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- 1. Management of Acute Poisonings Speaker : Dr. Vivekanand B Moderator : Dr. Dnyaneshwar M
- 2. Develop a Systematic Approach Look for Toxidromes Attention to ABCs and need for Antidote Know the Indications for Decontamination Procedures Enhance Elimination when possible and appropriate
- 3. A – Antidote B – Basics ; ABCs C – Change catabolism D – Decontamination/DONT E – Enhance elimination
- 4. Airway (When in doubt the airway should always be secured by intubation) Breathing – ABG, EtCO2 Circulation Do the DONT (COMA COCKTAIL) • Dextrose • Oxygen • Naloxone • Thiamine Consider a Head CT
- 5. Toxin/Drug Antidote CO, CN, H2S Oxygen Narcotics/Opiates Naloxone Benzodiazepine Flumazenil Acetaminophen, Carbon tet NAC Organophosphates Atropine, Pralidoxime As, Lead, Hg IRON DMSA Deferoxamine TCA Sodium Bicarbonate Intralipid Snake bites Anti-snake venom Toxin/Drug Antidote EG, (methanol) Ethanol, 4MP, Fomepizole Digoxin Digoxin-specific Fab Insulin Glucose CN Hydroxocobalamin* Anticholinergics, central Physostigmine INH, hydrazines Pyridoxine Beta-blockers Calcium channel blockers ( Atropine, Glucagon), Glucagon Intralipid Sulfonylureas Octreotide HF, Fl, Oxalates Hyperkalemia Iatrogenic Hypermagnesemia Calcium
- 6. Methods for Decontamination & enhanced elimination of poisons Multiple – dose activated charcoal Saline diuresis Urinary ion trapping Alkalinization Acidification Extracorporeal methods • Hemodialysis • Hemoperfusion • Hemofiltration • Peritoneal dialysis • Plasmapheresis • Exchange transfusion Hyperbaric Oxygen Chelation therapy Cerebrospinal fluid removal Specific antibody – toxin binding
- 7. Reduce Adsorption • Never used in 21st century • Generally not indicated or used in an ED setting • Contraindicated in patients < 6 months old, caustic ingestions, actual or potential loss of airway reflexes, need to give oral antidote Vomiting (Ipecac) • Most effective if given within one hour • Caution in the patient with altered mental status (need a protected airway) • Not effective for hydrocarbons, (alcohols), metals (Lead, Iron, Lithium) • Indications for Multiple dose activated charcoal (MDAC) • Carbamazepine, Dapsone, Phenobarbital, Quinine, Theophylline Multiple Dose Activated Charcoal • Rarely used • Consider in large, potentially life threatening ingestions not amenable to activated charcoal. Gastric Lavage • Indications : SLIP (Sustained release/enteric coated meds, Lithium, Iron, Packets – illicit drug packets) Whole Bowel Irrigation
- 11. E = Enhance Elimination • By increasing urinary pH to ≥ 8 and urinary output 2 -3 mL/kg/hr Alkalinization of urine • Phenobarbitone • Salicylates Indication
- 12. Lipid Emulsion Therapy Initially used to treat overdoses of local anesthetics, such as bupivacaine • emulsion acts as a “lipid sink,” surrounding a lipophilic drug molecule and rendering it ineffective. • fatty acids from the ILE provide the myocardium with a ready energy source, thereby improving cardiac function Two mechanisms effectiveness of ILE. Studied as a therapy for poisonings involving a number of lipophilic medication • Verapamil, beta blockers, some tricyclic antidepressants, bupivacaine, chlorpromazine, and some antidysrhythmics (Flecanide) • patients who are hemodynamically unstable from such poisonings Indications Dose : Intravenous bolus of 1 to 1.5 mL/kg given over one minute of a 20 percent lipid emulsion solution
- 13. 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. M A T T E R S Medication Amount Time Taken Emesis Reason Signs/symptoms
- 14. Hypothermia (COOLS) Carbon monoxide, Clonidine Opiates Oral hypoglycemics, Insulin Liquor Sedative-hypnotics Hyperthermia (NASA) Nicotine, Neuroleptic malignant syndrome Antihistamines Salicylates, Sympathomimetics Anticholinergics, Antidepressants
- 15. Bradycardia (PACED) Propranolol or other Beta blockers, Poppies (opiates) Anticholinesterases Clonidine, CCBs Ethanol or other alcohols, Ergotamine Digoxin Tachycardia (FAST) Free base or other forms of cocaine Anticholinergics, antihistamines, amphetamines Sympathomimetics (ephedrine, amphetamines), Solvent abuse Theophylline, Thyroid hormone
- 16. Hypotension (CRASH) Clonidine, CCBs (and B- blockers) Reserpine or other antihypertensives Antidepressants, Aminophylline, Alcohol Sedative-hypnotics Heroin or other opiates 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 Slow Respirations (SLOW) Sedative-hypnoptics, Strychnine, Snakes Liquor Opiates, OPs Weed (marijuana) Other causes: Nicotine, Clonidine, Chlorinated HC
- 20. Seizures? Hallucinations? CNS depressed? Movement Disorders?
