Health Info

The importance of Thiamine in Parenteral Nutrition Therapy Q & A

Jakarta, 22 September 2015

The importance of Thiamine in Parenteral Nutrition Therapy Q & A

Introduction

Although lactic acidosis and encephalopathy due to thiamine deficiency have been described as early as 1970s, most clinicians involved with nutrition therapy still generally focus on giving macronutrients and neglect the importance of vitamins and trace elements. This has prompted the US FDA to recently release an updated recommendation of providing parenteral multivitamin preparations recently to minimize the risk of thiamine deficiency during parenteral nutrition therapy. K Sriram at al published a review on Thiamine in Nutrition Therapy in 2012 (1) which highlighted the importance of thiamine in nutrition therapy and practical tips on the prevention and management of deficiency state (Nutr Clin Pract, 2012;27:41-50). Surprisingly, beri-beri which was thought to have disappeared   after 1950s is in fact still commonly found nowadays. Ironically, parenteral nutrition support has become one of the known risk factors.

What is the normal level of vitamin B1 in the body?

Being a water-soluble vitamin with short half-life the total body storage of thiamine is very low (25-30 mg). The concentration of vitamin B1 (tiamine) in  whole blood is 25-75 ng/mL, or  74-222 nmol/L.

Why is thiamine essential during parenteral nutrition therapy?

Thiamine in its active form TPP (thiamine pyrophosphate) or thiamine diphosphate is co-factor of three critical enzymes in carbohydrate metabolism (pyruvate dehydrogenase, alpha-ketoglutaric acid dehydrogenase and transketolase).


Most importantly, pyruvate dehydrogenase catalyzes the conversion of pyruvate to acetyl-CoA. Thus increased metabolism of glucose will result in thiamine consumption. In thiamine deficiency or depletion lactic acid will accumulate to produce severe lactic acidosis. Therefore thiamine deficiency should always be considered in unexplained lactic acidosis.


Why does lactic acidosis due to thiamine deficiency cause neurological manifestations (e.g Wernicke‘s encephalopathy)?

Focal damage due to lactic acidosis is its effect on vulnerable brain structures (mamillary bodies and postmedial thalamus). There is focal lactate production in the brain. Apoptotic cell death due to N-methyl-D-aspartate toxicity is responsbile for neurologic symptoms in thiamine deficiency (2)

When could    clinicans suspect Wernicke Encephalopathy?

The classic triad of WE includes ocular abnormalities, ataxia and changes in mental status. Most frequent ocular abnormalities are nystagmus, partial or complete opthalmoplegia, pupillary abnormalities and optic neuropathy. Perhaps not all components of the triad can be seen.

How much thiamine is required to avoid metabolic complications?

In general, daily maintenance requirement in adults ranges from 1.1-1.2 mg orally   and 3 mg parenterally. (1,2)  Recommendation from several sources is given in the following table:


Which groups of patients are susceptible to vitamin B1 (thiamine) deficiency and thus should alert the attending physician?

Thiamine deficiency is prone to occur in the following patient groups:

  • Medical and Surgical Patients receiving non-thiamine supplemented parenteral nutrition
  • Elderly patients
  • Pregnancy
  • Hyperemesis gravidarum
  • Trauma
  • Patients with critical illness (sepsis)
  • Diabetic patients
  • Alcoholics
  • Renal replacement therapy
  • Congestive heart failure
  • Postbariatric surgery
  • Refeeding syndrome etc


Based on various references, dosing recommendation for parenterally supplemented PPN and TPN is enough with daily maintanance of 3 mg. Does it apply for all hospitalized   patients ?

Maintenance dose of 3 mg is enough for prevention of thiamine deficiency. However in the following circumstances much higher intake will be required:
 

No

Condition

Dosage of Thiamine (iv)

1

Wernicke encephalopathy (WE)

200 mg 3 times a day (1,11)

2

Refeeding syndrome

300 mg before initiating nutrition therapy, 200-300 mg intravenously daily for at least 3 more days(1)

3

Renal Replacement therapy

100 mg daily(1)

4

Alcohol withdrawal states

50-100 mg daily(1)

5

Patients with critical illness (sepsis)

100 to 300 mg of thiamine during the first 3 days (12)

6

Hyperemesis gravidarum

(100mg/day IV or oral for three days (13,14)

7

Burn

100 mg daily for 14-21 days (15)

8

Major Trauma

100 mg daily for 15 days (15)


In there any correlation between thiamine concentration and critical illness?

