01Approach to the Critical Patient/attcp26

Immediate Stabilization

›Airway, breathing, circulation priorities

›Immediate IV access and continuous cardiac monitoring

›Pulse oximetry and supplemental oxygen for SpO2 below 94%

›If GCS below 8, prepare for definitive airway management

›Thiamine before glucose

›Thiamine 500 mg IV in 100 mL NS over 30 minutes before any dextrose-containing fluid

›If glucose-containing IV already running, administer thiamine immediately without delay

›Never withhold thiamine pending serum level results

›Hemodynamic targets

›Mean arterial pressure above 65 mmHg

›Heart rate below 100 beats/min

›Temperature above 35 degrees C; active rewarming if hypothermic

Key Concepts

›Diagnostic recognition pitfalls

›Classic triad present in only 10-33% of cases [1]

›Maintain high clinical suspicion in any malnourished or alcoholic patient with altered mental status

›Autopsy prevalence 0.4-2.8%; majority undiagnosed antemortem [1]

›Non-alcoholic patients often present with isolated altered mental status [2]

›Escalation triggers

›Escalate to resuscitation bay for coma, hypothermia, or hemodynamic instability

›Activate neurology consultation for atypical presentations or failure to improve after thiamine

›ICU admission for coma, respiratory failure, hemodynamic instability, or concurrent severe alcohol withdrawal [3]

PEARLS

›Clinical decision pearls

›Thiamine has an excellent safety profile; anaphylaxis from IV thiamine is exceedingly rare [2]

›Treatment must not be delayed for imaging or laboratory confirmation

›Ocular abnormalities respond within hours; confusion resolves over days to weeks [4]

02History/hx36

Presenting Symptoms

›Neurological symptoms

›Confusion, disorientation, or altered mental status

›Diplopia or blurred vision

›Unsteadiness or inability to walk

›Memory loss or confabulation

›Systemic symptoms

›Nausea, vomiting, anorexia, diarrhea

›Weight loss and poor oral intake

›Dyspnea or peripheral edema (wet beriberi)

›Numbness or tingling in extremities

Risk Factors

›Primary risk exposures

›Alcohol use disorder (quantity, frequency, date of last drink)

›Recent bariatric surgery, gastrectomy, or fundoplication

›Hyperemesis gravidarum

›Prolonged TPN without thiamine supplementation [5]

›Malignancy, especially GI cancers or chemotherapy-induced vomiting [6]

›Anorexia nervosa, bulimia, or prolonged fasting

›HIV/AIDS or end-stage liver disease [7]

›Renal dialysis

›Recent hospitalization with glucose-containing IV fluids without thiamine [8]

›Refeeding after prolonged starvation

Medication History

›Drugs that deplete or impair thiamine

›Loop diuretics (furosemide) increase urinary thiamine losses [5]

›Proton pump inhibitors combined with diuretics may exacerbate hypomagnesemia

›Metformin and chronic alcohol use contribute to lactic acidosis in thiamine deficiency

03Physical Exam/exam28

Vital Signs

›Hemodynamic and temperature assessment

›Hypothermia (posterior hypothalamic involvement) [2]

›Hypotension and tachycardia (cardiovascular beriberi or autonomic dysfunction) [2]

›High-output state (bounding pulses, tachycardia) in wet beriberi

Mental Status

›Cognitive and level-of-consciousness findings

›Confusion, apathy, disorientation, or inability to concentrate

›Confabulation (anterograde amnesia suggesting Korsakoff transition)

›Stupor or coma in severe presentations

›GCS score and trend

Ocular Findings

›Eye movement and pupillary assessment

›Horizontal nystagmus (most common ocular finding) [4]

›Bilateral lateral rectus palsy (CN VI palsy)

›Conjugate gaze palsy

›Sluggish pupillary response or anisocoria

›Papilledema or optic disc edema

›Retinal hemorrhages

Cerebellar and Gait Examination

›Ataxia assessment

›Wide-based gait ataxia ranging from mild unsteadiness to complete inability to ambulate [4]

