resus facilities in place </li></ul></ul>
  12. 12. Cholinergic <ul><li>Eg. organophosphates, nerve agents </li></ul><ul><li>DUMBELS </li></ul><ul><ul><li>D-diaphoresis, diarrhea, decreased BP </li></ul></ul><ul><ul><li>U-urination </li></ul></ul><ul><ul><li>M-miosis </li></ul></ul><ul><ul><li>B-bronchorrhea, bronchospasm, brady </li></ul></ul><ul><ul><li>E-emesis, excitiation of skeletal muscle </li></ul></ul><ul><ul><li>L-lacrimation </li></ul></ul><ul><ul><li>S-salivation, seizures </li></ul></ul>
  13. 13. Cholinergic Toxidrome - Management <ul><li>ABC, supportive care </li></ul><ul><li>Decontamination procedures </li></ul><ul><li>Atropine </li></ul><ul><ul><li>ACh antagonist </li></ul></ul><ul><ul><li>Antimuscarinic </li></ul></ul><ul><li>Pralidoxime (2-PAM) </li></ul><ul><ul><li>Regenerates Acetylcholinesterase </li></ul></ul><ul><ul><li>Removes phosphoryl group from enzyme </li></ul></ul><ul><ul><li>Must be given early before phosphorylation becomes irreversible (“aging”) </li></ul></ul>
  14. 14. Sympathomimetic (adrenergic) toxidrome <ul><li>Increased temp </li></ul><ul><li>Tachycardia </li></ul><ul><li>Hypertension </li></ul><ul><li>Dilated pupils </li></ul><ul><li>CNS excitiation </li></ul><ul><ul><li>Seizures </li></ul></ul><ul><li>Nausea/vomiting </li></ul><ul><li>Diaphoresis </li></ul>Cocaine, MDMA (“ecstasy”), Amphetamines, Phencyclidine (PCP), Theophylline, Decongestants ( Ephedrine Pseudoephedrine Phenylpropanolamine), Caffeine (very large doses)
  15. 15. Adrenergic Toxidrome - Management <ul><li>ABC, supportive care, consider GI decontamination </li></ul><ul><li>Investigations </li></ul><ul><ul><li>Screen for other drugs & treatable toxins (eg, acetaminophen, salicylate) </li></ul></ul><ul><ul><li>Electrolytes (esp. sodium), urea, creatinine, blood sugar, anion gap. </li></ul></ul><ul><ul><li>CK levels to check for rhabdomyolysis </li></ul></ul><ul><ul><li>Consider cranial CT </li></ul></ul><ul><ul><li>EKG & Cardiac biomarkers (eg, CPK-MB, troponin) </li></ul></ul><ul><li>Sedation – treats majority of effects </li></ul><ul><ul><li>Benzodiazepines </li></ul></ul><ul><li>Temperature control </li></ul><ul><li>Treat hypertension unresponsive to benzodiazepines </li></ul><ul><ul><li>Nitroprusside </li></ul></ul><ul><ul><li>Nitroglycerine </li></ul></ul><ul><ul><li>Labetalol (avoid isolated  -blockade in mixed adrenergic agonist toxicity) </li></ul></ul>
  16. 16. Narcotic <ul><li>Hypothermia </li></ul><ul><li>Bradycardia </li></ul><ul><li>Hypotension </li></ul><ul><li>Respiratory depression </li></ul><ul><li>Constricted pupils </li></ul><ul><li>CNS depression </li></ul>
  17. 17. Opioid-Narcotic Toxidrome - Management <ul><li>ABC, supportive care </li></ul><ul><li>GI decontamination for oral ingestion </li></ul><ul><li>Naloxone </li></ul><ul><ul><li>Specific antagonist </li></ul></ul><ul><ul><li>High doses may be needed for methadone & pentazocine </li></ul></ul><ul><ul><li>Short half-life compared to opioids </li></ul></ul><ul><ul><li>Infusion may be required </li></ul></ul><ul><ul><li>Pulmonary edema and seizures have been reported </li></ul></ul>
