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 (thiamine) 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 clinicians 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:
- Sriram K. Thiamine in Nutrition Therapy. Nutrition in Clinical Practice, February 2012; vol. 27, 1: pp. 41-50
- 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
- ASPEN Board of Directors. Guidelines for the Use of Parenteral and Enteral Nutritionin Adult and Pediatric Patients. JPEN 2002; 26(1) Sup: 22SA-24SA
- Mirtallo et al. Safe Practices for PN. JPEN Vol 28 No 6, 2004
- Osiezagha K et al. Thiamine Deficiency and Delirium. Innov Clin Neurosci. 2013;10(4):26-32
- Aviva Fattal-Valevski. Thiamine (Vitamin B1). Journal of Evidence-Based Complementary & alternative Medicine 2011; 16(1) 12-20
- 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
- Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Cholinehttp://www.nap.edu/catalog/6015.htm.
- Morino, Paul L. The ICU Book 3rd edition. 2007. Lippincott Williams & Wilkins
- Frank LL. Thiamin in Clinical Practice. JPEN Vol 39 No 5. July 2015 503-520
- Sechi G, Serra A: Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management.Lancet Neurol 2007, 6:442-455
- 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
- Anne-Marie Neill, Catherine Nelson-Piercy. Hyperemesis gravidarum. The Obstetrician & Gynaecologist 2003;5:204–7;
- Wilcox SR. Hyperemesis Gravidarum in Emergency Medicine Treatment & Management.Medscape Apr 11, 2013
- Burger MM. Antioxidant Micronutrients in Major Trauma and Burns: Evidence and Practice Nutrition in Clinical Practice, October 2006; vol. 21, 5: pp. 438-449
- Takuro Nakamura, et. al.: Japanese Journal of Surgical Metabolism and Nutrition 2002; 36 (6): 307-313