- 21. WITH LA COPS Withdrawals (alcohol, benzos) INH, Insulin, Inderal Tricyclics, theophylline Hypoglycemics Lithium, Lidocaine, Lead, Lindane Anticholinergics, Antiseizure 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
- 26. Flushed CO (rare) Anticholinergics Boric acid CN (rare) Cyanosis Phenazopyridine Aniline dyes Nitrates Nitrites Ergotamine Dapsone Any agent hypoxia, hypotension MetHb
- 28. Bitter Almonds Fruity Garlic Gasoline -Cyanide -DKA, Isopropanol -OP, As, DMSO, selenium, thallium, phosphorus -Petroleum distillates Mothballs Pears Oil of wintergreen Rotten eggs -Naphthlene, camphor -Chloral hydrate -Methyl salicylate -Sulfur dioxide, hydrogen sulfide
- 29. Differential Diagnosis of poisoning based on physiological state Stimulated Depressed Discordant state Normal state
- 30. Stimulated State : Increased pulse, blood pressure, temperature, neuromuscular activity, Mydriasis, hot & dry flushed skin, tachyarrythmias, CVS collapse, agitation, hyperactivity, later seizures and coma. Sympathetics Sympathomimetics Ergot alkaloids Methylxanthines Monoamine oxidase inhibitors Thyroid hormones Anticholinergics Antihistamines Anti parkinsonism drugs Antispasmodics Belladona alkaloids Cyclic antidepressants Mushrooms and plants Hallucinogens Cannabinoids (marijuana) LSD and analogues Mescaline and analogues Mushrooms Phencylidine & analogues Withdrawal Barbiturates Benzodiazepines Ethanol Opioids Sedative hypnotics Sympatholytics
- 31. Depressed : Decreased – pulse, blood pressure, respiratory rate, temperature and neuromuscular activity, Miosis, Cardiovasular depression & arrhythmias and CNS depression Sympatholytics α1- Adrenergic antagonists α2- Adrenergic agonists ACE inhibitors Angiotensin receptor blockers Antipsychotics β – Adrenergic blockers Calcium channel blockers Cyclic antidepressants Cholinergic Acetylcholinesterase inhibitors Muscarinic alkaloids Nicotinic agonists Opioids Analgesics GI antispasmodics Heroin Sedative – Hypnotics Alcohols Anticonvulsants Barbiturates Benzodiazepines GABA precursors Muscle relaxants GHB products
- 32. Discordant : Mixed Vital Signs and neuromuscular abnormalities Asphyxiants Cytochrome oxidase inhibitors Inert gases Irritant gases Methemoglobin Inducers Oxidative phosphorylation inhibitors AGMA Inducers Alcohol (ketoacidosis) Ethylene Glycol Iron Methanol Salicylate Toluene CNS Syndromes Extrapyramidal reactions Hydrocarbon inhalation Isoniazid Lithium Neuroleptic malignant syndrome Serotonin syndrome Strychninine Membrane active agents Amantidine Antiarrythmics Antihistamincs Antipsychotics Carbamazepine Cyclic antidepressants Local anesthetics Opioids Orphenadrine Quinoline antimalarials
- 33. Normal : Non-toxic Exposures Psychogenic illness “Toxic time bombs” Slow absorption Anticholinergics Carbamezepine Extended release phenytoin capsules Drug packets Lomotil (diphenoxylate-atropine) Opioids Salicylates Sustained release pills Valproate Slow Distribution Cardiac Glycosides Lithium Metals Salicylate Valproate Toxic Metabolites Acetaminophen Carbon tertracholride Cyanogenic glycosides Ethylene glycol Methanol Methemoglobin inducers Mushroom toxins Organophosphate insecticides Paraquat Metabolism Disruptors Anti-neoplastic agents Antivirals Colchicine Hypoglycemic agents Immunosuppressive agents MAO inhibitors Metals Salicylate Warfarin
- 34. Toxidromes
- 35. Toxicology Screens Urine Stat Drug Levels (if known poisoning) Acetaminophen level AChE levels Routine Tests CBC Blood metabolic profile LFT Anion Gap ABGs ECG Radiology : X rays & CT Scan
- 37. Causes of Elevated Anion Gap A MUD PILE CAT ASA Methanol Uremia DKA Paraldehyde, Phenformin INH, Iron, Ibuprofen Lactic acidosis Ethylene Glycol CO, CN, Caffeine Alcoholic Ketoacidosis Theophylline, Toluene Others Benzyl alcohol Metaldehyde Formaldehyde H2S
- 38. Decreased Anion Gap Bromide Lithium Hypermagnesemia Hypercalcemia
- 39. Calculated 2(Na)+[Glu/18] + [BUN/2.8] + EtOH(mg/dL)/4.6 Osm Gap = measured - calculated Significant if >10 Really significant if >19 Remember normal osmolar gap does not rule out toxic alcohol ingestion Increased Osmolar Ga MAD GAS Mannitol Alcohols (met, EG, Iso, Dyes, Diuretics, DMSO Glycerol Acetone Sorbitol
- 40. Oxygen Saturation Gap It describes differences between oxyhemoglobin percentages as measured by pulse oximetry (SpO2) or as estimated from arterial oxygen tension PaO2 when compared with the oxyhemoglobin percentage (SaO2) as measured by co- oximetry Indication CO poisoning Cyanide or Hydrogen sulfide Acquired hemoglobinopathy e.g.
- 44. Poisons causing hypoglycaemia & Electrolyte Imbalances
- 45. Other Lab Abnormalities Rhabdomylysis Hepatoxicity Methemoglobinemia Coagulopathy Rodenticides
- 47. 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 Yashoda Hospital. Examination • BP 90/60, P90, R-vent, T 1012 • Pupils 6mm unreactive but equal. • Skin warm, red, dry • Absent bowel sounds Labs were unremarkable • ABG:pH 7.50, 32, 140 • EKG - QRS 122, occasional Ectopics Is there a Toxidrome? A. Opioid B. Anticholinergic C. Cholinergic poisoning Is there an antidote?
