# Clinical Cases: Toxicology

## Case 1: Acetaminophen Overdose - The Silent Killer

### Patient Demographics
- **Age:** 19 years
- **Sex:** Female
- **Occupation:** College freshman

### Chief Complaint
"I took a bunch of Tylenol last night and my roommate made me come in."

### History of Present Illness
A 19-year-old female presents 14 hours after intentional ingestion of "a whole bottle" of extra-strength acetaminophen (500mg tablets, approximately 50 tablets = 25 grams). She reports taking them after a breakup with her boyfriend. Initially felt fine, developed nausea and vomiting 6 hours post-ingestion. Currently asymptomatic except for mild RUQ discomfort. She did not seek care earlier because she "felt okay."

### Initial Assessment

**ESI Level:** 2 - Potentially toxic ingestion requiring emergent intervention

**First Impression:**
- Appearance: Alert, anxious, tearful
- Work of breathing: Normal
- Circulation: Normal color

**Vital Signs:**
- Heart rate: 88 bpm
- Blood pressure: 118/72 mmHg
- Respiratory rate: 16 breaths/min
- SpO2: 99% on room air
- Temperature: 37.0C
- GCS: 15

### Primary Survey

**Airway:** Patent
**Breathing:** Normal respiratory effort
**Circulation:** Normal pulses, well-perfused
**Disability:** Alert and oriented, GCS 15
**Exposure:** No abnormalities

### Key Point: Acetaminophen Toxicity Stages

| Stage | Time Post-Ingestion | Symptoms |
|-------|---------------------|----------|
| I | 0-24 hours | Asymptomatic or mild GI symptoms |
| II | 24-72 hours | RUQ pain, elevated LFTs, possible AKI |
| III | 72-96 hours | Hepatic failure, coagulopathy, encephalopathy |
| IV | 4 days-2 weeks | Recovery or death |

**This patient is in Stage I-II transition** - deceptively well-appearing

### Secondary Survey

**SAMPLE History:**
- Symptoms: Mild nausea, RUQ discomfort
- Allergies: None
- Medications: Oral contraceptives
- PMH: Depression (not currently in treatment)
- Last Meal: Nothing since ingestion
- Events: Intentional ingestion after emotional stressor

**Ingestion Details:**
- Substance: Acetaminophen 500mg tablets
- Amount: ~50 tablets (25 grams; ~400 mg/kg for 60kg patient)
- Time: 14 hours ago
- Co-ingestants: Denies alcohol or other medications
- Vomiting: Yes, 2 episodes about 6 hours post-ingestion

### Diagnostic Testing

**Point-of-Care:**
- Glucose: 92 mg/dL
- Urine pregnancy: Negative

**Labs:**
- Acetaminophen level: 180 mcg/mL at 14 hours (TOXIC - above treatment line)
- AST: 1,842 IU/L (markedly elevated)
- ALT: 2,156 IU/L (markedly elevated)
- INR: 1.8
- Total bilirubin: 2.1
- BUN/Cr: 18/0.9
- Lipase: Normal
- Salicylate level: Undetectable
- Ethanol: Negative
- Urine drug screen: Negative

**Rumack-Matthew Nomogram:**
- Plot acetaminophen level against time
- At 14 hours, 180 mcg/mL is well above treatment line
- N-acetylcysteine (NAC) indicated

### Diagnosis

**Acute acetaminophen toxicity** with early hepatotoxicity

### Management

**N-Acetylcysteine (NAC) Protocol:**

*IV Protocol (21-hour):*
- Loading: 150 mg/kg in 200mL D5W over 1 hour
- Dose 2: 50 mg/kg in 500mL D5W over 4 hours
- Dose 3: 100 mg/kg in 1000mL D5W over 16 hours

**Monitoring:**
- Serial acetaminophen levels (should decline)
- Serial LFTs every 6-12 hours
- INR monitoring
- Renal function

**Additional Treatment:**
- IV fluids for hydration
- Antiemetics for nausea (NAC can cause nausea)
- Electrolyte repletion as needed

