Dry vs Wet Beriberi: Bedside Diagnosis of Thiamine Deficiency in Critical Care

A Clinical Review

Dr Neeraj Manikath , claude.ai

Abstract

Thiamine deficiency remains an underdiagnosed condition in critical care settings, manifesting as either "wet beriberi" (high-output heart failure) or "dry beriberi" (peripheral neuropathy). Early recognition and empirical treatment are crucial, as delayed diagnosis can result in irreversible cardiovascular collapse or permanent neurological damage. This review provides practical bedside diagnostic approaches, identifies high-risk populations, and establishes evidence-based guidelines for empirical thiamine supplementation in the intensive care unit.

Keywords: Thiamine deficiency, beriberi, high-output heart failure, peripheral neuropathy, critical care

Introduction

Thiamine (vitamin B1) deficiency, historically associated with malnutrition in developing countries, has emerged as a significant yet underrecognized problem in modern critical care practice. The condition presents in two primary forms: "wet beriberi" characterized by cardiovascular manifestations, and "dry beriberi" featuring predominantly neurological symptoms. The challenge for the contemporary intensivist lies not in exotic presentations, but in recognizing thiamine deficiency among patients with multiple comorbidities, polypharmacy, and complex pathophysiology.

Recent epidemiological studies suggest thiamine deficiency affects 10-90% of critically ill patients depending on the population studied, with particularly high prevalence among post-surgical patients (33-91%) and those with alcohol use disorder (up to 80%).^1,2^ The wide clinical spectrum and non-specific symptoms often lead to delayed diagnosis, making empirical supplementation a critical consideration in high-risk populations.

Pathophysiology: The Metabolic Foundation

Thiamine serves as a cofactor for multiple enzymes in carbohydrate metabolism, including pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Deficiency disrupts cellular energy production, leading to impaired ATP synthesis and subsequent organ dysfunction.^3^

The cardiovascular manifestations (wet beriberi) result from:

Peripheral vasodilation due to impaired vascular smooth muscle function
Increased cardiac output to compensate for reduced systemic vascular resistance
Direct myocardial depression from cellular energy failure
Sodium and water retention secondary to activation of the renin-angiotensin system^4^

Neurological manifestations (dry beriberi) develop from:

Impaired glucose utilization in neural tissue
Disrupted neurotransmitter synthesis
Axonal degeneration beginning distally in peripheral nerves
Central nervous system involvement in severe cases^5^

Pearl: The heart and nervous system are most susceptible to thiamine deficiency because of their high metabolic demands and dependence on aerobic glucose metabolism.

Clinical Presentations: Wet vs Dry Beriberi

Wet Beriberi: The Cardiovascular Masquerader

Wet beriberi presents as high-output heart failure, a condition that can mimic sepsis, hyperthyroidism, or arteriovenous malformations. The clinical presentation includes:

Cardiac manifestations:

Elevated cardiac output (often >8 L/min/m²)
Low systemic vascular resistance (<800 dynes·s·cm⁻⁵)
Warm extremities with bounding pulses
Elevated jugular venous pressure
S₃ gallop rhythm
Cardiomegaly on chest imaging^6^

Associated symptoms:

Dyspnea and orthopnea
Lower extremity edema
Fatigue and weakness
Palpitations
Chest discomfort

Oyster: Unlike typical heart failure, patients with wet beriberi often maintain warm extremities and strong peripheral pulses due to peripheral vasodilation. Cool extremities should prompt consideration of alternative diagnoses.

Dry Beriberi: The Neurological Enigma

Dry beriberi manifests primarily as peripheral neuropathy, often progressing in a predictable pattern:

Early manifestations:

Distal sensory symptoms (numbness, tingling)
Burning feet syndrome
Muscle cramps and weakness
Diminished deep tendon reflexes^7^

Progressive features:

Ascending motor weakness
Muscle atrophy
Footdrop and wrist drop
Gait abnormalities
Advanced cases: quadriplegia^8^

Central nervous system involvement:

Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia)
Korsakoff syndrome (memory impairment)
Beriberi cerebri (pseudotumor cerebri-like presentation)^9^

Hack: The "stocking-glove" distribution of sensory loss in dry beriberi is often asymmetric initially, unlike diabetic neuropathy which typically presents symmetrically.

High-Risk Populations in Critical Care

Alcohol Use Disorder

Alcohol interferes with thiamine absorption, storage, and utilization through multiple mechanisms:

Impaired intestinal absorption
Reduced hepatic storage
Increased renal excretion
Poor dietary intake^10^

Clinical pearl: Even patients with mild alcohol use disorder may develop thiamine deficiency during periods of stress or illness when metabolic demands increase.

