27 Toxicology

27.1 Key Resources

  • Poison Control: 1-800-222-1222
  • BCH Toxicology Fellow/Attending (on call 24/7)
  • BCH Chemistry Fellow (daytime hours, can help interpret labs and select specialized testing)
  • Hazmat Team: Boston Fire Department
  • MSDS: Material Safety Data Sheets
  • www.maripoisoncenter.com
  • www.aapcc.org

27.2 Approach to Poisoned Patient

27.2.1 Stabilization

Airway, Breathing, Circulation, Disability, Drugs/D-Stick, Decontamination

27.2.2 Physical Exam

Vital signs Neuro: MS, tone, clonus, abnormal movements Eyes: pupils, EOM, nystagmus Mouth: corrosive lesions, odors CV: rate, rhythm, perfusion Resp: rate, depth of respirations, air entry, wheeze GI: motility (?bowel sounds), corrosive effects (i.e. vomiting) Skin: color, bullae, burn, sweat, track marks

27.2.3 History

  • AMPLE: Allergies, Meds/Toxins (everyone in home), Past medical history, Last meal, Events
  • Known toxin: amount, time since ingestion, early sx, home tx
  • Concern for poisoning: h/o pica or ingestions, meds in home, recent illnesses, visitors/events

27.2.4 Basic Labs

Consider ABG, co-oximetry, CBC, D-stick, EKG, Chem, LFTs, serum OSM, UA, urine/serum tox

27.2.5 Tox Screens

  • Substances included, limits of detection vary hospital to hospital

  • Urine drug screens rarely inform acute management decisions

  • Urine tox screens: detect amphetamines, MDMA, barbiturates, benzos, cocaine, opioids, +/- THC

    • Qualitative (+/-)
    • Does not detect synthetic cathinones (i.e. “bath salts”); false + and false - (esp benzos, synthetic opioids) common
    • ADHD drugs: adderall → positive amphetamine

  • Urine THC - must order separately at BMC

  • Expanded opioid panel, urine (BMC): detects buprenorphine, oxycodone, methadone, fentanyl

  • Extended tox screen: GC/MS, urine better than serum, send out test

  • Meconium tox: amphetamines, THC, cocaine, opiates, PCP

  • Serum tox: APAP, ASA, EtOH (quantitative),TCAs (qualitative) Specific drug levels: can request agents not on tox screens (digoxin, lithium, AEDs, iron, etc.)

27.2.6 Management

  • Can I decontaminate?
  • Can I enhance the elimination of the toxin? (www.extrip-workgroup.org)
  • Is there an antidote?
  • How can I provide the best, targeted supportive care?

27.3 Toxidromes

toxidromes_table

27.4 Differential Diagnosis (non-exhaustive)

27.4.1 Temperature

Hyperthermia: NASA - NMS, nicotine - Antihistamines, alcohol withdrawal, anesthetics - Salicylates, sympathomimetics, serotonin syndrome - Anti: -cholinergics, -depressants, -psychotics

Hypothermia: COOLS - Carbon monoxide - Opioids - Oral hypoglycemics - Liquor - Sedative-hypnotics

27.4.2 Heart Rate

Tachycardia: FAST - Free base or other forms of cocaine - Anticholinergics, antihistamines, antipsychotics, amphetamines - Sympathomimetics - Theophylline, TCAs, thyroid hormones

Bradycardia: PACED

  • Propranolol (beta-blockers), poppies (opioids), physostigmine
  • Anticholinesterase drugs, antiarrhythmics
  • Clonidine, calcium channel blockers
  • Ethanol or other alcohols
  • Digoxin, digitalis

27.4.3 Blood Pressure

Hypertension: CT SCAN - Cocaine - Thyroid supplements - Sympathomimetics - Caffeine - Anticholinergics, amphetamines - Nicotine

Hypotension: CRASH - Clonidine, calcium channel blockers - Rodenticides (containing arsenic, cyanide) - Antidepressants, aminophylline, antihypertensives - Sedative-hypnotics - Heroin (opioids)

