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Toxicology National Review Course Dr. Marco Sivilotti Dr. Ian Ball October 17, 2013.

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1 Toxicology National Review Course Dr. Marco Sivilotti Dr. Ian Ball October 17, 2013

2 Acknowledgements Dr. Jason Lord, University of Calgary

3 Objectives 1.Clinical examination of the overdosed patient 2.General treatment strategies 3.Common poisonings 4.Toxicological concepts applicable to the ER 5.Examinable / Important Lists

4 History unreliable? What was ingested? How much and when? What was the patient doing when they became ill? Past medical records or d/c summaries Talk to family, friends, paramedics Search belongings All bottles and containers – pill count Search scene ie/ home or garage Track marks, packer and stuffer Query pharmacy or provincial datasets

5 Physical Examination Vital Signs including temp and glucose ABCs (Kussmaul, breath odour, Cspine) D = mental status, seizures, tone E = expose, skin findings Autonomic nervous system TOXIDROME

6 Odors in Toxicology Almonds – CN Mint – Methyl Salicylate Fruity – Acetone, ETOH, Isopropyl Alcohol Garlic – Organophosphates, Arsenic Glue – Toluene, solvents Rotten Eggs – Hydrogen Sulfide Pears – Paraldehyde, Chloral Hydrate

7 Know Your Toxidromes Mental Status Vital Signs Pupils Skin Secretions Motor Activity GI/GU



10 Toxidromes: Cholinergic Muscarinic symptoms – Peripheral: DUMBELS (diarrhea/diaphoresis, urination, miosis, bradycardia/bronchospasm, emesis, lacrimation, salivation) or SLUDGE Central: seizures, dec LOC Nicotinic symptoms – Fasciculations, weakness, respiratory arrest Organophosphates, carbamates, nerve agents

11 Anticholinergic = AntiMUSCARINIC Mad as a hatter, Blind as a bat, Dry as a bone, Hot as a hare, Red as a beet (Anti-DUMBELS) - hot, flushed and dry skin, tachycardia, hypertension, psychosis, mydriasis Cyclic antidepressants, atropine, benztropine, antihistamines, antiemetics, Jimson weed


13 Toxidromes: Opioid –Decreased LOC –Respiratory depression –Miosis miosis may be absent with meperidine microdose/titrated naloxone to reverse respiratory depression

14 Toxidromes: Sedative/Hypnotics CNS depression (respiratory depression late, and only at very high doses) hallmark is spared pupillary reactions and normal VS Barbiturates, Ethanol, Benzos, GHB

15 Toxidromes: Sympathomimetics Psychosis, diaphoresis, mydriasis, agitated, seizure, tremors, HTN (wide pulse pressure), tachycardic, tachypneic Amphetamines, cocaine

16 Cocaine: Pharmacokinetics Variable onset (Body packers vs stuffers) Duration of effect short Direct Na channel blocker, interferes with neurotransmitter uptake, vasoconstriction Sensitizes the myocardium to catecholamines and decreases myocardial blood flow Increased platelet adhesion Combines with EtOH to form cocaethylene (more potent, longer acting, inc CV injury)

17 Cocaine: Clinical Features Sympathomimetic Toxidrome CNS: excitation, psychosis, bleeds, seizure, washed out syndrome CV – ischemia, AMI, HTN, platelet aggregation, dysrhythmias, Ao dissection, sudden death 1.Vasospasm 2.Thrombus 3.Increased O2 demand – ischemia 4.Dissection 5.Cardiomyopathy

18 Cocaine: Clinical Features Resp – Asthma exacerbation, NCPE, PTX, airway burns, pneumomediastinum, pulmonary HTN MSK – Rhabdo and ARF Psych – cocaine bugs, excoriations, crack dancing (choreoathetoid movements)

19 Cocaine: Treatment AC if stuffer or WBI if packer Aggressively treat agitation with BENZOS Hyperthermia associated with death – paralyze with nondepolarizing agents and pack in ice Refractory HTN - Alpha blockade with phentolamine 1-5 mg Q5min PRN or Nitroprusside infusion AVOID Beta blockers (unopposed alpha stimulation), neuroleptics (lower seizure threshold)