**Psychiatry Consultation:**
- Mandatory for intentional overdose
- 1:1 observation until cleared
- Safety planning

### Clinical Course

**Labs at 24 hours:**
- Acetaminophen: 28 mcg/mL (declining)
- AST: 3,456 IU/L (peak expected 48-72 hours)
- ALT: 4,122 IU/L
- INR: 2.4
- Creatinine: 1.0

**Labs at 48 hours:**
- Acetaminophen: <10 mcg/mL
- AST: 2,100 IU/L (improving)
- ALT: 2,850 IU/L (improving)
- INR: 1.6 (improving)

**Decision:** Continue NAC until:
- Acetaminophen undetectable AND
- INR <2.0 AND
- AST/ALT declining AND
- Patient clinically improved

### Disposition
- Medical admission with 1:1 observation
- NAC continued for 48 hours total
- LFTs improving, INR normalizing
- Psychiatry evaluation: Patient engaged, safety plan established
- Discharged to psychiatric facility on day 4 for further stabilization

### Teaching Points

1. **Acetaminophen is deceptively dangerous:** Patients may appear well in Stage I while developing fatal hepatotoxicity
2. **Know the toxic dose:** >150 mg/kg is potentially toxic; >300 mg/kg severe
3. **Time matters:** NAC most effective within 8 hours; still beneficial up to 24+ hours
4. **Don't rely on symptoms:** Early acetaminophen toxicity is asymptomatic
5. **Rumack-Matthew nomogram:** Only valid for single acute ingestions 4-24 hours post-ingestion
6. **Extended NAC:** Continue until patient improving, not based on fixed protocol duration
7. **Always consider co-ingestion:** Check salicylate level, ethanol, and urine drug screen
8. **Psychiatric evaluation mandatory:** All intentional overdoses require mental health assessment

### Clinical Image
![Rumack-Matthew Nomogram](case_01_image.jpg)

**Image Description:** The Rumack-Matthew nomogram showing acetaminophen plasma concentration plotted against hours post-ingestion. The treatment line indicates when N-acetylcysteine therapy is indicated based on acetaminophen level and time.

**Attribution:** Image adapted from Wikimedia Commons, Rumack-Matthew Nomogram. Public domain. Source: https://commons.wikimedia.org/wiki/File:Rumack-Matthew_nomogram.svg

---

## Case 2: Opioid Overdose - Respiratory Arrest

### Patient Demographics
- **Age:** 28 years
- **Sex:** Male
- **Occupation:** Unemployed

### Chief Complaint
"Found down, not breathing."

### History of Present Illness
EMS called to a public restroom for an unresponsive male. Bystander found patient slumped against wall with blue lips and agonal respirations. Bystander administered intranasal naloxone from a community distribution kit before EMS arrival. On EMS arrival, patient had some respiratory effort but remained obtunded. Additional naloxone given en route.

### Initial Assessment

**ESI Level:** 1 - Immediately life-threatening

**First Impression:**
- Appearance: Obtunded, cyanotic, track marks visible on arms
- Work of breathing: Shallow, slow respirations
- Circulation: Pale with mottled extremities

**Vital Signs on Arrival:**
- Heart rate: 52 bpm
- Blood pressure: 88/56 mmHg
- Respiratory rate: 6 breaths/min
- SpO2: 78% on room air
- Temperature: 35.8C
- GCS: 6 (E2V1M3)
- Pupils: 2mm, minimally reactive (pinpoint)

### Primary Survey

**Airway:**
- Partially obstructed (tongue, secretions)
- Jaw thrust performed
- Oropharyngeal airway placed

**Breathing:**
- Hypoventilation (RR 6)
- Bag-valve-mask ventilation initiated
- Improving oxygenation with BVM

**Circulation:**
- Bradycardic
- Weak peripheral pulses
- IV access obtained

**Disability:**
- GCS 6
- Pinpoint pupils (classic opioid finding)
- No focal motor deficits noted

**Exposure:**
- Multiple track marks bilateral arms
- No trauma
- Drug paraphernalia in belongings (needle, spoon)

### Opioid Toxidrome

| Finding | Present in This Patient |
|---------|------------------------|
| CNS depression | Yes - obtunded |
| Respiratory depression | Yes - RR 6, hypoxia |
| Miosis (pinpoint pupils) | Yes - 2mm pupils |
| Bradycardia | Yes - HR 52 |
| Hypotension | Yes - 88/56 |
| Hypothermia | Yes - 35.8C |

