REFEEDING SYNDROME IN SEVERE ACUTE MALNUTRITION:

THE ROLE OF MAGNESIUM AND THIAMINE

L. Hiffler1, D. Martinez Garcia 2, B. Rakotoambinina 3
1,

Dakar Unit, Senegal and 2, Medical Department of MEDECINS SANS FRONTIERES (MSF), Barcelona, Spain. pediatrics@barcelona.msf.org ,
3, Unit of Nutrition Physiology, Antananarivo University, Madagascar

BACKGROUND: Refeeding syndrome in severe acute

malnutrition (SAM) is characterized by electrolyte
imbalances, including hypomagnesaemia, and is associated
with thiamine deficiency (TD). It leads to congestive heart
failure, neurological and hematological complications. Signs
are often misinterpreted as sepsis, primary cardiac failure,
pneumonia and sudden death. Diagnosis is rarely made and
therefore its prevalence is probably underestimated,
particularly in resource-limited settings where electrolyte
monitoring is often unavailable. We delve here into
thiamine and magnesium interaction and their potential
links with refeeding syndrome.

Table 1: TD prevalence in SAM and in critically ill children

Ghana

Jamaica

Brazil

USA

43 %
in SAM
children

40 %
in SAM
children

28 % upon
admission in
PICU

24 % in diabetic
ketoacidosis (35 % after
8h of insulin therapy)

N=28

N= 25

N= 202

N= 22

Neumann
1979

Hailemariam

Lima
2011

Rosner
2015

1985

Thiamine and magnesium requirements are underestimated

in critically ill, severely malnourished children in resourcelimited settings. In addition, hypomagnesaemic patients do
not respond well to thiamine supplementation only,
magnesium being a co-factor for thiamine-dependent
enzymes.
For this reason, both magnesium and thiamine should be
given at therapeutic doses during refeeding syndrome, along
with correction of other electrolytes where possible.
Therapeutic milk (F75) alone does not provide enough
thiamine or magnesium for this purpose (Table 3).
Table 3: Thiamine and magnesium content of F75

+ B1

Baseline hypomagnesaemia is also common in critically ill

children and those with SAM (Table 2). Iatrogenic factors, such
as the frequent use of gentamicin in resource-limited settings,
may contribute to hypomagnesaemia - up to 38% of adults
receiving aminoglycosides develop hypomagnesaemia.
Table 2: Hypomagnesaemia prevalence in SAM and in critically ill
children

METHOD: Literature review using PubMed and Google

Scholar from 1965 to 2016

India

India

Netherlands

Spain

Turkey

Guatemala

Bangladesh

Nigeria

RESULTS: Refeeding after a period of starvation initially

induces a rapid electrolyte shift inside cells causing
hypophosphatemia, hypokalaemia, and hypomagnaesemia.
Functional TD secondary to intracellular hyperutilization of
thiamine is also associated with refeeding. This further
depletes already suboptimal or low body stores of thiamine,
a common underlying finding in children with SAM and in
critically ill children (Table 1).

70 % in
PICU

44 %
in
PICU

20 % in PICU

47,5 %
in PICU

36 % in
SAM
and 68
% in
SAM/
PICU

50 % in
SAM

> 80 % in SAM

85 % in
SAM

N = 80

N=
179

N = 105

N= 360

N= 25

N=19

N = 60

N= 28

Hagu
e
2009

Hulst
2006

Ruiz
Magro
1999

Karake
lleoglu
2011

Nichols
1978

Khalil
2006

Caddell
1967

Deshmukh

2000

Hiffler L, Rakotoambinina B, Lafferty N, Martinez Garcia D: Thiamine Deficiency in Tropical Pediatrics: New insights into a Neglected but Vital Metabolic Challenge. Front. Nutr., 14 June 2016
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Ethical Review Board: not required.

Body
weight
(kg)

Approximate amount of F75 in mL given in 8 meals / day

in acute stabilization phase according to refeeding
protocols (WHO 2013) and (equivalence of thiamine and
magnesium content for this volume)

5 Kg

8 x 85 ml/day
(~ 0.5 mg of thiamine and ~ 57 mg of Mg)

7 Kg

8x120 ml/d
(~ 0.8 mg of thiamine and ~ 80 mg of Mg)

10 kg

8 x 170 ml/d
(~ 1.1 mg of thiamine and ~ 113 mg of Mg)

15 Kg

8x 250 ml/d
(~ 1.7 mg of thiamine and ~ 167 mg of Mg)

CONCLUSION: We recommend the therapeutic administration

of thiamine, 100mg IV (over 30 min) or IM every 8-12 h for 48
h, followed by 25mg PO daily; as well as Magnesium Sulphate
at a dose of 25 mg/kg IM or IV (over a minmum of 30 min
max 2 gr) every 12 h for 48 h, whenever refeeding syndrome is
clinically suspected in resource limited settings. Clinical
studies are urgently required to address current gaps on this
issue in the initial refeeding phase.

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