21 What Tests Should You Order? CBC, full lytes (anion gap) If altered mental status: capillary glucose, EtOH If deliberate self-harm: ASA, APAP, pregnancy test If suspect toxic alcohol: volatiles (serum osm if cannot) If sick: ABG or VBG, lactate Specific levels: Dig, Fe, DPH, VAL, CBZ, Li, theo 12-lead ECG

22 What Test Should You NOT Order? Urine drug screen –Tests for common drugs of abuse, at threshold appropriate to screen employees for recent use –Fun to guess results, but easier/faster to ask the patient –Results rarely change ED management

23 Extra tests to consider CXR –Caustics, Aspiration Abdominal XR –Body packer –CHIPES: Chloral hydrate, Heavy Metals, Iron, Phenothiazines, EC tablets, Solvents Urinalysis –FeCl 2 (ASA), pH, ketones, myoglobin

24 When is it Safe to Discharge My Patient? If intentional ingestion for self-harm, 6 hrs of observation recommended, provided: 1.History does not suggest a dangerous substance or toxic time bomb 2.Asymptomatic 3.Routine labs are negative 4.Reliable observer at discharge 5.Psychiatric issues addressed

25 Toxic Time Bombs AcetaminophenMethadone AnticoagulantsMAOIs AntimetabolitesHypoglycemics Body PackersSotalol Enteric coated products (ASA)SR products Heavy metalsThyroids meds IronToxic alcohols LithiumValproic acid LomotilTricyclics

26 When is it Safe to Discharge My Patient? Now, if accidental and assuredly non-toxic ingestion: 1.Product identified with certainty 2.Single product involved 3.Reliable estimate of maximal possible exposure 4.Asymptomatic 5.Assuredly unintentional/no self-harm intent 6.Reliable patient/parent 7.Poison-proofing advice given

27 Is the CPS a Useful Resource for the Poisoned Patient? Compendium of Pharmaceuticals and Specialties* –60% contain dangerous or misleading advice –Only 21% are adequate to allow clinician to manage overdose Brubacher J, et al. Salty Broth for Salicylate poisoning? CMAJ 165(9). Oct 2002

28 Where to Turn for Advice? Poisindex (Micromedex) Regional Poison Centre Local Toxicologist Textbooks Internet: –UpToDate –ToxBase –ToxiNZ

29 Whom Should I Decontaminate?* Step 1 – Determine risk of ingestion –How much? How toxic? Reliable historian? Step 2 – Decide if substance can be removed –Time of ingestion? Likelihood of recovery? Step 3 – Consider risk/benefit –Any contraindications to procedure? Step 4 – Determine the most appropriate technique –Lavage, Charcoal, WBI?

30 Decontamination 1. Syrup of Ipecac Rarely indicated: –no improved mortality/potential for harm –complicates care, including other GID –contraindicated when potential for seizures or dec LOC, as well as hydrocarbons, caustics –should be considered obsolete

31 Decontamination: 2. Gastric Lavage Life threatening ingestion despite maximal supportive care/antidote/elim going forward Drug in stomach (cf < 1 hr since ingestion) 10-30% reduction in absorption –ASA, colchicine, TCA 40 Fr Ewald (15-28 in peds) after RSI left lateral decubitus position 200 cc aliquots warm tap water until clear Finish off with AC and remove tube

32 Decontamination: 3. Activated Charcoal Recent, likely toxic ingestion (soft hour) Not useful – alcohols, metals, hydrocarbons C/I = caustics, aspiration, ileus, perforation 1 g/kg plain or with sorbitol OR 10:1 rule (for every ingested 1g toxin, give 10 g charcoal) –e.g. ASA, theophylline (10+g ingestions)

33 Decontamination: 4. Multidose Activated Charcoal Severe ingestions that are well adsorbed –EC or SR drugs, toxins that slow GI motility, enterohepatic recirculation, anticonvulsants –0.25 to 0.5 g/kg q2-4h PLAIN AC (no sorbitol) –Probably effective: phenobarb, CBZ, quinine, theophylline –Possibly effective: digoxin, VAL, sotalol

34 Decontamination: 5. Whole Bowel Irrigation Life-threatening ingestion in which MD-AC or GL of limited utility –Iron, body packers, heavy metals like Pb –sustained release CCBs Isotonic PEG solution –Not absorbed, no fluid shifts –2L/hr via ng until effluent clear (c. 6 hrs) –500 ml/hr in children

