Wernicke disease, opioids and stimulants

The Classic Diagnostic Triad

1. Acute Encephalopathy: Global confusion, disorientation, inattention, apathy, and drowsiness.
2. Ataxia: Broad-based, unsteady, cerebellar gait ataxia and vestibular dysfunction.
3. Oculomotor Dysfunction: Horizontal and vertical nystagmus, bilateral lateral rectus palsy (cranial nerve VI palsy), and conjugate gaze palsies.

Critical AMC Clinical Rule: The complete triad is present in fewer than 20% to 30% of patients with confirmed Wernicke encephalopathy. The presence of any single feature (e.g., isolated confusion or isolated ataxia) in an alcohol-dependent or malnourished individual mandates immediate empirical treatment.

Emergency Prophylaxis and Treatment Protocol

• Thiamine regimen: Well-nourished uncomplicated withdrawal may use oral prophylaxis. Malnutrition or suspected Wernicke encephalopathy warrants parenteral therapy, with suspected WE commonly treated using high-dose IV thiamine under the protocol. Prophylaxis and treatment are different regimens; imported branded preparations are not a universal Australian requirement.
• Thiamine and glucose: Give thiamine before or with carbohydrate when feasible in a deficient patient, but never delay lifesaving glucose for hypoglycaemia. Prolonged carbohydrate delivery without thiamine is dangerous; the rule must not be turned into withholding emergency rescue glucose.
• Korsakoff Syndrome: The chronic, irreversible sequela of untreated or inadequately treated Wernicke encephalopathy. Characterized by dense anterograde amnesia (inability to acquire new episodic memories), variable retrograde amnesia, confabulation (fabricating detailed memories to fill memory deficits without deceptive intent), and complete lack of insight.

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Opioid Misuse: Acute Overdose, Withdrawal & Substitution Therapy

Acute Opioid Overdose

• Clinical Presentation: The classic opioid toxidrome comprises the triad of:
  1. Respiratory Depression: Bradypnoea (respiratory rate $< 8-10\text{ breaths/min}$), shallow tidal volumes, hypercapnia, cyanosis, and respiratory arrest.
  2. Pinpoint Pupils (Miosis): Symmetrical pupillary constriction (note: severe hypoxia or concurrent sympathomimetic ingestion may cause pupillary dilation).
  3. Depressed Level of Consciousness: Stupor, unresponsiveness, or profound coma.
• Emergency Resuscitation:
  • Airway and bag-valve-mask ventilatory support with $100\%$ oxygen is the first priority.
  • Naloxone: Pure competitive mu-opioid receptor antagonist. Administered IV, IM, subcutaneous, or intranasal ($1.6-2\text{ mg}$ IN or $100-400\ \mu\text{g}$ IV).
  • Titration Goal: Titrate incrementally to restore adequate spontaneous ventilation (respiratory rate $> 10-12/\text{min}$) and airway protection, not to induce full consciousness. Overzealous dosing precipitates violent acute withdrawal, severe agitation, and non-cardiogenic pulmonary oedema.
• After naloxone: Recurrent respiratory depression is possible as naloxone wears off. Long-acting opioid overdose, particularly methadone, needs prolonged monitored admission, often at least 24 hours, and sometimes an infusion. A four-to-six-hour observation rule is not adequate for every opioid.

Opioid Withdrawal Syndrome

• Manifestations: Lacrimation, rhinorrhoea, yawning, piloerection ("cold turkey"), mydriasis, diaphoresis, severe diffuse myalgias, abdominal cramps, hyperactive bowel sounds, profuse vomiting, and diarrhoea.
• While subjectively agonizing, uncomplicated opioid withdrawal is not directly fatal (unlike alcohol or sedative withdrawal). Symptomatic management includes clonidine (blunts sympathetic hyperactivity), antiemetics (metoclopramide, ondansetron), loperamide, and NSAIDs.

Opioid Substitution Therapy (OST) in Australia

Long-term maintenance therapy reduces illicit opioid use, criminal involvement, blood-borne virus transmission (HIV, hepatitis C), and all-cause mortality.

• Long-Acting Injectable Buprenorphine (Buvidal, Sublocade): Monthly or weekly subcutaneous depot formulations eliminating daily pharmacy attendance, vastly improving treatment adherence and community stability.

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Stimulant Toxicity: Methamphetamine & Cocaine

Pathophysiology and Clinical Presentation

Stimulants (crystal methamphetamine ["ice"], amphetamines, MDMA, cocaine) provoke massive presynaptic release and blockade of reuptake of noradrenaline, dopamine, and serotonin.

• Sympathomimetic Toxidrome: Marked bilateral pupillary dilation (mydriasis), profuse diaphoresis, hyperpyrexia, sinus tachycardia, severe arterial hypertension, tachypnoea, tremor, hyperreflexia, extreme psychomotor agitation, persecutory paranoia, and tactile formication ("ice bugs" / delusional parasitosis).
• Life-Threatening Complications: Hypertensive encephalopathy, acute myocardial infarction, aortic dissection, intracranial haemorrhage, severe hyperthermia ($> 40.0^\circ\text{C}$), rhabdomyolysis, and renal failure.

Emergency Management

• Environmental Control: Quiet, low-stimulus environment; security containment if violent.
• First-Line Pharmacotherapy: Benzodiazepines (e.g., diazepam $5-10\text{ mg}$ IV or $10-20\text{ mg}$ orally, repeated every 10 to 15 minutes). Benzodiazepines enhance GABA inhibition, directly suppressing central sympathetic outflow, reducing agitation, lowering heart rate and blood pressure, and halting hypermetabolic heat production.
• Stimulant toxicity: Benzodiazepines and supportive care are first-line for agitation and sympathetic activation. Persistent cardiovascular toxicity needs expert treatment; beta-blockers are not the routine first step. The unopposed-alpha concern should not be described as an inevitable fatal effect of every beta-blocker, and combined alpha/beta agents may have selected specialist roles.

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Clinical Comparison Table: Intoxication & Withdrawal Toxidromes

• Alcohol: Intoxication Presentation: Intoxication: ataxia and possible respiratory depression; Withdrawal Presentation: Withdrawal: tremor, autonomic symptoms, seizures or delirium; First-Line Management Priorities: Benzodiazepines under protocol; thiamine without delaying emergency glucose
• Opioids: Intoxication Presentation: Pinpoint pupils (miosis), bradypnoea, coma (hypoventilation); Withdrawal Presentation: Mydriasis, rhinorrhoea, piloerection, cramps, diarrhoea; First-Line Management Priorities: Titrated IV/IN naloxone for overdose; buprenorphine/methadone for OST

For opioid overdose, improvement after naloxone does not establish sustained safety. Continue respiratory observation and reassess the opioid formulation and co-ingestants. A long-acting opioid can outlast the antagonist; recurrent sedation requires prompt reassessment, additional treatment and an appropriate monitored setting.

Primary references (checked 7 October 2026): Australian alcohol treatment guidance.