27.4.4 Respiratory Rate

Tachypnea: PANT - PCP - Aspirin and other salicylates, acute lung injury (hydrocarbons, vaping) - Noncardiogenic pulmonary edema - Toxin-induced metabolic acidosis

Hypopnea: SLOW - Sedative - hypnotics (benzodiazepines, barbiturates) - Liquor - Opioids - Weed

27.4.5 Blood Glucose

Hyperglycemia: CAPT ABC - Corticosteroids - Antibiotics (quinolones) - Protease inhibitors - Thiazides - Atypical antipsychotics - Beta-agonists - Corticosteroids

Hypoglycemia: HOBBIES - Hypoglycemics (oral) - Other (quinine, unripe ackee fruit) - Beta-blockers - Insulin - Ethanol - Salicylates (late)

27.5 Acetaminophen Overdose

27.5.1 Toxic Dose

200 mg/kg (7.5-10 g in older pts) as a single acute overdose

27.5.2 Pathophysiology

Saturation of glucuronidation/sulfate conjugation pathway → ↑ metabolism via P450 pathway and depletion of glutathione → build up of toxic NAPQI → hepatotoxicity +/- renal toxicity

27.5.3 Symptoms

See chart below

27.5.4 Evaluation

Acetaminophen levels (at ≥ 4 hours post-ingestion, LFTs, coags, electrolytes, BUN/Cr, UA w/ tox screen (serum and urine), urine pregnancy for females

27.5.5 Management

  • Activated charcoal if w/i 1-2 hrs of ingestion and no contraindications (unprotected airway and decreased LOC)

  • Goal: Initiate NAC ≤ 8 hours of ingestion (or ASAP if >8 hours post-ingestion)

  • APAP level → apply NOMOGRAM → estimate risk of hepatotoxicity

  • KEY POINT: NOMOGRAM can ONLY be used for: single acute ingestion, known time of ingestion, ingestion w/i 24hrs of presentation. Also, caution if coingestants that may affect GI motility

    • Risk of hepatotoxicity → give N-acetylcysteine
    • IV: loading dose of 150mg/kg over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours; check APAP levels, LFTs, coags 2 hours before 16h infusion is scheduled to end
    • PO/NG: Loading dose 140mg/kg then 70mg/kg 14hrs x24 hours
    • Guidelines for stopping NAC: clinically well, improving LFTs, normalizing coags, APAP level <10 (if patient does not meet guidelines, continue NAC (100mg/kg IV over 16 hours) until they meet criteria.

  • King’s College Criteria for Liver Transplant:

    • pH < 7.3 or

    • INR > 6.5 AND serum creatinine > 3.4mg/dL AND grade III - IV encephalopathy

    • West Haven Criteria for encephalopathy:

      • I: Changes in behavior with minimal change in level of consciousness
      • II: Gross disorientation, drowsiness, possible asterixis, behavior changes
      • III: Marked confusion, incoherent speech, sleepy but arousable to voice
      • IV: Comatose, unresponsive to pain, decorticate/decerebrate positioning

27.5.6 Rule of 150

  • Potentially toxic dose: 150mg/kg
  • Treatment line: 150mcg/mL at 4 hours
  • Loading dose of NAC 150mg/kg over one hour
A cute APAP To xici ty Symptoms Labs
S tage 1: 0-24 h ours N/V, diaphoresis, malaise May be asymptomatic Labs, PE generally normal
S tage 2: 2 4-72 h ours Initial symptoms resolve RUQ pain, liver enlargement/tenderness AST/ALT, ↑ PT/INR, renal d ysfunction, ↑ amylase
S tage 3: 7 2-96 h ours N/V, diaphoresis return - Jaundice, hepatic encephalopathy, hyperammonemia, bleeding, hypoglycemia, lactic acidosis - Renal failure, multi organ failure, death LFTs peak
S tage 4: 4-14 days Recovery phase Slow normalization of symptoms and lab values (Symptoms typically normalize well before transaminases do) Slow no rmalization

