African trial questions emergency treatment of children
in shock
Embargoed until 2100 BST Thursday 26 May
Giving fluids rapidly through a drip into a
vein (fluid resuscitation) as an emergency treatment for African
children suffering with shock from severe infections does not save
lives, according to a major clinical trial funded by the Medical
Research Council. The ground-breaking research showed that giving
children fluids slowly to replace the needs of a sick child who
cannot drink, rather than rapid fluid resuscitation, is safer and
more effective in aiding recovery. These findings challenge current
WHO guidelines on how best to provide fluids to children in Africa
with fever and shock caused by malaria, sepsis and other
infections.
The trial known as FEAST (Fluid Expansion As
Supportive Therapy) involved over 3000 children in six hospitals
across Tanzania, Uganda & Kenya. It examined the effectiveness
of a long-standing treatment used across the world called fluid
resuscitation. This treatment involves giving seriously ill
children large volumes or ‘boluses’ of intravenous fluids quickly
through a drip in their first hour at hospital to try to reverse
the deadly effects of shock.
The children on the trial were divided
randomly into three equally sized groups. Two groups were given
emergency boluses of either albumin or saline in the first hour of
arriving in hospital. After the first hour, the children were then
given fluids slowly, to replace the amounts a sick child should
drink. The third group were given fluids slowly but no additional
bolus treatment.
The trial results showed that children given
fluids more slowly did better, with a 48 hour survival rate of
92.7%, compared with 89.4% of those children given boluses.
Compared with giving children fluids slowly, fluid resuscitation
caused three additional children to die out of every hundred
treated.
The trial was stopped early because the
independent committee overseeing safety saw that giving boluses was
unsafe. However, all children who took part in FEAST had a better
chance of survival than is normally the case in Africa, in part due
to extra training given to hospital staff to give emergency
treatments, such as oxygen and providing medicines for malaria and
other infections.
Prof Kathryn Maitland, the Chief Investigator
for FEAST, Imperial College London and KEMRI-Wellcome Trust
Programme said:
“This is the first time anywhere
in the world that fluid resuscitation has been evaluated for safety
and effectiveness in such a large trial, even though it has been
standard treatment for the last two decades in the United States,
Europe and Australasia. The FEAST trial was set up with the hope
that fluid resuscitation would help the many African children with
malaria and septicemia. Around one in ten children in Africa
admitted to hospital with these deadly infections are in a state of
shock. Although there are effective medicines for these illnesses,
too often children arrive in hospital already very sick, with many
children dying within hours of admission. Large-scale
clinical trials of this nature carried out to the highest levels
are crucial if we are to find new ways to keep children alive when
they come into hospital. Disappointingly, across all parts of the
trial we found that fluid resuscitation had no benefit- our only
conclusion is that boluses are harmful when used for shock in the
illnesses we studied.”
Professor Sarah Kiguli, Chief Principal
Investigator in Uganda said:
“The results have surprised me,
particularly as I had seen some children getting better after being
given large volumes of fluids. But more importantly the results
went against the recommendations of the WHO and the normal practice
in wealthy countries, and this surprised me greatly. Finding this
out before we started to encourage the use of fluid resuscitation
children with severe infections and shock across Africa was
incredibly important. It will save many lives in future.”The
study authors agree that further research is needed in countries
where fluid resuscitation is already standard practice, although
the results in Africa may not be directly applicable to wealthy
countries. One reason for this is that sophisticated life
support equipment is available in wealthier countries and is
available along with fluid resuscitation as part of a ‘package of
care’.”
Professor Diana Gibb from the Medical Research Council Clinical
Trials Unit said:
“The treatment may not carry the
same risks in wealthy countries because children are healthier, and
in particular have few problems of underlying long-standing
malnutrition or anaemia. However the clear findings from the FEAST
trial do question the use of boluses for severe infections even in
wealthy countries and more research is needed.”
The researchers have stressed the need to
continue to use fluid resuscitation to treat diarrhoea and other
conditions like burns and trauma, where children lose fluids. For
these conditions, where fluid resuscitation will continue to be a
vital life-saving treatment, they advise that current WHO
recommendations should stay the same. Children with severe
malnutrition were not included in the trial as fluids are not
recommended as part of their treatment.
The study was coordinated by KEMRI-Wellcome
Trust Research Programme, Kilifi, Kenya in collaboration with
scientists from Imperial College and the Clinical Trials Unit of
the Medical Research Council in London
(MRC-CTU).
The trial is published today in the New
England Journal of Medicine, was funded by the Medical
Research Council (MRC) and sponsored by Imperial College London.
Notes to editors:
- The paper ‘Mortality after Fluid Bolus in African Children
with Severe Infections’ will be published online by the New
England Journal of Medicine on 2000 BST 26 May 2011.
- Shock is when the body restricts the blood flow to the vital
organs in an effort to stave off death. It can occur through
traumatic injuries, burns and many febrile illnesses, including
those studied in FEAST. When a child shows symptoms of shock,
it means they are extremely sick and need urgent treatment. They
become pallid and cold to the touch as the arms and legs become
drained of blood. The pulse becomes fast and weak. Gradually
as shock advances the body becomes deprived of blood flow and
starved of oxygen and this leads to a downward spiral towards
death.
- The researchers are very confident that the results are
accurate. Independent reviewers praised the conduct of the trial.
It scored 99.5% on its adherence to the trial plan, or "protocol"
and a similar amount for retention of patients, two key indicators
of a good trial.
- Overall trial co-ordination was carried out by KEMRI-Wellcome
Trust Research Programme, Clinical Trials Facilty Kilifi, Kenya in
collaboration with the Medical Research Council Clinical Trials
Unit, London who also undertook the statistical analysis. The trial
was designed by KEMRI-Wellcome Trust Research Programme in
collaboration with the MRC Clinical Trials Unit and the Department
of Paediatrics, Imperial College London; the London institutions
also provided technical and scientific support, advice and
training. In Uganda Logistics and co-ordination were carried out by
Malaria Consortium Africa, Kampala.
- Baxter Healthcare Corporation generously donated the
resuscitation fluids for the trial, but was not involved in any
other way.
Publication links
- Click here to
view the paper of the FEAST trial results in the New England
Journal of Medicine, available online 26/05/2011
- Click here for a
related editorial
Other links
Further information