›Inability to tandem walk

›Romberg sign positive

Peripheral Neurological Exam

›Neuropathy findings

›Diminished deep tendon reflexes

›Distal sensory loss (coexistent peripheral polyneuropathy) [10]

04Differential Diagnosis/ddx14

Life-Threatening Mimics

›Conditions requiring immediate exclusion

›Bilateral thalamic stroke (acute onset, vascular risk factors, DWI restricted diffusion in vascular territory)

›Bacterial meningitis (fever, meningismus, CSF pleocytosis)

›Toxic ingestion: methanol or ethylene glycol (osmolar gap, metabolic acidosis)

›Hypoglycemia (immediate POC glucose)

Alcohol-Related Conditions

›Overlapping alcohol-associated diagnoses

›Hepatic encephalopathy (asterixis, elevated ammonia, stigmata of liver disease; may coexist with WE) [1]

›Alcohol withdrawal or delirium tremens (tremor, autonomic hyperactivity, seizures, onset after cessation; may coexist) [12]

›Marchiafava-Bignami disease (corpus callosum lesions on MRI, alcohol-related) [5]

Neurological Conditions

›Other neurological diagnoses

›Autoimmune or viral encephalitis (CSF pleocytosis, antibodies against NMDAR or LGI1, fever) [9]

›Metronidazole-induced encephalopathy (similar MRI pattern; medication history critical)

›Central pontine myelinolysis (history of rapid sodium correction, pontine lesions on MRI)

›Non-convulsive status epilepticus (requires EEG confirmation)

05Laboratory Tests/lt20

Priority Labs

›Essential initial laboratory panel

›Point-of-care glucose before any IV dextrose administration

›Serum thiamine (vitamin B1) level drawn before supplementation; do not delay treatment for results [1]

›Serum magnesium (must be corrected for thiamine to be effective) [5]

›Serum lactate (elevated due to impaired pyruvate decarboxylase activity in thiamine deficiency) [5]

Metabolic Panel

›Electrolyte and organ function assessment

›Comprehensive metabolic panel (sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose)

›Phosphorus (refeeding syndrome risk; supplement if below 0.32 mmol/l) [13]

›Hepatic function panel (ALT, AST, bilirubin, albumin)

›Blood alcohol level

Hematology and Additional Labs

›Broader nutritional and hematologic workup

›Complete blood count

›Serum folate, B12, and B6 (concurrent nutritional deficiencies)

›Ammonia level (hepatic encephalopathy exclusion)

›Coagulation studies (INR, PTT) in liver disease

›Lipase (concurrent pancreatitis in alcohol use disorder)

Specialized Testing

›Confirmatory and research-level tests

›Erythrocyte transketolase activity (more specific marker of thiamine deficiency; not widely available) [2]

›Thiamine pyrophosphate level (most active form; reference range varies by laboratory)

›Urine toxicology screen

06Diagnostic Tests/dt37

Scoring Systems

›Caine Criteria for clinical diagnosis

›Requires at least 2 of 4 criteria to be met [4]

›Criterion 1: dietary deficiency or evidence of malnutrition

›Criterion 2: oculomotor abnormalities (nystagmus, gaze palsy, ophthalmoplegia)

›Criterion 3: cerebellar dysfunction (ataxia, wide-based gait)

›Criterion 4: altered mental state or mild memory impairment

›More sensitive than classic triad, particularly in alcoholic patients [4]

›Therapeutic diagnostic test: clinical improvement after parenteral thiamine supports diagnosis [4]

MRI

›MRI brain characteristics and performance

›Modality of choice for neuroimaging in suspected Wernicke's encephalopathy [4]

›Sensitivity approximately 53%; specificity approximately 93% [4]

›Typical findings: symmetric T2/FLAIR hyperintensities in medial thalami, mammillary bodies, periaqueductal gray, tectal plate, and floor of the fourth ventricle [1]

