What is the possible etiology of a 27-year-old male presenting with hypotension, severe metabolic acidosis, and cardiac dysfunction, with a history of vomiting, diarrhea, and protein supplement use?

Suspected Protein Supplement Toxicity with Possible Thiamine Deficiency ("Shoshin Beriberi")

This presentation is most consistent with acute thiamine deficiency (Shoshin beriberi) potentially triggered by protein supplement contamination or toxicity, and immediate high-dose intravenous thiamine should be administered while discontinuing all supplements. 1, 2

Critical Diagnostic Features Supporting This Diagnosis

The constellation of findings strongly suggests Shoshin beriberi:

• Severe metabolic acidosis with lactate ~15 mmol/L despite adequate resuscitation indicates Type B (non-circulatory) lactic acidosis 1, 3
• Profound cardiac dysfunction with broad QRS and recurrent VF in a previously healthy young person 2
• Hypotension and vasoconstriction (cold peripheries) rather than the typical high-output failure 2
• Vomiting and diarrhea as initial gastrointestinal prodrome 1, 3
• Normal coronaries on angiography excluding Type 1 MI 4
• Extreme IL-6 elevation (>3000) suggesting severe systemic inflammatory response 1

The classic triad of Shoshin beriberi includes vasoconstriction, hypotension, and severe metabolic acidosis—all present in this case 2.

Why Protein Supplements Are the Likely Culprit

Protein supplements can contain contaminants or adulterants that cause mitochondrial toxicity, leading to Type B lactic acidosis even with adequate tissue perfusion 1, 5. The patient's regular use of protein supplements combined with:

• Recent travel (potentially different supplement batch or contaminated product)
• Vegetarian diet (baseline lower thiamine intake)
• Acute gastrointestinal losses depleting thiamine stores further 1

This creates a perfect storm for acute thiamine depletion 6, 2.

Immediate Management Algorithm

1. Thiamine Replacement (URGENT - First Priority)

• Administer thiamine 500 mg IV over 30 minutes immediately 6
• Continue thiamine 100-250 mg IV three times daily until clinical improvement 6
• Do NOT wait for thiamine levels—treatment must be empiric 6, 2

2. Discontinue All Supplements

• Stop protein supplements immediately 5
• Consider these as potential source of mitochondrial toxins 1, 5

3. Address Persistent Acidosis

• The acidosis will NOT respond to bicarbonate alone if thiamine-deficient 4, 1
• Sodium bicarbonate may paradoxically worsen intracellular acidosis and cardiac function 7
• Focus on correcting underlying thiamine deficiency rather than aggressive bicarbonate therapy 1, 7

4. Supportive Cardiac Management

• Continue ECMO/IABP support as cardiac function may take 24-48 hours to improve after thiamine 2
• Expect gradual improvement in ventricular function with thiamine replacement 2
• Monitor for resolution of arrhythmias as metabolic state improves 2

5. Investigate for Toxins

• Send protein supplement samples for analysis if available 5
• Check for other mitochondrial toxins (though less likely given history) 1, 3
• Consider checking plasma amino acid levels for abnormal metabolites 1

Alternative Diagnoses to Consider (Less Likely)

Acute Mesenteric Ischemia

• CT showed only dilated bowel loops, no definitive ischemia 4
• Lactate would typically improve with ECMO restoring perfusion 4, 3
• Would not explain the severe cardiac dysfunction and recurrent VF 4

Medication/Toxin Ingestion

• Family denies self-harm, but obtain comprehensive toxicology screen 8
• Colchicine toxicity can present with multiorgan failure and acidosis but typically has prominent GI symptoms initially 8
• Hydroxyurea causes acidosis but patient has no indication for this medication 9

Fulminant Myocarditis

• IL-6 elevation supports this, but normal coronaries and acute presentation more consistent with metabolic cause 4
• Would not explain the extreme hyperphosphatemia (16 mg/dL) 1

Key Laboratory Abnormalities Explained

• Phosphorous 16 mg/dL: Massive cellular breakdown and impaired renal excretion 1
• CPK 3000: Modest elevation suggests some rhabdomyolysis but not primary cause 1
• LDH 2396: Reflects widespread cellular injury from metabolic crisis 1
• Ketones positive with GRBS 250: Stress response, not primary diabetic ketoacidosis 4
• Coagulopathy: Multiorgan dysfunction from prolonged shock state 4

Expected Clinical Course with Thiamine

If thiamine deficiency is the primary etiology:

• Lactate should begin declining within 6-12 hours of thiamine administration 1, 2
• Cardiac function improvement within 24-48 hours 2
• Acidosis correction within 24-36 hours 1, 2
• Reduction in vasopressor requirements within 12-24 hours 2

Critical Pitfalls to Avoid

• Do not delay thiamine while awaiting levels—this is a clinical diagnosis requiring immediate empiric treatment 6, 2
• Do not attribute acidosis solely to shock—persistent acidosis despite ECMO indicates non-circulatory cause 1, 5
• Do not aggressively push bicarbonate—may worsen intracellular acidosis and cardiac function 7
• Do not overlook supplement contamination—increasingly common cause of unexplained critical illness 5
• Do not assume normal nutrition in vegetarians—at baseline risk for thiamine deficiency 2

Prognosis

With immediate thiamine replacement, survival is possible even in severe Shoshin beriberi 2. However, the prolonged period of severe acidosis, multiple cardiac arrests, and multiorgan dysfunction significantly worsen prognosis 4, 2. The key is recognizing this as a treatable metabolic emergency rather than primary cardiac disease 6, 2.