IMMEDIATE PRIORITY: This Is a Medical Emergency First

Step 1: Recognize the Clinical Syndrome

What you're dealing with - two overlapping poisoning patterns:

1. Opioid agonist toxidrome (shared with morphine) - via mu-opioid receptors:
   • Classic triad: miosis (pinpoint pupils) + respiratory depression + decreased consciousness
   • Bradycardia, hypothermia, hypotension
2. Non-opioid toxicity - via serotonin/norepinephrine reuptake inhibition + GABA antagonism:
   • Seizures - this is the key point here
   • Serotonin syndrome features (if on SSRIs/MAOIs): hyperthermia, hyperreflexia, clonus, agitation

• Tintinalli's Emergency Medicine notes: "Seizures associated with overdoses of tramadol and meperidine" are a recognized feature distinct from other opioids.

Step 2: Immediate Bedside Assessment (Do This Now)

• Airway - is it patent? Jaw tone? Secretions?
• Breathing - respiratory rate, depth, SpO2 on pulse oximetry
• Circulation - pulse, BP, HR, capillary refill

• Pupil size - miosis (pinpoint) = opioid toxidrome; mydriasis = stimulant, serotonin syndrome, or withdrawal
• GCS - quantify level of consciousness
• Reflexes - hyperreflexia + clonus = serotonin syndrome
• Temperature - hyperthermia points toward serotonin syndrome
• Muscle tone - rigidity = serotonin syndrome; flaccidity = pure opioid
• Look for needle marks, patches, pill packets hidden in clothing (always undress fully)

• Continuous SpO2
• Cardiac monitor (tramadol + morphine both affect QT; arrhythmias are possible)
• IV access
• Blood glucose immediately (hypoglycemia mimics this entirely)

Step 3: Administer Naloxone - With Important Caveats

• Start IV: 0.4 mg naloxone IV, can repeat every 2-3 minutes
• Goal is restoration of adequate ventilation (RR >10/min, SpO2 >92%) - NOT full arousal
• If no IV access: IM or intranasal naloxone are acceptable alternatives
• If no response after 10 mg total naloxone, reconsider the diagnosis - think benzodiazepines, alcohol, other CNS depressants, or a structural CNS cause

• Naloxone only partially reverses tramadol toxicity
• The seizures from tramadol are NOT reversed by naloxone - they occur via the non-opioid (GABA antagonist/serotonergic) mechanism
• Naloxone will NOT stop those jerky movements
• (Katzung notes: tramadol's analgesic effect "is only weakly antagonized by naloxone")

Step 4: Manage the Seizure/Myoclonic Activity

• Benzodiazepines are first line for seizure control:
  • Diazepam 5-10 mg IV slowly OR
  • Lorazepam 2-4 mg IV
  • These also work synergistically with GABA
• Do NOT use phenytoin first-line for drug-induced seizures (less effective in metabolic/toxic causes)
• If seizures persist: move to phenobarbital (especially useful here as it has GABA-enhancing properties that directly counter tramadol's GABA antagonism)

Step 5: Differential Diagnosis to Keep in Mind

Step 6: Empirical IV Thiamine (Mandatory in Drug Users)

• Thiamine 100 mg IV BEFORE any dextrose
• This prevents precipitating/worsening Wernicke's encephalopathy

Step 7: Investigations to Order

• Blood glucose (do fingerstick NOW)
• ABG (most important - assesses respiratory failure, acidosis)
• ECG (QT prolongation from opioids, tramadol)
• CBC, BMP/electrolytes, renal and liver function
• Urine toxicology screen
• Serum acetaminophen/paracetamol (often co-ingested in tramadol combination tablets)
• Blood ethanol level

Step 8: Ongoing Management

• Airway: If respiratory rate drops below 10 or SpO2 <90% despite O2 and naloxone - prepare for bag-valve mask ventilation and call for intubation
• Naloxone infusion: Because morphine and tramadol have longer half-lives than naloxone (60-90 min), the patient may re-narcotize after initial reversal. If they respond to naloxone initially, start a naloxone infusion (typically 2/3 of the effective bolus dose per hour)
• Positioning: Left lateral decubitus (recovery position) if not intubated, to prevent aspiration
• Do NOT give more than 10 mg naloxone total without reassessing - if no response, the primary problem is not opioid toxicity alone

Your Role as Psychiatry Resident - Practical Points

1. Consult emergency medicine/toxicology immediately - you should not be managing this alone; psychiatry leads on the substance use history and long-term plan, but acute toxicology is EM/ICU territory
2. If in a setting without EM backup, you are the treating physician and must follow the ABCDE approach above
3. Document everything: time of discovery, GCS, pupils, vitals, interventions with timestamps
4. Do NOT administer antipsychotics (haloperidol, etc.) right now - they further lower seizure threshold
5. Avoid flumazenil empirically (can precipitate withdrawal seizures if benzos are on board)
6. Once stable, a formal psychiatric assessment, substance use disorder evaluation, and safety planning will be your domain

