4/12 - Toxicology

1. Identify the portions of the history and physical examination, diagnostic evaluation and management of a poisoning/toxicology patient
a. History
i. Medications
1. Dosages
2. Long acting?
3. Number of pills/bottles
4. Other meds
ii. Time taken
iii. Co-ingestion of other drugs, alcohol, substances
iv. Dietary, herbal, food supplements
v. Complete tox history requires someone to go back and check out the scene-
b. Physical Exam
i. ABCD
1. D=dextrose, thiamine for alcoholics or malnutrition -- 100mg IM
ii. Vital Signs
1. Rectal temperature is crucial
2. Glucose test
iii. Mental/Neurologic status
iv. heart/lungs
v. Pupils
vi. Skin
c. Diagnostic Eval
i. CBC, Chem 8, UCG
1. Calculate anion gap
ii. LFTs, coags, serum osmoles, CPK, Mg
1. Calculate osmolar gap
iii. Ethanol, asa and acetaminophen levels (drugs most likely to be taken in overdose) Also consider Valpate, phenytoin, lithium...
iv. EKG
v. ABG
vi. X-Ray: KUB
1. Body packers/stuffers
vii. URINE TOX NOT USEFUL IN ACUTE SETTING​ (signs will either be gone or irrelevant by then- also urine tox doesn’t screen for common overdosed drugs)
d. Initial Management
i. ABCs + Glucose if AMS
ii. Decontamination (activated charcoal, gastric lavage, whole bowel irrigation) before sx appear
iii. Coma cocktail: glucose, thiamine, narcan
iv. Specific antidote
v. Supportive care
2. Describe the evaluation and treatment of patients with the following toxicologic presentations including: ​STARTS ON PG. 17 OF READING
Toxidrome:​ signs that are characteristic of a particular toxin
● Opiate​: pinpoint pupils, respiratory depression
● Cocaine​: tachycardia, HTN, mydriasis, diaphoresis
● Anticholinergic​: same as cocaine except dry instead of diaphoretic

Urine Tox Screen:​ benzos, barbiturates, cocaine, amphetamines, maryjane, PCP, opiates (BB-CAMP-O)
*tool for work tox screen, not to make clinical decisions!
● False ​positives:
○ Amphetamines​: sudafed, trazodone, wellbutrin, ranitidine, amantadine, Vick’s
○ MJ​: ibuprofen, naproxen
○ Opiates​: rifampin, fluoroquinolones
○ PCP​: ketamine, dextromethorphan, benadryl
● False ​negatives:
○ Copious water digestion causes urinary dilution
○ Benzos​: lorazepam, xanax
○ Opioids​: fentanyl, meperidine, methadone
 Agent Clinical Manifestations Evaluation Management

Medication Toxicity

Acetaminophen Early: aSxatic Nomogram ​predicts hepatocellular injury Step 1: ​MDAC and gastro decontamination first​ (activated charcoal if
(APAP) Later: Anorexia, N/V, RUQ pain, jaundice (delayed injury not known what drug pt overdosed with)
24-72 hours after ingestion) Inc LFTs → hepatic failure
4hr APAP post-ingestion concentration Antidote: N- Acetylcysteine (NAC)​ (100% effective if used early)
4 clinical stages​: Serum salicylate concentration Check ​4 hr ​APAP post-ingestion concentrations
1. 0-24h: N/V, normal labs >150 ​microgram/mL → give acetylcysteine (NAC) + hospitalize
2. 1-3d: Asymptomatic, LFTs rise APAP concentration speaks to severity of Available PO/IV
3. 3-5d: Acute liver failure, LFTs peak poisoning Consider NGT and antiemetic
4. 5+d: Resolution (either live or die) Must be given w/in 12-16 hrs of ingestion of APAP (ideal: 8 hrs) 100%
Side effects: ​Hepatotoxicity protection (Video)
MC reported toxic medicine ingestion ​in US & UK
Toxic doses Don’t wait for APAP concentration to treat w/NAC
→ >150mg/kg in kids TREAT EMPIRICALLY
→ 7g in adults Need NAC? Hepatotoxicity? → hospitalize
Toxic levels → hepatic injury w/in 24-72 hrs
Consider liver transplant if:
Serum pH<7.3
Lactate >3mmol/L after resuscitation
Serum phos > 1.2mmol/L
Serum Cr > 3.3mg/dL +INR>6.5 +stupor/coma

