RATIONALE FOR THE USE OF SYSTEMATIC THIAMINE AT PHARMOCOLOGICAL DOSE MSF Ped Days 2016

E-poster 1416
IN MALNOURISHED CHILDREN REQUIRING HOSPITAL ADMISSION Ethical Review Board: not required.

L. Hiffler1 , D. Martinez Garcia 2, N. 3

Salse , N. 2
Lafferty , M.C . 4
Bottineau , B. Rakotoambinina5
1,
Pediatric Advisor, MSF OCBA, Dakar Unit, Senegal and 2, Pediatric Advisor, Medical Department of MSF OCBA, Barcelona, Spain. pediatrics@barcelona.msf.org ;
3, Nutrition advisor, Medical Department MSF OCBA; 4, Leader of MSF Paediatric Working group, Geneva, MSF OCG; 5 Unit of Nutrition Physiology, Antananarivo University, Antananarivo, Madagascar

BACKGROUND and AIMS: RESULTS:

Complicated severe acute malnutrition (SAM) remains a major Thiamine has dual coenzymatic and non-coenzymatic functions. It is In this randomised controlled trial by Donnino et al (2016), 35% of
challenge in MSF programmes and carries significant mortality. As the involved in the production of acetyl-CoA and succinyl-CoA, as a patients had TD on admission, while thiamine treatment in TD patients
body has a very limited, diet-dependent store of thiamine (vitamin B1), cofactor of pyruvate dehydrogenase and alpha-ketoglutarate with septic shock was associated with a lower mortality: 13% vs 46%.
deficiency is common in malnourished children. Thiamine has many dehydrogenase complexes respectively, thus is essential for the proper
functions, and is an essential component of key metabolic pathways functioning of the Krebs cycle (Fig 1). Consequently, TD is associated The thiamine content of therapeutic F75 alone is markedly lower than
involving glucose, nucleic acids and branched-chain amino acids. It is with lactic acidosis and reduced ATP production through disruption of the 2mg/kg recommended for the prevention of refeeding syndrome
also involved in the production of neurotransmitters, myelin and the Krebs cycle, and could be considered an acquired mitochondrial (Table 2), as well as the treatment doses used in critical illness.
nucleic acids. Aside from classic beriberi, thiamine deficiency (TD) is disease.
Table 2: Thiamine content of therapeutic milk and estimated thiamine needs in
implicated in a large spectrum of clinical and sub-clinical conditions Common risk factors for TD are SAM, monotonous diet, diarrhoea and children during the acute phase of refeeding in SAM
and may have an impact on the prognosis of critically ill children with malabsorption, while acute precipitating factors include refeeding-
Approximate amount of F75 in mL (and equivalent South African and Australian
SAM, however the diagnosis is frequently overlooked. induced cellular hyper-utilisation of thiamine, hypermetabolic states Body
of thiamine content -ref. F75 MSF 2014-) given in 8 guidelines for prevention of
Weight
associated with critical illness, and resuscitation with dextrose-based (kg)
meals / day in acute stabilization phase according refeeding syndrome (2 mg/kg
to refeeding protocols (WHO 2013) of thiamine) ref. below
METHOD: fluids, all of which increase cellular thiamine demand (Table 1).
Literature review of current knowledge including thiamine function in Table 1: TD prevalence in SAM and in critically ill children 5 Kg 8 x 85 ml/d (~ 0.75 mg of thiamine) 10 mg of thiamine

humans and clinical presentation of TD in the context of SAM Ghana Jamaica Brazil USA
7 Kg 8 x 120 ml/d (~ 1 mg of thiamine) 14 mg of thiamine
(PubMed, Google Scholar). 10 kg 8 x 170 ml/d (~ 1.5 mg of thiamine) 20 mg of thiamine
43% in SAM 40% in SAM 28% upon admission 24% in diabetic ketoacidosis
Fig 1: Thiamine-B1 functions (Hiffler et al 2016; Frontiers in Nutrition) children children in PICU (35% after 8h of insulin therapy)
15 Kg 8 x 250 ml/d (~ 2.2mg of thiamine) 30 mg of thiamine
N=28 N= 25 N= 202 N= 22
Legend: F-75 is the therapeutic milk used during early refeeding (75 Kcal/100 ml). As an example,
Neumann Hailemariam Lima Rosner a 7 kg child with complicated SAM would be given 8 meals of 120 ml of F-75 on admission. The
1979 1985 2011 2015 dose recommended in the above guidelines (third column) would give approximately 14 times
more thiamine than the amount found in F75 alone.

Recent evidence suggests that thiamine administration in TD patients

with septic shock significantly increases survival (Graph 1). CONCLUSION:
Graph 1: Kaplan Meier survival curves for the thiamine and placebo Complicated SAM is often associated with acute conditions such as
groups among patients with TD (Donnino et al 2016; Crit Care Med) severe malaria, pneumonia and septic shock. Pre-existing low or
borderline thiamine stores in SAM are rapidly consumed in these
hypermetabolic states, exacerbated by refeeding. We recommend
systematic thiamine for all complicated SAM patients at the
pharmacological dose of 25 mg (1/2 tablet) PO, preceded by a loading
dose of 100 mg (1 ml) by slow IV infusion for the first 48 hours in severe
acute conditions.

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