35 Enhanced Elimination: 1. Urinary Alkalinization Promotes ionization of the excreted drug which prevents tubular reabsorption –Useful for ingestions of weak acids ASA, phenobarb, chlorpropamide –Target urine pH >7 –Often difficult to achieve your target pH Replenish Na and K, Foley catheter and hourly pH ASA, lytes q2h –Do not use acetazolamide b/c of concomitant metabolic acidosis and inc toxicity –Not forced diuresis

36 HA H + + A - HA A - + H + Blood Urine HA H + + A - HA A - + H + Blood: lower pH Urine: higher pH Unionized molecules diffuse across renal tubular membranes from blood to renal filtrate but ionized ones cannot cross from one compartment into the other. When urine is alkalinized, weak acids like salicylates will dissociate into ions, become trapped and excreted in the urine. Unionized parent molecules then diffuse down their concentration gradient from blood into the urine.

37 Enhanced Elimination: 2. Hemodialysis Small Vd, low protein binding, small size, water soluble, low endogenous clearance –methanol, ethylene glycol, ASA, Li, Theophylline –Less commonly severe acetaminophen, VAL, atenolol, sotalol

38 Enhanced Elimination: 3. Continuous Renal Replacement NOT generally of benefit for removing toxins peritoneal dialysis also NOT helpful

39 Case A 24 year female presents to the emergency following a mixed drug ingestion. The paramedics find empty containers of acetaminophen, ASA and diazepam. The ingestion was witnessed approximately 45 min ago. She is now obtunded. What form of GI decontamination, if any, should be performed?

40 One good answer Following RSI for airway protection, I will give her 50g of activated charcoal with sorbitol after the position of the ng tube has been confirmed radiographically. The need for subsequent doses of charcoal could be predicated upon the serial serum salicylate concentrations.

41 Thou Shalt Know the Big Ones APAP ASA (Toxic) Alcohols CCBs Dig Cocaine Methamphetamine Opioids OP/nerve agents CO Cyanide Iron in a toddler TCAs Caustics Antidotes and maybe a few more

42 Acetaminophen Antidote: N-acetylcysteine Ideally administer within 8 hrs of ingestion Mechanism of action: 1.GSH precursor 2.GSH substitute 3.Substrate for sulfation 4.Non-specific free radical binder

43 Acetaminophen: 1. Single Ingestion < 8 Hours Toxic dose >150 mg/kg Rumack-Matthew Nomogram at 4+ hrs (use the lower line of 1000 M or 150 g/mL) Pre-4 hour level helpful? –If undetectable, excludes APAP overdose

44 Acetaminophen: 2. Single Ingestion Between 8-24 hrs Start NAC if likely toxic/symptomatic Send serum acetaminophen level, AST, INR Continue NAC based on level plotted on nomogram, until Stopping Criteria met Efficacy of NAC decreases with time if administered post 8 hours –Only rare fatalities if initiated within 24 hours

45 Acetaminophen: 3. Staggered, Unknown or Ingestion > 24 hrs Empirically start NAC if concerning history and symptomatic Draw serum acetaminophen, AST and INR –If any are abnormal (ie detectable APAP, AST > 100, OR INR > 1.5) – treat until Stopping Criteria met –If all normal (undetectable APAP, AST < 100, AND INR < 1.5) – D/C NAC Some countries use creatinine as well

46 Acetaminophen: 4. Slow Release Formulations Draw serum acetaminophen at 4 hrs –If above toxic threshold on nomogram = NAC –Subtoxic level – repeat serum level at 8 hrs, and treat if above threshold

47 Patient-tailored Acetylcysteine

48 Continue NAC until Stopping Criteria: –[APAP] undetectable –AST or ALT < 100 IU/L (or have peaked), AND –INR < 1.5 OR transplant/death

49 Patient-tailored Acetylcysteine Start NAC unless: –below Rumack-Matthew nomogram –Stopping Criteria are met at the outset

50 N-acetylcysteine IV protocol used in Canada –150 mg/kg over 60 minutes –12.5 mg/kg/hr for 4 hours –6.25 mg/kg/hr until Stopping Criteria met: –? double the 6.25 to 12.5 in high risk pt?? Do not write for finite duration APAP, AST, ALT, INR, lytes q12h

51 Anaphylactoid reactions to N-AC Stop the infusion diphenhydramine, fluids, rarely more Verify need for N-AC, and resume at slower rate if still indicated No need to withhold in future

52 Case A 75 year old alcoholic male fell and broke several ribs a few days ago. He has been taking 2 extra strength Tylenol every few hours for 3 days. He presents with abdominal pain and nausea. How would you manage this patient?