Nakamura et al (16) studied the correlation between thiamine concentration (before and after PPN) and CRP


This figure shows that there is a negative correlation between thiamine concentration and CRP. The C reaction protein (CRP) and the blood concentration of vitamin B1 showed negative correlations both before and after PPN.  The regression line was found to be y=34.5-.8x, and from this, the blood concentration of vitamin B1 after PPN was shown to be below the lower limit of reference value of 28 ng/mL at CRP of 8 mg/dL or higher.
It was thought as follows: In critically-ill  patients, the metabolism of glucose is promoted by aggravation of inflammation probably caused by promotion of metabolism, and this increases the demand for vitamin B1 resulting in lowering the blood concentration of vitamin B1.

How much thiamine is at least  required as daily maintenance for covering the metabolism parenteral glucose?

The body requires a minimum of 0.33mg thiamine for every 1000 kcal consumed, so individuals who consumed an average diet 2000kcal per day should receive thiamine 0.66mg daily at minimum (5)
BFLUID® contains 1.5 mg of thiamine for 75 g of glucose in 1000ml. This amount is sufficient to cover metabolism of 75g glucose


Conclusion

The role of thiamine should not be neglected in parenteral nutrition. All patients receiving parenteral nutrition require approximately  3 mg of thiamine maintenance dose daily to prevent serious complications such as lactic acidosis and Wernicke encephalopathy. In various clinical scenarios where thiamine dficiency should be sucpected, treatment should be initiated before or in the absence of laboratory confirmation.

References:
 

  1. Sriram K. Thiamine in Nutrition Therapy. Nutrition in Clinical Practice, February 2012; vol. 27, 1: pp. 41-50
  2. Darren Navarro, Claudia Zwingmann, Alan S. Hazell and Roger F. Butterworth Brain lactate synthesis in thiamine deficiency: A re-evaluation using 1H-13C nuclear magnetic resonance spectroscopy JOURNAL OF NEUROSCIENCE RESEARCH Volume 79, Issue 1-2, 1 - 15 January 2005, Pages: 33–41
  3. ASPEN Board of Directors. Guidelines for the Use of Parenteral and Enteral Nutritionin Adult and Pediatric Patients. JPEN 2002; 26(1) Sup: 22SA-24SA
  4. Mirtallo et al. Safe Practices for PN. JPEN Vol 28 No 6, 2004
  5. Osiezagha K et al. Thiamine Deficiency and Delirium. Innov Clin Neurosci. 2013;10(4):26-32
  6. Aviva Fattal-Valevski. Thiamine (Vitamin B1). Journal of Evidence-Based Complementary & alternative Medicine 2011; 16(1) 12-20
  7. A.S.P.E.N Position paper: Reccomendations for changes in Commercially Available Parenteral Multivitamin and Multi-Trace Element Products.JPEN 2014 Vol 28 No 6 S54
  8. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Cholinehttp://www.nap.edu/catalog/6015.htm.
  9. Morino, Paul L. The ICU Book 3rd edition. 2007. Lippincott Williams & Wilkins
  10. Frank LL. Thiamin in Clinical Practice. JPEN Vol 39 No 5. July 2015 503-520
  11. Sechi G, Serra A: Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management.Lancet Neurol 2007, 6:442-455
  12. Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A, Griffi ths R, Kreyman G, Leverve X, Pichard C, ESPEN: ESPEN Guidelines on Parenteral Nutrition: intensive care. Clin Nutr 2009, 28:387-400
  13. Anne-Marie Neill, Catherine Nelson-Piercy. Hyperemesis gravidarum. The Obstetrician & Gynaecologist 2003;5:204–7;
  14. Wilcox SR. Hyperemesis Gravidarum in Emergency Medicine Treatment & Management.Medscape Apr 11, 2013
  15. Burger MM. Antioxidant Micronutrients in Major Trauma and Burns: Evidence and Practice Nutrition in Clinical Practice, October 2006; vol. 21, 5: pp. 438-449
  16. Takuro Nakamura, et. al.: Japanese Journal of Surgical Metabolism and Nutrition 2002; 36 (6): 307-313



September 17, 2015
Dr Iyan Darmawan
Medical Director CIBG Division
iyan@ho.otsuka.co.id