- 48. Is there a Toxidrome? Anticholinergic Altered Mental Status, Mydriasis, Hot, Red skin, Dry skin = Anticholinergic Syndrome- physostigmine
- 49. Tricyclic antidepressant intoxication Clinical Features Neurologic – Sedation, coma, Seizures Cardiac – Tachycardia, hypotension, conduction abnormalities Anticholinergic – dilated pupils, dry mouth, absent bowel sounds and urinary retention Diagnostic Evaluation ECG QRS duration > 100 msec Rightward deflection the terminal 40 msec of the QRS complex Deep S wave in leads I. AVL; tall R wave in lead AVR R wave in AVR > 3 mm, R/S ratio in AVR > 0.7 Serum TCA Concentrations Treatment Airway and breathing Circulation : Hypotension IV isotonic crystalloids Vassopressor Conduction disturbances QRS > 100 msec IV sodium bicarbonate GI decontamination activated Charcoal Seizures benzodiazepines
- 50. 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 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 Is there a Toxidrome? A. Opioid B. Anticholinergic C. Sympathomimetic D. Cholinergic
- 51. Toxidromes: Case 2 Is there a Toxidrome? Sympathomimetic (symptoms can be like anticholinergic except you see diaphoresis) Sympathomimetics (cocaine, amphetamines, ephedrine, MDMA, theophylline, caffeine, energy drinks, cannabinoids)
- 52. General Stimulant increases energy and produces euphoria Toxicity in virtually all organs, via hemodynamic effects Clinical presentation Vital signs : Hypertension, tachycardia, hyperthermia CNS : Agitation, focal signs CVA Pupils : Mydriasis Lungs : Decreased breaths sounds after smoking crack pneumothorax Extremities : Decreased pulses suggest Vascular Catastrophe (aortic dissection) Lab Evaluation General : Fingerstick glucose, ECG, Acetaminophen and salicylate levels, Urine Preg in child bearing age Urine toxicology : Inconclusive of toxicity (only detection) Advanced testing clinical symptoms Cardiac biomarkers, CT
- 53. Treatment Airway management Succinylcholine relatively contraindicated in RSI, Consider Rocuronium, 1 mg/kg or other non-depolarizing agent Psychomotor agitation Administer benzodiazepines Severe symptomatic hypertension Diazepam, Phentolamine ( do not administer beta blockers, including labetalol) Cocaine Associated Myocardial Ischemia ECG, Diazepam, aspirin, NTG, Phentolamine QRS widening on ECG ( profound toxicity ) Sodium Bicarbonate
- 54. Toxidromes: Case 3 A 40 y/o female is brought by paramedics. 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 Yashoda Hospital. 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 Is there a Toxidrome? A. Opioid B. Anticholinergic C. Sympathomimetic D. Cholinergic Is there an antidote?
- 55. Toxidromes: Case 3 Is there a Toxidrome? A. Opioid (key is respiratory depression with miosis Is there an antidote? Naloxone. Can give 0.4mg - 2mg as first dose
- 56. Clinical and Laboratory Altered mental status ranging from mild euphoria or lethargy to coma Miotic pupils Decreased Bowel sounds Low to Normal heart ate and blood pressure Hypoventilation Diagnostic Evaluation Rapid bedside serum glucose concentration, to exclude hypoglycemia as cause of coma Obtain Creatinine Kinase Obtain Chest Radiograph Obtain Serum Acetaminophen Concentration Obtain ECG Treatment Provide Adequate Ventilation, utilize ETCO2 for monitoring Naloxone and look for response Watch for Seizures in case of sudden Opioid withdrawal
- 57. 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
- 58. Toxidromes: Case 4 A 50 y/o male farmer is brought in after being found in his shed. 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 at a local hospital and then transported to Yashoda Hospital. Examination • BP 110/65, P - 50, 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, diaphoretic Labs were unremarkable • EKG – Sinus bradycardia Is there a Toxidrome? A. Serotonin Syndrome B. Anticholinergic C. Sympathomimetic D. Cholinergic Is there an antidote?
- 59. Toxidromes: Case 4 Is there a Toxidrome? Cholinergic Is there an antidote? Atropine given until secretions are improved (no max dose) 2PAM/ Pralidoxime
- 60. Cholinergic (DUMBBELS or SLUG BAM) Salivation Lacrimation Urination GI complaints (nausea, vomiting, diarrhea) Bradycardia, Bronchoconstriction Bronchorrea Abdominal cramping Miosis, Muscle fasciculations Intermediate Syndrome : • Occurs 24 – 96 hours after exposure • Bulbar, Respiratory and Proximal muscle weakness • Resolves in 1 – 3 weeks
- 61. Organophosphate and carbamate poisoning Diagnosis Atropine Challenge Absence of anticholinergic signs Blood sample for RBC acetylcholinesterase measurement Treatment of acute Toxicity 100 % Oxygen via facemask, early intubation, avoid Succinylcholone Decontamination : Activated Charcoal, Dermal & Ocular irrigation, discard clothing Atropine 2 to 5 mg IV double dose every 3 to 5 mins until bronchial secretions and wheezing stop (Tachycardia and Mydriasis are not contraindications to atropine use) PAM (pradlidoxime) 2 g IV over 30 mins Infusion at 8 mg/hr in adults Benzodiazepine therapy in case of Seizures (do not give phenytoin) Clonidine
- 62. Case 5 A 19-year-old student is admitted after being found friends confused and sweating in her room. She is unable to give a history. On examination temperature is 38.1ºC, pulse 108/min, BP 130/70 mmHg and respiratory rate 30/min. Heart sounds are normal but she has bibasal fine inspiratory crackles on her chest. ABG : - Mixed Respiratory and Metabolic Acidosis What is the likely diagnosis ? A. Paracetamol B. Aspirin overdose C. Opioid D. TCA overdose
- 63. Altered MS Sweating Pulmonary edema Increased ventilation, temp, heart rate Ringing in ears Irritable Nausea and vomiting mixed respiratory alkalosis and metabolic acidosis Diagnostic Evaluation Plasma Salicylate conc, ABG, Electrolytes, BUN and Creatinine, Chest Radiograph Treatment If possible avoid intubation ABC as needed Volume resuscitation Multiple doses of activated Charcoal Glucose Alkalinize with Sodium Bicarbonate (do not use acetazolamide) Alert Nephrology team Altered MS, Pulmonary or cerebral edema, Renal insufficiency, overload preventing Sodabicarb use, Plasma salicylate Conc > 100mg/dL in acute and > 60 mg/dL in chronic Worsening clinical condition despite aggressive supportive care
- 64. Case 6 A 23 year-old male is brought to your ED by a friend. He appears anxious, distressed and confused. His vital signs are: T 37.4C P 110/min RR 19/min BP 160/100 mmHg SO2 98% OA GCS 13 The patient is unable to give a coherent history. His friend volunteers that the patient had seen a GP in the past few weeks as he was feeling depressed. The friend also admitted that the patient occasionally used recreational drugs such as marijuana and ecstasy. (E4V3M6) Q1. What is the likely diagnosis?