  18. 18. Serotoninergic Toxidrome Eg. SSRI’s, MAOI’s, ecstasy Diarrhoea, trismus, myoclonus, tremor, rhabdo Other Normal/decreased (SIADH possible) Urination Increased Bowel sounds Increased Reflexes Normal/flushed/sweating Skin Normal Mucous membranes Normal/unreactive Pupils Agitated/irritable Mental status Physical examination Normal/decreased Blood pressure Increased Temperature Increased Heart rate Normal/increased Respiratory rate Vital Signs
  19. 19. Serotoninergic Toxidrome - Features <ul><li>Mental status changes </li></ul><ul><ul><li>Confusion (51%) </li></ul></ul><ul><ul><li>Agitation (34%) </li></ul></ul><ul><ul><li>Hypomania (21%) </li></ul></ul><ul><ul><li>Anxiety (15%) </li></ul></ul><ul><ul><li>Coma (29%) </li></ul></ul><ul><li>Cardiovascular </li></ul><ul><ul><li>Sinus tachycardia (36%) </li></ul></ul><ul><ul><li>Hypertension (35%) </li></ul></ul><ul><ul><li>Hypotension (15%) </li></ul></ul><ul><li>Gastrointestinal </li></ul><ul><ul><li>Nausea (23%) </li></ul></ul><ul><ul><li>Diarrhea (8%) </li></ul></ul><ul><ul><li>Abdominal pain (4%) </li></ul></ul><ul><ul><li>Salivation (2%) </li></ul></ul><ul><li>Motor Abnormalities </li></ul><ul><ul><li>Myoclonus (58%) </li></ul></ul><ul><ul><li>Hyperreflexia (52%) </li></ul></ul><ul><ul><li>Muscle rigidity (51%) </li></ul></ul><ul><ul><li>Restlessness (48%) </li></ul></ul><ul><ul><li>Tremor (43%) </li></ul></ul><ul><ul><li>Ataxia/incoordination (40%) </li></ul></ul><ul><ul><li>Shivering (26%) </li></ul></ul><ul><ul><li>Nystagmus (15%) </li></ul></ul><ul><ul><li>Seizures (12%) </li></ul></ul><ul><li>Other </li></ul><ul><ul><li>Diaphoresis (45%) </li></ul></ul><ul><ul><li>Unreactive pupils (20%) </li></ul></ul><ul><ul><li>Tachypnea (26%) </li></ul></ul><ul><ul><li>Hyperpyrexia (45%) </li></ul></ul>Sternbach H. The serotonin syndrome. Am J Psychiatry 1991;148:705-13 Mills KC. Serotonin syndrome. Am Fam Physician 1995;52:1475-82
  20. 20. Serotoninergic Toxidrome - Management <ul><li>Stop intake of causative agent </li></ul><ul><li>ABC, supportive care </li></ul><ul><li>Absorption </li></ul><ul><ul><li>Gastric lavage in early acute ingestion (1hr) </li></ul></ul><ul><ul><li>Activated charcoal </li></ul></ul><ul><li>Benzodiazepines </li></ul><ul><li>Others </li></ul><ul><ul><li>Chlorpromazine </li></ul></ul><ul><ul><li>Diphenhydramine </li></ul></ul><ul><ul><li>? Serotonin antagonists e.g. cyproheptadine </li></ul></ul>
  21. 21. Diagnosis - Investigation <ul><li>Essential labs </li></ul><ul><ul><li>CBC, lytes, BUN, Cr, BS </li></ul></ul><ul><ul><li>Ptt, INR, LFTs </li></ul></ul><ul><ul><li>ABG (calculate AG) </li></ul></ul><ul><ul><li>Serum osmo (calculate osmo gap) </li></ul></ul><ul><ul><li>ASA </li></ul></ul><ul><ul><li>Acetaminophen </li></ul></ul><ul><li>Other </li></ul><ul><ul><li>Drug levels </li></ul></ul><ul><ul><li>Urine </li></ul></ul>