27.6 Aspirin Overdose

27.6.1 Toxic Dose

150 mg/kg

27.6.2 Pathophysiology

  • Stimulates medullary respiratory center → ↑RR, hyperpnea, respiratory alkalosis
  • Inhibits Kreb’s cycle enzymes → lactic acidosis, ketoacidosis
  • Inhibits platelet function + vitamin-K dependent clotting factors → coagulopathy

27.6.3 Symptoms

  • Mild toxicity: GI upset, tinnitus and tachypnea
  • Moderate toxicity: fever, diaphoresis, tachycardia, agitation, confusion
  • Severe toxicity: coma, pulmonary edema, seizures

27.6.4 Evaluation

Serum salicylate level (normal <30 mg/dL), ABG (primary respiratory alkalosis, primary anion-gap met acidosis), glucose (elevated - early, low - late), Electrolytes (hyper/hyponatremia, hypokalemia) +/- LFTs, CBC, coags, UA, serum/urine tox screen. Resulting acidosis and electrolyte changes MAY demonstrate EKG changes (ex. widened QRS, AV block, arrhythmias)

27.6.5 Management

  • GI decontamination: activated charcoal (consider repeat dose, prone to bezoar formation)
  • Aggressive fluid resuscitation (lots of insensible losses)
  • Urine alkalinization: goal URINE pH = 8, goal SERUM pH 7.45-7.55 to enhance ion trapping; can use D5 W150 mEq/L Na-bicarb
  • Potassium repletion
  • Follow salicylate levels q1-2 hours
  • Hemodialysis (ASA level >90-100mg/dL (acute overdose), >60 mg/dL (chronic overdose), severe acidosis or electrolyte disturbances, renal failure, pulm edema, neurologic symptoms, deterioration despite interventions)

27.7 Beta-Blocker Overdose

27.7.1 Toxic Dose

“One pill can kill” in toddlers

27.7.2 Pathophysiology

adrenergic antagonist → ↓ sympathetic outflow

27.7.3 Symptoms

Bradycardia, hypotension, bronchospasm, coma, seizures, hypoglycemia

27.7.4 Evaluation

DS (hypoglycemia), EKG (brady, AV block, accelerated junctional rhythm), serum/urine tox (in cases of suspected intentional ingestions)

27.7.5 Management

  • GI decontamination: activated charcoal (consider whole bowel irrigation) if indicated and no contraindications
  • Glucagon bolus: 0.15 mg/kg then infusion of 0.05-0.1 mg/kg/hr (for symptomatic bradycardia)
  • Fluids +/- pressors for hypotension
  • Hyperinsulinemia/euglycemia (HIE) therapy: sometimes used in severe BB OD

27.8 Calcium Channel Blocker Overdose

27.8.1 Toxic Dose

“One pill can kill” in toddlers; individual drug selectivity for cardioactive vs vasoactive effects lost in significant overdose

27.8.2 Pathophysiology

Block L-type Ca channel blockers (affect myocyte contractility, SA nodal AP initiation)

27.8.3 Symptoms

Bradycardia, hypotension, coma, seizures, dihydropyridine CCBs (amlodipine, nifedipine, etc) can present w/ TACHYcardia and relative hypotension, HYPERglycemia

27.8.4 Evaluation

DS (hyperglycemia), EKG (bradycardia, AV block, accelerated junctional rhythm, wide QRS, ST changes), serum/urine tox (in cases of suspected intentional ingestions)

27.8.5 Management

  • GI decontamination: activated charcoal (consider whole bowel irrigation) if indicated and no contraindications
  • IV calcium chloride or calcium gluconate
  • HIE (hyperinsulinemia/euglycemia) therapy: 1 unit/kg bolus of regular insulin then 0.5-1+unit/kg/hr infusion
  • Intralipid 20%: 1.5ml/kg during 2-3 mins, followed by 0.25 ml/kg/min IV x 30-60 min (consult Tox)