### Management

**Immediate Interventions:**

1. **Airway support:** BVM ventilation, improving SpO2 to 94%

2. **Naloxone Administration:**
   - Pre-hospital: 4mg intranasal (bystander) + 2mg IN (EMS)
   - ED: Naloxone 0.4mg IV, titrated
   - Goal: Adequate respirations, NOT full arousal
   - Avoid precipitating withdrawal if possible

3. **Response to Naloxone:**
   - After 0.4mg IV: RR improved to 12, GCS 10
   - After additional 0.4mg IV: RR 14, GCS 13
   - Patient becoming agitated (expected with naloxone)

**Naloxone Dosing Pearls:**
- Start low (0.04-0.4mg IV) in opioid-dependent patients
- Goal is respiratory support, not arousal
- Duration of action: 30-90 minutes (shorter than most opioids)
- May need repeated doses or infusion for long-acting opioids

### Secondary Survey (After Stabilization)

**SAMPLE History (from patient once arousable):**
- Symptoms: Reports using heroin "maybe fentanyl"
- Allergies: None known
- Medications: None prescribed
- PMH: Prior overdoses (x3), hepatitis C, opioid use disorder
- Last Meal: Yesterday
- Events: Injected heroin, doesn't remember after

**Physical Exam:**
- Track marks bilateral antecubital, dorsal hands
- No abscess or cellulitis
- Lungs: Coarse bilaterally (aspiration risk)
- Heart: Regular rate and rhythm
- Neuro: Now alert, oriented, moving all extremities

### Diagnostic Testing

**Point-of-Care:**
- Glucose: 78 mg/dL
- ECG: Sinus rhythm, normal QRS and QTc

**Labs:**
- CBC: WBC 11.2, Hgb 13.1
- BMP: Normal
- Troponin: Negative
- Lactate: 2.8 (mildly elevated, improving)
- VBG: pH 7.32, pCO2 48 (resolving respiratory acidosis)
- Urine drug screen: Positive for opioids (note: may miss synthetic opioids like fentanyl)

**Chest X-ray:** Mild bilateral perihilar infiltrates (possible aspiration vs. ARDS from hypoxia)

### Observation Period

**Rationale for Extended Monitoring:**
- Unknown opioid (fentanyl analogs have prolonged effects)
- Risk of re-sedation as naloxone wears off
- Aspiration pneumonia risk

**Monitoring:**
- Continuous pulse oximetry
- Frequent respiratory checks
- 4-6 hour observation minimum

**Course:**
- No recurrence of respiratory depression
- Oxygen weaned to room air
- Alert and conversant

### Harm Reduction and Disposition

**Interventions:**
1. Addiction medicine consultation
2. Offered medication-assisted treatment (MAT):
   - Buprenorphine initiation discussed
   - Patient interested, bridge prescription provided
3. Naloxone kit prescribed and training provided
4. Hepatitis C treatment referral
5. Social work involvement for resources
6. HIV testing offered

**Disposition:**
- Discharged after 6-hour observation
- Prescription for naloxone rescue kit
- Appointment with addiction medicine in 48 hours for buprenorphine induction
- Given list of resources (needle exchange, NA meetings, crisis line)

### Teaching Points

1. **Opioid overdose is reversible:** Naloxone is lifesaving; support respirations while it takes effect
2. **Titrate naloxone:** Start low to avoid precipitating severe withdrawal
3. **Fentanyl consideration:** May require higher doses of naloxone; prolonged monitoring needed
4. **Observation period:** Minimum 4-6 hours; longer for long-acting or sustained-release opioids
5. **Harm reduction:** Every overdose is an opportunity for intervention - offer MAT, naloxone kit, resources
6. **Aspiration risk:** Common complication; chest X-ray if hypoxia persists despite naloxone
7. **Community naloxone:** Bystander-administered naloxone saves lives; ED reinforcement important

### Clinical Image
![Opioid Overdose - Pinpoint Pupils](case_02_image.jpg)

**Image Description:** Close-up photograph demonstrating bilateral miotic (pinpoint) pupils, a classic finding in opioid toxicity. The pupils are constricted to approximately 2mm and poorly reactive to light.