  22. 22. General Management <ul><li>ABC </li></ul><ul><li>Consider thiamine, dextrose, naloxone if depressed GCS </li></ul><ul><li>Prevent further absorption </li></ul><ul><ul><li>Decontaminate eyes, clothes, skin, hair if appropriate </li></ul></ul><ul><ul><li>Activated charcoal + sorbitol (if < 1 hour from ingestion) </li></ul></ul><ul><ul><li>Gastric lavage (if < 1 hour from ingestion and life-threatening drug or dose) </li></ul></ul><ul><ul><ul><li>In general not used </li></ul></ul></ul><ul><ul><li>Whole bowel irrigation for “body packing” illicit drugs </li></ul></ul><ul><ul><ul><li>In general not used </li></ul></ul></ul><ul><li>Enhance elimination </li></ul><ul><ul><li>Forced diuresis and urinary alkalinisation (salicylates and barbiturates) </li></ul></ul><ul><ul><li>Multiple dose activated charcoal 0.5 g/kg every 2-4 hours </li></ul></ul><ul><ul><ul><li>binds toxin and interrupts enterohepatic recirculation </li></ul></ul></ul><ul><ul><ul><li>mainly life-threatening ingestion of carbamazepine, dapsone, phenobarbital, quinine or theophylline </li></ul></ul></ul><ul><ul><li>Extracorporeal removal (for active metabolites, delayed toxicity or poor organ clearance) </li></ul></ul><ul><ul><ul><li>Haemodialysis - low MW (<500 d), soluble, low Vd (< 1L/kg) e.g. methanol, ethylene glycol, salicylates, lithium </li></ul></ul></ul><ul><ul><ul><li>Haemoperfusion - e.g theophylline, phenobarbital, phenytoin, carbamazepine, paraquat </li></ul></ul></ul><ul><ul><ul><li>Haemofiltration for large Vd and extensive tissue bound toxins but removes virtually all drugs </li></ul></ul></ul><ul><li>Antidotes </li></ul>
  23. 23. Activated Charcoal <ul><li>Universal absorbent </li></ul><ul><li>Produced by the controlled burning of various organic products at >600C, washed with inorganic acids and dried </li></ul><ul><li>Small particle with highly developed internal pore system </li></ul><ul><ul><li>surface area of 50 gm AC = 10 football fields </li></ul></ul><ul><li>Absorbs substances in varying degrees </li></ul><ul><ul><li>If comes into contact with toxin in GI track prior to absorption, can bind and decrease systemic toxicity </li></ul></ul>
  24. 24. General Treatment <ul><li>Activated charcoal </li></ul><ul><ul><li>Inert, non-toxic, non-specific adsorption </li></ul></ul><ul><ul><li>Risk of aspiration </li></ul></ul><ul><ul><li>Dose 1g/kg patients weight </li></ul></ul><ul><ul><li>Ineffective for alcohols or heavy metals </li></ul></ul><ul><ul><li>? Multi-dose charcoal </li></ul></ul><ul><ul><ul><li>may cause GI dialysis for some drugs </li></ul></ul></ul><ul><ul><ul><li>Check with poison control!!! </li></ul></ul></ul>
  25. 25. Activated Charcoal <ul><li>Binds most compounds; easier to remember what it doesn’t </li></ul>
  26. 26. Activated Charcoal <ul><li>Big question in the use of AC is when to use it </li></ul><ul><li>Effectiveness is time dependent – the longer the time from ingestion, the less effective AC is </li></ul><ul><ul><li>Toxin already absorbed or past pyloris </li></ul></ul><ul><li>Effectiveness is lost between 1 and 2 hours </li></ul>