Supportive care
GI decontamination
Activated charcoal

Salicylates Toxicity occurs at concentrations > 150mg/kg Serum salicylate, potassium, blood gas, and -Tx:​ intensive supportive care and GI decontamination,​ ​MDAC
Aspirin, oil of -​Sx:​ early: n/v, hyperventilation,​ tinnitus​ initial resp urine pH Q2-4 hours to monitor -Correct dehydration, and imbalance, fluid resuscitation,​ ​sodium bicarb
wintergreen, pepto alkalosis which later becomes metabolic acidosis and potassium
bismol -Late sx: seizures, hyperpyrexia, coma -Hemodialysis may be needed for critically ill pts, sz, acidosis, cerebral pr
pulm edema
Low grade fever, ketonuria -​ventilate aggressively to induce respiratory alkalosis
-IV sodium bicarb = mainstay of tx (avoid metabolic acidosis)
Hypoglycemia is prominent in children
Death may result from pulm edema, cardiorespiratory arrest, cerebral
Hypokalemia edema, herniation

HOSPITALIZE

Anticholinergics “Blind as a bat, hot as Hades, red as a beet, dry as a bone, *Tx is generally supportive*: benzos, cooling, bladder emptying
and mad as a hatter” Antidote: ​physostigmine
Scopolamine, Antidote provided IF life-threatening toxicity = hemodynamically significant
Atropine, Other S/S: tachycardia, GI ileus, urinary retention, seizures, tachycardia, hyperthermia, seizures resistant to benzos
Diphenhydramine, delirium, hallucinations, mydriasis, HTN, AMS, urinary Treat abnormal QRS/QT intervals first
Jimson Weed, retention Works w/in mins, lasts 30-60 mins
Belladonna, Inc QRS/QT intervals Severe complications: bradycardia, heart block, seizures (atropine should
Antihistamines be present if physostigmine given)
ECG monitoring necessary
Be ready to administer atropine if needed
C/I in TCA OD

Beta Blockers Hypotension, bradycardia, somnolence or coma Antidote: glucagon, calcium, ​NE, high-dose insulin, lipid emulsion
𝛃 Adrenergic
Antagonists EKG: sinus brady, AV blocks, long QT (especially with Tx: ​Airway protection, treat hypoglycemia, GI decontamination (consider
 Agent Clinical Manifestations Evaluation Management

propranolol) whole bowel irrigation)

-Treat hypotension with fluids and IV glucagon, if that fails norepi or high
Pulmonary edema or bronchospasms dose insulin
-Persistent dysrhythmia:​ ​atropine​ or isoproterenol
Hypoglycemia, hyperkalemia -OBSERVE 6-8 hours

Barbiturates Drug-drug interaction - Decreases anticoag effect Risk of pulmonary edema CXR to examine for pulm edema
Hypothermia
Phenobarbital Hypotension

Calcium Channel Hypotension, bradycardia, hyperglycemia EKG: bradyarrhythmia and AV block Antidote: calcium, high-dose insulin, lipid emulsion
Blockers Later: CNS depression, preservation of cognition Tx:​ airway protection, GI decontamination, continuous monitoring and fluid
resuscitation
-Hypotensive not responding to therapy, IV calcium or glucagon, epi

Digoxin Cardiotoxic drugs cause conduction disturbances, Antidote: digoxin-specific antibodies ​for patients with severe
Cardiac Glycoside dysrhythmias, occasionally hyperkalemia arrhythmias or hyperkalemia
Colored vision disturbances (​green​ and ​yellow​) Tx:​ supportive care, GI decontamination
-Replace K+ if needed, Atropine for blocks, avoid pacing
Digoxin slows conduction through AV node -HOSPITALIZE in cardiac unit