- 65. VS: T, HR, BP (unstable) MS: Agitation, coma Pupils: Mydriasis Skin: Diaphoresis Other: LE rigidity, myoclonus, hyperreflexia, seizure Serotonin Syndrome is a clinical diagnosis Hunter Criteria for diagnosis of Serotonin syndrome CNS: AMS/confusion Autonomic instability: Brady/Tachycardia, HTN, hypotension Muscle involement: Nystagmus, clonus, hyperreflexia
- 66. MAOI and other drug Differential Diagnosis Neuroleptic Malignant syndrome Anticholinergic toxicity Malignant hyperthermia Sympathomimetic toxicity Meningitis and Encephalitis Treatment is supportive Symptoms resolve 24-72 hrs Lactic acidosis, rhabdo, hyperthermia Specific drugs SSRIs (i.e., Prozac) Dextromethorphan Demerol Ecstasy (MDMA): hallucinogenic amphetamine Cocaine
- 67. Case 7 A 34 year-old man presents to the Emergency Department after being rescued from a house fire. On examination he is short of breath, drowsy and confused, and complains of feeling dizzy with a worsening headache. He has no evidence of facial burns and no stridor. His observations show: blood pressure 110/82mmHg, heart rate 102bpm, oxygen saturations of 100% on air with a respiratory rate of 35/min. He appears markedly flushed but is afebrile. His venous blood gas results are shown be In view of the likely diagnosis, what is the most appropriate intervention? A. Intubate & Ventilate B. i.v. Hydrocobalamin C. 15. Litres of Oxygen via face mask D. IV Dexamethasone E. IV Sodium nitroprusside Answer : Acute Cyanide
- 70. Case 12 A 49-year-old homeless gentlemen is brought to the emergency department with a reduced glasgow coma scale of 14/15. His pupils are equal but poorly reactive to light and he is complaining of poor eyesight. An ABG is performed. Which substance is he most likely to have ingested? a. Aspirin b. Alcohol c. Methanol d. Amitriptyline e. Ethylene glycol
- 72. Acute Acetaminophen poisoning Acute Acetaminophen Poisoning : Rapid Overview Clinical Presentation : Nausea, Vomiting, Hepatic toxicity Diagnostic : S. Acetaminophen conc, Baseline liver function, PT/INR, basic chemistry panel S. Salicylate, fingerstick glucose, ECG, Qualitative pregnancy tests in Child bearing age Treatment • ABC • Activated Charcoal 50 g, within 4 hours of ingestion, Coingestants > 4 hr • Treat with N-acetylcysteine 1. S. APAP Conc at 4 hours or more > t/t line in nomogram 2. S. APAP conc is not available 3. Time of ingestion unknown 4. Hepatotoxicity • Oral dosing of NAC : 140mg/kg loading, followed by 17 doses of 70 mg/kg every 4 hours • IV dosing 150 mg/kg loading over 60 mins followed by 50 mg/kg over 4 hours, followed by 100 mg/kg over next 16 hours
- 73. 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
- 74. Hospital Acquired Intoxication Propofol Infusion Syndrome Hyperlipidemia, lactic acidosis, hyperkalemia, Renal failure Stop and supportive care Gabapentin Confusion, lethargy, recent change in renal function Discontinue and hemodialysis Propylene glycol intoxication (preservative) Lorazepam prolonged infusion Anion Gap metabolic acidosis, Renal failure and hypotension Hemodialysis & supportive care Methemoglobinemia Multiple causes (local anaesthetics, antibiotics trimethoprim, dapsone, sulphonamides, Metaclopramide, rasubiricase, nitrates)
- 75. Snake Bite
Editor's Notes
- In the patient with an ingestion, remember the basics (Airway, Breathing, Circulation), but also start thinking early about antidote and eliminating the toxin if indicated. Time matters.