53 Case Start NAC empirically (?orally), draw Acetaminophen level, AST and INR in addition to other bloodwork, and treat until normalize (if AST abnormal at baseline, treat until returns to prior baseline, or peaks and falls by >50% of peak)

54 Salicylates: Pharmacokinetics Rapidly absorbed in therapeutic doses –NOT after overdose! Rapidly eliminated in therapeutic doses –NOT after overdose! (zero order kinetics) No antidote! Toxicity = rate of absorption > rate of elimination Serum level cannot be interpreted in isolation, without knowing serum pH! Serum levels most helpful in hindsight!

55 Salicylates Done Nomogram NOT clinically useful –Modeled after single, acute ingestion of NON- EC ASA, in peds! –Nontoxic levels drawn before 6 hrs not useful –Patients may become rapidly toxic prior to 6 hr –Not useful for staggered or chronic ingestions –Does not correlate with serum pH or clinical status TREAT THE PATIENT, NOT THE LEVEL!

56 Salicylates: Toxicity Every organ system affected, but… …Brain toxicity kills patient Beware methyl salicylate (7.5 g ASA in 5cc); most toddler exposures die en route to pediatric hemodialysis centre!

57 Salicylates: Clinical Presentation Early = N/V, tinnitus, diaphoresis, confusion, deafness, tachypnea, vertigo, respiratory alkalosis (direct stimulation) Late = anion gap metabolic acidosis, LOC, NCPE, hypoglycemia, hepatic and renal dysfunction, death

58 Increased tissue and CNS penetration with acidosis is a very important concept! Fastest way to kill an ASA overdose is to sedate for agitation! Decreasing serum levels may reflect: Increased ASA excretion, OR Increased tissue penetration and toxicity

59 AcuteChronic AgeYoungerOlder EtiologyOverdoseAccidental DxClassicSubtle ComorbiditiesFewMany Suicide attemptOftenRarely Clinical courseRapid Progression Neurologic Predominate (nonspecific) Serum levels MortalityUncommon~ 25%

60 The Anion Gap Sodium – (Chloride + Bicarb) –N = 7 +/- 4 meq/L –MUDPILES CAT –Serum lactate (Elevated level does not rule out a toxic ingestion) –Serial measurements are very important –Venous gas can be substituted for ABG

61 Salicylates: Treatment Volume resuscitate! GL, MDAC and WBI all recommended Urinary alkalinization Empiric dextrose (low CNS Glc) Use pH and mental status to guide Rx

62 Salicylates: Alkalinization Indications: –Symptoms of salicylism Tinnitus Metabolic derangements –Serum level > 2 mmol/L (or expected to get there!)

63 Salicylates: Alkalinization Target Urine pH >7 Keep serum pH < 7.55 Avoid hypokalemia (K + /H + exchange in distal tubule) No role for forced diuresis q2h testing of lytes and salicylate levels

64 Salicylates: Hemodialysis Indications: –Worsening clinical status –End organ toxicity – AKI, NCPE, CNS –Severe acid base disturbance –Volume overload –Serum level > 7 mmol/L (acute) or > 4 mmol/L (chronic)… or expected to get there despite urine alkalinization and GID!

65 Tricyclic Antidepressants: Pharmacokinetics Rapidly absorbed, large Vd, variable protein binding, lipophilic Mechanism of action: –Inhibits voltage gated Na channels (prolongs phase 0 depolarization) and blocks K efflux –Negative cardiac inotrope –Blocks H1, H2 and D2 receptors –Blocks muscarinic receptors –Alpha blockade –Inhibits DA, serotonin & Norepinephrine reuptake & interacts with GABA receptors

66 Tricyclic Antidepressants: Clinical Presentation End organ effects 1.Cardiovascular : hypotension, widened QRS and Qt, dysrythmias 2.CNS: abrupt and unpredictable decreased LOC and seizure 3.Anticholinergic toxicity: Tachycardia, confused, flushed

