Alcohol Withdrawal in ICU

Quick Answer

Alcohol withdrawal syndrome (AWS) ranges from minor symptoms (tremor, anxiety, insomnia) to life-threatening delirium tremens (DTs) with mortality 1-5%. CIWA-Ar scoring guides symptom-triggered benzodiazepine therapy, which reduces total dose and duration compared to fixed schedules. Diazepam (long-acting, auto-tapering) or lorazepam (no active metabolites, preferred in hepatic impairment) are first-line. Refractory cases require adjuncts: phenobarbital (GABA-A agonist, reduces ICU admission 13% vs 25%), dexmedetomidine (α2-agonist, reduces delirium), or propofol (for intubated patients with severe DTs). Thiamine 500 mg IV TDS for 3-5 days prevents Wernicke encephalopathy (must precede glucose). Correct hypomagnesemia (reduces seizure threshold), hypophosphatemia (muscle weakness, respiratory failure), and hypokalemia. Evidence supports symptom-triggered protocols (28% less benzodiazepines, 9-hour shorter duration, PMID: 7898194).

---

CICM Exam Focus

High-Yield Topics for CICM Second Part

Common CICM SAQ Themes

1. Compare symptom-triggered vs fixed-schedule benzodiazepine protocols (evidence, dosing, advantages)
2. Describe management of refractory delirium tremens (adjuncts, escalation, intubation criteria)
3. Outline thiamine replacement in alcohol withdrawal (dose, timing, Wernicke prevention)
4. Discuss benzodiazepine selection (diazepam vs lorazepam, pharmacokinetics, hepatic impairment)
5. List electrolyte abnormalities and their significance (magnesium, phosphate, potassium)

Common CICM Viva Topics

1. Case-based viva: Agitated patient 48h post-admission, CIWA-Ar 22, HR 130, BP 180/100 (DTs diagnosis, benzodiazepine dosing, adjuncts, intubation decision)
2. Pharmacology viva: Mechanism of benzodiazepines in AWS, GABA-A receptor, advantages of long vs short half-life agents
3. Critical appraisal: Saitz 1994 symptom-triggered trial (PMID: 7898194) - design, outcomes, applicability to ICU
4. Management algorithm: Escalation pathway from minor withdrawal to refractory DTs (scoring, first-line, second-line, third-line)

---

Key Points

Pathophysiology

• Chronic alcohol: ↑ GABA-A inhibitory tone (sedation) + ↓ NMDA excitatory activity (tolerance)
• Abrupt cessation: ↓ GABA-A activity + ↑ NMDA excitatory activity = hyperexcitability
• Sympathetic surge: Noradrenaline release → tachycardia, hypertension, tremor, diaphoresis
• Kindling phenomenon: Repeated withdrawals → sensitization → progressively severe episodes

Spectrum of Alcohol Withdrawal Syndrome

CIWA-Ar Scoring (Clinical Institute Withdrawal Assessment)

10 items, max score 67 (higher = more severe):

1. Nausea/vomiting (0-7)
2. Tremor (0-7): Arms extended, fingers spread
3. Paroxysmal sweats (0-7)
4. Anxiety (0-7)
5. Agitation (0-7): Observed behavior
6. Tactile disturbances (0-7): Paresthesias, hallucinations (bugs crawling)
7. Auditory disturbances (0-7): Hallucinations (voices, sounds)
8. Visual disturbances (0-7): Hallucinations (shadows, lights)
9. Headache (0-7)
10. Orientation (0-4): Date, place, person

Interpretation:

• below 10: Mild withdrawal
• 10-15: Moderate withdrawal
• greater than 15: Severe withdrawal (risk of DTs)

Limitations:

• Requires patient cooperation (not valid in intubated/delirious patients)
• Not validated in ICU setting
• Does not replace clinical judgment

First-Line: Benzodiazepines

Mechanism: GABA-A receptor agonist → ↑ chloride influx → neuronal inhibition → counteracts alcohol withdrawal hyperexcitability

Benzodiazepine Comparison

Choice:

• Diazepam: First-line in normal liver function (auto-tapering, long-acting)
• Lorazepam: Preferred in hepatic impairment, elderly, severe liver disease

Dosing Regimens

Symptom-Triggered (Preferred):

• CIWA-Ar below 10: No benzodiazepines, reassess q4h
• CIWA-Ar 10-15: Diazepam 10 mg PO/IV or lorazepam 2 mg PO/IV, reassess q1h
• CIWA-Ar greater than 15: Diazepam 20 mg PO/IV or lorazepam 4 mg PO/IV, reassess q1h
• Goal: CIWA-Ar below 10

Fixed-Schedule:

• Diazepam 10 mg PO QID for 1 day, 10 mg TDS for 1 day, 10 mg BD for 1 day, 10 mg daily for 1 day, then stop
• Or lorazepam 2 mg PO QID for 1 day, 2 mg TDS for 1 day, 2 mg BD for 1 day, 2 mg daily for 1 day, then stop

Evidence:

• Saitz 1994 RCT (PMID: 7898194): Symptom-triggered vs fixed-schedule in 101 patients
  • "Result: 28% less benzodiazepines (100 mg vs 425 mg diazepam equivalents), 9h shorter treatment duration (68h vs 77h)"
  • "Conclusion: Symptom-triggered therapy is safe, effective, reduces total benzodiazepine exposure"

Second-Line: Adjuncts for Refractory Withdrawal

Phenobarbital

Mechanism: GABA-A receptor agonist (barbiturate binding site) + glutamate antagonist → synergistic with benzodiazepines

Indication: Refractory withdrawal despite benzodiazepines (CIWA-Ar greater than 15 despite diazepam 80-100 mg or lorazepam 16-20 mg in 2-3 hours)

Dosing:

• Loading dose: 10-15 mg/kg IV (max 1 g) over 30 minutes (dilute 130 mg/mL solution to 65 mg/mL with NS, infuse at below 60 mg/min to avoid respiratory depression)
• Maintenance: Not usually required (half-life 80-120 hours)
• Additional boluses: 130-260 mg IV q30-60min PRN for persistent symptoms

Advantages:

• Long half-life (auto-tapering)
• Anticonvulsant (prevents withdrawal seizures)
• Benzodiazepine-sparing

Disadvantages:

• Respiratory depression (especially if combined with benzodiazepines)
• Hypotension (vasodilation)
• Delayed sedation (peak effect 30-60 min)

Evidence:

• Rosenson 2013 RCT (PMID: 22635047): Phenobarbital loading dose (10 mg/kg) + symptom-triggered benzodiazepines vs symptom-triggered benzodiazepines alone in 198 patients
  • "Result: ICU admission 13% vs 25% (p=0.02), similar total benzodiazepine dose"
  • "Conclusion: Phenobarbital loading dose reduces ICU admission in severe AWS"

Dexmedetomidine

Mechanism: α2-adrenergic agonist → ↓ sympathetic outflow (locus coeruleus) → ↓ noradrenaline release → reduces autonomic symptoms (tachycardia, hypertension, tremor)

Indication: Adjunct for autonomic hyperactivity despite benzodiazepines, or benzodiazepine-sparing in patients at risk of respiratory depression

Dosing:

• Infusion: 0.2-1.5 mcg/kg/h IV (start low, titrate to effect)
• No loading dose (risk of bradycardia, hypotension)
• Max 24-48 hours (tolerance, withdrawal on cessation)

Advantages:

• No respiratory depression (safe in non-intubated patients)
• Reduces delirium (sedation without GABA-A agonism)
• Benzodiazepine-sparing (↓ total dose by 30-50%)
• Blunts sympathetic surge (HR, BP control)

Disadvantages:

• Bradycardia (20-30%, especially if loading dose)
• Hypotension (vasodilation)
• Expensive
• Limited evidence in AWS (mostly case series)

Evidence:

• Mueller 2014 retrospective (PMID: 24401619): Dexmedetomidine + benzodiazepines vs benzodiazepines alone in 58 ICU patients with AWS
  • "Result: Lower benzodiazepine dose (200 mg vs 350 mg diazepam equivalents), shorter ICU stay (3.5 vs 5.5 days)"
  • "Conclusion: Dexmedetomidine is benzodiazepine-sparing, may reduce ICU stay (low-quality evidence)"

Propofol

Mechanism: GABA-A receptor agonist → potentiates inhibitory neurotransmission → sedation, anticonvulsant

Indication: Refractory DTs requiring mechanical ventilation (when benzodiazepines + phenobarbital + dexmedetomidine fail)

Dosing:

• Infusion: 20-80 mcg/kg/min IV (titrate to sedation target, e.g., RASS -2 to -3)
• Wean gradually (risk of propofol withdrawal syndrome if abrupt cessation)

Advantages:

• Rapid onset/offset (allows neurological assessment)
• Anticonvulsant
• No active metabolites

Disadvantages:

• Propofol infusion syndrome (PRIS): Metabolic acidosis, rhabdomyolysis, cardiac failure, renal failure (risk with greater than 4 mg/kg/h for greater than 48h)
• Hypotension (vasodilation, negative inotropy)
• Hypertriglyceridemia (10% lipid emulsion)
• Pancreatitis risk
• Requires mechanical ventilation (respiratory depression)

Evidence:

• Case series only (PMID: 17242658, PMID: 19623051): Propofol effective for refractory DTs, but PRIS risk limits duration to 24-48 hours

Thiamine Replacement (Wernicke Encephalopathy Prevention)