- Resp depression, loss of airway reflexes , aspiration. Lethargy and Seizures – rapid intubation Ventilatory failure – ABG and ETCO2, Bronchospasm Arrythmias, hypotension and circulatory failure and shock- Venous access, ECG monitoring Hypoglycemia Head CT
- Hyperbaric Oxygen has a role for the treatment of carbon monoxide (CO) Poisoning and may have some potential benefit in the treatment of cyanide and hydrogen sulfide poisoning. (210 times greater affinity) Opioid Agonist to the mu receptor creating euphoria, analgesia, dependance, sedation and respiratory depression. Normally paracetamol is conjugated with glucuronide and excreted in the urine. 5% converts to toxic NAPQI (N-acetyl-p-benzoquinone imine) but conjugates to glutathione, which is non-toxic and is excreted in the urine. In overdose both systems are overwhelmed and NAPQI accumulates causes hepatic toxicity. Hence NAC works as a glutathione donor preventing NAPQI accumulation Atropine is a competitive muscarinic antagonist, used to treat drug-induced bradycardia and poisoning by acetylcholinesterase inhibitors Pralidoxime reactivates acetylcholinesterase only if irreversible binding to the OP has not already occurred (“ageing”). The acetylcholinesterase enzyme has two parts to it. In organophosphate poisoning, an organophosphate binds to just one end of the acetylcholinesterase enzyme (the esteric site), blocking its activity. Pralidoxime is able to attach to the other half (the unblocked, anionic site) of the acetylcholinesterase enzyme. It then binds to the organophosphate, the organophosphate changes conformation, and loses its binding to the acetylcholinesterase enzyme. The conjoined poison / antidote then unbinds from the site, and thus regenerates the enzyme, which is now able to function again. An oral chelating agent called Succimer (Dimercaptosuccinic acid, also known as DMSA) is FDA-approved for treatment of lead poisoning Desferrioxamine is an effective iron chelator that is used to treat systemic iron toxicity or prevent the development of systemic toxicity following acute iron overdose. It should ideally be given before iron moves intracellularly and systemic toxicity develops. Hyperosmolar sodium bicarbonate solutions are widely used in clinical toxicology both as an antidote to drugs that impair fast sodium channel function and as an alkalinising agent to manipulate drug distribution and excretion (salicylate and phenobarbitone). It is also used in profound metabolic acidosis with cyanide, isoniazid and toxic alcohol toxicity. Finally, it can also increase the urinary solubility of methotrexate toxicity and drug-induced rhabdomyolysis Anti-snake venom (ASV) is the mainstay of treatment. In India, polyvalent ASV, i.e. effective against all the four common species; Russell’s viper, common cobra, common Krait and saw-scaled viper. Initial Dose • Mild envenomation (systemic symptoms manifest > 3 hours after bite) neurotoxic/hemotoxic 8–10 Vials • Severe envenomation (systemic symptoms manifest < 3 hours after bite) neurotoxic or hemotoxic 8 Vials Each vial is 10 ml of reconstituted ASV. Children should receive the same ASV dosage as adults. Further Doses It will depend on the response to the initial dose. ASV should be administered either as intravenous infusion (5–10 mL/kg body weight) Competitively blocks the formation of toxic metabolites in toxic alcohol ingestions by having a higher affinity for the enzyme Alcohol Dehydrogenase (ADH). Its chief application is in methanol and ethylene glycol ingestions, although it has been used with other toxic alcohols. Ethanol is now regarded as the second choice antidote in those countries with access to the specific ADH blocker, fomepizole ( 15 mg/kg IV infusion over 30 min), 10 mg/kg IV q12hr for 4 doses, THEN increase to 15 mg/kg q12hr Maintain serum level of 8.6-24.6 mg/L Treat until ethylene glycol or methanol levels are <20 mg/dL Dialysis may also be required 10. Digoxin FAB It is made from immunoglobulin fragments from sheep that have already been immunized with a digoxin derivative, digoxindicarboxymethoxylamine (DDMA). Its brand names include Digibind (GlaxoSmithKline) and DigiFab (BTG plc).t works by binding to the digoxin, rendering it unable to bind to its action sites on target cells. The complexes accumulate in the blood and are expelled by the kidney. Hemodynamically unstable arrhythmia, End organ damage digoxin level > 4 ng/ml if chronic ingestion digoxin level > 10 ng/ml if acute ingestion potassium > 5 mEq/L and symptomatic 12. significant inotropic response in severe calcium channel blocker (CCB) overdose and occasionally in beta blocker overdose. 13. Hydroxocobalamin is a vitamin B12 (cyanocobalamin) precursor. In high doses, it is an effective chelator of cyanide. It is also the preferred antidote to cyanide poisoning due to its low side effect profile, thus if given to a patient without cyanide poisoning there is low risk of an adverse outcome 14. A reversible acetylcholinesterase inhibitor useful in the treatment of central anticholinergic delirium that is not easily controlled by benzodiazepine sedation and there is high risk for aspiration and excessive sedation. Only for those patients who have an isolated anticholinergic agent toxicity (not the polypharmacy overdose). It can also be considered in the management of a recovering TCA overdose but not in the acute management as you will precipitate seizures. Contraindications include bradydysrhythmias, intraventricular and AV block and bronchospasm. This is because in excess it produces a cholinergic toxicity (remember organophosphate toxicity). 15. Intravenous pyridoxine is used in high doses to control the metabolic acidosis and seizures associated with isoniazid overdose and poisoning from other hydrazine compounds (Gyromitramushrooms and jet/rocket fuel). It is also used as a adjunct to ethylene glycol toxicity. Vitamin B6 or pyridoxal-5-phosphate (P5P) is the active form of pyridoxine. P5P is essential for many enzymatic reactions but importantly for the conversion of L-glutamic acid to GABA. In an hydrazine overdose (typically isoniazid) P5P is inhibited, effectively inhibiting the production of GABA and promoting seizures. Large doses of P5P (vitamin B6) are required to overcome the inhibition. 16. Polypeptide hormone secreted by the alpha-cells of the pancreas. Supra-physiological doses have previously been advocated in the management of beta-blocker and calcium channel blocker poisoning but this practice is now largely abandoned. 17. Long-acting synthetic octapeptide analogue of somatostatin useful in the control of sulfonylurea-induced hypoglycaemia (BSL <4 mol/L) either from overdose or an iatrogenic source. It is also useful in hypoglycaemia induced from Quinine. 18. Intravenous lipid emulsion (IVLE) is a sterile emulsion of soyabean oil in water, used in parenteral nutrition. It is a novel antidote which requires further study but may have a role to play in the resuscitation of patients with refractory cardiac arrest induced by local anaesthetics that are resistant to standard protocols. It may also have a role when standard therapy has failed in the arrest of a propranolol, tricyclic antidepressant and verapamil overdose (limited evidence).