Post-Surgical Patients

Multiple factors contribute to thiamine deficiency in the perioperative period:

Preoperative fasting
Increased metabolic demands
Glucose loading (parenteral nutrition, IV dextrose)
Gastrointestinal dysfunction
Increased losses through dialysis or plasmapheresis^11^

High-risk surgical populations:

Bariatric surgery patients
Major abdominal surgery
Prolonged ICU stays
Patients requiring continuous renal replacement therapy^12^

ICU-Specific Risk Factors

Nutritional factors:

Prolonged NPO status
Inadequate enteral nutrition
Parenteral nutrition without adequate thiamine supplementation
Chronic malabsorption disorders^13^

Metabolic stressors:

Sepsis and systemic inflammatory response
Burns and trauma
Hyperthyroidism
Pregnancy and lactation
Chronic kidney disease^14^

Medications:

Loop diuretics (increase urinary thiamine excretion)
Metformin (impairs thiamine uptake)
Digoxin (may worsen thiamine-related cardiac dysfunction)^15^

Bedside Diagnostic Approach

Clinical Assessment Framework

History taking pearls:

Alcohol history (quantity, duration, recent changes)
Nutritional status (weight loss, dietary restrictions)
Gastrointestinal symptoms (nausea, vomiting, diarrhea)
Recent surgical procedures or prolonged hospitalization
Medication review (diuretics, metformin)

Physical examination priorities:

Cardiovascular assessment:

Heart rate and rhythm
Blood pressure (may be normal or elevated)
Jugular venous distension
Cardiac auscultation for gallops
Peripheral pulse examination
Assessment for edema^16^

Neurological evaluation:

Mental status examination
Cranial nerve assessment (especially extraocular movements)
Motor strength testing
Sensory examination (vibration, position, light touch)
Deep tendon reflexes
Gait assessment^17^

Oyster: The absence of classic neurological findings does not exclude thiamine deficiency, particularly in early stages or predominantly cardiac presentations.

Laboratory and Imaging Studies

Biochemical markers:

Thiamine levels:

Whole blood thiamine (normal: 70-180 nmol/L)
Erythrocyte transketolase activity
Thiamine pyrophosphate effect (>25% suggests deficiency)^18^

Limitations of thiamine measurements:

Results often unavailable acutely
Poor correlation with tissue stores
Recent supplementation affects accuracy
Laboratory variability^19^

Supporting laboratory findings:

Elevated lactate (impaired pyruvate metabolism)
Metabolic acidosis with normal anion gap
Hyperglycemia (impaired glucose utilization)
Elevated liver enzymes (hepatic dysfunction)^20^

Cardiac evaluation:

Echocardiography: elevated cardiac output, normal or mildly reduced ejection fraction
Electrocardiography: nonspecific ST-T changes, prolonged QT interval
Chest X-ray: cardiomegaly, pulmonary edema^21^

Neurophysiological studies:

Electromyography: axonal sensorimotor neuropathy
Nerve conduction studies: reduced amplitudes with preserved conduction velocities
Magnetic resonance imaging: signal changes in mammillary bodies (Wernicke encephalopathy)^22^

Differential Diagnosis

Wet Beriberi Mimics

Sepsis and distributive shock
Hyperthyroidism
Arteriovenous malformations
Severe anemia
Liver disease
Pregnancy-related cardiomyopathy^23^

Distinguishing features:

Sepsis: fever, elevated inflammatory markers, source of infection
Hyperthyroidism: elevated TSH, tremor, weight loss
AV malformation: localized findings, imaging confirmation

Dry Beriberi Differential

Diabetic neuropathy
Chronic inflammatory demyelinating polyneuropathy
Guillain-Barré syndrome
Toxic neuropathies (chemotherapy, heavy metals)
Chronic kidney disease-related neuropathy^24^

Key differentiators:

Diabetic neuropathy: symmetric presentation, associated retinopathy
CIDP: demyelinating pattern on nerve conduction studies
Guillain-Barré: acute onset, ascending paralysis

Empirical Thiamine Supplementation: When and How

Evidence-Based Indications for Empirical Treatment

Strong indications (treat immediately):

Clinical suspicion of wet or dry beriberi
Alcohol use disorder patients presenting to ICU
Post-bariatric surgery complications
Unexplained high-output heart failure
Unexplained peripheral neuropathy in at-risk patients^25^