Summary Algorithm

Unresponsive drug user suspected tramadol/morphine
        ↓
ABC + O2 + monitoring + IV access + fingerstick glucose
        ↓
Empirical thiamine 100mg IV
        ↓
Naloxone 0.4mg IV (repeat q2-3 min, titrate to RR>10)
        ↓
If seizures/myoclonus → benzodiazepine IV (lorazepam/diazepam)
        ↓
No naloxone response → consider mixed overdose (BZD, EtOH, structural)
        ↓
Consider naloxone infusion if initial response then re-narcotization
        ↓
ECG, ABG, labs, ICU/HD monitoring
        ↓
Call toxicology/EM if available

• Tintinalli's Emergency Medicine, Chapter 186 (Opioids)
• Kaplan & Sadock's Comprehensive Textbook of Psychiatry - Treatment of Opioid Overdose
• Katzung's Basic and Clinical Pharmacology, 16th Ed - Tramadol mechanism
• Tramadol poisoning scoping review, Manouchehri et al., Ann Med Surg 2023 (PMID 37554850)

Your Immediate Role in the ER

1. Hand Off the Acute Medical Management to ER Team

• Airway management
• Naloxone administration
• Seizure control
• Vitals monitoring and resuscitation

2. What YOU Should Be Doing Right Now

• Question the informant more carefully:
  • What drugs does he usually take? In what combinations?
  • Does he use tramadol for recreational or pain purposes?
  • Is he on any prescribed medications (SSRIs, TCAs, MAOIs)? - critical for serotonin syndrome risk
  • Any recent dose changes or binging?
  • How long has he been unresponsive?
  • Did anyone witness the episode?
  • Any empty bottles, blister packs, syringes at the scene?
  • Has this happened before? What happened last time?

3. Watch the Jerky Movements Closely

• Are they symmetrical or asymmetrical?
• Which body parts? (whole body vs limbs vs face)
• Is there eye deviation?
• Any postictal drowsiness after each episode?
• Any tongue bite, urinary incontinence?
• Frequency changing (improving, worsening)?

• Myoclonus (sudden brief jerks, no loss of further tone, no postictal phase) = tramadol-specific, treat with benzodiazepines, not phenytoin
• Generalized tonic-clonic = broader anticonvulsant strategy needed
• Decerebrate/decorticate posturing = structural brain event, needs CT head urgently

4. Communicate One Critical Point to the ER Team

"Tramadol seizures do NOT respond to naloxone - they need benzodiazepines."

5. Monitor the Naloxone Response Together

6. Flag Serotonin Syndrome to the Team

• Tramadol + those drugs = serotonin syndrome risk
• Look for: hyperthermia, clonus (especially ankle), hyperreflexia, diaphoresis, agitation
• Treatment is cyproheptadine + benzodiazepines - NOT naloxone

7. What NOT to Do

• Don't give haloperidol or any antipsychotic - lowers seizure threshold further
• Don't give flumazenil empirically - can trigger severe withdrawal seizures if benzodiazepines are on board
• Don't assume the seizures will stop with naloxone
• Don't discharge or transfer to psych ward until medically cleared and stable for at least 4-6 hours post last seizure

8. Your Documentation Right Now

• Time of presentation
• Collateral history obtained
• Known substance use history
• Any psychiatric comorbidities
• Medications prescribed
• Your clinical observations

Stop and Clarify First: What Do the Pupils Look Like?

• Size in mm (or small/medium/large)
• Equal or unequal
• Any reaction at all, even sluggish?

If Pupils Are PINPOINT + Non-reactive

• Naloxone should already be going - if not, give 0.4 mg IV now
• Pinpoint non-reactive pupils in this context = heavy opioid load
• Expect pupils to dilate within 2-3 minutes of naloxone if this is the cause
• If they dilate → diagnosis confirmed, continue naloxone titration

If Pupils Are MID-SIZE or DILATED + Non-reactive

• Intracranial hemorrhage (subdural, subarachnoid, intracerebral)
• Cerebral herniation from any mass lesion
• Severe anoxic brain injury from prolonged respiratory depression before arrival
• Pontine hemorrhage (classically pinpoint + non-reactive mimicking opioids exactly)

• Inform ER physician immediately - "pupils non-reactive, need urgent CT head"
• GCS needs to be formally scored - if GCS ≤8, intubation should be considered
• Neurosurgery on call needs to be alerted

If One Pupil is Larger Than the Other (Anisocoria)

• Blown pupil (dilated, non-reactive) = CN III compression = uncal herniation
• Call neurosurgery immediately
• CT head is urgent - not optional

The Key Clinical Decision Right Now

Give naloxone IV if not already given
        ↓
Wait 2-3 minutes
        ↓
Did pupils change at all?
    YES (miosis improving, some dilation)
        → Opioid toxidrome confirmed
        → Continue naloxone, titrate
        → Still need CT if GCS doesn't improve sufficiently
    
    NO change at all
        → Structural cause must be ruled out
        → CT head URGENTLY
        → GCS ≤8 → intubation
        → Neurosurgery alert

Do Not Assume It's "Just Drugs"

• Drug users fall, hit their heads, and bleed intracranially
• They can have subdural hematomas from trauma while intoxicated
• The seizure activity + unresponsive + non-reactive pupils triad needs a CT head regardless of suspected drug cause
• Missing a bleed in a "known drug user" is a serious and common clinical error