67 Tricyclic Antidepressants: Diagnosis Drug levels do NOT correlate with toxicity EKG diagnostic of Na channel blockade:* –limb QRS >100 msec = 30% risk seizure –>160 msec = 50% risk arrhythmias –R axis deviation in terminal 40 msec QRS of aVR (tall slurred R wave > 3mm) –Sinus tachycardia with prolonged QT interval Boehnert & Lovejoy, NEJM, 1985

68 Lead I Lead aVR

69 Tricyclic Antidepressants: Treatment Consider gastric lavage and AC Beware rapid LOC and seizures Avoid acidosis at all costs (seizures, BP, CO 2 ) Sodium bicarbonate boluses for wide QRS

70 Tricyclic Antidepressants: Treatment Indications for Alkalinization: –QRS >100 msec in limb leads –VT (Second Line = Lidocaine, Amiodarone) –Cardiac arrest in young adult

71 Tricyclic Antidepressants: Treatment Hypertonic Saline (when serum pH > 7.55) Benzos for sedation or seizure, propofol if refractory Fluids and -agonists for hypotension Physostigmine can be considered if survive cardiac toxicity Hoffman, Votey et al., Am J Emerg Med 1993 Hoegholm & Clementsen, J Toxicol Clin Toxicol 1991

72 Digitalis: Pharmacokinetics Binds to the Na-K ATPase (inhibits active transport of Na and K) –Increased intracellular Ca Enhanced automaticity with decreased conduction + Vagolytic –ECG: Slow A. Fib, Nonparoxsymal junctional tachycardia, Atrial tachycardia with block, Bidirectional V. Tach

73 Digitalis: Clinical Presentation Acute hyperkalemia G/I = sine qua non: N/V, anorexia, abdominal pain CNS – confusion, dec LOC, headache, seizures Visual – blurred, scotoma, altered color vision, halos

74 Digitalis: Treatment MDAC Correct serum electrolytes Atropine for bradycardia (may not be effective) Avoid 1A, 1C antidysrhythmics Avoid Calcium if concomitant AKI Digoxin specific FAB fragments (Digibind)

75 Digoxin: Digibind Binds free drug and promotes transport of bound digoxin from tissue to serum Bound drug excreted renally Onset ~ 15 min (complete by 90 min) Downside – cost.

76 Digoxin FAB Indications A.Adults: 1.Ventricular dysrhythmia 2.Progressive/refractory hemodynamic instability or bradycardia 3.K > 5 mmol/L (acute) 4.Ingested Plant + dysrhythmia 5.Acute ingestion > 10 mg (adult) or 4 mg (peds)

77 Digoxin FAB Indications B.Pediatrics: 1.Ingested dose > 0.1 mg/kg or serum level > 5 ng/ml with progressive symptoms or K > 5 2.Coingestion with other CV med or TCA 3.Ingested plant + other indication

78 Digoxin: FAB Dosing 1.Empiric: Acute: adults and peds 5 vials Chronic: adults 2-4 vials, peds 1 vial 2.Based on steady state Vd (~6 hrs): (serum dig level x wt in kg) / 100 = # vials

79 Pitfalls of Using the Serum Digoxin Level Interpreted with other electrolytes Pre-redistribution levels high (within 6 hr of ingestion) False positives can occur Assays vary after FAB treatment; may be very high if measure total dig Other cardiac steroids variably detected

80 Iron: Pharmacokinetics Prescribed as Ferrous gluconate, sulfate and fumarate with differing elemental Fe concentrations; other forumulations available –< 20 mg/kg elemental Fe – likely asymptomatic –> 20 mg/kg – self limiting GI symptoms –> 40 mg/kg – potentially serious –> 60 mg/kg – may be lethal (~ 5 tabs for a toddler) Toxicity: –Direct caustic injury to GI mucosa –Impaired intracellular metabolism – liver, CNS and CV collapse

81 Iron: Clinical Manifestations 1.Stage I: 0-6 hrs Acute corrosive effects on GI tract N/V, diarrhea, abd pain and hypovolemia If asymptomatic at 6 hours – no sig OD 2.Stage II: 6-12 hrs Latent stage with apparent recovery Never asymptomatic, just less violently ill