  27. 27. AC: problem <ul><li>Patients with toxin ingestions will present to the ED >3 hours after poisoning </li></ul><ul><li>“should not be administered routinely” </li></ul>
  28. 28. Drugs and Extracorporeal Removal <ul><li>Haemodialysis </li></ul><ul><li>M ethanol </li></ul><ul><li>Ethylene glycol </li></ul><ul><li>Salicylates </li></ul><ul><li>Lithium </li></ul><ul><li>Haemofiltration </li></ul><ul><li>Procainamide </li></ul><ul><li>Methotrexate </li></ul><ul><li>Haemoperfusion (Charcoal) </li></ul><ul><li>Theophylline </li></ul><ul><li>Carbamazepine </li></ul><ul><li>Amanita toxin (if early) </li></ul><ul><li>Aminoglycosides </li></ul><ul><li>Paraquat </li></ul><ul><li>Phenobarbital </li></ul><ul><li>Phenytoin </li></ul><ul><li>Sotalol </li></ul>
  29. 29. Urinary Alkalinisation <ul><li>Fluoride </li></ul><ul><li>Isoniazid </li></ul><ul><li>Salicylic acid </li></ul><ul><li>Barbiturates </li></ul><ul><li>Methotrexate </li></ul>
  30. 30. Specific Ingestions
  31. 31. Acetaminophen <ul><li>Peak plasma <1hr post ingestion </li></ul><ul><li>Metabolized in liver d/t glucuronidation </li></ul><ul><li>Toxic metabolite NAPQ1 </li></ul><ul><ul><li>NAPQ1 binds to hepatocytes and causes necrosis </li></ul></ul><ul><ul><li>Detoxified by glutathione & eliminated by kidneys </li></ul></ul><ul><li>Toxic threshold adults - 7.5-10g </li></ul>
  32. 32. Acetaminophen <ul><li>Phase I (<24 hrs): </li></ul><ul><ul><li>Anorexia, malaise, N/V, diaphoresis </li></ul></ul><ul><li>Phase II (24-48 hr): </li></ul><ul><ul><li>RUQ pain,  LFTs, sx of phase I resolve </li></ul></ul><ul><li>Phase III (48-96 hr) </li></ul><ul><ul><li>Severe liver failure </li></ul></ul><ul><ul><ul><li>Encephalopathy, coagulopathy,  BS </li></ul></ul></ul><ul><ul><li>Pancreatitis </li></ul></ul><ul><ul><li>ARF </li></ul></ul><ul><li>Phase IV (>4 days) </li></ul><ul><ul><li>Death/full recovery/transplant </li></ul></ul>
  33. 33. Acetaminophen <ul><li>Limitations: </li></ul><ul><ul><li>Requires time of ingestion </li></ul></ul><ul><ul><li>Very early or late ingestions </li></ul></ul><ul><ul><li>Chronic ingestions </li></ul></ul><ul><ul><li>Extended release preparations </li></ul></ul><ul><ul><li>At risk populations </li></ul></ul><ul><ul><ul><li>ETOH abuse </li></ul></ul></ul>
  34. 34. Acetaminophen <ul><li>Treatment </li></ul><ul><ul><li>Activated charcoal </li></ul></ul><ul><ul><ul><li>Given w/I 4-6 hr </li></ul></ul></ul><ul><ul><ul><li>Reduced absorption by 50-90% </li></ul></ul></ul><ul><li>NAC </li></ul><ul><ul><li>Replete glutathione </li></ul></ul><ul><ul><li>combines directly with NAPQ1 </li></ul></ul><ul><ul><li>Antioxident properties </li></ul></ul><ul><ul><li>vasodilatory properties </li></ul></ul><ul><ul><li>Treat: </li></ul></ul><ul><ul><ul><li>Based on nomogram </li></ul></ul></ul><ul><ul><ul><li>Level >5 w/o ingestion time known </li></ul></ul></ul><ul><ul><ul><li>Evidence of hepatotoxicity or level unknown </li></ul></ul></ul>