Iron -​Sx:​ 4 stages Antidote= ​Deferoxamine

-I: severe n/v and abdominal pain within 1-4 hours Tx:​ supportive care, GI decontamination​, ​IV deferoxamine is TOC
-II: 6-12 hours up to 24 hours, may improve
-III: shock, acidosis, coagulopathy, hypoglycemia HOSPITALIZE
-IV: hepatic poisoning with possible progression to inj

Lithium -​Sx:​ N/V, tremors, slurred speech, ataxia, apathy, lethargy,
fasciculations
-Severe: choreoathetosis, seizures, coma, death
Na+/H2O depletion → reabsorption of lithium → inc serum
lithium
NDI, diuresis, dehydration → ​chronic lithium toxicity
Toxicity
→ >2mEq/L chronically OR >4mEq/L acutely
→ ​hospitalized!
Acute → serial serum lithium concentrations +
serial assessments of mental status (Q4hrs)
1st line: intense supportive care/whole bowel irrigation, IV saline
Severe → hemodialysis
HOSPITALIZE
Prevention: frequent serum lithium checks for pts taking lithium. Pt edu on
staying hydrated while taking lithium
*Very narrow therapeutic window*

Opiates -​Sx:​ CNS depression, miosis, resp depression, decreased Antidote: Naloxone
Heroin, Morphine bowel sounds, hypotension, bradycardia, and hypothermia -Intensive supportive care and GI decontamination, bag-valve mask
-Pinpoint pupils ventilation