82 Iron: Clinical Manifestations 3.Stage III: hrs Acidosis, CV collapse, GI bleed, lethargy and coma 4.Stage IV: 2-5 days Hepatic failure / death 5.Stage V: delayed corrosive effects GI scarring, strictures and obstruction

83 Iron: Diagnosis AXR if suspicious, does not rule out Serum Fe level 4 hours post ingestion –<55 umol/L – Do not treat –55-90 umol/L – Treat if s/s –>90 umol/L – Treat all Repeat level at 8 hours with SR or EC preps

84 Iron Treatment Fluid resuscitation WBI No role for AC Deferoxamine IV x 24 hrs –chelates Fe renally excreted –Resp toxicity (ARDS) with prolonged infusion –Slow infusion if hypotension develops –Yersinia sepsis…

85 Iron: Causes of Metabolic Acidosis Conversion of Fe2+ to Fe3+ liberates H+ Vasodilation and BP – lactic acidosis Direct neg inotrope = Cardiac output Disrupts oxidative metabolism

86 Toxic Alcohols Ethylene Glycol, Methanol, Isopropanol Same kinetics as ethanol: –peak serum levels by 1 hour –rapidly distribute into body water –small Vd, not protein bound –easily dialyzable Toxic acid metabolites of EG and MeOH

87 Ethylene Glycol Present in antifreezes and coolants Metabolized by alcohol dehydrogenase glycoaldehyde, glycolic acid and oxalic acid Inhibit oxidative phosphorylation and are directly toxic to lungs, kidney and CNS Calcium oxalate crystals

88 Methanol Present in window cleaning solutions, solvents, some antifreezes Metabolized by alcohol dehydrogenase formaldehyde and formic acid Inhibit cellular respiration and directly toxic to CNS (including retina)

89 Ethylene Glycol: Clinical Presentation 1.Acute Neurologic Stage (30 min – 12 hrs) Inebriation, seizure, N/V, coma, osmolar gap 2.Cardiopulmonary Stage (12-24 hrs) HTN, tachycardia, tachypnea, AKI, metabolic acidosis +/- pulmonary edema or circulatory collapse Hypocalcemia and dysrhythmias

90 Ethylene Glycol: Clinical Presentation 3.Renal Stage (24-72 hrs) Crystalluria, hematuria, proteinuria, ATN and flank pain 4.Delayed Neurologic Stage (6-12 d) Cranial nerve palsies, deafness, cognitive and motor abnormalities, personality changes

91 Methanol: Clinical Presentation Early – inebriation, gastritis, altered LOC, ataxia Late – Visual changes snowstorm blindness, altered LOC, metabolic acidosis, seizures –Optic disc hyperemia, papilledema, sluggish pupils

92 Toxic Alcohols Diagnosis and the Gaps Forget the Woods lamp and crystals! Increased Anion Gap metabolic acidosis Increased Osmolar Gap = Calculated Osmolality – Measured Osmolality 2 Na + Glucose + BUN Etoh (N = -2 +/- 6 mOsm) –(Ethanol, Ethylene glycol, Methanol, Isopropyl alcohol, Mannitol, Glycerol)

93 Gap Dynamics…

94 Toxic Alcohols: Treatment 1.Correct acidosis with Bicarb –Prevents diffusion of toxic metabolites into target tissues

95 Toxic Alcohols: Treatment 2.Inhibit alcohol dehydrogenase –Suspected ingestion and 2 of: Osmolar gap > 10 pH < 7.3 Bicarb < 20 Urinary oxalate crystals –Serum EG > 3mmol/l or Meoh level > 6 mmol/L –Documented ingestion and Osm Gap > 10 a.Etoh: Target serum Etoh level > 20 mmol/L b.Fomepizole (4MP) – easier administration, predictable, more potent inhibitor of ADH, safer, avoids labs, longer half-life, no altered LOC

96 Toxic Alcohols: Treatment 3.Enhanced metabolite elimination with Hemodialysis –Serum EG > 8 mmol/L or Meoh > 15 mmol/L –Metabolic acidosis –Renal impairment –Electrolyte abnormalities –Unstable VS –END ORGAN DYSFUNCTION