  35. 35. Alcohols <ul><li>Ethylene glycol, methanol, isopropanol </li></ul><ul><li>Lab: </li></ul><ul><ul><li>Anion gap MA, elevated osmolar gap </li></ul></ul><ul><ul><li>Exceptions: </li></ul></ul><ul><ul><ul><li>Normal AG </li></ul></ul></ul><ul><ul><ul><ul><li>Not yet formed metabolites </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Isopropanol ingestion </li></ul></ul></ul></ul><ul><li>Sx may be delayed if co-ingested with ethanol </li></ul>
  36. 36. Ethylene Glycol <ul><li>Oxalic acid  Ca oxalate  ARF </li></ul><ul><li>Hypocalcemia </li></ul><ul><li>Myocardial dysfunction (2 0  Ca) </li></ul><ul><li>100ml can be lethal </li></ul>Ethylene glycol ETOH dehydrogenase Oxalic acid
  37. 37. Ethylene Glycol <ul><li>Phase I (30min-12hr) </li></ul><ul><ul><li>Inebriation, ataxia, seizures, AG-MA, OG, hypocalcemia, crystalluria, cerebral edema </li></ul></ul><ul><li>Phase II (12-24hr) </li></ul><ul><ul><li>Myocardial dysfunction, CHF </li></ul></ul><ul><li>Phase III (2-3 days) </li></ul><ul><ul><li>ARF </li></ul></ul>
  38. 38. Methanol <ul><li>150-240ml is lethal </li></ul><ul><li>Presents with: </li></ul><ul><ul><li>Headache, inebriation </li></ul></ul><ul><ul><li>Dizziness, ataxia, confusion </li></ul></ul><ul><ul><li>Vision loss </li></ul></ul><ul><ul><li>Pancreatitis </li></ul></ul>Methanol ETOH dehydrogenase Formic Acid
  39. 39. Treatment <ul><li>Inhibit alcohol dehydrogenase </li></ul><ul><ul><li>Ethanol </li></ul></ul><ul><ul><li>Fomepizole </li></ul></ul><ul><li>Removal of alcohol & it’s metabolites </li></ul><ul><ul><li>Hemodialysis </li></ul></ul><ul><ul><ul><li>Levels >50mg/dL </li></ul></ul></ul><ul><ul><ul><li>Significant MA </li></ul></ul></ul><ul><ul><ul><li>Evidence of end-organ damage </li></ul></ul></ul>
  40. 40. Isopropanol <ul><li>Ketonuria </li></ul><ul><li>Absent AG or MA </li></ul><ul><li>Hemorrhagic gastritis </li></ul><ul><li>Generally just supportive care </li></ul><ul><ul><li>Hemodialysis if: </li></ul></ul><ul><ul><ul><li>Lethal ingestion (150-240ml) </li></ul></ul></ul><ul><ul><ul><li>Refractory shock/prolonged coma </li></ul></ul></ul>Isopropanol ETOH dehydrogenasez Acetone
  41. 41. Salicylate Intoxication <ul><li>Adult lethal dose - 10-30g </li></ul><ul><li>Sx include: </li></ul><ul><ul><li>Tinnitus </li></ul></ul><ul><ul><li>Fever </li></ul></ul><ul><ul><li>Vertigo </li></ul></ul><ul><ul><li>Nausea/vomiting/diarrhea </li></ul></ul><ul><ul><li>AG MA & resp alkalosis </li></ul></ul><ul><ul><li>Altered LOC/coma </li></ul></ul><ul><ul><li>ARDS </li></ul></ul>
  42. 42. Salicylate Treatment <ul><li>Level check q2h until 2 values decreased from peak </li></ul><ul><li>Activated charcoal </li></ul><ul><ul><li>?multiple dosing </li></ul></ul><ul><li>Supplemental glucose </li></ul><ul><li>Alkalinization of serum & urine </li></ul><ul><ul><li>Resp alkalosis not C/I to HCO3 </li></ul></ul><ul><ul><li>Urine pH = 8 </li></ul></ul><ul><li>Dialysis </li></ul>