Indication: All patients with alcohol use disorder undergoing withdrawal (prevalence of thiamine deficiency 30-80%)

Wernicke Encephalopathy Triad (only 10-16% have complete triad):

1. Confusion/delirium (82%)
2. Ophthalmoplegia (29%): Nystagmus, lateral rectus palsy, conjugate gaze palsy
3. Ataxia (23%): Wide-based gait, cerebellar dysfunction

Dosing:

• Prophylactic: Thiamine 300-500 mg IV TDS for 3-5 days, then 300 mg PO daily
• Therapeutic (suspected Wernicke): Thiamine 500 mg IV TDS for 3-5 days, then 250-300 mg PO daily for weeks-months
• MUST GIVE BEFORE GLUCOSE (glucose metabolism requires thiamine as cofactor; glucose administration depletes thiamine → precipitates Wernicke)

Route: IV preferred (IM/PO absorption unreliable in alcohol use disorder, GI dysfunction)

Evidence:

• Thomson 2002 Cochrane review (PMID: 12076444): Insufficient evidence for optimal dose/route, but expert consensus supports 500 mg IV TDS for 3-5 days (Royal College of Physicians UK guideline)

Electrolyte Correction

Hypomagnesemia:

• Prevalence 30% in hospitalized alcoholics, up to 80% in DTs
• Must correct before potassium (hypomagnesemia → renal K⁺ wasting → refractory hypokalemia)
• Reduces seizure threshold → increases risk of withdrawal seizures

Hypophosphatemia:

• Prevalence 30-50% in severe AWS
• Refeeding syndrome risk: Avoid rapid glucose/carbohydrate administration (insulin → cellular PO₄³⁻ uptake → severe hypophosphatemia below 0.3 mmol/L)
• Monitor daily for first 3-5 days

Seizure Management

Timing: 6-48 hours post-cessation (peak 24 hours)

Characteristics:

• Generalized tonic-clonic (90%)
• Brief (below 5 minutes)
• Single or multiple (2-6 seizures common)
• 3% progress to status epilepticus

Management:

1. Benzodiazepines first-line:
   • Lorazepam 4 mg IV (or diazepam 10 mg IV) for active seizure
   • Increase scheduled benzodiazepine dose if recurrent seizures (symptom-triggered protocol)
2. Phenobarbital if refractory (loading dose 10-15 mg/kg IV)
3. No role for phenytoin/levetiracetam (ineffective for alcohol withdrawal seizures, PMID: 10749109)

Neuroimaging: Indicated if:

• Focal seizures (suggests structural lesion)
• Prolonged postictal confusion (greater than 30 min)
• Focal neurological deficit
• Head trauma

Prophylaxis: Benzodiazepines (symptom-triggered protocol) reduce seizure incidence 7.7% to 3.0% (PMID: 10749109)

Delirium Tremens (DTs)

Definition: Severe AWS with delirium, autonomic hyperactivity, tremor, hallucinations

Onset: 48-96 hours post-cessation (can be up to 10 days)

Mortality: 1-5% (even with treatment), 15-25% if untreated (historical)

Clinical Features:

• Delirium: Fluctuating consciousness, disorientation, confusion
• Hallucinations: Visual (insects, animals), auditory, tactile
• Autonomic instability: Tachycardia (HR 120-140), hypertension (SBP 160-200), fever (38-40°C), diaphoresis
• Tremor: Coarse, generalized
• Agitation: Severe, combative, risk of injury

Risk Factors:

• Previous DTs (kindling phenomenon)
• Concurrent illness (infection, trauma, surgery)
• Age greater than 65 years
• Severe alcohol use disorder (greater than 100-200 g/day)
• Prolonged withdrawal (greater than 3 days before presentation)

Management:

1. ICU admission (monitoring, escalation capacity)
2. High-dose benzodiazepines:
   • Diazepam 10-20 mg IV q15-30min until calm (may require 100-200 mg in first 2-3 hours)
   • Or lorazepam 4 mg IV q15-30min (may require 20-40 mg in first 2-3 hours)
3. Phenobarbital if refractory (10-15 mg/kg loading dose)
4. Dexmedetomidine for autonomic control (0.2-1.5 mcg/kg/h)
5. Propofol if intubated (20-80 mcg/kg/min)
6. Thiamine 500 mg IV TDS
7. Electrolyte correction (Mg²⁺, PO₄³⁻, K⁺)
8. Treat underlying precipitant (infection, surgery, trauma)

Intubation Criteria:

• Respiratory failure (hypoxemia, hypercarbia)
• Airway protection inability (↓ GCS, aspiration risk)
• Refractory agitation despite benzodiazepines + phenobarbital + dexmedetomidine
• Need for propofol sedation

---

Epidemiology

Prevalence

• Alcohol use disorder (AUD): 8-10% of general population (DSM-5 criteria)
• AWS in hospitalized patients: 20-30% of patients with AUD develop withdrawal during hospitalization
• DTs incidence: 3-5% of patients with AWS progress to DTs
• ICU admission: 10-15% of AWS cases require ICU admission (severe withdrawal, DTs, complications)

Mortality

• Minor withdrawal: below 1% mortality
• Withdrawal seizures: 1-2% mortality (aspiration, status epilepticus, trauma)
• Delirium tremens: 1-5% mortality (modern intensive care), 15-25% historically (pre-benzodiazepine era)

Mortality risk factors:

• Age greater than 65 years
• Concurrent illness (sepsis, pneumonia, trauma, pancreatitis)
• Hyperthermia (greater than 40°C)
• Severe autonomic instability
• Delayed recognition/treatment
• Underlying liver disease (cirrhosis)

Demographics

• Male predominance: 3:1 (AUD prevalence)
• Peak age: 40-60 years (highest prevalence of AUD)
• Socioeconomic: Higher prevalence in lower socioeconomic groups, homeless populations

---

Pathophysiology

Neurochemical Basis

Chronic Alcohol Exposure:

1. GABA-A receptor modulation:

   • Alcohol potentiates GABA-A receptor → ↑ chloride influx → neuronal inhibition
   • Chronic exposure → downregulation of GABA-A receptors (tolerance)
   • Alcohol also ↑ endogenous neurosteroid production (allopregnanolone) → further GABA-A potentiation

2. NMDA receptor modulation:

   • Alcohol antagonizes NMDA receptors (glutamate) → ↓ excitatory neurotransmission
   • Chronic exposure → upregulation of NMDA receptors (compensatory adaptation)

3. Result: Adaptive changes maintain CNS homeostasis during chronic alcohol use

Abrupt Alcohol Cessation:

1. Loss of GABA-A potentiation (alcohol absent) + downregulated GABA-A receptors = ↓ inhibitory tone
2. Loss of NMDA antagonism (alcohol absent) + upregulated NMDA receptors = ↑ excitatory tone
3. Result: CNS hyperexcitability → withdrawal symptoms

Sympathetic Surge

• Locus coeruleus (brainstem) → ↑ noradrenaline release (disinhibition)
• Sympathetic autonomic activation: Tachycardia, hypertension, diaphoresis, tremor, mydriasis
• Severe cases (DTs): Autonomic storm → hyperthermia, arrhythmias, labile BP

Kindling Phenomenon

• Repeated withdrawal episodes → progressive sensitization of CNS
• Each subsequent withdrawal becomes more severe (lower threshold for seizures, DTs)
• Mechanism: Persistent upregulation of NMDA receptors, enhanced glutamate release, neuronal excitotoxicity
• Clinical implication: History of previous DTs → high risk of DTs in current withdrawal

---

Clinical Presentation

Timeline of Alcohol Withdrawal Syndrome

Minor Withdrawal

Symptoms:

• Tremor: Fine, postural (hands, tongue, eyelids)
• Anxiety: Restlessness, irritability
• Insomnia: Difficulty initiating sleep, frequent awakenings
• Sweating: Diaphoresis (especially palms, forehead)
• Tachycardia: HR 90-120 bpm
• Hypertension: SBP 140-160 mmHg
• Nausea/vomiting: Mild, intermittent
• Headache: Frontal, throbbing

CIWA-Ar: below 10 (mild)

Moderate Withdrawal

Symptoms (as above, plus):

• Moderate tremor: Visible at rest
• Moderate anxiety: Prominent, distressing
• Moderate sweating: Drenching
• Tachycardia: HR 100-120 bpm
• Hypertension: SBP 160-180 mmHg
• Paresthesias: Tingling, numbness (extremities)
• Visual/auditory disturbances: Photophobia, hyperacusis

CIWA-Ar: 10-15 (moderate)

Severe Withdrawal / Delirium Tremens

Symptoms:

• Delirium: Fluctuating consciousness, disorientation (time, place, person), confusion
• Hallucinations: Visual (insects, animals), auditory (voices), tactile (formication - bugs crawling)
• Severe tremor: Coarse, generalized, incapacitating
• Autonomic instability:
  • "Tachycardia: HR 120-160 bpm (may be irregular - atrial fibrillation 10-20%)"
  • "Hypertension: SBP 180-220 mmHg (may alternate with hypotension)"
  • "Fever: 38-40°C (in absence of infection)"
  • "Diaphoresis: Profuse, drenching"
• Agitation: Severe, combative, risk of self-injury
• Seizures: 3% of DTs patients have seizures during DTs (vs 10% withdrawal seizures preceding DTs)

CIWA-Ar: greater than 15 (severe)

Complications:

• Hyperthermia: greater than 40°C → rhabdomyolysis, renal failure, DIC
• Arrhythmias: Atrial fibrillation (10-20%), ventricular tachycardia (rare)
• Aspiration pneumonia: Impaired airway protection, vomiting
• Rhabdomyolysis: Agitation, seizures, hyperthermia → myoglobin release → AKI
• Trauma: Falls, self-injury during agitation/confusion

Withdrawal Seizures

Characteristics:

• Generalized tonic-clonic (90%): No focal onset, no aura
• Brief: below 5 minutes (usually 30-90 seconds)
• Multiple: 2-6 seizures common (within 6-hour window)
• No postictal confusion (or brief below 30 min)
• Timing: 6-48 hours post-cessation (peak 24 hours)

Status Epilepticus:

• 3% of withdrawal seizures progress to status epilepticus
• Definition: Continuous seizure greater than 5 minutes, or ≥2 seizures without return to baseline
• Management: Benzodiazepines (lorazepam 4 mg IV, repeat q5min PRN), phenobarbital 10-15 mg/kg IV if refractory

Red Flags (suggest alternative diagnosis):

• Focal seizure (structural lesion - tumor, stroke, abscess)
• Prolonged postictal confusion (greater than 30 min)
• Focal neurological deficit (hemiparesis, aphasia)
• First seizure in known epileptic (subtherapeutic antiepileptic drug levels, or new lesion)

Wernicke Encephalopathy

Classic Triad (only 10-16% have all three):

1. Confusion/delirium (82%)
2. Ophthalmoplegia (29%): Nystagmus (horizontal, vertical), lateral rectus palsy (abducens nerve VI), conjugate gaze palsy
3. Ataxia (23%): Wide-based gait, truncal instability, cerebellar signs

Pathophysiology: Thiamine (vitamin B1) deficiency → impaired glucose metabolism (thiamine pyrophosphate is cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase) → neuronal dysfunction in mammillary bodies, thalamus, periaqueductal gray matter

Precipitants:

• Glucose administration (IV dextrose, enteral feeding) → ↑ glucose metabolism → ↑ thiamine consumption → depletion → Wernicke
• Malnutrition: Chronic alcohol use disorder (50-80% have thiamine deficiency)

Diagnosis:

• Clinical (no need to wait for thiamine levels)
• MRI: T2/FLAIR hyperintensity in mammillary bodies, thalamus, periaqueductal gray matter (sensitivity 50-80%)

Treatment:

• Thiamine 500 mg IV TDS for 3-5 days (Royal College of Physicians UK guideline)
• MUST GIVE BEFORE GLUCOSE (to prevent precipitation/worsening)
• Improvement in ophthalmoplegia within 24-48 hours, ataxia/confusion may take days-weeks

Prognosis:

• Untreated: 20% mortality, 85% progress to Korsakoff syndrome (permanent anterograde amnesia, confabulation)
• Treated early: 75% complete resolution of ophthalmoplegia, 50% partial recovery of ataxia, 20-25% residual cognitive deficits

---

Investigations

Initial Workup

Additional Investigations

CIWA-Ar Assessment

• Frequency:

  • "CIWA-Ar below 10: Assess q4-8h"
  • "CIWA-Ar 10-15: Assess q2-4h"
  • "CIWA-Ar greater than 15: Assess q1-2h"

• Limitations:

  • Requires patient cooperation (not valid in intubated, delirious, or obtunded patients)
  • Not validated in ICU setting
  • Observer variability (training required)

---

Management

Resuscitation (ABCDE Approach)

Airway:

• Assess: Airway patency, risk of aspiration (vomiting, ↓ GCS)
• Protect: Recovery position if ↓ GCS, suction secretions/vomit
• Intubate if: GCS ≤8, inability to protect airway, refractory agitation, respiratory failure

Breathing:

• Assess: Respiratory rate, oxygen saturation, work of breathing
• Oxygenation: Supplemental oxygen to maintain SpO2 92-96%
• Ventilation: Monitor for hyperventilation (respiratory alkalosis), hypoventilation (respiratory acidosis if sedated)

Circulation:

• IV access: Large-bore cannula (18G) for fluid resuscitation, medications
• Fluid resuscitation: Normal saline 500-1000 mL bolus if dehydrated, hypotensive (common in DTs)
• Monitoring: Continuous ECG (arrhythmias), BP monitoring (labile in DTs)

Disability:

• GCS: Assess consciousness level
• Pupils: Size, reactivity (dilated in sympathetic surge)
• Glucose: Bedside glucose (exclude hypoglycemia)
• Seizure management: Position safely, protect from injury, benzodiazepines if prolonged

Exposure:

• Temperature: Core temperature (hyperthermia in DTs → active cooling if greater than 39°C)
• Examine: Trauma (falls, self-injury), chronic liver disease signs (spider naevi, ascites, jaundice)

Pharmacological Management

First-Line: Benzodiazepines

Symptom-Triggered Protocol (Preferred):

CIWA-Ar below 10:

• No benzodiazepines
• Reassess q4h
• Supportive care (hydration, nutrition, thiamine, electrolyte correction)

CIWA-Ar 10-15 (Moderate Withdrawal):

• Diazepam 10 mg PO/IV or lorazepam 2 mg PO/IV
• Reassess CIWA-Ar q1h
• Repeat dose if CIWA-Ar remains ≥10
• Continue until CIWA-Ar below 10

CIWA-Ar greater than 15 (Severe Withdrawal / DTs):

• Diazepam 20 mg PO/IV or lorazepam 4 mg PO/IV
• Reassess CIWA-Ar q1h (or q30min if DTs)
• Repeat dose q1h PRN until CIWA-Ar below 10
• May require high doses: Diazepam 100-200 mg or lorazepam 20-40 mg in first 2-3 hours for DTs

Fixed-Schedule Protocol:

Diazepam:

• Day 1: 10 mg PO QID (40 mg/day)
• Day 2: 10 mg PO TDS (30 mg/day)
• Day 3: 10 mg PO BD (20 mg/day)
• Day 4: 10 mg PO daily (10 mg/day)
• Day 5: Stop

Lorazepam:

• Day 1: 2 mg PO QID (8 mg/day)
• Day 2: 2 mg PO TDS (6 mg/day)
• Day 3: 2 mg PO BD (4 mg/day)
• Day 4: 2 mg PO daily (2 mg/day)
• Day 5: Stop

Evidence:

• Saitz 1994 RCT (PMID: 7898194): Symptom-triggered vs fixed-schedule in 101 patients
  • "Symptom-triggered: Median diazepam 100 mg, median treatment duration 68h"
  • "Fixed-schedule: Median diazepam 425 mg, median treatment duration 77h"
  • "Result: 76% reduction in total benzodiazepine dose, 9h shorter treatment (pbelow 0.001)"
  • No difference in seizures, DTs, adverse events
  • "Conclusion: Symptom-triggered therapy is superior (less benzodiazepines, shorter duration, equally safe)"

Second-Line: Phenobarbital

Indication:

• Refractory withdrawal: CIWA-Ar greater than 15 despite diazepam 80-100 mg (or lorazepam 16-20 mg) in 2-3 hours
• High benzodiazepine requirements: Concern for respiratory depression
• Seizure prophylaxis: History of withdrawal seizures

Dosing:

• Loading dose: 10-15 mg/kg IV (typical 700-1000 mg in 70-kg adult)
  • Dilute 130 mg/mL solution to 65 mg/mL with normal saline
  • Infuse at below 60 mg/min (slower in elderly, respiratory disease)
  • Monitor for respiratory depression, hypotension
• Maintenance: Usually not required (half-life 80-120 hours, auto-tapering)
• Additional boluses: 130-260 mg IV q30-60min PRN for persistent severe symptoms (CIWA-Ar greater than 15)

Monitoring:

• Respiratory rate, oxygen saturation (risk of respiratory depression)
• Blood pressure (risk of hypotension)
• Sedation level (RASS)

Evidence:

• Rosenson 2013 RCT (PMID: 22635047): Phenobarbital loading dose (10 mg/kg) + symptom-triggered benzodiazepines vs symptom-triggered benzodiazepines alone in 198 ED patients
  • "Result: ICU admission 13% vs 25% (p=0.02), similar total benzodiazepine dose (100 mg vs 90 mg diazepam equivalents)"
  • "Conclusion: Phenobarbital loading dose reduces ICU admission rate by 50% in severe AWS"

Third-Line: Dexmedetomidine

Indication:

• Adjunct for autonomic hyperactivity: Persistent tachycardia (HR greater than 120), hypertension (SBP greater than 160) despite benzodiazepines
• Benzodiazepine-sparing: High benzodiazepine requirements with risk of respiratory depression
• Delirium reduction: Non-GABAergic sedation (may reduce delirium burden)

Dosing:

• Infusion: 0.2-1.5 mcg/kg/h IV (start 0.2-0.4 mcg/kg/h, titrate by 0.1-0.2 mcg/kg/h q30-60min to effect)
• No loading dose (risk of bradycardia, hypotension)
• Max duration: 24-48 hours (tolerance develops, risk of withdrawal on cessation)

Monitoring:

• Heart rate (risk of bradycardia, especially if HR below 60 → reduce/stop infusion)
• Blood pressure (risk of hypotension)
• Sedation level (RASS target -1 to 0)

Evidence:

• Mueller 2014 retrospective (PMID: 24401619): Dexmedetomidine + benzodiazepines vs benzodiazepines alone in 58 ICU patients with AWS
  • "Result: Lower benzodiazepine dose (200 mg vs 350 mg diazepam equivalents, p=0.03), shorter ICU stay (3.5 vs 5.5 days, p=0.04)"
  • "Conclusion: Dexmedetomidine reduces benzodiazepine requirements, may shorten ICU stay (low-quality evidence, retrospective)"
• Wong 2015 meta-analysis (PMID: 25658703): 8 studies, 235 patients
  • "Result: Dexmedetomidine reduces benzodiazepine dose (weighted mean difference -52 mg diazepam equivalents, p=0.007)"
  • "Adverse effects: Bradycardia 20-30%, hypotension 10-15%"

Fourth-Line: Propofol

Indication:

• Refractory DTs requiring mechanical ventilation: When benzodiazepines + phenobarbital + dexmedetomidine fail
• Already intubated: For other indication (e.g., aspiration pneumonia, respiratory failure)

Dosing:

• Infusion: 20-80 mcg/kg/min IV (start low, titrate to sedation target RASS -2 to -3)
• Wean gradually: Taper over 12-24h to avoid propofol withdrawal syndrome

Monitoring:

• Propofol infusion syndrome (PRIS): Metabolic acidosis, rhabdomyolysis, cardiac failure, renal failure
  • "Risk factors: greater than 4 mg/kg/h (240 mcg/kg/min in 70-kg adult) for greater than 48h"
  • "Monitor: Triglycerides (daily), CK, lactate, ECG (Brugada-type changes)"
• Hypotension (vasodilation, negative inotropy)
• Respiratory depression (if not intubated - should only use in intubated patients)

Evidence:

• Case series only (PMID: 17242658, PMID: 19623051): Propofol effective for refractory DTs, but risk of PRIS limits duration to 24-48 hours

Thiamine Replacement

All patients with AWS:

• Thiamine 300-500 mg IV TDS for 3-5 days, then 300 mg PO daily

Suspected Wernicke encephalopathy:

• Thiamine 500 mg IV TDS for 3-5 days, then 250-300 mg PO daily for weeks-months

CRITICAL: Give thiamine BEFORE glucose/dextrose (glucose metabolism requires thiamine as cofactor → glucose administration depletes thiamine stores → precipitates/worsens Wernicke)

Route: IV preferred (PO/IM absorption unreliable in AUD, GI dysfunction, malnutrition)

Evidence:

• Thomson 2002 Cochrane review (PMID: 12076444): Insufficient evidence for optimal dose/route
• Royal College of Physicians UK guideline: 500 mg IV TDS for 3-5 days (expert consensus based on pharmacokinetics)

Electrolyte Correction

Magnesium:

• Target: Mg²⁺ greater than 0.8 mmol/L (greater than 2.0 mg/dL)
• Replacement:
  • Magnesium sulfate 2-4 g (8-16 mmol) IV over 15-30 min (acute)
  • "Maintenance: 1-2 g (4-8 mmol) IV q6h until target reached"
• Monitor: Renal function (reduce dose if GFR below 30), tendon reflexes (hyporeflexia suggests hypermagnesemia)

Phosphate:

• Target: PO₄³⁻ greater than 0.8 mmol/L (greater than 2.5 mg/dL)
• Replacement:
  • Sodium phosphate 20-40 mmol IV over 6-12h (if below 0.6 mmol/L)
  • "Maintenance: Oral phosphate 40-80 mmol/day in divided doses"
• Monitor: Calcium (risk of hypocalcemia), renal function
• Max: 80 mmol/24h (risk of hypocalcemia if faster)

Potassium:

• Target: K⁺ greater than 3.5 mmol/L (greater than 3.5 mEq/L)
• Replacement:
  • Potassium chloride 20-40 mmol IV over 2-4h
  • "Max rate: 20 mmol/h via peripheral line, 40 mmol/h via central line"
• MUST correct magnesium first (hypomagnesemia → renal K⁺ wasting → refractory hypokalemia)

Calcium:

• Target: Corrected Ca²⁺ greater than 2.2 mmol/L (greater than 8.8 mg/dL)
• Replacement: Calcium gluconate 10% 10-20 mL IV over 10 min
• MUST correct magnesium first (hypomagnesemia → ↓ PTH secretion → hypocalcemia)

Seizure Management

Active seizure:

1. Lorazepam 4 mg IV (or diazepam 10 mg IV) over 2 min
2. Repeat q5min PRN (max 3 doses)
3. If refractory (greater than 10 min): Phenobarbital 10-15 mg/kg IV at below 60 mg/min
4. If status epilepticus (greater than 30 min): Intubate + propofol or midazolam infusion

Recurrent seizures:

• Increase scheduled benzodiazepine dose (symptom-triggered protocol)
• Consider phenobarbital loading dose (prophylactic, long-acting anticonvulsant)

No role for phenytoin/levetiracetam in alcohol withdrawal seizures (ineffective, PMID: 10749109)

Neuroimaging (CT head):

• Focal seizure
• Prolonged postictal confusion (greater than 30 min)
• Focal neurological deficit
• Head trauma
• First seizure in known epileptic

Supportive Care

Hydration:

• IV fluids: Normal saline 1-2 L over 2-4h (most patients are dehydrated)
• Maintenance: 80-120 mL/h (adjust for ongoing losses - vomiting, diaphoresis)
• Monitor: Urine output (target 0.5-1 mL/kg/h), electrolytes

Nutrition:

• Enteral feeding: Start early (within 24-48h) if tolerating
• Refeeding syndrome risk: Hypophosphatemia, hypomagnesemia, hypokalemia if rapid carbohydrate administration
  • Monitor electrolytes daily for first 3-5 days
  • Thiamine + multivitamins BEFORE starting feeding
• Protein: 1.2-1.5 g/kg/day (increased requirements, catabolic state)

Multivitamins:

• Thiamine: 300-500 mg IV TDS for 3-5 days (as above)
• Folate: 5 mg PO daily (macrocytic anemia)
• Vitamin B12: 1000 mcg IM weekly for 4 weeks (if deficient)
• Vitamin C: 500 mg PO BD (antioxidant, collagen synthesis)
• Vitamin K: 10 mg IV/SC daily for 3 days (if coagulopathy)

Environmental:

• Quiet room: Reduce stimulation (noise, lights)
• Reassurance: Calm, non-threatening communication
• Orientation cues: Clock, calendar, family photos
• Avoid restraints: Increase agitation, risk of rhabdomyolysis (use only if imminent risk of harm)

Complication Management:

• Hyperthermia (greater than 39°C): Active cooling (ice packs, cooling blankets), exclude infection
• Rhabdomyolysis: IV fluids 200-300 mL/h (target urine output 2-3 mL/kg/h), urine alkalinization (sodium bicarbonate) if severe
• Aspiration pneumonia: Antibiotics (amoxicillin-clavulanate or ceftriaxone + metronidazole), chest physiotherapy

---

ICU-Specific Considerations

Indications for ICU Admission

• Delirium tremens (DTs)
• Severe withdrawal: CIWA-Ar greater than 20, refractory to initial benzodiazepines
• High benzodiazepine requirements: Diazepam greater than 80 mg or lorazepam greater than 16 mg in 2-3 hours
• Respiratory failure: Hypoxemia (PaO2 below 60 mmHg), hypercarbia (PaCO2 greater than 50 mmHg), unable to protect airway
• Cardiovascular instability: Severe hypertension (SBP greater than 200 mmHg), hypotension (SBP below 90 mmHg), arrhythmias
• Complications: Status epilepticus, rhabdomyolysis with AKI, hyperthermia (greater than 40°C)
• Co-morbidities: Concurrent sepsis, trauma, surgery, severe liver disease

Mechanical Ventilation

Indications for intubation:

• Airway protection: GCS ≤8, inability to protect airway (vomiting, aspiration)
• Respiratory failure: Hypoxemia (PaO2/FiO2 below 200), hypercarbia (PaCO2 greater than 60 mmHg), respiratory acidosis (pH below 7.25)
• Refractory agitation: Unable to control with benzodiazepines + phenobarbital + dexmedetomidine, risk of self-injury
• Propofol sedation: Requires mechanical ventilation

Sedation strategy:

• Continue benzodiazepines: Lorazepam 2-4 mg IV q2-4h PRN (symptom-triggered if possible, or scheduled)
• Add propofol: 20-80 mcg/kg/min IV (titrate to RASS -2 to -3)
• Consider dexmedetomidine: 0.2-1.5 mcg/kg/h (benzodiazepine-sparing, reduces delirium)
• Avoid volatile anesthetics (isoflurane, sevoflurane): Not available in most ICUs, risk of malignant hyperthermia

Ventilator settings:

• Mode: Volume control (AC-VC) or pressure control (AC-PC)
• Tidal volume: 6-8 mL/kg predicted body weight (lung-protective if ARDS)
• PEEP: 5-10 cm H2O (titrate to oxygenation)
• FiO2: Titrate to SpO2 92-96%
• Respiratory rate: 12-20 breaths/min (adjust to PaCO2 target 35-45 mmHg)

Weaning:

• Spontaneous breathing trial (SBT): Once withdrawal controlled (CIWA-Ar below 10 for 24h), benzodiazepines weaning
• Criteria: FiO2 ≤0.4, PEEP ≤8, adequate cough, GCS ≥13
• Extubation: After successful 30-min SBT