- Activated Charcoal (1g/kg), Whole Bowel Irrigation Gastric lavage, esp sustained release preparations MDAC 1 g/kg followed by 0.5 gm/kg every 2 to 4 hours for atleast 3 doses, cathartics should not be used Whole Bowel polyethylene glycol electrolyte solution
- Pneumonic for which toxins are able to be removed via dialysis SSA > 100, Hemodynamic detoriation, Persistent CNS derangement, Severe Acid-base disturbances, Electrolyte disturbances, Renal failure and Acute lung injury Theophy hemoperfusion – Serizures, arrhythmias, persistent hypotension Uraemia Methanol – New visual deficit, severe acidosis, level >50mg/dl Barbiturates/bromide : Clinical detoriation – Hemoperfusion Lithium – Renal failure, coma, seizures, cardiovascular instability, myoclonus Ethylene Glycol : severe acidosis, renal failure, level > 50mg/dl Valproic acid – Rapid detoriation, hepatic dysfunction and level > 1000 mg/L CCB – Nicardipine, nifedipine, nimodipine – cardiotoxicity, heart block, requiring cardiac pacing, refractory hypotension Isopropranalol – Hypotension, clinical worsening, level > 400 mg/dl, rarely needed Beta blockers – Limited to acebutolol, atenolol, esp sotalol with cardiovascular instability and renal failure Carbemazepine – Life threatning ingestion
- alkaline urine pH promotes the ionisation of highly acidic drugs. This prevents reabsorption across the renal tubular epithelium thus promoting excretion in the urine. To be effective the drug must be filtered at the glomerulus, have a small volume of distribution and be a weak acid
- Lipid emulsions are the fats used in total parenteral nutrition (TPN). Initially used to treat overdoses of local anesthetics, such as bupivacaine, intravenous lipid emulsion (ILE) is being studied as a therapy for poisonings involving a number of lipophilic medications. Studies of ILE therapy are preliminary. Systematic reviews of lipid emulsion therapy for acute poisoning have found the overall quality of studies supporting this treatment to be low or very low but included human case reports provide some evidence of benefit in patients with toxicity from verapamil, beta blockers, some tricyclic antidepressants, bupivacaine, chlorpromazine, and some antidysrhythmics (eg, flecainide) [33-35]. ILE may have a useful role in the treatment of patients who are hemodynamically unstable from such poisonings [36-39]. We suggest consultation with a medical toxicologist or poison control center to determine whether ILE therapy is appropriate. The dosing protocol most widely reported consists of an intravenous bolus of 1 to 1.5 mL/kg given over one minute of a 20 percent lipid emulsion solution [36,37,40]. If there is no response, the same dose may be repeated in cases of cardiac arrest every three to five minutes, for a total of three bolus doses. Following the initial bolus, an infusion is started at a rate of 0.25 to 0.5 mL/kg per minute until hemodynamic recovery occurs. The infusion is generally maintained for 30 to 60 minutes. The infusion rate may be increased if the patient’s blood pressure drops. Possible adverse effects from standard ILE treatment include hypertriglyceridemia, fat embolism, infection, and hypersensitivity reactions. Although these and other potential complications from ILE treatment have been reported, further study is needed to determine the risk of complications from circumscribed treatment in the setting of acute overdose. ILE therapy interferes with some laboratory measurements and may affect therapeutic drug monitoring [41,42]. As examples, serum glucose concentrations when determined by colorimetric testing and serum magnesium concentrations become inaccurate following the administration of ILE, while creatinine and lipase become unmeasurable. Potassium and troponin-I are not affected. Centrifugation of blood samples substantially reduces any interference. Two mechanisms are believed to account for the effectiveness of ILE. The first is that the emulsion acts as a “lipid sink,” surrounding a lipophilic drug molecule and rendering it ineffective. The second is that the fatty acids from the ILE provide the myocardium with a ready energy source, thereby improving cardiac function [40].
- Remember to focus on the time of ingestion, how much (ask paramedics or family for pill bottles, count pills if necessary), ask about vomiting. Pay attention on your physical to vital signs, mental status and Pupillary response as this may clue you in to a toxidrome.
- As predicted beta-blockers competitively block beta-1 and beta-2 receptors. This results in decreased production of intracellular cyclic adenosine monophosphate (cAMP) with a resultant blunting of multiple metabolic and cardiovascular effects of circulating catecholamines. In therapeutic doses this leads to a reduced heart rate and blood pressure. In overdose this causes the heart to enter a shock state. Utilising glucose instead of fatty acids which produce less ATP, perpetuating the cycle. Propranolol has the added effect of causing sodium channel blockade, widening the QRS and promoting ventricular dysrhythmias and entering the CNS to exert direct toxicity. Sotalol blocked the cardiac potassium channels causing QT prolongation and the risk of torsades de pointes. Neostigmine, physostigmine Centrally acting alpha 2 adrenergic agonist. It act as a sympathoplegic agent and also increases endothelial nitric oxide levels and decreases renin activity.