›DWI sequences showing restricted diffusion (reversible cytotoxic edema) [14]

›Contrast enhancement of mammillary bodies [15]

›Atypical sites include corpus callosum splenium, fornix, cerebral cortex, and cerebellar vermis [16]

›Imaging is supportive but NOT required to initiate treatment; WE is a clinical diagnosis [2]

CT

›CT head role and limitations

›Usually negative in acute Wernicke's encephalopathy [2]

›May show hypodensities in bilateral thalami in some severe cases [2]

›Useful for excluding hemorrhage, mass lesion, or acute stroke

›Indicated urgently if diagnosis is uncertain or patient cannot undergo MRI

Ultrasound

›Point-of-care ultrasound applications

›Cardiac POCUS for signs of wet beriberi (dilated cardiomyopathy, high-output state)

›IVC assessment for volume status in hypotensive patients

07Disposition/dispo19

ICU Admission

›Criteria for intensive care unit level

›Coma or GCS below 13 with declining trajectory

›Hemodynamic instability (hypotension or persistent tachycardia)

›Hypothermia below 35 degrees C

›Respiratory failure requiring ventilatory support

›Concurrent severe alcohol withdrawal with seizures or delirium tremens [13]

›Extensive brainstem involvement on MRI [17]

General Admission

›Ward-level admission criteria

›All patients with suspected or confirmed Wernicke's encephalopathy require hospital admission [1]

›Mild presentations responding to thiamine may be managed on monitored step-down unit

›Neurology consultation for atypical presentations, diagnostic uncertainty, or failure to improve [4]

›Psychiatry or addiction medicine consultation for concurrent alcohol use disorder [7]

›Nutrition and dietetics consultation for refeeding syndrome management

Discharge

›Discharge criteria (met only after full clinical response)

›Near-complete resolution of oculomotor abnormalities and confusion

›Ability to ambulate safely or return to baseline

›Reliable oral thiamine absorption established

›Outpatient follow-up within 1-2 weeks arranged

›Alcohol use disorder treatment plan in place

08Treatment/t39

Thiamine Replacement

›High-dose IV thiamine (preferred for confirmed or strongly suspected WE)

›Thiamine 500 mg IV in 100 mL NS over 30 minutes three times daily [4]

›Duration: 2-3 days for acute treatment phase (Royal College of Physicians guideline) [1]

›High-dose regimen increasingly favored as 100 mg doses may be insufficient to restore thiamine status [4]

›Anaphylaxis exceedingly rare; benefit-risk strongly favors high-dose IV therapy [2]

›Maintenance phase after acute treatment

›Thiamine 250 mg IV or IM once daily for 3-5 additional days [1]

›Transition to oral thiamine 100 mg daily for long-term supplementation [8]

Alternative Dosing Regimens

›Standard and guideline-referenced dosing options

›EFNS guideline: thiamine 200 mg IV three times daily, then transition to oral [2]

›ASAM guideline (alcohol withdrawal prophylaxis): thiamine 100 mg IV or IM daily for 3-5 days [13]

›FDA label: thiamine 100 mg IV initially, then 50-100 mg IM daily until balanced diet [17]

›Administer thiamine before or concurrent with any glucose-containing fluid [8]

Magnesium Repletion

›Magnesium correction (required for thiamine efficacy)

›Serum magnesium target above 0.7 mmol/l

›Magnesium sulfate 2-4 g IV over 15-30 minutes for severe hypomagnesemia

›Magnesium sulfate 1-2 g IV over 1-2 hours for moderate deficiency

›Hypomagnesemia may cause failure to respond to thiamine therapy [5]

›Oral magnesium supplementation after IV correction for maintenance

Electrolyte and Nutritional Repletion

›Additional deficiency correction

›Phosphorus repletion for refeeding syndrome prevention [13]

