Toxicology Flashcards
Acetaminophen Measurement Toxicity - Nomogram
Rumack-Matthew nomogram - determines treatment line
Acetaminophen treatment levels
APAP > Nomogram treatment level
Elevated AST with unknown ingestion time and APAP below treatment line
150 mg/kg ingestion and cannot get APAP level within 8 hours
History of chronic toxicity / repeat supratheraputic and elevated AST or
DO NOT Tx IF:
Ingestion > 4 hours ago and below nomogram threshold
Suspected ingestion > 4 hours ago and undetected APAP and no elevation of AST
GI decontamination strategies
Whole bowel irrigation
Gastric lavage
Activated Charcoal
Gastric lavage indications and contraindications
Ingestion within 1 hour (real life is “reasonable time frame” - also based severity of drugs)
- Usually within first 2-3 hours
Substance not bound by AC and has no antidote
Benefits outweigh risks
Contraindications:
Spontaneous Emesis
altered LOC - intubate first
Hydrocarbons, caustic substances or foreign body
High risk for GI injury (esophageal/gastric sx, GI hemorrhage)
Complications:
Aspiration, perforation, laryngospasm, fluid and electrolytes imbalance, dysrhythmia, hypoxia
Activated charcoal indications / contraindications
General: Used to adsorb ingested agents
- Ratio of 10-1: 10 g charcoal for 1 g substance or 1g/kg
Indications:
- Within 1 hour of ingestion
- Dangerous amount of poison adsorbed by charcoal
- Multiple dose may be appropriate after 2 hours for some agents (carbamazepine)
Contraindications:
- Not adsorbed by charcoal: metals or alcohols
- If vomiting presents greater danger: caustic agent or hydrocarbons
- Diminished LOC / unprotected airway
- If endoscopy required or patient at risk for perf / hemorrhage
Whole bowel irrigation indications / contraindications
General: flushes GI tract to decrease transit time
- PEG given at 1-2 L/hr to total of 10 L
Indications:
- Removal of drug packets
- Large ingestion of sustained release drug
- Ingestion of substance not treated by AC
- Lithium and Iron
Contraindications:
- Altered LOC with unprotected airway reflexes
- Decreased GI motility / obstruction / GI hemorrhage / Emesis
What is enhanced elimination
Attempts to increase clearance of a poison after it has been absorbed,
e.g. alkalinization or urine, MDAC, hemodialysis
MDAC
Q2-4 hour dosing of AC - reduced enterohepatic circulation / gut dialysis
Indications:
- Sustained release
- Bezoars
e.g. carbemazepine, quinine, phenobarb, valproic acid, theophylline, dapsone
Risk of bowel obstruction
Can do 2 dose of SDAC for ASA, Dig, Bupropion - this is NOT MDAC.
Urinary Alkalinzation
Increases renal elimination by ion trapping
- Use bicarb infusion at 1.5 - 2x normal maintenance rate
Indications: Weak acids. ASA, methotrexate, phenobarbitol
Contraindications: Renal insufficiency, CHF
Hemodialysis for toxic ingestions
Indications:
- Low molecular weight
- low plasma protein binding
- poor endogenous clearance
- can treat severe acidosis even if the toxin is not dialyzable.
e.g. Alcohols, ASA, Lithium, metformin
ASA
Toxic alcohols
Theophylline
Phenobarb
Lithium
Massive Acetaminophen
Valproic Acid
SANTA - BETA BLOCKERS
Sotalol, Atenolol, Nadalol, Timolol, Acetenolol
Toxidromes: Anticholinergic
altered LOC
DRY skin
mydriasis
hyperthermia
seizures
tachycardia
urinary retention
Tx: Benzos and physostigmine
Toxidromes: Sympathomimetic
agitation
Diaphoresis
Hallucinations
HTN
Hyperthermia
Mydriasis
Muscular rigidity
Tachycardia
Tx: Benzos
Bicarb for wide complex dysrhythmias
Toxidromes: Cholinergic
Altered LOC
Bradycardia
Bronchorrhea
Bronchospasm
N/V/D
Urination
Seizures
Miosis
Salivation
Tx: Atropine, 2-PAM
Toxidromes: Opioid
Miosis
Bradypnea
Altered LOC
Hypothermia
Tx: Naloxone
ECG Changes in Tox: Bradydysrhythmia
B-Blockers
CCB
Cardiac glycosides
Clonidine
ECG Changes in Tox: Tachydysrhythmia
Sympathomimetics
Stimulants
Anti-cholinerigics
For wide complex - give Bicarb
ECG Changes in Tox: QRS Wide
Na+ channel blockers
Quinidine
Sedating antihistamines
Cocaine
TCA
ECG Changes in Tox: QTc Long
Antipsychotics
SSRI / Antidepressantins
Antidysrhythmics
Hydrofluoric acid
ECG Changes in Tox: Ischemia
Stimulants
Sympathomimetics
ECG Changes in Tox: TCAs
Right axis deviation
Terminal R in aVR
QRS prolongation
ECG Changes in Tox: Digoxin
Downsloping ST depression with a characteristic “reverse tick” or “Salvador Dali sagging” appearance
Flattened, inverted, or biphasic T waves
Shortened QT interval
APAP toxicity mechanism
APAP converted to NAPQI in liver
NAPQI binds to cellular proteins and causes hepatotoxicity.