- Paraquat is used in pesticides
- Hemlock is a plant
- Sympathomimetics – A1 adrenergic agonists (phenylephrine/ B2 adrenergic agonists (albuterol, terbutaline) Release of Cen & Perip norepinep / sometimes dopamine, T/t Phentolamine (non selective A1 adrenergic receptor antagonist) Propranalol – B2 ad agonist (hypotension & tachycardia), Labetatol or phentolamine with esmolol or cardioselective Beta blocker. Ergot – methylsergide/bromocriptine - Sti – Serotonergic and inbhi of Alph adrenergic stimulationformication, vasospasm with limb, myocardial or cerebral ischemia, gangrene. T/t Nitroprusside/NTG vasospasm, prazosin (alpha 1 blocker), captopril, nifedipine and cyproheptadine – serotonin receptor antagonist, for mild to moderate limb ischemia. Dopamine receptor antagonists – hallucinations and movement disorders Methylxanthines – Caffeine/Theophylline -> decreased Adenosine synthesis or adenosine receptor antagonism, rel epinephrine/nor epin, phys stimulation, GI symptoms, Multidose charcoal, hemodialysis MOI inhibitors : Phenelzine, tranylcypromine, selegiline, impaired metabolism of endogenous cathecolaminesslow progressive stimulationShort acting, esmolol or nitroprusside Antihistamines : diphendyramine, doxylamine inhibition of central and post ganglionic parasympathetic muscuranic cholinergic receptors Belladona Alkaloids – Atropine, hyoscyamine, scopolamine inhibition of central and postganglionic parasympathetic muscuranic cholinergic recp Cyclic antidepressants – amityptilline, doxepin -> inhibits, alp adrenergic, dopaminergic, GABA, histaminergic, and serotoninergic recep, inbhibits sodium channels, and inhibition of norepinephrine, and serotonin reuptake – sodabicarbonate or hypertonic saline Mushrooms and plants – ICPPMC - physostigmine
- Alpha adrenergic agnoists : - clonidine, guanabenzn, tetrahydrozoline (imidazoline decongesants) – Alpha 2 adrenergic stimulation leading to inhibiton of cns sympathetic outflow: Dopamine and norephinephrine for hypotension. Atropine for bradycardia Antisphycotics like – cholorphromazine, clozapine, haloperidol, risperidone – inhibits aldpha adrenergic, dopaminergic, histaminergic, muscuranic, serotoninergic receptors prolonged QRS and PR intervals – ventricular tachydysarrythmias amd torsedes de pointes – sodabicarbonate and cardiac pacing Beta- adrenergic blockers – Cardioselective b1 – atenolol, esmolol, metaprolol Non selective – nadolol A1 – antagonists – carvedilol and labetalol Memberane active agents acebutalol, proprnalol and sotalol glucagon, atropine, dopamine, dobutamine, high dose insulin with glucose and potassium to maintain euglycemia and normokalemia, electical pacing, mechanical cardiovascular support for refractory cases Calcium channel blockers – Acetylcholine esterase inhibitors : Carbamate insectisides (aldicarb, propxur, carbaryl), Medicinals ( neostigmine, physostigmine, tacrine), nerve agents (sarin, soman), OP insectisides ( diazinon, chlorphyrifos, malathion) increased synaptic acetylcholine at muscuranic and nicotinic cholinergic receptor sites Anticonvulsants potentiation of neuroncal GABA A chloride channel receptor complex
- If you find an elevated anion gap on your lab workup – consider these potential poisonings
- B. Altered Mental Status, Mydriasis, Hot, Red skin, Dry skin = Anticholinergic Syndrome Antidote - physostigmine
- C - Sympathomimetic
- Clinical features Medications contraindicated
- Clinical features Medications contraindicated
- A – opioid Treatment - naloxone
- Tetrahydrozoline, a derivative of imidazoline, is found in over-the-counter eye drops and nasal sprays. Other derivatives include naphazoline, oxymetazoline, and xylometazoline.
- D - cholinergic Treatment – 2PAM, atropine (lots)
- The mixed respiratory alkalosis and metabolic acidosis in a sweaty, confused patient point towards salicylate overdose. The development of pulmonary oedema suggests severe poisoning and is an indication for haemodialysis Salicylate overdose A key concept for the exam is to understand that salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis. In children metabolic acidosis tends to predominate Features hyperventilation (centrally stimulates respiration) tinnitus lethargy sweating, pyrexia* nausea/vomiting hyperglycaemia and hypoglycaemia seizures coma Treatment general (ABC, charcoal) urinary alkalinization with intravenous sodium bicarbonate - enhances elimination of aspirin in the urine haemodialysis Indications for haemodialysis in salicylate overdose serum concentration > 700mg/L metabolic acidosis resistant to treatment acute renal failure pulmonary oedema seizures coma *salicylates cause the uncoupling of oxidative phosphorylation leading to decreased adenosine triphosphate production, increased oxygen consumption and increased carbon dioxide and heat production Salicylate overdose A key concept for the exam is to understand that salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis. In children metabolic acidosis tends to predominate Features hyperventilation (centrally stimulates respiration) tinnitus lethargy sweating, pyrexia* nausea/vomiting hyperglycaemia and hypoglycaemia seizures coma Treatment general (ABC, charcoal) urinary alkalinization with intravenous sodium bicarbonate - enhances elimination of aspirin in the urine haemodialysis Indications for haemodialysis in salicylate overdose serum concentration > 700mg/L metabolic acidosis resistant to treatment acute renal failure pulmonary oedema seizures coma *salicylates cause the uncoupling of oxidative phosphorylation leading to decreased adenosine triphosphate production, increased oxygen consumption and increased carbon dioxide and heat production
