About FEAST

About the FEAST (Fluid Expansion as Supportive Therapy) Trial

The FEAST trial was a large randomised controlled trial examining the effectiveness of fluid resuscitation of children with severe infections in Africa. 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 trial was carried out in six hospitals in Africa (in Kenya, Uganda and Tanzania). More than 3,000 children took part.

The trial looked at whether rapid fluid infusion (fluid resuscitation or expansion) at admission to hospital improves survival compared to standard management alone.

Why is this trial important?

In sub-Saharan Africa between 15-30% of children admitted to hospital because of severe infections die. Over a million children die of severe infection in hospital each year in sub-Saharan Africa. Currently, antimalarial and antimicrobial drugs are the mainstay of treatment, however most deaths occur early, before definitive treatments have time to act. In this situation doctors have to rely upon supportive therapies to treat complications to try to improve outcome. But there have not been enough clinical studies to determine which are the best life-saving treatments.

Rapid fluid infusion to correct fluid deficits is a standard supportive treatment. It is practised routinely in developed countries for the emergency management of children with severe illness. But there have been no large trials anywhere to evaluate the safety and effectiveness of this treatment. There were considerable doubts over whether such an approach would work in sub-Saharan Africa, where intensive care facilities to deal with any side-effects of the treatment do not exist.

What did the trial show?

The trial found that fluid resuscitation as an emergency treatment for African children suffering with shock from severe infections does not save lives. Giving children fluids slowly to maintain normal levels, rather than rapid fluid resuscitation, is safer and more effective in aiding recovery. 92.7% of children given fluids more slowly survived the first 48 hours in hospital, compared to 89.4% of those given boluses.

While fluid resuscitation did not help children in the trial, all those taking part were less likely to die than is usual in hospitals in sub-Saharan Africa. This may be because of the training that hospital staff were given on emergency triage and treatment of children. This meant staff could identify the sickest children and make sure they get treated first.

What do these results mean?

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. 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’.

It is important that fluid resuscitation is still used 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. Children with severe malnutrition were not included in the trial as fluids are not recommended as part of their treatment.

Trial Information

FULL TITLE: A randomised trial of fluid resuscitation strategies in African children with severe febrile illness and clinical evidence of impaired perfusion

Short Title: Fluid Expansion As Supportive Therapy in critically ill African children

ACRONYM: FEAST

International Trial registration number: ISRCTN 69856593

DESIGN

A 3-arm randomised open comparative trial of fluid resuscitation strategies:

(1) Immediate volume resuscitation with normal (0.9%) saline;

(2) Immediate volume expansion with 5% human albumin solution (HAS);

(3) Control: no immediate volume expansion.

AIMS

In hospitals throughout sub-Saharan Africa, mortality from malaria and other severe infections in childhood remains at 15-30%, with over 50% of deaths occurring within 24 hours of admission. Currently, antimalarial and antimicrobial drugs are the mainstay of treatment, with little consideration being given to the use of adjunctive supportive therapies. There is considerable debate about the degree to which intravascular volume depletion (hypovolaemia) contributes to the pathophysiology of malaria and other severe infections, and clinical practice varies widely across the continent. To resolve the continuing uncertainty, this multi-centre randomised clinical trial will evaluate different fluid resuscitation strategies in children presenting to hospital with severe febrile illness and clinical evidence of impaired perfusion, with the intention of generating data of practical value to clinicians working in resource-poor settings in Africa.

OUTCOME MEASURES

Primary Endpoint: In-hospital mortality at 48 hours after randomisation.

Secondary Endpoints: Mortality at 4 weeks, neurological sequelae at 4 weeks and 24 weeks, episodes of hypotensive shock within 48 hours of randomisation, adverse events related to fluid resuscitation (pulmonary oedema, intracranial hypertension or severe allergic reaction to those receiving albumin).

POPULATION

Sample size

The total sample size is 3,600 children.

ELIGIBILITY

Inclusion criteria

Children aged >60 days and <12 years with severe febrile illness (impaired consciousness or respiratory distress) plus clinical evidence of impaired perfusion.

Exclusion criteria

Children with the following conditions will be excluded: severe acute malnutrition; gastroenteritis; chronic renal failure, pulmonary oedema and other conditions in which volume expansion is contraindicated; non-infectious causes of severe illness; children who have already received an isotonic volume expander during the current illness.

TRIAL TREATMENT

3,600 eligible children will be randomly assigned in a ratio of 1:1:1 to one of three fluid management arms:

(1) Rapid volume expansion with 40mls/kg intravenous 0.9% saline;

(2) Rapid volume expansion with 40mls/kg 5% human albumin solution (HAS);

(3) Maintenance fluids with no volume expansion (control arm).

Children will be reassessed at 1, 4, 8, 24 and 48 hours, and further fluid boluses will be given in strict accordance with the protocol. Children will receive a maximum of 100mls/kg in 24 hours of fluid boluses. The small number of eligible children that are anticipated to have hypotensive shock (severe hypotension plus impaired perfusion) at the time of admission (n=144) will be randomly allocated in a ratio of 1:1 to rapid volume expansion with either saline or HAS.

Follow-up

Children will be clinically assessed at 1, 4, 8, 24 and 48 hours. Neurological assessments will be carried out at 4 weeks and, for those with sequelae at 4 weeks, at 24 weeks from the time of randomisation. Follow-up neurological assessments will be carried out by a clinician or nurse who is blind to treatment allocation.

DURATION

The trial will enrol over 24 months and started in January 2009.