**Attribution:** Image from Wikimedia Commons, Miosis. Licensed under CC BY-SA 3.0. Source: https://commons.wikimedia.org/wiki/File:Miosis.jpg

---

## Case 3: Sympathomimetic Toxidrome - Methamphetamine Intoxication

### Patient Demographics
- **Age:** 32 years
- **Sex:** Male
- **Occupation:** Unknown

### Chief Complaint
"He's acting crazy and won't calm down."

### History of Present Illness
Police bring a 32-year-old male to the ED for altered mental status and combative behavior. Found at a convenience store throwing items and threatening customers. He is agitated, paranoid, and appears to be responding to internal stimuli. Bystanders report patient was "smoking something" outside the store. He is known to police for prior methamphetamine-related arrests.

### Initial Assessment

**ESI Level:** 1 - Immediate intervention for safety and medical stabilization

**First Impression:**
- Appearance: Extremely agitated, diaphoretic, pupils dilated
- Work of breathing: Tachypneic
- Circulation: Flushed, diaphoretic

**Vital Signs (obtained with difficulty):**
- Heart rate: 142 bpm
- Blood pressure: 198/112 mmHg
- Respiratory rate: 28 breaths/min
- SpO2: 96% on room air
- Temperature: 39.4C (102.9F) - HYPERTHERMIA
- GCS: 14 (E4V4M6 - confused)

### Sympathomimetic Toxidrome

| Finding | Present |
|---------|---------|
| Agitation/psychosis | Yes - severe |
| Tachycardia | Yes - HR 142 |
| Hypertension | Yes - 198/112 |
| Hyperthermia | Yes - 39.4C |
| Diaphoresis | Yes |
| Mydriasis (dilated pupils) | Yes - 7mm |
| Tremor | Yes |

### Immediate Safety and Stabilization

**Agitation Management:**
1. Verbal de-escalation attempted - unsuccessful
2. Security and police assistance for safety
3. Chemical restraint:
   - Midazolam 5mg IM (unable to obtain IV initially)
   - Repeated midazolam 5mg IV after access obtained
4. Physical restraints for safety (removed once sedation effective)

**Critical Point:** Benzodiazepines are first-line for sympathomimetic toxicity - treat agitation, hypertension, tachycardia, and hyperthermia simultaneously

### Primary Survey (After Sedation)

**Airway:** Patent, maintaining own airway
**Breathing:** Tachypneic but adequate
**Circulation:** Tachycardic, hypertensive, warm and flushed
**Disability:** Sedated but arousable, GCS 13
**Exposure:** No trauma, no injection sites, dental caries (meth mouth)

### Hyperthermia Management

**Temperature 39.4C - requires active cooling:**
1. Remove clothing
2. Ice packs to axillae, groin, neck
3. Evaporative cooling (mist and fan)
4. Cold IV fluids
5. Target temperature <38.5C
6. Avoid shivering (counterproductive; additional benzos if needed)

**Avoid antipyretics:** Hyperthermia is not due to pyrogens; acetaminophen/ibuprofen ineffective

### Secondary Survey

**SAMPLE History (limited):**
- Symptoms: Agitation, paranoia, hallucinations
- Allergies: Unknown
- Medications: Unknown
- PMH: Per police - prior meth use, psychiatric history
- Last Meal: Unknown
- Events: Witnessed smoking substance