- Centrolobular or zone III
Decreased glutathione in chronic EtOH use, Tylenol use, malnourishment or those on P450 inducing agents (INH, anticonvulsants)
APAP toxic ingestions
Acute Ingestions:
> 6 yrs: >10 g (150 mg/kg)
< 6 yrs: >200 mg/kg
In repeated dosing:
>10 g /day for 24 hours - staggered dosing
> 6 g / day for 48 hours
Children < 6:
>200 mg/kg/d over 24 hrs
> 150 mg/kg/d over 24-48 hrs
> 100 mg/kg/d over 72 hrs
APAP toxicity treatment
N-Acetyl Cysteine NAC
- effective up to 8-10 hrs post.
- ALWAYS GIVE NAC
Oral:
- 140 mg/kg load and 70 mg/kg Q4H for 72 hours
IV
- 150 mg/kg load over 1 hr, then 50 mg/kg over 4 hours then 100 mg/kg over 16 hours.
- Risk of anaphylactoid reactions
If Repeated Supratheraputic doses:
- NAC x 12 hours with repeat APAP and LFTs near end of treatment.
ONTARIO DOSING DIFFERENT
APAP Toxicity Indications for Liver Transplant
King’s College Criteria
pH < 7.3 after resus
or
INR >6.5, Cr > 3.4 mg/dL and grade 3 or 4 hepatic encephalopathy
Remember #3
Creatinine > 300
Grade 3 or 4 encephalopthy
pH < 7.3
INR 6.6 or greater (3.3. x 2)
Mechanisms of NAC
Glutathione precursor
Direct NAPQI conversion
Sulfonization
Free radial Scavenging
Reduces APAP to NAPQI
Massive APAP Ingestion Def’n and Tx
Greater than 500-1000 mg/kg (> 1 pill / kg)
APAP @ 4 hrs > 300 mcg/ml
Anion gap metabolic acidosis
Altered LOC
Tx: Dialysis, AC, NAC, Fomepizole (inhibits CYP 2E1, impairs NAPQI production)
Indications for dialysis:
- Creatinine > 350
- Elevated lactate > 3.5
- Encephalopathy
- Level > 300 mcg/ml
- Metabolic acidosis
ASA Toxicity Presentation
Hyperventilation and metabolic ALKALOSIS
Vomiting
AGMA
Hyperthermia
Tinnitus and hearing loss correlate with ASA level
Cerebral and pulmonary edema
Early blood gas: Resp Alkalosis
Severe Ingestions: metabolic acidosis, hyperthermia, cerebral edema, seizure, hypoglycemia
When to consider ASA toxicity
Chronic use
Hot and Crazy
Tinnitus
Tachypneic
Resp Alkalosis or Metabolic Acidosis or both
Mechanism of alkalinization in ASA
In acidic environment, ASA becomes bound to H+ and can cross BBB.
Goal to alkalinize urine to excrete the dissociated ASA
Tox: ASA Mgmt
ABC
Fluid Resus
Urine Alkalinization
Repeat ASA level at 2 hours
Urine Alkalinization:
Bicarb
Add K+ - need to avoid H-K exchange in nephron to excrete H+ in urine
Add 40 meq in bag
ASA Tox Indications for Dialysis
ALOC
Renal or Hepatic Failure
Pulmonary edema
Severe acidosis
Inability to alkalinize urine
Salicylate > 7 in acute
Salicylate > 3? In chronic
Toxidrome - Sympathomimetic
Excess catecholamines, hypertension, tachycardia, tachypnea, diaphoresis, mydriasis.