- Selective-serotonin reuptake inhibitors (SSRIs) — fluoxetine, paroxetine, citalopram. Selective noradrenergic reuptake inhibitors (SNRIs) — duloxetine, reboxetine (not so selective in overdose or in combination with others!) Opioids and related drugs —- pethidine, fentanyl, tramadol, dextromethorphan. tricyclic antidepressants (TCAs) — amitryptyline, nortriptyline, dothiepin. monamine oxidase inhibitors (MAOIs) — moclobemide, tranylcypramine. Antibiotics — linezolid Antiemetics — metoclopramide, ondansetron. Mood stabilisers — lithium, sodium valproate. Recreational drugs — amphetamines, ecstasy, lysergic acid (LSD) Herbal agents — St. John’s Wort, Ginseng. Drugs, poisons and toxins anticholinergic syndrome neuroleptic malignant syndrome sympathomimetic syndromes salicylism theophyline toxicity nicotinic toxicity Encephalopathies metabolic infective organic brain disorders Psychiatric disorders including lethal catatonia Malignant hyperthermia Drugs, poisons and toxins anticholinergic syndrome neuroleptic malignant syndrome sympathomimetic syndromes salicylism theophyline toxicity nicotinic toxicity Encephalopathies metabolic infective organic brain disorders Psychiatric disorders including lethal catatonia Malignant hyperthermia Home | Medical Specialty | Toxicology | Serotonin toxicity Serotonin toxicity by Chris Nickson, Last updated October 9, 2017 aka Toxicology Conundrum 024 A 23 year-old male is brought to your ED by a friend. He appears anxious, distressed and confused. His vital signs are: T 37.4C P 110/min RR 19/min BP 160/100 mmHg SO2 98% OA GCS 13 (E4V3M6) The patient is unable to give a coherent history. His friend volunteers that the patient had seen a GP in the past few weeks as he was feeling depressed. The friend also admitted that the patient occasionally used recreational drugs such as marijuana and ecstasy. Further of examination of the patient was notable for the presence of shaking eye movements, brisk deep tendon reflexes and stiffness of the lower limbs. Before answering the questions – do you remember this from Toxicology Conundrum #017? Questions Q1. What is the likely diagnosis? show answer Serotonin toxicity, aka serotonin syndrome Q2. Describe the clinical manifestions of this condition? show answer Serotonin syndrome typical resolves within 12 -24 hours. Exceptions may occur following massive overdoses, in the presence of multiple serotonergic agents (especially MAOIs) and in the context of intercurrent illness. Serotonin syndrome has 3 types of clinical manifestations(‘CAN’): central nervous system — altered mental state (agitation, anxiety, confusion or stupor), seizures autonomic dysfunction — hypertension or hypotension, tachycardia or bradycardia, hyperthermia, dysrhythmias, flushing, sweating, mydriasis neuromuscular dysfunction — rigidity (lower limbs more so than upper limbs), hyper-reflexia, clonus (including ocular), tremor, myoclonus
- This man has developed acute cyanide toxicity secondary to burning plastics in the house fire. Cyanide ions inhibit mitochondrial cytochrome oxidase, preventing aerobic respiration. This manifests in normal oxygen saturations, a high pO2 and flushing (or 'brick red' skin) brought on by the excess oxygenation of venous blood. In the question above it is important to note that the blood gas sample given is venous rather than arterial. His blood gas also demonstrates a increased anion gap, consistent with his high lactate (generated by anaerobic respiration due to the inability to use available oxygen). The recommended treatment for moderate cyanide toxicity in the UK is one of three options: sodium thiosulfate, hydroxocobalamin or dicobalt edetate. Although any one of these may be used, the only option given is that of hydroxocobalamin and this is therefore the correct answer. Hydroxocobalamin additionally has the best side-effect profile and speed of onset compared with other treatments for cyanide poisoning. Intubation would be appropriate treatment in the context of airway burns but this patient has no evidence of these, although close monitoring would be advised. High-flow oxygen is the treatment for carbon monoxide poisoning - a sensible differential, but this man's very high lactate and high venous pO2 fit better with cyanide toxicity. Intravenous dexamethasone would be another treatment for airway oedema once a endotracheal tube had been placed. Intravenous sodium nitroprusside is a treatment for high blood pressure that can cause cyanide poisoning, and would therefore be inappropriate. Cyanide poisoning Cyanide may be used in insecticides, photograph development and the production of certain metals. Toxicity results from reversible inhibition of cellular oxidising enzymes Presentation 'classical' features: brick-red skin, smell of bitter almonds acute: hypoxia, hypotension, headache, confusion chronic: ataxia, peripheral neuropathy, dermatitis Management supportive measures: 100% oxygen definitive: hydroxocobalamin (intravenously), also combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously)
- The inclusion of an ABG with a metabolic acidosis invites the reader to calculate the anion gap. In this case {[Na+] + [K+]} - {[HCO3-] + [Cl-]} = 27.6 mmol/l A raised anion gap metabolic acidosis - all of the possible answers here may produce this picture. As this man is homeless and we are given no further information the most likely causes for his presentation are alcohol, methanol and ethylene glycol (anti-freeze). The answer here is indicated by the reduced vision and poorly reactive pupils - a common complication of methanol poisoning. A metabolite of methanol, formic acid, accumulates in the optic nerve causing visual disturbance and eventually blindness. Alcohol and ethylene glycol would not produce these visual changes. Aspirin overdose might also be associated with a respiratory alkalosis - not seen here. Despite the limited information this presentation does not suggest tricyclic overdose - you would expect dilated pupils and a history of depression. Methanol poisoning causes both the effects associated with alcohol (intoxication, nausea etc) and also specific visual problems, including blindness. These effects are thought to be secondary to the accumulation of formic acid. The actual pathophysiology of methanol-associated visual loss is not fully understood but it is thought to be caused by a form of optic neuropathy Management fomepizole or ethanol haemodialysis