**Physical Examination:**
- Head: Atraumatic, pupils 7mm and reactive
- Mouth: Severe dental decay, dry mucous membranes
- Neck: Supple, no meningismus
- Cardiac: Tachycardic, regular, no murmurs
- Lungs: Clear, tachypneic
- Abdomen: Soft, non-tender
- Skin: Diaphoretic, no injection marks, multiple excoriations (picking)
- Neuro: Agitated, moving all extremities, no focal deficits

### Diagnostic Testing

**Labs:**
- WBC: 14,200
- BMP: Na 138, K 3.2, Cl 102, HCO3 18, BUN 24, Cr 1.4
- Glucose: 168
- CPK: 4,850 IU/L (elevated - rhabdomyolysis)
- Troponin: 0.08 ng/mL (mildly elevated)
- Lactate: 4.2 mmol/L
- Urine drug screen: Positive for amphetamines
- Urinalysis: Brown urine, positive blood (myoglobinuria)

**ECG:**
- Sinus tachycardia at 138 bpm
- No ischemic changes
- QTc 440ms (normal)

**CT Head (given altered mental status):** No acute intracranial abnormality

### Diagnosis

**Acute methamphetamine intoxication** with:
- Sympathomimetic toxidrome
- Hyperthermia
- Rhabdomyolysis
- Acute kidney injury

### Management

**Continued Treatment:**

1. **Benzodiazepines:** Total midazolam 20mg over first 2 hours for adequate sedation

2. **Rhabdomyolysis Prevention/Treatment:**
   - Aggressive IV fluids: LR at 200-300 mL/hour
   - Goal UOP >200-300 mL/hour
   - Serial CPK monitoring (peak expected 24-72 hours)
   - Monitor potassium, calcium, phosphorus

3. **Hypertension Management:**
   - Primarily with benzodiazepines
   - If refractory: Nicardipine or phentolamine
   - AVOID beta-blockers (unopposed alpha stimulation)

4. **Hyperthermia:**
   - Active cooling continued
   - Temperature normalized to 37.8C within 2 hours

5. **Supportive Care:**
   - Cardiac monitoring
   - Electrolyte repletion (K+)
   - NPO until mental status clear

### Clinical Course

**At 6 hours:**
- Temperature: 37.4C
- HR: 102 bpm
- BP: 148/88 mmHg
- Mental status improving
- CPK: 8,200 (rising, expected)
- Creatinine: 1.6 (worsening)

**At 24 hours:**
- Calm, cooperative
- CPK: 12,400 (peak)
- Creatinine: 1.4 (improving with fluids)
- UOP >150 mL/hour

### Disposition
- Medical admission for rhabdomyolysis management
- Continued IV fluids
- Psychiatry consultation
- Addiction services consultation
- Social work involvement
- Discharged on day 3 with CPK trending down, creatinine normalized
- Outpatient addiction treatment arranged

### Teaching Points

1. **Benzodiazepines are cornerstone:** Treat agitation, hyperthermia, hypertension, and tachycardia simultaneously
2. **Avoid antipsychotics initially:** May lower seizure threshold, worsen hyperthermia
3. **Avoid beta-blockers:** Risk of unopposed alpha stimulation and worsening hypertension
4. **Hyperthermia kills:** Active cooling essential; not responsive to antipyretics
5. **Rhabdomyolysis common:** Check CPK, aggressive hydration, monitor for AKI and hyperkalemia
6. **Medical clearance before psychiatric:** Ensure no life-threatening toxicity before transfer
7. **Excited delirium:** Severe agitation with hyperthermia carries risk of sudden death; aggressive treatment needed

### Clinical Image
![Dilated Pupils in Sympathomimetic Toxicity](case_03_image.jpg)

**Image Description:** Photograph showing bilateral mydriasis (dilated pupils) measuring approximately 7mm, characteristic of sympathomimetic toxicity. The pupils are symmetrically dilated but remain reactive to light.

**Attribution:** Image from Wikimedia Commons, Mydriasis. Licensed under CC BY-SA 4.0. Source: https://commons.wikimedia.org/wiki/File:Mydriasis.jpg