Moderate indications (consider treatment):

Prolonged ICU stay (>7 days)
Poor nutritional status
Chronic diuretic use
Sepsis with unexplained lactate elevation
Pre-procedural prophylaxis in high-risk patients^26^

Dosing Protocols

Acute treatment (suspected deficiency):

Thiamine 100-500 mg IV/IM daily × 3-5 days
Followed by 100 mg PO daily
Higher doses (500-1000 mg) for neurological manifestations^27^

Prophylactic supplementation:

Standard ICU patients: 100 mg daily
High-risk patients: 100-200 mg daily
Parenteral nutrition: minimum 6 mg/day (often inadequate)^28^

Special considerations:

Give before glucose administration (prevents precipitation of Wernicke encephalopathy)
Water-soluble vitamin, minimal toxicity risk
Intravenous preferred for suspected deficiency
Duration: continue until clinical improvement or discharge^29^

Hack: The "glucose-thiamine rule" - always give thiamine before or concurrent with glucose in any patient at risk for deficiency to prevent precipitating Wernicke encephalopathy.

Clinical Pearls and Pitfalls

Diagnostic Pearls

The "warm shock" presentation: High-output heart failure with warm extremities should prompt thiamine deficiency consideration
Asymmetric neuropathy: Early thiamine neuropathy may be asymmetric, unlike other metabolic neuropathies
Rapid response to treatment: Cardiac symptoms often improve within 24-48 hours of adequate thiamine replacement
Concurrent deficiencies: Look for other B-vitamin deficiencies (B12, folate, niacin)^30^

Common Pitfalls

Waiting for laboratory confirmation: Thiamine levels take days to return; treat based on clinical suspicion
Inadequate dosing: Standard multivitamin doses (1-2 mg) are insufficient for treatment
Glucose before thiamine: Can precipitate Wernicke encephalopathy in deficient patients
Short treatment duration: Neurological recovery requires weeks to months^31^

Monitoring Response to Treatment

Cardiac response (wet beriberi):

Heart rate normalization (24-48 hours)
Improved urine output
Resolution of edema (3-7 days)
Normalization of cardiac output^32^

Neurological response (dry beriberi):

Improved mental status (hours to days)
Sensory symptom improvement (days to weeks)
Motor recovery (weeks to months)
May have residual deficits if treatment delayed^33^

Future Directions and Research Needs

Current research priorities include:

Development of rapid point-of-care thiamine assays
Optimization of dosing protocols for different populations
Investigation of thiamine deficiency in specific ICU populations
Economic analysis of empirical supplementation strategies
Long-term outcomes following thiamine deficiency in critical illness^34^

Conclusion

Thiamine deficiency represents a treatable cause of significant morbidity and mortality in critically ill patients. The dichotomy between wet beriberi (cardiovascular) and dry beriberi (neurological) presentations requires vigilance from intensivists caring for high-risk populations. Given the safety profile of thiamine supplementation and the devastating consequences of untreated deficiency, empirical treatment should be strongly considered in patients with compatible clinical presentations or significant risk factors.

The key to successful management lies in maintaining a high index of suspicion, particularly in patients with alcohol use disorder, post-surgical complications, or prolonged critical illness. Early recognition and aggressive supplementation can lead to dramatic clinical improvement, while delayed treatment may result in irreversible complications.

Take-home message: When in doubt, supplement thiamine. The risk-benefit ratio strongly favors empirical treatment in suspected cases, and the clinical response to supplementation can serve as both therapeutic intervention and diagnostic confirmation.