  43. 43. Salicylate Treatment <ul><li>Hemodialysis Indications </li></ul><ul><ul><li>Altered LOC </li></ul></ul><ul><ul><li>Pulmonary or cerebral edema </li></ul></ul><ul><ul><li>Renal failure </li></ul></ul><ul><ul><li>Fluid overload that prevents HCO3 </li></ul></ul><ul><ul><li>Plasma level >7.2 </li></ul></ul><ul><ul><li>Deterioration despite therapy </li></ul></ul>
  44. 44. TCA Intoxication <ul><li>Rapidly absorbed - peak dose 2-8h </li></ul><ul><ul><li>T1/2 - 24-72hr </li></ul></ul><ul><ul><li>Enterohepatic recirculation </li></ul></ul><ul><ul><li>Delayed absorption d/t anticholinergic effects </li></ul></ul>
  45. 45. TCA - Clinical Presentation <ul><li>Cardiac </li></ul><ul><ul><li>Inhibits fast Na channels - slowed depolarization </li></ul></ul><ul><ul><ul><li>QRS prolongation </li></ul></ul></ul><ul><ul><ul><li>Reentry arrhythmias - V-tach, torsade </li></ul></ul></ul><ul><ul><ul><li>Hypotension, Decreased CO </li></ul></ul></ul><ul><li>CNS </li></ul><ul><ul><li>Delerium, seizures, coma </li></ul></ul><ul><li>Anticholinergic </li></ul><ul><ul><li> temp, flushed, dilated pupils, ilieus, urinary retention, sinus tach </li></ul></ul>
  46. 46. TCA - Treatment <ul><li>ABCs </li></ul><ul><li>Activated charcoal - ?multidose </li></ul><ul><li>Gastric decontamination </li></ul><ul><li>NaHCO3 - most effective therapy! </li></ul><ul><ul><li>D/t raised pH and serum [Na] </li></ul></ul><ul><ul><li>Recommend for QRS >100msec </li></ul></ul><ul><ul><li>Push amps for arrhythmias </li></ul></ul><ul><li>Do not give dilantin for seizures! </li></ul><ul><li>No role for dialysis!!!! </li></ul>
  47. 47. B-Blocker Overdose <ul><li>Most are symptomatic within 4 hours of ingestion </li></ul><ul><ul><li>Asymptomatic pts with a normal EKG after 6hrs generally don’t need ICU </li></ul></ul><ul><li>SX: </li></ul><ul><ul><li>Hypotension </li></ul></ul><ul><ul><li>Bradycardia/A-V block </li></ul></ul><ul><ul><li>CHF </li></ul></ul><ul><ul><li>Bronchospasm </li></ul></ul><ul><ul><li>Decreased LOC, seizures, coma </li></ul></ul>
  48. 48.  -blocker Treatment <ul><li>ABCs </li></ul><ul><li>Activated charcoal </li></ul><ul><li>Temporary pacing/vasopressors prn </li></ul><ul><li>Glucagon </li></ul><ul><ul><li>+ve inotropic and chronotropic effect d/t increased AMP and intracell Ca </li></ul></ul><ul><ul><li>5-10mg bolus followed by 1-10mg/h gtt </li></ul></ul><ul><li>High dose insulin/glucose drip </li></ul><ul><li>**Atenolol is dialyzable** </li></ul>
  49. 49. Ca channel Blocker OD <ul><li>Selectively inhibit the movement of Ca through cardiac and vascular smooth mm </li></ul><ul><li>Present with </li></ul><ul><ul><li>Hypotension </li></ul></ul><ul><ul><li>Bradycardia/conduction delays </li></ul></ul><ul><ul><li>Confusion/ altered LOC </li></ul></ul>
  50. 50. Ca Channel Treatment <ul><li>ACBs </li></ul><ul><li>Activated charcoal </li></ul><ul><li>?Gastric lavage </li></ul><ul><li>Ca gluconate </li></ul><ul><li>Glucagon </li></ul><ul><li>Insulin/glucose infusion </li></ul>
