What is the role of thiamine (Vitamin B1) in managing refractory shock?

Role of Thiamine in Refractory Shock

The most recent pediatric sepsis guidelines recommend against routine thiamine supplementation in children with septic shock, though thiamine should be considered as adjunctive therapy in adults with refractory vasodilatory shock, particularly when thiamine deficiency is suspected or confirmed. 1

Guideline-Based Recommendations

Pediatric Population

• The 2020 Surviving Sepsis Campaign guidelines explicitly recommend against using thiamine to treat children with sepsis-associated organ dysfunction (weak recommendation, low quality of evidence). 1
• This represents a departure from potential benefit, as the guidelines found insufficient evidence to support routine use in pediatric refractory shock. 1

Adult Population

• The 2012 Surviving Sepsis Campaign guidelines do not specifically address thiamine supplementation for refractory shock in adults. 1
• However, more recent evidence suggests thiamine may have a role as adjunctive therapy in specific adult populations with refractory vasodilatory shock. 2

Evidence-Based Clinical Approach

When to Consider Thiamine in Refractory Shock

High-risk populations who may benefit from thiamine supplementation include:

• Patients with documented or suspected thiamine deficiency presenting with refractory lactic acidosis despite adequate resuscitation. 3, 4
• Critically ill patients with risk factors including malnutrition, alcoholism, gastrointestinal surgery, refeeding syndrome, severe burns, or end-stage renal disease. 4
• Patients on continuous renal replacement therapy (CRRT), as daily thiamine losses in effluent can reach approximately 4 mg/day, far exceeding standard nutritional intake. 1

Dosing Strategy for Refractory Shock

For suspected thiamine deficiency in refractory shock:

• Administer 100-300 mg IV daily for 3-4 days as the initial therapeutic dose. 5, 6
• Do not delay administration waiting for laboratory confirmation, as thiamine reserves can be depleted within 20 days of inadequate intake. 6
• Always give thiamine before glucose-containing IV fluids to avoid precipitating acute Wernicke encephalopathy. 6

For established thiamine deficiency with neurological symptoms:

• Escalate to 500 mg IV three times daily if Wernicke encephalopathy is suspected. 6

Triple Therapy Consideration

Combination therapy with hydrocortisone, vitamin C, and thiamine:

• A 2020 propensity-matched study showed that triple therapy (steroids + vitamin C + thiamine) in refractory septic shock reduced mechanical ventilation duration and showed trends toward lower 30-day mortality compared to steroids alone. 7
• This approach should be considered in patients with refractory vasodilatory shock already receiving hydrocortisone who remain poorly responsive to vasopressors. 2, 7

Evidence Supporting Thiamine in Septic Shock

The strongest recent evidence comes from a 2018 retrospective matched cohort study:

• Thiamine administration within 24 hours of admission in septic shock patients was associated with improved lactate clearance (subdistribution hazard ratio 1.307) and reduced 28-day mortality (hazard ratio 0.666). 8
• This represents the highest quality recent evidence supporting thiamine use in adult septic shock. 8

Monitoring and Safety

Laboratory Assessment

• Measure RBC or whole blood thiamine diphosphate (ThDP) if laboratory confirmation is needed, though treatment should not be delayed. 1, 6
• Plasma thiamine measurement is not useful for acute assessment. 6
• Monitor lactate clearance as a functional marker of thiamine adequacy in shock states. 8

Safety Profile

• Thiamine has no established upper toxicity limit, with excess excreted in urine. 5, 6
• High IV doses rarely cause anaphylaxis, though this remains a theoretical risk. 9, 6
• Doses exceeding 400 mg may cause mild nausea, anorexia, and mild ataxia, but these effects are generally well-tolerated. 9, 6

Critical Pitfalls to Avoid

Common errors in thiamine management:

• Do not use low maintenance doses (2.5-6 mg/day) for suspected deficiency in refractory shock—these doses are inadequate for therapeutic repletion. 1, 5
• Do not withhold thiamine due to lack of laboratory confirmation—clinical suspicion should drive treatment in critically ill patients. 6, 4
• Do not forget to assess for ongoing losses in patients on CRRT, as replacement beyond standard PN may be required. 1

Practical Algorithm for Refractory Shock

Step 1: Identify if patient has refractory vasodilatory shock (inadequate response to high-dose vasopressors). 2

Step 2: Assess for thiamine deficiency risk factors (malnutrition, alcoholism, GI surgery, CRRT, refractory lactic acidosis). 3, 4

Step 3: If risk factors present or deficiency suspected, administer thiamine 100-300 mg IV daily for 3-4 days without delay. 5, 6

Step 4: Consider triple therapy (hydrocortisone + vitamin C + thiamine) in patients already receiving steroids for refractory shock. 7

Step 5: Monitor lactate clearance and hemodynamic response over 24-48 hours. 8

Reconciling Contradictory Evidence

The key divergence exists between pediatric and adult recommendations:

• Pediatric guidelines explicitly recommend against routine thiamine use based on low-quality evidence showing no benefit. 1
• Adult observational data suggests potential mortality benefit in selected populations with septic shock. 8
• This discrepancy likely reflects different study populations, with adult studies enriched for patients with underlying thiamine deficiency risk factors. 3, 4

The most prudent approach: Reserve thiamine for adult patients with refractory shock who have identifiable risk factors for deficiency, rather than universal supplementation. 3, 4, 8