27.9 Antidepressants: SSRIs and SNRIs

27.9.1 Toxicity

  • SSRIs: less toxic than MAOIs or TCAs; most fatalities due to co-ingestion
  • SNRIs: greater toxicity than SSRIs (but less than MAOIs or TCAs)

27.9.2 Pathophysiology

Inhibit serotonin +/- norepinephrine reuptake (primarily in CNS)

27.9.3 Symptoms

  • Vomiting, CNS depression, tachycardia
  • Serotonin syndrome: altered mental status, neuromuscular hyperexcitability (clonus, rigidity, hyperreflexia), autonomic instability (hyperthermia, tachy, HTN) → can lead to rhabdo, seizures, renal failure, DIC

27.9.4 Evaluation

Electrolytes, serum/tox screen, EKG (↑QTc, rare ↑ QRS w/ some SNRIs); levels not helpful

27.9.5 Management

  • Decontamination and supportive care
  • Benzos and/or serotonin antagonists (cyproheptadine) for serotonin syndrome, consider cooling and paralysis for severe serotonin syndrome

27.10 Antidepressants: TCAs

27.10.1 Toxic Dose

“One pill can kill” in toddlers

27.10.2 Pathophysiology

Peripheral and central anticholinergic, peripheral alpha-1 adrenergic blockade, inhibits CNS NE and serotonin reuptake, blocks cardiac fast Na channels, blocks GABA receptors

27.10.3 Symptoms

  • Anticholinergic toxidrome (see toxidrome chart)
  • Neurotoxicity (seizures, coma)
  • Cardiovascular toxicity (arrhythmias, refractory hypotension, widened QRS)

27.10.4 Evaluation

Electrolytes, CK, D-stick, urinalysis, tox screens, TCA level not useful (other than to confirm ingestion), EKG (prolonged QRS (>100ms a/w seizure, dysrhythmias), sinus tach, vent arrhythmias, lead aVR prominent R waves)

27.10.5 Management

  • Gastric decontamination, close monitoring, EKGs
  • NaHCO3 titrated to serum pH 7.45-7.55 (indicated for QRS > 100ms w/ other signs of TCA toxicity, vent. arrhythmias, CV collapse, seizures). Mechanism: increase pH -> increase non-ionized TCA = cannot bind sodium channels. Also increases gradient across cardiac cell membranes -> attenuates TCA-induced blockade of rapid sodium channels.
  • Supportive care (treat refractory hypotension w/ alpha-agonist pressors)
  • For severe TCA overdoses, consider intralipid

27.11 Antidepressants: Buproprion

27.11.1 Toxic Dose

“One pill can kill” in toddlers

27.11.2 Pathophysiology

Dopamine and NE reuptake inhibitor w/ some serotonin reuptake blockade; contraindicated in eating disorder patients given ↑ seizures

27.11.3 Symptoms

Seizures, agitation, HTN, tachycardia, arrhythmias

27.11.4 Evaluation

Levels not helpful, electrolytes, EKG (QRS and QTc prolongation). May cause +amphetamine screen

27.11.5 Management

Supportive care, benzos for seizures, admit for >24 hours to monitor for late onset seizures if ingested Wellbutrin SR, ↑ QRS treated w/ IV sodium bicarb (though may not be as effective)

27.12 Iron

27.12.1 Toxic Dose

  • Less than 20mg/kg elemental iron usually asymptomatic
  • 20-60 mg/kg: variable response
  • Greater than 60 mg/kg: greatest risk of serious toxicity (death reported at 60-300+ mg/kg)

27.12.2 Pathophysiology

Direct caustic effect on GI mucosa → hemorrhagic necrosis; multisystem toxicity 2/2 mitochondrial poison; iron absorbed at duodenum/jejunum

27.12.3 Symptoms

If no significant GI symptoms w/i first 6 hrs after overdose, very low likelihood of significant toxicity