HOSPITALIZE
Death may result from respiratory arrest/pum edema

Tricyclic Average toxic dose is 5 mg/kg Hx, PE, widened QRS, prolonged QT and PR. Antidote: Sodium bicarbonate (for Ventricular dysrhythmias)​, also
antidepressants Vitamin K, Folinic acid, octreotide, lipid emulsion, L-Carnitine
Mydriasis, agitation, tachycardia, seizure, coma. Constant monitoring of ECG for at least 6
Amitriptyline, (results from anticholinergic activity of these drugs) hours is mandatory Lidocaine or bicarb IV bolus frequently effective
Imipramine, Doxepin
QRS widening, profound hypotension, AV block, ventricular Tx:​ HOSPITALIZE, observe 6-8 hrs at least, provide intensive supportive
dysrhythmias (Torsades) care and consider GI decontamination. Do not induce emesis due to risk of
seizure/coma (aspiration risk)
3Cs: ​cardiac abnormalities, convulsions and coma -Admin activated charcoal if the patient has ingested a toxic amount and is
seen w/i 1 hr
Rapid onset of sxs Monitor on EKG at least 6 hrs, treat seizures w/ diazepam or
 Agent Clinical Manifestations
Anticoagulants Inhibits clotting by interfering w. Synthesis of NEW vit K
clotting factors (2, 7, 9, 10)
Has to wait for old factors to degrade so effects aren’t seen
until 8-12 hrs after ingestion (factor 2)
Other clotting factors have longer ½ life so full effects
observed 1-2 days after ingestion
Warfarin bound to albumin and has ½ life of 35 hrs
→ chronic warfarin admin = greater risk of excessive
anticoag and bleeding
Superwarfarin (brodifacoum, indandiones), severe bleeding
wks to months
-​Sx:​ ecchymoses, hematuria, uterine bleeding, meelan,
epistaxis, gingival bleeding, hemoptysis, hematemesis,
hematomas, cardiac tamponade and ICH are
life-threatening potential risks
Carbon Monoxide Eti: ​Colorless, odorless gas that binds to Hgb (200x more
than oxygen)
From incomplete combustion of organic materials, engine
exhaust, kerosene heaters, burning charcoal briquettes,
fireplace
Tissue hypoxia sxs​ → ​HA​ (earliest reliable diagnostic
symptom), nausea, syncope, end-organ injury
*patient appears pink
Severity of sxs correlates w/ COHb concentrations
Delayed CNS effects such as parkinsonism, memory loss,
& personality changes can occur after recovery
Caustics and Consider agents that include strong acids, alkalis, oxidizing
Corrosives agents, other chem such as pheno, house cleaners
-Can result in coagulative (acids) or liquefactive (alkalis)
necrosis of tissue
Sx:​ Mouth and throat pain, dysphagia, drooling, stridor,
Evaluation
Baseline PT and repeat after 24 and 48 hours
Household Ingestions
COHb conc from arterial or venous blood
Incorrect est of O2 carrying capacity
Measuring O2 sat from PO2 or pulse oximetry
EKG - ischemia and infarction in pt w/ CAD
Less than 35ppm: no sx
50ppm: slight HA, dyspnea
100ppm: throbbing HA, dyspnea
200ppm: severe HA, irritable, fatigue, vision
change
300-500ppm: HA, tachy, confusion, syncope
800-1200ppm: coma, convulsions
1900ppm: death
CT ​is easier than endoscopy but not yet
validated
*Endoscopy ​→ symptomatic pt w/ or w/o oral
burns
Also for safe placement of feeding tube
beyond injury.
Management
phenobarbital (do not use physostigmine since it may induce
bradydysrhythmias/asystole)
-Tx: ​rarely needed, consider MDAC (esp if superwarfarin)
For major hemorrhage → Warfarin antidote and fluids
● Vit K 5-10mg IV + FFP (15 ml/kg)​ or
● Prothrombin complex concentrates (​25-100 units/kg)
For patients w/ asymp INR >10
● Vit K 2-5 mg PO w/o FFP
● Recheck INR 6-12 hrs
If INR 6-10
● Vit K 2 mg PO w/o FFP
● Recheck INR 12-24 hrs
-Direct Thrombin Inhibitors typically reverse with FFP or PCC as well as
Factor Xa inhibitors
Never give Vit K IM - risk of erratic abs & hematoma formation
HOSPITALIZE all pts w/ long PTs, evidence of bleeding or hx of ingestion
of massive amts of anticoags, superwarfarin needs vitamin K dosing for
several weeks
Antidote: 100% O2, hyperbaric O2
*Delay in tx may worsen neurologic dmg
General
Move pt to fresh air
Admin 100% O2 in nonrebreathing face mask​ or endotracheal tube ​(not
by nasal cannula or loose fitting face mask)
Blood tests
Obtain COHb & consider blood gases +/- lactate conc. Fire victims - lactate
conc > 8mmol/L → cyanide poisoning (consider cyanide antidotes for pts
rescued from fire w/ syncope, altered sensorium and metabolic acidosis)
CXR
For CO poisoning + smoke inhalation → consider hospitalization for
noncardiogenic pulm edema
CS + mannitol for cerebral edema rec’d
Hospitalize all pts that ingest or inhale caustic or corrosive agents
Skin burns mgmt outpt based on severity
Eye injuries - copiously irrigated and eval by ophthal
Dilution with water, normal saline or milk (8oz for adults, 4oz for
children)
 Agent Clinical Manifestations Evaluation Management

substernal or abd pain, skin and eye burns
-Significant gastric or esophageal burns w/ or w/o oral
lesions
Severe injury -​ tachycardia, hypotension, met acidosis,
hematemesis, alt sensorium
Best modality for detecting small perforations
Endoscopy performed > 24 hrs post poisoning
= a/w perforation due to friable tissues
Any perforation warrants emergent surgical
consultation
Do Not
● Neutralizer - increase heat of hydration & worsen tissue destruction
● Induce vomiting - further tissue damage
● Corticosteroids
Activated charcoal - C/I - interferes w/ endoscopy
Abx for suspected perforation or infection

