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

Your Psychiatric Consultation: ADS in Acute Ischemic Stroke

Step 1: Reframe the Clinical Problem

• Is chronically alcohol dependent
• Last drank 2 days ago (1 glass, reportedly low dose)
• Cannot speak (dysarthria/aphasia from stroke) - so verbal CIWA items are invalid
• Cannot cooperate with motor exam (left hemiparesis) - so tremor assessment is invalid
• Has fatty liver + hepatomegaly but normal LFTs - important for drug choice

Step 2: Collateral History - This Is Your Most Important Tool Now

• How much per day, how many years?
• When did she last drink heavily (not just yesterday's 1 glass - what was the baseline)?
• Has she tried to stop before? What happened?

• Has she ever had seizures during stopping?
• Has she ever had DTs (confusion, hallucinations, severe shaking)?
• Has she ever been hospitalized for detox?
• Did she ever need medication to stop drinking?

• Is she unusually sweaty?
• Is she restless, agitated, picking at sheets?
• Are her eyes moving strangely (nystagmus)?
• Any vomiting?
• Any episodes of shaking beyond the stroke-related weakness?

• Any outpatient notes, old prescriptions, past psych/medicine records?
• Check for prior admissions for alcohol-related issues

Step 3: What You CAN Assess Clinically

Key insight: The right side is neurologically intact. Tremor of the right hand, right arm, and right leg can still be assessed - don't skip this just because the left side is paretic.

Step 4: The CIWA-Ar Problem - What to Do Instead

1. Modified CIWA approach - score only the items you CAN observe objectively:
   • Tremor (right side)
   • Sweating
   • Agitation (observable behavior)
   • Vital sign changes
   • Nausea/vomiting (nurse report)
   • Use this partial score with clinical judgment
2. Fixed-dose prophylactic regimen - because the patient CANNOT reliably report symptoms, symptom-triggered therapy is unsafe here. A fixed scheduled dose protocol is more appropriate.
3. PAWSS (Prediction of Alcohol Withdrawal Severity Scale) - uses history and objective labs, does not require verbal responses, better suited here.

Step 5: Risk Stratification

• Last drink was only 1 glass, 2 days ago
• Normal AST/ALT/GGT (suggesting preserved synthetic function despite fatty liver)
• She is still alive and not in severe withdrawal 48 hours later

• Chronic alcoholism (duration, quantity unknown - need from collateral)
• Fatty liver + hepatomegaly = long-term heavy use
• Any prior history of withdrawal seizures/DTs would escalate this immediately
• She is now medically stressed (acute stroke) - physiological stress accelerates withdrawal

• Mild withdrawal (anxiety, tremor, sweating): 6-24 hours after last drink - she's already past this
• Withdrawal seizures: 24-48 hours - she is in this window RIGHT NOW
• Delirium tremens: 48-72 hours - approaching this window
• You are consulting at approximately the highest-risk window for both seizures and DTs

Step 6: Critical Complication to Rule Out - Wernicke's Encephalopathy

• Chronic alcoholism
• Likely nutritional deficiency (fatty liver, hepatomegaly)
• Acute neurological event (stroke)
• Reduced/absent speech

• Thiamine 100 mg IV TDS (three times daily) for at least 3-5 days
• Give IV, not oral - alcoholics have impaired GI absorption of thiamine
• Give BEFORE or with any dextrose/glucose-containing fluids
• This is low-risk, high-benefit in any chronic alcoholic with acute neurological change
• Kaplan & Sadock: "Alcohol has indirect effects by causing thiamine, nicotinic acids, B vitamins, and folate deficiencies... indirect neuronal damage through thiamine deficiency causes Wernicke-Korsakoff syndrome"

Step 7: Benzodiazepine Choice - Liver Disease Matters Here

• Diazepam (long-acting, active metabolites - accumulates in liver disease)
• Chlordiazepoxide (same problem)
• Clonazepam (active metabolites)

• Lorazepam - no active metabolites, direct glucuronidation, best tolerated in liver disease, can be given IV/IM - this is your drug of choice here
• Oxazepam - also acceptable but oral only

Maudsley Prescribing Guidelines: "Lorazepam, oxazepam and temazepam do not have active metabolites and are preferred. Lorazepam is considered the best tolerated in advanced liver disease and is commonly used in alcohol withdrawal."

• Given she cannot reliably report symptoms: fixed scheduled lorazepam rather than symptom-triggered
• Typical: Lorazepam 1-2 mg orally/IV every 6-8 hours for 48-72 hours, then taper over 3-5 days
• Titrate based on observable signs (HR, BP, sweating, agitation, tremor of right side)
• Be cautious with doses - post-stroke patients are sensitive to sedation; excessive sedation masks neurological deterioration

Step 8: The Stroke Team Communication

1. ADS confirmed by history (chronic alcoholism, last use 2 days ago)
2. CIWA-Ar cannot be used reliably due to stroke deficits - recommend fixed-dose protocol
3. Withdrawal risk window is active (48-72 hours post last drink)
4. Recommend prophylactic lorazepam (preferred over diazepam given liver findings)
5. Empirical thiamine IV immediately - cannot clinically exclude Wernicke's
6. Monitor observable withdrawal signs - vitals q4h, right-sided tremor, agitation, diaphoresis
7. Seizure precautions already in place (stroke team should have these, but confirm)
8. Do not use haloperidol for agitation if it arises - lowers seizure threshold; use lorazepam instead
9. Re-consult psychiatry once she can communicate for full MSE, substance use assessment, and discharge planning

Step 9: What You Cannot Do Yet (Document This)

• MSE not performed - patient unable to communicate due to acute stroke (dysarthria/aphasia)
• Tremor assessment limited to right upper/lower limbs only
• Formal ADS severity assessment (CIWA-Ar, AUDIT) deferred until neurologically stable
• Suicidality/insight/motivation for treatment cannot be assessed at present
• Full psychiatric evaluation to be completed once medically and neurologically stable

Summary of Your Consultation Recommendations

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry - Alcohol Intoxication and Withdrawal
• The Maudsley Prescribing Guidelines in Psychiatry, 15th Ed - Sedatives in Hepatic Impairment (Table 8.5)