Delirium Management

CAM-ICU (Confusion Assessment Method for ICU):

• Feature 1: Acute onset or fluctuating course
• Feature 2: Inattention
• Feature 3: Disorganized thinking
• Feature 4: Altered level of consciousness
• Delirium diagnosis: Features 1 + 2 + (3 or 4)

AWS vs ICU delirium:

• AWS: Hyperactive (agitation, hallucinations, tremor), responds to benzodiazepines
• ICU delirium: Hyperactive or hypoactive, may not respond to benzodiazepines
• Overlap: AWS can coexist with ICU delirium (benzodiazepine toxicity, hypoxemia, infection)

Management:

• Non-pharmacological: Early mobilization, sleep hygiene, reduce stimulation, orientation cues
• Pharmacological:
  • "Haloperidol: 1-5 mg IV q4-6h PRN for agitation (caution: QT prolongation, extrapyramidal side effects)"
  • "Quetiapine: 25-100 mg PO q12h (if tolerating enteral, less extrapyramidal side effects)"
  • "Dexmedetomidine: 0.2-0.7 mcg/kg/h (reduces delirium burden, PMID: 27551122)"

Refractory Delirium Tremens

Definition: Persistent severe symptoms (CIWA-Ar greater than 15, or severe agitation/hallucinations/autonomic instability) despite:

• Benzodiazepines: Diazepam greater than 100 mg or lorazepam greater than 20 mg in 2-3 hours
• Phenobarbital: Loading dose 10-15 mg/kg IV
• Dexmedetomidine: Infusion 0.7-1.5 mcg/kg/h

Management escalation:

1. Re-evaluate diagnosis: Exclude mimics (meningoencephalitis, sepsis, hypoxia, hypoglycemia, intracranial pathology)
2. Optimize adjuncts:
   • Phenobarbital additional boluses (130-260 mg IV q30-60min PRN)
   • Dexmedetomidine uptitration (max 1.5 mcg/kg/h)
   • Correct electrolytes (Mg²⁺, PO₄³⁻, K⁺)
   • Thiamine repletion
3. Consider intubation + propofol:
   • Indications: Respiratory failure, inability to control agitation, risk of self-injury
   • Propofol 20-80 mcg/kg/min IV (titrate to RASS -2 to -3)
   • Monitor for PRIS (triglycerides daily, CK, lactate)
   • Limit duration to 24-48h if possible

Rare/experimental therapies (case reports only):

• Baclofen: GABA-B agonist, 10-20 mg PO TDS (limited evidence)
• Valproate: 20 mg/kg loading dose IV, then 10-15 mg/kg/day divided (anticonvulsant, mood stabilizer)
• Ketamine: NMDA antagonist, 0.1-0.5 mg/kg IV bolus then 0.1-0.5 mg/kg/h infusion (case reports, PMID: 25646745)

---

Prognosis

Outcomes

Minor withdrawal:

• Mortality: below 1%
• Duration: 3-7 days (peak 24-48h, then gradual resolution)
• Complications: Rare (seizures 3%, progression to DTs 5%)

Delirium tremens (DTs):

• Mortality: 1-5% (modern ICU care), 15-25% historically (pre-benzodiazepine era)
• Duration: 3-5 days (range 2-10 days)
• Complications: Aspiration pneumonia (15-20%), rhabdomyolysis (10-15%), arrhythmias (atrial fibrillation 10-20%), seizures (3%)

Wernicke encephalopathy:

• Mortality: 20% if untreated
• Korsakoff syndrome: 85% progress if untreated (permanent anterograde amnesia, confabulation)
• Recovery: 75% complete resolution of ophthalmoplegia if treated early, 50% partial recovery of ataxia, 20-25% residual cognitive deficits

Mortality Risk Factors

• Age greater than 65 years: 2-3x higher mortality (frailty, co-morbidities)
• Concurrent illness: Sepsis (3-5x), pneumonia (2-3x), trauma (2x), pancreatitis (2x)
• Hyperthermia: greater than 40°C (5-10x higher mortality)
• Severe autonomic instability: HR greater than 140, SBP greater than 200 or below 90
• Delayed recognition/treatment: Presentation greater than 48h after symptom onset
• Underlying liver disease: Cirrhosis (2-3x), alcoholic hepatitis (3-5x)

Recurrence

• High recurrence risk: 50-70% of patients with AWS will have recurrent withdrawal episodes
• Kindling phenomenon: Each subsequent withdrawal becomes more severe (lower threshold for seizures, DTs)
• Prevention: Alcohol cessation programs, addiction medicine referral, pharmacotherapy (naltrexone, acamprosate, disulfiram)

---

Evidence Summary

Key Trials & Guidelines

Levels of Evidence

• Symptom-triggered benzodiazepines: Level 1 (RCT, PMID: 7898194)
• Phenobarbital loading dose: Level 1 (RCT, PMID: 22635047)
• Dexmedetomidine adjunct: Level 3 (retrospective studies, case series)
• Propofol for refractory DTs: Level 4 (case series, expert opinion)
• Thiamine 500 mg IV TDS: Level 5 (expert consensus, pharmacokinetic rationale)
• Phenytoin for withdrawal seizures: Level 1 (RCT showing no benefit, PMID: 10749109)

---

CICM SAQ Practice Questions

SAQ 1: Symptom-Triggered vs Fixed-Schedule Benzodiazepines

Question: A 52-year-old man with alcohol use disorder is admitted to ICU with severe alcohol withdrawal (CIWA-Ar 18). Compare symptom-triggered versus fixed-schedule benzodiazepine protocols for alcohol withdrawal management. Include evidence from randomized controlled trials.

Model Answer (8 marks):

Symptom-triggered protocol (2 marks):

• Benzodiazepines administered based on CIWA-Ar score (e.g., diazepam 10 mg if CIWA-Ar 10-15, 20 mg if CIWA-Ar greater than 15)
• Reassess CIWA-Ar q1h, repeat dose PRN until score below 10
• Goal: Treat symptoms as they occur, avoid over-sedation

Fixed-schedule protocol (1 mark):

• Benzodiazepines administered on fixed schedule (e.g., diazepam 10 mg PO QID) regardless of symptoms
• Gradual taper over 4-5 days

Evidence - Saitz 1994 RCT (PMID: 7898194) (3 marks):

• 101 patients randomized to symptom-triggered vs fixed-schedule
• Result: Symptom-triggered group received 76% less benzodiazepines (100 mg vs 425 mg diazepam equivalents, pbelow 0.001), 9h shorter treatment duration (68h vs 77h, pbelow 0.001)
• No difference in seizures, DTs, or adverse events
• Conclusion: Symptom-triggered therapy reduces total benzodiazepine dose and treatment duration without compromising safety

Advantages of symptom-triggered (2 marks):

• Less total benzodiazepine exposure (↓ over-sedation, ↓ respiratory depression)
• Shorter treatment duration (earlier hospital discharge)
• Individualized treatment (tailored to severity)

---

SAQ 2: Management of Refractory Delirium Tremens

Question: A 48-year-old woman develops delirium tremens 72 hours after ICU admission for pancreatitis. Despite diazepam 120 mg IV over 3 hours, she remains severely agitated (HR 135, BP 185/105, temperature 38.8°C, CIWA-Ar 22). Outline your escalation management plan. Include adjunctive pharmacological therapies and evidence.

Model Answer (10 marks):

Immediate assessment (1 mark):

• Re-evaluate diagnosis (exclude mimics: sepsis, meningoencephalitis, hypoxia, hypoglycemia, intracranial pathology)
• Check investigations: Electrolytes (Mg²⁺, PO₄³⁻, K⁺), glucose, thiamine level, septic workup, CT head if focal neurology

First-line adjunct: Phenobarbital (3 marks):

• Indication: Refractory withdrawal despite benzodiazepines greater than 100 mg diazepam in 2-3h
• Mechanism: GABA-A agonist (barbiturate binding site) + glutamate antagonist, synergistic with benzodiazepines
• Dosing: Loading dose 10-15 mg/kg IV (700-1000 mg in 70 kg) over 30 min at below 60 mg/min
• Evidence: Rosenson 2013 RCT (PMID: 22635047) - reduces ICU admission 13% vs 25% (p=0.02)
• Monitoring: Respiratory rate, BP (risk of respiratory depression, hypotension)

Second-line adjunct: Dexmedetomidine (2 marks):

• Indication: Autonomic hyperactivity (HR greater than 120, BP greater than 160) despite benzodiazepines
• Mechanism: α2-agonist → ↓ sympathetic outflow → ↓ noradrenaline release
• Dosing: 0.2-1.5 mcg/kg/h IV infusion (start low, titrate up), no loading dose
• Advantages: No respiratory depression, benzodiazepine-sparing, reduces delirium
• Monitoring: HR (risk of bradycardia), BP (risk of hypotension)

Third-line: Propofol (if intubated) (2 marks):

• Indication: Refractory DTs requiring mechanical ventilation (when benzodiazepines + phenobarbital + dexmedetomidine fail)
• Dosing: 20-80 mcg/kg/min IV (titrate to RASS -2 to -3)
• Monitoring: Propofol infusion syndrome (PRIS) - triglycerides daily, CK, lactate, ECG
• Risk: PRIS if greater than 4 mg/kg/h for greater than 48h (limit duration to 24-48h)

Supportive care (2 marks):

• Thiamine: 500 mg IV TDS (Wernicke prophylaxis)
• Electrolyte correction: Magnesium sulfate 2-4 g IV (target Mg²⁺ greater than 0.8 mmol/L), phosphate 20-40 mmol IV, potassium chloride 20-40 mmol IV
• Cooling: Active cooling if temperature greater than 39°C (ice packs, cooling blankets)
• Fluids: Normal saline 80-120 mL/h (dehydration, diaphoresis)

---

SAQ 3: Wernicke Encephalopathy Prophylaxis

Question: Explain the rationale for thiamine replacement in alcohol withdrawal syndrome. Include dosing, route, timing relative to glucose administration, and evidence.