›Target serum phosphorus above 0.8 mmol/l

›IV potassium phosphate if phosphorus below 0.32 mmol/l with symptoms

›Potassium repletion to maintain serum potassium above 3.5 mmol/l

09Special Populations/sp36

Pregnancy

›Wernicke's encephalopathy in pregnancy

›Hyperemesis gravidarum is a major risk factor for WE in pregnancy [1]

›Prolonged vomiting depletes thiamine stores within days to weeks

›Often misdiagnosed as worsening hyperemesis or preeclampsia

›Thiamine dosing in pregnancy

›Thiamine 500 mg IV three times daily is considered safe in pregnancy

›Thiamine is classified as FDA Category A; no known fetal harm

›High-dose IV thiamine is preferred over oral due to unreliable absorption

›Fetal considerations

›Maternal thiamine deficiency impairs fetal brain development

›Neonatal monitoring for thiamine deficiency if maternal deficiency untreated

›Obstetrics consultation required; coordinate thiamine supplementation with obstetric team

Geriatric

›Wernicke's encephalopathy in older adults

›Presentation often atypical with isolated cognitive decline or delirium [2]

›Classic triad even less common in elderly patients

›May be misattributed to dementia or metabolic encephalopathy

›Increased vulnerability factors

›Reduced dietary intake and malabsorption with age

›Polypharmacy including diuretics that deplete thiamine

›Comorbid conditions: heart failure, malignancy, renal disease

›Treatment considerations

›High-dose IV thiamine indicated without dose reduction

›Fall risk extremely high; immediate mobility restrictions

›Delirium management with non-pharmacologic strategies preferred

Pediatrics

›Wernicke's encephalopathy in children

10Background/b35

Epidemiology

›Prevalence and population data

›Autopsy studies show WE prevalence of 0.4-2.8% in general population; majority undiagnosed antemortem [1]

›Alcohol use disorder accounts for the majority of cases in Western countries [2]

›Non-alcoholic causes account for 20-40% of cases in high-income countries [1]

›Mortality approximately 20% in untreated or delayed-treatment cases [1]

›Approximately 80% of survivors progress to Korsakoff syndrome without prompt treatment [1]

›Risk population distribution

›Bariatric surgery patients have substantially increased risk due to malabsorption [1]

›Hyperemesis gravidarum affects 0.3-2% of pregnancies; WE is a rare but serious complication

›Cancer patients: particularly those with GI malignancies or receiving chemotherapy [6]

›HIV/AIDS patients with wasting syndrome [7]

Pathophysiology

›Mechanism of thiamine deficiency and neural injury

›Thiamine (vitamin B1) is an essential cofactor for pyruvate decarboxylase, alpha-ketoglutarate dehydrogenase, and transketolase

›Deficiency impairs oxidative glucose metabolism and causes accumulation of lactate

›Cerebral energy failure preferentially affects metabolically active regions

›Vulnerable brain regions

›Medial thalami and mammillary bodies most susceptible due to high metabolic demand

›Periaqueductal gray matter and tectal plate also characteristically affected

›Vasogenic then cytotoxic edema leads to T2/FLAIR hyperintensities on MRI

›Absorption and depletion kinetics

›Chronic alcohol impairs thiamine absorption in the jejunum and inhibits conversion to active thiamine pyrophosphate [13]

›Thiamine stores deplete within 2 weeks of deficient intake [9]

›Glucose infusion without thiamine consumes remaining stores and precipitates acute WE [8]

Therapeutic Considerations

›Evidence base and treatment rationale

›Cochrane systematic review: insufficient randomized controlled trial evidence to define optimal dose, route, or duration; high-dose IV thiamine recommended by expert consensus [12]

11Patient Discharge Instructions/pdi32

copy discharge instructions

›Diagnosis and key information

›You were treated for Wernicke's encephalopathy, a serious brain condition caused by severe vitamin B1 (thiamine) deficiency

›Your brain requires thiamine to function normally; without it, critical areas are damaged