Organophosphates Eti:Inhibits acetylcholinesterase & allow accumulation of Measurement of plasma or RBC Antidote: Atropine, Pralidoxime (2PAM) + Intensive supportive care
Insecticides AcH at muscarinic and nicotinic receptors in nerve endings cholinesterase activity - confirm acute toxicity and GI decontamination
but pts may req tx before results
Organophosphates bind irreversibly with AcHesterase Serially doubled doses of ​atropine ​→ 10-mL dropper of 1% ophthalmic
atropine = 100mg req’d to adequately dry airway secretions
Abs from skin, GI and resp tract ● 1-2 mg IV (0.5mg in children)
● Double dose Q3-5mins until sxs of atropinization occure (flushing,
Works chronically exposed and infants w/ underdeveloped
mydriasis, drying of secretions, tachycardia)
cholinesterase activity → greater risk for intoxication
● Can go up to 100mg in 24 hrs
Muscarinic signs: “SLUDGE M and the Killer Bs”
● Salivation Pralidoxime (Protopam, 2PAM)
● Lacrimation ● 1-2 g (25-50 mg/kg in children) in saline IV over 5-10mins
● Urination ● restore nl cholinesterase fx - decrease atropine needed
● Diaphoresis ● Need to have adequate renal function
● Gastrointestinal hypermotility
● Emesis Careful mgmt of airway due to bronchospasms
● Miosis
● Bronchorrhea Wash pt’s skin and avoid skin contact with clothes
● Bronchospasm
● Bradycardia Prompt tx - recover from acute toxicity
Nicotinic signs: “MTWHFSS”
● Muscle paralysis Sequelae - organophosphate-induced delayed neuropathy and
● Tachycardia intermediate syndrome
● Weakness
● HTN HOSPITALIZE
● Fasciculations
● Sweating
● Seizures

Alcohols

Ethanol/other CNS depressants Obtained the concentrations of all alcohol Antidote: thiamine & glucose ​(give Thiamine first)
alcohols *ALL Alcohol can be toxic Methanol and ethylene glycol antidote:​ supportive care, fomepizole and
ethanol
Ethanol, methanol, -​Ethanol sx:​ ataxia, dysarthria, depressed sensorium,
ethylene glycol, nystagmus Video: 4-methylpyrazole has highest affinity for ADH (only for ethylene
isopropanol -​Methanol sx:​ CNS depression, ​visual disturbance​, HA, glycol & methanol)
dizzy, breathless (found in paint, windshield wiper fluid)
Parkinsonian​ symptoms -Correct metabolic acidosis with sodium bicarb
-​Ethylene glycol sx:​ CNS depression, heart failure, pulm
edema, renal failure, in 3 stages (antifreeze) HOSPITALIZE all patients
Anion-gap metabolic acidosis, blindness, Parkinsonian sx
-Isopropanol​: Ketosis w/o acidosis, normal anion gap,
CNS/myocardial infarction (rubbing alcohol) →coma and
death
 Agent Clinical Manifestations Evaluation Management

“Street Drugs”

Cocaine MCC of illicit drug ED visits 12h observation for low-risk patients w/ cocaine-induced chest pain

Reuptake inhibition of NTs: dopamine, norepi, 5HT

Rate of onset: inhaled > IV > intranasal > PO

Sympathomimetic toxidrome: coronary vasospasm

(prinzmetal angina), platelet aggregation, CNS stimulation,
seizures

Chest pain = MC sx

Cocaethylene = cocaine + ethanol (4x longer half-life)

Heroin Aka Diacetylmorphine Naloxone

Opioid agonist at the mu, kappa & delta receptors

Half-life = 30min (naloxone half-life = 20-40 min, so may

need multiple doses)

MCC of mortality = respiratory depression

2% develop noncardiogenic pulmonary edema

PCP Aka Phencyclidine Benzos = DOC for calming agitated patients

Dissociative anesthetic & sympathomimetic

Glutamate agonist at NMDA receptor

Clinical Sx:
- Psychosis, violent behavior
- Vertical or rotary nystagmus

Ecstasy (MDMA) Sympathomimetic & hallucinogenic (aka cross between

cocaine & LSD)

Intended effects: euphoria, sensory enhancement

Adverse effects:
- Thirst → copious water ingestion → hyponatremia →
seizure
- Bruxism (pacifiers at raves)
- Hyperthermia, Serotonin Syndrome
- Acute hepatic failure
Agent Clinical Manifestations Evaluation Management
Agent Clinical Manifestations Evaluation Management