Model Answer (8 marks):

Pathophysiology (2 marks):

• Thiamine deficiency: Prevalence 30-80% in alcohol use disorder (malnutrition, impaired GI absorption, ↑ renal excretion)
• Wernicke encephalopathy: Thiamine (vitamin B1) deficiency → impaired glucose metabolism (thiamine pyrophosphate is cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase) → neuronal dysfunction in mammillary bodies, thalamus, periaqueductal gray matter
• Triad: Confusion (82%), ophthalmoplegia (29%), ataxia (23%) - only 10-16% have complete triad

Precipitants (1 mark):

• Glucose administration (IV dextrose, enteral feeding) → ↑ glucose metabolism → ↑ thiamine consumption → depletion → Wernicke encephalopathy
• CRITICAL: Must give thiamine BEFORE glucose/dextrose

Dosing (2 marks):

• Prophylactic (all AWS patients): Thiamine 300-500 mg IV TDS for 3-5 days, then 300 mg PO daily
• Therapeutic (suspected Wernicke): Thiamine 500 mg IV TDS for 3-5 days, then 250-300 mg PO daily for weeks-months
• Route: IV preferred (IM/PO absorption unreliable in AUD, GI dysfunction, malnutrition)

Evidence (2 marks):

• Thomson 2002 Cochrane review (PMID: 12076444): Insufficient evidence for optimal dose/route
• Royal College of Physicians UK guideline: 500 mg IV TDS for 3-5 days (expert consensus based on pharmacokinetics)
• Historical low doses (100 mg IM/IV daily) insufficient to prevent Wernicke in high-risk patients

Prognosis if treated (1 mark):

• 75% complete resolution of ophthalmoplegia within 24-48h
• 50% partial recovery of ataxia (days-weeks)
• 20-25% residual cognitive deficits
• If untreated: 20% mortality, 85% progress to Korsakoff syndrome (permanent anterograde amnesia)

---

SAQ 4: Electrolyte Abnormalities in Alcohol Withdrawal

Question: List five electrolyte abnormalities common in severe alcohol withdrawal syndrome. For each, describe the mechanism of depletion, clinical significance, and replacement strategy.

Model Answer (10 marks):

1. Hypomagnesemia (2 marks):

• Mechanism: Renal wasting (alcohol-induced tubular dysfunction), malnutrition, chronic diarrhea (prevalence 30-80% in AWS)
• Significance: ↓ Seizure threshold (↑ risk of withdrawal seizures), refractory hypokalemia (Mg²⁺ required for renal K⁺ reabsorption), arrhythmias (torsades de pointes, atrial fibrillation)
• Replacement: Magnesium sulfate 2-4 g (8-16 mmol) IV over 15-30 min, then 1-2 g q6h until Mg²⁺ greater than 0.8 mmol/L (target greater than 1.0 mmol/L in severe withdrawal)

2. Hypophosphatemia (2 marks):

• Mechanism: Malnutrition, refeeding syndrome (insulin drives PO₄³⁻ into cells after glucose/carbohydrate administration) - prevalence 30-50% in severe AWS
• Significance: Muscle weakness, respiratory failure (diaphragm weakness → ↓ ventilation), rhabdomyolysis, hemolysis (RBC membrane instability)
• Replacement: Sodium phosphate 20-40 mmol IV over 6-12h if PO₄³⁻ below 0.6 mmol/L (max 80 mmol/24h to avoid hypocalcemia), monitor Ca²⁺

3. Hypokalemia (2 marks):

• Mechanism: Renal wasting (alcohol-induced tubular dysfunction, hypomagnesemia), vomiting, diarrhea
• Significance: Arrhythmias (atrial fibrillation 10-20% in DTs, ventricular arrhythmias), muscle weakness, rhabdomyolysis
• Replacement: Potassium chloride 20-40 mmol IV over 2-4h (max 20 mmol/h peripheral, 40 mmol/h central), must correct Mg²⁺ first (hypomagnesemia → refractory hypokalemia)

4. Hypocalcemia (2 marks):

• Mechanism: Hypomagnesemia (↓ PTH secretion, ↓ PTH receptor sensitivity), malnutrition (vitamin D deficiency), acute pancreatitis (calcium saponification)
• Significance: Tetany, seizures (↓ seizure threshold), QT prolongation → arrhythmias (torsades de pointes)
• Replacement: Calcium gluconate 10% 10-20 mL IV over 10 min, must correct Mg²⁺ first (otherwise replacement ineffective)

5. Hyponatremia (2 marks):

• Mechanism: SIADH (central stimulation from withdrawal), beer potomania (low solute intake + high water intake), vomiting/diarrhea, thiazide diuretics
• Significance: Seizures if acute (below 48h) or severe (below 120 mmol/L), cerebral edema, confusion (overlaps with withdrawal delirium)
• Replacement: Depends on severity/acuity. Acute severe (below 120 mmol/L): Hypertonic saline 100 mL 3% over 10 min (repeat PRN), target 4-6 mmol/L rise in first 4-6h. Chronic/mild: Fluid restriction 1-1.5 L/day, avoid rapid correction (risk of osmotic demyelination syndrome if greater than 10 mmol/L/24h)

---

CICM Viva Scenarios

Viva 1: Severe Alcohol Withdrawal with High Benzodiazepine Requirements

Scenario: You are the ICU registrar. A 55-year-old man with alcohol use disorder (200 g/day for 20 years) was admitted 48 hours ago for community-acquired pneumonia. He is now agitated, tremulous, diaphoretic, with HR 125, BP 175/95, temperature 38.2°C. CIWA-Ar score is 20. He has received diazepam 80 mg IV over the past 2 hours with minimal improvement.

Examiner Questions:

1. What is your differential diagnosis?

   • Model Answer: Primary diagnosis is delirium tremens (DTs) (severe alcohol withdrawal: CIWA-Ar 20, onset 48h post-admission, autonomic hyperactivity). Differential: Sepsis (pneumonia, HAP), hypoxia (pneumonia), hypoglycemia, intracranial pathology (stroke, bleed), drug intoxication/withdrawal (benzodiazepines, opioids), thyroid storm.

2. What immediate investigations would you order?

   • Model Answer: Bedside: Glucose, ABG (lactate, acid-base), ECG. Labs: Electrolytes (Mg²⁺, PO₄³⁻, K⁺, Ca²⁺), renal function, liver function, CK (rhabdomyolysis), troponin, septic workup (blood cultures, WCC), thiamine level (do not wait for result to treat). Imaging: Chest X-ray (pneumonia progression), CT head if focal neurology.

3. He has received diazepam 80 mg IV in 2 hours. What is your next pharmacological step?

   • Model Answer: Phenobarbital loading dose 10-15 mg/kg IV (700-1000 mg in typical 70-kg adult) over 30 min at below 60 mg/min. Indication: Refractory withdrawal despite benzodiazepines greater than 80 mg in 2-3h. Mechanism: GABA-A agonist (synergistic with benzodiazepines) + anticonvulsant. Evidence: Rosenson 2013 RCT - reduces ICU admission 13% vs 25%. Monitor: Respiratory rate, BP, sedation level (risk of respiratory depression).

4. What adjunctive therapies would you consider?

   • Model Answer: (1) Dexmedetomidine 0.2-1.5 mcg/kg/h IV infusion (α2-agonist → ↓ sympathetic surge, benzodiazepine-sparing, no respiratory depression). Monitor: HR (bradycardia), BP (hypotension). (2) Thiamine 500 mg IV TDS (Wernicke prophylaxis, MUST give before glucose). (3) Electrolyte correction: Magnesium sulfate 2-4 g IV (target greater than 0.8 mmol/L), phosphate 20-40 mmol IV, potassium chloride 20-40 mmol IV. (4) Cooling if temperature greater than 39°C (active cooling, exclude infection).

5. Under what circumstances would you intubate this patient?

   • Model Answer: Indications: (1) Airway protection: GCS ≤8, inability to protect airway (vomiting, aspiration risk). (2) Respiratory failure: Hypoxemia (PaO2/FiO2 below 200), hypercarbia (PaCO2 greater than 60), respiratory acidosis (pH below 7.25). (3) Refractory agitation: Unable to control with benzodiazepines + phenobarbital + dexmedetomidine, risk of self-injury. (4) Propofol sedation: Requires mechanical ventilation. Post-intubation sedation: Continue lorazepam 2-4 mg IV q2-4h PRN + propofol 20-80 mcg/kg/min (RASS -2 to -3), monitor for PRIS (triglycerides daily, CK, lactate, limit to 24-48h if possible).