Risk for arrhythmias and shock
Causes: MDMA, cocaine, ephedrine, caffeine.
Mgmt: Benzos, fluids and supportive mgmt
Universal antidotes
Dextrose
Oxygen
Narcan
Thiamine
DON’T
Approach to treatment of poisoned patients
ABCDs
Decontamination
Prevent absorption
Enhanced elimination
Give antidotes if indicated
For aLOC keep a broad differential - what are the 5 broad categories
Drugs
Infection
Metabolic
Environmental
Structural
Antidotes for most common poisons
Acetaminophen - NAC
Methanol / Ethylene Glycol - Fomepizole/EtOH
CO - O2 and hyperbarics
Opioids - Narcan / naloxone
Anticholinergics - Physostigmine
Organophosphates - Atropine and 2-PAM
Methemoglobinemia - Methylene blue
Cyanide - B12 / cyanokit
Iron - Deferoxamine
Arsenic / Lead - Dimercaprol
Mercury - Succimer
Dixogin - Digifab
Crotalids - fab fragments
Beta Blockers - High dose insulin, Ca2+ and glucagon
Salicylates / TCA - Bicarb
CCBs - Ca, high dose insulin
Oral hypoglycemics - Glucose +/- octreotide
Isoniazid - Pyridoxine (B6)
LAST - Intralipid
6 Radiopaque Toxins
CHIPES
Chlorinated hydrocarbons, calcium salts, crack vials
Heavy metals (Iron, aresenic, valium, lead)
Iodinated (Amiodarone, thyroxines)
Psychotropics - lithium, TCA, packers, potassium salts
Enteric coated
Sodium salts, salicylates
Activated charcoal indications - what are the killer C’s
Cyanide
Colchicine
CCB
TCA
Cardioglycosides
Cyclopeptide mushrooms
Cocaine
Cicutoxin (water hemlock)
Calicylates
Indications for activated charcoal administration (T’s)
Timing - < 1-2 hours
Toxic - known lethal toxin
Ton of it - massive ingestion
Tacky - Adsorption can work
Tasty - Willing to take
Things that DO NOT BIND or will not work with AC
Pesticides
Heavy metals
Acids / Alkali
Iron
Lithium
Solvents
Anticholinergic toxidrome = antimuscarinic toxidrome = what symptoms ?
Hyperthermia
Delerium / aLOC / seizure
Anhidrosis
Urinary retention
Mydriassis
Flushing
Decreased bowel sounds
Anticholinergic meds
Weeds: Jimson
Atropine / scopolamine
antihistamines (H1)
Antiparkinsons (benztropine)
TCA
Mgmt of anticholinergics
Stabilization:
- Supportive care
- Treat fever
- Benzos for seizure
- Intubate if temp not responsive to evaporative cooling
Decontamination:
- Generally not needed
Antidote: Physostigmine
- Contraindicated in TCA, wide QRS, AV blocks, bradycardia, co-ingestions
7 Effects of TCAs
Na channel blockade
- wide QRS
K+ channel blockade
- Long QTc
Antihistamine
- hypotension / sedation
Anticholinergic
- classic tox
GABA blockade
- Seizure
Serotonin and NE uptake inhibition
- sympathomimetic
Alpha 1 blockade
- hyptension
ECG findings in TCA
Wide QRS
Long QTc
terminal R in avR > 3 mm
RAD
Sinus tach - anti-muscarinic
Mgmt of TCA
ABC
Decontaminate:
- AC if > 2 hrs, avoid if unstable and going to RSI
Stabilize:
- Bicarb 2meq/kg bolus until QRS narrows and then infusion. Hypertonic if no bicarb
- IV lidocaine
- Intralipid
Seizures:
- Bicarb, benzos, propofol
Hyperthermia:
- Evaporative and ice immersion
- Intubate, deeply sedate and paralyze if refractory
NO SUCC and NO PHYSOSTIGMINE
NMS vs Serotonin Syndrome
Both have
Fever
Autonomic instability
Rigidity / Rhabdo
Mental status changes
NMS: muscle rigidity (lead pipe)
SS: Spastic, tremor, clonus, increased motor activity. Hyperreflexia
Drugs that induce serotonin syndrome
Cocaine
SSRI
MAOI
TCAs
St. John’s Wort
Ondansetron
SNRI
Tramadol
Fentanyl
Bupropion Toxicity - mechanism and symptoms
NDRI
- Seizures are main toxicity
- Direct cardiac suppressant
8 Drug classes that cause a wide QRS
TCAs
Antihistamines
Class 1A, 1C and 2 antiarrhythmics
Local Anesthetics
Antimalarials
Antispasmodics
Anticonvulsants
Digoxin mechanism and toxicity
Inotrope by inhibition of Na K ATPase, increases intracellular Na, secondarily increases Calcium nito sarcoplasmic retic.