97 Toxic Alcohols: Treatment 4.Adjunctive Treatments Folic/Folinic Acid 50 mg IV q6h for methanol (very important) Thiamine 100 mg IV and Pyridoxine for ethylene glycol (not so important) Calcium replacement for EG Serial monitoring of acidosis and electrolytes

98 Toxic Alcohols: Triage Tools Fixed and dilated pupils very poor prognostic sign following methanol ingestion ABG allows you to make immediate decisions regarding fomepizole and hemodialysis A loading dose of fomepizole buys you hours of time in non-acidotic patient Serial testing without ADH blockade following accidental sipif pH remains normal after 6 hours can discharge (*unless EtOH or fomepizole on board*)

99 Carbon Monoxide Most common cause of death by poisoning in the US (20% accidental) Mild (5-10%) - mild headache, mild dyspnea Mod (10-30%) - headache, weakness, dizzyness, dyspnea, irritability, N/V Severe (>30%) - coma, seizures, MSOF, death Delayed neuropsychiatric sequelae in 10-30% of survivors (levels not predictive) Pulse oximeter falsely normal

100 So why is 50% carboxyhemoglobin fatal?


102 Carbon Monoxide 1/2 life carboxyhemoglobin on room air = 5-6 hrs 1/2 life 100% O2 = min 1/2 life HBO (3 atm) = min* –Indications controversial (dec LOC, severe symptoms or levels, met acidosis, age >50 or preg - d/w toxicologist) –Reduced delayed sequelae if dived within 24hrs (maybe…) Juurlink et al., Cochrane Database Sys Rev 2000 Weaver et al., NEJM 2002 Thom et al., Ann Emerg Med 1995 Kao & Nanogas, Med Clin NA, Review

103 There is insufficient evidence to support the use of hyperbaric oxygen for treatment of patients with carbon monoxide poisoning Bottom line:

104 Toxins and Seizures AnticholinergicsMethylxanthines AntidepressantsOpiods ASAPropranolol CamphorStimulants CarbamazapineTCAs TegretolWithdrawal INH

105 Intractable Seizures ABCs, glucose, benzos benzos benzos Propofol, Phenobarbital, Pyridoxine Preeclampsia / hyponatremia (MDMA) / INH INH overdose –Inhibits the formation of an important substrate required for GABA –Pyridoxine replaces this substrate

106 Tox – ACLS Sodium bicarbonate first line agent for wide complex tachycardias (Cocaine, TCA) or tox arrest Avoid procainamide Direct pressor (norepi) for refractory hypotension Prolonged resuscitative efforts not always futile Extracorporeal circulatory assistance in extremis

107 Single Tablet/Dose Toxins That Kill CamphorTheophylline SulfonylureasMethyl salicylate Essential oilsQuinine ChloroquinePhenothiazines Ca blockersTCAs Beta blockersLomotil Methadone

108 Nifty antidotes Octreotide Physostigmine High dose insulin Intralipid Hydroxocobalamin

109 Clinical Syndromes from Chemical Exposures SyndromeEtiology CholinergicOrganophosphates, nicotine, carbamates Muscle Rigidity or seizuresStrychnine Oropharyngeal pain and ulcersParaquat, diquat, caustics, inorganic mercuric salts, mustards Cellular hypoxiaCyanide, CO, methemoglobin causing agents Peripheral neuropathies or neurocognitive Organic mercurics, Lead, Arsenic Severe GI distressRicin, Arsenic, Colchicine MMWR 52(39) Oct 3, 2003

110 Hyperthermia, Altered Mental Status and Rigidity Malignant hyperthermia Serotonin Syndrome Neuroleptic Malignant Syndrome MAOI overdose

111 DiseaseMechanismClinicalOnsetTreatment NMS Central DA activity in thalamus Neuroleptic use, Rigid Gradual, daysBenzos, hydrate, cool, paralysis ? Bromocriptine or Dantrolene Serotonin Syx Serotonin in CNS Recent SSRI or DA agonist DTR, clonus Rapid with recent dose or drug change Benzos, hydrate, cool Cyproheptadine Malignant Hyperthermia Genetically unstable sarc. Retic. massive Ca release Inhalational anesthetic or sux Rigid ImmediateHydrate, cool Dantrolene MAOI ODInhibited monoamine oxidase Adrenergic overdrive VariableHydrate, cool, paralysis

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