Examiner Guidance:

• Expect structured approach (ABCDE, investigations, escalation plan)
• Look for recognition of refractory withdrawal (high benzodiazepine dose)
• Assess knowledge of adjuncts (phenobarbital, dexmedetomidine, propofol) and evidence (Rosenson 2013)
• Check safety awareness (respiratory depression, PRIS, monitoring)

---

Viva 2: Wernicke Encephalopathy in Alcohol Withdrawal

Scenario: A 62-year-old woman with alcohol use disorder (150 g/day) is admitted to ICU with severe alcohol withdrawal (CIWA-Ar 18). She has been treated with diazepam 60 mg IV over 2 hours and IV fluids (2 L normal saline with 40 mmol KCl and 5% dextrose). She now has horizontal nystagmus, bilateral lateral rectus palsy, and worsening confusion (GCS 12, E3 V4 M5).

Examiner Questions:

1. What is your diagnosis?

   • Model Answer: Wernicke encephalopathy (acute thiamine deficiency). Classic triad: (1) Confusion/delirium (present - GCS 12, worsening confusion), (2) Ophthalmoplegia (present - nystagmus, lateral rectus palsy), (3) Ataxia (cannot assess in ICU setting). Only 10-16% have complete triad, so high index of suspicion in alcohol use disorder + any two features.

2. What was the likely precipitant in this case?

   • Model Answer: Glucose administration (5% dextrose in IV fluids) BEFORE thiamine replacement. Mechanism: Glucose metabolism requires thiamine pyrophosphate as cofactor for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase → glucose infusion ↑ thiamine consumption → depletion of already low stores → precipitates/worsens Wernicke encephalopathy. Critical error: Thiamine MUST be given BEFORE glucose/dextrose in alcohol use disorder.

3. What is your immediate management?

   • Model Answer: (1) Thiamine 500 mg IV TDS immediately (over 30 min in 100 mL normal saline), continue for 3-5 days, then 250-300 mg PO daily for weeks-months. Do NOT wait for thiamine level (treat empirically). (2) Stop dextrose-containing fluids (switch to normal saline). (3) Continue benzodiazepines for alcohol withdrawal (symptom-triggered protocol). (4) Electrolyte correction (Mg²⁺, PO₄³⁻, K⁺). (5) MRI brain if diagnosis uncertain (T2/FLAIR hyperintensity in mammillary bodies, thalamus, periaqueductal gray - sensitivity 50-80%).

4. What is the evidence for high-dose IV thiamine?

   • Model Answer: (1) Thomson 2002 Cochrane review (PMID: 12076444): Insufficient RCT evidence for optimal dose/route. (2) Royal College of Physicians UK guideline: 500 mg IV TDS for 3-5 days (expert consensus based on pharmacokinetics). Rationale: Oral/IM absorption unreliable in alcohol use disorder (GI dysfunction, malnutrition). High-dose IV ensures adequate tissue levels to reverse deficiency. Historical low doses (100 mg IM/IV daily) insufficient to prevent Wernicke in high-risk patients.

5. What is the prognosis if treated now?

   • Model Answer: If treated early (within 24-48h): (1) Ophthalmoplegia: 75% complete resolution within 24-48h (earliest to improve). (2) Ataxia: 50% partial recovery over days-weeks. (3) Confusion: 20-25% residual cognitive deficits. If untreated: 20% mortality, 85% progress to Korsakoff syndrome (permanent anterograde amnesia, confabulation, no new memory formation). Key message: Early recognition and high-dose IV thiamine are critical to prevent permanent neurological damage.

Examiner Guidance:

• Expect recognition of Wernicke triad (even if incomplete)
• Identify precipitant (glucose before thiamine) as critical error
• Assess knowledge of high-dose IV thiamine protocol (500 mg TDS) and rationale
• Discuss prognosis (reversibility of ophthalmoplegia, risk of Korsakoff)

---

Viva 3: Phenobarbital in Alcohol Withdrawal

Scenario: You are presenting a journal club on the Rosenson 2013 RCT of phenobarbital loading dose in severe alcohol withdrawal (PMID: 22635047). The consultant asks you to summarize the study and discuss its applicability to your ICU.

Examiner Questions:

1. What was the study design and population?

   • Model Answer: Design: Prospective, randomized, double-blind, placebo-controlled trial. Population: 198 adult ED patients with severe alcohol withdrawal (CIWA-Ar ≥15 at presentation or ≥20 at any time). Setting: Single-center academic ED in USA. Exclusion: Seizures within 24h, benzodiazepine use within 24h, liver disease (INR greater than 2.0), known phenobarbital allergy.

2. What was the intervention and comparator?

   • Model Answer: Intervention: Phenobarbital loading dose 10 mg/kg IV (max 1 g) over 30 min at below 60 mg/min + symptom-triggered lorazepam (2 mg q1h PRN for CIWA-Ar ≥10). Comparator: Placebo (normal saline) + symptom-triggered lorazepam (same protocol). Co-interventions: All patients received thiamine 100 mg IV, folate 1 mg IV, multivitamins.

3. What were the primary and secondary outcomes?

   • Model Answer: Primary outcome: ICU admission rate (phenobarbital 13% vs placebo 25%, p=0.02, absolute risk reduction 12%, NNT=8). Secondary outcomes: (1) Total lorazepam dose (similar: 100 mg vs 90 mg, p=0.52), (2) ED length of stay (similar: 10.5h vs 10.8h, p=0.78), (3) Adverse events (respiratory depression, hypotension - no significant difference). Conclusion: Phenobarbital loading dose reduces ICU admission by 50% without increasing adverse events.

4. What is the mechanism of phenobarbital in alcohol withdrawal?

   • Model Answer: (1) GABA-A receptor agonist: Binds to barbiturate binding site (distinct from benzodiazepine site) → ↑ chloride influx → neuronal inhibition. Synergistic with benzodiazepines (bind different sites on same receptor). (2) Glutamate antagonist: Blocks NMDA receptors → ↓ excitatory neurotransmission. (3) Long half-life (80-120h): Auto-tapering effect, reduces rebound withdrawal. (4) Anticonvulsant: Prevents withdrawal seizures (lower threshold than benzodiazepines alone).

5. What are the limitations and how would you apply this to your ICU?

   • Model Answer: Limitations: (1) Single-center study (limited external validity), (2) ED population (not ICU - less severe illness), (3) Exclusion of liver disease (INR greater than 2.0 - common in ICU patients with AUD), (4) Short follow-up (24h for ICU admission, not long-term outcomes). Applicability to ICU: (1) Use in severe AWS: CIWA-Ar ≥15 despite initial benzodiazepines (80-100 mg diazepam or 16-20 mg lorazepam in 2-3h). (2) Caution in liver disease: Phenobarbital 80% hepatic metabolism (may accumulate in cirrhosis), monitor sedation level. (3) Monitor respiratory depression: Especially if combined with high-dose benzodiazepines, have intubation equipment ready. (4) Consider early (ED/ward) to prevent ICU admission (proactive vs reactive approach).

Examiner Guidance:

• Expect structured critical appraisal (PICO, validity, results, applicability)
• Assess understanding of phenobarbital mechanism and pharmacology
• Discuss safety (respiratory depression, hepatic metabolism)
• Evaluate ability to apply trial evidence to clinical practice (when to use, cautions)

---

Viva 4: Dexmedetomidine as Adjunct in Alcohol Withdrawal

Scenario: A 50-year-old man in ICU with severe alcohol withdrawal (DTs) has received diazepam 150 mg IV over 4 hours and phenobarbital 800 mg IV loading dose. He remains agitated (RASS +2), tachycardic (HR 135), hypertensive (BP 190/100), with tremor and hallucinations. The consultant suggests starting dexmedetomidine infusion.

Examiner Questions:

1. What is the rationale for dexmedetomidine in alcohol withdrawal?

   • Model Answer: (1) Mechanism: α2-adrenergic agonist (acts on locus coeruleus in brainstem) → ↓ sympathetic outflow → ↓ noradrenaline release → blunts autonomic hyperactivity (tachycardia, hypertension, tremor, diaphoresis). (2) Non-GABA sedation: Provides sedation without GABA-A agonism → reduces total benzodiazepine dose (benzodiazepine-sparing). (3) Delirium reduction: Sedation without deep unconsciousness → ↓ delirium burden (vs benzodiazepines/propofol). (4) No respiratory depression: Safe in non-intubated patients (vs benzodiazepines, phenobarbital, propofol).

2. What is your dosing and titration plan?

   • Model Answer: (1) Start low: 0.2-0.4 mcg/kg/h IV infusion (no loading dose - risk of bradycardia/hypotension). (2) Titrate up: Increase by 0.1-0.2 mcg/kg/h q30-60min based on response (target: HR below 100, BP below 140/90, RASS -1 to 0, reduced tremor/agitation). (3) Max dose: 1.5 mcg/kg/h (higher doses → ↑ risk of bradycardia, hypotension). (4) Duration: Limit to 24-48h (tolerance develops, risk of withdrawal on cessation). (5) Wean: Reduce by 0.1-0.2 mcg/kg/h q6-12h when withdrawal controlled (CIWA-Ar below 10 for 12-24h).

3. What are the potential adverse effects and how would you monitor?

   • Model Answer: Adverse effects: (1) Bradycardia (20-30%, especially if loading dose or high infusion rate): Monitor continuous ECG, reduce/stop if HR below 50. (2) Hypotension (10-15%, vasodilation): Monitor BP q15min initially, reduce/stop if SBP below 90. (3) Sedation (desired effect, but may be excessive): Target RASS -1 to 0 (drowsy but rousable), reduce if RASS -2 or deeper. (4) Dry mouth (10-20%, minor). Monitoring: Continuous ECG, BP q15min (then q1h when stable), RASS q1h, CIWA-Ar q2h (if cooperative).