  51. 51. CO poisoning <ul><li>Seen with: </li></ul><ul><ul><li>smoke inhalation </li></ul></ul><ul><ul><li>SA with car exhaust </li></ul></ul><ul><ul><li>poorly vented wood or gas stoves </li></ul></ul><ul><li>CO binds Hg 240X> then O 2 </li></ul><ul><ul><li>Causes tissue hypoxia </li></ul></ul><ul><li>Serum CO up to 5-10% in smokers or large cities </li></ul>
  52. 52. CO poisoning <ul><li>Presentation </li></ul><ul><ul><li>5-10% CO </li></ul></ul><ul><ul><ul><li>H/A, mild dyspnea </li></ul></ul></ul><ul><ul><li>10-30% </li></ul></ul><ul><ul><ul><li>H/A, dizziness, weakness, N/V, dyspnea, cardiac ischemia </li></ul></ul></ul><ul><ul><li>>50% </li></ul></ul><ul><ul><ul><li>Coma, seizures, cardiovascular collapse, death </li></ul></ul></ul><ul><ul><ul><li>10-30% survivors have delayed neuro deficits </li></ul></ul></ul>
  53. 53. CO poisoning - Diagnosis <ul><li>High index of suspicion </li></ul><ul><li>Serum CO level </li></ul><ul><ul><li>Measured by co-oximeter of an ABG </li></ul></ul><ul><ul><li>Pulse oximetry can’t distinguish carboxyHg from oxyHg </li></ul></ul><ul><ul><li>PO2 on ABG may be normal since it represents dissolved oxygen </li></ul></ul><ul><li>CT head may specifically demonstrate globus pallidus abnormalities </li></ul>
  54. 54. CO Poisoning - Treatment <ul><li>ABCs </li></ul><ul><li>100% FiO2 </li></ul><ul><ul><li>T1/2 R/A - 5-6hr </li></ul></ul><ul><ul><li>T1/2 100% - 40-90min </li></ul></ul><ul><li>Hyperbaric O2 </li></ul><ul><ul><li>T1/2 - 15-30 min </li></ul></ul><ul><ul><li>If accessible, suggested for: </li></ul></ul><ul><ul><ul><li>CO>25% </li></ul></ul></ul><ul><ul><ul><li>Loss of consciousness, EKG changes, chest pain </li></ul></ul></ul><ul><ul><ul><li>pH<7.1 </li></ul></ul></ul>
  55. 55. Antidotes Naloxone Opioids Atropine, pralidoxime Organophosphates Methylene blue Methaemoglobinaemia Ethanol/fomepizole, folate Methanol Pyridoxine Isoniazid Deferoxamine Iron Dextrose, glucagon, ocreotide Hypoglycaemic agents Dimercaprol, EDTA, penicillamine Arsenic, copper, gold, lead, mercury Ethanol/fomepizole, thiamine, pyridoxine Ethylene Glycol Digoxin-specific antibodies Digoxin Amyl nitrite/sodium nitrite/thiosulphate ( Taylor Cyanide Antidote Package) hydroxycobalamin Cyanide Oxygen Carbon Monoxide Flumazenil Benzodiazepines Atropine Anticholinesterases Physostigmine Anticholinergics N-acetylcysteine Acetaminophen Antidote Toxin/effect
  56. 56. Summary <ul><li>Familiarity with toxidromes will allow you to assess and manage unconscious overdose/poisoning victims </li></ul><ul><li>Supportive care and decontamination is the mainstay of most treatments </li></ul><ul><li>Calculation of the anion gap and osmolar gap will allow you to identify and treat toxic alcohol ingestions prior to end organ damage </li></ul><ul><li>In known overdoses and poisonings early involvement of a toxicologist/poison control is very helpful to direct specific antidote therapies </li></ul>

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