›Early treatment with IV thiamine can reverse most symptoms, but delays can lead to permanent memory problems

›Medications after discharge

›Take thiamine 100 mg by mouth every day without stopping

›Take all prescribed vitamins and supplements as directed

›Do not miss doses; skipping thiamine can cause your symptoms to return

›Diet and nutrition

›Eat regular balanced meals including thiamine-rich foods: whole grains, legumes, pork, and fortified cereals

›Avoid diets consisting mainly of refined carbohydrates or polished rice, which increase thiamine requirements

›Attend any scheduled nutrition counseling appointments

›Alcohol cessation

›Alcohol consumption was a primary cause of your thiamine deficiency; continued drinking will cause recurrence

›Resources for alcohol treatment: your family doctor, addiction medicine referral, or local support groups

›Naltrexone or acamprosate may be prescribed by your doctor to help reduce alcohol craving

›Activity and safety

›Balance and walking problems may persist; use caution on stairs and uneven surfaces

›Do not drive until your doctor confirms it is safe

›Arrange for someone to stay with you if you still feel confused or unsteady

›Return to emergency department immediately for

›New or worsening confusion, disorientation, or inability to recognize familiar people

›Sudden changes in vision, double vision, or inability to move your eyes normally

›Inability to walk or sudden worsening of unsteadiness

›Seizure

›Chest pain, severe shortness of breath, or leg swelling

›High fever, severe headache, or stiff neck

12References/r16

Guidelines and Key Sources

›Primary clinical guidelines

›Li S, Xing C. Wernicke Encephalopathy: A Mini Review of the Clinical Spectrum, Atypical Manifestations, and Diagnostic Challenges. Frontiers in Neurology. 2025. PMID: 40740851

›Sinha S, Kataria A, Kolla BP, et al. Wernicke Encephalopathy-Clinical Pearls. Mayo Clinic Proceedings. 2019. PMID: 31171116

›Day E, Bentham PW, Callaghan R, et al. Thiamine for Prevention and Treatment of Wernicke-Korsakoff Syndrome. Cochrane Database of Systematic Reviews. 2013

›Goldstein DN, Hunter AJ, Riquelme PA. A Case for Early High-Dose Thiamine. JAMA Internal Medicine. 2025

›Wijnia JW. A Clinician's View of Wernicke-Korsakoff Syndrome. Journal of Clinical Medicine. 2022. PMID: 36431232

›Sechi G, Serra A. Wernicke's Encephalopathy: New Clinical Settings and Recent Advances. Lancet Neurology. 2007. PMID: 17434099

›Anika Alvanzo MD, et al. Clinical Practice Guideline on Alcohol Withdrawal Management. ASAM. 2020

Imaging and Diagnostic References

›MRI and diagnostic studies

›Manzo G, De Gennaro A, Cozzolino A, et al. MR Imaging Findings in Alcoholic and Nonalcoholic Acute Wernicke's Encephalopathy. BioMed Research International. 2014

›Hiraga A, Kojima K, Kuwabara S. Typical and Atypical MRI Abnormalities in Wernicke's Encephalopathy. Journal of Neurological Sciences. 2024. PMID: 38749282

›Chu K, Kang DW, Kim HJ, et al. Diffusion-Weighted Imaging Abnormalities in Wernicke Encephalopathy. Archives of Neurology. 2002

›Li H, Ding Q, Wang K, et al. Wernicke-Korsakoff Syndrome With Extensive Brainstem Involvement. Neurology. 2025. PMID: 41086378

›Gwathmey KG, Grogan J. Nutritional neuropathies. Muscle and Nerve. 2020

›Isenberg-Grzeda E, Rahane S, DeRosa AP, et al. Wernicke-Korsakoff Syndrome in Patients With Cancer: A Systematic Review. Lancet Oncology. 2016. PMID: 27300674

›FDA Drug Label: thiamine hydrochloride. Food and Drug Administration. Updated 2025-02-27

Evidence & Review

Evidence & Review