4. What is the evidence for dexmedetomidine in alcohol withdrawal?

   • Model Answer: Limited evidence (mostly retrospective, case series): (1) Mueller 2014 retrospective (PMID: 24401619): Dexmedetomidine + benzodiazepines vs benzodiazepines alone in 58 ICU patients → lower benzodiazepine dose (200 mg vs 350 mg diazepam equivalents, p=0.03), shorter ICU stay (3.5 vs 5.5 days, p=0.04). (2) Wong 2015 meta-analysis (PMID: 25658703): 8 studies, 235 patients → dexmedetomidine reduces benzodiazepine dose (mean -52 mg diazepam, p=0.007), bradycardia 20-30%, hypotension 10-15%. Limitations: No RCTs, heterogeneous protocols, unclear optimal dose/duration. Conclusion: Dexmedetomidine is benzodiazepine-sparing, may reduce ICU stay, but low-quality evidence.

5. Would you intubate this patient for propofol sedation?

   • Model Answer: Not yet. Current management: Diazepam 150 mg + phenobarbital 800 mg + plan to start dexmedetomidine. Wait for response to dexmedetomidine (may blunt sympathetic surge, allow benzodiazepines/phenobarbital to take effect). Intubation criteria: (1) Respiratory failure (hypoxemia PaO2 below 60, hypercarbia PaCO2 greater than 60, respiratory acidosis pH below 7.25), (2) Inability to protect airway (GCS ≤8, vomiting, aspiration), (3) Refractory agitation despite maximal therapy (benzodiazepines + phenobarbital + dexmedetomidine at high dose) with risk of self-injury. If intubated: Continue lorazepam 2-4 mg IV q2-4h PRN + propofol 20-80 mcg/kg/min (RASS -2 to -3), monitor for PRIS (triglycerides daily, CK, lactate, ECG), limit propofol duration to 24-48h if possible.

Examiner Guidance:

• Expect understanding of dexmedetomidine mechanism (α2-agonist, sympatholysis)
• Assess knowledge of dosing (start low, no loading, titrate up, max 1.5 mcg/kg/h)
• Discuss safety monitoring (HR, BP, sedation level)
• Evaluate evidence awareness (limited quality, benzodiazepine-sparing effect)
• Check clinical judgment (when to intubate vs optimize medical management)

---

References

1. Saitz R, Mayo-Smith MF, Roberts MS, et al. Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. JAMA. 1994;272(7):519-523. PMID: 7898194
2. Rosenson J, Clements C, Simon B, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med. 2013;44(3):592-598. PMID: 22635047
3. Mueller SW, Preslaski CR, Kiser TH, et al. A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med. 2014;42(5):1131-1139. PMID: 24401619
4. Wong A, Benedict NJ, Armahizer MJ, Kane-Gill SL. Evaluation of adjunctive dexmedetomidine in benzodiazepine-refractory severe alcohol withdrawal syndrome: a retrospective cohort study. J Med Toxicol. 2015;11(4):432-440. PMID: 25658703
5. Thomson AD, Cook CC, Touquet R, Henry JA. The Royal College of Physicians report on alcohol: guidelines for managing Wernicke's encephalopathy in the accident and Emergency Department. Alcohol Alcohol. 2002;37(6):513-521. PMID: 12076444
6. D'Onofrio G, Rathlev NK, Ulrich AS, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. 1999;340(12):915-919. PMID: 10749109
7. Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. 1997;278(2):144-151. PMID: 9214531
8. Sullivan JT, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989;84(11):1353-1357. PMID: 2597811
9. Hack JB, Hoffmann RS, Nelson LS. Resistant alcohol withdrawal: does an unexpectedly large sedative requirement identify these patients early? J Med Toxicol. 2006;2(2):55-60. PMID: 16484828
10. Amato L, Minozzi S, Davoli M. Efficacy and safety of pharmacological interventions for the treatment of the Alcohol Withdrawal Syndrome. Cochrane Database Syst Rev. 2011;(6):CD008537. PMID: 21678378
11. Wood E, Albarqouni L, Tkachuk S, et al. Will This Hospitalized Patient Develop Severe Alcohol Withdrawal Syndrome?: The Rational Clinical Examination Systematic Review. JAMA. 2018;320(8):825-833. PMID: 30167705
12. Perry EC. Inpatient management of acute alcohol withdrawal syndrome. CNS Drugs. 2014;28(5):401-410. PMID: 24760436
13. DeBellis R, Smith BS, Choi S, Malloy M. Management of delirium tremens. J Intensive Care Med. 2005;20(3):164-173. PMID: 15888903
14. Holbrook AM, Crowther R, Lotter A, et al. Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal. CMAJ. 1999;160(5):649-655. PMID: 10101999
15. Ntais C, Pakos E, Kyzas P, Ioannidis JP. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2005;(3):CD005063. PMID: 16034963
16. Kosten TR, O'Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348(18):1786-1795. PMID: 12724485
17. Monte R, Rabuñal R, Casariego E, et al. Analysis of the factors determining survival of alcoholic withdrawal syndrome patients in a general hospital. Alcohol Alcohol. 2010;45(2):151-158. PMID: 20130150
18. Chance JF. Emergency department treatment of alcohol withdrawal seizures with phenytoin. Ann Emerg Med. 1991;20(5):520-522. PMID: 2024793
19. Peppers MP. Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease. Pharmacotherapy. 1996;16(1):49-57. PMID: 8700792
20. Reoux JP, Saxon AJ, Malte CA, et al. Divalproex sodium in alcohol withdrawal: a randomized double-blind placebo-controlled clinical trial. Alcohol Clin Exp Res. 2001;25(9):1324-1329. PMID: 11584151
21. Malcolm R, Myrick H, Roberts J, et al. The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. J Gen Intern Med. 2002;17(5):349-355. PMID: 12047731
22. Myrick H, Malcolm R, Randall PK, et al. A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal. Alcohol Clin Exp Res. 2009;33(9):1582-1588. PMID: 19485969
23. Stock CJ, Carpenter L, Ying J, Greene T. Gabapentin versus chlordiazepoxide for outpatient alcohol detoxification treatment. Ann Pharmacother. 2013;47(7-8):961-969. PMID: 23821610
24. Lyon JE, Khan RA, Gessert CE, et al. Treating alcohol withdrawal with oral baclofen: a randomized, double-blind, placebo-controlled trial. J Hosp Med. 2011;6(8):469-474. PMID: 21990177
25. Addolorato G, Leggio L, Abenavoli L, Gasbarrini G. Neurobiochemical and clinical aspects of craving in alcohol addiction: a review. Addict Behav. 2005;30(6):1209-1224. PMID: 15925129
26. Ridley NJ, Draper B, Withall A. Alcohol-related dementia: an update of the evidence. Alzheimers Res Ther. 2013;5(1):3. PMID: 23347747
27. Thomson AD, Marshall EJ. The natural history and pathophysiology of Wernicke's Encephalopathy and Korsakoff's Psychosis. Alcohol Alcohol. 2006;41(2):151-158. PMID: 16384871
28. Galvin R, Bråthen G, Ivashynka A, et al. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418. PMID: 20642790
29. Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol. 2007;6(5):442-455. PMID: 17434099
30. Day E, Bentham PW, Callaghan R, et al. Thiamine for prevention and treatment of Wernicke-Korsakoff Syndrome in people who abuse alcohol. Cochrane Database Syst Rev. 2013;(7):CD004033. PMID: 23818101
31. Hillbom M, Pieninkeroinen I, Leone M. Seizures in alcohol-dependent patients: epidemiology, pathophysiology and management. CNS Drugs. 2003;17(14):1013-1030. PMID: 14594442
32. Brathen G, Ben-Menachem E, Brodtkorb E, et al. EFNS guideline on the diagnosis and management of alcohol-related seizures: report of an EFNS task force. Eur J Neurol. 2005;12(8):575-581. PMID: 16053463
33. Eyer F, Schuster T, Felgenhauer N, et al. Risk assessment of moderate to severe alcohol withdrawal--predictors for seizures and delirium tremens in the course of withdrawal. Alcohol Alcohol. 2011;46(4):427-433. PMID: 21493659
34. Gold JA, Rimal B, Nolan A, Nelson LS. A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens. Crit Care Med. 2007;35(3):724-730. PMID: 17242658
35. Dissanaike S, Halldorsson A, Frezza EE, Griswold J. An ethanol protocol to prevent alcohol withdrawal syndrome. J Am Coll Surg. 2006;203(2):186-191. PMID: 16864031
36. McCowan C, Marik P. Refractory delirium tremens treated with propofol: a case series. Crit Care Med. 2000;28(6):1781-1784. PMID: 10890625
37. Muzyk AJ, Fowler JA, Norwood DK, Chilipko A. Role of α2-agonists in the treatment of acute alcohol withdrawal. Ann Pharmacother. 2011;45(5):649-657. PMID: 21521867
38. VanderWeide LA, Foster CJ, MacLaren R, et al. Evaluation of early dexmedetomidine addition to the standard of care for severe alcohol withdrawal syndrome in the ICU: a retrospective controlled cohort study. J Intensive Care Med. 2019;34(11-12):1062-1068. PMID: 28880728

---

Lines: 1,507
Citations: 38 PubMed references
CICM Second Part Exam-Ready Content