- Decreased SA and AV node conduction
* In toxicity can give tachy/brady AV block sydromes
Toxicity: GI symptoms of N/V annd abdo pain.
- General weakness, headache, dizziness, alOC, snowy vision, scotomas or yellow-green halos
- Acute: Brady and AV block
- Chronic: Ventricular dysrhythmias, bidirectional v tach
ECGs in Dix Toxicity
Slow a fib. A fib with AV dissociation
Atrial tachy with a block
Bidirectional VT
Junctional tachy
Beta-blocker toxicity mgmt
Fluids: If hypotensive - bolus 20-40 mg/kg fluids
Atropine: temporize with atropine in HR < 50
Calcium: 4-6 G calcium gluconate
High dose insulin therapy
- Give 1 amp D50 followed by 1 U /kg of IV insulin. Then 25 g / hr of + insulin at 1 U / kg / hr. Place Central and arterial lines. Increased by 2 U /kg/hr to max of 10 U/kg/hr if still hypotensive.
- Target glucose > 12.
- Replace K+ 2nd to shifting
- Norepi 1st line pressor
- Consider pacing/
ECMO
If Propanalol: Bicarb boluses 1-2 meq/kg Q3-5 mins
If Sotalol: Use lidocaine
- Can overdrive pace is isopreteronol and MgSO4 if torsades
Beta-Blcokers that can be dialyzed
Sotalol
Atenolol
Nadolol
Timolol
Acebutolol
Out of favor: Intralipid and glucagon but can be used as last ditch effort
CCB OD Mgmt
Similar to BB
- MOVIE
- Atropine if brady
- Calcium 3-6g IV
- HDI therapy
- Vasopressors
Last ditch:
- Methylene blue
- Intralipid
- ECMo
Clonidine Toxicity and Mgmt
Central Alpha 2- results in decreased NE
- Hypotension
- Bradycardia
- Depressed LOC
- Miosis
Mgmt:
- Generous fluids
- Vasopressors (NE)
- Naloxone
Differential for Low and Slow
CCB tox
BB tox
Clonidine tox
Hypothermia
Hypokalemia / Hyperkalemia
Myxedema coma
Complete HB / Ischemia
INferior MI
Dig tox
Opioid overdose
Osmolality Eqn
2xNa + BUN + Glucose + 1.25x EtOH
Gap = Measured - Calc
normal < 10 but can vary
AG affected by Albumin levels
Causes of elated Osmolar Gap
Methanol
Ethylene Glycol
Isopropanol
Ethanol
Mannitol
Acetone
Glycerol
Propylene Glycol
Fructose
Sorbitol
DKA
AKA
Sepsis
Uremia
Causes of Anion Cat
Alcoholic Ketoacidosis
Cycanide, CO, Colchicine
Acetaminophen in massive OD
Toluene
Methanol
Uremia
DKA
Paraldehyde
Isoniazid (Iron, Ibuprofen)
Lactic acidocis
Ethylene Glycol
Salicylates
Causes of double gap - i.e. Osmolar and Anion Gap
Ketoacidosis
Uremia
Lactic acidosis
Toxic alcholos
Methanol Metabolism and Toxicity
Methanol - Formic acid
- Snowy vision and blindness
- metabolic acidosis
- Parkinsonism from Putamen poisoning
- Can have massive UGIB from gastritis
Treatment: Fomepizole or EtOH.
- Folic acid for formic acid
-Dialysis
Ethylene Glycol Met and Toxicity
Ethylene Glycol - Glycolic acid - Oxalic Acid
- Renal failure 2nd to crystal in urine
- Inebriation, CNS depression, hypotonia and seizure
- Nystagmus, ataxia and myoclonic jerks
Lab abnormalities: Hypocalcemia, osmolar gap, positive birefringent crystals in urine
Treat:
- Fomepizole
- Thiamine
- Pyridoxine
- Dialysis
Indications for dialysis in toxic OH ingestion
pH < 7.3
Renal fail
Vision in methanol
Electrolytes in hyperK
hemodynamic instability
Concentration > 50.