References

Donnino MW, Carney E, Cocchi MN, et al. Thiamine deficiency in critically ill patients with sepsis. J Crit Care. 2010;25(4):576-581.
Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol. 2007;6(5):442-455.
Butterworth RF. Thiamin deficiency and brain disorders. Nutr Res Rev. 2003;16(2):277-284.
Sica DA. Loop diuretic therapy, thiamine balance, and heart failure. Congest Heart Fail. 2007;13(4):244-247.
Koike H, Iijima M, Sugiura M, et al. Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy. Ann Neurol. 2003;54(1):19-29.
Attas M, Hanley HG, Stultz D, et al. Fulminant beriberi heart disease with lactic acidosis: presentation of a case with evaluation of left ventricular function and review of pathophysiologic mechanisms. Circulation. 1978;58(3):566-572.
Koike H, Takahashi M, Ohyama K, et al. Clinicopathologic features of acute autonomic and sensory neuropathy. Neurology. 2010;75(11):1020-1027.
Singleton CK, Martin PR. Molecular mechanisms of thiamine utilization. Curr Mol Med. 2001;1(2):197-207.
Hazell AS, Butterworth RF. Update of cell damage mechanisms in thiamine deficiency: focus on oxidative stress, excitotoxicity and inflammation. Alcohol Alcohol. 2009;44(2):141-147.
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.
Francini-Pesenti F, Brocadello F, Manara R, et al. Wernicke encephalopathy during parenteral feeding: not an unusual complication. Nutrition. 2009;25(2):142-146.
Oudman E, Postma A, Van der Stigchel S, et al. The Montreal Cognitive Assessment (MoCA) is superior to the Mini Mental State Examination (MMSE) in detection of Korsakoff's syndrome. Clin Neuropsychol. 2014;28(7):1123-1132.
Shimon I, Almog S, Vered Z, et al. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med. 1995;98(5):485-490.
Baines M, Davies G. The evaluation of erythrocyte transketolase activity and the effect of thiamine diphosphate on transketolase activity for detecting thiamine deficiency. Ann Clin Biochem. 1988;25(Pt 6):698-705.
Rindi G, Laforenza U. Thiamine intestinal transport and related issues: recent aspects. Proc Soc Exp Biol Med. 2000;224(4):246-255.
Nishimura T, Nakatake Y, Konishi M, Itoh N. Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim Biophys Acta. 2000;1492(1):203-206.
Vasconcelos MM, Silva KP, Vidal G, et al. Early diagnosis of pediatric Wernicke's encephalopathy. Pediatr Neurol. 1999;20(4):289-294.
Tallaksen CM, Sande A, Böhmer T, et al. Kinetics of thiamine and thiamine phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally. Eur J Clin Pharmacol. 1993;44(1):73-78.
Wilkinson TJ, Hanger HC, George PM, Sainsbury R. Is thiamine deficiency in elderly people related to age or co-morbidity? Age Ageing. 2000;29(2):111-116.
Lynch PL, Young IS. Determination of thiamine by high-performance liquid chromatography. J Chromatogr A. 2000;881(1-2):267-284.
Amato AA, Barohn RJ. Peripheral neuropathy in critical illness. Neurocrit Care. 2007;6(2):98-105.
Antunez E, Estruch R, Cardenal C, et al. Usefulness of CT and MR imaging in the diagnosis of acute Wernicke's encephalopathy. AJR Am J Roentgenol. 1998;171(4):1131-1137.
DiNicolantonio JJ, Niazi AK, Lavie CJ, et al. Thiamine supplementation for the treatment of heart failure: a review of the literature. Congest Heart Fail. 2013;19(4):214-222.
Koike H, Sobue G. Alcoholic neuropathy. Curr Opin Neurol. 2006;19(5):481-486.
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.
Zuccoli G, Pipitone N. Neuroimaging findings in acute Wernicke's encephalopathy: review of the literature. AJR Am J Roentgenol. 2009;192(2):501-508.
Thomson AD, Guerrini I, Marshall EJ. The evolution and treatment of Korsakoff's syndrome: out of sight, out of mind? Neuropsychol Rev. 2012;22(2):81-92.
Schorah CJ, Smithells RW, Scott J. Vitamin B1, B2 and B6 in hospitalized elderly patients. J Am Geriatr Soc. 1979;27(9):411-414.
Moskowitz A, Donnino MW, Giberson T, et al. The association between reduced lactate clearance and in-hospital mortality in patients with sepsis. Resuscitation. 2016;96:13-18.
McCormick DB. Thiamin deficiency and its prevention and control in major emergencies. World Health Organization; 1999.
Pacitti A, Coppi F, Pulcini A, et al. Wernicke encephalopathy in nonalcoholic patients: clinical and pathological study of 22 cases. Clin Neuropathol. 2013;32(2):114-129.
Crumbs ES, Bozeman WP, Swanson JF, et al. Wet beriberi in an alcoholic patient. Am J Emerg Med. 2014;32(6):678.e1-4.
Katta N, Balla S, Alpert MA. Does long-term furosemide therapy cause thiamine deficiency in patients with heart failure? A focused review. Am J Med. 2016;129(7):753.e7-753.e11.
Wooley JA. Characteristics of thiamin and its relevance to the management of heart failure. Nutr Clin Pract. 2008;23(5):487-493.

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Tuesday, August 5, 2025