  • *Phase I (30min –
6h)**		 GI sx: vomiting, diarrhea, GI bleeding
  • *Phase II (6h – 24h)**
 Latent period: apparent improvement
  • *Phase III (4h-4d ays)**
 Hepatotoxicity: hepatocellular injury, AG metabolic acidosis (↑ lactic acid), coma, seizures, multi-organ failure, shock Labs: ↑ bili, ↑ LFTs, ↑ glucose, ↑ PT/INR, ↑ BUN
  • *Phase IV (2-8 wks)**
 Late effects: possible bowel obstruction secondary to strictures

27.12.4 Evaluation

KUB (radio-opaque pills), Fe level, VBG/ABG, lytes, BUN/Cr, glucose, LFTs, PT/INR, CK

27.12.5 Management

Support ABC’s, replace fluid/blood losses, GI decontamination, IV deferoxamine (severe sx, iron level > 500 mcg/d w/ clinical symptoms, sig AG met acidosis)

27.13 Lead

27.13.1 Toxic Dose

No safe lead level exists

27.13.2 Pathophysiology

Interferes w/ interactions of divalent cations and sulfhydryl groups leading to widespread physiologic effects and clinical toxicity

27.13.3 Symptoms

  • Lower levels: Abdominal pain, constipation, anorexia, vomiting, developmental delays, aggression, hyperactivity
  • Higher levels: drowsiness, clumsiness, ataxia
  • Severe levels: decreased consciousness, coma, seizures, death (usually 2/2 cerebral edema)

27.13.4 Evaluation

Lead levels, CBC (microcytic anemia + basophilic stippling of RBC), FEP (free erythrocyte protoporphyrin), BUN/Cr, AST/ALT, x-ray (radiopaque flecks)

27.13.5 Management

27.14 Drugs of Abuse

27.14.1 Ethanol

27.14.1.1 Hx/PE

Euphoria, loss of coordination, ataxia, slurred speech, nystagmus, nausea, vomiting, hypoglycemia (especially in young children), seizures, coma, respiratory depression

27.14.1.2 Dx

Blood ethanol level, D-stick

27.14.1.3 Management

Supportive; secure airway if unresponsive, no gag reflex

27.14.2 Marijuana

27.14.2.1 Hx/PE

Pupils unchanged, injected conjunctiva, tachycardia, increased appetite, euphoria, anxiety, time-space distortions, panic reaction, psychotic reaction; can cause ataxia and significant sedation in toddlers. Ask about routes of exposure (smoking, vaping, dabbing, edibles, etc.); edibles particularly problematic in young children.

27.14.2.2 Dx

Urine drug screen (note, synthetic cannabinoids not detected on standard urine toxicology screens

27.14.2.3 Management

Supportive care, can treat w/ anxiolytics if needed. Some young children may require airway protection due to degree of sedation.

27.14.3 Stimulants (Amphetamines, Cocaine, Ecstasy/MDMA, “Bath Salts”)

27.14.3.1 Hx/PE

Tachycardia, hyperthermia, mydriasis, diaphoresis, restlessness, tremors, panic, agitations, psychosis, seizures

27.14.3.2 Dx

Urine drug screen; EKG (cocaine may cause QRS widening); troponin if chest pain; CK if concern for rhabdo; electrolytes (hyponatremia w/ MDMA)

27.14.3.3 Management

Supportive care including fluids, avoid beta blockers in HTN due to unrestrained alpha-agonism, benzos for agitation, HTN, and tachycardia

27.14.4 Opioids

27.14.4.1 Hx/PE

Respiratory depression (hallmark), miosis, CNS depression, hypotension, hypothermia, pulmonary edema

27.14.4.2 Dx

Urine drug screen (extended screen available at BMC, typically done as send-out at BCH); EKG (methadone can cause QTc prolongation)

27.14.4.3 Management

Naloxone for severe respiratory/CNS depression, titrate dosing to severity of presentation (may precipitate withdrawal in chronic users); otherwise supportive

27.14.4.4 Notes

Opioids are one of the “one pill can kill” medications in toddlers